Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care

INTRODUCTION — The first task of any clinician managing an acutely unstable patient is to secure the airway. In most circumstances, emergency clinicians use rapid sequence intubation (RSI) when active airway management is required. RSI incorporates neuromuscular blocking agents (NMBA) and rapidly acting sedative (ie, induction) medications to create optimal intubating conditions.

This topic review will discuss the basic clinical pharmacology and selection of NMBAs for use in RSI outside the operating room. The practice of RSI and other medications used as part of RSI are discussed elsewhere, as are other aspects of airway management both inside and outside the operating room. (See "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" and "Pretreatment medications for rapid sequence intubation in adults for emergency medicine and critical care" and "Basic airway management in adults" and "Rapid sequence induction and intubation (RSII) for anesthesia".)

NMBAs IN RAPID SEQUENCE INTUBATION — Rapid sequence intubation (RSI) is the standard of care in emergency airway management for intubations not anticipated to be difficult [1-4]. RSI involves the use of a sedative and a neuromuscular blocking agent (NMBA) to render a patient rapidly unconscious and flaccid in order to facilitate emergency endotracheal intubation, mitigate unwanted physiologic responses to laryngoscopy and intubation, and minimize the risk of aspiration. Multiple prospective observational studies confirm the excellent success rate of RSI using the combination of a sedative and a NMBA in the emergency department (ED) [2-4]. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

NMBAs are integral to the performance of RSI. Multiple randomized trials and observational studies demonstrate that the use of NMBAs improves success rates for emergency endotracheal intubation and reduces the risk of complications [1,5-10]. One prospective trial performed in a prehospital air medical setting and using a crossover design found the use of NMBAs improved the view of the larynx by a full grade in most patients when performing direct laryngoscopy [6].

In RSI, a NMBA is given in conjunction with a sedative agent. Patients undergoing RSI may be fully aware of their environment and painful stimuli, but unable to respond [11,12]. If such patients are not adequately sedated, potentially adverse physiologic responses to airway manipulation can occur, including tachycardia, hypertension, and elevated intracranial pressure (ICP) [13]. Sedative use prevents or minimizes these effects, and may also improve the laryngoscopic view obtained after neuromuscular paralysis [14,15]. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care".)

Prior to intubation, clinicians should whenever possible assess the patient's airway for potential management difficulty. Predicted airway difficulty may require modification of the intubation sequence, or avoidance of a NMBA altogether. Prediction and management of the difficult airway is discussed elsewhere. (See "Approach to the difficult airway in adults for emergency medicine and critical care".)

Clinical circumstance may necessitate the use of a NMBA in a patient despite anticipation of a difficult airway. In such patients, the practitioner must anticipate a possible failure to visualize the glottis and pass an endotracheal tube. If the patient cannot be adequately oxygenated with a bag and mask or extraglottic airway device, decompensation can occur, requiring the placement of a surgical airway. (See "Basic airway management in adults" and "Emergency cricothyrotomy (cricothyroidotomy) in adults".)

Neurologic evaluation becomes more difficult after the use of NMBAs for RSI. However, pupillary response appears to be preserved in most such patients, according to a prospective study of 94 patients who received either succinylcholine or rocuronium as part of RSI [16].

MECHANISMS OF ACTION — Neuromuscular blocking agents (NMBA) are classified by their mechanism of action (ie, depolarizing or nondepolarizing). The only depolarizing agent in common clinical use is succinylcholine.

●Succinylcholine (SCh), the classic depolarizing agent, is an analogue of acetylcholine (ACh) that stimulates all cholinergic receptors throughout the parasympathetic and sympathetic nervous systems. SCh binds directly to the postsynaptic ACh receptors of the motor endplate, causing continuous stimulation of these receptors. This leads to transient fasciculations followed by muscular paralysis.

Only a small percentage of SCh reaches the motor endplate. Most SCh is rapidly hydrolyzed in the bloodstream by the enzyme pseudocholinesterase. Paralysis persists until enough SCh dissociates from the ACh receptor and is hydrolyzed by pseudocholinesterase to allow normal receptor and motor endplate function.

