Patients with sepsis frequently have hypotension, altered mental status, and altered circulatory physiology anywhere on the spectrum of impending collapse, which presents time-critical windows to act and sometimes with limited options. Antibiotics are not immediately effective, and fluid resuscitation may worsen hypoxia depending on the underlying pathophysiologic state. Hypoxemic respiratory failure in sepsis may be caused by multiple mechanisms such as limited gas exchange, pneumonia with airspace consolidations and volume loss, or by diffuse alveolar edema related to increased capillary permeability in acute respiratory distress syndrome (ARDS).⁴ In early sepsis, respiratory failure can be caused by the oxygen consumption required to maintain the high work of breathing (WOB) that accompanies the high cardiac output state induced by inflammatory mediators and endo- or exotoxins. Sepsis is a generalized state of inflammation often characterized by high metabolic states and increased oxygen consumption. Varying states of vasoplegia, cardiac contractility, and intravascular volume (among other variables) determine whether those increased needs can be met. Often later in sepsis, or in patients with comorbid cardiomyopathies or myocardial
stunning leads to a reduced cardiac output and can fail to meet those requirements.⁵ When the brain experiences hypoperfusion, the patient becomes somnolent and there is an increased risk of aspiration, hypoventilation, and loss of airway reflexes and tone. Taken together this hypoxia, with inadequate tissue oxygenation, and risk for altered mental status leads to a particularly vulnerable patient during intubation.⁶

Septic physiology can be especially dangerous before adequate fluid resuscitation, in instances where vasopressors are unavailable, and when adjunct oxygenation devices such as high-flow nasal cannula (HFNC) are unavailable. Patients should be adequately resuscitated prior to intubation and not just be in the process of resuscitation. Shock index (SI = HR/SBP) can be useful to identify patients at high risk but are not yet in florid shock.

There are some specific features beyond the standard airway exam that deserve notice when evaluating a septic patient with respiratory failure. First, evaluate the patient’s current oxygenation obstacles and opportunities to better de-nitrogenate and maximize lung recruitment (functional residual capacity [FRC]). This may include the use of HFNC and/or noninvasive positive pressure ventilation (NIPPV). Monitor vital signs, including temperature, and consider antipyretics to decrease metabolic demand. Careful evaluation of intravascular volume responsiveness and tolerance should guide fluid resuscitation, and occasionally diuresis in a patient with mixed distributive and cardiogenic shock features. It is beneficial to perform bedside ultrasonography to evaluate for large pleural effusions and characterize the underlying hemodynamic phenotypes that require attention to stabilize the patient prior to intubation (Chapter 11, Applied ultrasonography). Neurologic exams can be focused on the patient’s ability to protect their airway, maintain respiratory effort, and tolerate adjunct airway support such as NIPPV. Evaluate the abdomen for signs of acute pathology or obesity. Patients may have full stomachs; however, this does not alleviate the necessity to intubate a patient with sepsis and respiratory failure. Ensure that appropriate suction devices are available and be prepared to use techniques described for the soiled airway to mitigate the risk of aspiration-related complications.

For patients with shock refractory to vasopressors and fluids, it is reasonable to consider reduced dose induction agents, particularly when patients may already have a reduced level of consciousness before induction (Chapter 13, Sedative agents for RSI). Preoxygenation, and apneic oxygenation to prolong safe apnea time are essential. Anticipate hemodynamic response and have vasopressors available with a plan to adjust ventilator settings to the expected physiology. For example, the acidotic patient should have initial ventilator settings consistent with hyperventilation and avoid apnea periods while transitioning from bag-valve mask (BVM) to the ventilator. A patient with very low BP may be intolerant of high positive end-expiratory pressure (PEEP) until resuscitation is more fully achieved or lung space is recruited to improve compliance.

Acute hypoxemic respiratory failure is one of the most common reasons for nonoperating room intubations and one of the highest risk conditions for intubation-related complications.⁷ Acute respiratory distress syndrome (ARDS), the most severe cause of acute hypoxemic respiratory failure, caused approximately 10,000 annual deaths in the United States prior to the COVID-19 pandemic. This number increased three to five times during the pandemic and has been a focus of health care during the rolling waves of respiratory illness since 2020.⁸ When a patient is hypoxic prior to intubation, there is a fourfold increase in adjusted odds of a peri-intubation cardiac arrest.⁹ Therefore, the goals for airway management in acute hypoxemic respiratory failure are to optimize preoxygenation and apneic oxygenation physiology, and chances of first-pass success to minimize the risk of hypoxic injury or cardiovascular collapse.¹⁰

Hypoxemia, or low oxygen content in the blood, can be caused by many factors, such as poor gas diffusion across injured or obstructed alveoli as in pneumonia or pulmonary edema, poor oxygen uptake when perfusion is limited as in a pulmonary embolism, or by poor oxygen delivery as in cardiogenic shock. Any of these factors, which limit the oxygen delivery to organs, can cause organ injury or lead to hemodynamic collapse. When a patient is transitioned from baseline negative pressure ventilation to positive pressure ventilation (PPV) the ventilation-perfusion matching may change, leading to some unpredictability in oxygenation response to this transition. As intrathoracic pressure increases, venous return may also be impeded and may further decrease pulmonary circulation in patients who are under-resuscitated or those with preload-dependent cardiac physiology. However, despite the risks associated with the transition to PPV, this is often the best option to stabilize patients, improve alveolar recruitment, and provide lung protective ventilation while the causative insult is treated. These risk factors highlight the importance of preintubation oxygenation, apneic oxygenation, appropriate positioning, and the use of appropriate tools to promote the best chances of first-pass successful airway intubation.

