Rapid sequence intubation in adults for emergency medicine and critical care

INTRODUCTION — Rapid sequence intubation (RSI) is the preferred method for securing the airway in the critically ill or injured patient. RSI involves the administration of an anesthetic induction agent followed quickly by a neuromuscular blocking agent (NMBA) to create optimal intubating conditions and minimize both the duration of the patient's apnea and the time the airway is unprotected. RSI presupposes the patient is at risk for aspiration of gastric contents and incorporates medications and techniques to minimize this risk. Use of RSI also helps to mitigate the potential adverse effects of airway manipulation.

This topic reviews the central concepts and techniques needed to perform RSI in adults in the emergency setting outside the operating room. RSI for anesthesia, RSI in children, the medications used for emergency RSI, and other subjects related to emergency airway management are reviewed separately:

●Medications used for RSI in adults (see "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care")

●RSI in children (see "Rapid sequence intubation (RSI) in children for emergency medicine: Approach" and "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis")

●Basic and advanced airway management (see "Basic airway management in adults" and "Extraglottic devices for emergency airway management in adults" and "Direct laryngoscopy and endotracheal intubation in adults" and "Video laryngoscopes and optical stylets for airway management for anesthesia in adults")

DEFINITION AND KEY CONCEPTS — RSI is the virtually simultaneous administration of an induction agent and a neuromuscular blocking agent to induce unconsciousness and paralysis to facilitate rapid tracheal intubation. The technique is designed to maximize the likelihood of successful intubation and minimize the risk of aspiration. Maximal preoxygenation and hemodynamic optimization are essential prior to drug administration. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care".)

RSI is associated with increased first-pass success rates (ie, successful endotracheal tube [ETT] placement on the first intubation attempt) and reduced incidence of complications [1-3]. Maximizing first-pass success hinges primarily on:

●Robust preoxygenation

●Correct dosages and timing of intubation medications

●Use of a videolaryngoscope

Adequate preoxygenation allows maximal time for successful tube placement without hypoxemia. Administering the right doses of induction agent and NMBA, and allowing sufficient time for the drugs to distribute and exert their effects, ensures that the patient is unconscious and has adequate muscle relaxation to permit intubation. In a large meta-analysis involving many thousands of intubations, videolaryngoscopy was found to improve first-pass success and reduce complications [4]. This meta-analysis included findings from over 200 studies, including 21 conducted outside the operating room (six prehospital, seven emergency department, and eight intensive care unit). A study from the National Emergency Airway Registry demonstrated that the advantage of videolaryngoscopy over direct laryngoscopy for first-pass intubation success extends from novice to experienced intubators [5].

Preoxygenation creates a large intrapulmonary and tissue reservoir of oxygen that allows patients to tolerate a period of apnea without clinically significant oxygen desaturation. This avoids the need for positive-pressure ventilation during the apneic phase of RSI, during which the patient is not breathing spontaneously but is not yet sufficiently paralyzed to facilitate intubation. Patients undergoing emergency intubation are presumed to have full stomachs and are therefore considered at high risk for aspiration. Accordingly, interposed face mask ventilation is generally avoided to help prevent gastric insufflation and the risk of aspiration. When the risk and consequences of desaturation are judged to exceed those of aspiration, oxygenation may be provided using gentle face mask ventilation between the time of drug administration and initiation of laryngoscopy. (See 'Preoxygenation' below.)

Induction agents are given by rapid intravenous (IV) push during RSI, putting critically ill patients at risk for developing hypotension. When circumstances allow, such risk can be mitigated by the choice and dose of the induction agent, as well as by optimization of cardiovascular status, as clinically indicated, using crystalloids, blood products, vasopressors, or inotropes prior to administering RSI drugs. (See 'Physiologic optimization' below.)

When performing RSI in a patient with a predicted difficult airway, the clinician must have a backup plan to execute in the event intubation is unsuccessful, including immediate access to the equipment necessary to restore oxygenation. Such equipment generally includes a bag and mask device, extraglottic airway, and instruments for providing a surgical airway. (See "Approach to the difficult airway in adults for emergency medicine and critical care" and "Basic airway management in adults" and "Extraglottic devices for emergency airway management in adults" and "Emergency cricothyrotomy (cricothyroidotomy) in adults".)

INDICATIONS — RSI is the most common and preferred method for securing control of the airway in critically ill patients when not contraindicated by the presence of significant anatomic or physiologic abnormalities. [6-12].

RSI may also be the preferred approach in the patient with an anatomically difficult airway if the intubator is confident that gas exchange can be maintained, either by successful intubation or by use of a bag and mask or extraglottic airway. In a registry study of emergency department intubations, 80 percent of patients with predicted anatomically difficult airways were managed with RSI using a videolaryngoscope with a high first-pass success rate [13]. (See "Approach to the difficult airway in adults for emergency medicine and critical care".)

