Category Archives: Nursing

“But doctor, he’s vomiting blood!!!” – The NEJM GI Bleed article by Villanueva: Yup, time to reassess transfusion in GI bleed! @FOAMed, @FOAMcc

thinking critical care

Screen Shot 2014-01-08 at 3.13.37 PM

Last january a highly anticipated paper came out in the NEJM (, which should be a game changer, given a few provisos.  Villanueva et al reported on their large (almost 1,000 patients) randomized study on liberal (<90 mg/dl) vs restrictive (<70 mg/dl) strategy.  Interestingly but no longer surprisingly, the patients in the restrictive strategy did better.

Hmmm…sound familiar?  By now everyone  accepts the TRICC trial threshold of 70 in ICU patients, but when it first came out, there were a fair bit of disbelievers and concerned health care workers.  At the time, they excluded GI bleeds and acute coronary syndromes, understandably,

So what do the numbers say?  First lets see if there was any difference in the actual treatment. Definitely. In the restrictive group, 51% of patients required transfusion, vs 86% in the liberal group.  Sizeable difference. Now in terms of outcomes:

a. rebleeding decreased: 10% vs 16%

b. 6 week…

View original post 1,030 more words

Fluid Management

Fluid Management

Clinical Problems

    There are several clinical problems associated with the need to understand fluid management related to patient care.

  1. How to identify patients who need fluid therapy or are becoming hemodynamically unstable before they progress too far?
  2. How to determine the most appropriate therapy to reverse the primary cause for impending circulatory shock/problem(s)?
    1. For instance,
      1. Which fluid, when to give fluid, how much fluid to give
      2. Predicting fluid response
  3. How to implement the most appropriate therapy for your individual patients?
  4. How to assess your patients fluid response?
    1. Is Cardiac Output Adequate? (Preload Responsiveness)
    2. Is blood flow adequate to meet metabolic demands?
      1. Does the patient have adequate organ perfusion
    3. Will increasing intravascular volume increase cardiac output?
    4. Will decreasing the driving pressure for venous return decrease cardiac output?
    5. Is cardiac output responsive to intravascular fluid loading?
  5. What end points/results from your therapy demonstrate success or a need for further action?





“Classic” Blalock 1937

  1. Hematogenic
  2. Neurogenic
  3. Vasogenic
  4. Cardiogenic

Low Cardiac Output states (Carrico: ACS Early Care of the Injured Patient 4th Ed.)

  1. Hypovolemic shock
    1. volume loss
    2. Internal volume loss
  2. Cardiac shock
    1. Impaired inflow
    2. Primary pump dysfunction
    3. Impaired outflow
  3. Low peripheral resistance states
    1. Neurogenic shock
      1. Loss of sympathetic tone
    2. Vasogenic Shock
      1. Septic
      2. Anaphylactic

Tissue oxygen saturation predicts the development of organ dysfunction during traumatic shock resuscitation

SMACC: Johnston on the Assessment of Shock

Fluid resuscitation of hemorrhagic shock

Epocrates – Evaluation of Shock



Acute coagulopathy of trauma shock (ACoTS)

Acute Coagulopathy of Trauma Shock (ACoTS)

  1. Syn:ETIC (Early Trauma Induced Coagulopathy)
  2. Starts in the prehospital period.
  3. Shock & Hypoperfusion is the cause.
  4. Dilution,Hypothermia,Loss of coagulation factors not significant at this stage.
  5. Thrombomodulin-ProteinC pathway is activated in hypoperfusion.
  6. Hypercoagulable state and risk of thrombosis due to Protein C depletion.

LITFL – Shock… Do We Know It When We See It?

Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion



The Lethal Six Pack

  1. Tissue Injury
  2. Shock
  3. Dilution
  4. Hypothermia
  5. Acidosis
  6. Inflammation


  1. Causes of Hypothermia
    1. Environmental factors: extrication and transport time
    2. IV fluids and ongoing blood loss
    3. Alteration of normal heat producing metabolism
  2. Effects of Hypothermia
    1. Decreases platelet aggregation and adhesion
    2. Decrease coagulation factor activity by 10% for each degree decrease in core temperature
    3. Both R (Rx Time) & K (Fibrin) prolonged on TEG
    4. 100% fatal when core temperature reaches < 32°C
  3. Coagulation assays are run at 37 °C!

Hypothermia References and Resources

  1. Emcrit – Targeted Temperature Management for Post-Arrest and Critical Care
  2. Hypothermic Resuscitaiton
  3. Induced Hypothermia After Anoxic Brain Injury
  4. Iced Saline in the Field – Induced Hypothermia for EMS
  5. Induced hypothermia does not impair coagulation system in a swine multiple trauma model
  6. Induced Hypothermia in Post Cardiac Arrest Patients
  7. Steady-state and time-dependent thermodynamic modeling of the effect of intravenous infusion of warm and cold fluids
  8. Therapeutic Hypothermia in Survivors of Cardiac Arrest
  9. Therapeutic Hypothermia – The Pharmacologic Inhibition of Thermoregulation
  10. University of Penn – Med – Center for Resuscitation Science – Hypothermia

Impact of prehospital hypothermia on transfusion requirements and outcomes



Hypothermia in massive transfusion: have we been paying enough attention to it?



  1. Causes of Acidosis
    1. Decreased perfusion leads to anaerobic metabolism and lactic acid production
    2. LR pH 6.0, normal saline 4.5, no buffering capacity
    3. Red cell unit at two weeks have pH < 7.0
  2. Effects of Acidosis
    1. Reduced clot formation demonstrated by TEG
    2. Spherical platelets devoid of pseudopods
    3. Reduced fibrinogen levels, platelet counts & FXa
  3. Prevention of Acidosis
      1. Dependent on restoration of perfusion
      2. Exogenous bicarb has mixed results

Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway?

Chapter 19: Using the Stewart Model at the Bedside



Coagulopathy and blood component transfusion in trauma

The interplay between metabolic acidosis, hypothermia and progressive coagulopathy in trauma “Bloody Vicious Cycle”




Surgical Treatment: Evidence-Based and Problem-Oriented – Abdominal compartment syndrome

Initial Management of Life-Threatening Trauma. Ch 6 Trauma and Thermal Injury. ACS Surgery: Principles and Practice

Abdominal Compartment Syndrome

Abdominal compartment syndrome has emerged as a virtual epidemic in busy trauma centers that practice damage-control surgery and goal-oriented ICU resuscitation. This syndrome is an early event, and its clinical trajectory can be accurately predicted within 3 to 6 hours after ED admission. At admission to the ICU, high-risk patients have significant intra-abdominal hypertension and are in persistent shock. Contrary to conventional wisdom, they do not respond well to pre-load directed resuscitation. In fact, continued aggressive resuscitation precipitates the full-blown syndrome [figure 13].


Stress Repair Mechanism

The capillary gate component (red) corresponds to the intrinsic pathway of the coagulation cascade. The tissue repair component (blue) corresponds to the extrinsic pathway of the coagulation cascade. Both the SRM and the coagulation cascade generate thrombin (orange), plus soluble fibrin and insoluble fibrin. Inhibitory pathways appear in green.  View a list of SRM terms and concepts here. (30 Years Lost in Anesthesia Theory)


Hemodynamic Values

From Crashing Patient



Catheters and Flow Rates

(Marino, The ICU Book, 109-110)



Intravenous extension sets: when more is less



Winters – Fluids in the Critically Ill


In 1861, Thomas Graham’s investigations on diffusion led him to classify substances as crystalloids or colloids based on their ability to diffuse through a parchment membrane. Crystalloids passed readily through the membrane, whereas colloids (from the Greek word for glue) did not. Intravenous fluids are similarly classified based on their ability to pass from intravascular to extravascular (interstitial) fluid compartments.

From Wikipedia – Volume Expanders

There are two main types of volume expander; crystalloids and colloids. Crystalloids are aqueous solutions of mineral salts or other water-soluble molecules. Colloids contain larger insoluble molecules, such as gelatin. Blood is a colloid.

  • Colloids preserve a high colloid osmotic pressure in the blood, while, on the other hand, this parameter is decreased by crystalloids due to hemodilution.[1] However, there is still controversy with regard to the actual difference in efficacy between colloids and crystalloids.[1] Crystalloids generally are much cheaper than colloids.[1]
  • The most commonly used crystalloid fluid is normal saline, a solution of sodium chloride at 0.9% concentration, which is close to the concentration in the blood (isotonic). Lactated Ringer’s (also known as Ringer’s lactate) and the closely related Ringer’s acetate, are mildly hypotonic solutions often used for large-volume fluid replacement.

Additional information:

  1. Crystalloid solutions – clear fluids made up of water and electrolyte solutions; Will cross a semi-permeable membrane e.g Normal, hypo and hypertonic saline solutions; Dextrose solutions; Ringer’s lactate and Hartmann’s solution.
  2. Colloid solutions – Gelatinous solutions containing particles suspended in solution. These particles will not form a sediment under the influence of gravity and are largely unable to cross a semi-permeable membrane. e.g. Albumin, Dextrans, Hydroxyethyl starch [HES]; Haemaccel and Gelofusine
    1. The colloid solutions contain particles which do not readily cross semi-permeable membranes such as the capillary membrane
    2. Thus the volume infused stays (initially) almost entirely within the intravascular space
    3. Stay intravascular for a prolonged period compared to crystalloids
    4. However they leak out of the intravascular space when the capillary permeability significantly changes e.g. Severe trauma or sepsis
    5. Until recently they were regarded as the gold standard for intravascular resuscitation
    6. Because of their gelatinous properties they cause platelet dysfunction and interfere with fibrinolysis and coagulation factors (factor VIII) – thus they can cause significant coagulopathy in large volumes.


Common Examples


Paucis Verbis: Composition of intravenous fluids (Medscape – An Update on Intravenous Fluids)

Fluid Therapy in Hemorrhagic Shock: The ability of sodium to replace interstitial fluid deficits, not blood volume deficits, is the reason that crystalloid fluids containing sodium chloride (saline fluids) gained early popularity as resuscitation fluids for acute blood loss.


A physicochemical model of crystalloid infusion on acid-base status



(LifeInTheFastLane – Strong Ion Difference = SID & Stewart’s Strong Ion Difference)

Crystalloid infusion changes plasma SID by changing the proportion of strong cations to strong anions and, thus, the net charge balance. After crystalloid infusion, plasma SIDad
(admixture) reflects the admixture of the crystalloid SID and plasma SID. The major strong cations and anions will also be diluted by the increment in plasma volume by the infusate. The plasma SIDad from standard state conditions is calculated as follows: SIDss (standard state) plasma volume + SIDci (crystalloid infusate) infusate volume divided by plasma volume + infusate volume. The plasma SIDad calculation after a 1 L infusion of normal saline from standard state can be found in the appendix.


Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults


Clinical review: Volume of fluid resuscitation and the incidence of acute kidney injury – a systematic reviewimage

Base Deficit or Base Excess

The base deficit is the amount (in millimoles) of base needed to titrate one liter of whole blood to a pH of 7.40 (at temperature of 37°C and PCO2 = 40 mm Hg). Because base deficit is measured when the pCo2 is normal, it was introduced as a more specific marker of non-respiratory acid-base disturbances than serum bicarbonate (16). In the injured or bleeding patient, an elevated base deficit is a marker of global tissue acidosis from impaired oxygenation (17). One advantage of the base deficit is its availability. Most blood gas analyzers determine the base deficit routinely using a pC02/HC03 nomogram, and the results are included in the blood gas report. The base deficit (BD) can also be calculated
using the equation below (18), where BD is base deficit in mmol/L, Hb is the hemoglobin concentration in blood, and HC03 is the serum bicarbonate concentration.

BD = [(1 – 0.014 Hb) X HC03] – 24 + [(9.5 + 1.63 Hb) X (pH – 7.4)]

The normal range for base deficit is +2 to -2 mmol/L. Abnormal elevations in base
deficit are classified as mild (-2 to -5 mmol/L), moderate (-6 to -14 mmol/L),
and severe (<-15 mmol/L).

Clinical studies in trauma patients have shown a direct correlation between the magnitude of increase in base deficit at presentation and the extent of blood loss (19). Correction of the base deficit within hours after volume replacement is associated with a favorable outcome (19), while persistent elevations in base deficit are often a prelude to multiorgan failure.

(Marino, The ICU Book, 218)

(Best utilized in combination with serum lactate early (24-36 hours) in the patients ICU stay.)

P-Video: Rule of 15 for Anion Gap Metabolic Acidosis

    2. Acid-Base Physiology
      1. Acid-Base Physiology – Quantitative Acid-Base Analysis: The Variables
      2.  Acid-Base Physiology – Quantitative Acid-Base Analysis: The Equations
    3. Acid-base balance in peritoneal dialysis patients: a Stewart-Fencl analysis
    4. Wikipedia – Base Excess
    5. Base Excess & Calculated Bicarbonate
    6. Cornell – Base Excess & Calculated Bicarbonate Calculator
    7. EMCrit
      1. Podcast 44 – Acid Base: Part I
      2. Podcast 45 – Acid Base: Part II
      3. Podcast 46 – Acid Base: Part III
      4. Podcast 50 – Acid Base Part IV – Choose the Solution Based on the Problem
      5. Podcast 96 – Acid Base in the Critically Ill – Part V – Enough with the Bicarb Already
      6. Podcast 97 – Acid-Base VI – Chloride-Free Sodium
    8. Life In The Fast Lane – Base Excess Vs Standard Base Excess
    9. Life In The Fast Lane – Strong Ion Difference
    10. P-Video: Rule of 15 in anion gap metabolic acidosis
    11. Stewarts Strong Ion Difference
    12. Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders
    13. YouTube Acid Base Videos
      1. Application of Base Deficit in Resuscitation of Trauma Patients
      2. Eric Strong – Introduction and Course Overview (Understanding ABGs – Lecture 1 of 23)
      3. MEDCRAMvideos – Medical Acid Base Explained Clearly! 1 of 8



When using the base deficit to guide fluid resuscitation in trauma patients, the base deficit should be monitored serially along with the patient’s clinical response.

Elevated Arterial Base Deficit in Trauma Patients: A Marker of Impaired Oxygen Utilization




Chapter 19: Using the Stewart Model at the Bedside


The Stewart approach–one clinician’s perspective




Physical Exam


Physical exam in general is not sensitive or specific

  1. Acute weight loss; however, obtaining an accurate weight over time may be difficult
  2. Decreased skin turgor – if you pinch it it stays put
  3. Dry skin, particularly axilla
  4. Dry mucus membranes
  5. Low arterial blood pressure (or relative to patient’s usual BP)
  6. Orthostatic hypotension can occur with significant hypovolemia; but it is also common euvolemic elderly subjects.
  7. Decreased intensity of both the Korotkoff sounds (when the blood pressure is being measured with a sphygmomanometer) and the radial pulse (“thready”) due to peripheral vasoconstriction.
  8. Decreased Jugular Venous Pressure
  9. The normal venous pressure is 1 to 8 cmH2O, thus, a low value alone may be normal and does not establish the diagnosis of hypovolemia.

The rational clinical examination. Is this patient hypovolemic?

(Marik et al. Annals of Intensive Care 2011, 1:1)


Volume Depletion with Depleted Extravascular Compartment

  1. Acute blood loss
    1. Trauma
    2. GI bleed
  2. Gastrointestinal tract losses (diarrhea, vomiting, fistula)
  3. Decreased fluid intake due to acute medical conditions
  4. Diabetic ketoacidosis
  5. Heat exhaustion
  6. “Dehydration”

Volume Depletion with Expanded Extravascular Compartment

  1. Sepsis
  2. Pancreatitis
  3. Trauma
  4. Surgery
  5. Burns
  6. Liver failure
  7. Cardiac failure

Also: P.E. Marik, Handbook of Evidence-Based Critical Care, DOI 10.1007/978-1-4419-5923-2_8

Permissive Hypotension

Damage Control Resuscitation: The New Face of Damage Control

Permissive Hypotension

The concept behind permissive hypotension involves keeping the blood pressure low enough to avoid exsanguination while maintaining perfusion of end organs. Although hypotensive resuscitation is evolving into an integral part of the new strategy of DCR, the practice itself is not a new concept. Walter Cannon and John Fraser remarked on it as early as 1918 when serving with the Harvard Medical Unit in France during World War I. They made the following observations on patients undergoing fluid resuscitation: “Injection of a fluid that will increase blood pressure has dangers in itself. Hemorrhage in a case of shock may not have occurred to a marked degree because blood pressure has been too low and the flow to scant to overcome the obstacle offered by the clot. If the pressure is raised before the surgeon is ready to check any bleeding that may take place, blood that is sorely needed may be lost.”13 Dr. Cannon’s endpoint of resuscitation before definitive hemorrhage control was a systolic pressure of 70 mm Hg to 80 mm Hg, using a crystalloid/colloid mixture as his fluid of choice.

In World War II, Beecher promulgated Cannon’s hypotensive resuscitation principles in the care of casualties with truncal injuries. “When the patient must wait for a considerable period, elevation of his systolic blood pressure (SBP) to 85 mm Hg is all that is necessary … and when profuse internal bleeding is occurring, it is wasteful of time and blood to attempt to get a patient’s blood pressure up to normal. One should consider himself lucky if a systolic pressure of 80 mm Hg to 85 mm Hg can be achieved and then surgery undertaken.”14

Although these anecdotal reports from earlier generations of surgeons are interesting, more scientific attempts to examine outcomes for permissive hypotension after serious injury have been mixed. The most well-known study that displayed a benefit for delayed aggressive fluid resuscitation until after operative intervention with surgical hemostasis was published in 1994 by Bickell et al. This randomized controlled trial of patients with penetrating truncal injuries compared mortality rates of patients who received immediate versus delayed administration of intravenous (IV) fluids and discovered improved survival, fewer complications, and shorter hospital stays in the delayed group. They demonstrated that, regardless of the victim’s blood pressure, survival was better in their urban “scoop and run” rapid transport system when no attempt at prehospital resuscitation was made.15 The same group published a follow-up abstract in 1995, which was a subgroup analysis of the previous study dividing patients into groups by their injury type. This study demonstrated a lack of affect on survival, in most groups, for patients treated with delayed fluid resuscitation with a survival advantage only for patients with penetrating injuries to the heart (p 0.046).16 This called into question whether study by Bickell et al. was generalizable to trauma population at large. Four years later, Burris et al.17 also suggested that patients could benefit in the short-term by resuscitating to a lower blood pressure. Other studies attempting to replicate these results were unable to find a difference in survival.18,19 Also of note is whether these results in a penetrating trauma population can be extrapolated to the trauma population at large remains to be seen.

In 2006, Hirshberg et al.20 used computer modeling to demonstrate that the timing of resuscitation has different effects on bleeding, with an early bolus delaying hemostasis and increasing blood loss and a late bolus triggering rebleeding. Animal models exploring the effect of fluid administration on rebleeding have been equally contradictory, with some demonstrating that limiting fluids reduces hemorrhage, 21 whereas others demonstrate that fluids do not increase bleeding.22 Moreover, the limited use of fluids during resuscitation efforts is in direct opposition to guidelines put forth by the American College of Surgeons and the Advanced Trauma Life Support protocol.23

The discussion about the risks and benefits of permissive hypotension beg additional questions: even if one believes that permissive hypotension is beneficial, it seems intuitive that some low threshold of safety should exist. How low of a blood pressure can the injured patients tolerate? For how long? Does this theoretical lower limit change when considering not only the initial hypotensive/hypoxic injury but reperfusion injury as well? At the other end of the spectrum, at what level of blood pressure do we “pop the clot” off of spontaneously clotted vessels? Does this point vary with types of resuscitation fluid, time of onset, rate of resuscitation, and the nature of the wound? How does permissive hypotension come into play in the setting of multiple injuries? Most of the work in this modality has been done in penetrating trauma. What is the role of permissive hypotension in blunt trauma? This is an especially pertinent question in injuries where hypotension has been shown to be detrimental, such as brain injury. This important point of contention that, in severe traumatic brain injury (TBI), denying fluids can attenuate the injury by decreasing the intracerebral perfusion pressure has been entertained before.24,25

Unfortunately, no evidence-based recommendations exist from any of the field’s leading trauma organizations. In their absence, the findings from historical military medical sources, modern urban transport studies, and recent laboratory animal models suggest that trauma patients without definitive hemorrhage control should have a limited increase in blood pressure until definitive surgical control of bleeding can be achieved. The potential for rebleeding against the detrimental effects of systemic ischemia and reperfusion require further study. Until more detailed studies are conducted, hard guidelines cannot be put forth.

  1. Anaesthesia for vascular emergencies
  2. Hypotensive Resuscitation in Patients with Ruptured Abdominal Aortic Aneurysm
  3. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries
  4. Jem’s – Permissive Hypotension in Trauma Resuscitation
  5. LifeInTheFastLane – Permissive Hypotension
  6. Permissive hypotension and desmopressin enhance clot formation
  7. Permissive hypotension does not reduce regional organ perfusion compared to normotensive resuscitation: animal study with fluorescent microspheres
  8. Permissive hypotensive resuscitation–an evolving concept in trauma
  9. Target blood pressure for hypotensive resuscitation
  10. Trauma – Permissive Hypotension
  11. Wikipedia – Permissive Hypotension

Anaesthesia for vascular emergencies

For aortic rupture, permissive hypotension should be a standard of care with the aim of keeping the systolic blood pressure 50–100 mmHg as long as consciousness is maintained [1, 36, 57]. Excessive fluid administration, in an attempt to normalise blood pressure, dilutes coagulation factors, disrupts thrombus and can cause expansion and rupture of a contained retroperitoneal haematoma [11].

Haemorrhagic shock, therapeutic management

Full-size image (77 K)


Damage control resuscitation from major haemorrhage in polytrauma


Traumatic Brain Injury or TBI

Why does TBI require a higher systolic BP than required for permissive hypotension?

  1. CPP = MAP- ICP
  2. MAP = [DBP+1/3 (SBP-DBP)]

Progressive Blood Loss

(Committee on Trauma Advanced Trauma Life Support Manual. Chicago: American College of Surgeons; 1997. pp. 103–112.)

(These are ideal conditions/scenario’s and rarely occur together in real life as described below.)

The American College of Surgeons identifies four categories of acute blood loss based on the percent loss of blood volume.

Class I: Loss of 15% or less of the total blood volume. This degree of blood loss is usually fully compensated by transcapillary refill. Because blood volume is maintained, clinical findings are minimal or absent.

Class II: Loss of 15-30% of the blood volume. The clinical findings at this stage may include orthostatic changes in heart rate and blood pressure. However, these clinical findings are inconsistent. Sympathetic vasoconstriction maintains blood pressure and perfusion of vital organs, but urine output can fall to 20-30 ml/hr, and splanchnic flow may also be compromised. Splanchnic hypoperfusion is a particular concern because it can lead to breakdown of the intestinal barrier and translocation of microbes and inflammatory cytokines, setting the stage for systemic inflammation and multiple organ failure.

Class III: Loss of 30-40% of the total blood volume. This marks the onset of decompensated hypovolemic shock, where the vasoconstrictor response to hemorrhage is no longer able to sustain blood pressure and organ perfusion. The clinical consequences include hypotension and reduced urine output (usually 5-15 ml/hr). Systemic vasoconstriction may be attenuated or lost at this stage, resulting in exaggerated hypotension.

Class IV: Loss of more than 40% of blood volume. Hypotension and oliguria are profound at this stage (urine output may be <5 ml/hr, and these changes may be irreversible.

American College of Surgeon’s Classes of Acute Hemorrhage


The rational clinical examination. Is this patient hypovolemic?

 Oxygen Consumption vs Delivery

(Marino, The ICU Book, 218)


Clinical review: Hemorrhagic shock

Diagnostic Accuracy of Vital Signs for Acute Blood Loss


Tachycardia in the supine position is absent in a majority of patients with moderate-to-severe blood loss. In fact, bradycardia may be more prevalent in acute blood loss. Orthostatic vital signs have limited value in the evaluation of hypovolemia. According to ATLS the use of the hematocrit to estimate blood loss is unreliable and inappropriate. In the early hours after acute hemorrhage, the hematocrit is a reflection of the resuscitation effort (the type of infusion fluid and the volume infused), not the severity of blood loss. (Marino, The ICU Book, 214-6)



  Diagnostic Accuracy of Physical Signs for Hypovolemia Not Due to Blood Loss


The Trendelenburg Position

Elevation of the pelvis above the horizontal plane in the supine position was introduced in the latter part of the 19th century as a method of facilitating surgical exposure of the pelvic organs. The originator was a surgeon name Friedrich Trendelenburg, who specialized in the surgical correction of vesicovaginal fistulas. The body position that now bears his name was later adopted during World War I as an antishock maneuver that presumably promotes venous return by shifting blood volume from the legs toward the heart. This maneuver continues to be popular today, despite evidence that it does not perform as expected. (Marino, The ICU Book, 219-220)

  1. Trendelenburg position and oxygen transport in hypovolemic adults
  2. Failure of the Trendelenburg position to improve circulation during clinical shock
  3. Blood volume distribution in the Trendelenburg position





One of the important discoveries, I believe…is the realization that anemia is well tolerated… providing blood volume is maintained. Daniel J. Ullyot, M.D. (1992)

Anemia is almost universal in patients who spend more than a few days in the ICU (1), and about half of ICU patients with anemia are given one or more transfusions of concentrated erythrocytes (packed red blood cells) to correct the problem (2). This practice of transfusing red blood cells to correct anemia is one of the most fickle and arbitrary interventions in critical care medicine…The fear of anemia is pervasive but unfounded, because (as indicated in the introductory quote) anemia does not compromise tissue oxygenation as long as the intravascular volume (and hence cardiac output) is maintained. The relative importance of blood volume over blood cells is demonstrated by the fact that hypovolemia is a recognized cause of circulatory shock (impaired tissue oxygenation), whereas anemia is not. (Marino, The ICU Book, 659)

Adverse Events Associated with RBC Transfusions


The viability of platelets in whole blood and erythrocyte concentrates (packed cells) is almost completely lost after 24 hours of storage. Therefore, large-volume transfusions can produce dilutional thromocytopenia. This effect becomes prominent when the transfusion volume exceeds 1.5 times the blood volume (25). (Marino, The ICU Book, 687)

Transfusion for Massive Blood Loss

Questions from LifeInTheFastLane:

  1. Managing The Critical Bleeder!!
  2. Trauma! Massive Transfusion

LifeInTheFastLane – Transfusion Reactions

MDCalc: TASH Score (Trauma Associated Severe Hemorrhage) for Massive Transfusion

Predicts the need for massive transfusion based on clinical and laboratory data.






Parameters For Fluid Replacement

Static Fluid Measures*

Static tests (less sensitive, less specific and less useful that dynamic tests)

  • Clinical static endpoints (e.g. heart rate, blood pressure, collapsed veins, capillary refill time, previous urine output)
    — not sensitive
    — poor inter-observer reliability
  • CVP/PCWP (also delta CVP post fluid challenge)
    — poor predictors
  • CXR
    — look for pulmonary edema
    — unreliable
  • PiCCO – “PiCCO” means Pulse Contour Cardiac Output. The “i” is only included to have an easy sounding and pronounceable word
    — EVLW and ITBV 
  • ‘one off’ lactate or SvO2 (not useful)

Dynamic Fluid Measures*

Dynamic tests

  • Passive leg raising
    — see Passive leg raise
    — can use with pulse pressure change, PPV, VTI (echo), NICOM, carotid Doppler flow, or ETCO2 (if ventilation and metabolic status constant)
  • End-expiratory occlusion test
    — Occluding the circuit at end-expiration prevents the cyclic effect of inspiration to reduce left cardiac preload and acts like a fluid challenge.
    — A 15 second expiratory occlusion is performed and an increase in pulse pressure or cardiac index predicts fluid responsiveness with a high degree of accuracy.
    — The patient must be able to tolerate the 15 second interruption to ventilation without initiating a spontaneous breath.

Ultrasound (can be used dynamically)

  • Echocardiography
    — subaortic velocity time index (VTI) allows measurement of stroke volume
    — EDV approximates preload
  • Lung ultrasound
    — can be used to detect pulmonary edema, i.e. lack of fluid tolerance
  • IVC ultrasound (see below)

Respiratory variation tests (can be used dynamically)

  • IVC ultrasound
    — assess size and degree of inspiratory collapse
    — correlates with CVP, but CVP is a poor indicator of fluid responsiveness
  • Plethmysography
  • systolic pressure, pulse pressure (PPV) and stroke volume (SVV)
    — see Systolic Pressure Variation
    — generally limited to mechanically ventilated patients in sinus rhythm
  • aortic blood velocity


  • Fluid responsiveness does not mean that a patient should be given fluids
  • However, if a patient has low cardiac output that requires correction, fluid responsiveness means that cardiac output will improve if fluids are given
  • It means patients are on the ascending portion of their Starling curve, in other words, they have ‘preload reserve’
  • We should probably use different cutoff values for fluid responsiveness depending on the clinical context. Patient’s with severe respiratory failure need higher specificity and lower sensitivity tests of fluid responsiveness, whereas the opposite may be appropriate in patients with pre-renal failure.