The initial evaluation of a patient with severe acute hypoxemic respiratory failure is to take stock of what may be known of the precipitating events, the patient’s medical history, and known airway risk factors including anatomy, physiology, and recent medications. It is worth considering a list of immediately reversible causes that may obviate intubation or make the procedure significantly safer such as pneumothorax, cardiac tamponade, large hemothorax or pleural effusion, or pulmonary edema. If such a cause is identified, the preferred approach would be to have one operator address the known pathology, and another provider continue to plan for and set up for potential intubation. When a single provider is available it will be necessary to have an established plan for the order of events based on patient presentation, available resources, and the provider’s ability to perform other necessary procedures. During any attempt to treat these additional pathologies, it would be prudent to provide preoxygenation and accrue necessary resources if intubation is still required.

If intubation does become required there are several available options including awake intubation and RSI (see Chapter 9, Developing your strategy). An exam focused on selecting the appropriate approach should include an evaluation of the patient’s mental status with a focus on the feasibility of an awake intubation approach. Also, note the patient’s facial and neck anatomy to assess the ability to provide NIPPV or BVM support, if necessary, between intubation attempts. Evaluate the patient’s neck anatomy in the event of necessary cricothyrotomy as a hypoxic patient may not tolerate failed attempts at oral intubation raising the possibility of a necessary surgical airway.

Patient hemodynamics and trends in oxygenation also provide valuable information when evaluating the feasibility of awake intubation. A patient who appears to be agonal breathing or near cardiac arrest will not have time to complete oral topical anesthesia, however, a patient who is maintaining mental status and ventilation even in the setting of severe hypoxia may tolerate the few additional minutes to prepare for awake intubation better than they would tolerate even seconds of apnea or a recumbent position.

The choice of preoxygenation methods may depend on several factors such as resource availability, patient tolerance of NIPPV mask, or risk of vomiting. Patients with ARDS have shunt physiology and often have hypoxemia refractory to increased FiO₂. For these reasons, advanced preoxygenation modalities with either NIPPV or HFNO are necessary to provide a higher FiO₂ and promote alveolar recruitment. If possible, NIPPV may recruit lung units and reveal how the patient will potentially respond to positive pressure. If NIPPV is unavailable, not tolerated, or inappropriate for a given patient, then high-flow nasal oxygen should be used. Heated, humidified HFNCs are often more comfortable and can support up to 70 L/min of 100% oxygen. High-flow nasal oxygen should be left in place during apnea to increase safe apnea duration in the event of prolonged intubation and thus may present an attractive edge compared to NIPPV in patients who are at high risk of desaturation, but RSI is still planned. Data comparing HFNC devices to standard methods of preoxygenation in critically ill patients have been mixed, but in all but the most severely hypoxemic patients where RSI is planned, they appear equivalent. Finally, low-dose inhaled vasodilators such as inhaled nitric oxide or inhaled prostaglandins may decrease ventilation-perfusion mismatch and improve preoxygenation.

Awake intubation may be an appropriate option for severely hypoxemic patients. The benefits of awake oral intubation include the ability to avoid sedating medications and the vasoplegic effects of induction agents. This option keeps the patient spontaneously breathing until the time the endotracheal tube (ETT) is passed through the vocal cords, and the option to keep the patient fully upright and intubate using the flexible endoscope while the patient is maintaining their own oropharyngeal tone. There are instances where awake intubation will not be an available option, such as times when the patient is already rendered obtunded due to a medical condition, or when topicalization or flexible endoscopes are unavailable in your setting.

Cirrhosis is one of the leading causes of morbidity and mortality worldwide. Patient demographics and etiology of cirrhosis are changing as younger people are being diagnosed.¹¹ A patient with decompensated cirrhosis often has altered mentation, sepsis syndrome, and gastrointestinal bleeding.¹² In the medical ICU, cirrhosis is among the leading causes of upper gastrointestinal bleeding (UGIB).

Massive UGIB due to esophageal varices presents a challenge for airway management in multiple ways. Encephalopathy can limit the ability to preoxygenate, make airway assessment more difficult, and mostly eliminate awake intubation options. Active vomiting or soiled upper airway can make airway assessment, laryngoscopy, and mask ventilation more difficult, and coagulopathy will complicate the surgical airway. Ascites can limit preoxygenation efficacy and increase the risk of aspiration. Patients are hypovolemic and hypotensive, frequently infected, and often have a high cardiac output and vasoplegic hemodynamic state making resuscitation difficult and induction risky.