CONTRAINDICATIONS AND PRECAUTIONS — Contraindications to RSI are relative. The most important contraindication to RSI is anticipation of difficult or impossible rescue oxygenation. In patients who cannot tolerate apnea (eg, refractory hypoxemia or severe metabolic acidosis is present), neuromuscular blockade may be undesirable, and an "awake" intubation approach (ie, use of topical anesthesia and light sedation) is preferred to minimize the likelihood of precipitous deterioration.

Medications and doses for induction and neuromuscular blockade should be selected to achieve airway management goals while minimizing side effects. Particular drugs used for RSI are discussed in detail separately. (See "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care" and "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care".)

Many critically ill patients experience significant hypoxemia or hypotension during the peri-intubation period. To minimize the risk of these complications, patients should be physiologically optimized prior to intubation whenever time allows. (See 'Physiologic optimization' below.)

Properly performed preoxygenation using the most appropriate methods given clinical circumstances is the most important measure to prolong safe apnea time and prevent desaturation during intubation. However, hypoxemic patients may have severe intrapulmonary shunting and refractory hypoxemia despite supplemental oxygen. Optimization in patients with high shunt fractions includes preoxygenation with high-flow nasal oxygen (HFNO) or noninvasive positive-pressure ventilation (NIPPV). If oxygen saturation (SpO₂) ≥93 percent cannot be achieved with these methods, the risk of severe hypoxemia during RSI is high, and an "awake" technique maintaining spontaneous ventilation may be preferred. In patients with hypotension and shock, RSI remains the preferred approach provided deranged hemodynamics are mitigated with fluid or blood administration and norepinephrine [14,15].

PERFORMANCE OF RSI — The updated "seven Ps of RSI" is a mnemonic that outlines the key steps of RSI planning and performance (table 1) [16-18]:

●Preparation

●Preoxygenation

●Physiologic optimization

●Paralysis with induction

●Positioning

●Placement with proof

●Postintubation management

Pretreatment with medications to reduce the effects of laryngoscopy and intubation on the nervous system should be viewed as a supplementary (ie, nonessential) step in RSI to be performed in specific clinical circumstances if time permits. The role of such pretreatment is reviewed separately. (See "Pretreatment medications for rapid sequence intubation in adults for emergency medicine and critical care".)

Preparation — The goal of preparation is to maximize the chances for successful intubation on the first attempt without adverse events [19]. Studies suggest that the risk of an adverse event during emergency tracheal intubation (eg, hypoxemia, hypotension, esophageal intubation) increases significantly with the number of attempts [20-22]. An observational emergency department study of 1828 intubations reported that 14 percent of patients intubated on the first pass experienced an adverse event compared with 47 percent of those intubated on the second attempt and 64 percent of those intubated on the third attempt [20].

Basic preparation steps — Preparation for RSI includes:

●Assessing the patient's airway for potential anatomic or physiologic difficulty (see 'Identifying anatomic or physiologic difficult airways' below)

●Developing an airway management plan (including a backup strategy)

●Assembling all necessary personnel, equipment, and medications

The following table summarizes these steps (table 2). A detailed discussion of the steps needed to prepare for intubation is provided separately. (See "Direct laryngoscopy and endotracheal intubation in adults", section on 'Preparation'.)

Prior to proceeding with RSI, at least one, but preferably two, functioning intravenous (IV) lines should be in place, as should cardiac and blood pressure monitors, pulse oximetry, and capnography. (See "Pulse oximetry" and "Carbon dioxide monitoring (capnography)".)

Patients undergoing airway management should be in an appropriate clinical area where all necessary airway and resuscitation equipment is available. The airway manager should have easy access to the head of the bed and should adjust the height of the bed and position of the patient to facilitate intubation. The equipment and steps necessary to prepare for and perform tracheal intubation are reviewed separately. (See "Direct laryngoscopy and endotracheal intubation in adults" and "Video laryngoscopes and optical stylets for airway management for anesthesia in adults", section on 'Videolaryngoscopy'.)

Identifying anatomic or physiologic difficult airways — Once the need for intubation is determined, and prior to committing to RSI as the method of intubation, the clinician assesses the patient for anatomic features and clinical findings that indicate the patient may be difficult to intubate or to ventilate using a bag-mask, or in whom it may be difficult to use a rescue airway, such as an extraglottic device. (See "Approach to the difficult airway in adults for emergency medicine and critical care".)

Although the presence of markers for difficult intubation or difficult bag-mask ventilation is not an absolute contraindication to RSI, if such features are identified, alternatives to RSI may be preferred. If the clinician chooses to proceed with RSI in the presence of such markers, comprehensive backup plans are required, and all resources needed to enact each plan must be available at the bedside.

In addition, an assessment must be performed for the presence of any physiologic derangements that increase the risk of cardiovascular collapse after the administration of RSI medications and transition to positive-pressure ventilation. The strongest predictors of peri-intubation circulatory arrest are hypotension (systolic blood pressure <100 mmHg), elevated shock index (heart rate divided by systolic blood pressure >0.8), and hypoxemia (oxygen saturation [SpO₂] <93 percent) [23-25]. Therefore, these must be recognized and, whenever possible, corrected before RSI medications are given. (See 'Physiologic optimization' below.)