(Clinical Judgment is the most important consideration in evaluating patients needs using the information below, especially consider the many other static and dynamic ways discussed)

Volume status and Frank-Starling curves:

Schema Frank Starling curves.jpg

For the same baseline pre-load (A, assessed by CVP) and same increase in pre-load (amount of fluid given: A -> B), the hemodynamic response assessed by the variation in stroke volume is not significant in patients on the flat portion of the Frank Starling curve (poor LV systolic function) : a = b. In these patients, pre-load increase won’t have beneficial effects and may worsen the patient’s condition. In patients who are on the steep portion of the curve, the same increase of pre-load (A -> B) will lead to significant increase in stroke volume: b’ > a’.

Ideally, the volume status is a “functional assessment”: to induce a change in cardiac preload and observe the effects on cardiac output and arterial pressure.

Predictive Value of Techniques Used to Determine Fluid Responsiveness


Fluid Challenge

Fluid Resuscitation

What is a fluid challenge?

The fluid challenge is a test that allows the clinician to give fluids and at the same time to test the preload reserve of the patient. The judicious administration of intravenous
fluid is an essential part of the management of many sick patients. An inadequate cardiac output (CO) and systemic arterial pressure reduces the delivery of oxygen to a level below the necessary requirements, leading to a cascade of cellular changes that ultimately can result in organ dysfunction and failure.

When the decision of increasing the CO is made, optimization of preload is usually the first step taken. It goes without saying, therefore, that the primary target of a fluid challenge is an increase in SV or CO. An increase of at least 10–15% is considered a positive response [10].

Corrected flow time
The corrected flow time (FTc), derived from oesophageal Doppler monitoring, has been described as indicating fluid challenge and predicting response in surgical patients [32]. The FTc should not be considered an accurate marker of left ventricular preload [33], being
inversely proportional to systemic vascular resistance, and therefore describing left ventricular afterload.

What fluid?
Fluid challenges may be performed with crystalloid (isotonic or hypertonic) or colloids. The ability of colloids to maintain or increase CO should reduce fluid extravasation into the lung, but increased capillary permeability may negate this advantage…Colloid will stay in the intravascular compartment for longer, and hyperoncotic fluid will draw fluid out of the interstitial space, increasing plasma volume beyond the administered volume. Whether this has clinical relevance for the fluid challenge is unclear.

Rate of administration
Rate of administration is probably more important than the amount of fluid and the type of fluid. The best evidence in terms of outcome comes from studies where the fluid challenge technique has been used in goal directed therapy [5–7,9,24]. In these studies, small
boluses of fluid (250 ml, or 3 ml/kg of usually colloids) were given in a short period of time (5–10 min). A response in terms of SV with a CO monitor was considered positive if the SV increased by 10–15%. An algorithm mandates the clinician to repeat this process until the SV
fails to increase above the chosen threshold. This process is called SV maximization.


Key points

  1. A fluid challenge identifies and simultaneously corrects volume depletion in order to optimize tissue perfusion.
  2. Administration of fluid using a fluid challenge protocol avoids unnecessary fluid administration and may improve outcome in critically ill and elective surgical patients.
  3. Dynamic noninvasive predictors of volume responsiveness such as SV, PLR and DScVO2 should be used in preference to the CVP and PAOP for guiding fluid therapy.
  4. Continuous CO monitors are the best option to monitor the response to a fluid challenge.
  5. The physiological properties of the fluid and the clinical picture should be considered when choosing which fluid to use.

Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence

Volume expansion is frequently used in critically ill patients to improve hemodynamics. Because of the positive relationship between ventricular end diastolic volume and stroke volume,[1] the expected hemodynamic response to volume expansion is an increase in right ventricular end-diastolic volume (RVEDV), left ventricular end-diastolic volume, stroke volume, and cardiac output. The increase in end-diastolic volume as a result of fluid therapy
depends on the partitioning of the fluid into the different cardiovascular compliances organized in series. The increase in stroke volume as a result of end-diastolic volume increase depends on ventricular function since a decrease in ventricular contractility
decreases the slope of the relationship between end-diastolic volume and stroke volume.[1] Therefore, only 40 to 72% of critically ill patients have been shown to respond to volume expansion by a significant increase in stroke volume or cardiac output in studies [2–13] designed to examine fluid responsiveness. This finding emphasizes the need for predictive
factors of fluid responsiveness in order to select patients who might benefit from volume expansion and to avoid ineffective or even deleterious volume expansion (worsening in gas exchange, hemodilution) in nonresponder patients, in whom inotropic and/or vasopressor support should preferentially be used.



Intraoperative fluid restriction improves outcome after major elective gastrointestinal surgery

Monitoring of peri-operative fluid administration by individualized goal-directed therapy

  1. Oesophageal Doppler


Fluid Challenge is potentially risky

Pcap-PAOP difference is high in ALI/ARDS

  1. Collee et al. Anesthesiology 1987
  2. Radermacher et al. Anesthesiology 1989
  3. Radermacher et al. Anesthesiology 1990
  4. Teboul et al J. Appl Physiol 1992
  5. Benzing et al. Acta Anaesthesiol Scand.1994
  6. Rossetti et al. Am J Respir Crit Care Med 1996
  7. Benzing et al. Br J Anaesth. 1998
  8. Nunes et al. Intensive Care Med. 2003
  9. Her et al. Anesthesiology 2005

Degree of pulmonary edema poorly evaluated by Pcap and  lung capillary permeability is often altered in ICU pts



Cardiovascular Physiology Concepts – Central Venous Pressure



CVP Measurement (Synopsis shown listed below, but see the link for more details)


  • Central venous pressure (CVP) is the pressure in the central veins (internal jugular, subclavian or femoral)
  • typically referred to as the blood pressure in the proximal SVC, near the junction with the right atrium
  • normal is 0-6mmHg in a spontaneously breathing non-ventilated patient
  • CVP represents the driving force for filling the right atrium and ventricle
  • measurement reflects vascular compliance and changes in volume status
  • Despite the widespread belief that CVP reflects the adequacy of cardiac preload in critically ill patients, there is a large body of evidence suggesting that the relationship between CVP and cardiac output is tenuous
  • CVP represents the interaction between pump function and venous return and can give meaningful information about volume status if some measurement of cardiac function is known


a = atrial contraction
c = closing and bulging of the tricuspid valve
x = atrial relaxation
v = passive filling of atrium
y = opening of the tricuspid valve


Diagnosis of:

  • right ventricular infarction
  • PE
  • ARDS
  • cor pulmonale
  • tamponade

Do not use CVP to assess fluid responsiveness

  • very poor relationship between CVP and blood volume and CVP/DeltaCVP is a poor predictor of the hemodynamic response to a fluid challenge.

Venous Function and Central Venous Pressure

Measuring Central Venous Pressure

CVP and Fluid Responsiveness

  • Central venous pressure (CVP) has been used over the last 50 years to assess volume status and fluid responsiveness in critically ill patients.
  • Despite widespread practice habit, CVP has not been shown to reliably predict fluid responsiveness in the critically ill.
  • In a recent updated meta-analysis, Marik et al reviewed 43 studies, totaling over 1800 patients.
    • 57% of patients were fluid responders
    • The mean CVP was 8.2 mm Hg for fluid responders and 9.5 mm Hg for non-responders
    • For studies performed in ICU patients, the correlation coefficient for CVP and change in cardiac index was just 0.28.
  • Bottom line: Current literature does not support the use of CVP as a reliable marker of fluid responsiveness.


Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med 2013:41:1774-1781.

Emcrit – Pressure Transducer Set-up for CVP and A-Lines


  1. Accurate characterization of extravascular lung water in acute respiratory distress syndrome
  2. Extravascular lung water in sepsis-associated acute respiratory distress syndrome: indexing with predicted body weight improves correlation with severity of illness and survival
  3. Extravascular lung water measurements and hemodynamic monitoring in the critically ill: bedside alternatives to the pulmonary artery catheter
  4. Train the Trainer – Advanced Hemodynamic Monitoring – PiCCO Technology
  5. Case Study – Acute Burn Injury with Unclear Fluid Resuscitation
  6. Pulmonary artery catheter versus pulse contour analysis: a prospective epidemiological study
    1. On direct comparison, the use of PiCCO was associated with a greater positive fluid balance and fewer ventilator-free days. After correction for confounding factors, the choice of monitoring did not influence major outcomes, whereas a positive fluid balance was a significant independent predictor of outcome
    2. More recently, new technology (PiCCO [pulse contour cardiac output] System; PULSION Medical Systems AG, Munich, Germany) that provides an alternative to the PAC has been developed and applied [5]. This new technology uses transpulmonary thermodilution and pulse contour analysis to calculate cardiac output, stroke volume variation, intra-thoracic blood volume, and extra-vascular lung water (EVLW). In patients who already have a central line, PiCCO requires only the insertion of a 4-French femoral catheter. Several small studies have been conducted to compare the PAC to PiCCO in terms of physiological relevance (for example, ability to predict fluid responsiveness). They have suggested that PiCCO obtained data such as stroke volume variation or intra-thoracic blood volume index (ITBI) may better predict fluid responsiveness [5-10]. This may or may not affect clinical outcome.
    3. Pulsion – PiCCO Technology – FAQ
    4. Swan Ganz Catheters – A Learning Guide – PiCCO
PiCCO2 – 1. Configuration & Navigation

Passive Leg Raise

  1. Increase in right ventricular preload (Thomas et al 1965)
  2. Increase in left ventricular preload (Rocha 1987, Takagi 1989, De Hert 1999, Kyriades 1994 )
  3. Changes in BP induced by passive leg raising predict response to fluid loading in critically ill patients
    1. Image not available.
    2. Image not available.
    3. Image not available.
    4. In most of the patients, PPrad (radial artery pulse pressure) slightly increased during PLR (Fig 2). This increase in PPrad was positively correlated to the increase in SV during PLR (r 0.77;p  0.001) [Fig 3]
  4. Passive leg raising does not produce a significant or sustained autotransfusion effect
  5. Monitoring volume and fluid responsiveness: From static to dynamic indicators
    1. The passive leg raising (PLR) test has been proposed as another preload challenge taking its advantage to be independent of heart–lung interactions and thus to be used in all patients, even those who are not intubated[45]. Lifting the legs from the horizontal position induces a gravitational transfer of blood from the lower limbs towards the intrathoracic compartment. This significantly increases the right and left cardiac preload[46], supporting the fact that the volume of blood transferred to the heart during PLR is sufficient for challenging the Frank–Starling curve.
    2. The excellent ability of PLR to serve as a test of preload responsiveness was demonstrated in patients with acute circulatory failure [47]. A 10–12% increase in cardiac output or stroke volume during PLR enables us to predict fluid responsiveness, even in patients with cardiac arrhythmias and/or spontaneous ventilator triggering [28]. It is important to note that: (1) changes in arterial pressure cannot be used to assess the hemodynamic response to PLR as it can result in false-negative cases [28] and (2) the cardiac output response to PLR must be assessed with a real-time monitoring device as the effects of PLR are transient and reach their maximum after only 30–90 s [45]. Indeed, probably because of the development of some compensatory mechanisms, the increase in cardiac output during PLR is not sustained when the leg elevation is prolonged. This is particularly marked in septic patients in whom an important capillary leak may account for an attenuation of the PLR effects after 1 min. Thus, real-time cardiac output monitoring technologies and devices such as PiCCO,  FloTrac/Vigileo, oesophageal Doppler, USCOM and echocardiography are perfectly suitable for this purpose as demonstrated by clinical studies [35]. More recently, the real-time changes in end-tidal carbon dioxide, which reflect the changes in cardiac output, were shown to assess the response to PLR and thus to predict fluid responsiveness in mechanically ventilated patients [49,50].
    3. Beyond its reliability and easiness, the PLR test has some limitations [45]. First, it cannot be used in instances in which mobilizing the patient is not possible or allowed, like in the operating theatre or in the case of head injury [51]. Second, the value of the PLR has been questioned in cases of increased intra-abdominal pressure [52], although this has to be confirmed.
  6. Non-invasive assessment of fluid responsiveness by changes in partial end-tidal CO2 pressure during a passive leg-raising maneuver
  7. End-tidal carbon dioxide is better than arterial pressure for predicting volume responsiveness by the passive leg raising test

End-expiratory occlusion test

The end-expiratory occlusion test

This test is another method that takes advantage of heart-lung interactions to predict fluid responsiveness in ventilated patients. During mechanical ventilation, each insufflation increases the intrathoracic pressure and impedes venous return. Thus, interrupting the respiratory cycle at end-expiration inhibits the cyclic impediment in venous return. The resulting increase in cardiac preload may thus help to test preload responsiveness (Figure 1). Indeed, it was demonstrated that if a 15-second end-expiratory occlusion test increased the arterial pulse pressure or the pulse contour-derived cardiac output by more than 5%, the response of cardiac output to a 500 ml saline infusion could be predicted with good sensitivity and specificity [31]. Noticeably, all patients of the latter study were arrhythmic or had mild spontaneous breathing activity. These initial results were recently confirmed [26].

Beyond its simplicity, the main advantage of the end-expiratory occlusion test is that it exerts its hemodynamic effects over several cardiac cycles and thus remains valuable in case of cardiac arrhythmias [31]. Also, the end-expiratory occlusion test can be used in patients with spontaneous breathing activity, unless marked triggering activity interrupts the test. Another limitation is that the effects of the end-expiratory occlusion test, which must be observed over 15 s, are much easier to observe on a continuous display of cardiac output than on the arterial pulse pressure because the value of the latter is not continuously calculated and displayed by bedside monitors.

Hemodynamic parameters to guide fluid therapy





End-Expiratory Occlusion Test Predicts Preload Responsiveness Independently of Positive End-Expiratory Pressure During Acute Respiratory Distress Syndrome




Predicting fluid responsiveness with transthoracic echocardiography is not yet evidence based

Echocardiography is a well-established method to assess cardiac anatomy and biventricular function. When Doppler technique is added, stroke volume (SV) may be estimated across the aortic valve.(3) When transthoracic echocardiography (TTE) is performed, the method is non-invasive and may be applicable to most intensive care patients.(4) The clinical interest in utilizing TTE by non-cardiologist in intensive care medicine has resulted in echocardiography protocols such as the Focus Assessed Transthoracic Echocardiography and Critical Care Echocardiography.(5,6) Thus, major intensive care societies now recommend that echocardiography should be part of the curriculum of intensive care physicians.(7) As TTE is becoming an integrated tool for circulatory assessment in the intensive care unit, it is imperative to know TTE’s validity as a test for fluid responsiveness. Therefore, the aim of this systematic review was to assess the predictive value of TTE for fluid responsiveness.


Trans-thoracic Echo Standard Views Intro Part 1 of 2 [UndergroundMed]


Trans-thoracic Echo Standard Views Intro part 2 of 2 [UndergroundMed]


FATE Exam: Focused Assessed Transthoracic Echo


Focus Assessed Transthoracic Echocardiography (FATE)

R.U.S.H. Exam

  1. Mount Sinai Emergency Medicine Ultrasound – RUSH
  2. Emcrit – Rapid Ultrasound for Shock and Hypotension – the RUSH Exam
  3. Bedside Ultrasound in Resuscitation and the Rapid Ultrasound in Shock Protocol
  4. SonoCase: 45 yr old female acute respiratory distress…. RUSH, part deux
  5. SonoCase: 78 yr old, hypotensive, altered…Welcome to “RUSH” week!
Rapid Ultrasound for Shock and Hypotension — the RUSH Exam


RUSH: Rapid Ultrasound in Shock
Echocardiographic Evaluation of Hypovolemia and Volume Responsiveness


Audio for this is found at: Sharon Kay: Echo for Everyone: 5 Things Never to Miss

Trauma Fast Exam (from my previous post)

Lung ultrasound

  1. Fluid administration limited by lung sonography: the place of lung ultrasound in assessment of acute circulatory failure (the FALLS-protocol) – Ultrasound for Dyspnea


Lung ultrasound: a new tool for the cardiologist

  1. The main application of LUS for the cardiologist is the assessment of B-lines. B-lines are reverberation artifacts, originating from water-thickened pulmonary interlobular septa. Multiple B-lines are present in pulmonary congestion, and may help in the detection, semiquantification and monitoring of extravascular lung water, in the differential diagnosis of dyspnea, and in the prognostic stratification of chronic heart failure and acute coronary syndromes.
  2. LUS limitations are essentially patient dependent. Obese patients are frequently difficult to examine because of the thickness of their ribcage and soft tissues. The presence of subcutaneous emphysema or large thoracic dressings alters or precludes the propagation of ultrasound beams to the lung periphery.
  3. The main limitation of B-lines is the lack of specificity. As already mentioned, they are a sign of interstitial syndrome, therefore they are a very sensitive but not specific sign of cardiogenic pulmonary edema. How to distinguish the different etiologies of B-lines has been discussed. However, it must be always reminded that all instrumental data should be evaluated within the clinical context and integrated with patient’s history. No single test alone allows to establish the diagnosis.

Figure 2

Figure 3

Figure 4

Figure 1

Figure 5

Ultrasound Podcast – Lung Ultrasound with Vicki Noble – Part 1


Ultrasound Podcast – Lung Ultrasound with Vicki Noble – Part 2

IVC Ultrasound


  1. The inferior vena cava returns blood from the body to the right atrium
  2. Formed by the convergence of the iliac veins
  3. Retroperitoneal
  4. Right of the aorta
  5. Normal size <2.5 cm
  6. Varies w respiration

Stanford University – IVC


ICU Sonography – Tutorial 4 – Volume status and preload responsiveness assessment

Figure 1: Longitudinal view of the inferior vena cava (IVC): RA: right atrium. From;task=view&amp;id=36&amp;Itemid=93

Figure 3: Simultaneous measurements of the central venous pressure (CVP) and IVC diameter at the end of expiration in 108 mechanically ventilated patients.: From:;task=view&amp;id=36&amp;Itemid=93

IVC Ultrasound for Fluid Responsiveness



Podcast 86 – IVC Ultrasound for Fluid Tolerance in Spontaneously Breathing Patients – EAT IT STONE

Emcrit – IVC for Fluid Responsiveness

SMACC: The Dark Art Of IVC Ultrasound

IVC diameter (cm) IVCCI Estimated RA pressure (mm Hg)
<1.7 >50% 0-5
>1.7 >50% 6-10
>1.7 <50% 11-15
‘dilated’ none >15

Use M-mode assessment in the subxiphoid ling axis, and ideally a sniff test.

It’s probably better for ventilated patients than spontaneously breathing patients (you can remove much of the breath-to-breath variation that confounds so many of these assessment tools). It’s also probably OK at extremes (flat versus full) and serial measurements are probably a good idea.

  • No-one knows where we should measure the IVC. The IVC collapses non-uniformly. Most studies measure the IVC at or around the confluence with the hepatic veins. An influential study by Wallace et al warned against measuring at the junction with the right atrium, but with no gold standard in their study they had no actual justification for this advice.
  • No-one knows how to measure it. Many experts love M-mode, but this has serious flaws when measuring the IVC.
  • We don’t even know where to place the probe. Most studies use the subxiphoid long axis. Some recommend the subxiphoid short axis. Others (such as ACEP) recommend the midaxillary long axis. But every approach has theoretical and actual flaws. Probably the worst is the midaxillary long axis, but then again… no-one knows.
  • The sniff test is a great party trick but not validated. It seems like a waste of time to me.
  • That table above is probably useless. Everyone’s IVC is different and there are plenty of confounding factors (patient size and position, manner of breathing, measurement site…)

Ultrasound Guided Volume Assessment Using Inferior Vena Cava Diameter


Audio for the following presentation is located at:


Emcrit – Ultrasound of the IVC in the Non-Intubated Patient

The respiratory variation in inferior vena cava diameter as a guide to fluid therapy





Examining amplitude variation between inspiration and expiration phases has been extended to the plethysmographic waveform. Although this technique has several
similarities to arterial pulse pressure variation, there are several important differences.
The plethysmographic waveform obtained from a standard pulse oximeter probe is
based on transmission and reflection of infrared wavelengths of light by tissue. The
pulsatility is a function of changing tissue volume between systole and diastole,
producing the familiar wave tracing.

The pulse oximeter as a gauge of volume status first was suggested by Partridge [26] in
1987. Variation in the plethysmographic waveform has been referred to by many names:
change in pulse oximetry plethysmography (dPOP), ventilation-induced plethysmographic
variation (VPV), and DPPLET. For the sake of this article, the authors will refer to VPV (VPV(%) 5 100 ([Max amplitude Min amplitude]/[(Max amplitude Min amplitude)/2])). Cannesson and colleagues [27] reported the strong correlation (r2 5 .82,P<.001) of VPV with PPV in 22 mechanically ventilated patients. It should be noted that the precision of this correlation appears to decrease as variation increases. The Cannesson study did not demonstrate volume responsiveness, but only that VPV of greater than or equal to 15% was predictive of having PPV greater than or equal to 13%, the threshold value for volume responsiveness sited in many studies. Wyffels and colleagues [28] reported that in 32 postoperative cardiac surgery patients, PPV and VPV reliably predicted at least a 15% increase in cardiac index in response to administration of 500 mL 6% hydroxyethylstarch with an AUC (95%CI) of 0.937 (0.792 to 0.991) and 0.892 (0.731 to 0.972), respectively. Feissel and colleagues [29] demonstrated in 23 septic patients that a VPV of 14% allowed discrimination of volume responders and nonresponders with a sensitivity of 84% and specificity of 80%.

Although the obvious and tantalizing advantage to the use of the pulse oximeter to
determine fluid responsiveness is the complete noninvasiveness of the technique, at
this time, evidence does not support reliance on this method.

Adapted from Cannesson M. et. al. Br J Anesth 2008;101(2):200-206


Masimo – Clinical Evidence – Pleth Variability Index (PVI®)

Systolic pressure, pulse pressure (PPV) and stroke volume (SVV)

  1. Advanced Hemodynamic Monitoring – Can We Use Fluid to Improve Hemodynamics?
    1. In clinicians’ quest to achieve optimal oxygen delivery (DO2) they are often faced with imprecise, non-specific information in which to guide their therapy. Traditional hemodynamic monitoring parameters (HR, MAP, CVP, and PAOP) are often insensitive and sometimes misleading in the assessment of circulating blood volume. However, the appropriateness of their interventions is often crucial to avoid the deleterious effects of over-, under-, or inappropriate resuscitation. Volume is one of the first therapeutic interventions clinicians turn to when optimizing DO2.
    2. Stroke volume variation is a naturally occurring phenomenon in which the arterial pulse pressure falls during inspiration and rises during expiration due to changes in intra-thoracic pressure secondary to negative pressure ventilation (spontaneously breathing). Variations over 10mmHg have been referred to as pulsus paradoxus. The normal range of variation in spontaneously breathing patients has been reported between 5-10mmHg.
      Reverse pulsus paradoxus is the same phenomenon with controlled mechanical ventilation, however, in reverse. Arterial pressure rises during inspiration and falls during expiration due to changes in intra-thoracic pressure secondary to positive pressure ventilation. In addition to reverse pulsus paradoxus, it has also been referred to as paradoxical pulsus, respiratory paradox, systolic pressure variation and pulse pressure variation. Traditionally SVV is calculated by taking the SVmax – SVmin / SV mean over a respiratory cycle or other period of time.
    3. SVV and assessing fluid response
      SVV and its comparable measurement, pulse pressure variation (PPV), are not indicators of actual preload but of relative preload responsiveness. SVV has been shown to have a very high sensitivity and specificity when compared to traditional indicators of volume status (HR, MAP, CVP, PAD, PAOP), and their ability to determine fluid responsiveness. The following table of studies demonstrates SVV sensitivity and specificity in predicting fluid responsiveness against a specified infused volume and defined criteria for a fluid responder.
    4. image

        1. Berkenstadt H, et al. Stroke volume variation as a predictor of fluid responsiveness in patients undergoing brain surgery. Anesth Analg 2001;92:984-989.
        2. Michard F. Changes in arterial pressure during mechanical ventilation. Anesthesiology 2005; 103:419-428.
        3. Reuter DA, et al. Usefulness of left ventricular stroke volume variation to assess fluid responsiveness in patients with reduced cardiac function. Crit. Care Med 2003; 31:1300-404.

  2. Pulse pressure variation: beyond the fluid management of patients with shock
    1. In the previous issue of Critical Care, Keyl and colleagues [1] have investigated the effects of cardiac resynchronization therapy on arterial pulse pressure variation (PPV). Many studies [2] have shown that PPV is much more accurate than cardiac filling pressures and volumetric markers of preload to predict fluid responsiveness (that is, the hemodynamic effects of volume loading). PPV is also more reliable than other dynamic parameters such as systolic pressure variation [3,4] or pulse contour stroke volume variation [4]. In this respect, PPV is used increasingly in the decision-making
      process regarding volume expansion in patients with hemodynamic instability [2]. Limitations to the use of PPV do exist (mainly active breathing, cardiac arrhythmia, and low tidal volume) and have been described in detail elsewhere [2,5].
    2. As an indicator of the position on the Frank–Starling curve, PPV is as useful to predict the deleterious hemodynamic effects of fluid depletion as it is to predict the beneficial
      effects of fluid loading [6].
    3. In such clinical situations, fluid management could be refined by PPV monitoring: a large PPV or an increase in PPV indicates that the patient is operating on the steep portion of the Frank–Starling curve, and hence indicates that further ultrafiltration or further fluid restriction/depletion will induce hemodynamic
    4. Another potential field of application for PPV is the intraoperative fluid optimization of patients undergoing high-risk surgery. Several studies [11-13] have shown that monitoring and maximizing stroke volume by fluid loading (until the stroke
      volume reaches a plateau, actually the plateau of the Frank–Starling curve) during high-risk surgery is associated with improved postoperative outcome.
    5. image
  3. Pulse pressure variation: where are we today?
    1. The dynamic parameters of fluid responsiveness are related to cardiopulmonary
      interactions in patients under general anesthesia with mechanical ventilation. This is far superior to static indicators (such as central venous pressure) [1]. The advantage of these dynamic measurements is that they can be derived from a single arterial pressure waveform [systolic pressure variations (SPV), and pulse pressure variations (PPV)]. Measurement of these indicators can predict an increase in cardiac output induced by volume expansion before volume expansion is actually performed.
    2. Moreover, it is now possible to obtain PPV non invasively using respiratory variations in the pulse oximeter plethysmographic waveform amplitude (DPOP) [7, 8,17, 24–28].
    3. The goal of perioperative fluid optimization is the same than that of the cardiovascular system under normal conditions: an adequate blood flow in vitals and in traumatized
      tissues, as not to compromise the first and to enable effective wound healing in the latter [64].
    4. image
  4. Geneva Hemodynamic Research Group – How to explain simply: Pulse Pressure Variation (PPV)
  5. Systolic Pressure Variation And Stroke Volume Variation
  6. Advanced Hemodynamic Monitoring – Stroke Volume Variation
  7. The effect of graded hemorrhage and intravascular volume replacement on systolic pressure variation in humans during mechanical and spontaneous ventilation
    1. imageimage
    2. Overall, the change in SPV with each 500-mL volume shift was not as consistent during spontaneous ventilation in comparison to mechanical ventilation (Figure 5).

PPV = (Pmax–Pmin)/([Pmax+ Pmin])/2)

Criteria for calculation
–Sinus rhythm
–Passive breathing (AC mode with good synchrony)
–Tidal volume > 8 cc/kg
–Pmax and Pmin must be calculated over the same respiratory cycle

Ability of Pulse Power, Esophageal Doppler and Arterial Pulse Pressure to Estimate Rapid Changes in Stroke Volume in Humans


Clinical use of respiratory changes in arterial pulse pressure to monitor the hemodynamic effects of PEEP.


