While hypoxemia and hypotension are the primary drivers for the physiologically difficult airway, severe metabolic acidosis, induction agent choice, and the effects of transitioning to positive pressure ventilation can all contribute to pushing a patient past the point of no return. This chapter focuses on each of those elements of the physiologically difficult airway and should be considered in the context of hemodynamics (Chapter 6, The Physiologically Difficult Airway: Hemodynamics) and used to inform the strategy (Chapter 9, Developing Your Strategy).

Metabolic derangements have widespread, varying, and complex effects on the respiratory and cardiovascular systems. Metabolic acidosis is the most troublesome of these derangements. Although mild metabolic acidosis can increase cardiac output modestly, it does so at the cost of increased myocardial oxygen demand and higher propensity for dysrhythmias. Severe metabolic acidosis results in myocardial depression. Blunting of myocardial response to circulating catecholamines is also an important factor. Catecholamine release in response to metabolic acidosis results in arterioconstriction, which again can lead to tachycardia, shortened filling time, and dysrhythmias resulting in ventriculoarterial uncoupling.

When patients with severe metabolic acidosis have maximized alveolar ventilation to maintain a pH barely compatible with life, the RSI-induced apnea can often be the tipping point into cardiac arrest as the PaCO₂ can rise rapidly and result in a plummeting pH. PaCO₂ can rise rapidly during the first minute of apnea, generally 10 to 13 mm Hg, dropping the pH between 0.1 and 0.2.^1,2 This is not trivial in a patient with severe metabolic acidosis prior to intubation (e.g., salicylate toxicity, metformin overdose, severe lactic acidosis, diabetic ketoacidosis) where a starting pH of 7.0 could become 6.8 or 6.9 just by the rise in PaCO₂ during a minute of apnea, not to mention any effect of ongoing organic acid production during that time.

Before RSI is performed in these patients, one must treat the underlying etiology of the metabolic acidosis as best as possible, feel confident that the patient can tolerate a drop in pH, and ensure that the patient’s current alveolar ventilation (minute ventilation-dead space) can be matched with mechanical ventilation.

Safely transitioning a patient with limited or no cardiovascular reserve through apnea and laryngoscopy to positive pressure ventilation requires a working knowledge of all components associated with risk, including those the patient brings to the table with their underlying physiology and those that we impose on them with our induction agents. Inducing unconsciousness in a critically ill patient blunts the intrinsic survival (sympathetic) drive and all sedatives have independent hemodynamic consequences of their own. Knowing this, selecting the right sedative induction
agent requires a personalized approach based on the underlying hemodynamic profile (Chapter 6, Chapter 13, Sedative Agents for RSI).

At the doses required for RSI, propofol and midazolam result in venodilation, reducing both preload and blood pressure. In one study, propofol decreased mean arterial pressure without a change in cardiac output. This occurs from venodilation and converting stressed volume into unstressed volume. The decrease in stressed volume leads to an afterload reduction on the left ventricle and thus preserved cardiac output despite a lower blood pressure.³ For patients with high cardiac output states with borderline hemodynamics (e.g., septic shock), this venodilation could be the tipping point to cardiovascular collapse. A secondary analysis of the INTUBE study identified propofol as the induction agent to be an independent predictor of postintubation hypotension.⁴

Etomidate is considered a hemodynamically neutral drug, but recent evidence shows that hypotension associated with etomidate is due to an increase in arterial compliance that reduced arterial elastance.⁵ All patients in that study had reduced vascular resistance and stroke volume after induction, but patients who did not develop hypotension had a compensatory tachycardia while those that developed hypotension did not. The increased arterial compliance resulted in hypotension. Thus, a patient with increased arterial compliance (e.g., advanced cirrhosis with sepsis) may have a higher risk of hypotension than a patient intubated for pneumonia and sepsis.