Right ventricular failure and severe metabolic acidosis are less common conditions, but they too can cause rapid physiologic deterioration with RSI [14]. Patients with profound metabolic acidosis may experience a precipitous deterioration even during brief periods of apnea when compensatory elimination of carbon dioxide is halted. Severe asthma, active myocardial ischemia, tachydysrhythmias, and all forms of shock require a tailored approach that results in successful tube placement and minimal risk of hypoxic insult or circulatory collapse.

Choosing between RSI and awake intubation — If an anatomically difficult airway is predicted, rapid desaturation is anticipated, or refractory hemodynamic instability is present, RSI may not be the safest way to achieve airway control. Instead, an "awake intubation," in which topical anesthesia is applied to the upper airway, sometimes in combination with light sedation, may be preferred [26,27]. The benefit of the awake intubation is that the patient maintains spontaneous ventilation, thereby avoiding the dangers of apnea and hemodynamic compromise associated with RSI medications. However, awake intubation has potential drawbacks. It may be poorly tolerated, requires adequate time for topical anesthesia to take effect, and takes longer to achieve intubation. In rare cases, awake intubation can precipitate complete airway obstruction, emphasizing the importance of a rescue plan in the event this occurs [28].

Choosing between RSI and awake intubation can be difficult, and the clinician must carefully consider the pros and cons of each approach in the individual patient, including available equipment, medications, and personnel, to determine the best course. Discussions of how to determine the need for intubation and to identify airways that are potentially difficult to intubate or ventilate are provided separately. (See "The decision to intubate" and "Approach to the difficult airway in adults for emergency medicine and critical care".)

With RSI as the chosen technique, the clinician selects the appropriate induction and neuromuscular blocking agents (NMBAs) to be used and determines the doses. The medications to be used are drawn up into labeled syringes, and standard closed-loop communication protocols are used to ensure proper dosing. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care".)

Preoxygenation

General guidelines and common scenarios — Preoxygenation increases the safety of RSI. Any patient requiring urgent tracheal intubation ideally should be preoxygenated for a minimum of three minutes using oxygen delivered at the highest flow rate available (ideally at flush rate: 40 to 70 liters per minute) via a nonrebreather mask [29,30]. Using the flush rate (wide open) should be encouraged and is advantageous compared with the "standard" 10 to 15 liters per minute commonly used with nonrebreather masks in other circumstances.

Preoxygenation replaces the nitrogen in the gas-exchanging portions of the lung (functional residual capacity) with oxygen, thereby creating a large oxygen reservoir. This significantly prolongs the safe apneic period of RSI [31,32]. Common conditions that cause oxygen desaturation or exacerbate hypoxemia during RSI and interventions to help prevent or manage them are summarized in the following table (table 3).

Researchers have characterized the expected time to desaturation below 90 percent after apnea is induced in properly preoxygenated patients of various ages and comorbid conditions (figure 1) [33]:

●Healthy 70-kg male: 6 to 8 minutes

●Young children (10 kg): <4 minutes

●Adults with chronic illness or obesity: <3 minutes

●Patient at near full-term pregnancy: <3 minutes

Critically ill patients in the emergency department or intensive care unit often desaturate even more quickly.

The important concept is that preoxygenation provides a longer period before clinically significant desaturation, regardless of the patient's condition, age, and body habitus. Continuous monitoring of oxyhemoglobin saturation by pulse oximetry is essential during RSI. This task should be assigned to an individual who can reliably track and regularly report the information without other tasks or distractions. When assessing SpO₂, remember that pulse oximetry readings obtained with a finger probe may lag behind the central arterial circulation, particularly in critically ill patients [29,34].

There are multiple ways to perform preoxygenation in the critically ill depending on the clinical scenario:

●Inadequate spontaneous ventilation ‒ In the patient with inadequate spontaneous ventilation, preoxygenation should be performed using gentle positive-pressure ventilation with a bag mask at flush-flow rate with a synchronous bag-assist technique (ie, clinician delivers ventilations simultaneously with the patient's inhalation). It is important to ventilate these patients with pressures less than 20 cm H₂O to avoid gastric insufflation. However, in patients with high intrinsic airway pressures (eg, morbid obesity, severe asthma), greater force may be required to ventilate. In such patients, we recommend that cricoid pressure be applied during bag-mask ventilation. This maneuver compresses the cervical esophagus, thereby minimizing gastric insufflation and reducing the risk of aspiration [35,36]. (See 'Cricoid pressure (Sellick maneuver)' below.)

●Adequate spontaneous ventilation and cooperative ‒ In cooperative patients with adequate spontaneous ventilation, preoxygenation can be performed with a nonrebreather mask with flush-flow rate oxygen. Flush-flow rate oxygen is obtained by opening the knob on the flow meter completely (ie, until it won't turn any farther in the "open" direction).