●Nondepolarizing agents (eg, rocuronium) competitively inhibit the postsynaptic ACh receptors of the neuromuscular motor endplate. This action prevents depolarization and inhibits all muscular function. Nondepolarizing NMBAs do not cause membrane depolarization, so the side effects seen with succinylcholine do not occur. The time to clinical effect and the duration of action are uniformly longer than SCh.

Two categories of nondepolarizing NMBAs exist: the benzylisoquinolinium agents (eg, atracurium and mivacurium) and the aminosteroid agents (eg, rocuronium, vecuronium, and pancuronium). The benzylisoquinolinium agents are not routinely used in the emergency setting because they more often cause histamine release and some cause autonomic ganglionic blockade. The aminosteroids are generally used in RSI when a contraindication to succinylcholine (SCh) exists and for prolonged neuromuscular paralysis after intubation [17]. (See 'Nondepolarizing agents' below.)

SUCCINYLCHOLINE — The use of succinylcholine for rapid sequence intubation in the emergency setting is reviewed below; a more detailed review of the pharmacology of succinylcholine and a discussion of its use for anesthesia are provided separately. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Succinylcholine'.)

Clinical use — Succinylcholine (SCh) is used extensively in the emergency setting, due to its rapidity of onset and offset, and the consistent intubating conditions it provides. For rapid sequence intubation (RSI), SCh is given as a 1.5 mg/kg intravenous (IV) dose, with intubation-level paralysis occurring 45 to 60 seconds after dosing [18]. Its duration of action is approximately 6 to 10 minutes [18].

A systematic review of 50 controlled trials involving 4151 participants concluded that SCh is superior to rocuronium for achieving excellent intubating conditions (risk ratio [RR] 0.86; 95% CI 0.81-0.92) and clinically acceptable intubating conditions (RR 0.97; 95% CI 0.95-0.99) [19]. A subsequent randomized trial involving 1248 patients requiring out-of-hospital emergency tracheal intubation reported a higher rate of successful first-attempt intubation in patients given succinylcholine compared with rocuronium (79.4 versus 74.6 percent) [20]. In clinical use, there likely is little difference between the agents, except for the substantially longer duration of action of rocuronium.

It is far better to overestimate the dose of succinylcholine than to underdose. Larger doses result in the same level of paralysis and do not increase the risk to the patient; inadequate doses can leave the patient inadequately paralyzed and difficult to intubate. Dosing of SCh is based on total body weight. This holds true in both morbidly obese and pregnant patients [21-23]. (See "Airway management in the morbidly obese patient for emergency medicine and critical care".)

SCh can be used safely in patients with myasthenia gravis without risk of precipitating severe hyperkalemia. Patients with myasthenia gravis are relatively resistant to SCh, and when undergoing RSI should receive 2 mg/kg in order to stimulate sufficiently the remaining acetylcholine receptors unaffected by the disease [24].

SCh slowly degrades at room temperature, but retains 90 percent of its activity for up to three months when so stored [25]. The degradation rate can be reduced by refrigeration. If SCh is stored at room temperature, a quality management system is necessary to ensure removal of stock before the SCh becomes outdated.

Contraindications and side effects

Absolute contraindications overview — Succinylcholine (SCh) is absolutely contraindicated in patients with a personal or family history of malignant hyperthermia and in patients deemed to be at high risk of developing severe hyperkalemia.

We recommend the clinician use a nondepolarizing neuromuscular blocking agent, and not succinylcholine, when performing RSI on patients with the following conditions [26,27]:

●Malignant hyperthermia history (personal or family)

●Neuromuscular disease involving denervation (note SCh is safe in myasthenia gravis) (see 'Clinical use' above)

●Muscular dystrophy

●Stroke over 72 hours old

●Rhabdomyolysis

●Burn over 72 hours old

●Significant hyperkalemia (eg, suggested by characteristic changes on an electrocardiogram)

Malignant hyperthermia — SCh can cause malignant hyperthermia in patients predisposed to the condition. Malignant hyperthermia is a life-threatening, myopathic metabolic disorder that is characterized by sympathetic hyperactivity, muscular rigidity, acidosis, and hyperthermia. Onset is usually acute, but delayed presentations can occur. A history of malignant hyperthermia or a known genetic predisposition to the condition are absolute contraindications to the use of SCh, although this history is often unavailable prior to an emergency intubation. The emergency management of malignant hyperthermia is outlined in the following table and consists primarily of cooling techniques, sedation, and administration of dantrolene sodium (table 1). (See "Malignant hyperthermia: Diagnosis and management of acute crisis" and "Susceptibility to malignant hyperthermia: Evaluation and management".)

