The Physiologically Difficult Airway

Author Affiliation
Jarrod M. Mosier, MD University of Arizona, Department of Emergency Medicine, Tucson, Arizona;
University of Arizona, Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep, Tucson, Arizona
Raj Joshi, MD University of Arizona, Department of Emergency Medicine, Tucson, Arizona;
University of Arizona, Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep, Tucson, Arizona
Cameron Hypes, MD University of Arizona, Department of Emergency Medicine, Tucson, Arizona;
University of Arizona, Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep, Tucson, Arizona
Garrett Pacheco, MD University of Arizona, Department of Emergency Medicine, Tucson, Arizona
Terence Valenzuela, MD University of Arizona, Department of Emergency Medicine, Tucson, Arizona
John C. Sakles, MD University of Arizona, Department of Emergency Medicine, Tucson, Arizona




Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications. This focus on difficult airway management has traditionally referred to identifying anatomic characteristics of the patient that make either visualizing the glottic opening or placement of the tracheal tube through the vocal cords difficult. This paper will describe the physiologically difficult airway, in which physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management. The four physiologically difficult airways described include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. The emergency physician should account for these physiologic derangements with airway management in critically ill patients regardless of the predicted anatomic difficulty of the intubation.


The “difficult airway” has traditionally been used to describe intubations that have anatomic characteristics that make visualization of the vocal cords and placement of the tracheal tube challenging. Although scoring systems and prediction rules to identify the potentially difficult airway may be helpful, the performance of these prediction methods is only moderately successful. Additionally, the last decade has seen an incredible expansion of devices available to successfully ventilate, visualize the vocal cords, and place a tracheal tube leaving these prediction methods less useful.1 However, even with the expansive armamentarium available for emergent airway management, contextual factors such as operator experience, time pressures, and the patient’s underlying physiologic alterations still often result in difficulty with optimizing gas exchange, which is the primary goal of airway management.2

Critically ill patients represent the highest risk patients to intubate because of these contextual factors that increase the incidence of adverse events leading to dangerous hypoxemia, hemodynamic collapse and cardiac arrest.3-11 This baseline physiologic risk is exaggerated when intubations require more than one attempt,12-15 with difficult intubations being an independent predictor of death.16 As a result of the higher risk of these untoward events at intubation, first pass success has become the goal. Research in airway management has lead to advances that have greatly improved the management of the anatomically difficult airway, yet critically ill patients remain high-risk patients due to underlying pathophysiologic abnormalities. While the anatomically difficult airway is one in which obtaining a glottic view or passing an endotracheal tube is challenging, the physiologically difficult airway is one in which physiologic derangements place the patient at higher risk of cardiovascular collapse with intubation and conversion to positive pressure ventilation. These physiologic derangements should be accounted for in the intubation plan even if one does not predict anatomic difficulty with intubation. This paper will review four clinically important physiologically difficult airways that the emergency physician will encounter: hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. Unfortunately, the physiologically difficult airway is not well described and there are very limited data available on management methods. In this paper we will provide physiologically and experience-based recommendations and, where available, evidence-based recommendations to decrease the risk of hemodynamic collapse when faced with one of these four high-risk airway management scenarios.


Hypoxemic respiratory failure (Type I) in which there is failure to maintain adequate arterial oxygenation is a relatively common indication for intubation and invasive mechanical ventilation in the emergency department (ED). The mechanism of acute hypoxemic respiratory failure is most commonly due to any etiology that disrupts optimal alveolar-capillary gas exchange, such as pneumonia, acute respiratory distress syndrome (ARDS), and cardiogenic or non-cardiogenic pulmonary edema. In each of these instances a portion of the blood passing through the pulmonary circulation shunts past the remaining functional alveoli without the opportunity to participate in gas exchange. This hypoxemia is different than that which occurs with hypercapneic respiratory failure (Type II), which is due to decreased alveolar ventilation or an increase in dead space. Hypoxemia from Type II respiratory failure is relatively easily corrected with supplemental oxygen or an increase in minute ventilation. Hypoxemic respiratory failure patients are at high risk for rapid desaturation during intubation, which may result in hemodynamic instability, hypoxic brain injury, and potentially cardiopulmonary arrest.7,17-19 Identification of patients at risk for desaturation, such as the patient with limited reserve from acute hypoxemic respiratory failure or obesity, and utilization of all techniques available to prolong this time to desaturation, or safe apnea time, regardless of one’s assessment of the anatomic difficulty of the intubation is critical for the emergency physician.