Traditional flow rates of 15 liters per minute provide inadequate preoxygenation since leak around the margin of the mask limits the fraction of inspired oxygen (FiO₂) to approximately 65 percent. Flush rate oxygen (40 to 70 liters per minute depending on the oxygen source and flow meter type) attenuates entrainment of room air around the margin of the mask and increases the FiO₂ to 90 percent or more, thereby providing maximal nitrogen washout and, thus, a larger oxygen reservoir [37]. However, flush rates of oxygen vary considerably among hospitals. Flush rates as low as 20 liters per minute have been reported [38,39]. If circumstances do not allow for three minutes of preoxygenation, eight full, vital-capacity breaths (the deepest breaths the patient can be coached to take) can provide adequate preoxygenation in cooperative patients within one minute.

●Adequate spontaneous ventilation but uncooperative ‒ In patients who are uncooperative and unable to tolerate any preoxygenation efforts, some advocate using a delayed sequence intubation (DSI) technique. DSI involves the administration of a dissociative dose of ketamine (1 mg/kg IV or 3 to 5 mg/kg intramuscularly [IM]) intended to sedate the patient sufficiently to allow effective preoxygenation without depressing respiratory drive. Once ketamine takes effect, preoxygenation is performed as for a cooperative patient with adequate spontaneous ventilation.

Great care must be taken when using DSI, as even a small dose of ketamine in the critically ill can cause apnea or hypotension. The clinician should be ready to assume complete control of the airway and manage hypotension as soon as ketamine is administered.

There are few reports or studies of DSI, and the safety of this technique has not been demonstrated, nor is it known whether this approach reduces adverse events compared with RSI in such patients. Specifically, it is not known whether DSI is superior to simply providing oxygenation via positive pressure using a bag mask beginning immediately after induction. (See 'Adjunct strategies to maximize preoxygenation' below.)

In a small observational study in intensive care unit and emergency department patients, those managed with DSI showed improvements in preoxygenation [40]. A before-and-after prehospital study reported that the implementation of a multi-interventional airway "bundle," including routine administration of ketamine to facilitate preoxygenation, reduced the rate of peri-intubation hypoxemia from 44 to 4 percent [41]. The bundle also required that oxygenation targets (>93 percent SpO₂ for three minutes) be met before RSI could be performed. Therefore, the direct impact of ketamine was difficult to determine.

Right-to-left intrapulmonary shunting — When airspace disease (eg, pneumonia, acute respiratory distress syndrome) causes significant right-to-left intrapulmonary shunting, the above methods of preoxygenation may not be effective. Patients with such shunts require positive end-expiratory pressure (PEEP) to promote alveolar recruitment and maximize the efficacy of preoxygenation efforts. Although a bag mask with a PEEP valve may be used, we recommend noninvasive ventilation in this setting [42-44]. The use of noninvasive ventilation for acute respiratory failure and the benefits of positive-pressure ventilation to improve preoxygenation are reviewed separately. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

If a patient cannot tolerate noninvasive ventilation for preoxygenation, the use of a high-flow nasal oxygen (HFNO) system (eg, Optiflow or Vapotherm) is a reasonable alternative (figure 2) [45-47]. Studies on HFNO for preoxygenation in the critically ill are mixed, but some have demonstrated favorable results [48,49]. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications" and "Preoxygenation and apneic oxygenation for airway management for anesthesia".)

Adjunct strategies to maximize preoxygenation — Additional strategies to prevent or delay oxygen desaturation during emergency airway management include the following [29]:

●Proper positioning ‒ When immobilization for possible spinal injury is not required, preoxygenation is improved by placing the patient in at least a 30-degree head-up position [50-52]. Alternatively, reverse Trendelenburg positioning (bed kept flat but tilted at an angle with patient's head up (figure 3)) may be used for patients requiring spinal injury precautions. The benefits of the head-up or ramp position for obese patients (figure 4) are discussed separately. (See "Airway management in the morbidly obese patient for emergency medicine and critical care", section on 'Preoxygenation'.)

●Continuous passive oxygenation during apnea ‒ During the apneic period of RSI, the airway manager can provide oxygen via nasal cannula at a flow rate of 15 liters per minute. As passive oxygenation (also known as apneic oxygenation) is a simple, low-cost intervention, we encourage its routine use during emergency intubation, particularly if intubation is anticipated to be difficult or prolonged, or the patient has reduced oxygen reserves. HFNO can be used instead of standard nasal tubing when higher levels of apneic oxygenation are needed due to hypoxemia or a high risk of desaturation (figure 2).

The evidence supporting the efficacy and safety of passive oxygenation during emergency RSI comes from randomized trials and meta-analyses involving patients undergoing RSI in the intensive care unit and emergency department settings [53-59]. In a meta-analysis of six trials including 1015 patients undergoing RSI in the intensive care unit (five trials) or emergency department (one trial), mortality was lower for patients who received passive oxygenation during RSI compared with those who did not receive apneic oxygenation (24 versus 31 percent, respectively), a finding that was of borderline statistical significance (RR 0.84, 95% CI 0.7-1.0) [59]. A possible mortality benefit was observed in these trials despite lack of a clear difference in the incidence of severe hypoxemia (defined as SpO₂ <80 percent) during RSI in the two groups (17 versus 19 percent, respectively; RR 0.89, 95% CI 0.68-1.16).