Rhabdomyolysis — Rhabdomyolysis, preexisting hyperkalemia associated with electrocardiographic changes, and disease states that cause upregulation of postjunctional acetylcholine receptors constitute the conditions that place patients at high risk of severe hyperkalemia (table 2). (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Treatment and prevention of hyperkalemia in adults".)

Fatal cases of hyperkalemia have occurred in patients with rhabdomyolysis given SCh. Standard treatment for hyperkalemia should be given, but is less effective in patients with hyperkalemia related to SCh and rhabdomyolysis than SCh and ACh receptor upregulation [26]. (See "Rhabdomyolysis: Clinical manifestations and diagnosis".)

Receptor upregulation — Upregulation of acetylcholine (ACh) receptors is the mechanism that increases the risk of severe hyperkalemia from SCh in susceptible patients. Such upregulation is perpetual in chronic conditions but is not clinically significant until approximately three to five days after an acute injury (eg, burn or crush). Receptor upregulation results from the disease states listed below:

●Denervating injuries (eg, stroke, spinal cord injury), after 72 hours

●Denervating diseases (eg, multiple sclerosis, amyotrophic lateral sclerosis)

●Inherited myopathies

●Burns, after 72 hours

●Crush injuries, after 72 hours

●Severe infection with exotoxin production (eg, tetanus, botulism)

●Prolonged total body immobilization

Receptor upregulation can take several days to develop, but once it is present hyperkalemia develops within a few minutes after SCh is given. Fatal episodes of hyperkalemia have occurred after doses of SCh in patients with upregulation of ACh receptors due to neuropathy (eg, following stroke) and myopathy (eg, muscular dystrophy). Some conditions (eg, muscular dystrophy, amyotrophic lateral sclerosis) result in lifelong receptor upregulation. Other diseases (eg, stroke, moderate or major burn) manifest receptor upregulation that can persist from six months to years. (See "Initial assessment and management of acute stroke" and "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis" and "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease" and "Emergency care of moderate and severe thermal burns in adults".)

Hyperkalemia — The most important side effect of succinylcholine (SCh) is hyperkalemia. Studies suggest that SCh may raise the serum potassium up to 0.5 mEq/L, even in normal patients [28-30]. This rise is clinically insignificant unless the patient is predisposed to severe hyperkalemia due to disease states that cause upregulation of postjunctional acetylcholine receptors or rhabdomyolysis (table 2). If such a condition exists, SCh is contraindicated. (See 'Receptor upregulation' above.)

SCh should also be avoided in the presence of hyperkalemia sufficient to cause electrocardiographic changes. A competitive (ie, nondepolarizing) NMBA is preferred when the risk of hyperkalemia is great. The ECG manifestations of hyperkalemia are described elsewhere. (See "Clinical manifestations of hyperkalemia in adults", section on 'ECG changes'.)

Although a number of case reports suggest that patients with chronically elevated serum potassium levels (eg, patients with renal failure on hemodialysis) are at risk for acute hyperkalemia if given SCh, a summary of several controlled studies suggests this is not true [31]. SCh does not cause an abnormally large potassium increase in patients with renal failure (unlike neuromuscular disease). Nevertheless, it is prudent to avoid SCh if the serum potassium level is sufficiently elevated to cause electrocardiographic changes. We suggest using a nondepolarizing agent, and not succinylcholine, when performing RSI in any patient who requires hemodialysis for treatment of renal failure and is suspected to have a significantly elevated serum potassium (eg, missed dialysis treatment with suggestive ECG).