Preoxygenation is an important step in every intubation with the goals of achieving the following: 1) maximal hemoglobin saturation and, 2) maximal partial pressure of arterial oxygen.20,21 The current standard method of preoxygenation includes the use of a non-rebreather (NRB) mask with tidal breathing for 3–5 minutes. This standard was extrapolated from studies in the operating room that used tight-fitting facemasks that prevented any air leak from the anesthesia circuit.22-25 Safe apnea time is prolonged with preoxygenation, but variable depending on factors that change the rate of oxygen consumption or functional residual capacity (FRC) such as critical illness and obesity.26,27 While a NRB provides an oxygen reservoir designed to breathe a higher fraction of inspired oxygen (FiO2), the rigid mask does not create an adequate seal and thus ambient air is entrained around the mask and decreases the effective FiO2 to much less than 100%. The higher the minute ventilation, the more this ambient air dilutes the FiO2 by admixing with the oxygen reservoir from the NRB. This relationship of FiO2 with underlying minute ventilation makes preoxygenation with a NRB less effective in critically ill patients. Noninvasive positive pressure ventilation (NIPPV) has been shown to improve oxygenation beyond usual preoxygenation methods, particularly in patients with obesity and shunt physiology.28,29 NIPPV increases mean airway pressure with the benefit of alveolar recruitment, temporarily decreasing shunt fraction and improving oxygenation.28,30-33 Indications and contraindications for the use of NIPPV may not apply when the sole purpose of applying NIPPV is preoxygenation for intubation as the intubating clinician is physically present and prepared to intervene during this short period of time. When hypoxemic patients preoxygenated with NIPPV are removed from positive pressure for the intubation procedure, there is a risk of derecruitment of alveoli causing rapid desaturation. Maintaining continuous positive pressure during the intubation with the use of a nasal mask has been shown in the operating room to be beneficial in patients with hypoxemic respiratory failure and may be useful in the ED.34

Occasionally NIPPV is inadequate due to anatomic characteristics that make obtaining or maintaining an adequate mask seal difficult. In these patients that have significant mask leaks, or when higher pressures are required for preoxygenation, such as in patients with pulmonary edema or morbid obesity, supraglottic airways may be an option for preoxygenation. Current data for the use of supraglottic airways for preoxygenation in the ED are limited to a case report; however, there are some limited data showing success with prolonging safe apnea time in morbidly obese patients in the operating room.35,36 Limiting insufflation pressures to a maximum of 20cmH20 should not result in increased gastric distention or aspiration events.28,37,38

Pharmacologic assistance to decrease anxiety or even induce sedation may be useful if chosen carefully to improve patient tolerance of either the NIPPV mask or supraglottic airway. A recent observational study formalized a protocol, termed delayed sequence intubation (DSI), in which ketamine was administered to induce a dissociated state to allow preoxygenation with a NRB mask or NIPPV prior to the administration of a neuromuscular blocking agent, and showed most patients had improved preoxygenation.39

Apneic oxygenation, also known as “diffusion respiration” or “aventilatory mass flow,” occurs because oxygen removal from the aveoli by circulating blood brings alveolar pressure to slightly subatmospheric levels, generating a negative pressure gradient, drawing oxygen from the upper airway into the lungs.40 Nasal oxygen administration as a method of apneic oxygenation has repeatedly been shown to prolong safe apnea time, including in obese patients.41-43 Apneic oxygen supplementation has been found to prevent desaturation for as long as 100 minutes at the expense of severe hypercapnea and decreased pH in operative patients. However, the effects of hypercapnea during apnea can be deleterious leading to ventricular arrhythmias, neurologic compromise, and even death.44-48 Transnasal humidifed rapid-insufflation ventilatory exchange (THRIVE) has recently been shown to not only increase apnea time by delivering high-flow humidified oxygen via nasal cannula at 70L/pm, but also reduce the rate of carbon dioxide increase by gaseous mixing and flushing of dead space.49

Recent evidence with the use of a high-flow nasal cannula (HFNC) capable of delivering a humidified, adjustable FiO2 up to 60Lpm for preoxygenation and apneic oxygenation is mixed. Vourc’h and colleagues found no difference in desaturation rates when HFNC for preoxygenation and apneic oxygenation was compared to high-flow facemask in hypoxemic patients.50 However, Miguel-Montanes et al. found that preoxygenation and apneic oxygenation with the same HFNC reduced desaturation compared to NRB in patients intubated in the intensive care unit. HFNC resulted in higher O2 saturation after preoxygenation, during intubation, and at 5- and 30-minutes post-intubation.51 A benefit of HFNCs is varying amounts of continuous positive airway pressure achieved at higher flow rates.52 A low-cost, low-risk application of apneic oxygenation is via standard or wide-bore nasal prongs at 10–15L/pm. This flow rate is well tolerated,53 provides near 100% FiO2 to the nasopharynx during the apneic period and may prevent desaturation in some patients. For a more detailed description of preoxygenation and apneic oxygenation, see Weingart and Levitan’s comprehensive review.54


Preoxygenation and apneic oxygenation should be performed in all critically ill patients. Despite mixed data, apneic oxygenation is a low-risk intervention that may provide significant benefit in prolonging the safe apneic period. If a HFNC system is not available, a wide-bore nasal cannula or standard nasal prongs should be used to augment preoxygenation and provide apneic oxygenation.