Use of passive oxygenation in this setting is also supported by observational studies [55,56,60-62]. In a meta-analysis that pooled the results of four of the trials above plus four observational studies (1834 patients in total), the incidence of clinically significant hypoxemia (variably defined as SpO₂ <90 or <93 percent) was lower in the group who received passive oxygenation during RSI compared with those who did not (20 versus 28 percent, RR 0.70, 95% CI 0.59-0.82) [55].

Additional support for passive oxygenation comes from studies involving patients undergoing elective intubation in the operating room. These data are discussed in detail separately. (See "Preoxygenation and apneic oxygenation for airway management for anesthesia".)

●Gentle ventilation for patients who cannot tolerate apnea ‒ Many patients who are physiologically deranged (eg, hypotension, acidosis, refractory hypoxemia from intrapulmonary shunting) but require emergency intubation have a greatly reduced tolerance for apnea [14,60]. In such cases, the clinician may wish to perform a modified RSI technique that includes gentle, manual, positive-pressure ventilation during the "apneic" period of RSI [61]. Alternatively, RSI can be avoided altogether and an awake intubation performed, although this technique too can lead to hypoxemia [26]. Regardless of technique, it is essential to address underlying physiologic compromise prior to beginning RSI. (See 'Physiologic optimization' below.)

A reasonable approach when deciding whether to provide mask ventilation during RSI is to assess the patient’s relative risk for hypoxemia and aspiration. If the risk of desaturation and hypoxemia is high, gentle mask ventilation can be performed during induction; if the risk of aspiration is higher, mask ventilation should be avoided if possible.

Bag-mask ventilation during the apneic period of RSI is most likely to benefit patients with severe hypoxemia or those who are anticipated to desaturate rapidly following the administration of RSI medications. These scenarios are more common among patients with severe respiratory disease, who are often being treated in the intensive care unit. Such patients are often hypoxemic at baseline and, although gastroparesis places some at risk for aspiration, they are usually at lower risk for aspiration than emergency department patients. Thus, the risk-benefit assessment often favors mask ventilation during RSI. (See "Basic airway management in adults", section on 'Bag-mask ventilation'.)

Conversely, it is best not to perform bag-mask ventilation during the apneic period of RSI in patients at relatively high risk for aspiration. Such patients are more common in the emergency department. They may include patients with active upper gastrointestinal bleeding, hematemesis, or vomiting; victims of trauma with full stomachs or blood in their airway; or patients who have deteriorated rapidly and whose gastric contents are unknown. The risk-benefit assessment favors not performing mask ventilation during RSI in these patients.

The efficacy of gentle mask ventilation in this setting is supported by a multicenter trial performed in seven intensive care units across the United States [62]. In this trial, 401 patients requiring intubation were randomly assigned to RSI with or without assisted ventilation using a bag mask during the induction phase. Patients in the ventilation group received bag-mask ventilation using 15 liters per minute of oxygen, peak end-expiratory pressure of 5 to 10 cm H₂O, a rate of 10 breaths per minute, a two-handed mask seal, an oropharyngeal airway, and the smallest volume necessary to generate visible chest rise. The ventilation group experienced a significantly lower prevalence of severe hypoxemia (SpO₂ <80 percent) compared with the no ventilation group (10.9 percent [21 patients] versus 22.8 percent [45 patients], relative risk [RR] 0.48, 95% CI 0.30-0.77), while witnessed aspiration rates were similar (2.5 versus 4 percent). While these findings support the approach described, it should be noted that the study lacked standardized preoxygenation protocols or a flush-rate oxygen control group, and patients identified as being at high risk for aspiration (eg, recent episodes of emesis, hematemesis, hemoptysis) were excluded from the trial.

●Techniques to increase airway patency ‒ If necessary, patency of the upper airway can be maintained with adjuncts (nasal or oropharyngeal airways) and positioning maneuvers (jaw thrust and/or chin lift). The chin lift is not used when spine injury precautions are in place. (See "Basic airway management in adults", section on 'Airway maneuvers'.)

Physiologic optimization — Historically, the concept of the difficult airway was related to anatomic factors that made laryngoscopy and delivery of the ETT through the laryngeal inlet difficult. Subsequently, greater emphasis has been placed on physiologic abnormalities that complicate emergency airway management.

"The physiologically difficult airway" is one in which physiologic derangements place the patient at great risk of cardiovascular collapse during the peri-intubation period [14,24,63-66]. The most frequent derangements in patients requiring emergency intubation are hypotension and hypoxemia. Physiologic optimization involves recognizing and addressing areas of physiologic vulnerability that may complicate resuscitative efforts, even if tracheal intubation goes quickly and smoothly.

●Common conditions that cause or exacerbate hypotension following RSI and interventions to help prevent or manage them are summarized in the following table (table 4).

●Common conditions that cause or exacerbate hypoxemia following RSI and interventions to help prevent or manage them are summarized in the following table (table 3).