Trismus — Trismus/masseter muscle spasm occurs after SCh administration in 0.001 to 0.1 percent of patients [32,33]. Treatment consists of either a standard dose of a nondepolarizing neuromuscular blocking agent to relax the masseter muscles, or in extreme cases, a surgical airway (ie, cricothyrotomy) [34,35]. Masseter spasm may occur in isolation or, rarely, with malignant hyperthermia [36]. Unexplained hyperthermia and metabolic derangements in association with masseter spasm should raise suspicion for malignant hyperthermia [37].

Fasciculations — SCh causes nicotinic activation that manifests as muscle fasciculations, along with muscarinic stimulation that may lead to bradycardia in selected patients, especially children. It is important to be prepared for both of these side effects. Muscle fasciculation may contribute to an increase in intracranial pressure. Fasciculations can be mitigated by giving a pretreatment dose of a nondepolarizing NMBA two to three minutes prior to giving SCh, but this is of no value in the emergency setting [38]. A pretreatment dose is equivalent to one tenth the dose used for full paralysis. (See "Rapid sequence intubation in adults for emergency medicine and critical care".)

Use in children — SCh use in children has been questioned due to the small but important fraction of pediatric patients who have undiagnosed muscular dystrophy and are at risk for hyperkalemia [39]. Although SCh remains the preferred NMBA for emergency intubation during resuscitation of pediatric patients, the US Food and Drug Administration (FDA) has determined that SCh should not be used for elective surgery in children. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Bradycardia — Succinylmonocholine, the initial metabolite of SCh, sensitizes the cardiac muscarinic receptors in the sinus node, and repeat doses of SCh may cause bradycardia [40]. Bradycardia in children has been described, but the attribution of this effect to SCh is controversial. Pretreatment with atropine may help to prevent this side effect, although no large randomized trials have been performed to assess this [17]. Bradycardia may also occur in adults who receive a second dose of SCh or a prolonged infusion. Clinicians should be prepared to administer atropine to any child or adult receiving SCh if bradycardia occurs. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

Intraocular pressure — Intraocular pressure rises have been purported to result from SCh, but evidence for this is lacking and many patients with globe injuries are managed safely using SCh [41,42]. We feel it is acceptable for emergency clinicians to use succinylcholine in open globe injuries. The use of sedative agents may mitigate any rise in intraocular pressure [41]. (See "Open globe injuries: Emergency evaluation and initial management".)

For RSI in such patients, we suggest proper induction with a sedative agent and paralysis with a competitive NMBA or pretreatment with a defasciculating dose of a nondepolarizing agent in advance of SCh. (See "Rapid sequence intubation in adults for emergency medicine and critical care".)

NONDEPOLARIZING AGENTS — The use of nondepolarizing agents for rapid sequence intubation in the emergency setting is reviewed below; a more detailed review of the pharmacology of nondepolarizing agents and a discussion of their use for anesthesia are provided separately. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Nondepolarizing neuromuscular blocking agents'.)

Rocuronium — We suggest nondepolarizing neuromuscular blocking agents (NMBAs) be used for rapid sequence intubation (RSI) when succinylcholine (SCh) is contraindicated or when prolonged neuromuscular blockade is required. (See 'Contraindications and side effects' above.)

When a nondepolarizing NMBA is indicated to perform RSI, we suggest rocuronium be used. We use a dose of 1.5 mg/kg intravenously (IV) for RSI, using total body weight to calculate that dose.

Rocuronium has a shorter time to onset and shorter duration of action compared with other agents in its class. The time to intubation-level paralysis is approximately 45 to 60 seconds when an IV dose of 1 to 1.2 mg/kg (using ideal body weight) is given. However, in the emergency setting, clinicians often estimate patient body weight incorrectly [43-45]. Furthermore, in a multicenter observational study involving over 8000 intubations with rocuronium, a rocuronium dose of ≥1.4 mg/kg IV was associated with a higher rate of first-attempt intubation success than lower dosing strategies when RSI was performed using direct laryngoscopy or in patients with pre-existing hypotension [46]. Thus, we prefer the higher dose.