In patients with shunt physiology due to atelectasis or alveolar filling from pneumonia, ARDS or pulmonary edema, NIPPV can improve alveolar recruitment and oxygenation. In select patients, supraglottic airways may be considered when higher pressures are needed or a mask seal with NIPPV cannot be achieved. One must balance this potential benefit of a supraglottic airway with the risk of aspiration or upper airway injury. Nasal continuous positive airway pressure with a nasal mask may be useful to maintain alveolar recruitment during intubation in patients at high risk.

For patients who cannot tolerate the NIPPV mask (e.g. delirium), analgesia, anxiolysis, or DSI may be considered to optimize preoxygenation. If procedural sedation for preoxygenation is performed, one must be prepared to intubate at the onset of DSI, even with ketamine, due risk of cardiac arrest, laryngospasm and apnea, which have all been reported with ketamine.55,56


Peri-intubation hypotension is common and roughly one-quarter of patients develop transient hypotension after emergent intubation and transition to positive pressure ventilation.57 A recent report shows that nearly 30% of critically ill patients had cardiovascular collapse after intubation.11 Peri-intubation hypotension is a major risk factor for adverse events, including cardiopulmonary arrest related to airway management, longer intensive care unit stays and increased hospital mortality.10,58-62 Griesdale and colleagues report that a SBP<70mmHg complicates 10% of intubations in critically ill patients6 and pre-induction shock index (heart rate/systolic blood pressure) >0.8 and hypotension have been shown to predict patients at risk for post-intubation hypotension.58,59,62

Venous return to the heart is driven by the difference between venous pressure (i.e. mean systemic pressure) and right atrial pressure. During spontaneous respiration, the negative intrathoracic pressure augments this pressure gradient, which in essence “pulls” blood back to the right heart. Any physiologic disturbance that disrupts this driving pressure gradient will decrease venous return. Transition to positive pressure ventilation increases intrathoracic pressure and thus right atrial pressure, decreasing the pressure differential driving venous return.63-66 Common causes of shock such as volume depletion, capillary leak, or a loss of systemic vascular resistance will decrease the mean systemic pressure and venous return making these patients particularly susceptible to positive pressure ventilation induced hypotension.

Fluid resuscitation is important in critically ill patients, as an increase in circulating volume will increase mean systemic pressure and venous return.65,67 If the right heart can accommodate the increased venous return, the patient will be a “volume responder” and cardiac output will increase. Volume responsiveness is typically defined as an increase in cardiac output by >15% in response to a fluid challenge. Rapid evaluation of volume responsiveness is easily performed at the bedside by a number of techniques evaluating cardiopulmonary interactions, such as respiratory changes in inferior vena cava diameter, arterial waveform analysis, or Doppler assessment of aortic flow velocities.68 Not all patients will be volume responsive, in which case vasopressors may be helpful for maintaining vascular tone and perfusion pressure and norepinephrine is preferred vasopressor in critically ill patients.69,70 Pure vasoconstrictors such as phenylephrine will increase vascular resistance and blood pressure, but will depress the cardiac output and decrease venous return. In patients who are in shock, or under-resuscitated, this decrease in venous return and depressed cardiac output may actually worsen hemodynamics despite improved blood pressure.64 In patients with transient hypotension during intubation from vasodilation or a positive pressure induced decrease in venous return, peripherally administered vasopressors may be useful for maintaining adequate end-organ perfusion pressure until adequate fluid resuscitation is achieved. Diluted phenylephrine boluses may be useful for ameliorating the decrease in vascular tone induced by anesthetic agents and maintain systemic vascular resistance and diastolic perfusion of the coronary arteries until the transient hypotension resolves or fluid resuscitation can be optimized.79-82 When given for a short duration, peripherally administered vasopressors have been shown to be low risk.71

The choice of induction agents can contribute to peri-intubation hypotension as many have adverse hemodynamic effects. Benzodiazepines and propofol have a sympatholytic effect, leading to myocardial depression and a decrease in vascular tone.72 Etomidate is a non-benzodiazepine sedative, which has been shown to be relatively hemodynamically neutral.73,74 Ketamine is also an attractive choice for an induction agent given its sympathomimetic properties,75 although there have been reports of cardiac arrest after ketamine administration.55 Jabre and colleagues compared etomidate and ketamine for emergency intubation in septic patients and found no difference in serious complications.76 Although generally considered hemodynamically neutral, some neuromuscular blocking agents have indirect cardiovascular effects through histamine release and parasympathetic activity.77,78 Thus, pre-intubation fluid resuscitation and thoughtful pharmacologic intervention will optimize the hemodynamic stability with airway management in the hypotensive patient.


Patients with conditions that reduce venous return are particularly susceptible to hypotension and patients at risk are suggested by pre-intubation hypotension or an elevated shock index >0.8. These patients should be hemodynamically optimized prior to intubation. This includes aggressive volume resuscitation if the patient is likely to be a volume responder. Hemodynamically stable induction agents should be used when possible.