Hemodynamic compromise should be managed aggressively to optimize conditions prior to intubation whenever time permits. In patients with hypotension from volume depletion or other clinical signs of hypovolemic shock, either isotonic fluid (20 to 30 mL/kg IV bolus) or blood (1 to 2 units of packed red blood cells), tailored to the presumed cause, should be rapidly administered. Patients unable to receive additional fluid (eg, acutely decompensated heart failure), those who experience persistent hemodynamic derangements despite a fluid challenge, and those who have vasodilatory shock are treated with a norepinephrine infusion (starting dose 5 to 15 mcg/minute IV). The therapeutic target is normalization of the systolic blood pressure, a mean arterial pressure of 65 mmHg, or resolution of clinical signs of poor perfusion. In patients with cardiogenic shock, infusion of an inotrope (eg, dobutamine or milrinone) can be initiated. (See "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Use of vasopressors and inotropes".)

Patients with hypoxemia due to significant air space disease and large right-to-left physiologic shunts require aggressive preoxygenation incorporating positive-pressure ventilation, as described above. (See 'Right-to-left intrapulmonary shunting' above.)

Noninvasive ventilation with high levels of PEEP helps to recruit alveoli and decrease the shunt fraction, thereby increasing SpO₂. The goal is an SpO2 >93 percent before induction medications are administered. (See "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation" and "Mechanical ventilation of adults in the emergency department", section on 'Approach to ventilated patient in distress'.)

Nearly all induction agents can cause peripheral vasodilation and myocardial depression. Therefore, patients with reduced ejection fraction, depleted intravascular volume, or ongoing bleeding can suffer circulatory collapse after RSI drugs are administered. The risk is compounded by subsequent positive-pressure ventilation, which can further compromise blood pressure through increased intrathoracic pressure and diminished venous return.

Several studies have investigated the prevalence of peri-intubation arrest associated with critically ill patients in the emergency department and intensive care unit and report rates ranging from 1 to 4 percent [23,67-70]. The two factors consistently found to be associated with peri-intubation cardiac arrest were hypotension and hypoxemia, suggesting that optimization of these two physiologic disturbances can help to reduce intubation-associated morbidity and mortality.

A prospective observational study involving 244 intensive care unit intubations reported that the introduction of a 10-point intubation care bundle resulted in the reduction of severe life-threatening complications from 34 to 21 percent [15]. Three of the components of this intubation bundle were aimed at optimization of physiology: preoxygenation with noninvasive ventilation, IV fluid loading (in the absence of heart failure), and early vasopressor use. In a multicenter trial of intensive care unit patients (n = 1065), those randomized to receive a 500 mL IV bolus of isotonic fluid prior to intubation did not experience lower rates of circulatory collapse compared with patients given no additional fluid [71]. However, overall fluid status was not reported for enrolled patients, and some had decompensated heart failure, limiting our ability to extrapolate from these results. While these findings suggest that routine prophylactic fluid administration is not likely to be helpful, targeted fluid resuscitation prior to RSI in hypotensive patients with volume depletion remains a sensible intervention when time allows.

Paralysis with induction — The concept of RSI is based on the virtually simultaneous IV administration of a rapidly acting induction agent and an NMBA (paralytic agent). Medication selection and dosing are aimed at producing unconsciousness and complete muscular relaxation quickly. RSI does not involve titration of either agent to reach this state. The dose of each agent is precalculated to achieve the desired effect, and the drugs are administered in sequence by rapid IV push. Onset of action after administration is variable depending on the agent chosen, but the goal is to achieve unconsciousness and paralysis 45 to 60 seconds after the drugs are given by IV push. A table summarizing RSI drug selection based upon the clinical scenario is provided (table 5).

Induction agents — The ideal induction agent for RSI acts quickly to provide a deep state of unconsciousness without causing hemodynamic side effects. No available agent meets all criteria. Drugs currently available include etomidate, ketamine, midazolam, and propofol. The induction agents used for RSI are discussed in detail separately (see "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care"). A summary table of induction agents is provided (table 6).

While data about the safest induction agent are conflicting, what is certain is that all induction agents can cause hypotension in the critically ill. Thus, we reduce the dose of the induction agent in patients with hemodynamic instability. Fortunately, patients in shock have compromised peripheral circulation, and lower doses reach the brain sufficiently to produce unconsciousness.

Neuromuscular blocking agents — Use of an NMBA to produce rapid paralysis is the cornerstone of RSI. For RSI, the NMBA is given immediately following administration of the induction agent. Only two NMBAs have onset times short enough for RSI: succinylcholine (standard RSI dose 1.5 mg/kg IV) and rocuronium (standard RSI dose 1.5 mg/kg IV). NMBAs do not provide analgesia or sedation. NMBAs for RSI by emergency and critical care clinicians are discussed in detail separately. (See "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care".)