PPV Predicts the Decrease in Cardiac Index with the addition of 10 cm H2O PEEP


Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure

Baseline PPV Predicts Volume Responsiveness


Receiver Operator Characteristic (ROC) Curve for >15% increase in cardiac output to a 500 ml volume challenge in patients in septic shock


imagePPV >13%
SPV > 13%
Pra > 8 mm Hg > 8 mm Hg
Ppao > 12 mm Hg





Technical Limitations of PPV and SVV for Assessment of Preload for Assessment of Preload-Responsiveness

  1. Requires fixed HR Requires fixed HR
    1. Atrial fibrillation, frequent PVCs Atrial fibrillation, frequent PVCs
  2. Requires positive Requires positive-pressure ventilation pressure ventilation
  3. Requires no spontaneous ventilatory efforts
    1. Can not use during CPAP, PSV, A/C Can not use during CPAP, PSV, A/C
  4. Cor Pulmonale and ventricular interdependence Cor Pulmonale and ventricular interdependence
  5. Magnitude of PPV or SVV will change if tidal Magnitude of PPV or SVV will change if tidal volume changes
  6. Changes in vasomotor tone will alter the Changes in vasomotor tone will alter the PPV/SVV relation

Aortic blood velocity

  1. Respiratory Changes in Aortic Blood Velocity as an Indicator of Fluid Responsiveness in Ventilated Patients With Septic Shock
    1. image
    2. To summarize, our findings suggest that, in contrast with EDAI, DeltaVpeak is an accurate indicator of fluid responsiveness in sedated septic shock patients who are receiving mechanical ventilation and who have preserved LV systolic function. Therefore, an analysis of the DeltaVpeak could facilitate the hemodynamic management of such patients

Other Basic Fluid Management Methods

  1. Maintenance
  2. Deficits
  3. Insensible loss
  4. Estimated blood loss


  1. 4:2:1 Rule or Calculate Wt + 40 cc  [For any person weighing more than 20kg] (Miller, Basics of Anesthesia: Expert Consult, 552)
    1. MD Calc – Maintenance Fluids Calculations
    2. Steps
      1. 4 ml/kg/hr for first 10 kg (=40ml/hr)
      2. then 2 ml/kg/hr for next 10 kg (=20ml/hr)
      3. then 1 ml/kg/hr for any kgs over that
  2. Calculated weight: (IBW + ABW)/2
  3. IBW male: 110 lbs + 7 lbs * in > 5’
  4. IBW female: 100 lbs + 6 lbs * in > 5’
Maintenance Fluids Overview [UndergroundMed]



4-2-1 Rule for Maintenance Fluid Rate


Maintenance Fluids Calculation Derivations [UndergroundMed]


  1. NPO status: Calculated Wt x hrs NPO x 0.7
  2. Bowel prep ~ 1200cc
  3. Diuretics/ Urine output
  4. NGT drainage
  5. CT drainage

Insensible loss

(Volume based on Calculated Weight)

(4:6:8 Rule – The postoperative patient and his fluid and electrolyte requirements;  Mass General Handbook, Barash, 5th edition, Miller, 5th edition, Miller and Stoelting, 5th edition)

  1. Replace with Crystalloid (NS, LR, Plasmalyte)
    1. Minor: 4 mL/kg/hr
    2. Moderate: 6 mL/kg/hr
    3. Major: 8 mL/kg/hr
Case Type Volume
Non-open 2-3 cc/kg/hr

4-6 cc/kg/hr

Major Abdominal 6-10 cc/kg/hr
Trauma > 10 cc/kg/hr

Estimated blood loss

  1. The 3: 1 Rule, replace 3 cc crystalloid : 1 cc blood loss (Initial resuscitation of hemorrhagic shock)
  2. The 1:1 Rule, replace 1 cc colloid : 1 cc blood loss

Further Estimating the Total Resuscitation Volume



(Marino, The ICU Book, 236)

Hemodynamic monitoring over the past 10 years

Importantly, no monitoring device, no matter how accurate or complete, would be expected to improve patient outcome, unless coupled to a treatment that itself improves outcome [6].

End Points of Resuscitation

The goal of resuscitation in hemorrhagic shock is to restore three parameters: blood flow, oxygen transport, and tissue oxygenation. The parameters are defined by the end-points shown below.

  1. Cardiac index = 3 L/min/m2
  2. Systemic oxygen delivery (DO2)  > 500 ml/minm2
  3. Systemic oxygen uptake (VO2) > 100 ml/min/m2
  4. Arterial lactate <2 mmol/L or base deficit >-2 mmol/L

Oxygen Delivery (DO2)

The oxygen that enters the bloodstream in the lungs is carried to the vital organs by the cardiac output. The rate at which this occurs is call the oxygen delivery (DO2) The DO2 describes the volume of oxygen (in milliliters) that reaches the systemic capillaries each minute. It is equivalent to the product of the O2 content in arterial blood (CaO2) in mL/L and the cardiac output (Q) in L/min (2,5-7).

DO2 = Q x CaO2 x 10

(The multiplier of 10 is used to convert the CaO2 from mL/dL to mL/L, so the DO2 can be expressed in mL/min.) If the CaO2 is broken down into its components (1.34 x Hb x SaO2), the equation can be rewritten as,

DO2 = Q x 1.34 x Hb x SaO2 x 10

The normal DO2 in adults at rest is 900-1,100 mL/min, or 500-600 mL/min/m2 when adjusted for body size.


(Marino, The ICU Book, 27)

Oxygen Uptake (VO2)

When blood reaches the systemic capillaries, oxygen dissociates from hemoglobin and moves into the tissues. The rate at which this occurs is called the oxygen uptake (VO2). The VO2 describes the volume of oxygen (in mL) that leaves the capillary blood and moves into the tissues each minute. Since oxygen is not stored in tissues, the VO2 is also a measure of the oxygen consumption of the tissues.


(Marino, The ICU Book, 28)


Trend is more important than absolute value

Unfortunately, it is not always possible to reach these end-points despite aggressive volume replacement, and the ability to reach the desired end points is a principal determinant of survival. This is demonstrated in Figure 12.7. The graph in this figure shows the effects of controlled hemorrhage and resuscitation on oxygen uptake (VO2) in an animal model of hemorrhagic shock. Note that in the survivors, the VO2 increases and returns to the baseline (pre-hemorrhage) level in response to resuscitation. In contrast, the VO2 in the nonsurvivors shows no response to resuscitation and actually deteriorates further. Thus when hemorrhagic shock becomes refractory to volume resuscitation, the prognosis is bleak.


(Marino, The ICU Book, 203)

Blood Lactate vs. % Survival


Endpoints of Resuscitation What Should We Be Monitoring?

Major resuscitation goals in the management of shock include restoration of adequate tissue perfusion and oxygen balance and normalization of cellular metabolism…Traditional endpoints, such as heart rate, blood pressure, mental status, and urine output are useful in the initial identification of inadequate perfusion, but are limited in their ability to identify ongoing, compensated shock. Many clinicians continue to use these parameters as indicators that systemic oxygenation imbalances have resolved, even though they have been found to be poor indicators of ongoing tissue hypoxia. Additional resuscitation endpoints that more closely evaluate the adequacy of perfusion and oxygenation at the tissue level should also be used when managing the critically ill. Selected endpoints should include a variety of global and regional indicators to guide and evaluate the effectiveness of treatment.

Currently, many clinicians are using additional global and regional indicators of oxygen
transport as endpoints of resuscitation (Table 1). Evaluation of these additional endpoints will allow for rapid treatment and stabilization of systemic oxygenation during resuscitation.
Early detection and aggressive management of tissue hypoxia will assist in decreasing complications, limiting organ dysfunction, and improving outcomes. [11]


Measurement of acid-base resuscitation endpoints: lactate, base deficit, bicarbonate or what?


  1. Acid-Base Physiology – Lactic Acidosis
  2. ALiEM – Geriatric Blunt Trauma: Respect the Lactate
  3. BroomDocs – The Lactate “Debate” with Dr Seth Trueger
  4. Don’t take vitals, take a lactate
  5. EMCrit Podcast 37 – Lactate in Sepsis
  6. Emcrit Lactate FAQ
  7. EMCrit Wee – Is Lactate Clearance a Flawed Paradigm?
  8. Surviving Sepsis Campaign
  9. Trick of the Trade: Serial lactate measurements in sepsis?

Bellomo R, Ronco C. The pathogenesis of lactic acidosis in sepsis. Current Opinion in Critical Care 1999;5:452-7.

Lactic acidosis is a common finding in critically ill patients during severe sepsis/septic shock, and a powerful predictor of mortality. Because of the knowledge that lactate is the end product of anaerobic glycolysis, the presence of hyperlactatemia in sepsis has been taken to indicate the development of anaerobic glycolysis within tissues. Such anaerobic glycolysis is understood to result from oxygen “debt” at cellular level. The metabolic acidosis frequently associated with hyperlactatemia has thus been ascribed to hydrogen ions released from adenosine triphosphate hydrolysis. This simplistic view of the pathogenesis and meaning of hyperlactatemia, however, is not supported by available data. Systemic oxygen transport is usually increased rather than decreased in septic patients. Whenever studied, tissue oxygenation is either preserved or increased in septic animals and humans. In addition, lactate levels may fluctuate in response to inotropic drugs and do not consistently decrease when tissue oxygen delivery is increased. Furthermore, there is strong evidence that large amounts of lactate can be produced and released under aerobic conditions and that the pathogenesis of hyperlactatemia in septic states is complex. Such pathogenesis may involve accelerated glycolytic fluxes, the inhibition of pyruvate dehydrogenase activity, and changes in intermediary metabolism. It may also involve the need to modulate the rate and efficiency of glycolytic flux by controlling the redox state of cytoplasm and mitochondria through lactate accumulation.


Bench-to-bedside review: Lactate and the kidney

Lactate clearance as a target of therapy in sepsis: a flawed paradigm

RenalFellow – Differential Diagnosis: Lactic Acidosis – Some causes of a raised lactate

Marik PE, Bellomo R, Demla V. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. OA Critical Care 2013 Mar 01;1(1):3.

Glycolytic pathway. Epinephrine-increased glycolysis is coupled to Na[+]/K[+]-ATPase activity. From James et al.[39].

Etiology and Therapeutic Approach to Elevated Lactate Levels

2013 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2013;88(10):1127-1140

Lactate levels in clinical practice are often used as a surrogate for illness severity
and to gauge response to therapeutic interventions. The use of lactate as a clinical
prognostic tool was first suggested in 1964 by Broder and Weil1 when they observed
that a lactate level of more than 4 mmol/L was associated with poor outcomes in patients
with undifferentiated shock. Since then, much has been published on the use of lactate in a
variety of patient populations. Moreover, causes of elevated lactate levels apart from tissue
hypoperfusion have been recognized and should be considered in the appropriate clinical

Elevated lactate levels are not clearly and universally defined, but most studies use cutoff
values of 2.0 to 2.5 mmol/L,7 whereas “high” lactate levels have been defined as greater than
4.0 mmol/L in several studies.8-11 Furthermore, the “normal value” may vary depending on the assay used. The terms lactate and lactic acid are often used interchangeably, but lactate (the component measured in blood) is strictly a weak base, whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate levels, but it should be reserved for cases in which there is a corresponding acidosis (pH <7.35).12 The exact pathogenesis of elevated lactate levels in various conditions is likely multifactorial, patient specific, and disease specific. In general, lactate level elevation may be caused by increased production, decreased clearance, or a combination of both. The etiology of elevated lactate levels is perhaps best studied in shock states. Contributing factors seem to include hypoperfusion due to macrocirculatory or microcirculatory dysfunction, mitochondrial dysfunction (including a potential lack of key enzymatic cofactors), and the presence of a hypermetabolic state, among others.13-18 Liver dysfunction may contribute to increased production and decreased clearance, which becomes even more important in states of hypoperfusion.





An Evaluation of the End Points of Resuscitation

An integration of the following parameters will allow the intensivist to determine the adequacy of volume resuscitation and if/when a vasopressor agent should be initiated:

  1. Urine output
  2. Urine sodium and osmolarity
  3. Mean arterial pressure (cerebral and abdominal perfusion pressure)
  4. BUN
  5. PPV (or SVV)
  6. Heart rate
  7. Lactate
  8. Arterial pH, BE, and HCO3
  9. Mixed venous oxygen saturation SmvO2 or ScvO2
  10. Mixed venous pCO2
  11. Tissue pCO2 (sublingual capnometery or equivalent)
  12. Gastric impedance spectroscopy
  13. Skeletal muscle tissue oxygenation StO2 as measured by NIRS
  14. Extravascular lung water
  15. Intra-abdominal pressure
  16. Technology yet to be developed

Currently, the preponderance of supporting literature favors blood lactate as the optimal resuscitative end point. Because its measurement does not require specialized or invasive equipment, and because today’s technology provides rapid assay results, it possesses many advantages in addition to its validated accuracy. Other techniques that indirectly reflect
BL, such as BD, gastric mucosal pH, and venous hypercarbia, may in time prove as useful as BL, because they may correct more rapidly to adequate resuscitation than BL (less lag time). Tissue oxygen monitoring also holds promise as an emerging technique to gauge resuscitation adequacy. Further prospective goal-directed human studies in all these latter
modalities should be encouraged.



Limitations of Static Measures Central Venous Pressure

This systematic review demonstrated a very poor relationship between CVP and blood volume as well as the inability of CVP/DeltaCVP to predict the hemodynamic response to a fluid challenge. CVP should not be used to make clinical decisions regarding fluid management.

Image not available.

ROC AUC = 0.56

Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares

AUC data were available for 33 studies and correlation data for 20 studies. Overall 57% ± 13% of patients were fluid responders, with 52% ± 11% of ICU patients being fluid responders as compared to 63% ± 15% of patients in the operating room. The mean baseline CVP was 8.2 ± 2.3 mm Hg in the fluid responders and 9.5 ± 2.2 mm Hg in the nonresponders. The summary AUC was 0.56 (95% CI, 0.54–0.58), with no heterogenicity between studies (Q statistic p = 0.9, I2 = 0%). The summary AUC was 0.56 (95% CI, 0.52–0.60) for those studies done in the ICU and 0.56 (95% CI, 0.54–0.58) for those done in the operating room. Similarly, the summary AUC was 0.56 (95% CI, 0.51–0.61) for the cardiac surgery patients and 0.56 (95% CI, 0.54–0.58) for the noncardiac surgery patients. The summary correlation coefficient between the baseline CVP and the delta SVI/CI was 0.18 (95% CI, 0.1–0.25), being 0.28 (95% CI, 0.16–0.40) in the ICU patients, and 0.11 (95% CI, 0.02–0.21) in the operating room patients.

Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense

Organ Specific


Acidosis Algorithm


MUDPILES (methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, lactic acidosis, ethylene glycol, salicylates)

Both lactate and BD levels may be used to identify lactic acidosis and predict mortality at admission. Increased lactate levels predict mortality and a prolonged course regardless of the associated BD level, whereas an increased BD level has no predictive value if the lactate level is normal.

Discordance between lactate and base deficit in the surgical intensive care unit: which one do you trust?


Figure 1. Mean (±SE) Cardiac Index, Oxygen Delivery, and Oxygen Consumption in the Three Study Groups.

For each variable, the incremental area under the curve differed significantly among the three groups (P<0.001). B denotes base line. Measurements were made twice a day for five days after randomization.

A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group

Don’t Overshoot Your Mark!


Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome

During resuscitation from traumatic hemorrhagic shock, normalization of standard clinical parameters such as blood pressure, heart rate, and urine output are not adequate to guarantee survival without organ system dysfunction. Numerous parameters including hemodynamic profiles, acid-base status, gastric tonometry, and regional measures of tissue O2 and CO2 levels have been studied. Many can be useful for predicting risk of organ failure and death. Studies comparing use of these parameters as endpoints for resuscitation protocols, however, have failed to show clear benefit in terms of patient outcomes. At present, it seems prudent to use one of these endpoints rather than relying on standard clinical parameters.

East Association for the Surgery of Trauma – Resuscitation Endpoints

Concise Evolution in Treatment Strategies (I know this leaves a lot of great people out)

  1. Auto transfusion (“Cell Saver”)
  2. Hyperdynamic “Supranormal” Resuscitation (Shoemaker)
  3. Less is More – Mattox
  4. Trauma Vaccine – Vedder, et al.
  5. Hypertonic Saline
  6. Glue Grant
    1. standardization, endpoints, genetics



Dr. Rivers speaking on Sepsis from 2008

Emcrit – Fluid Resus in Severe Sepsis (Chad Meyers)







Scalea – Principles of Resuscitation

Hemostatic Resuscitation with Richard Dutton


Hypovolemia and Fluid Responsiveness


Fluid Responsiveness in the Critically Ill Patient


MEDCRAMvideos – Shock Explained Clearly!


MEDCRAMvideos – Shock Treatment Explained Clearly!




Other Coagulation presentations















SlideShare: Cardiac Output, Blood Flow, and Blood Pressure

Hypotension Flow Diagram

Hypotension and Shock

Water Balance


Indications for Damage Control Surgery

Damage control surgery: it’s evolution over the last 20 years



Management of the Bleeding Cardiac Surgical Patient



  1. 2006 – Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies: An Updated Report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies
  2. 2010 – Management of bleeding following major trauma: an updated European guideline
  3. 2012 – Clinical Practice Guide on Red Blood Cell Transfusion
  4. Ann Intern Med – Red blood cell transfusion: a clinical practice guideline from the AABB
  5. Australia – National Blood Authority – Patient Blood Management Guidelines
  6. Blood transfusion: indications, administration and adverse reactions
  7. Guidelines for Prehospital Fluid Resuscitation in the Injured Patient
  8. Translating resuscitation guidelines into practice: health care provider attitudes, preferences and beliefs regarding pediatric fluid resuscitation performance
  9. Preferences of critical care registrars in fluid resuscitation of major trauma patients: concordance with current guidelines
  10. Inflammation and the Host Response to Injury, a Large-Scale Collaborative Project: Patient-Oriented Research Core—Standard Operating Procedures for Clinical Care: III. Guidelines for Shock Resuscitation
  11. Trauma Exsanguination Protocol Improves Survival and Blood Product Use
  12. East Association for the Surgery of Trauma – Resuscitation Endpoints
  13. East Association for the Surgery of Trauma – Prehospital Fluid Resuscitation in the Injured Patient
  14. East Association for the Surgery of Trauma – Red Blood Cell Transfusion in Adult Trauma and Critical Care
  15. East Association for the Surgery of Trauma – Geriatric Trauma: Parameters for Resuscitation
  16. Suviving Sepsis 2012 Guidelines

Interesting Studies and Clinical Trials

  1. ARISE-RCT: Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial
  2. Crash 2
  3. Falls Protocol
  4. FEAST (Fluid Expansion as Supportive Therapy) Trial
  5. Harborview Study – 7.5% Saline and 7.5% Saline/6% Dextran for Hypovolemic Shock
  6. Matters Study (JAMA Surgery)
  7. ProCESS – Protocolized Care for Early Septic Shock
  8. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks
  9. Resuscitation Outcomes Consortium
  10. Saline vs. Albumin Fluid Evaluation Study (SAFE)
  11. TRICC trial

Blogs, Podcasts, and other Resources

  1. ALiEM
    1. Choosing the right vasopressor agent in hypotension
    2. Deciphering Acid-Base Disorders
    3. Do you know your resuscitation room?
    4. Geriatric Blunt Trauma: Respect the Lactate
    5. P-Video: Rule of 15 in anion gap metabolic acidosis
    6. Patwari Academy video: Early goal directed therapy
    7. Paucis Verbis: Composition of intravenous fluids
    8. Trick of Trade: Rule of 10′s for burn fluid resuscitation
    9. RUSH protocol: Rapid Ultrasound for Shock and Hypotension
    10. Sneak Peak “Trick of the Trade”: IO line for failed IV access
    11. Trick of the Trade: Serial lactate measurements in sepsis?
  2. BoringEM
    1. Normal Saline: The Coke of Crystalloid Fluids
  3. BroomeDocs
    1. Should Normal saline be the norm?
    2. The Lactate “Debate” with Dr Seth Trueger
    3. Remote Resuscitation
  4. CrashingPatient
    1. Fluid Resuscitation
    2. Hemodynamic Monitoring
    3. Predicting Fluid Responsiveness
  5. CriticalCareReviews
    1. Fluid Responsiveness
  6. CriticalEcho
    1. Tutorial 4 – Volume status and preload responsiveness assessment – Volume status and preload responsiveness assessment
  7. Emcrit
    1. Hemostatic Resuscitation by Richard Dutton, MD
    2. Podcast 12 – Trauma Resus: Part I
      1. Thoughts on the Resuscitation of the Critically Ill Trauma Patient
      2. Damage Control Anesthesia
    3. Podcast 13 – Trauma Resus II: Massive Transfusion
    4. Podcast 30 – Hemorrhagic Shock Resuscitation
    5. EMCrit Podcast 37 – Lactate in Sepsis
    6. EMCrit Wee – Is Lactate Clearance a Flawed Paradigm?
    7. EMCrit Podcast 49 – The Mind of a Resus Doc: Logistics over Strategy
    8. Emcrit Acid Base Series

      1. Podcast 44 – Acid Base: Part I
      2. Podcast 45 – Acid Base: Part II
      3. Podcast 46 – Acid Base: Part III
      4. Podcast 50 – Acid Base Part IV – Choose the Solution Based on the Problem
      5. Podcast 96 – Acid Base in the Critically Ill – Part V – Enough with the Bicarb Already
      6. Podcast 97 – Acid-Base VI – Chloride-Free Sodium
    9. Podcast 50 – Acid Base Part IV – Choose the Solution Based on the Problem
      1. Vimeo – Acid Base Lecture Part II
      2. Vimeo – Acid Base III
    10. Podcast 64 – Fluid Responsiveness with Dr. Paul Marik
    11. Podcast 85 – A Confirmation of Prejudices: Chloride and Pressure Poisoning
    12. Podcast 86 – IVC Ultrasound for Fluid Tolerance in Spontaneously Breathing Patients – EAT IT STONE – Can the Inferior Vena Cava Ultrasound guide our fluid administration in the ED? Of course it can!
    13. Podcast 90 – Mind of the Resuscitationist Series: Cliff Reid’s Own the Resus Room
    14. Podcast 109 – Mind of the Resuscitationist from SMACC 2013
    15. Rapid Ultrasound for Shock and Hypotension – the RUSH Exam
      1. Original RUSH Article
    16. SMACC Back 2 – IVC for Decisions on Fluid Status
    17. What Will it Take to Kill off CVP?
  8. Emergency Medicine Literature of Note
    1. Chloride-Restriction & More JAMA Inadequacy
    2. Put Hydroxyethyl Starch Away
  9. ERCast
    1. Chest Trauma with Kenji Inaba
    2. How to put in a chest tube
  10. Intensive Care Network
    1. Cath Hurn: There will be Blood! (Massive Transfusion & Hemostatic Resuscitation)
    2. Drenzla on the Fluid Debate
    3. Fluid Therapy by Prof John Myburgh
    4. Podcast 32: Holley on Transfusion
    5. SMACC: Harris – Cardiac Output in the Resuscitation Room – Have you considered the right side?
    6. SMACC: Myburgh on Fluid Resuscitation
    7. SMACC: Johnston on the Assessment of Shock
    8. SMACC: Weingart – The Mind of the Resuscitationist
  11. LifeInTheFastLane
    1. Shock… Do We Know It When We See It?
    2. Fluid Responsiveness
      1. CCC — Fluid challenge
      2. CCC — Passive leg raise
      3. CCC — Systolic Pressure Variation
    3. Managing the Critical Bleeder
    4. SMACC: The Dark Art Of IVC Ultrasound
    5. CVP Measurement
  12. Medscape
    1. An Update on Intravenous Fluids
    2. Dehydration Treatment & Management
    3. Early Fluid Resuscitation Reduces Sepsis Mortality
    4. Fluid Replacement in Critical Care: A New Look at an Old Issue
    5. Fluid Resuscitation in Sepsis and Hemorrhagic Shock: What Do the Data Show?
    6. Fluid Resuscitation in Septic Shock
    7. Fluid Resuscitation Ups Mortality Risk in Children
    8. Hemodynamic Tools in the ICU
    9. The Great Fluid Debate Revisited
    1. Collapsible IVC predicts ‘low’ CVP
    2. End expiratory occlusion
    3. European Trauma Bleeding Guidelines updated
    4. Evidence refutes ATLS shock classification
    5. Fluids contribute to acid-base disturbance on ICU
    6. Predicting volume responsiveness
  14. Sancrit
    1. Fluid Challenges and Arterial Blood Pressure
  15. ShortCoatsInEM
    1. What’s Your Trigger?
  16. SonoSpot: Topics in Bedside Ultrasound
      1. SonoCase: 45 yr old female acute respiratory distress…. RUSH, part deux
      2. SonoCase: 78 yr old, hypotensive, altered…Welcome to “RUSH” week!
  17. UltrasoundPodcast
    1. Integrated ultrasound approach to Fluid Responsiveness……Canadian Style. #FOAMED