For patients unresponsive to volume resuscitation, a norepinephrine infusion should be initiated.

If pre-intubation resuscitation is not feasible due to impending cardiopulmonary arrest in patients with shock, peripherally administered vasopressor boluses can be prepared quickly at the bedside and may maintain blood pressure during intubation and resuscitation. This intervention has not been studied in critically ill adults; however, diluted epinephrine (given as 10–50mcg boluses with a concentration of 1–10mcg/mL) may be preferred due to its inotropic effect.

For patients without shock who have a transient drop in blood pressure after intubation due to the vasodilatory effects of induction agents or transition to positive pressure ventilation, diluted phenylephrine (given as 50–200mcg boluses with a concentration of 100mcg/mL) may be useful.

Severe metabolic acidosis

When acidemia develops from a respiratory acidosis, rapid correction of that acidemia can occur by increasing the alveolar ventilation. Doubling the alveolar ventilation will reduce the PaCO2, roughly by half. Respiratory acidosis is then usually corrected easily by interventions that increase the alveolar ventilation such as bag-valve mask ventilation, NIPPV, or mechanical ventilation. When acidemia develops from a metabolic acidosis, maintenance of acid-base homeostasis depends on a compensatory respiratory alkalosis from alveolar hyperventilation.83 Unlike the rapid decrease in PaCO2 possible during hypoventilatory states, when hypocapnia is already present due to a compensatory respiratory alkalsosis, further hyperventilation results in incrementally smaller decreases in PaCO2 and eventually reaches a plateau at which point there is no effect of further increasing alveolar ventilation.83 Thus, in severe metabolic acidosis from diseases such as diabetic ketoacidosis (DKA), salicylate toxicity, and even severe lactic acidosis, the organic acid production demands an alveolar ventilation requirement that sometimes cannot be met and patients can subsequently develop profound acidemia. In the event that patients with severe acidemia require intubation, even a brief apneic period can lead to a precipitous drop in pH given the loss of the already inadequate respiratory compensation. Further, the pre-intubation alveolar ventilation sometimes cannot be matched by the mechanical ventilator, which has physical limits on the volume and rate that can be delivered. For example, a patient with DKA and Kussmaul respirations may have a minute ventilation of >40L due to a respiratory rate of 40 breaths per minute and a tidal volume of >1L. Mechanically ventilating this patient with a set rate of 30 and tidal volume of 1L will result in an inadequate minute ventilation of 30L. Consequently, even if lung protective ventilation strategies are abandoned, the maximal attainable minute ventilation may be less than the pre-intubation minute ventilation, leading to a precipitous drop in pH and a high risk of hemodynamic deterioration after intubation. Patients with extremely high minute ventilation requirements are at high risk of developing relative hypoventilation, flow starvation, patient-ventilator dysynchrony and worsened acidosis. In these situations, a pressure-targeted mode, such as pressure support ventilation or pressure control, may allow better patient-ventilator synchrony and maintenance of the minute ventilation, especially in the spontaneously breathing patient.


Intubation should be avoided, if possible, in patients with severe metabolic acidosis who have a minute ventilation requirement not likely to be met by the mechanical ventilator, despite a low pH. A short trial of NIPPV may adequately support the respiratory work of breathing until correction of the underlying metabolic acidosis can occur and will provide an estimate of the patient’s intrinsic minute ventilation by measuring the patient’s respiratory rate and tidal volume delivered with each breath.

If intubation is necessary, maintaining spontaneous respiration becomes the critical action both during intubation and with mechanical ventilation. This will allow the patient to maintain their own high minute ventilation and includes using sedative agents that are less likely to reduce the patient’s respiratory drive. Rapid sequence intubation should be avoided if possible, and if one is deemed necessary, a short-acting neuromuscular blocker such as succinylcholine should be used.

After intubation, we recommend choosing a ventilator mode that allows the patient to set and maintain their own minute ventilation in order to best maintain their respiratory compensation. A pressure-targeted ventilator mode such as pressure support ventilation or pressure control mode will allow the patient to set the rate and tidal volume received. Special care should be taken to monitor for air trapping given the high rates and tidal volumes reached as well as monitor for respiratory muscle fatigue, which will result in a loss of compensation.