The onset of effect for rocuronium is dose dependent, but at higher doses (eg, 1.5 mg/kg), onset and intubation conditions are comparable to those provided by succinylcholine, without its numerous potential side effects. Rocuronium has a prolonged duration of effect relative to succinylcholine, and clinicians must make certain that timely and adequate longer-term sedation is given when rocuronium is used. Studies suggest that following RSI performed with rocuronium, the administration of sedative medications is often delayed [72]. (See 'Postintubation management' below.)

Positioning and protection — This phase of RSI refers to positioning the patient for laryngoscopy and protecting against aspiration prior to placement of the ETT. This can be accomplished in part by elevating the head of the bed to approximately 30 degrees. This elevates the laryngeal inlet above the level of the stomach, thereby minimizing the risk of passive regurgitation and aspiration. Proper positioning for direct laryngoscopy is discussed separately. (See "Direct laryngoscopy and endotracheal intubation in adults", section on 'Positioning the patient'.)

Once drugs are administered, respiratory activity decreases and then ceases entirely. Bag-mask ventilation is deliberately avoided for adequately preoxygenated patients. Interposed bag-mask ventilation may be necessary for patients at risk for severe hypoxemia. We routinely use continuous passive oxygenation during RSI. (See 'Preoxygenation' above.)

Cricoid pressure (Sellick maneuver) — Although cricoid pressure (Sellick maneuver) was once widely used during RSI, we no longer recommend routine application of cricoid pressure during laryngoscopy and intubation. The use of cricoid pressure during RSI for anesthesia is discussed separately (see "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Cricoid pressure during RSII').

Cricoid pressure has been shown to reduce gastric insufflation during bag-mask ventilation, but there is no convincing evidence that it reduces the incidence of aspiration of gastric contents during intubation [36,73-77]. Several studies suggest it may contribute to airway obstruction and difficulty intubating in some cases, even when a video laryngoscope is used [73,78-81]. However, it is reasonable to apply cricoid pressure during RSI if bag-mask ventilation is necessary, and we encourage doing so if high pressures are needed to provide adequate ventilation using a bag mask.

A systematic review of cricoid pressure studies noted the following [73]:

●Case series and retrospective reviews describe both the success and failure of cricoid pressure to prevent aspiration.

●Cricoid pressure is often used inconsistently and applied improperly in all airway management settings.

●Cricoid pressure may impair the function of the lower esophageal sphincter.

●Possible risks from cricoid pressure include movement of unstable cervical spine fractures and esophageal injury.

Placement with proof — After complete neuromuscular blockade is achieved, as assessed by absence of masseter muscle tone (ie, laxity of the jaw with no resistance to mouth opening), laryngoscopy is performed. The time to muscular relaxation will vary depending on the NMBA used and dosing. When used with an appropriate induction agent, both succinylcholine and rocuronium at 1.5 mg/kg IV generally produce excellent intubating conditions within 45 seconds. If full neuromuscular paralysis is not achieved by 45 seconds, we recommend waiting an additional 15 to 30 seconds for this to occur, while continuing to monitor oxyhemoglobin saturation.

The goal of laryngoscopy is full and clear visualization of the glottic aperture. Once the glottis is visualized, the clinician places the ETT between the vocal cords, inflates the cuff, withdraws the stylet, and confirms placement. The performance of laryngoscopy is described in detail separately. (See "Direct laryngoscopy and endotracheal intubation in adults" and "Devices for difficult airway management in adults for emergency medicine and critical care" and "Video laryngoscopes and optical stylets for airway management for anesthesia in adults", section on 'Videolaryngoscopy'.)

Confirmation of proper ETT placement is crucial; unrecognized esophageal intubation leads to devastating complications [82]. Waveform capnography is the most accurate means of confirming ETT placement, and we recommend it be used with every intubation. If not available, then capnometry or colorimetric end-tidal carbon dioxide (EtCO₂) devices can be used. For clinicians experienced with ultrasound, this provides another accurate method for confirming proper tube position [83].

Clinical indicators alone, such as visualization of the ETT through the cords, misting of the tube with ventilation, and auscultation of breath sounds over both lung fields, cannot be relied upon to confirm proper ETT placement. A single-view chest radiograph is only useful to determine depth of placement (eg, supraglottic versus tracheal versus mainstem). It is not useful for distinguishing tracheal from esophageal intubation.

The methods for proving proper ETT placement are discussed in greater detail separately. (See "Direct laryngoscopy and endotracheal intubation in adults", section on 'Confirming proper tracheal tube placement'.)

Postintubation management — RSI remains incomplete until the properly placed ETT is secured. Several techniques are commonly used to secure the tube, including taping, tying, and using proprietary tube-holders. The technique employed for emergency department airway management should be readily available, easy to apply, and secure. A post-procedural chest radiograph is obtained to confirm depth of tube placement and to evaluate for evidence of barotrauma as a consequence of positive-pressure ventilation. Mechanical ventilation is initiated. Ventilator settings may need modification according to clinical circumstance. (See "Direct laryngoscopy and endotracheal intubation in adults", section on 'Post-intubation management' and "Mechanical ventilation of adults in the emergency department", section on 'Disease-specific ventilatory management'.)