  1. 7.5% Saline and 7.5% Saline/6% Dextran for Hypovolemic Shock
  2. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit
  3. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
  4. A novel method for the assessment of the accuracy of computing laminar flow stroke volumes using a real-time 3D ultrasound system: In vitro studies
  5. A physicochemical model of crystalloid infusion on acid-base status
  6. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers
  7. A rational approach to perioperative fluid management
  8. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group
  9. Ability of Pulse Power, Esophageal Doppler and Arterial Pulse Pressure to Estimate Rapid Changes in Stroke Volume in Humans
  10. Accurate characterization of extravascular lung water in acute respiratory distress syndrome
  11. Acid-base balance in peritoneal dialysis patients: a Stewart-Fencl analysis
  12. Aggressive early crystalloid resuscitation adversely affects outcomes in adult blunt trauma patients: an analysis of the Glue Grant database
  13. An Evaluation of the End Points of Resuscitation
  14. Application of Base Deficit in Resuscitation of Trauma Patients
  15. Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock
  16. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a “gray zone” approach
  17. Assessment of fluid responsiveness during increased intra-abdominal pressure: keep the indices, but change the thresholds
  18. Assessment of intravascular fluid status and fluid responsiveness during  mechanical ventilation in surgical and intensive care patients
  19. Assessment of intravascular volume: a comedy of errors
  20. Assessment of intravascular volume status and volume responsiveness in critically ill patients
  21. Assessment of volume responsiveness during mechanical ventilation – recent advances
  22. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults
  23. Base deficit as a guide to volume resuscitation
  24. Bench-to-bedside review: Resuscitation in the emergency department
  25. Bioreactance is not reliable for estimating cardiac output and the effects of passive leg raising in critically ill patients
  26. Brachial artery peak velocity variation to predict fluid responsiveness in mechanically ventilated patients
  27. Can changes in arterial pressure be used to detect changes in cardiac index during fluid challenge in patients with septic shock?
  28. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge
  29. Cardiac output measurements using the bioreactance technique in critically ill patients
  30. Causes of death after fluid bolus resuscitation – New Insights from FEAST
  31. Central venous blood oxygen saturation: an early, accurate measurement of volume during hemorrhage
  32. Changes in BP induced by passive leg raising predict response to fluid loading in critically ill patients
  33. Changes in Arterial Pressure during Mechanical Ventilation
  34. Changes in pulse pressure variability during cardiac resynchronization therapy in mechanically ventilated patients
  35. Clinical controversies in the management of critically ill patients with severe sepsis: Resuscitation fluids and glucose control
  36. Clinical review: Acid–base abnormalities in the intensive care unit – part II
  37. Clinical review: Hemorrhagic shock
  38. Clinical review: Myocardial depression in sepsis and septic shock
  39. Clinical review: The meaning of acid–base abnormalities in the intensive care unit – effects of fluid administration
  40. Clinical review: The role of ultrasound in estimating extra-vascular lung water
  41. Clinical review: Update on hemodynamic monitoring – a consensus of 16
  42. Clinical review: Volume of fluid resuscitation and the incidence of acute kidney injury – a systematic review
  43. Clinical use of respiratory changes in arterial pulse pressure to monitor the hemodynamic effects of PEEP.
  44. Colloids and crystalloids: does it matter to the kidney?
  45. Colloids versus crystalloids for fluid resuscitation in critically ill patients
  46. Comparison of an automated respiratory systolic variation test with dynamic preload indicators to predict fluid responsiveness after major surgery
  47. Comparison of arterial pressure and plethysmographic waveform-based dynamic preload variables in assessing fluid responsiveness and dynamic arterial tone in patients undergoing major hepatic resection
  48. Comparison of monitoring performance of Bioreactance vs. pulse contour during lung recruitment maneuvers
  49. Comparison of stroke volume and fluid responsiveness measurements in commonly used technologies for goal-directed therapy
  50. Comparison of three techniques using the Parkland Formula to aid fluid resuscitation in adult burns
  51. Crystalloids vs. colloids: KO at the twelfth round?
  52. Current practice in hemodynamic monitoring and management in high-risk surgery patients – a national survey of Korean anesthesiologists
  53. Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization
  54. Damage control resuscitation from major haemorrhage in polytrauma
  55. Damage Control Resuscitation: The New Face of Damage Control
  56. Damage control surgery: it’s evolution over the last 20 years
  57. Decreases in organ blood flows associated with increases in sublingual PCO2 during hemorrhagic shock
  58. Determination of the optimal mean arterial pressure for postbleeding resuscitation after hemorrhagic shock in rats
  59. Differences in acid-base behavior between intensive care unit survivors and nonsurvivors using both a physicochemical and a standard base excess approach: a prospective, observational study
  60. Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS)
  61. Discordance between lactate and base deficit in the surgical intensive care unit: which one do you trust?
  62. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study
  63. Do colloids in comparison to crystalloids for fluid resuscitation improve mortality?
  64. Does Central Venous Pressure Predict Fluid Responsiveness
  65. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares
  66. Does the central venous pressure predict fluid responsiveness – An updated meta-analysis and a plea for some common sense
  67. Don’t take vitals, take a lactate
  68. Dynamic and volumetric variables of fluid responsiveness fail during immediate postresuscitation period
  69. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients – a systematic review of the literature
  70. Echocardiographic Assessment of Preload Responsiveness in Critically Ill Patients
  71. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study
  72. Effect of blood pressure on hemorrhage volume and survival in a near-fatal hemorrhage model incorporating a vascular injury
  73. Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic Shock – The CRISTAL Randomized Trial
  74. Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis
  75. Elevated Arterial Base Deficit in Trauma Patients: A Marker of Impaired Oxygen Utilization
  76. Emergency Department Bedside Ultrasonographic Measurement of the Caval Index for Noninvasive Determination of Low Central Venous Pressure
  77. Emerging trends in minimally invasive haemodynamic monitoring and optimization of fluid therapy
  78. End-diastolic volume. A better indicator of preload in the critically ill
  79. Endpoints of Resuscitation What Should We Be Monitoring?
  80. End-Expiratory Occlusion Test Predicts Preload Responsiveness Independently of Positive End-Expiratory Pressure During Acute Respiratory Distress Syndrome
  81. End-tidal carbon dioxide is better than arterial pressure for predicting volume responsiveness by the passive leg raising test
  82. Evaluation of stroke volume variations obtained with the pressure recording analytic method
  83. Excess mortality associated with the use of a rapid infusion system at a level 1 trauma center
  84. Extravascular lung water in sepsis-associated acute respiratory distress syndrome: indexing with predicted body weight improves correlation with severity of illness and survival
  85. Extravascular lung water measurements and hemodynamic monitoring in the critically ill: bedside alternatives to the pulmonary artery catheter
  86. Fluid administration limited by lung sonography: the place of lung ultrasound in assessment of acute circulatory failure (the FALLS-protocol)
  87. Fluid challenge revisited
  88. Fluid resuscitation in patients with traumatic brain injury: what is a SAFE approach?
  89. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality
  90. Fluid resuscitation in traumatic hemorrhagic shock
  91. Fluid Status and Fluid Responsiveness
  92. Fluid Therapy in Resuscitated Sepsis: Less is More
  93. Functional hemodynamic monitoring and dynamic indices of fluid responsiveness
  94. Graphic aids for calculation of fluid resuscitation requirements in pediatric burns
  95. Goal-Directed Fluid Management Based on the Pulse Oximeter–Derived Pleth Variability Index Reduces Lactate Levels and Improves Fluid Management
  96. Goal-directed intraoperative fluid therapy guided by stroke volume and its variation in high-risk surgical patients – a prospective randomized multicentre study
  97. Goal-directed therapy in intraoperative fluid and hemodynamic management
  98. Goal-directed resuscitation in the prehospital setting: A propensity-adjusted analysis
  99. Greater cardiac response of colloid than saline fluid loading in septic and non-septic critically ill patients with clinical hypovolaemia
  100. Hemodynamic monitoring over the past 10 years
  101. Hemodynamic parameters to guide fluid therapy
  102. Hemodynamic pressure waveform analysis in predicting fluid responsiveness
  103. How to measure and interpret volumetric measures of preload
  104. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis
  105. Hydroxyethyl starch in severe sepsis: end of starch era?
  106. Hypertonic resuscitation of hemorrhagic shock prevents alveolar macrophage activation by preventing systemic oxidative stress due to gut ischemia/reperfusion
  107. Hypotensive Resuscitation in Patients with Ruptured Abdominal Aortic Aneurysm
  108. Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion
  109. Hypothermia in massive transfusion: have we been paying enough attention to it?
  110. Hypovolemic Shock Evaluated by Sonographic Measurement of the Inferior Vena Cava During Resuscitation in Trauma Patients
  111. Hypovolemic shock resuscitation
  112. The ideal crystalloid – what is ‘balanced’?
  113. Ideal permissive hypotension to resuscitate uncontrolled hemorrhagic shock and the tolerance time in rats
  114. Immediate versus Delayed Fluid Resuscitation for Hypotensive Patients with Penetrating Torso Injuries
  115. Impact of prehospital hypothermia on transfusion requirements and outcomes
  116. Impairment of coagulation by commonly used resuscitation fluids in human volunteers
  117. Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model
  118. Induced hypothermia does not impair coagulation system in a swine multiple trauma model
  119. In Search of the Optimal End Points of Resuscitation in Trauma Patients: A Review
  120. Inferior Vena Cava Distensibility as a Predictor of Fluid Responsiveness in Patients with Subarachnoid Hemorrhage
  121. Inferior Vena Cava Percentage Collapse During Respiration Is Affected by the Sampling Location: An Ultrasound Study in Healthy Volunteers
  122. Intensivist Bedside Ultrasound (INBU) for Volume Assessment in the Intensive Care Unit: A Pilot Study
  123. Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis
  124. Intraoperative fluid restriction improves outcome after major elective gastrointestinal surgery
  125. Intravenous fluid resuscitation: was Poiseuille right?
  126. Initial resuscitation of hemorrhagic shock
  127. Integrating lung ultrasound in the hemodynamic evaluation of acute circulatory failure (the fluid administration limited by lung sonography protocol)
  128. Is albumin use SAFE in patients with traumatic brain injury?
  129. Lactate clearance as a target of therapy in sepsis: a flawed paradigm
  130. Language Guiding Therapy: The Case of Dehydration versus Volume Depletion
  131. Less invasive methods of advanced hemodynamic hemodynamic monitoring principles, devices, and their role in the perioperative hemodynamic optimization
  132. Limits of corrected flow time to monitor hemodynamic status in children
  133. Lung ultrasound: a new tool for the cardiologist
  134. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte
  135. Measurement of acid-base resuscitation endpoints: lactate, base deficit, bicarbonate or what?
  136. Measuring cardiac index with a focused cardiac ultrasound examination in the ED
  137. Minimal invasive cardiac output monitoring: get the dose of fluid right
  138. Monitoring of peri-operative fluid administration by individualized goal-directed therapy
  139. Monitoring fluid responsiveness
  140. Monitoring volume and fluid responsiveness – From static to dynamic indicators
  141. Mortality after Fluid Bolus in African Children with Severe Infection
  142. New approaches to trauma management using severity of illness and outcome prediction based on noninvasive hemodynamic monitoring
  143. New insights into fluid resuscitation
  144. New strategies for massive transfusion in the bleeding trauma patient
  145. Non-invasive assessment of fluid responsiveness by changes in partial end-tidal CO2 pressure during a passive leg-raising maneuver
  146. Noninvasive Cardiac Output Monitors: A State-of the-Art Review
  147. Noninvasive Hemoglobin Monitoring: How Accurate Is Enough?
  148. Noninvasive Monitoring of the Autonomic Nervous System and Hemodynamics of Patients With Blunt and Penetrating Trauma
  149. Non-invasive prediction of fluid responsiveness during major hepatic surgery
  150. Novel rapid infusion device for patients in emergency situations
  151. The Use of Normal Saline for Resuscitation in Trauma
  152. Optimizing perioperative hemodynamics – what is new
  153. Outcome prediction by a mathematical model based on noninvasive hemodynamic monitoring
  154. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial
  155. Passive leg raising: good for everyone?
  156. Passive leg-raising and end-expiratory occlusion tests perform better than pulse pressure variation in patients with low respiratory system compliance
  157. Passive leg raising-induced changes in mean radial artery pressure can be used to assess preload dependence
  158. Passive leg raising predicts fluid responsiveness in the critically ill
  159. Permissive hypotension and desmopressin enhance clot formation
  160. Permissive hypotension does not reduce regional organ perfusion compared to normotensive resuscitation: animal study with fluorescent microspheres
  161. Pleth variability index is a weak predictor of fluid responsiveness in patients receiving norepinephrine
  162. Plethysmographic variation index predicts fluid responsiveness in ventilated patients in the early phase of septic shock in the emergency department – A pilot study
  163. Post hoc ergo propter hoc: the story of the Resuscitation Outcomes Consortium.
  164. Pred of Responsiveness to an IV Fluid Challenge in Patients After Cardiac Surgery with Cardiopulmonary Bypass – A Comparison Arterial Pulse Pressure Variation and Digital Plethysmographic Var Index
  165. Predicting cardiac output responses to passive leg raising by a PEEP-induced increase in central venous pressure, in cardiac surgery patients
  166. Predicting Fluid Responsiveness in ICU Patients – a critical analysis of the evidence
  167. Predicting fluid responsiveness in patients undergoing cardiac surgery: functional haemodynamic parameters including the Respiratory Systolic Variation Test and static preload indicators
  168. Predicting fluid responsiveness
  169. Predicting fluid responsiveness with transthoracic echocardiography is not yet evidence based
  170. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients
  171. Prediction of fluid responsiveness by a continuous non-invasive assessment of arterial pressure in critically ill patients – comparison with four other dynamic indices
  172. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence
  173. Prediction of fluid responsiveness in patients during cardiac surgery
  174. Predictors of pulmonary edema formation during fluid loading in the critically ill with presumed hypovolemia
  175. Pre-ejection period variations predict the fluid responsiveness of septic ventilated patients
  176. Principles of Doppler Echocardiography and the Doppler Examination #1
  177. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients    (commentary)
  178. Pulmonary artery catheter versus pulse contour analysis: a prospective epidemiological study
  179. Pulmonary lactate release in patients with sepsis and the adult respiratory distress syndrome
  180. Pulmonary lactate release in patients with acute lung injury is not attributable to lung tissue hypoxia
  181. Pulse pressure variation: beyond the fluid management of patients with shock
  182. Pulse pressure variation and stroke volume variation: from flying blind to flying right?
  183. Pulse pressure variation: where are we today?
  184. Relation between Respiratory Changes in Arterial Pulse Pressure and Fluid Responsiveness in Septic Patients with Acute Circulatory Failure
  185. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock
  186. Respiratory variation in aortic blood flow velocity as a predictor of fluid responsiveness in children after repair of ventricular septal defect
  187. Respiratory variations in aortic blood flow predict fluid responsiveness in ventilated children
  188. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use
  189. Resuscitation and transfusion management in trauma patients: emerging concepts
  190. Resuscitation Fluids
  191. Resuscitation from severe hemorrhage
  192. Resuscitation of the Critically Ill in the ED – Responses of Blood Pressure, Heart Rate, Shock Index, Central Venous Oxygen Saturation, and Lactic Acid
  193. Role of colloids in traumatic brain injury: Use or not to be used?
  194. Sodium Bicarbonate for the Treatment of Lactic Acidosis
  195. Shock: Ultrasound to Guide Diagnosis and Therapy
  196. Steady-state and time-dependent thermodynamic modeling of the effect of intravenous infusion of warm and cold fluids
  197. Stroke volume variation: from applied physiology to improved outcomes
  198. Stroke volume variations
  199. Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders
  200. Sublingual capnometry for diagnosis and quantitation of circulatory shock
  201. Sublingual capnometry for rapid determination of the severity of hemorrhagic shock
  202. Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome
  203. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock
  204. Target blood pressure for hypotensive resuscitation
  205. The acute coagulopathy of trauma shock: clinical relevance
  206. The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan
  207. The biochemical effects of restricting chloride-rich fluids in intensive care
  208. The effect of graded hemorrhage and intravascular volume replacement on systolic pressure variation in humans during mechanical and spontaneous ventilation
  209. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients
  210. The effect of breathing manner on inferior vena caval diameter
  211. The effects of propofol and dexmedetomidine infusion on fluid responsiveness in critically ill patients
  212. The effects of saline or albumin resuscitation on acid-base status and serum electrolytes
  213. The Efficacy and Safety of Colloid Resuscitation in the Critically Ill
  214. The history of 0.9% saline
  215. The impact of phenylephrine, ephedrine, and increased preload on third-generation Vigileo-FloTrac and esophageal doppler cardiac output measurements
  216. The influence of the airway driving pressure on pulsed pressure variation as a predictor of fluid responsiveness
  217. The Interrater Reliability of Inferior Vena Cava Ultrasound by Bedside Clinician Sonographers in Emergency Department Patients
  218. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks
  219. The rational clinical examination. Is this patient hypovolemic?
  220. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy
  221. The rule regulating pH changes during crystalloid infusion
  222. The Sonodynamic Study: Comparison of Qualitative Versus Quantitative Assessment and Inter-Rater Reliability In Serial Ultrasonography Evaluations of Inferior Vena Cava Dynamics and Left Ventricular Systolic Function In Fluid Resuscitation of Emergency Department Patients With Symptomatic Hypotension
  223. The status of massive transfusion protocols in United States trauma centers: massive transfusion or massive confusion?
  224. The Stewart approach–one clinician’s perspective
  225. The use of bioreactance and carotid Doppler to determine volume responsiveness and blood flow redistribution following passive leg raising in hemodynamically unstable patients
  226. The use of volume kinetics to optimize fluid therapy
  227. The utility of base deficit and arterial lactate in differentiating major from minor injury in trauma patients with normal vital signs
  228. Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock
  229. Tissue oxygen saturation predicts the development of organ dysfunction during traumatic shock resuscitation
  230. Transthoracic echocardiography does not improve prediction of outcome over APACHE II in medical-surgical intensive care
  231. Treatment of lactic acidosis: appropriate confusion
  232. Ultrasound lung comets: a clinically useful sign of extravascular lung water
  233. Ultrasound for the detection of intraperitoneal fluid: the role of Trendelenburg positioning
  234. Ultrasound Guided Volume Assessment Using Inferior Vena Cava Diameter
  235. Ultrasound of the Inferior Vena Cava Does Not Predict Hemodynamic Response to Early Hemorrhage
  236. Use of the Trendelenburg Position as the Resuscitation Position: To T or Not to T?
  237. Use of Ultrasound to Assess Fluid Responsiveness in the Intensive Care Unit
  238. Volume Management in Critically Ill Patients – New Insights
  239. What is a fluid challenge?
  240. What’s new in critical illness and injury science? the ongoing debate on the optimal resuscitative fluid and monitoring parameters
  241. What’s new in resuscitation strategies for the patient with multiple trauma

Ventilation and Perfusion


  1. Oxygen delivery (DO2)
    1. The amount of oxygen pumped to the tissues by the heart
  2. Oxygen consumption (VO2)
    1. The amount of oxygen consumed by the tissues
    2. Oxygen demand
      1. The amount of oxygen required by the tissues to function aerobically
      2. May exceed both oxygen delivery and consumption during critical illness
  3. Eupnea – normal breathing pattern
  4. Dyspnea – difficulty breathing, shortness of breath, air hunger
  5. Orthopnea – difficulty breathing unless in a sitting or standing position; not uncommon in severe cardiac and pulmonary disease
  6. Paroxysmal nocturnal dyspnea –  attacks of severe shortness of breath and coughing that generally occur at night
  7. Apnea – cessation of breathing
  8. Tachypnea – >24/min and shallow
  9. Bradypnea – <10/min and regular
  10. Hypoxia – – inadequate cellular O2, partial pressure is around 100 mmHg (13.3 kPa)
  11. Hypercapnia – excess CO2 in the blood, (generally PaCO2 greater than 10 kPa or 75 mmHg
  12. Hypoxemia – deficient arterial PO2, abnormally low level of oxygen in the blood
  13. Hyperventilation – Increased rate and increased depth
  14. Hypoventilation – Decreased rate, decreased depth, and irregular pattern

Measured Parameters

  1. P- partial pressure – In a mixture of gases, each gas has a partial pressure which is the hypothetical pressure of that gas if it alone occupied the volume of the mixture at the same temperature. The partial pressure of a gas is a measure of thermodynamic activity of the gas’s molecules. Gases dissolve, diffuse, and react according to their partial pressures, and not according to their concentrations in gas mixtures or liquids.
  2. Arterial oxygen tension (PaO2) – (Normal range: 80-100 mm Hg) partial pressure of oxygen in arterial blood, typically measured via ABG. It describes the amount of oxygen dissolved in arterial blood plasma.
  3. Arterial carbon dioxide tension (PaCO2) – (Normal range: 35-45 mmHg) partial pressure of arterial carbon dioxide in blood
  4. PVO2 – partial pressure of venous oxygen – (Normal Range: 40 mm Hg)
  5. PVCO2 – partial pressure of venous carbon dioxide – (Normal Range: 46 mm Hg)
  6. P50 – partial pressure of oxygen when the hemoglobin is 50% saturated (Normal Range: 26-28 mmHg).

    Roughly speaking all other things being equal PaO2 and SaO2 relate as follows:
    SaO2 50% = Pa02 26.6 mmHg (aka P50); 70=40; 90=60; 95=80; 99=100 (These numbers change depending on which way the curve shifts.)

  7. Arterial oxygen saturation (SaO2 or SpO2) – (Normal Range: 95-100%) is an estimation of the oxygen saturation level usually measured with a pulse oximeter device. It can be calculated with the pulse oximetry according to the following formula (where HbO2 is the concentration of oxyhemoglobin and Hb is the concentration of deoxyhemoglobin):


    *Don’t confuse #2 and #7 they are similar, but not the same

  8. Mixed venous oxygen saturation (SvO2) – (Normal Range: 65-70%) Pulmonary artery catheterization allows for obtaining true mixed venous oxygen saturation. Venous O2 saturations differ among several organ systems, since they extract different amounts of O2.
  9. Central venous oxygen saturation (ScvO2)(Normal Range: 25-30%) Central venous catheter reflects principally the degree of oxygen extraction from the brain and the upper part of the body. ScvO2 is usually less than SvO2 by about 2–3% because the lower body extracts less O2 than the upper body making inferior vena caval O2 saturation higher. The primary cause of the lower O2 extraction is that many of the vascular circuits that drain into the inferior vena cava use blood flow for nonoxidative phosphorylation needs (e.g., renal blood flow, portal flow, and hepatic blood flow).
  10. Venous oxygen tension (PvO2) – (Normal Range: 35-45) is the partial pressure of Oxygen in venous blood.
  11. Hemoglobin (Hgb) – (Normal Range: Male: 13.8 to 17.2 gm/d, Female: 12.1 to 15.1 gm/d) is the iron-containing oxygen-transport metalloproteinin the red blood cells. It is a globular protein consisting of four subunits, with each subunit containing a heme moiety, which is an iron-binding porphyrin, and a polypeptid chain, which is designated either alpha or beta. Adult hemoglobin (hemoglobin A) is called alpha 2 beta 2 hemoglobin; two of the subunits have alpha chains and two have beta chains. Each subunit can bind one molecule of O2 per molecule of hemoglobin. When hemoglobin is oxygenated, it is call oxyhemoglobin. For the subunits to bind to O2, iron in the heme moieties must be in the ferrous state (i.e. FE2+). There are several variants of the hemoglobin molecule, the main other varieties include Methemoglobin, Fetal hemoglobin, and Hemoglobin S.
    1. Hemoglobin Synthesis
    2. Oxyhemoglobin Dissociation Curve
      1. Hemoglobin saturation
        1. Rightward shift ==> lower SO2 for given PO2
          1. Hb releases O2 more readily
          2. increased temperature
          3. increased PCO2 (Bohr shift)
            1. The effect of PCO2 & H+ on oxyhemoglobin dissociation curve
          4. increased H+ (decreased pH)
        2. Leftward shift ==> higher SO2 for
          1. given PO2
          2. decreased temperature
          3. decreased PCO2
          4. decreased H+ (increased pH)
          5. decreased 2,3 diphosphoglycerate
          6. (DPG)- associated with stored blood interferes with release of O2 to tissues
      2. Fetal Hemoglobin
        1. The RBCs of a developing fetus contain fetal hemoglobin . The structure of fetal hemoglobin, which differs from that of adult hemoglobin, gives it a much higher affinity for oxygen. Also, fetal hemoglobin binds more oxygen than does adult hemoglobin

    Fetal Hemoglobin



    Oxygen Hemoglobin Dissociation Curve Explained
    Oxygen Hemoglobin Dissociation Curve
    Bohr Effect vs. Haldane Effect
  12. Cardiac output (CO) – (Normal Range: 4-8 L/min)
    1. CO= Stroke Volume X Heart Rate
    Physiologic Determinants of Cardiac Output
  13. Alveolar–arterial gradient (A–a gradient)
    1. is a measure of the difference between the alveolar concentration (A) of oxygen and the arterial (a) concentration of oxygen.
    2. It is used in diagnosing the source of hypoxemia.
    3. Calculated as PAO2 – PaO2
      1. PAO2 is the ‘ideal’ compartment alveolar PO2 determined from the alveolar gas equation
      2. PAO2 = PiO2 – PaCO2/0.8
    4. Increased age affects A-a Gradient (at sea level) (Normal Values)
      1. Age 20 years: 4 to 17 mmHg
      2. Age 40 years: 10 to 24 mmHg
      3. Age 60 years: 17 to 31 mmHg
      4. Age 80 years: 25 to 38 mmHg
    5. Interpretation: Hypoxemia causes differentiated by A-a Gradient
      1. Increased A-a Gradient
        1. V/Q Mismatch
          1. Congestive Heart Failure
          2. Adult Respiratory Distress Syndrome (ARDS)
          3. Pneumonia
          4. Atelectasis
        2. Pulmonary shunt
          1. Pulmonary Embolism
          2. Patent Foramen Ovale
          3. Atrial Septal Defect
        3. Alveolar hypoventilation
          1. Interstitial Lung Disease
      2. Normal A-a Gradient
        1. Hypoventilation
          1. Neuromuscular disorders
          2. Central nervous system disorder
        2. Low inspired FIO2 (e.g. high altitude)

Respiratory Volumes and Rates


  1. Total Lung Capacity (TLC) – 6.0 L (averages around 6000 ml in males and 4500 ml in females)
    1. is the total volume of your lungs. The sum of the vital capacity and the residual volume
  2. Functional Residual Capacity (FRC) – 2.4 L
    1. is the amount of air remaining in your lungs after you have completed a quiet respiratory cycle. The FRC is the sum of the expiratory reserve volume and the residual volume.
  3. Vital Capacity (VC) – 4.7 L
  4. (Resting) Tidal Volume (VT) – 0.5 L
    1. is the amount of air you move into or out of your lungs during a single respiratory cycle under resting conditions.
  5. Expiratory Reserve Volume – 1000 ml
    1. is the amount of air that you can voluntarily expel after you have completed a normal, quiet respiratory cycle. As an example, if, with maximum use of the accessory muscles, you can expel an additional 1000 ml of air, your expiratory reserve volume is 1000 ml.
  6. Residual Volume – about 1200 ml in males and 1100 ml in females
    1. is the amount of air that remains in your lungs even after a maximal exhalation
  7. Minimal Volume – ranges from 30 to 120 ml
  8. Inspiratory Reserve Volume – males averages 3300 ml, compared with 1900 ml in females
    1. is the amount of air that you can take in over and above the tidal volume. Inspiratory reserve volumes differ significantly by gender, because, on average, the lungs of males are larger than those of females.
  9. Breathing Rate – 15-20 breaths/min
  10. Physiologic Dead Space (VD) – Normal Values ~0.15 L
    1. VD = VT x ((Paco2 – PEco2)/Paco2)
      1. VD = Physiologic Dead Space (mL)
      2. VT = Tidal Volume (mL)
      3. Paco2 = PCO2 of arterial blood (mm Hg)
      4. PEco2 = PCO2 of mixed expired air (mm Hg)
    2. The concept of physiologic dead space is more abstract than the concept of anatomic dead space. By definition, the physiologic dead space is the total volume of the lungs that does not participate in gas exchange. Physiologic dead space includes the anatomic dead space of the conducting airways plus a functional dead space in the alveoli.
    3. The functional dead space can be thought of as alveoli that do not participate in gas exchange. The most important reason that alveoli do not participate in gas exchange is a mismatch of ventilation and perfusion, or so-called ventilation/perfusion defect, in which ventilated alveoli are not perfused by pulmonary capillary blood.
    4. In normal persons, the physiologic dead space is nearly equal to the anatomic dead space. The ratio of physiologic dead space to tidal volume provides an estimate of how much ventilation is “wasted” (either in the conducting airways or in nonperfused alveoli).
      1. Anatomic Dead Space can increase via:
        1. Body size
        2. Lung Volume
        3. Posture
          1. supine posture supine ~ 101 ml
          2. sitting ~ 147 ml (Fowler)
        4. Respiratory flow pattern
          1. decreased, using Fowler technique, with low VT due to the mixing effect of the heart beat below the carina, and the cone advance of laminar flow, seen at low flow velocities
        5. Lung Disease – emphysema
        6. Loss or excision of lung
        7. Endotracheal Intubation, but there is the additional volume of the circuit
        8. Position of the Jaw & Neck – increases with jaw protrusion in non-intubated
  11. Forced Vital Capacity (FVC) – 4.7 L
    1. This is the total volume of air expired after a full inspiration. Patients with obstructive lung disease usually have a normal or only slightly decreased vital capacity. Patients with restrictive lung disease have a decreased vital capacity
  12. Forced Expiratory Volume in 1 Second (FEV1) – 80-120% is normal
    1. This is the volume of air expired in the first second during maximal expiratory effort. The FEV1 is reduced in both obstructive and restrictive lung disease. The FEV1 is reduced in obstructive lung disease because of increased airway resistance. It is reduced in restrictive lung disease because of the low vital capacity.
  13. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) – (Normal Value: 75-125%)
    1. The DLCO is designed to reflect properties of the alveolar-capillary membrane, specifically the ease with which oxygen moves from inhaled air to the red blood cells in the pulmonary capillaries. The uptake of most soluble gases (such as nitrous oxide or acetylene) is limited by (and varies with) pulmonary blood flow. In contrast, the strong affinity of hemoglobin for carbon monoxide (CO), combined with the enormous capacity of the red cell mass to absorb CO, make the uptake of CO less dependent on cardiac output. Thus, diseases in which the uptake of oxygen is reduced cause parallel decreases in the uptake of CO, as measured by the DLCO.
    2. Carbon monoxide can be used to measure the diffusing capacity of the lung. The diffusing capacity of the lung is decreased in parenchymal lung disease and COPD (especially emphysema) but is normal in asthma.


  1. Atmospheric (barometric) pressure (PATM or PB) – 760 mm Hg (at sea level)
  2. Water vapor pressure (PH2O) – 47 mm Hg (37C)
  3. Standard temperature, pressure, dry (STPD) – 273 K, 760 mm Hg
  4. Body temperature, pressure, saturated (BTPS) – 310 K, 760 mm Hg, 47 mm Hg
  5. Solubility of O2 in blood – 0.003 ml O2/100 ml blood/mm Hg
  6. Solubility of CO2 in blood – 0.07 ml CO2/100 ml blood/mm Hg

Calculated Parameters

  1. Cardiac index (CI) – (Normal Range: 2.6 – 4.2 L/min per square meter) 

    The index is usually calculated using the following formula: CI = \frac{CO}{BSA} = \frac{SV*HR}{BSA}

        1. CI=Cardiac index
        2. BSA=Body surface area
        3. SV=Stroke volume
        4. HR=Heart rate
        5. CO=Cardiac output


  2. Alveolar Oxygen Tension
    1. PAO2 = FiO2 x [(PB-PH20)–(PaCO2/RQ)]
    2. PB= barometric pressure,
    3. PH2O = water vapor pressure
    4. RQ = respiratory quotient
    5. For example, PAO2= 0.30 x [(760 torr – 47 torr) – (40 torr / 0.8)]
      1. assuming normal values described below
      2. 0.30 = FiO2
      3. 760 = barometric pressure
      4. 47 = water vapor pressure
      5. 40 = PaCO2
      6. 0.8 = Respiratory Coefficient
    6. PAO2= 0.30 x 663 torr = 199 torr
    7. PAO2 can also be approximated rapidly at the bedside as 700 as torr x FiO2- 50 torr
    8. PAO2 can also be approximated with the formula (patient age in years/4)+4 if the actual is much greater than this it can indicate a possible pulmonary embolism
    9. The torr is a traditional unit of pressure, now defined as exactly 1/760 of a standard atmosphere, which in turn is defined as exactly 133.322368 pascals. Historically, one torr was intended to be the same as one “millimeter of mercury”.
  3. Pulmonary end-capillary oxygen content (CcO2) in vol% –
    1. (1.34 * Hgb * 1) + (PAO2 * 0.0031)

      Oxygen Bound + Oxygen Dissolved

      (Normal value depends on the Hgb level and the FiO2)

      1. Hgb = hemoglobin content in g%
      2. 1.34 = Amount of oxygen that 1 g of fully saturated hemoglobin can hold
      3. PAO2 = Alveolar oxygen tension in mm Hg, used in place of end-capillary PO2 (PCO2)
      4. 0.0031 = Amount of dissolved oxygen for 1 mm Hg of PaO2
    2. Note again that alveolar (PAO2) and not arterial (PaO2) oxygen tension is used in this equation
    3. The oxygen content of pulmonary end-capillary blood as it leaves the alveolus.
    4. Represents the best oxygen content possible at the end-capillary level and reflects the optimal oxygen carrying capacity of the cardiopulmonary system. The oxygen saturation is assumed to be 100%. The major determinant of CCO2 is the hemoglobin level. Therefore, a low hemoglobin level like in anemia significantly lowers the end-capillary oxygen content.
    5. It is also used in other calculations like the shunt equation.
  4. Arterial oxygen content (CaO2) (Normal Range: 17-20ml/dl)
    1. CaO2 = 1.34 X Hgb X SaO2
    2. CaO2 = O2 dissolved in Plasma + O2 combined with Hgb
    3. Calculated by adding the volume of oxygen dissolved in the plasma and the volume of combined oxygen
    4. YouTube Example – Calculating Total Oxygen Content / CaO2 (not the one shown below)
    Content of Arterial Oxygen Calculation
  5. Venous oxygen content (CvO2)  – Normal Range 12-15 vol%
    1. CvO2 = (Hgb x 1.34 x SvO2) + (PvO2 x 0.0031)
      1. Hgb = hemoglobin content in g%
      2. 1.34 = Amount of oxygen that 1 g of fully saturated hemoglobin can hold
      3. SvO2 = mixed venous oxygen saturation in Vol%
      4. PvO2 = mixed venous oxygen tension mm Hg, measured via blood gas, or estimated as 35 torr
        1. (1.34 x 15 g x 0.75) + (35 torr x 0.0031) (assuming normal mixed venous oxygen saturations) = 15.1 ml O2/dl blood + 0.11 ml O2/dl blood = 15.2 ml O2/dl blood
      5. 0.0031 = Amount of dissolved oxygen for 1 mm Hg of PaO2
    2. Mixed venous oxygen content reflects the overall oxygen level of the blood returning to the right heart, and is affected by a number of factors. Low hemoglobin levels (e.g. anemia), low oxygen saturation (e.g. hypoxemia), decrease in cardiac output (e.g. congestive heart failure), or an increase in metabolic rate (e.g. exercise) significantly lower the CvO2
  6. Arterial-venous oxygen content difference (Ca-vO2) (Normal Range: 4.2-5.0ml/dl)
    1. Ca-vO2 = CaO2 – CvO2
      1. Ca or CaO2 = Oxygen content of the arterial blood (mL O2/ 10 mL blood) in Vol% 
      2. CvO2 = mixed venous oxygen content in Vol%
    2. Myocardial Oxygen Extraction
    3. The difference in oxygen content between arterial and venous blood
      1. Represents the amount of oxygen used during one pass of blood through the body
      2. Can be used as an estimate of the patient the patient’s physiologic oxygen reserve
      3. Useful in assessing changes in oxygen consumption and cardiac output
      4. Under conditions of normal oxygen consumption and cardiac output, about 25% of the available oxygen is used for tissue metabolism. Therefore, a Ca-vO2 of 5 vol% (CaO2 20% vol%  – CvO2 15 vol%) reflects a balanced relationship between oxygen consumption and cardiac output.
      5. If the cardiac output stays unchanged or is unable to compensate for hypoxia, an increase of oxygen consumption (metabolic rate) will cause an increase Ca-vO2. A decrease oxygen consumption will cause a decrease in Ca-vO2.
      6. Central Venous and Mixed Venous Oxygen Saturation in Critically Ill Patients


      7. Factors that decrease Ca-vO2
        1. Increased cardiac output
        2. Skeletal muscle relaxation (e.g. induced by drugs)
        3. Peripheral Shunting (e.g. sepsis, trauma)
        4. Certain Poisons (e.g. cyanide prevents cellular metabolism)
        5. Hypothermia
  7. Oxygen Utilization Coefficient = Oxygen Extraction Ratio or O2ER (Normal Range: 24-28%)
    1. Oxygen utilization coefficient (OUC) = VO2I / DO2I = ~0.25
      1. If the SaO2 is maintained at a relatively high level (> 0.92), the OUC can be approximated as: = 1- SvO2
    2. Shown again, the OUC or oxygen extraction ratio (O2ER) is the ratio of Formula to Formula and represents the fraction of oxygen delivered to the microcirculation that is taken up by the tissues.