Administration of a 20 mL bolus of isotonic saline immediately following the administration of rocuronium may decrease the time to onset of effect [47]. Rocuronium's duration of action is approximately 45 minutes. Multiple studies and systematic reviews demonstrate that it creates intubating conditions comparable to succinylcholine [48-51]. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Airway management in the morbidly obese patient for emergency medicine and critical care", section on 'Medication dosing'.)

While traditional dosing for rocuronium was based upon ideal body weight, using total body weight is more intuitive for clinicians and helps to ensure that adequate amounts of the drug reach neuromuscular endplates, especially in low-flow states (eg, septic shock). More consistent paralysis probably improves laryngoscopy through the mechanical advantage gained from having the patient completely paralyzed at the start of the first intubation attempt.

Certain drugs used for pretreatment or commonly given to patients who may subsequently require RSI can alter the duration of paralysis induced by rocuronium. Remifentanil appears to delay the onset of paralysis by approximately 30 to 45 seconds [52], while magnesium appears to prolong paralysis [53]. Lidocaine does not appear to alter the duration of paralysis [54]. (See "Pretreatment medications for rapid sequence intubation in adults for emergency medicine and critical care".)

A predicted difficult airway is the most common relative contraindication to the use of nondepolarizing NMBAs for RSI. Should the preintubation examination predict a difficult airway, the clinician may select an alternative method to RSI, modify the sequence of drugs for RSI, or develop a more detailed back-up plan in the event of a failed intubation. It is best to avoid a situation where intubation cannot be performed and the patient is apneic. Assessment and management of the difficult airway are discussed separately. (See "Approach to the difficult airway in adults for emergency medicine and critical care".)

Vecuronium and pancuronium — Vecuronium is an alternative competitive NMBA to rocuronium for RSI, but it has fallen out of favor due to its delayed time of onset [55].

When vecuronium is used for emergency intubation, a "priming," non-paralytic dose of 0.01 mg/kg is administered three minutes before the actual intubating dose of 0.15 mg/kg [56]. The priming dose accelerates the onset of paralysis from the intubation dose that follows. Administered in this way, vecuronium achieves intubation level paralysis in approximately 75 to 90 seconds and reduces the period the patient is apneic. The duration of action is approximately 20 to 30 minutes.

Without the priming dose, approximately three minutes are needed until the onset of full paralysis. This can lead to hypoxia and force the clinician to interpose bag-mask ventilation before intubation can be performed.

Pancuronium should not be used for RSI. It can cause tachycardia and histamine release, and has a longer time to onset and duration of action than alternative agents.

Reversal of nondepolarizing agents

Neostigmine — The nondepolarizing NMBAs, unlike SCh, can be reversed by the use of neostigmine (0.06 to 0.08 mg/kg IV) after approximately 40 percent of neuromuscular function has returned [37]. Neostigmine is an acetylcholinesterase inhibitor which allows ACh to continue to stimulate the neuromuscular junction and cause muscular stimulation, thereby competing more effectively with the nondepolarizing NMBA. However, reversal is rarely indicated or of use in the emergency setting due to the need for a full return of neuromuscular function.

Sugammadex — Sugammadex is a novel agent that encapsulates and binds with molecules of rocuronium and other steroidal NMBAs (eg, vecuronium and pancuronium), thereby rapidly reversing their neuromuscular blocking effects. Although variations in individual patient response have been noted, a dose of 16 mg/kg based on total body weight [57] can reverse profound rocuronium-induced blockade within three minutes. Cardiac arrhythmias, including marked bradycardia, may occur after administration of sugammadex in up to 1 percent of patients. Patients with cardiac disease appear to be at increased risk. Although rare, anaphylaxis within minutes after sugammadex administration has occurred, and the incidence is proportional to the administered dose. Thus, full ECG monitoring should be continued during and after administration of sugammadex, and resuscitation drugs, including atropine and epinephrine, should be immediately available. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Sugammadex'.)