Multiple simultaneous interventions will likely be necessary and whenever feasible tasks should be delegated and coordinated in parallel. Assess the urgency to intubate. An awake patient who may be vomiting is usually capable of airway protection unless encephalopathy is severe. The presence of large-volume ascites will compromise FRC and will limit the success of preoxygenation. In addition, NIPPV for preoxygenation is probably best avoided given the risk of further stomach insufflation. Porto-pulmonary disease also causes a high shunt fraction limiting safe apnea time. Given all these limitations to preoxygenation, high-flow nasal oxygen for preoxygenation and apneic oxygenation may be the best option. Ultrasonography can help estimate stomach contents and nasogastric decompression prior to induction can help decrease aspiration risk. Hemodynamic compromise due to hypovolemia and distributive shock state will place these patients at a high risk of cardiovascular collapse. Adequate intravenous access with large bore catheters should be placed for resuscitation for blood loss and early vasopressor administration for the underlying vasoplegic state. In patients with severe encephalopathy and active large-volume hematemesis, induction and paralysis are often required to stop the active vomiting and aspiration. These patients may be managed with induction followed by placing a supraglottic airway in parallel with aggressive blood-product-based resuscitation prior to intubation. However, this requires a highly coordinated effort and usually more than one clinician (one focused on the airway and one on the resuscitation).

In 2021, over 100,000 deaths were attributed to overdoses in the United States.¹⁵ Opioids, cocaine, and psychostimulants are the most attributed drugs.¹⁶ The clinical presentation is widely variable depending on the substance used and the balance between respiratory depression and cardiotoxicity. The old dictum of “GCS 8, Intubate” was originally intended for the trauma patient and is not always accurate in identifying patients who may need an artificial airway placed.¹⁷

The exam is initially focused on hemodynamic assessment and airway protection. The gag reflex is not a reliable sign of airway protection.¹⁸ Intact swallowing and a robust cough are reassuring signs. The decision to intubate depends on the immediate clinical situation and the projected trajectory. An immediate reversal medication, like naloxone in cases of opiate overdose, may obliviate the need for airway protection. Conversely, the need for control of a patient who is a danger to themselves or others, in need of transport or testing, or is requiring significant doses of sedating medications may require intubation if pharmacologic restraints prove inadequate. History and exam may be limited by clinical presentation. Choice and dose of medications may need to be modified, such as reduced dose of sedatives in an obtunded patient, and use of benzodiazepines preinduction. Ketamine may be used cautiously in patients with sympathomimetic overdose. Nondepolarizing muscle relaxants are preferred.¹⁹ Timing and use of antidote/reversal should be deliberate. Reversing benzodiazepines with flumazenil may lead to seizures in a chronic user or due to an unopposed effect of another substance. Activated charcoal has a risk of aspiration with long-term adverse effects and may have to be delayed till the airway has been controlled and gastric tubes placed.¹⁹

For overdoses with respiratory depressants, it may be necessary to support both oxygenation and ventilation. An HFNC or flush rate nonrebreather can be used to support oxygenation without the risk of emesis with NIPPV. Position the head of the bed up during initial resuscitation and provide bag-mask ventilation if the patient is not spontaneously breathing.

Patients who have overdosed on stimulants often present with hyperactive delirium syndrome that presents a problem for airway assessment and preparation. Stimulants often produce a hyperdopaminergic and high catecholamine state that leads to agitation and hyperactive delirium. There are essentially three options for these patients:

The best option depends on the anatomic, physiologic, and situational factors for that particular patient. Awake intubations are often not an option given the hyperactive delirium. If pharmacologic interventions improve compliance, then awake intubations may become an option, otherwise, you are forced to RSI. Delayed sequence intubation has its risks but if successful may allow for denitrogenation, time for physiologic optimization, and appropriate airway assessment. Induction would result in an apneic patient without preoxygenation, so the team must be prepared to optimize mask ventilation after induction and move quickly to rescue oxygenation if needed.

Overdoses with cardiotoxic medications can lead to cardiogenic or vasoplegic shock and will almost certainly require vasopressors for resuscitation prior to airway management. Metabolic toxins such as metformin or aspirin are ultimately treated with dialysis or antidotes however resuscitation and airway management may be prerequisites to tolerate therapies such as gastrointestinal decontamination or dialysis and central line placement.

This is a complex picture of a patient with PAH and potentially viral pneumonia. The combination of these creates a situation where the patient may have multiple reasons for hypoxia including acute RV failure. RV function can be acutely decompensated by increases in preload or afterload, reduced inotropy or lusitropy, and often in combination. Acute ischemia, massive pulmonary embolism, or acute decompensated pulmonary hypertension commonly leads to acute RV failure.²⁰ Right ventricular-pulmonary artery (RV-PA) uncoupling is the final step in the cascade of RV failure, which leads to cardiogenic shock and death. Induction agents can cause hypotension by a variety of mechanisms, leading to RV ischemia from poor systemic BP and coronary artery perfusion pressure. Hypoxia leads to pulmonary vasoconstriction and increased pulmonary vascular resistance. Increased intrathoracic pressures with mechanical ventilation increase RV afterload as
well. All these are detrimental in a failing RV making intubation a very high risk and sometimes the terminal event in this group of patients.