    The normal O2ER is 0.2 to 0.3, indicating that only 20–30% of the delivered oxygen is utilized. This spare capacity enables the body to cope with a fall in Formula without initially compromising aerobic respiration and Formulavaries between organs; the heart has a high O2ER (∼0.6) so it is particularly sensitive to reductions in coronary artery Formula.

  8. Oxygen delivery index (DO2I) (Normal Range: 550-650ml/min/m2)
    1. Volume of gaseous oxygen pumped from the left ventricle per minute per meter squared BSA
    2. DO2I = CI x CaO2 x 10 x dL/L
      1. The 10 dL/L corrects for the fact that CI is measured in L/min/m2 and oxygen content is measured in ml/dl
      2. This is a very important resuscitation endpoint for ensuring adequate oxygen delivery to the tissues
    Delivery of Oxygen to the Tissues–Explained without the indexes used here
  9. Oxygen consumption index (VO2I) (Normal Range: 115-165ml/min/M2)
    1. Volume of gaseous O2 returned to the right atrium per minute per meter squared BSA
    2. VO2I = CI x Ca-v O2 x 10 x dL/L
      1. The 10 dL/L corrects for the fact that CI (Cardiac Index) is measured in L/min/m2 and oxygen content is measured in ml/dl
    3. VO2I = oxygen consumption index = volume of gaseous O2 consumed by the body per minute per meter squared BSA = volume of oxygen leaving the heart – volume of oxygen returning to the heart = [(CI x CaO2) – (CI x CvO2)] x 10dL/L = CI x Ca-vO2 x 10 dL/L = ~150 ml O2/min.m2
    4. It is the amount of oxygen consumed by the tissue per minute indexed to BSA
  10. Intrapulmonary shunt (Qsp/Qt) or venous admixture (Normal Range: 3-5) 

    Venous Admixtureimage

  11. Intrapulmonary Shunt
    1. A V/Q ratio below 1.0 describes the condition where capillary blood flow is excessive relative to ventilation. The excess blood flow, know as intrapulmonary shunt, does not participate in pulmonary gas exchange. There are two types of intrapulmonary shunt.
      1. True shunt indicates the total absence of exchange between capillary blood and alveolar gas (V/Q = 0), and is equivalent to an anatomic shunt between the right and left sides of the heart.
      2. Venous admixture represents the capillary flow that does not equilibrate completely with alveolar gas (0 < V/Q < 1). As the venous admixture increases, the V/Q ratio decreases until it reaches true shunt conditions (V/Q = 0).
    2. The fraction of the cardiac output that represents intrapulmonary shunt is known as the shunt fraction.
      1. In normal subjects, intrapulmonary shunt flow (Qs) represents less than 10% of total cardiac output (Qt), so the shunt fraction (Qs/Qt) is less than 10%.
      2. Intrapulmonary shunt fraction increases when small airways are occluded (e.g. asthma), when alveoli are filled with fluid (e.g. pulmonary edema, pneumonia), when alveoli collapse (e.g. atelectasis), or when capillary flow is excessive (e.g. nonembolized regions of lung in pulmonary embolism).
    3. For individuals who are breathing spontaneously
      1. Qsp/Qt = (CcO2 – CaO2) / (5 + CcO2 – CaO2)
    4. For critically ill patients receiving mechanical ventilation with or without PEEP
      1. Qsp/Qt = (CcO2 – CaO2) / (3.5 + CcO2 – CaO2)
        1. CcO2 = end capillary oxygen content vol%
        2. CaO2 = arterial oxygen content vol%
        3. Constants are either 5 or 3.5 cm H2O
    5. Blood which does not pass through ventilated portions of the lung and leaves the lung desaturated
      1. Normal  intrapulmonary shunt sun is 2-5%
      2. May exceed 50% in patients with severe acute respiratory distress syndrome (ARDS)
    6. The estimated shunt equation does not require a mixed venous blood sample. It is less accurate than the physiologic shunt equation. In normal subjects 5 vol% may be used as the estimated arterial mixed venous oxygen content difference Ca-vO2 as a result of the increased cardiac output or decreased oxygen consumption (extraction).
    7. Degree of Intrapulmonary Shunt
      1. A calculated shunt of less than 10% is normal in clinical settings.
      2. A shunt of 10-20% indicates mild intrapulmonary shunting, and
      3. a shunt of 20-30% indicates a significant intrapulmonary shunting.
      4. Greater than 30% of the calculated shunt reflects critical and severe intrapulmonary shunting.


    8. With a 50 % shunt of QT , increase in FIO2 results in no increase in PAO2, therefore, in this case treatment of hypoxemia is not increasing the FIO2 , and is decreasing the percentage of the shunt ( bronchoscopy , peep , positioning , antibiotics , suctioning , diuretics )
      1. PAO2 is directly related to FIO2 in normal patients
    9. Qsp/Qt is increased in one or more of the following categories of shunt producing disease:
      1. Anatomic shunt (congenital heart disease, intrapulmonary fistulas, vascular lung tumors)
      2. Capillary shunt (atelectasis, alveolar fluid)
      3. venous admixture (hypoventilation, uneven distribution of ventilation, diffusion defects)
    10. Abnormal Intrapulmonary shunt
      1. There are a number of sources of Qsps/Qt in the critically ill
        1. Atelectasis
        2. Lobar pneumonia
        3. Inhalation injury
        4. Drowning
        5. Acute Respiratory Distress Syndrome (ARDS)
        6. Abdominal Compartment Syndrome (ACS)
      2. Represents an “oxygen refractory” hypoxemia
        1. Shunted blood is not exposed to ventilated alveoli
        2. Can not be improved with supplemental oxygen regardless of the oxygen fraction administered
      3. Knowing how Qsps/Qt is calculated is important
        1. Definitions
          1. Qt = total cardiac output in L/min
          2. Qs = shunted portion of cardiac output
          3. Qns = normal pulmonary end-capillary blood flow that is not shunted past abnormal alveoli
          4. Therefore, Qt = Qs + Qns
          5. Total blood flow = shunted + non-shunted blood
        2. Further definitions
          1. Qt * CaO2 = total oxygen delivered to the body
            *The equation for oxygen delivery (DO2)
          2. Qs * CvO2 = total oxygen within shunted blood
            *No oxygen is added; content remains CvO2
          3. Qns * CcO = total oxygen within end-capillary blood capillary blood
          4. Therefore,
            Qt (CaO2) = Qs (CvO2) + Qns (CcOc2)
            *Total oxygen delivered = sum of the oxygen within shunted and non-shunted blood
          5. Qt (CaO2) = Qs (CvO2) + (Qt – Qs)(CcO2)
            1. Substituting (Qt – Qs) for Qns…
          6. Qt (CaO2) = Qs (CvO2) + Qt (CcO2) – Qs (CcO2)
            1. Rearranging…
          7. Qs (CcO2 – CvO2) = Qt (CcO2 – CaO2)
            1. Further rearranging…
          8. Qs/Qt = (CcO2 – CaO2) / (CcO2—CvO2)
            1. The Shunt Equation
        3. Shunt Calculation Example

Darcy’s Equation

  1. Flow = Blood Pressure / Peripheral Vascular Resistance
  2. When applied to the circulatory system, we get
    1. Q = (MAP – RAP)/TPR
      1. Q = Cardiac Output
      2. Where MAP = Mean Aortic (or Arterial) Blood Pressure in mmHg
      3. RAP = Mean Right Atrial Pressure in mmHg and
      4. TPR = Total Peripheral Resistance in dynes-sec-cm-5.
    2. However, as MAP>>RAP, and RAP is approximately 0, this can be simplified to
    3. Q ≈ MAP/TPR
    4. For the right heart Q ≈ MAP/PVR, while for the left heart Q ≈ MAP/SVR.
      1. MAP = Mean Arterial Pressure
      2. PVR = Pulmonary Vascular Resistance
      3. SVR = Systemic Vascular Resistance
  3. Physiologists will often re-arrange this equation, making MAP the subject, to study the body’s responses.As has already been stated, Q is also the product of the heart rate (HR) and the stroke volume (SV), which allows us to say:
  4. Q ≈ (HR × SV) ≈ MAP / TPR
  5. It is a generalized relationship for flow in porous media. It shows the volumetric flow rate is a function of the flow area, elevation, fluid pressure and a proportionality constant. It may be stated in several different forms depending on the flow conditions. Since its discovery, it has been found valid for any Newtonian fluid.
  6. Darcy’s Law Basics and More
Darcy’s Equation for Linear Flow

    Darcy’s Law – Example

    Oxygen Calculations

    1. Knowledge of the oxygen transport equations is essential to understanding the pathophysiology and appropriate treatment for the various shock states
    2. Pulmonary artery and central venous oximetry catheters provide the ability to monitor oxygen transport balance at the bedside
      1. Continuous mixed venous oximetry (SvO2)
      2. Continuous central venous oximetry (ScvO2)
      3. SvO2 Vs ScvO2
      4. SvO2 Vs ScvO2
      5. The SvO2 and ScvO2 change in parallel when the whole body ratio of O2 supply to demand is altered. For instance, the difference between the absolute value of ScvO2 and SvO2 changes under conditions of shock. In septic shock ScvO2 often exceeds SvO2 by about 8%. During cardiogenic or hypovolemic shock mesenteric and renal blood flow decreases followed by an increase in O2 extraction in these organs. In septic shock regional O2 consumption of the gastrointestinal tract and hence regional O2 extraction increases despite elevated regional blood flows. On the other hand, cerebral blood flow is maintained over some period in shock. This would cause a delayed drop of ScvO2 in comparison to SvO2, and the correlation between these two parameters would worsen. Some authors therefore argued that ScvO2 cannot be used as surrogate for SvO2 under conditions of circulatory shock.

        However, changes in SvO2 are closely mirrored by changes in ScvO2 under experimental and clinical conditions despite a variable difference between these two variables.

        This may explain why Rivers et al. were able to use ScvO2 higher than 70% in addition to conventional hemodynamic parameters as therapeutic endpoint for hemodynamic resuscitation to improve outcome in patients with severe sepsis and septic shock.

        From a physiological point of view, SvO2 monitoring for “early goal directed therapy” should provide similar results. Given the fact that ScvO2 exceeds SvO2 on average by 8% in patients with septic shock, a SvO2 of about 62–65% should suffice as endpoint for hemodynamic resuscitation in these conditions, although this has not been tested prospectively. However, the placement of pulmonary artery catheters and the potentially higher risk of this should not result in a delay in the start of the resuscitation of critically ill patients.

        Venous oximetry can reflect the adequacy of tissue oxygenation only if the tissue is still capable of extracting O2. In the case of arteriovenous shunting on the microcirculatory level or cell death, SvO2 and ScvO2 may not decrease or even show elevated values despite severe tissue hypoxia.

      6. Intermittent calculation of oxygen delivery
        1. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I)
        2. Once the oxygen contents throughout the vascular circuit have been calculated, the amount of oxygen delivered to the tissues (oxygen delivery index or DO2I) and the amount of oxygen consumed by the tissues (oxygen consumption index or VO2I) can be calculated.
        3. DO2I = oxygen delivery index = volume of gaseous O2 pumped from the left ventricle per minute per meter squared BSA = CI x CaO2 x 10 dL/L (the 10 dL/L corrects for the fact that CI is measured in L/min/m2 and oxygen content is measured in ml/dl) = ~600 ml O2/min.m2
        4. VO2I = oxygen consumption index = volume of gaseous O2 consumed by the body per minute per meter squared BSA = volume of oxygen leaving the heart – volume of oxygen returning to the heart = [(CI x CaO2) – (CI x CvO2)] x 10dL/L = CI x Ca-vO2 x 10 dL/L = ~150 ml O2/min.m2
        5. Two oxygenation parameters characterize the relative balance between oxygen delivery and oxygen consumption (“supply versus demand”):
          1. the oxygen utilization coefficient (OUC) and
          2. the mixed venous oxygen saturation (SvO2).
        6. The OUC, also known as the oxygen extraction ratio or O2ER, is the percentage of delivered oxygen which is consumed by the body and is calculated as follows:
          1. OUC = Oxygen utilization coefficient = VO2I / DO2I = ~0.25
          2. If the SaO2 is maintained at a relatively high level (> 0.92), the OUC can be approximated as: = 1- SvO2
        7. If the SaO2 is maintained at a relatively high level (> 0.92), the OUC can be approximated as: = 1- SvO2

    3. Fraction of Inspired Oxygen
      1. Fraction of inspired oxygen (FiO2) is the fraction or percentage of oxygen in the space being measured. Medical patients experiencing difficulty breathing are provided with oxygen-enriched air, which means a higher-than-atmospheric FiO2. Natural air includes 20.9% oxygen, which is equivalent to FiO2 of 0.21. Oxygen-enriched air has a higher FiO2 than 0.21, up to 1.00, which means 100% oxygen. FiO2 is typically maintained below 0.5 even with mechanical ventilation, to avoid oxygen toxicity.
      2. Example:
        with a nasal cannula, we assume that the fraction of oxygen that is inspired (above the normal atmospheric level or 20%) increases by 4% for every additional liter of oxygen flow administered.
      Oxygen tank FLOW RATE in liters / min FiO2 — Fraction of Inspired Oxygen value
      0 (no oxygen, just room air) .20
      1 L / min .24
      2 L / min .28
      3 L / min .32
      4 L / min .36
      5 L / min .40
      6 L / min .44
    4. Oxygen bound = Hgb conc x oxygen Hgb can carry x Hgb saturation
      1. The O2-binding capacity is the maximum amount of O2 that can be bound to hemoglobin per volume of blood, assuming that hemoglobin is 100% saturated (i.e., all four heme groups on each molecule of hemoglobin are bound to O2). The O2-binding capacity is measured by exposing blood to air with a very high PO2 (so that hemoglobin will be 100% saturated) and by correcting for the small amount of O2 that is present in the dissolved form. (To correct for dissolved O2, remember that the solubility of O2 in blood is 0.003 ml O2/100 ml blood/mm Hg.) Other information needed to calculate the O2-binding capacity is that 1 g of hemoglobin A can bind 1.34  ml O2 and that the normal concentration of hemoglobin A in the blood is 15 g/100 ml. The O2-binding capacity of blood is therefore
        1. 20.1 ml O2/100 ml blood = 15 g/100 ml x  1.34 ml O2/g hemoglobin = 20.1 ml O2/100 ml blood
      2. The figure below illustrates the MWC model for a hypothetical tetrameric protein that binds a ligand A. There are only two states the subunits can adopt, T (low affinity for A – squares) and R (high affinity, circles). In addition, no subunit can be t state unless all subunits are in the T state, and the same for the R state. Thus, there are only 2 fully symmetric quaternary states of the protein, T and R. Each protein molecule, whether T or R, can bind 0, 1, 2, 3, or 4 ligands, giving rise to all the equilibriums shown.


    Gas Laws

    1. Atmospheric Gas
      1. Barometric pressure is the sum of all gases exerting pressure on the earths surface. At sea level Atmospheric pressure is 760 mmHg. The primary components of this pressure is nitrogen, oxygen, argon and carbon dioxide.
    2. Ideal Gas Law
      1. The ideal gas law is the equation of state of a hypothetical ideal gas. It is a good approximation to the behavior of many gases under many conditions, although it has several limitations.
      2. PV = nRT
        1. P = pressure
        2. V = volume
        3. n = # of moles
        4. R = 8.31441 J K-1 mol-1
        5. T = Temperature
      3. Khan Academy – Ideal Gas Law

    3. Fick’s Law
      1. The diffusion of gas takes place according to Fick’s law it states that the rate of gas transfer across a sheet of tissue is directly proportional to
        1. the surface area of the tissue,
        2. to the diffusion constant
        3. the difference in partial pressure of the gas between the two sides of the tissue
        4. inversely proportional to the thickness of the tissue.
      2. Khan Academy – Fick’s Law of Diffusion
    4. Henry’s Law
      1. Henry’s law states that at a constant temperature, the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid.
      2. The amount of gas that can be dissolved by 1 ml of a given liquid at standard pressure and specified temperature is known as the solubility coefficient.
        1. Water Solubility of CO2 = 0.592
        2. Water Solubility of O2 = 0.0244
      3. The solubility of CO2 is about 24 times greater than O2.
      4. Khan Academy – Henry’s Law
    5. Graham’s Law
      1. Graham’s law states states the rate of diffusion or effusion for a gas is inversely proportional to the square root of the molar mass of the gas of a gas
      2. The diffusion rate of CO2 is 20 times greater than that of O2
      3. Khan Academy – Graham’s Law of of Effusion
      4. BrightStorm – Graham’s Law
    6. Boyle’s Law
      1. Boyle’s Law states that the product of the pressure and volume for a gas is a constant for a fixed amount of gas at a fixed temperature
      2. BrightStorm – Boyle’s Law
    7. Charles’s Law
      1. The volume of a given mass of an ideal gas is directly proportional to its temperature on the absolute temperature scale (in Kelvin) if pressure and the amount of gas remain constant; that is, the volume of the gas increases or decreases by the same factor as its temperature
      2. V/T = k
        1. V = the volume of the gas
        2. T = the temperature of the gas (measured in Kelvin)
        3. K = is a constant
      3. This law explains how a gas expands as the temperature increases; conversely, a decrease in temperature will lead to a decrease in volume. For comparing the same substance under two different sets of conditions, the law can be written as:

      \frac{V_1}{T_1} = \frac{V_2}{T_2} \qquad \mathrm{or} \qquad \frac {V_2}{V_1} = \frac{T_2}{T_1} \qquad \mathrm{or} \qquad V_1 T_2 = V_2 T_1.

    8. Avogadro’s Law
      1. The principle that equal volumes of all gases under identical conditions of pressure and temperature contain the same number of molecules
      2. Stated another way that under equal conditions of temperature and pressure, equal volumes of gases contain an equal number of molecules.
      3. V/n = k
        1. V = volume of the gas
        2. n = is the amount of the substance of the gas
        3. k = is a proportionality constant
      4. One mole of an ideal gas occupies 22.4 liters (dm³) at STP, and occupies 24.45 liters at SATP (Standard Ambient Temperature and Pressure = 273K and 1 atm or 101.325 kPa). This volume is often referred to as the molar volume of an ideal gas. Real gases may deviate from this value.
      5. STP corresponds with 1 atm pressure (760 torr) and 0 oC.

    4 Primary Questions

      1. PCO2 equation
        1. PACO2 = VCO2 x 0.863 / VA
          1. where VA=VE-VD
            1. VE = minute ventilation
            2. VD = dead space per minute
          2. 0.863 = is necessary to equate dissimilar units for VCO2 (ml/min) and VA (L/min) to PACO2pressure units (mm Hg)
          3. VA = alveolar ventilation
        2. The PCO2 equation puts into physiologic perspective one of the most common of all clinical observations: a patient’s respiratory rate and breathing effort. The equation states that alveolar PCO2 (PACO2) is directly proportional to the amount of CO2 produced by metabolism and delivered to the lungs (VCO2) and inversely proportional to the alveolar ventilation (VA). While the derivation of the equation is for alveolar PCO2, its great clinical utility stems from the fact that alveolar and arterial PCO2 can be assumed to be equal.
        3. We primarily need to know if VA is adequate for VCO2; if it is, then PaCO2 will be in the normal range (35-45 mm Hg). Conversely, a normal PaCO2 means only that alveolar ventilation is adequate for the patient’s level of CO2 production at the moment PaCO2 was measured.  From the PCO2 equation it is evident that a level of alveolar ventilation inadequate for CO2 production will result in an elevated PaCO2 (> 45 mm Hg; hypercapnia). Thus patients with hypercapnia are hypoventilating (the term hypoalveolar ventilating would be more appropriate but hypoventilating is the conventional term). Conversely, alveolar ventilation in excess of that needed for CO2 production will result in a low PaCO2 (< 35 mm Hg; hypocapnia) and the patient will be hyperventilating. (Confusion sometimes arises because the prefix (hyper-, hypo-) differs for the same condition depending on whether one is describing a blood value or the state of alveolar ventilation.)
        4. From the PCO2 equation it follows that the only physiologic reason for elevated PaCO2 is a level of alveolar ventilation inadequate for the amount of CO2 produced and delivered to the lungs. Thus arterial hypercapnia can always be explained by:
            1. not enough total ventilation (as may occur from central nervous system depression or respiratory muscle weakness); or
            2. too much of the total ventilation ending up as dead space ventilation (as may occur in severe chronic obstructive pulmonary disease, or from rapid, shallow breathing); or
            3. some combination of 1) and 2)
        5. An important clinical corollary of the PaCO2 equation is that we cannot reliably assess the adequacy of alveolar ventilation – and hence PaCO2 – at the bedside. Although VE can be easily measured with a handheld spirometer (as tidal volume times respiratory rate), there is no way to know the amount of VE going to dead space or the patient’s rate of CO2 production. A common mistake is to assume that because a patient is breathing fast, hard and/or deep he or she must be “hyperventilating.” Not so, of course.
        What determines pCO2
      2. Henderson-Hasselbalch equation
        1. pH = pK + log HCO3 / 0.03(PaCO2)
          1. pH ~ HCO3 / PaCO2
          2. .03  mmol/L/mm Hg solubility of CO2
          3. pKa = acid dissociation constant
        2. It is used to calculate the PH of a buffered solution. This equation is derived from the behavior of weak acids (and bases) in solution, which is described by the kinetics of reversible reactions.
        3. EMCrit Podcast 44 – Acid Base: Part I
        Buffers and Hendersen-Hasselbalch
        How Do Buffers Work? (Henderson-Hasselbalch Example)
        Henderson-Hasselbach Equation

      3. Alveolar Gas equation, and
        1. PAO2 = FIO2(PATM-PH2o)-PACO2[FIO2 + (1-FIO2) / R]
          1. Abbreviated form
            1. PAO2=FIO2(PATM-47)-1.2(PaCO2)
              1. R = 0.8 (assuming identical values for arterial and alveolar PCO2)
              2. 47 = Water vapor pressure in the airways is dependent only on body temperature and is 47 mm Hg at normal body temperature (37 degrees C)
              3. PATM = is usually not necessary to measure PATM if you know its approximate average value where the blood was drawn (e.g. sea level 760 mm Hg; Cleveland 747 mm Hg; Denver 640 mm Hg)
              4. 1.2 = is a factor based on assumed respiratory quotient (CO2 excretion over O2 uptake in the lungs) of 0.8; this factor becomes 1.0 when the FIO2is 1.0.
        2. All physicians know that hemoglobin carries oxygen and that anemia can lead to severe hypoxemia. Making the necessary connection between PaO2 and O2 content requires knowledge of the oxygen content equation.
        3. The alveolar gas equation predicts the change in PAO2 that will occur for a given change in PACO2. Because the normal value for the respiratory exchange ratio is 0.8, when alveolar ventilation is halved, the decrease in PAO2 will be slightly greater than the increase in PACO2. To summarize, when VA is halved, PACO2 is doubled and PAO2 is slightly more than halved.
        Alveolar Gas Equation – Part 1
        Alveolar Gas Equation – Part 2
        Oxygen Movement from Alveoli to Capillaries
      4. Oxygen Content equation
        1. CaO2 = (SaO2 x Hb x 1.34) + .003(PaO2)
          1. where:
            1. SaO2 = is an estimation of the oxygen saturation level usually measured with a pulse oximeter device
            2. 1.34 = ml O2/gram Hb = Amount of oxygen that 1 g of fully saturated hemoglobin can hold
            3. .003 = ml   O2/mm Hg  PaO2/dl =  represents the amount of oxygen dissolved in plasma
            4. Hb = hemoglobin content in grams/dl
            5. PaO2 = is a measurement of pressure exerted by uncombined oxygen molecules dissolved in plasma
          2. The oxygen content is the actual amount of O2 per volume of blood. The O2 content can be calculated from the O2-binding capacity of hemoglobin and the percent saturation of hemoglobin, plus any dissolved O2.
          3. Examples Oxygen Content Calculator
    Oxygen Content

    Vascular Circuit

    1. Central to any assessment of oxygen transport is the ability to calculate the
      amount of oxygen in the blood at any point in the body

    Such calculations are dependent upon both the measured oxygen tension
    and oxygen saturation at each point




    Hypoxia Shunts and Ventilation Perfusion Mismatch


    Control of Breathing

    1. Rhythmicity of respiration is primarily controlled by specific neural areas in the medulla and pons of the brain.
    2. These areas possess monitoring, stimulating and inhibiting properties that continually adjust ventilatory pattern to meet specific metabolic needs
    3. To understand how control of ventilation occurs, one must have a basic knowledge of:
      1. the function of respiratory components of the medulla
      2. the influence of the pontine respiratory centers on the respiratory components of the medulla
      3. the monitoring systems that influence respiratory components of the medulla
      4. the reflexes that influence ventilation

    The Respiratory Components of the Medulla

    1. Two groups of respiratory neurons in the medulla oblongata are responsible for coordinating the intrinsic rhythmicity of respiration:
      1. dorsal respiratory group (DRG)
      2. ventral respiratory group (VRG)
      The Respiratory Center

      Dorsal Respiratory Group

      1. The dorsal respiratory group (DRG) consists chiefly of inspiratory neurons.
      2. Believed to be responsible for the basic rhythm of ventilation.
      3. The DRG:
        1. receive signals regarding respiratory needs
        2. evaluate and prioritize various signals
        3. emit neural impulses every few seconds to the muscles of inspiration
      4. cells within the DRG are thought (West) to posses inherent rhythmicity, generating bursts of neuronal activity to the diaphragm and respiratory muscles in the absence of any other input
      5. input from the vagal and glossopharyngeal nerves via the nearby nucleus of the tractus solitarius modulates activity in the DRG

      Ventral Respiratory Group

      1. The ventral respiratory group (VRG) contains both inspiratory and expiratory neurons.
      2. During normal quiet breathing, the VRG is almost entirely dormant.
      3. During heavy exercise or stress, the VRG sends impulses to the muscles of exhalation and the accessory muscles of inspiration innervated by the vagus nerve.
      4. the neurones of the expiratory VRG are quiescent during tidal respiration, however become active with forced expiration, exercise, etc.
      5. the VRG is divided into 2 divisions,
        1. cranial division – neurones of the nucleus ambiguus
          1. the cranial division innervates muscles of the ipsilateral accessory muscles of respiration, principally via the vagus
        2. caudal division – neurones of the nucleus retroambiguus
          1. the caudal division provides inspiratory and expiratory drive to the motor neurones of the intercostal muscles

      The Pontine Centers

      1. The pontine respiratory centers consist of:
        1. Apneustic center – if unrestrained, sends neural impulses to the DRG that cause prolonged, gasping types of inspiration. It’s located in the caudal part of the pons, and causes slow deep breathing.
          1. situated in the lower pons in the floor of the 4th ventricle, near the middle cerebellar peduncle
          2. impulses from these neurones –> inspiratory DRG and increased “ramp” AP’s
          3. section of the brainstem immediately above this group –> apneusis
          4. prolonged inspiratory gasps interrupted by transient expiratory efforts
          5. this is restrained by the pneumotaxic centre and the inflation reflex
        2. Pneumotaxic center – enhances the rhythmicity of breathing pattern by causing the depth of breathing to decrease and the rate of breathing to increase in almost an equal amount. It’s located in the rostral or upper part of the pons.
          1. located in the upper pons, in the nucleus parabrachialis and the Kolliker Fuse nucleus
          2. acts to limit the activity of the inspiratory DRG
          3. therefore regulating the inspired volume and rate of respiration
          4. acts only as a modulator, as normal respiratory rhythm can exist in its absence
      Advanced Anatomy and Physiology: Respiratory System, Neural Control of Breathing

      Respiratory Component Failure

      1. Several clinical conditions can depress the function of the respiratory components of the medulla.
      2. They include:
        1. reduced blood flow
        2. acute poliomyelitis
        3. CNS depressant drugs

      Monitoring Systems of Medulla Rhythmicity Center

      1. The major known monitoring systems that act on the medulla (DRG and VRG) are the:
          1. central chemoreceptors
          2. peripheral chemoreceptors

      Central Chemoreceptors

      1. situated near (beneath) the ventral surface of the medulla, near the origins of the vagi and glossopharyngeal nerves
      2. The most powerful stimulus known to influence the respiratory components of the medulla is an excess concentration of hydrogen ions [H+] in the CSF.
      3. The central chemoreceptors are responsible for monitoring the H+ ion concentration of the CSF.
      4. Increased PaCO2 also causes cerebral vasodilatation which enhances diffusion of CO2
        into the CSF and brain ECF
      5. A portion of the central chemoreceptors is actually in contact with the CSF.
        1. these are anatomically separate from the respiratory centers, and are bathed in brain ECF, the composition of which is determined by CSF, blood flow and local metabolism
      Central Chemoreceptors

      Monitoring Mechanism

      1. Central chemoreceptors transmit signals to the medulla by the following mechanism:
        1. as CO2 levels increase in the arterial blood, the CO2 molecules diffuse across a semipermeable membrane, called the blood-brain barrier, which separates the blood from the CSF
        2. the blood-brain barrier is very permeable to CO2 molecules and relatively impermeable to H+ and HCO3- ions
      2. The H+ ion generated from the CO2 combined with water in the CSF to diffuse into bicarbonate and H+ rapidly increase and significantly reduces pH in the CSF.
      3. The liberated H+ ions cause the central chemoreceptors to transmit signals to the respiratory component of the medulla, which, in turn, increases alveolar ventilation.
      4. The increased ventilation reduces CO2 in the blood and subsequently CSF.