Right Ventricular Failure

Under normal circumstances, the right ventricle is a low-pressure, high-compliance, flow-based chamber geared to propel venous blood returning to the heart into the pulmonary circulation.84,85 However, any process that increases right ventricular (RV) afterload, such as chronic pulmonary hypertension from lung or left ventricular disease, pulmonary arterial hypertension, or acute pulmonary embolism strains the RV, which adapts by increasing both contractility and preload.86,87 The critical action for the emergency physician is to determine if the patient has RV dysfunction, where the RV has some reserve and is able to perform some of its pumping function, or overt RV failure, in which the RV is unable to meet increased demands leading to RV dilation, retrograde flow, decreased coronary perfusion, and ultimately systemic hypotension and cardiovascular collapse.85

Intrathoracic pressure changes with respiration have an exaggerated effect on hemodynamics in the patient with RV failure, worsening cardiopulmonary interactions and making intubation extremely risky. Unlike left ventricular function, which improves with positive pressure ventilation, RV function worsens with the increase in intrathoracic pressure induced by positive pressure ventilation. This occurs because the intrathoracic pressure is transmitted to the alveolar capillary bed, leading to collapse of these small vessels and increases the pulmonary vascular resistance against which the RV must pump.88 When patients with RV failure require intubation, the increased RV afterload and decreased preload associated with invasive mechanical ventilation can often lead to cardiovascular collapse.89 When possible, work of breathing and gas exchange should be supported with medications, oxygen, and if positive pressure ventilation is needed then NIPPV and low positive end-expiratory pressure with the goals of decreasing work of breathing, limiting atelectasis, and reducing hypoxic vasoconstriction. These methods of support allow the patient to breathe spontaneously, resulting in a smaller rise in intrathoracic pressure than control modes.

Patients with increased RV afterload often present with varying degrees of RV strain on bedside echocardiography, including a dilated RV and inferior vena cava, septal flattening during systole in pressure overloaded states, and septal flattening during diastole in volume overloaded states. While patients with RV dysfunction may respond to small fluid challenges or an inotropic agent, further increasing preload with a fluid challenge in patients with RV failure is unlikely to be fruitful, and may be deleterious as volume overloading a pressure overloaded RV increases diastolic wall tension and left ventricular diastolic dysfunction, directly worsening left ventricular filling and stroke volume.87 Thus, determining volume responsiveness is quite challenging and critically important as the volume-starved left ventricle will always appear volume responsive when using the usual techniques such as pulse pressure variation (PPV) or stroke volume variation (SVV). The tricuspid valve regurgitation jet velocity, tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak velocity or isovolumetric contraction velocity (IVV) and RV outflow tract velocity-time integral are easy to perform and useful methods of determining the degree of RV strain, volume responsiveness, and contractile reserve on bedside echocardiography.90,91 Hemodynamic optimization, including RV afterload reduction with inhaled pulmonary artery vasodilators such as inhaled nitric oxide (iNO) or inhaled epoprostenol (Flolan), should be performed in patients with RV failure prior to intubation to avoid cardiovascular collapse with positive pressure ventilation. For a more detailed review of hemodynamic assessment methods, see Dalabih et al. and Krishnan et al.90,91


Bedside echocardiographic assessment of RV function should be performed to assess RV dysfunction versus RV failure. If the patient has some contractile reserve (RV dysfunction), cautious fluid resuscitation should be performed.

Preoxygenation is essential despite the difficulties resulting from intracardiac shunt and ventilation-perfusion (V/Q) mismatch, which commonly occur in right heart failure.28

Apneic oxygenation should be performed given the potential for benefit.54 INO at low concentrations (<30ppm), delivered in-line continuously through the nasal cannula, can augment oxygenation by improving V/Q matching in the hypoxemic patient but may worsen V/Q mismatch at higher concentrations. In the RV failure patient without hypoxemia, 30–80ppm of iNO delivered through the nasal cannula, or inhaled epoprostenol during preoxygenation and apneic oxygenation can reduce pulmonary vascular resistance.90

Induction agents should be considered carefully. Hemodynamically neutral sedatives such as etomidate should be used for induction. Intravenous fentanyl premedication may be useful to blunt the hypertensive response to laryngoscopy.

Continuous norepinephrine infusion should be started prior to induction in hypotensive patients with the goal of increasing mean arterial pressure higher than pulmonary artery pressure, which can be determined by bedside echocardiography. For patients without hypotension, norepinephrine should be primed and “in-line” in the event of post intubation or sedative induced hypotension.

The goals of mechanical ventilation include maintenance of a low mean airway pressure and avoidance of hypoxemia, atelectasis, and hypercapnea, which increase RV afterload.92-95


The difficult airway is well recognized as a clinical entity and is classically based on anatomic considerations. In this paper we describe another aspect of the difficult airway that involves physiologic abnormalities that must be considered in developing an intubation plan. These physiologic abnormalities must be considered and addressed prior to intubation. If they are not, significant untoward outcomes can result. We present four physiologic disturbances that must be considered carefully when planning for and performing tracheal intubation in the ED to avoid complications from the very procedure intended to be life saving. Many of the recommendations presented are based on clinical experience and physiologic principles and thus represent opportunities for formal investigation.


Section Editor: Todd Slesinger, MD

Full text available through open access at

Address for Correspondence: Jarrod M. Mosier, MD, University of Arizona, Department of Emergency Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep, Department of Medicine, University of Arizona, Tucson, AZ 85724. Email: 12 / 2015; 16:1109 – 1117

Submission history: Revision received May 13, 2015; Submitted August 16, 2015; Accepted August 17, 2015

Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.