Minor reductions in SpO₂ and blood pressure may be observed in the immediate post-intubation period as a result of apnea and administration of the induction agent. If these do not rebound quickly with fluids and positive-pressure ventilation, or if previously stable vital signs suddenly deteriorate after tube placement, the clinician should quickly search for signs of a peri-intubation adverse event. This may include tension pneumothorax, ETT cuff rupture, mucus plugging, interruption of the oxygen circuit, or esophageal intubation. (See "Mechanical ventilation of adults in the emergency department", section on 'Approach to ventilated patient in distress'.)

If longer-term neuromuscular blockade is needed, the timing of subsequent doses of both NMBA and sedative agents should be anticipated. Providing both longer-term analgesia and sedation is crucial for all patients following RSI given the relatively short duration of action of the agents frequently used and the inability of paralyzed patients to communicate pain or distress. In a retrospective review of over 800 emergency intubations performed in the emergency department, 66 patients (7.4 percent) reported being aware while paralyzed [84], while a multicenter registry study reported that nearly 14 percent of patients who underwent RSI in the emergency department did not receive additional sedation within 15 minutes following administration of the initial induction agent [85]. Lapses in providing adequate sedation were associated with peri-intubation hypotension and the use of rocuronium.

Increases in heart rate or blood pressure may be an indication of inadequate sedation while paralyzed. Appropriate analgesia and sedation guided by a validated sedation scale (eg, Richmond Agitation Sedation Scale [RASS] (table 7)) often obviate the need for neuromuscular paralysis to permit mechanical ventilation. (See "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Airway management in adults".)

SUMMARY AND RECOMMENDATIONS

●Definitions and basic concepts – Rapid sequence intubation (RSI) uses a rapidly acting induction agent and a neuromuscular blocking agent (NMBA) to create optimal intubating conditions and enable rapid control of the airway. RSI presupposes the patient is at risk for aspiration of gastric contents and incorporates medications and techniques to minimize this risk. The basic approach to RSI consists of the "seven Ps" as outlined below and in the text.

●Preparation – Assess the patient for anatomic features and clinical findings that indicate the patient may be difficult to intubate or to ventilate using a bag mask. Make an airway management plan, including a backup approach, based on the clinical scenario. Gather equipment and medications. (See 'Preparation' above.)

●Preoxygenation – Preoxygenation performed with the patient sitting upright or in reverse Trendelenburg (figure 3) using a face mask or flush-flow oxygen via nonrebreather mask for at least three minutes, and passive oxygenation via high-flow nasal cannula thereafter, is recommended for all patients managed with RSI. Strategies to maximize preoxygenation are provided. (See 'Preoxygenation' above.)

Preoxygenation enables patients to tolerate a longer period of apnea without desaturation. The oxygen saturation (SpO₂) of adults with severe illness or obesity, and pregnant patients nearing the end of their third trimester, falls below 90 percent in less than three minutes, even if ideal preoxygenation is achieved. Time to desaturation in emergency practice is often more rapid than anticipated.

●Physiologic optimization – Unless the need for intubation is immediate, patients undergoing emergency intubation should be physiologically optimized prior to the procedure. This includes hemodynamic optimization with intravenous (IV) fluids, blood products, vasopressors, and inotropes as necessary; relief of hemopneumothorax and hemostasis for trauma patients; and maximal preoxygenation for all. (See 'Physiologic optimization' above.)

•Hypotension following RSI and interventions to help prevent or manage it are summarized in the following table (table 4).

•Hypoxemia following RSI and interventions to help prevent or manage it are summarized in the following table (table 3).

●Paralysis with induction – RSI involves the virtually simultaneous IV administration of a rapidly acting induction agent and NMBA to produce deep sedation and muscular relaxation. The characteristics of the induction agents used for RSI are summarized in the following table (table 6). A table summarizing RSI drug selection based upon the clinical scenario is also provided (table 5). (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care" and "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care".)

●Positioning – This step includes positioning to improve laryngoscopy. Bag-mask ventilation is not required if the patient has been successfully preoxygenated and is at low risk for oxygen desaturation but can be performed when the risk of hypoxia is greater than the risk of aspiration. (See 'Positioning and protection' above.)

●Placement with proof – Once intubation is performed, confirmation of proper endotracheal tube (ETT) placement is crucial. End-tidal carbon dioxide (EtCO₂) determination (preferably with waveform capnography) must be performed to determine proper placement. (See "Direct laryngoscopy and endotracheal intubation in adults", section on 'Confirming proper tracheal tube placement'.)

●Postintubation management – The ETT must be secured, a postintubation chest radiograph checked for positioning and evidence of complications, and appropriate ventilator management implemented. Drugs used for RSI are generally short acting, and the clinician must provide adequate longer-term sedation, analgesia, and sometimes paralysis. (See 'Postintubation management' above and "Mechanical ventilation of adults in the emergency department".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Aaron Bair, MD, MSc, FAAEM, FACEP (deceased), who contributed to an earlier version of this topic review.