      Peripheral Chemoreceptors

      1. The peripheral chemoreceptors are special oxygen-sensitive cells that react to reductions of oxygen levels in the arterial blood.
      2. They are located high in the neck at the bifurcation of the carotid arteries and on the aortic arch.
      3. The peripheral chemoreceptors are also called carotid and aortic bodies.
      4. Although the peripheral chemoreceptors also monitor changes in PCO2 and PH, they play a more important role in monitoring PO2 levels. These receptors exert little control over ventilation until the PO2 has dropped below 60 mm Hg. Thus hypoxia is the main stimulus for ventilation in persons with chronically elevated levels of CO2. If these patients are given oxygen therapy at a level sufficient to increase the PO2 above that needed to stimulate the peripheral chemoreceptors, their ventilation may be seriously depressed.
      Peripheral Chemoreceptors

      Monitoring Mechanism

      1. The carotid and aortic bodies are composed of epithelial-like cells and neuron terminals in intimate contact with arterial blood.
      2. When activated by a low PaO2 (<60 mm Hg) , sensory signals are transmitted to the respiratory components in the medulla.
      3. Compared to the aortic bodies, the carotid bodies play a much greater role in initiating an increased ventilatory rate in response to reduced PaO2.
      4. Other factors that stimulate the peripheral chemoreceptors include:
        1. decreased pH
        2. hypoperfusion
        3. increased temperature
        4. nicotine
        5. PaCO2

      Responses Activated by Peripheral Chemoreceptors

      1. In addition to increased ventilation activated by the peripheral chemoreceptors, other responses include:
        1. peripheral vasoconstriction
        2. increased pulmonary vascular resistance
        3. systemic hypertension
        4. tachycardia
        5. increase left ventricular performance
      2. Factors effecting extra-alveolar vessels
        1. smooth muscle tone largely determines vessel caliber, therefore,


      Reflexes that Influence Ventilation

      1. A number of reflexes are known to influence the rate of ventilation, they include:
        1. Hering-Bruer Inflation Reflex
        2. Deflation Reflex
        3. Irritant Reflex
        4. Juxtapulmonary-Capillary Receptors
        5. Baroreceptors
        6. Stimuli

      Hering-Bruer Inflation Reflex

      1. The Hering-Bruer inflation reflex is generated by stretch receptors located in the smooth muscle walls of the bronchi and bronchioles that become excited when the lungs overinflate.
      2. These produce sustained discharge on lung inflation (no adaptation)
      3. These stretch receptors send signals to the medulla via the vagus verve, causing inspiration to stop.
        1. Afferents travel in large myelinated fibers of the vagus to the medulla
      4. The Hering-Bruer reflex appears to be a protective mechanism against pneumothorax.
      5. The receptors are stimulated by the rate as well as extent of inflation, and are sensitized by reduced compliance, such as with trilene
      6. Stimulation leads to a decrease, or cessation, of inspiratory muscle activity
      7. May possibly be of some importance in the newborn

      Deflation Reflex

      1. Opposite of the Hering-Breuer reflex
      2. The deflation reflex is stimulated when the lungs are compressed or deflated, causing an increased rate of breathing.
      3. Precise mechanism for this reflex is not known.
      4. Possibly related to the sigh mechanism
      5. Produces an increase in ventilation with a reduction in FRC below normal

      Irritant Reflex

      1. When the lungs are exposed to toxic gases, the irritant receptors may be stimulated.
      2. These irritant receptors are subepithelial mechanoreceptors located in the trachea, bronchi, and bronchioles.
      3. When these receptors are activated, a reflex response causes the ventilatory rate to increase as well as cough and bronchoconstriction.
      4. Discharge in response to nociception, impulses travel in myelinated vagal fibres, –> bronchoconstriction and hyperpnoea
      5. These show rapid adaptation and are involved with mechanoreception

      Juxtapulmonary-Capillary Receptors

      1. J receptors are located in the interstitial tissues between the pulmonary capillaries and the alveoli.
      2. When these J receptors are stimulated, a reflex response triggers rapid, shallow breathing.
      3. Respond very quickly to chemicals injected into the pulmonary circulation
      4. May also possibly respond to chemicals in alveolar air
      5. Impulses travel in slow, non-myelinated vagal fibres, –> rapid, shallow breathing (intense stimulation –> apnoea)
      6. J receptors are activated by:
        1. pulmonary capillary congestion
        2. capillary hypertension
        3. edema – lung deflation
        4. serotonin – emboli
      7. These may be responsible for the hyperpnoea and dyspnoea of CCF and interstitial lung disease


      1. The normal function of the aortic and carotid sinus baroreceptors, located near the aortic and carotid peripheral chemoreceptors, is to initiate reflexes that cause:
        1. decreased heart rate and ventilatory rate in response to an elevated systemic BP
        2. increase heart rate and ventilatory rate in response to a reduced systemic BP
      Regulation of blood pressure with baroreceptors

      Other Stimuli that Affect Ventilation

      1. Many stimuli can influence ventilation:
        1. sudden cold stimulus may lead to arrest
        2. sudden pain may cause arrest, however, prolonged pain may lead to tachypnea
        3. irritation of the pharynx and larynx may trigger arrest followed by coughing
        4. stretching the anal sphincter triggers an increase in respiratory rate
        5. light pressure applied to the thorax may increase ventilation

          Obesity Hypoventilation Syndrome

          Obesity Hypoventilation Syndrome


          Over the past few decades the incidence of obesity has doubled worldwide and current estimates classify more than 1.5 billion adults as overweight and at least 500 million of them as clinically obese, with body mass index (BMI) over 25 kg/m2and 30 kg/m2, respectively [57]. Obesity prevalence rates are steadily rising in the majority of the modern Western societies, as well as in the developing world. Moreover, alarming trends of weight gain are reported for children and adolescents, undermining the present and future health status of the pediatric population [58]. To highlight the related threat to public health, the World Health Organization has declared obesity a global epidemic, also stressing that it remains an under-recognized problem of the public health agenda [59, 60].

          Because obesity has become both a national and global epidemic, it is imperative that physicians are able to recognize and treat obesity-associated diseases. Evidence suggests that obesity hypoventilation syndrome is under-recognized and undertreated. Obesity hypoventilation syndrome (OHS) (also known as Pickwickian syndrome from Charles Dickins character in the Pickwick Papers) is defined as the triad of obesity, daytime hypoventilation, and sleep-disordered breathing in the absence of an alternative neuromuscular, mechanical or metabolic explanation for hypoventilation.

          During the last 3 decades the prevalence of extreme obesity has markedly increased in the United States and other countries. With such a global epidemic of obesity, the prevalence of OHS is bound to increase. Patients with OHS have a lower quality of life, with increased healthcare expenses, and are at higher risk of developing pulmonary hypertension and early mortality, compared to eucapnic patients with sleep-disordered breathing.

          OHS often remains undiagnosed until late in the course of the disease. Early recognition is important, as these patients have significant morbidity and mortality. Effective treatment can lead to significant improvement in patient outcomes, underscoring the importance of early diagnosis [6].

          What is obesity?

          Obesity is described anatomically as an elevated level of fat storage in the form of hypertrophy (increased size) and/or hyperplasia (increased number) of fat cells, known as adipocytes. Given the complexities of body composition analysis, the body mass index (BMI) acts as a surrogate for the amount of bodily fat and facilitates patient comparison
          and grouping for the purposes of research or discussion. Body mass index is defined as the body weight in kg divided by the square of the body height in meters (kg*m-2). Obesity has been defined as a BMI>30 kg*m-2, and morbid obesity has been referred to as a BMI>40 kg*m-2 or a BMI>35 kg*m-2 with an obesity-related comorbidity (Chart Below). Body mass index alone is not a good predictor of the distribution of excess body fat; central obesity with elevated visceral fat levels is associated with greater metabolic impact and complications than widespread subcutaneous fat. Body mass index may be misleading in patients with significant muscle bulk. It is also critical to understand that patients can have elevated body fat content despite a normal BMI, so-called ‘‘normal weight obesity’’, and this too can have an impact on organ function, with the risk of metabolic abnormalities and hypertension increasing as the percent of body fat (%BF) increases. Obesity  impacts virtually all organ systems and is an independent risk factor for both morbidity and mortality [55].



          The literature clearly highlights the complexity of severe obesity as a multisystem disease, and individuals caring for these patients must have a sound understanding of the changes in order to offer the highest quality care to these patients.

          Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species.

          Obesity is a multisystem chronic proinflammatory disorder associated with increased morbidity and mortality. Adipocytes are far more than storage vessels for lipids. They secrete a large number of physiologically active substances called adipokines that lead to inflammation, vascular and cardiac remodeling, airway inflammation, and altered microvascular flow patterns. They contribute to linked abnormalities, such as insulin
          resistance and the metabolic syndrome, and they attract and activate inflammatory cells such as macrophages. These changes can lead ultimately to organ dysfunction,
          especially cardiovascular and pulmonary issues [55].

          The fat cell, or adipocyte, is central to the pathophysiological changes that terminate in obesity-associated comorbidity. Adipocytes have two main roles. The first role is lipid handling, where adipose tissue can be viewed as an adaptive response aimed at controlling the potential toxicity of free fatty acid (FFA) levels. The second role is an endocrine and paracrine function central to the adverse impact of obesity. These cells actively produce and secrete a large number of important biologically active hormones referred to as adipokines, which include substances with metabolic and growth regulation roles as well as cytokines
          and collagens (see figure below). Pro-inflammatory substances are secreted mainly by visceral fat cells, whereas adiponectin and leptin are the key substances produced by subcutaneous adipocytes.7 These pro-inflammatory signals reach a point where they lead to macrophage and T-cell recruitment to the adipose tissue, further contributing to the inflammatory state. This adipocyte and inflammatory cell mix is the potent combination at the core of the metabolic disturbances in obesity [55].


          Obesity-related changes in respiratory function are, intuitively, related to the severity of the body mass increase and the location of the excess fat deposits. Clearly, upper body
          (waist and above) fat will have a greater impact on diaphragmatic excursion, chest wall mechanics, and work of breathing. The major physiological changes are listed in table 2 below [55].




            Mechanisms resulting in Hypercapnia

          [Obesity Hypoventilation Syndrome]


          Excessive daytime sleepiness (EDS) is the primary concern for many patients presenting with sleep disorder and a significant public health problem. The International Classification of Sleep Disorders (ICSD-2) includes EDS as an essential feature for three diagnostic categories: narcolepsy, hypersomnia and behaviorally induced insufficient sleep syndrome. However, it is also associated with a wide range of diseases, including psychiatric and neurological disorders, pulmonary and cardiac conditions (listed in the Table below). Frequently, there may not be an identifiable cause and the only diagnosis possible is that of idiopathic hypersomnia. However, the most common causes may be found in a disturbance of sleep quality, sleep quantity or other contributors. Most frequently, insufficient sleep duration is responsible for this symptom. This review will give an overview of some of the most common causes of EDS encountered in clinical practice and identify important risk factors for sleepiness in the community.


          When investigating potential causes of EDS, it is important to distinguish between fatigue and excessive sleepiness, or hypersomnia. Fatigue is, like hypersomnia, a common complaint in general practice; it is a poorly defined feeling of exhaustion or strain associated with many chronic diseases and psychiatric disorders. Importantly, severely fatigued patients will not necessarily be sleepy, suggesting that the underlying pathologies are distinct. However, in clinical practice it can be difficult to distinguish between the two and there are recognized cases where fatigue and sleepiness may not be clearly defined.

          The clinical manifestations of hypoventilation syndromes usually are nonspecific, and in most cases, they are secondary to the underlying clinical diagnosis. Manifestations vary depending on the severity of hypoventilation, the rate of development of hypercapnia, and the degree of compensation for respiratory acidosis that may be present.All patients with OHS are obese (BMI >30 kg/m2) and most have coexisting obstructive sleep apnea (OSA). The most common symptoms and signs are due to the coexisting OSA [6], which include [4]:

          1. excessive daytime sleepiness,
          2. loud snoring,
          3. choking during sleep,
          4. resuscitative snorting (i.e., a loud snort that follows an apnea as the patient partially awakens and reopens the upper airway),
          5. fatigue,
          6. hypersomnolence,
          7. impaired concentration and memory,
          8. a small oropharynx, and a thick neck

          Many patients as listed in the charts above have symptoms and signs of pulmonary hypertension with right-sided heart failure (e.g., elevated jugular venous pressure, hepatomegaly, and pedal edema) and, occasionally, a plethoric complexion (ruddy in complexion, congested or swollen with blood) from polycythemia [1,7]. Patients can also present with hypercapnic respiratory failure of unknown etiology. Generally speaking, patients with OHS tend to have more comorbidities than patients with eucapnic obesity, including systemic hypertension, heart failure, angina, and insulin resistance [8].

          It can be difficult to distinguish individuals who have both OHS and OSA from individuals who have OSA alone. Dyspnea on exertion is a clue that OHS is present because patients with OSA alone generally do not develop dyspnea on exertion [1,4,7,9]. Severe obesity (BMI >50 kg/m2) is another clue that OHS may be present, since nearly 50 percent of such individuals have OHS [4].

          Thoracic examination

          Upon thoracic examination, patients with obstructive lung disease generally have

          1. Diffuse wheezing, hyperinflation (barrel chest),
          2. Diffusely decreased breath sounds,
          3. Hyperresonance upon percussion,
          4. Prolonged expiration,
          5. Coarse crackles beginning with inspiration may be heard,
          6. Wheezes frequently are heard upon forced and unforced expiration
          7. Cyanosis may be noted if accompanying hypoxia is present
          8. Clubbing may be present.

          Pulmonary hypertension

          Patients with central alveolar hypoventilation (Congentially Ondine’s Curse), COPD, and OHS may show evidence of pulmonary hypertension from examination findings. These findings may include:

          1. A narrowly split and loud pulmonary component (P2) of the second heart sound,
          2. A large a-wave component in the jugular venous pulse,
          3. A left parasternal (right ventricular) heave,
          4. An S4 of right ventricular origin,
          5. A diastolic murmur indicative of pulmonic valve regurgitation may be auscultated


          Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index (BMI) >30kg/m2) has awake alveolar hypoventilation (PaCO2 >45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology [1-3].

          Most patients with OHS present with chronic hypoventilation, although some may develop acute cardiopulmonary compromise. Cardiovascular comorbidities represent the main factor predicting mortality in patient with obesity-associated hypoventilation treated by NIV. In this population, NIV should be associated with a combination of treatment modalities to reduce cardiovascular risk [51]. Prompt diagnosis and therapy are important to avoid the adverse effects of OHS, especially since untreated patients with OHS have a high mortality rate [4,5].

          [Thorax 2008;63:925–931. doi:10.1136/thx.2007.086835]

          Effects of Obesity on Physiological Parameters


          Potential factors complicating endotracheal intubation in obesity



          Diagnostic testing is necessary for the evaluation of suspected OHS. This section reviews the common diagnostic tests, including arterial blood gases, pulmonary function tests, polysomnography, chest radiographs, electrocardiography, and echocardiography. The role of these tests in the evaluation of suspected OHS is described in the next section.

          Arterial blood gases — Arterial blood gas testing must be performed, since hypercapnia must be identified to diagnose OHS. The following abnormalities occur in patients with OHS:

          • Hypercapnia (PaCO2 >45 mmHg) is always present during wakefulness. The PaCO2 can be reduced or normalized, however, by voluntary hyperventilation [10]. It can also be reduced or normalized by involuntary hyperventilation caused by the arterial blood gas procedure.
          • Hypoxemia (PaO2 <70 mmHg) is usually present. The calculated alveolar-arterial (A-a) oxygen gradient may be normal when there is no coexisting lung or heart disease [1,11-13]. An elevated hematocrit is common and may be a clue that the patient is hypoxemic [4,14].

          Serum bicarbonate — A high serum bicarbonate level is a clue that the patient is chronically hypercapnic. This test is helpful if arterial blood gases cannot be obtained or are delayed [6,15].

          Pulmonary function tests — The primary use of pulmonary function tests is to exclude obstructive lung disease. Most patients with OHS have pulmonary function tests that are characteristic of obesity. These include [7,14,16]

          1. A low forced vital capacity (FVC),
            1. FVC – Forced Vital Capacity – after the patient has taken in the deepest possible breath, this is the volume of air which can be forcibly and maximally exhaled out of the lungs until no more can be expired. FVC is usually expressed in units called liters. This PFT value is critically important in the diagnosis of obstructive and restrictive diseases.
          2. A low forced expiratory volume in one second (FEV1),
            1. FEV1 – Forced Expiratory Volume in One Second – this is the volume of air which can be forcibly exhaled from the lungs in the first second of a forced expiratory maneuver. It is expressed as liters. This PFT value is critically important in the diagnosis of obstructive and restrictive diseases.
          3. A normal FEV1/FVC ratio, and
            1. FEV1/FVC – FEV1 Percent (FEV1%) – This number is the ratio of FEV1 to FVC – it indicates what percentage of the total FVC was expelled from the lungs during the first second of forced exhalation – this number is called FEV1%, %FEV1 or FEV1/FVC ratio. This PFT value is critically important in the diagnosis of obstructive and restrictive diseases.
          4. A low expiratory reserve volume (ERV)
            1. Expiratory reserve volume: the maximal volume of air that can be exhaled from the end-expiratory position
          5. Total lung capacity (TLC) may also be diminished in some patients
            1. Total lung capacity: the volume in the lungs at maximal inflation, the sum of VC and RV.

          Polysomnography — Most patients with OHS have an abnormal number of apneas and hypopneas per hour of sleep (i.e., a high apnea hypopnea index [AHI]) due to coexisting OSA. The converse is not true; an elevated AHI does not predict the presence of coexisting OHS [17]. In addition, patients with OHS usually have more profound oxyhemoglobin desaturation during sleep than patients with OSA alone [17-19].

          AHI = Apnea-Hypopnea Index, IPAP = Inspiratory Positive Airway Pressure, EPAP = Expiratory Positive Airway Pressure , SaO2 = percentage of available hemoglobin that is saturated with oxygen

          Chest radiograph — On a routine chest radiograph, both hemidiaphragms are usually elevated due to the obese abdomen and the heart is frequently enlarged due to right ventricular hypertrophy. Asymmetrical elevation of a hemidiaphragm suggests diaphragmatic paralysis, another condition that can cause hypoventilation. Hyperinflation and bullous disease suggest that the chronic hypercapnia may be due to pulmonary disease rather than OHS.

          Cardiac studies — Patients with OHS often have an abnormal electrocardiogram (ECG), echocardiogram, and/or cardiac catheterization. The ECG and echocardiogram may show right atrial and right ventricular hypertrophy, while the cardiac catheterization frequently reveals pulmonary hypertension [9].

          DIAGNOSTIC APPROACH — The diagnostic evaluation should be performed quickly because untreated OHS is associated with high mortality [4,5].

          OHS is diagnosed when the following criteria are confirmed:

          • Obesity (BMI be >30 kg/m2)
          • Awake alveolar hypoventilation (PaCO2 >45 mmHg)
          • An alternative cause of the hypoventilation cannot be identified

          The absence of an alternative cause of hypoventilation is an important requirement for the diagnosis of OHS. In clinical practice, patients frequently have additional diseases that cause hypoventilation (e.g., COPD). If the other disease is mild and unlikely to cause hypercapnia, then it is reasonable to give the patient a diagnosis of OHS. If the other disease is more severe and probably contributing to hypercapnia, the situation becomes more complicated. In this setting, OHS cannot be diagnosed with certainty. However, if the patient has severe obesity, severe sleep apnea, and severe oxyhemoglobin desaturation during sleep, it is generally presumed that OHS may be contributing and treat the patient accordingly.

          All individuals with suspected OHS should have their BMI measured and arterial blood gases (ABGs) performed. The purpose of the ABGs is to confirm alveolar hypoventilation. ABGs are most helpful when performed while the patient is breathing room air because the A-a oxygen gradient can be calculated. A normal A-a oxygen gradient excludes pulmonary parenchymal or airways disease. A normal A–a gradient for a young adult non-smoker breathing air, is between 5–10 mmHg.

          Additional testing is necessary to exclude other diseases that can cause alveolar hypoventilation, such as [20-22]

          1. chronic obstructive pulmonary disease (COPD),
          2. restrictive disease (e.g., neuromuscular weakness (or neuromuscular weakness), interstitial lung disease, chest wall disease),
          3. hypothyroidism, and
          4. diaphragmatic paralysis
          5. primary CNS disorders
            1. primary central hypoventilation syndromes
            2. brain stem infarction and tumors
          6. myxedema
          7. drugs
            1. narcotics
            2. sedatives
          8. metabolic abnormalities
            1. hypokalemia
            2. hypophosphatemia
            3. hypomagnesaemia
            4. metabolic alkalosis

          This generally requires the following tests:

          1. Thyroid function tests (or Thyroid function tests) and serum electrolytes (including magnesium and phosphorus) to look for hypothyroidism and electrolyte-related neuromuscular weakness, respectively.
          2. Pulmonary function tests (or Pulmonary function tests), including (in patients with severe respiratory failure, these tests will need to be deferred until the patients are stabilized)
            1. spirometry,
            2. lung volumes,
            3. diffusing capacity, and
            4. inspiratory and expiratory pressures, to look for evidence that COPD or a restrictive disease may be a prominent contributor to the alveolar hypoventilation.
          3. A chest radiograph to look for parenchymal lung disease, chest wall disease, asymmetrical elevation of a hemidiaphragm (ie, diaphragm paralysis), and cardiomegaly.
          4. Comprehensive Metabolic Chemistry Panel

          Although polysomnography is not required for the diagnosis of OHS, it should be performed in all patients with OHS for several reasons. First, in-laboratory polysomnography is the gold-standard diagnostic test for OSA, which frequently coexists with OHS and should be both identified and treated. Second, positive airway pressure therapy, the preferred treatment for OHS, can be titrated during polysomnography. Finally, polysomnography can give the clinician an impression of disease severity by determining the severity and duration of oxyhemoglobin desaturation, as well as the presence of cardiac dysrhythmias. The role of level 3 portable monitoring rather than in-laboratory polysomnography in OHS is unclear.

          The preceding discussion assumes that the patient with suspected OHS presented with chronic alveolar hypoventilation. However, presentation with acute or chronic hypercapnic respiratory failure is also common [6]. When a patient presents with severe acute respiratory failure due to OHS, diagnostic polysomnography with positive airway pressure titration during the same night is optimal if the patient is stable enough to go to the sleep laboratory. However, the diagnostic evaluation may need to be postponed and therapy immediately initiated if the patient is not well enough to go to the sleep laboratory. Overnight oximetry is a reasonable surrogate diagnostic test in this situation. Significant oxyhemoglobin desaturation not corrected by oxygen administration after several hours of recording should prompt empiric positive airway pressure therapy.

          Finally, acute pulmonary embolism is a frequent cause of death in patients with OHS. Therefore, a diagnostic evaluation should be pursued whenever thrombophlebitis or pulmonary embolism is suspected.


          • Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index (BMI) >30kg/m2) has awake alveolar hypoventilation (PaCO2 >45 mmHg), which cannot be attributed to other conditions, such as pulmonary parenchymal disease, skeletal restriction, neuromuscular weakness, hypothyroidism, or pleural pathology.
          • All patients with OHS are obese and most have coexisting obstructive sleep apnea (OSA). The most common symptoms and signs are due to the coexisting OSA, which include excessive daytime sleepiness, loud snoring, choking during sleep, resuscitative snoring, fatigue, hypersomnolence, impaired concentration and memory, a small oropharynx, and a thick neck. Some patients present with hypercapnic respiratory failure or uncertain etiology.
          • Diagnostic testing is necessary for the evaluation of suspected OHS. Commonly performed diagnostic tests include arterial blood gases, pulmonary function tests, polysomnography, and chest radiographs.
          • The diagnostic evaluation should be performed quickly because untreated OHS is associated with high mortality. All individuals with suspected OHS should have arterial blood gases (ABGs) performed. The purpose of the ABGs is to confirm alveolar hypoventilation. Additional testing is necessary to exclude other diseases that can cause alveolar hypoventilation, such as chronic obstructive pulmonary disease (COPD), restrictive disease (e.g., neuromuscular weakness, interstitial lung disease, chest wall disease), hypothyroidism, and diaphragmatic paralysis.


          Treatment is important because untreated OHS can progress to acute, life-threatening cardiopulmonary compromise. In addition, untreated OHS is associated with a high mortality rate, a reduced quality of life, and numerous morbidities, including pulmonary hypertension, right heart failure, angina, and insulin resistance [4,5,8,23].

          The therapeutic goals for patients with OHS include:

          1. normalization of the arterial carbon dioxide tension (PaCO2) during wakefulness and sleep (ie, PaCO2 <45 mmHg);
          2. prevention of oxyhemoglobin desaturation during
            1. sleep and wakefulness,
            2. erythrocytosis,
            3. pulmonary hypertension, and
            4. cor pulmonale;
          3. relief of hypersomnia and altered mentation.

          Therapeutic interventions for OHS therapy include four main components: PAP (positive airway pressure) therapy, supplemental oxygen, weight reduction surgery, and pharmacologic respiratory stimulants [54]. Therefore, all patients with OHS are managed with nocturnal positive airway pressure and lifestyle modifications directed at losing weight. Bariatric surgery may be considered for patients who fail to lose sufficient weight with lifestyle modifications and either hope to eventually discontinue nocturnal noninvasive positive airway pressure or do not tolerate nocturnal noninvasive positive airway pressure. Routine treatment of comorbid conditions and the prevention of complications are also necessary in all patients with OHS.

          POSITIVE AIRWAY PRESSURE — Nocturnal noninvasive positive airway pressure is first-line treatment for OHS, regardless of whether or not the patient has a coexisting sleep-related breathing disorder. It is indicated for all patients with OHS and should NOT be delayed while the patient tries to lose weight. Patients with OHS alone are generally managed with bilevel positive airway pressure (BPAP). In contrast, patients with OHS and coexisting obstructive sleep apnea (OSA) are usually managed initially with continuous positive airway pressure (CPAP) and then changed to BPAP if the CPAP is insufficient.