1. Huitink JM, Bouwman RA. The myth of the difficult airway: airway management revisited. Anaesthesia. 2015;70:244-9.

2. Hung O, Murphy M. Context-sensitive airway management. Anesth Analg. 2010;10:982-3.

3. Mort TC. Complications of emergency tracheal intubation: immediate airway-related consequences: part II. J Intensive Care Med. 2007;22:208-15.

4. Mort TC. Complications of emergency tracheal intubation: hemodynamic alterations–part I. J Intensive Care Med. 2007;22:157-65.

5. Jaber S, Amraoui J, Lefrant JY, et al. Clinical practice and risk factors for immediate complications of endotracheal intubation in the intensive care unit: a prospective, multiple-center study. Crit Care Med. 2006;34:2355-61.

6. Griesdale DE, Bosma TL, Kurth T, et al. Complications of endotracheal intubation in the critically ill. Intensive Care Med. 2008;34:1835-42.

7. Mort TC. The incidence and risk factors for cardiac arrest during emergency tracheal intubation: a justification for incorporating the ASA Guidelines in the remote location. J Clin Anesth. 2004;16:508-16.

8. Simpson GD, Ross MJ, McKeown DW, et al. Tracheal intubation in the critically ill: a multi-centre national study of practice and complications. Br J Anaesth. 2012;108:792-9.

9. Heffner AC, Swords D, Kline JA, et al. The frequency and significance of postintubation hypotension during emergency airway management. J Crit Care. 2012;27(4):417.e9-13.

10. Heffner AC, Swords DS, Neale MN, et al. Incidence and factors associated with cardiac arrest complicating emergency airway management. Resuscitation. 2013;84:1500-4.

11. Perbet S, De Jong A, Delmas J, et al. Incidence of and risk factors for severe cardiovascular collapse after endotracheal intubation in the ICU: a multicenter observational study. Crit Care. 2015;19:257.

12. Mort TC. Emergency tracheal intubation: complications associated with repeated laryngoscopic attempts. Anesth Analg. 2004;99:607-613.

13. Sakles JC, Chiu S, Mosier J, et al. The importance of first pass success when performing orotracheal intubation in the emergency department. Acad Emerg Med. 2013;20:71-8.

14. Hasegawa K, Shigemitsu K, Hagiwara Y, et al. Association between repeated intubation attempts and adverse events in emergency departments: an analysis of a multicenter prospective observational study. Ann Emerg Med. 2012;60:749-54.e742.

15. Martin LD, Mhyre JM, Shanks AM, et al. 3,423 emergency tracheal intubations at a university hospital: airway outcomes and complications. Anesthesiology. 2011;114:42-8.

16. Jabre P, Avenel A, Combes X, et al. Morbidity related to emergency endotracheal intubation–a substudy of the KETAmine SEDation trial. Resuscitation. 2011;82:517-522.

17. Schwartz DE, Matthay MA, Cohen NH. Death and other complications of emergency airway management in critically ill adults. A prospective investigation of 297 tracheal intubations. Anesthesiology. 1995;82:367-76.

18. Davis DP, Hoyt DB, Ochs M, et al. The effect of paramedic rapid sequence intubation on outcome in patients with severe traumatic brain injury. J Trauma. 2003;54:444-53.

19. Davis DP, Dunford JV, Poste JC, et al. The impact of hypoxia and hyperventilation on outcome after paramedic rapid sequence intubation of severely head-injured patients. J Trauma. 2004;57:1-8.

20. Campbell IT, Beatty PC. Monitoring preoxygenation. Br J Anaesth. 1994;72:3-4.

21. Tanoubi I, Drolet P, Donati F. Optimizing preoxygenation in adults. Can J Anaesth. 2009;56:449-66.

22. Hamilton WK, Eastwood DW. A study of denitrogenation with some inhalation anesthetic systems. Anesthesiology. 1955;16:61-867.

23. Baraka AS, Taha SK, El-Khatib MF, et al. Oxygenation using tidal volume breathing after maximal exhalation. Anesth Analg. 2003;97:1533-5.

24. Baraka AS, Taha SK, Aouad MT, et al. Preoxygenation: comparison of maximal breathing and tidal volume breathing techniques. Anesthesiology. 1999;91:612-6.

25. Baraka A, Haroun-Bizri S, Khoury S, et al. Single vital capacity breath for preoxygenation. Can J Anaesth. 2000;47:1144-6.

26. Farmery AD, Roe PG. A model to describe the rate of oxyhaemoglobin desaturation during apnoea. Br J Anaesth. 1996;76:284-91.

27. Benumof JL, Dagg R, Benumof R. Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine. Anesthesiology. 1997;87:979-82.

28. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med. 2006;174:171-7.

29. De Jong A, Futier E, Millot A, et al. How to preoxygenate in operative room: healthy subjects and situations “at risk”. Ann Fr Anesth Reanim. 2014;33:457-61.