There is insufficient evidence to recommend that RSI always be performed using rocuronium plus sugammadex instead of succinylcholine. When rocuronium is used, sugammadex should be immediately available for rapid reversal of neuromuscular blockade whenever possible. However, sugammadex may have limited availability in some settings outside of the operating room.

NMBAs FOR MYASTHENIA GRAVIS — Patients with myasthenia gravis (MG) requiring emergency airway management present a novel pharmacologic problem for airway managers. We believe that either a depolarizing or non-depolarizing neuromuscular blocking agent (NMBA) may be used for patients with MG requiring rapid sequence intubation (RSI). Overall, the pathophysiology of MG (summarized below) argues for a modest increase in the dose of succinylcholine for these patients, and a reduction of dose when a competitive non-depolarizing NMBA is used. If succinylcholine is used, we suggest increasing the intubating dose to 2 mg/kg IV from our usual recommended dose of 1.5 mg/kg IV. If a non-depolarizing NMBA is used, we suggest giving a smaller dose than is typically used for RSI. For rocuronium, we suggest a dose of 0.6 mg/kg IV, compared with the 1 to 1.2 mg/kg dose used for RSI in patients without MG. For vecuronium, we suggest a dose of 0.06 mg/kg, compared with the standard dose of 0.15 mg/kg. In addition, the priming dose used when giving vecuronium should not be given to patients with MG. The rationale for the approach outlined here is described below. (See "Myasthenic crisis".)

The pathophysiology of MG includes antibodies to either the acetylcholine (Ach) receptors on the neuromuscular endplate of skeletal muscles or, less frequently, antibodies to specific proteins involved in skeletal muscle contraction. Most myasthenic patients have fewer working Ach receptors, as antibodies destroy the majority of receptors produced. The Ach receptors at the endplate are also dysfunctional, and more Ach is required at the receptor to depolarize muscle than in non-myasthenic patients. In addition, the treatment of MG includes cholinesterase inhibitors, which prolong the effect of succinylcholine [58,59]. Any strategy for RSI in patients with MG must account for the reduced numbers and dysfunction of Ach receptors, and the effect of treatments. A detailed description of the pathophysiology of MG is provided separately. (See "Pathogenesis of myasthenia gravis".)

When used for intubation during routine induction of general anesthesia, the depolarizing agent succinylcholine must be given in higher than usual doses to cause adequate depolarization and muscle relaxation in patients with MG. Dose-response studies in patients with MG show that the average dose of succinylcholine required to cause paralysis in the operating room is approximately three times greater than that required for standard general anesthesia, and the authors recommend higher doses [24,60-63]. The typical dose of succinylcholine in the operating room is 0.6 mg/kg. Therefore, when emergency RSI is performed on a patient with MG, the succinylcholine dose should be increased to 2 mg/kg. Patients with MG do not experience exaggerated potassium elevations when given succinylcholine, unlike patients with established neurologic conditions involving denervation of the motor end plate [24].

Non-depolarizing agents (eg, rocuronium, vecuronium) act by competitively blocking Ach receptors, thereby reducing the endplate stimulation that maintains muscle tone. Dose-response studies using these agents show that the average dose required to cause train-of-four paralysis in the operating room is less than one-third that required for standard anesthesia [63-69]. However, the rocuronium dose used for RSI (1 to 1.2 mg/kg) is approximately twice that used in the operating room (0.6 mg/kg). Therefore, a smaller than usual intubating dose of a non-depolarizing NMBA, such as rocuronium, is appropriate when performing RSI in patients with myasthenia gravis. Although the evidence available to guide dosing for RSI is limited and indirect, we believe that a rocuronium dose of 0.6 mg/kg balances concerns about the prolonged effect that may result from higher doses and the risk of inadequate paralysis and compromised intubating conditions that may result from lower doses.