          [Internet Journal of Pulmonary Medicine]

          Negative pressure ventilation is not a useful alternative because there are numerous practical problems and its efficacy has not been established in patients with OHS. The rationale for considering negative pressure ventilation is that it may mitigate or prevent chronic respiratory failure by decreasing the work of breathing and ventilatory muscle fatigue. However, its practical limitations include the following:

          1. fitting the various negative pressure ventilation systems (e.g., shells, poncho wraps, and tank ventilators) is difficult due to the obesity,
          2. even if a negative pressure ventilation system is found that fits the patient, the level of ventilatory support is limited by reduced chest wall and abdominal compliance, and
          3. patients with OHS are predisposed to obstructive sleep apnea and negative pressure ventilation during sleep may promote upper airway occlusion.

          Medication – Pharmacologic therapy for obesity is not universally accepted because of concerns about efficacy and safety, the observation that weight loss slows with ongoing treatment, and the observation that most patients regain their weight when the medications are discontinued. Regarding efficacy, many of the weight loss medications initially achieve weight loss of 5 to 10 kg over 3 to 12 months before the weight loss plateaus [24,25], but this is typically not enough to normalize the awake PaCO2. Regarding safety, pharmacologic therapy has the potential to cause drug-induced pulmonary hypertension [26]. This is a particular concern in patients with OHS whose respiratory abnormalities already place them at increased risk for this complication.

          Bariatric surgery – Considerable attention has been directed towards surgical methods of weight loss (ie, bariatric surgery), since lifestyle modifications alone are generally insufficient and pharmacological therapy is of uncertain efficacy and safety [27]. Bariatric surgery leads to a restriction of caloric intake alone or in combination with malabsorption of nutrients, thereby causing weight loss. Bariatric techniques include Roux-en-Y gastric bypass, adjustable gastric banding, sleeve gastrectomy, biliopancreatic diversion, duodenal switch, intragastric balloon, vertical banded gastroplasty endoluminal vertical gastroplasty, jejunoileal bypass, and liposuction. Perioperative mortality related to bariatric surgery is dependent on comorbidities and the procedure performed, but is reported to be less than 2 percent of patients who undergo bariatric surgery [28,29]. Reassessment of OHS following bariatric surgery is performed after significant weight loss has occurred, usually within one to two years after the surgery. It consists of an arterial blood gas to reassess the awake PaCO2 and PaO2 in all patients, as well as in-laboratory polysomnography in patients who had coexisting OSA to assess for resolution or improvement of the OSA. A 2005 evidence-based analysis of the effectiveness and cost-effectiveness of bariatric surgery used as a method of last resort concluded that the evidence to support the use of such programs was suboptimal. However, a 2009 systematic review and economic evaluation found bariatric surgery appears to be a clinically effective and cost-effective intervention for moderately to severely obese people compared with non-surgical interventions


          Comorbid conditions that impair ventilation or reduce the ventilatory response to hypoxemia or hypercapnia are likely to contribute to the impairment caused by obesity. As a result, the clinician should make an effort to identify and treat such comorbid conditions. Examples include chronic obstructive pulmonary disease (COPD) and hypothyroidism.

          When total respiratory compliance is considered in obese patients, the effects of obesity on the chest wall must be separated from the effects attributable to decreased lung compliance, as seen in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This distinction has major implications for the application of mechanical ventilation
          in obese patients.

          COPD – COPD may exacerbate the symptoms and signs of OHS because both diseases impair alveolar ventilation and increase the work of breathing. It is reasonable to perform spirometry in patients with OHS, in order to detect coexisting COPD. Treatment of the COPD is indicated for all patients who are found to have coexisting COPD. This includes the cessation of smoking, bronchodilators, and, possibly, inhaled corticosteroids.

          Bronchodilators — Medications that help open the airways, called bronchodilators, are a mainstay of treatment for chronic obstructive pulmonary disease. Bronchodilators help to keep airways open and possibly decrease secretions.

          Bronchodilators are most commonly given in an inhaled form using a metered dose inhaler (MDI), dry powder inhaler (DPI), or nebulizer. It is important to use the inhaler properly to deliver the correct dose of medication to the lungs. If you do not use the inhaler correctly, little or no medicine reaches the lungs.

          There are several types of bronchodilators that can be used alone or in combination.

          • Short-acting beta agonists – Short-acting beta agonists, sometimes called rescue inhalers, can quickly relieve shortness of breath and can be used when needed. Examples of short-acting beta agonists include albuterol, levalbuterol, and pirbuterol.
          • Short-acting anticholinergics – Short-acting anticholinergic medication (ipratropium, Atrovent) improves lung function and symptoms. If symptoms are mild and infrequent, short-acting anticholinergic medication may be recommended only when you need it. Or, if symptoms are more severe or more frequent, it may be recommended on a regular basis.
          • Short-acting combination inhaler – A combination inhaler that contains albuterol and ipratropium (Combivent) is also available. Combination inhalers may be used just when needed or regularly, depending on the frequency and severity of your symptoms.

          Long-acting treatments are often recommended for people who must use medication on a regular basis to control COPD symptoms.

          • Long-acting beta agonists – Long-acting beta agonists may be recommended if your symptoms are not adequately controlled with other treatments. Examples of long-acting beta agonists include salmeterol, formoterol, and arformoterol.
          • Long-acting anticholinergics – The long-acting anticholinergic medication, tiotropium (Spiriva), which is taken once daily, improves lung function while decreasing shortness of breath and flares of COPD symptoms. Aclidinium (Tudorza), a long-acting anticholinergic that is taken twice daily, also improves lung function. This type of medication may be recommended if your symptoms are not adequately controlled with other treatments, such as the short-acting bronchodilators.
          • Theophylline – Theophylline in slow release form (e.g., Theo-Dur, Slo-bid) is a long-acting bronchodilator that is taken in pill form. Theophylline is not commonly used, but may be beneficial to some people with more severe, but stable chronic obstructive pulmonary disease. The dose of theophylline must be monitored carefully by blood tests because of its potentially toxic effects.

          Glucocorticoids — Glucocorticoids (also called steroids, although they are very different from muscle building steroids) are a class of medication that has anti-inflammatory properties. Glucocorticoids can be taken with an inhaler, as a pill, or as an injection. Inhaled glucocorticoids may be recommended if your symptoms are not completely controlled with bronchodilators and/or if you have frequent flares of chronic obstructive pulmonary disease.

          Glucocorticoids taken in pill form are sometimes used for short term treatment (e.g., for flares of COPD), but are not generally used long-term because of the risk of side effects.

          Combination treatments — Combinations of short and long-acting bronchodilators, anticholinergics, and/or glucocorticoids are often used in people whose symptoms are not completely controlled with one medication.

          Supplemental Oxygen – Supplemental oxygen therapy is a widely accepted therapy for hypoxemic patients with COPD alone; it has been shown to improve survival and it is not associated with worsening hypercapnia [30-32]. In contrast, supplemental oxygen therapy may worsen hypercapnia in coexisting OHS and COPD. In situations in which a patient with OHS and COPD requires supplemental oxygen, it should be used along with noninvasive positive airway pressure therapy because there is evidence that hypercapnia may not worsen if the supplemental oxygen is used with noninvasive positive airway pressure. If the patient cannot tolerate noninvasive positive airway pressure therapy, the patient should be carefully monitored to ensure that worsening of nocturnal asphyxia does not have adverse effects on hemodynamics, symptoms, or alveolar ventilation.

          Hypothyroidism – Hypothyroidism may contribute to the chronic ventilatory failure of OHS by decreasing chemo-responsiveness, causing OSA (due to macroglossia and/or upper airway dilator muscle dysfunction), or causing either a myopathy or neuropathy that affects the respiratory muscles [33-36]. These consequences of hypothyroidism may be improved with thyroid hormone replacement. Screening for hypothyroidism by measuring the serum thyroid stimulating hormone (TSH) concentration is warranted in all individuals presenting with OHS, since the clinical presentation of the hypothyroidism may be quite similar to that of euthyroid patients with OHS.

          In cases of subclinical hypothyroidism, which are characterized by mild elevation of the serum TSH (<10 mU/L) and a normal free T4 level, there are no data to strongly support either treating OHS patients with supplemental thyroid hormone or observing them. Given the potential contribution of superimposed hypothyroidism to the respiratory failure present in OHS and also the potential for a substantial portion of individuals with subclinical hypothyroidism to eventually progress to overt hypothyroidism over a number of years, the decision to observe patients with OHS who have laboratory evidence of subclinical hypothyroidism mandates periodic laboratory and clinical monitoring for the development of overt hypothyroidism.


          Patients with OHS should be advised to abstain from alcohol. In addition, benzodiazepines, opiates, and barbiturates should be avoided if possible. While most of the dangers of these agents have been described as worsening sleep-related breathing abnormalities in patients with coexisting OHS and OSA, however this evidence is relevant to all patients with OHS, since most patients with OHS also have OSA and there are theoretical risks of adversely affecting ventilatory chemoresponsiveness and upper airway function in OHS.

          In addition to the sedatives described above, supplemental oxygen must be approached cautiously in patients with OHS because it may increase hypercapnia [37]. In situations in which a patient with OHS requires supplemental oxygen, it should be used along with noninvasive positive airway pressure therapy because there is evidence that hypercapnia may not worsen if the supplemental oxygen is used with noninvasive positive airway pressure. If supplemental oxygen is necessary and the patient cannot tolerate noninvasive positive airway pressure therapy, the patient should be carefully monitored to ensure that worsening of nocturnal asphyxia does not have adverse effects on hemodynamics, symptoms, or alveolar ventilation.

          (ARDS) – When total respiratory compliance is considered in obese patients, the effects of obesity on the chest wall must be separated from the effects attributable to decreased lung
          compliance, as seen in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This distinction has major implications for the application of mechanical ventilation
          in obese patients.

          In all these commonly encountered clinical scenarios obesity magnifies patient risk, by predisposing to the underlying condition, contributing to the associated pathophysiological
          derangements and complicating management from a technical and logistical point of view. Regrettably, the problem of morbid obesity is flourishing and an increasing proportion of patients in the ICU suffer from its pervasive effects, adding to its status as the one of the greatest challenges to the health of communities in the developed world.


          Few drugs known for their respiratory stimulant effects, like progesterone, acetazolmide, almitrine and aminophylline, have been tried in patients with sleep apnea syndromes; however, the two most widely quoted drugs when dealing with OHS patients are medroxyprogesterone and acetazolmide [56].

          Respiratory stimulants (i.e., progestins and acetazolamide) are a therapy of last resort for patients with who continue to have serious alveolar hypoventilation despite positive airway pressure therapy. Progestins have been shown to improve awake hypercapnia and hypoxemia in patients with OHS [38,39], while acetazolamide has been shown to improve alveolar ventilation in patients with OHS [40-42]. Medroxyprogesterone acetate stimulates respiration at the hypothalamic level. Acetazolamide is a carbonic anhydrase inhibitor that increases minute ventilation by inducing metabolic acidosis through increased excretion of bicarbonate by the kidneys. Acetazolamide has been shown to improve AHI, increase PaO2, and reduce PaCO2 in patients with OSA [54].

          Despite these benefits, neither is considered an appropriate primary therapy for OHS because they do not affect all of the pathogenic contributors to OHS, in particular the recurrent upper airway collapse that occurs during sleep in patients who have coexisting obstructive sleep apnea (OSA) [43-46] or the altered respiratory mechanics [47]. Leaving these contributors untreated may have adverse long-term consequences. In addition, progestins and acetazolamide have potentially serious side effects [48,49]. The respiratory stimulant, theophylline, has not been studied in patients with OHS.  


          Tracheostomy has no role in patients with OHS alone, but it may be effective in patients with coexisting OHS and obstructive sleep apnea (OSA) because it relieves upper airway obstruction during sleep with subsequent improvement in alveolar ventilation and the arterial carbon dioxide tension (PaCO2) during wakefulness [40]. Not all patients return to eucapnia following tracheostomy because upper airway obstruction is just one of several factors responsible for chronic hypoventilation in patients with coexisting OHS and OSA; other factors include decreased compliance of the respiratory system and decreased ventilatory muscle strength, which are unaltered by tracheostomy.

          Tracheostomy is rarely necessary since the same goals can be achieved without surgery using noninvasive positive airway pressure therapy. This is fortunate since tracheostomy is associated with many problems, including the following: The surgery is more difficult in obese individuals, debulking excess subcutaneous tissue may be required, obesity may limit the use of tracheostomy buttons during wakefulness to facilitate speech, recurrent episodes of purulent bronchitis may occur, and psychosocial problems after the procedure have been reported in a majority of patients, including disability, adjustment disorders, and marital discord [50].


          1. Obesity Hypoventilation Syndrome (OHS) exists when an obese individual (body mass index [BMI] >30kg/m2) has awake alveolar hypoventilation (arterial carbon dioxide tension [PaCO2] >45 mmHg), which cannot be attributed to other conditions such as pulmonary disease, skeletal restriction, neuromuscular weakness, untreated hypothyroidism, or pleural pathology.
          2. Treatment is indicated because untreated OHS can progress to acute, life-threatening cardiopulmonary compromise. Untreated OHS is also associated with a high mortality rate, a reduced quality of life, and numerous morbidities.
          3. For all patients with OHS, it is recommended immediate initiation of noninvasive positive airway pressure therapy, rather than delaying the initiation of noninvasive positive airway pressure therapy until the outcome of the attempted weight loss is known (Grade 1B).
          4. All patients with OHS should undergo lifestyle modifications (ie, dietary changes, exercise, behavioral modifications) in an effort to lose weight. For those patients in whom weight loss due to lifestyle modifications is insufficient to correct the OHS, it is suggested NOT treating with weight loss medication (Grade 2B). For the same patients, referral to a bariatric surgeon is reasonable if they either hope to eventually discontinue or are not tolerating nocturnal noninvasive positive airway pressure.
          5. Comorbid conditions that impair ventilation or reduce the ventilatory response to hypoxemia or hypercapnia are likely to contribute to the impairment caused by obesity. As a result, the clinician should make an effort to identify and treat such comorbid conditions. Examples include chronic obstructive pulmonary disease (COPD) and hypothyroidism.
          6. Patients with OHS should be advised to abstain from alcohol. In addition, benzodiazepines, opiates, and barbiturates should be avoided in patients with OHS if possible. Supplemental oxygen must be approached cautiously in patients with OHS because it may increase hypercapnia.
          7. Pharmacological therapy with respiratory stimulants does not treat all of the pathogenic components of OHS and has potential side effects; therefore, it is regarded as a therapy of last resort for patients with who continue to have serious hypoventilation despite positive airway pressure therapy.
          8. Tracheostomy has no role in patients with OHS alone. It may be effective in patients with coexisting OHS and obstructive sleep apnea (OSA) because it relieves upper airway obstruction during sleep; however, not all patients return to eucapnia following tracheostomy because upper airway obstruction is just one of several factors responsible for chronic hypoventilation. In addition, tracheostomy has attendant surgical risks.

          Survival Rates

          In the study, Long-Term Outcome of Noninvasive Positive Pressure Ventilation for Obesity Hypoventilation Syndrome, the Kaplan-Meier analysis, 1-, 2-, 3-, and 5-year survival probabilities were 97.5%, 93%, 88.3%, and 77.3%, respectively. Using the Swedish Home Mechanical Ventilation Register, Laub and Midgren found a similar 5-year survival (≈ 75%) in Pickwick patients. The 5-year survival rate was higher (88%) in the study from Janssens et al, but that study included patients with lower baseline Paco2 than the original studies patients, (mean value of 49 ± 10 mm Hg and 42% of patients with baseline Paco2 < 45 mm Hg) [53].

          Furthermore, these results correlate with the study Mortality and Prognostic Factors in Patients with Obesity-Hypoventilation Syndrome Undergoing Noninvasive Ventilation. In that study the authors found all-cause mortality was 12.7%, with 1-, 2- and 5-year survival of 97.1%, 92.0% and 70.2%, respectively. In univariate analysis, patients with PaO2 <50 mmHg, C-reactive protein >= 5.1 mg L-1, leucocytes >= 7.8 · 103 micro l-1, or pH >= 7.44 at baseline had poor prognosis (P < 0.05 each). In Cox multivariate analysis, PaO2, pH and leucocytes were independent predictors of mortality. Reduction in nocturnal PaCO2 by >=23.0% and haemoglobin at follow-up was associated with improved survival (P < 0.05 each) whilst a decrease in pH was a predictor of increased mortality. In contrast, neither baseline BMI nor its change was linked to survival [52].


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          Trauma Fast Exam

          Focused Abdominal Sonography for Trauma (FAST)

          Introduction (

          The use of focused ultrasonography has now become an extension of the physical examination of the trauma patient. Performed in the trauma room by properly trained and credentialed staff, it allows the timely diagnosis of potentially life-threatening hemorrhage and is a decision-making tool to help determine the need for transfer to the operating room, CT scanner or angiography suite.

          “The most important preoperative objective in the management of the patient with abdominal trauma is to ascertain whether or not a laparotomy is needed, and
          not the diagnosis of specific injury” – Polk 1983

          Blunt Abdominal Trauma

          Blunt abdominal trauma is a leading cause of morbidity and mortality among all age groups. Identification of serious intra-abdominal pathology is often challenging; many injuries may not manifest during the initial assessment and treatment period.

          Ultrasound in Trauma (Focused assessment with sonography for trauma (FAST))

          The aim is to identify life-threatening intra-abdominal bleeding or cardiac tamponade with a view to expediting definitive surgical management. It does not aim to exclude abdominal or thoracic injury.

          1. It helps to detect haemoperitoneum and haemopericardium.
          2. The primary benefit is to rapidly direct appropriate operative interventions in unstable
          3. It is useful in both blunt and penetrating abdominal trauma.
          4. A high specificity means a positive FAST indicates an intra-abdominal injury.
          5. Moderate sensitivity means a negative FAST (apparent absence of free fluid) does not exclude significant injury.
          6. FAST alters the management of trauma patients, such that
            1. there is more rapid disposition to the operating theatre,
            2. it indicates a more rapid search for other causes of hypotension when negative,
            3. it reduces the number of computed tomography (CT) scans and diagnostic peritoneal lavage examinations (DPLs) performed and
            4. it is associated with shorter hospitalizations, less complications and lower charges.
          7. At this stage, however, there is little conclusive evidence that its use improves patient
          8. Extended FAST (EFAST) includes assessment of the thorax for haemothorax and pneumothorax.

          Anatomical References

          1. The first is the intrathoracic abdomen, which is the portion of the upper abdomen that lies beneath the rib cage. Its contents include the diaphragm, liver, spleen, and stomach. The rib cage makes this area inaccessible for palpation and complete examination.
          2. The second is the pelvic abdomen, which is defined by the bony pelvis. Its contents include the urinary bladder, urethra, rectum, small intestine, and in females, the ovaries, fallopian tubes, and uterus.
          3. The third is the retroperitoneal abdomen, which contains the kidneys, ureters, pancreas, abdominal aorta, and inferior vena cava.
          4. The fourth is the true abdomen, which contains the small and large intestines, the uterus (if gravid), and the bladder (when distended).

          FAST Anatomy

          Peritoneal and Retroperitoneal Anatomy

          Anatomical Description of main pelvic arteries and veinsmalebladder

          Fast Exam Anatomical Reference

          Ultrasound in Trauma (Focused assessment with sonography for trauma (FAST) – Indications and role of FAST in penetrating trauma)

          The aim of FAST in penetrating trauma is to determine whether one or more of the abdominal, pericardial or pleural cavities has blood in it. This indicates breach in the integrity of the cavity and potentially significant injury. Lack of free fluid in the abdomen does not exclude significant injury, as penetrating bowel injury is frequently not associated with free abdominal fluid.

          1. Unstable patient with multiple wounds
            1. It helps to locate and quantify bleeding and direct initial therapeutic measures.
          2. Unstable patients with a single penetrating thoraco-abdominal wound of uncertain trajectory
            1. To locate and quantify bleeding and direct initial therapeutic measures.
          3. Stable patient with one or more penetrating wounds
            1. When it is not certain whether immediate surgery is required
            2. To locate and quantify bleeding and direct therapeutic measures.

          Other imaging and/or surgical exploration is generally required to exclude significant injury.

          Mount Sinai Emergency Medicine Ultrasound

          Focused Questions:

          1. Is there fluid in the peritoneal cavity?
          2. Is there a pericardial effusion?
          3. Is there fluid in the thorax (ie. hemoperitoneum)?
          4. Is there a pneumothorax? (see separate pneumothorax tutorial)

          UCSF-East Bay Trauma Service – FAST Exam


          Focused Abdominal Sonography for Trauma (FAST) allows rapid and noninvasive determination of the presence of free intra-abdominal fluid.  In patients sustaining blunt truncal trauma who are in shock, this information will allow the clinician to forego other diagnostic tests and quickly transfer the patient to the operating room for emergency celiotomy and control of intra-abdominal hemorrhage.  The use of FAST has all but supplanted the diagnostic peritoneal lavage (DPL) in the evaluation of unstable patients after blunt truncal trauma.

          Technique The FAST exam is performed as part of the initial evaluation of the trauma patient in the emergency center.  It consists of four separate views of four anatomic areas (see diagrams below):

          1. The right upper abdomen (Morison’s space between liver and right kidney)
          2. The left upper abdomen (perisplenic and left perirenal areas)
          3. Suprapubic region (perivesical area)
          4. Subxyphoid region (pericardium)

          above: diagram of the RUQ and Morison’s space

          Excerpts From Dr. Geoffrey Hayden Notes (Trauma Ultrasound and the FAST exam):

          Pericardial view:


          1. Look at the interface between the right ventricle and the liver to identify pericardial fluid
          2. Cardiac tamponade identification is the immediate aim of this study
          3. A little fluid (non-circumferential) may be completely normal
          4. Circumferential pericardial fluid +/- RV or RA collapse is concerning

          Sono technique:

          1. Probe in the subxiphoid area and angled toward the patient’s left shoulder, with the pointer at 9 o’clock
          2. Transducer is almost parallel to the skin of the torso
          3. Press firmly just inferior to the xiphoid
          4. May need to move the transducer further to the patient’s right in order to use the liver as an acoustic window
          5. Normal pericardium is seen as a hyperechoic (white) line surrounding the heart


          1. A pericardial fat pad can be hypoechoic or contain gray-level echoes; almost always located anterior to the right ventricle and is not present posterior to the left ventricle
          2. Small pericardial fluid (non-circumferential) may be normal; do not immediately ascribe hypotension to a small amount of pericardial fluid
          3. Scan may be limited by obesity, protuberant abdomen, abdominal tenderness, gas, as well as pneumoperitoneum/pneumothoraces
          4. Sometimes hard to differentiate pleural fluid versus pericardial fluid


          1. Transducer should be flat to the skin (overhand technique with probe)
          2. Have the patient take a breath in and “hold it”
          3. If the subxiphoid window is not available, may substitute with the parasternal long or short axis; know your alternatives

          Perihepatic view (RUQ):


          1. Evaluating Morison’s pouch=potential space between the liver and the right kidney
          2. 4 areas to evaluate for “free fluid”:
            1. Pleural space
            2. Sub-diaphragmatic space
            3. Morison’s pouch
            4. Inferior pole of the kidney/paracolic gutter

          Sono technique:

          1. Probe indicator in the subcostal window points cranially (stay midclavicular, fluid is dependent)
          2. Probe indicator in the intercostal window should point toward the right posterior axilla along the angle of the ribs (oblique angle)
          3. Right intercostal oblique and right coronal views: evaluate for right pleural effusion, free fluid in Morison’s pouch, and free fluid in the right paracolic gutter
          4. The paracolic gutter may be visualized by obtained by placing the transducer in either the upper quadrant in a coronal plane and then sliding it caudally from the inferior pole of the kidney
          5. The liver appears homogenous, with medium-level echogenicity; Glissen’s capsule is echogenic
          6. The kidneys have a brightly echogenic surface (Gerota’s fascia)


          1. Perinephric fat is a mimic for hematoma
          2. Duodenal fluid, the gallbladder, and the IVC are all mimics for free fluid (follow these carefully)


          1. Perinephric fat has even thickness (not pointy), and is symmetric with the opposite kidney
          2. Pleural fluid will present as an anechoic strip superior to the diaphragm, instead of the usual “mirror artifact”

          Perisplenic view (LUQ):


          1. 4 areas to evaluate for “free fluid”:
            1. Pleural space
            2. Sub-diaphragmatic space
            3. Splenorenal recess
            4. Inferior pole of the kidney/paracolic gutter

          Sono technique:

          1. Reach across the patient
          2. Probe indicator should point toward the left posterior axilla along the angle of the ribs (oblique angle, pointer toward 2 o’clock)
          3. Think more posterior and more cephalad than would be expected
          4. The left intercostal oblique and left coronal views may be used to examine for left pleural effusion, free fluid in the subphrenic space and splenorenal recess, and free fluid in the left paracolic gutter
          5. The spleen has a homogenous cortex and echogenic capsule and hilum


          1. Fluid-filled stomach can mimic fluid, as can loops of bowel and perinephric fat (see above)


          1. Posterior posterior posterior
          2. Angle probe with ribs

          Pelvic view:


          1. Evaluating for free fluid around the bladder
          2. Most dependent part of the abdomen (though RUQ is still the most sensitive for FF)

          Sono technique:

          1. Probe should be placed 2cm superior to the symphysis pubis along the midline of the abdomen
          2. Both transverse and longitudinal images should be obtained
          3. Angle probe down until the prostate or vaginal stripe is identified (any lower and you will be inferior to the peritoneal reflection)
          4. Sweep all planes of the bladder
          5. In the longitudinal plane, scan side to side to identify pockets of free fluid between bowel loops


          1. Fluid within a collapsed bladder or an ovarian cyst may appear as free intraperitoneal fluid
          2. Seminal vesicles may also be incorrectly identified as free fluid
          3. Premenopausal females may normally have a small amount of free fluid in the pouch of Douglas
          4. Watch out for gain artifact; turn your gain down for this exam
          5. The iliopsoas muscles can mimic free fluid (they look like kidneys)


          1. A full bladder is essential for an adequate scan (can’t do much about this with sick trauma patients)

          Pneumothorax study:


          1. Evaluating for a pneumothorax
          2. Absence of a “sliding sign” and comet tail artifact supports the diagnosis

          Sono technique:

          1. The pleural space is just deep to the posterior aspect of the ribs
          2. There is a notable echogenic line with a “sliding appearance” composed of the visceral and parietal pleura
          3. This is considered the normal “sliding sign” and is considered negative for pneumothorax
          4. May use a high-frequency, linear transducer or your abdominal probe
          5. The transducer is placed longitudinally (pointed cranially) in the midclavicular line over the third or fourth intercostal space
          6. The transducer is then moved inferiorly in a systematic fashion, ensuring an appropriate “sliding sign”


          1. Bilateral pneumothoraces may limit your comparison of sides
          2. Any movement of the probe may give you a false negative study (see pleural sliding when there isn’t…..)