30. Gander S, Frascarolo P, Suter M, et al. Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients. Anesth Analg. 2005;100:580-4.

31. Futier E, Constantin JM, Pelosi P, et al. Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients: a randomized controlled study. Anesthesiology. 2011;114:1354-63.

32. Delay JM, Sebbane M, Jung B, et al. The effectiveness of noninvasive positive pressure ventilation to enhance preoxygenation in morbidly obese patients: a randomized controlled study. Anesth Analg. 2008;107:1707-13.

33. Cressey DM, Berthoud MC, Reilly CS. Effectiveness of continuous positive airway pressure to enhance pre-oxygenation in morbidly obese women. Anaesthesia. 2001;56:680-4.

34. Barjaktarevic I, Berlin D. Bronchoscopic intubation during continuous nasal positive pressure ventilation in the treatment of hypoxemic respiratory failure. J Intensive Care Med. 2015;30:161-6.

35. Sinha A, Jayaraman L, Punhani D. ProSeal LMA increases safe apnea period in morbidly obese patients undergoing surgery under general anesthesia. Obes Surg. 2013;23:580-4.

36. Braude D, Southard A, Swenson K, et al. Using Rapid Sequence Airway to Facilitate Preoxygenation and Gastric Decompression Prior to Emergent Intubation. J Anesth Clin Res. 2010;1:113.

37. Vyas H, Milner AD, Hopkin IE. Face mask resuscitation: does it lead to gastric distension?. Arch Dis Child. 1983;58:373-5.

38. Ho-Tai LM, Devitt JH, Noel AG, et al. Gas leak and gastric insufflation during controlled ventilation: face mask versus laryngeal mask airway. Can J Anaesth. 1998;45:206-11.

39. Bartlett RG, Brubach HF, Specht H. Demonstration of aventilatory mass flow during ventilation and apnea in man. J Appl Physiol. 1959;14:97-101.

40. Teller LE, Alexander CM, Frumin MJ, et al. Pharyngeal insufflation of oxygen prevents arterial desaturation during apnea. Anesthesiology. 1988;69:980-2.

41. Taha SK, Siddik-Sayyid SM, El-Khatib MF, et al. Nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique. Anaesthesia. 2006;61:427-30.

42. Ramachandran SK, Cosnowski A, Shanks A, et al. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. J Clin Anesth. 2010;22:164-8.

43. Sims JL, Morris LE, Orth OS, et al. The influence of oxygen and carbon dioxide levels during anesthesia upon postsurgical hepatic damage. J Lab Clin Med. 1951;38:388-96.

44. Mitchell JH, Wildenthal K, Johnson RL. The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Int. 1972;1(5):375-89.

45. Joels N, Samueloff M. Metabolic acidosis in diffusion respiration. J Physiol. 1956;133:347-59.

46. Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation in man. Anesthesiology. 1959;20:789-98.

47. Busse EW, Parry TM, Goldensohn ES, et al. Alteration of cerebral function in man produced by diffusion respiration and prolonged inhalation of carbon dioxide. Dis Nerv Syst. 1952;13(2):35-41.

48. Patel A, Nouraei SA. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015;70:323-9.

49. Vourc’h M, Asfar P, Volteau C, et al. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med. 2015;41(9):1538-48.

50. Miguel-Montanes R, Hajage D, Messika J, et al. Use of High-Flow Nasal Cannula Oxygen Therapy to Prevent Desaturation During Tracheal Intubation of Intensive Care Patients With Mild-to-Moderate Hypoxemia*. Crit Care Med. 2015;43:574-83.

51. Spoletini G, Alotaibi M, Blasi F, et al. Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications. Chest. 2015;148(1):253-61.

52. Brainard A, Chuang D, Zeng I, et al. A randomized trial on subject tolerance and the adverse effects associated with higher- versus lower-flow oxygen through a standard nasal cannula. Ann Emerg Med. 2015;65:356-61.

53. Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med. 2012;59:165-75.e161.

54. Dewhirst E, Frazier WJ, Leder M, et al. Cardiac arrest following ketamine administration for rapid sequence intubation. J Intensive Care Med. 2013;28:375-9.

55. Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008;26:985-1028.

56. Heffner AC, Swords D, Kline JA, et al. The frequency and significance of postintubation hypotension during emergency airway management. J Crit Care. 2012;27:417.e419-3.

57. Kim WY, Kwak MK, Ko BS, et al. Factors associated with the occurrence of cardiac arrest after emergency tracheal intubation in the emergency department. PLoS One. 2014;9:e112779.

58. Green RS, Edwards J, Sabri E, et al. Evaluation of the incidence, risk factors, and impact on patient outcomes of postintubation hemodynamic instability. CJEM. 2012;14:74-82.

59. Green R, Hutton B, Lorette J, et al. Incidence of postintubation hemodynamic instability associated with emergent intubations performed outside the operating room: a systematic review. CJEM. 2014;16:69-79.

60. Griesdale DE, Henderson WR, Green RS. Airway management in critically ill patients. Lung. 2011;189:181-92.

61. Heffner AC, Swords DS, Nussbaum ML, et al. Predictors of the complication of postintubation hypotension during emergency airway management. J Crit Care. 2012;27:587-93.

62. Manthous CA. Avoiding circulatory complications during endotracheal intubation and initiation of positive pressure ventilation. J Emerg Med. 2010;38:622-31.

63. Funk DJ, Jacobsohn E, Kumar A. Role of the venous return in critical illness and shock: part II-shock and mechanical ventilation. Crit Care Med. 2013;41:573-9.

64. Funk DJ, Jacobsohn E, Kumar A. The role of venous return in critical illness and shock-part I: physiology. Crit Care Med. 2013;41:255-62.

65. Lansdorp B, Hofhuizen C, van Lavieren M, et al. Mechanical ventilation-induced intrathoracic pressure distribution and heart-lung interactions*. Crit Care Med. 2014;42:1983-90.

66. Berlin DA, Bakker J. Understanding venous return. Intensive Care Med. 2014;40:1564-6.

67. de Witt B, Joshi R, Meislin H, et al. Optimizing oxygen delivery in the critically ill: assessment of volume responsiveness in the septic patient. J Emerg Med. 2014;47:608-15.

68. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362:779-789.

69. Monnet X, Letierce A, Hamzaoui O, et al. Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine. Crit Care Med. 2011;39:1394-9.

70. Loubani OM, Green RS. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care. 2015;30:653.e659-617.

71. Schwab TM, Greaves TH. Cardiac arrest as a possible sequela of critical airway management and intubation. Am J Emerg Med. 1998;16:609-12.

72. Ebert TJ, Muzi M, Berens R, et al. Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. Anesthesiology. 1992;76:725-33.

73. Tassani P, Martin K, Janicke U, et al. Bolus administration of eltanolone, thiopental, or etomidate does not affect systemic vascular resistance during cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 1997;11:562-4.

74. Morris C, Perris A, Klein J, et al. Anaesthesia in haemodynamically compromised emergency patients: does ketamine represent the best choice of induction agent?. Anaesthesia. 2009;64:532-9.

75. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374:293-300.

76. Naguib M, Magboul MM. Adverse effects of neuromuscular blockers and their antagonists. Middle East J Anaesthesiol. 1998;14:341-73.

77. Claudius C, Garvey LH, Viby-Mogensen J. The undesirable effects of neuromuscular blocking drugs. Anaesthesia. 2009;64(Suppl1):10-21.

78. Habib AS. Phenylephrine versus ephedrine for the management of hypotension in the obstetric patient; do we have an updated answer?. CNS Neurosci Ther. 2013;19(3):199-200.

79. Habib AS. A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg. 2012;114:377-90.

80. Dyer RA, Reed AR, van Dyk D, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009;111:753-65.

81. Panchal AR, Satyanarayan A, Bahadir JD, et al. Efficacy of Bolus-dose Phenylephrine for Peri-intubation Hypotension. J Emerg Med. 2015;49(4):488-94.

82. Marini JJ, Dries D. Principles of Gas Exchange. Texbook of Critical Care. 2011:288-94.

83. Haddad F, Hunt SA, Rosenthal DN, et al. Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008;117:1436-48.

84. Haddad F, Doyle R, Murphy DJ, et al. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation. 2008;117:1717-31.

85. Lupi-Herrera E, Santos Martinez LE, Figueroa Solano J, et al. Arch Cardiol Mex. 2007;77(4):330-48.

86. Szabo G, Soos P, Bahrle S, et al. Adaptation of the right ventricle to an increased afterload in the chronically volume overloaded heart. Ann Thorac Surg. 2006;82:989-95.

87. Naeije R. Pulmonary vascular resistance. A meaningless variable?. Intensive Care Med. 2003;29:526-9.

88. Zamanian RT, Haddad F, Doyle RL, et al. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med. 2007;35:2037-50.

89. Dalabih M, Rischard F, Mosier JM. What’s new: the management of acute right ventricular decompensation of chronic pulmonary hypertension. Intensive Care Med. 2014;40:1930-3.

90. Krishnan S, Schmidt GA. Acute right ventricular dysfunction: real-time management with echocardiography. Chest. 2015;147:835-46.

91. Howell JB, Permutt S, Proctor DF, et al. Effect of inflation of the lung on different parts of pulmonary vascular bed. J Appl Physiol. 1961;16:71-6.

92. Rudolph AM, Yuan S. Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes. J Clin Invest. 1966;45:399-411.

93. Harvey RM, Enson Y, Betti R, et al. Further observations on the effect of hydrogen ion on the pulmonary circulation. Circulation. 1967;35:1019-27.

94. Jardin F, Vieillard-Baron A. Right ventricular function and positive pressure ventilation in clinical practice: from hemodynamic subsets to respirator settings. Intensive Care Med. 2003;29:1426-34.