          1. The abdominal probe is a reasonable alternative to the linear probe for the pneumothorax study; it may make the “sliding sign” easier to visualize
          2. Systematic scanning from cranial to caudal

          Keys to the FAST exam:

          1. Complete exam in every view
          2. Identify pathology, not VIEWS
          3. All abnormalities should be imaged in 2 orthogonal planes
          4. Note incidental findings

          Limitations to the FAST exam:

          1. Though the quantity of free intraperitoneal fluid that can be accurately detected on ultrasound has been reported as little as 100mL, the typical cut-off is around 500-600mL; smaller amounts of free fluid may be missed (one reason why a repeated exam can be helpful)
          2. Can’t detect a viscus perforation
          3. Can’t detect a bowel wall contusion
          4. Can’t detect pancreatic trauma
          5. Can’t detect renal pedicle injuries

          Points to Consider

          1. Pelvis – most dependent
          2. Hepatorenal fossa – most dependent area in the supramesocolic region
          3. Pelvis and Supramesocolic Areas communicate – Phrenicolic ligament prevents flow
          4. Liver/Spleen Injuries – represents about 2/3 of cases of blunt abdominal trauma
          5. Intraperitoneal Fluid may consist of
            1. Blood
              1. Fresh Blood
                1. Anechoic (black)
              2. Coagulated Blood
                1. Hypoechoic
            2. Preexisting ascites
            3. Urine
            4. Intestinal contents
          6. Mimics of fluid in RUQ
            1. Perinephric fat
              1. May be hypoechoic like blood
              2. Usually evenly layered along kidney
              3. If in doubt, compare it to the left kidney
            2. Abdominal Inflamation
              1. Widened extra-renal space
              2. Echogenicity of kidney becomes more like the liver parenchyma
          7. LUQ (near ribs 9 and 10)
            1. Acoustic window (spleen) is smaller than the liver
            2. Mild inspiration will optimize image
            3. Bowel interference is common
          8. Pelvis (suprapubic)
            1. Helpful to image before placement of a Foley catheter
            2. If bladder is empty or Foley already placed
              1. Place an IV bag on the abdomen and scan through the bag
            3. A very large bladder can displace fluid from the pouch of Douglas
              (cul-de-sac) in females and cause a false-negative study
          9. Increased sensitivity with
            1. increased number of views
            2. Trendelenberg
            3. Serial Examinations
          10. Normal echo does not definitively rule out major pericardial injury
          11. Epicardial fat pad may easily be misinterpreted as a clot

          SonoSite (Videos)

          FAST RUQ Exam: Normal Exam (Hepatorenal)

          FAST RUQ Exam: Hemorrhage (Hepatorenal)

          FAST LUQ Exam: Normal and Abnormal (Splenorenal or Perisplenic)

          FAST Suprapubic Exam: Normal (Bladder or Pelvic)


          Mike Stone

          1. FAST Bonus – RUQ Exam Technique
          2. FAST Bonus – LUQ Exam Technique
          3. FAST Bonus – Subcostal Exam Technique
          4. FAST Bonus – Pelvis Technique


          1. FAST Part 2 – Getting the Right Upper Quadrant Right…
          2. FAST Part 3 – Heidi Kimberly Does the Left Upper Quadrant
          3. FAST Part 4 – The Pelvic View
          4. FAST Part 5 – Pneumothorax (E-FAST)
          5. FAST Part 6 – Josh Rempell covers hemothorax and reviews pneumothorax

          Flow Diagrams

          Schwartz’s Principles of Surgery

          Fast Exam Chart

          Wikipedia – Interpretation

          File:FAST Algorithm.svg


          Penetrating Thoracoabdominal Trauma

          Blunt Abdominal Trauma

          Summary of FAST vs. CT vs. DPL (Diagnostic Peritoneal Lavage)

          1. Speed – FAST>DPL>CT
          2. Sensitivity – DPL>CT and FAST
          3. Specificity – CT>FAST>DPL
          4. Localization – CT>FAST>DPL
          5. Ease/portability – FAST>DPL>CT
          6. Safety – FAST>CT>DPL
          7. Cost – DPL<FAST<CT


          1. Anechoic Stripe Size Influences Accuracy of FAST Examination Interpretation
          2. Deep Impact of Ultrasound in the Intensive Care Unit – The “ICU-sound” Protocol
          3. Diagnostic accuracy of surgeon-performed focused abdominal sonography (FAST) in blunt paediatric trauma
          4. Emergency ultrasound-based algorithms for diagnosing blunt abdominal trauma
          5. EAST – Evaluation of Blunt Abdominal Trauma
          6. eMedicine
            1. Bedside Ultrasonography for Pneumothorax
            2. Focused Assessment With Sonography for Trauma (FAST): Slideshow
            3. Focused Assessment with Sonography in Trauma (FAST)
            4. Imaging in Kidney Trauma
            5. Pneumothorax
            6. Intra-abdominal injuries in polytrauma
          7. FAST scan – Is it worth doing in hemodynamically stable blunt trauma patients
          8. Focused abdominal sonogram for trauma – the learning curve of nonradiologist clinicians in detecting hemoperitoneum
          9. Focused Assessment with Sonography for Trauma (FAST): results from an international consensus conference
          10. Pediatric Abdominal Trauma Imaging
          11. Penetrating stab wounds to the abdomen: use of serial US and contrast-enhanced CT in stable patients
          12. Prospective analysis of the effect of physician experience with the FAST examination in reducing the use of CT scans
          13. Role of ultrasonography in penetrating abdominal trauma: a prospective clinical study
          14. The technical errors of physicians learning to perform focused assessment with sonography in trauma
          15. Test Characteristics of Focused Assessment of Sonography for Trauma for Clinically Significant Abdominal Free Fluid in Pediatric Blunt Abdominal Trauma
          16. The ultrasound screen for penetrating truncal trauma
          17. Ultrasound detection of blunt urological trauma: a 6-year study
          18. Ultrasound in Abdominal Trauma
          19. Ultrasound in Trauma
          20. Use of focused abdominal sonography for trauma at pediatric and adult trauma centers – a survey
          21. Validation of nurse-performed FAST ultrasound
          22. What is the utility of the Focused Assessment with Sonography in Trauma (FAST) exam in penetrating torso trauma



          Capnography (end-tidal CO2 monitoring) is a non-invasive measurement of carbon dioxide in exhaled air to assess a patients’ ventilatory status. It may also be referred to as partial pressure end tidal carbon dioxide monitoring (PETCO2). The end-tidal CO2 (EtCO2) level is a reflection of global CO2 production in the body. Cardiac function, pulmonary function, and metabolic rate all influence the amounts of CO2 produced. The end-tidal CO2 provides information on systemic CO2 production (from exhaled alveolar gas), pathologic dead space, pulmonary blood flow, and confirmation of endotracheal tube placement. Capnography allows trending of CO2 levels using fewer arterial blood gas analyses, but does not completely replace arterial blood gas analysis. Age, smoking, general anesthesia, and systemic diseases can increase the difference between the CO2 value obtained from non-invasive monitoring and arterial blood gas monitoring. Note that capnography measures ventilation, not oxygenation.

          Comparison of Capnography and Pulse Oximetry
          Capnography Pulse Oximetry
          Measures CO2 Measures oxygen saturation
          Reflects ventilation Reflects oxygenation
          Hypoventilation / apnea detected immediately Changes lag with hypoventilation / apnea
          Should be used with pulse oximeter Should be used with capnography

          Maintenance of a patient’s airway is always a primary patient care objective. If the airway
          patency is lost, no other treatment modalities can prevent death.


          1. Alveolar Dead Space: When gas exchange doesn’t occur because air is present, but no blood is available to exchange gas. Or there is blood but no air. It could also be because the exchange surface is compromised by pulmonary edema, pulmonary effusion, or swollen membranes
          2. Alveolar volume (Va) – Air that is available for gas exchange, which is typically about 350 cc (Vt – Vd = Va); Anything that affects the tidal volume only affects the alveolar volume.
          3. Anatomical Dead Space (Vd) – Air not available for gas Exchange, which is typically about 150 cc
          4. Bradypnea – slower than normal rate (<10 breaths/min), with normal depth and regular rhythm. Associated with ICP, brain injury, and drug overdose.
          5. Capnogram – the wave form.
          6. Capnography – the measurement of carbon dioxide (CO2) in exhaled breath.
          7. Capnometer – the numeric measurement of CO2.
          8. Dyspnea – air hunger, difficult or labored breathing, shortness of breath
          9. End Tidal CO2 (ETCO2 or PetCO2) – the level of (partial pressure of) carbon dioxide released at end of expiration. Normal values range between 35 and 45 mmHg
          10. Hyperventilation – Increased rate and depth of breathing that results in decreased PaCO2 level. Fast breathing (tachypnea) doesn’t necessarily increase tidal volume, which can be caused by anxiety, head injuries, diabetic emergencies, PE, AMI, and others
          11. Hypoventilation – Shallow, irregular breathing. Slow breathing (bradypnea) does not necessarily decrease tidal volume. Causes include CNS disorders, narcotic use and others.
          12. PACO2 – Partial pressure of CO2 in the alveoli.
          13. PaCO2 – Partial pressure of CO2 in arterial blood.
          14. PCO2 – Partial pressure of CO2 in the blood
          15. PETCO2 – Partial pressure of CO2 at the end of expiration. ~ 38 mm Hg (usually 1 – 6 mm Hg less than PaCO2)
          16. (a-ET)PCO2 – Arterial to end-tidal CO2 tension/pressure difference or gradient.
          17. PvCO2 – Partial pressure of CO2 in mixed venous blood.
          18. Physiologic Dead Space – is the alveolar gas that does not equilibrate fully with capillary blood. In normal subjects, dead space ventilation (VD) accounts for 20 to 30% of the total ventilation (VT), so VD/VT = 0.2 to 0.3
          19. Respiration (or diffusion) is measured by the amount of oxygen in the blood.
          20. Tachypnea – rapid, shallow breathing (>24 breaths/min). Associated with pneumonia, pulmonary edema, metabolic acidosis, septicemia, severe pain, or rib fracture.
          21. Tidal Volume (Vt) – The amount of air moved in one breath, which is typically around 500 cc in an adult at rest
          22. Ventilation is measured by the amount of carbon dioxide in the blood.


          Upper and Lower Airways


          The Lungs

          The lungs are cone-shaped organs that hold between 4 – 8 liters of volume. The top portion is known as the apex, and the bottom is known as the base. The apex of each lung rises above the clavicles a few centimeters and the base rests against the diaphragm. The right lung has 3 lobes: upper, middle, and lower. The left has two lobes: upper and lower.



          Aspiration pneumonias are often located in the right middle lobe due to the shorter, straighter right mainstem bronchus.

          The Diaphragm

          The diaphragm is the major muscle of ventilation. It is a dome-shaped musculofibrous partition located between the thoracic and abdominal cavities. It is composed of two muscles: the right and left hemidiaphragms. The diaphragm allows the esophagus, the aorta, several nerves, and the inferior vena cava to exit through it. The phrenic nerve exits the central nervous system between cervical vertebrae 3 – 5 and extends down to innervate the diaphragm assisting in controlling ventilation.



          Patients with cervical spine injuries of C3, C4 and C5 are often dependent on mechanical ventilation. This is due to interruption of nerve transmission to the diaphragm and other ventilatory muscles.

          Accessory muscles of ventilation

          During vigorous exercise and the advanced stages of pulmonary disease processes (e.g. COPD) the accessory muscles of inspiration and expiration are activated to assist the diaphragm.

          Muscles of Inspiration (I)

          Muscles of Expiration (E)

          Scalene muscles

          Rectus abdominis muscles

          Sternocleidomastoid muscles

          External abdominal obliquus muscles

          Pectoralis major muscles

          Internal abdominis obliquus muscles

          Trapezius muscles

          Transversus abdominis muscles

          External intercostal muscles

          Internal intercostal muscles

          PaCO2 Equation – PaCO2 reflects ratio of metabolic CO2 production to alveolar ventilation

          The PCO2 equation puts into physiologic perspective one of the most common of all clinical observations: a patient’s respiratory rate and breathing effort. The equation states that alveolar PCO2 (PACO2) is directly proportional to the amount of CO2 produced by metabolism and delivered to the lungs (VCO2) and inversely proportional to the alveolar ventilation (VA). While the derivation of the equation is for alveolar PCO2, its great clinical utility stems from the fact that alveolar and arterial PCO2 can be assumed to be equal. Thus,



          Condition in Blood

          State of Alveolar Ventilation

          > 45 mm Hg



          35 – 45 mm Hg


          Normal ventilation

          < 35 mm Hg



          The constant 0.863 is necessary to equate dissimilar units for VCO2 (ml/min) and VA (L/min) to PACO2 pressure units (mm Hg). Alveolar ventilation is the total amount of air breathed per minute (VE; minute ventilation) minus that air which goes to dead space per minute (VD). Dead space includes all airways larger than alveoli plus air entering alveoli in excess of that which can take part in gas exchange.


          In the clinical setting we don’t need to know the actual amount of CO2 production or alveolar ventilation. We just need to know if VA is adequate for VCO2; if it is, then PaCO2 will be in the normal range (35-45 mm Hg). Conversely, a normal PaCO2 means only that alveolar ventilation is adequate for the patient’s level of CO2 production at the moment PaCO2 was measured.  From the PCO2 equation it is evident that a level of alveolar ventilation inadequate for CO2 production will result in an elevated PaCO2 (> 45 mm Hg; hypercapnia). Thus patients with hypercapnia are hypoventilating (the term hypoalveolar ventilating would be more appropriate but hypoventilating is the conventional term). Conversely, alveolar ventilation in excess of that needed for CO2 production will result in a low PaCO2 (< 35 mm Hg; hypocapnia) and the patient will be hyperventilating. (Confusion sometimes arises because the prefix (hyper-, hypo-) differs for the same condition depending on whether one is describing a blood value or the state of alveolar ventilation.) For reasons that will be discussed below, the terms hypo- and hyper- ventilation refer only to high or low PaCO2, respectively, and should not be used to characterize any patient’s respiratory rate, depth, or breathing effort.

          From the PCO2 equation it follows that the only physiologic reason for elevated PaCO2 is a level of alveolar ventilation inadequate for the amount of CO2 produced and delivered to the lungs. Thus arterial hypercapnia can always be explained by:

          1. Not enough total ventilation (as may occur from central nervous system depression or respiratory muscle weakness); or
          2. Too much of the total ventilation ending up as dead space ventilation (as may occur in severe chronic obstructive pulmonary disease, or from rapid, shallow breathing); or
          3. Some combination of 1) and 2).

          Excess CO2 production is omitted as a specific cause of hypercapnia because it is never a problem for the normal respiratory system unimpeded by a resistive load. During submaximal exercise, for example, where CO2 production is increased, PaCO2 stays in the normal range because VA rises proportional to the rise in VCO2. With extremes of exercise (beyond anaerobic threshold) PaCO2 falls as compensation for the developing lactic acidosis. In a healthy patient PaCO2 may be reduced but is never elevated.

          An important clinical corollary of the PaCO2 equation is that we cannot reliably assess the adequacy of alveolar ventilation – and hence PaCO2 – at the bedside. Although VE can be easily measured with a handheld spirometer (as tidal volume times respiratory rate), there is no way to know the amount of VE going to dead space or the patient’s rate of CO2 production. Other clinical factors include respiratory effort, mental status, body habitus, temperature, etc.

          A common mistake is to assume that because a patient is breathing fast, hard and/or deep he or she must be “hyperventilating.” Not so, of course.









          PCO2 vs. Alveolar Ventilation

          The relationship is shown for metabolic carbon dioxide production rates of 200 ml/min and 300 ml/min (curved lines). A fixed decrease in alveolar ventilation (x-axis) in the hypercapnic patient will result in a greater rise in PaCO2 (y-axis) than the same VA change when PaCO2 is low or normal.
          This graph also shows that if alveolar ventilation is fixed, an increase in carbon dioxide production will result in an increase in PaCO2.


          Effect of Increasing Arterial PCO2 or Reducing pH on Ventilation

          Guyton & Hall, Textbook of Medical Physiology, 10th ed., 2000, Saunders p. 477.


          The effect of PCO2 on ventilation is primarily due to a region of the ventral medulla referred to as the chemosensitive area. In this area, there are sensor neurons that are excited by hydrogen ions. As arterial PCO2 rises, CO2 easily and rapidly diffuses through the blood brain barrier where it combines with water to form carbonic acid which releases a hydrogen ion. So, the net effect of increased arterial PCO2 is increased cerebrospinal fluid (CSF) and brain interstitial acidity. This strongly stimulates these sensor neurons which stimulate the respiratory centers to increase ventilation (this will tend to reduce the arterial PCO2 back to baseline).

          Hydrogen ions themselves do not diffuse as easily across the blood brain barrier making the direct effect of pH less. The effect of PCO2 on ventilation is strongest in the acute phase. If the person has a high PCO2 for a prolonged period (days or longer, perhaps due to a lung or neurological problem), the pH of the CSF tends to return toward normal because of adaptive effects related to bicarbonate. The person becomes accustomed to the higher PCO2 and it causes less stimulus to hyperventilate.

          Ventilation Increases as PaO2 Decreases at Constant PaCO2

          Guyton & Hall, Textbook of Medical Physiology, 10th ed., 2000, Saunders p. 479.


          Integrated Effects of PCO2, PO2 & pH on Alveolar Ventilation

          Guyton & Hall, Textbook of Medical Physiology, 10th ed., 2000, Saunders p. 479.



          Currently, there are 2 basic types of CO2 detectors: quantitative and qualitative.

          1. Qualitative CO2 detectors are colorimetric detectors that contain material that reversibly reacts with CO2. This reaction causes the color to change, most commonly, from purple to yellow. Qualitative capnography units can be broken down into mainstream and sidestream configurations.
            1. Mainstream units, or in-line units, are used for ventilated patients who are intubated endotracheally. The sensor is placed directly on an adapter attached to the endotracheal tube. From there, EtCO2 can be directly measured.
            2. Sidestream units have a sensor that is located on the main unit itself. These systems aspirate the gas sample from the patient’s airway, which then measures the EtCO2. In turn, sidestream units can be used in awake or intubated patients.
          2. Quantitative CO2 detectors give a measured value of EtCO2. This numeric value is referred to as capnometry. Quantitative detectors can also be displayed as a waveform called a capnogram. This waveform of inspiratory/expiratory CO2 can be displayed over time or volume and is referred to as a capnograph.

          How medical equipment works – Capnography

          Levels or Phases

          Information from Capnography can be broken down into levels, each with increasing degrees of information

          1. Level 1

          1. Breathing or not, i.e. apnoea monitor
          2. Respiratory rate

          2. Level 2

          1. Expired CO2 levels (4.5% or 35mmHg)
          2. Inspired CO2 levels (0%)
          3. From these parameters we can now begin to deduce the state of the patient with regard to respiration i.e. normocapnic, hypocapnic or hypercapnic

          3. Level 3

          1. Waveform profile
          2. There are 4 recognised parts to a typical capnogram, each one having characteristics that impart specific information
          3. A typical capnogram obtained during controlled mechanical ventilation showing:
            1. i. Inspiratory baseline (A to B)
            2. ii. Expiratory upstroke (B to C)
            3. iii. Expiratory plateau (C to D)
            4. iv. Inspiratory down stroke (D to E)


          Advanced Emergency Nursing Journal Vol. 28, No. 4, pp. 301–313



          1. “α” (Alpha) angle – Used to assess the Ventilation/ Perfusion (V/Q) status of lung. During mismatches, the alpha angle is > ~ 90 degrees. The more damaged and less uniform the alveoli, the larger the angle. Bronchospasm (sharkfin), COPD, etc.
          2. “β” (Beta) angle – Used to assess rebreathing. During rebreathing, the beta angle is > 90 degrees. May see in infants who are breathing faster than capnograph can account for.

          A normal capnogram look like the following.


          Its analysis should include the following:

          1. Verify presence of exhaled CO2
            1. Is a waveform present?
          2. Inspiratory baseline
            1. Is there rebreathing?
          3. Expiratory upstroke
            1. Is it steep, sloping, or prolonged?
          4. Expiratory plateau
            1. Is it flat, prolonged, notched, or sloping?
          5. Inspiratory down stroke
            1. Is it steep, sloping, or prolonged?
          6. Check PICO2 min and PECO2max
          7. Estimate or measure PaCO2 – PECO2 max
          8. Search for causes of hypercapnia or hypocapnia, if either is present

          Clinical Application Examples of Capnography

          Slap the Cap – The Role of Capnography in EMS

          1. One of two sure signs of endotracheal intubation.

            1. This is probably the most common use of capnography, yet limiting oneself to this use only is a huge waste. In the beginning, color change devices would detect CO2 levels. This is widely believed to be able to accurately predict when the endotracheal tube is misplaced in the esophagus. Theoretically, there should be no CO2 exhaled from the esophagus, on the trachea. However, in low perfusion states, this is not a very accurate reading and the manufacturer even suggests using another confirming device besides this one. Therefore, waveform capnography is the gold standard for endotracheal tube confirmation. Tube confirmation is confirmed with a SQUARE waveform. With a square waveform, the tube cannot be in the esophagus, or the hypopharynx. It must be in the trachea, regardless of the value of the return of CO2.


            2. Right mainstem intubation. A square waveform can occur with a right mainstem intubation because the tube is still in the main airway.Therefore, auscultation in the fifth intercostal space midaxillary, bilaterally, is necessary to rule out right mainstem intubation.
          2. Detection of untoward events e.g… Disconnections or inadvertent extubation.
          3. Maintenance of normocapnia
          4. Cardiopulmonary resuscitation
            1. As an assessment tool during CPR, capnography is a direct measurement of ventilation in the lungs, and it also indirectly measures metabolism and circulation. For example, a decrease in perfusion (cardiac output) will lower the delivery of carbon dioxide to the lungs. This will cause a decrease in the ETCO2 (end-tidal CO2), and this will be observable on the waveform as well as with the numerical measurement.
            2. Two very practical uses of waveform capnography in CPR are: 1.) evaluating the effectiveness of chest compressions; and 2.) identification of ROSC. Evaluating effectiveness of chest compressions is accomplished in the following manner: Measurement of a low ETCO2 value (< 10 mmHg) during CPR in an intubated patient would indicate that the quality of chest compressions needs improvement.
            3. An abrupt increase in PETCO2 may indicate return of spontaneous circulation (ROSC), Increase in pulmonary circulation brings more CO2 into lungs for elimination.  In most cases that have ROSC the ETCO2 goes into the 70-90’s!
          5. Weaning from mechanical ventilation
          6. Monitoring the seizure patient
            1. Generalized seizure, such as a tonic/clonic, can affects both hemispheres of the brain and the medulla. When the medulla is involved, the patient may not breath during seizure activity. Following the post-ictal state capnography can determine the need for further ventilation.
          7. Metabolic Uses: DKA
            1. Since CO2 is carried in the blood stream and bicarbonate Ion, it has a
              direct clinical relationship to serum bicarb levels. Therefore, if the patient
              has a high Blood glucose, measure their ETCO2. If it is less than 29, then
              the patient has DKA. The blood gas bicarb will show a very low level as
              well, indication metabolic acidosis.
          8. Pulmonary Embolism: This is easy. The combination of ETCO2 and an ABG CO2 can easily call a V/Q mismatch. All you need then is a CT scan to figure out where it is and
            they are on their way. A high blood gas CO2 and a low ETCO2 tells us the
            CO2 is not getting to the lungs to be exhaled.
          9. Trauma?
            1. In Tension Pneumothorax, pressure in the chest collapses a lung and then
              presses on the right side of the heart making it hard to fill with blood. It
              only takes about 7mm/hg pressure to stop the blood flow into the right
              atria. The first and must reliable sign of a TENSION pneumothorax is the
              sudden drop in perfusion that is picked up immediately on a capnogram.
              By the same token, when the chest is successfully decompressed, it is not
              a rush of air but a sudden increase in ETCO2 that confirms decompression
              success. Furthermore, the capnogram can be used to keep watch in case
              it develops again.
            2. The same is true for Pericardial Tamponade and cardiocentesis. In each
              of these obstructive forms of hypoperfusion, the capnogram will remain
              square because it is a perfusion problem, not an airway problem, but you
              knew that, right?
          10. Closed Head Injury. ITLS and the Brain Trauma Foundation have taken the
            lead in recommending capnography as the way titrate CO2 ventilations in
            the patient with a closed head injury. If the patient has a GCS of less than
            9 and they are posturing, have unequal pupils, or dropped two in front of
            you, then they should be selectively ventilated to an ETCO2 between 30-
            35mm/hg. If the patient does not the signs (above) of deterioration, then
            ventilate the patient to levels, 35-45. Never ever bag them to lower than
            25mm/hg. It causes cerebral vasoconstriction and creates an alkalosis not
            allowing O2 to dissociate from hemoglobin, make the brain injury worse.
          11. Monitoring the non-intubated patient
            1. Capnography helps conscious patients too

          Specific Waveforms to Know

          There are a few specific waveforms that you need to know.





          Capnography Outside the Operating Rooms

          Kodali, Bhavani Shankar Anesthesiology. 118(1):192-201, January 2013. doi: 10.1097/ALN.0b013e318278c8b6


          A, Prolonged phase II, increased α angle, and steeper phase III suggest bronchospasm or airway obstruction.

          B, Expiratory valve malfunction resulting in elevation of the baseline, and the angle between the alveolar plateau and the downstroke of inspiration is increased from 90°. This is due to rebreathing of expiratory gases from the expiratory limb during inspiration.

          C, Inspiratory valve malfunction resulting in rebreathing of expired gases from inspiratory limb during inspiration (reference 5 for details).

          D, Capnogram with normal phase II but with increased slope of phase III. This capnogram is observed in pregnant subjects under general anesthesia (normal physiologic variant and details in reference 9).

          E, Curare cleft: Patient is attempting to breathe during partial muscle paralysis. Surgical movements on the chest and abdomen can also result in the curare cleft. (You have maybe 3 minutes to sedate the patient before they begin to waken or start to fight the tube.)

          F, Baseline is elevated as a result of carbon dioxide rebreathing.

          G, Esophageal intubation resulting in the gastric washout of residual carbon dioxide and subsequent carbon dioxide will be zero.

          H, Spontaneously breathing carbon dioxide waveforms where phase III is not well delineated.

          I, Dual capnogram in one lung transplantation patient. The first peak in phase III is from the transplanted normal lung, whereas the second peak is from the native disease lung. A variation of dual capnogram (steeple sign capnogram – dotted line) is seen if there is a leak around the sidestream sensor port at the monitor. This is because of the dilution of expired PCO2 with atmospheric air.

          J, Malignant hyperpyrexia where carbon dioxide is raising gradually with zero baseline suggesting increased carbon dioxide production with carbon dioxide absorption by the soda lime.

          K, Classic ripple effect during the expiratory pause showing cardiogenic oscillations. These occur as a result of to-and-for movement of expired gases at the sensor due to motion of the heartbeat during expiratory pause when respiratory frequency of mechanical ventilation is low. Ripple effect like wave forms also occur when forward flow of fresh gases from a source during expiratory pause intermingles with expiratory gases at the sensor.

          L, Sudden raise of baseline and the end-tidal PCO2 (PETCO2) due to contamination of the sensor with secretions or water vapor. Gradual rise of baseline and PETCO2 occurs when soda lime is exhausted.

          M, Intermittent mechanical ventilation (IMV) breaths in the midst of spontaneously breathing patient. A comparison of the height of spontaneous breaths compared to the mechanical breaths is useful to assess spontaneous ventilation during weaning process.

          N, Cardiopulmonary resuscitation: capnogram showing positive waveforms during each compression suggesting effective cardiac compression generating pulmonary blood.

          O, Capnogram showing rebreathing during inspiration. This is normal in rebreathing circuits such as Mapleson D or Bain circuit.


          1. AHRQ Guideline – Capnography/capnometry during mechanical ventilation: 2011 
          2. BCEMS
            1. Capnography Part I
            2. Capnography Part II
          3. Capnography
          4. Capnography Outside the Operating Rooms
          5. Capnography/Capnometry During Mechanical Ventilation: 2011 (pdf)
          6. Cecil medicine – Chapter 104 – Respiratory Monitoring in Critical Care
          7. Council of the Intensive Care Society – Capnography Guidelines
          8. Difficult Airway Society – Capnography the Future
          9. Emergency Nurses Association – Wave Form Capnography The 12 Lead of the Lungs!
          10. Interpreting your capnogram
          11. Life in the Fast Lane
            1. Capnography
            2. Respiratory Monitoring in the ED
          12. NIAA – National Audit Project 4
          13. Noninvasive Monitoring of End-Tidal Carbon Dioxide in the Emergency Department
          14. Phillips – Clinical Measurements – A Quick Guide to Capnography 
          15. Physiology of Oxygenation and Ventilation
          16. Slap the Cap – The Role of Capnography in EMS
          17. Rapid Results – Capnography: A Key Patient Assessment Tool
          18. Riding the Waves (pdf)
          19. The Alveolar Gas Equation (pdf)

          Efficacy of Nimodipine Administration on Vasospasm after Subarachnoid Hemorrhage

          I reviewed three articles on the efficacy of Nimodipine administration on vasospasm after subarachnoid hemorrhage in order to produce improved clinical outcomes.

          Efficacy of Nimodipine Administration on Vasospasm after Subarachnoid Hemorrhage

          Although the outcomes for these patients continues to remain poor, the current evidence suggests that calcium antagonist like Nimodipine can play an integral part of providing the best possible care for this populuation subset. The authors demonstrate that continuous local intra-arterial nimodipine administration (CLINA) is both safe and effective in helping reverse vasospasm and prevent delayed ischemic neurological deficit commonly associated with subarachnoid hemorrhage. They show that intra-arterial nimodipine administration shows good vessel widening effects against vasospasm. Additionally, the authors observed a positive correlation between the degree of blood vessel expansion and the improvement in clinical symptoms.

          Here are the three main articles referenced in the paper. Unfortunately, only the first article is available without a fee.

          1. Angiographic Features and Clinical Outcomes of Intra-Arterial Nimodipine Injection in Patients with Subarachnoid Hemorrhage-Induced Vasospasm
          2. Continuous intra-arterial infusion of nimodipine at the onset of resistant vasospasm in aneurysmal subarachnoidal hemorrhage – A technical resport ($)
          3. Continuous Local Intra-arterial Nimodipine Administration in Severe Symptomatic Vasospasm after Subarachnoid Hemorrhage ($)

          Here are the supporting related references, and fortunately most of them are available without a fee.

          1. American Association of Neurological Surgeons – Cerebral Aneurysm
          2. American Association of Neuroscience Nurses – Care of the Patient with Aneurysmal Subarachnoid Hemorrhage
          3. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association
          4. The Chocrane Library – Calcium Antagonists in Aneurysmal Subarachnoid Hemorrhage ($)
          5. Intra-Arterial Nimodipine for Severe Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: Influence on Clinical Course and Cerebral Perfusion
          6. The role of transcranial Doppler ultrasonography in the diagnosis and management of vasospasm after aneurysmal subarachnoid hemorrhage ($)
          7. Inflammation and cerebral vasospasm after subarachnoid hemorrhage ($)
          8. Angiographic Features and Clinical Outcomes of Intra-Arterial Nimodipine Injection in Patients with Subarachnoid Hemorrhage-Induced Vasospasm