Some argue that an NMBA is unnecessary when intubating a patient with a myasthenic crisis, as the typical reason a myasthenic patient requires intubation is muscular weakness and fatigue causing respiratory failure. In addition, NMBA duration of action can be prolonged in myasthenic patients who are therefore at risk for requiring extended mechanical ventilation after being given an NMBA [70,71]. Although some patients with MG may be sufficiently weak that intubation may be successful using a sedative agent alone, we believe this approach may be hazardous and that an NMBA should be used in all cases for which RSI is the selected method [58,72-74]. The combination of an NMBA and a sedative ensures optimal intubating conditions, while use of a sedative agent alone for emergency intubation of a myasthenic patient risks inadequate muscle relaxation, allowing the patient to clench their jaw, develop laryngospasm, or vomit when intubation is attempted.

INTRAMUSCULAR ADMINISTRATION OF NMBA FOR RSI — The intravenous (IV) route is strongly preferred for all medications used during rapid sequence intubation (RSI). When IV access is not possible, administration through an intraosseous line is a reasonable alternative. On rare occasions, it may be necessary to intubate a patient for whom neither IV nor intraosseous access is possible.

In the rare circumstance when RSI is deemed necessary and medications must be given by intramuscular (IM) injection, we suggest the use of succinylcholine, 4 mg/kg IM, along with an induction agent (eg, ketamine 4 mg/kg IM or midazolam 0.1 to 0.3 mg/kg IM). The slower onset of effect for the neuromuscular blocking agent (NMBA) may result in a longer period of respiratory inadequacy before sufficient relaxation is obtained for intubation. Therefore, the clinician must ensure full pre-oxygenation if possible and provide continuous oxygen by nasal cannula at a rate of at least 5 L/minute throughout the procedure. In addition, the clinician should be prepared to supplement the patient's oxygenation with a bag mask device if desaturation occurs before the patient is fully paralyzed for the intubation attempt.

Studies of IM administration of NMBAs are limited. A systematic review identified nine studies involving 303 adult and pediatric patients that evaluated the onset of effect for NMBAs given by an IM route [75]. Six studies focused on succinylcholine, with IM doses ranging from 1 mg/kg to 4 mg/kg. At a dose of 4 mg/kg, the mean time to onset of effect was approximately 2 minutes for adults but 4 to 5.6 minutes in children. Available data suggest the onset of effect for IM rocuronium is six to nine minutes in children, with no data in adults. None of the studies addressed the IM use of NMBAs specifically for emergency RSI.

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

●Rapid sequence intubation (RSI) involves combining a sedative (induction medication) and a neuromuscular blocking agent (NMBA) to render a patient rapidly unconscious and flaccid to facilitate emergency tracheal intubation and to minimize the risk of aspiration. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)

●NMBA mechanisms and characteristics – The use of NMBAs for RSI improves success rates for emergency endotracheal intubation and reduces the risk of complications. The characteristics of the NMBAs used most often are described in the text. (See 'NMBAs in rapid sequence intubation' above and 'Mechanisms of action' above.)

●When to use succinylcholine – When not contraindicated, we suggest succinylcholine (SCh) be used as the NMBA in RSI due to its rapidity of onset and offset, and the consistent intubating conditions it provides (Grade 2A). SCh is given as a 1.5 mg/kg intravenous (IV) dose (using total body weight) in adults. Intubation-level paralysis is achieved within 45 to 60 seconds and its duration of action is approximately 6 to 10 minutes. (See 'Clinical use' above.)

●When to use a nondepolarizing NMBA – We recommend using a nondepolarizing NMBA, and not succinylcholine, when performing RSI on patients with the following conditions (Grade 1B):

•Malignant hyperthermia history (personal or family)

•Neuromuscular disease

•Muscular dystrophy

•Stroke over 72 hours old

•Rhabdomyolysis

•Burn over 72 hours old

•Significant hyperkalemia (eg, suggested by characteristic changes on an electrocardiogram)

The contraindications to SCh are discussed in detail in the text. (See 'Absolute contraindications overview' above and 'Contraindications and side effects' above.)

●Rocuronium is the preferred nondepolarizing NMBA – When succinylcholine (SCh) is contraindicated for RSI, we suggest rocuronium be used over other nondepolarizing NMBAs (Grade 2B). Rocuronium is given as at a dose of 1.5 mg/kg IV (using total body weight). The time to intubation-level paralysis is approximately 45 to 60 seconds, and its duration of action is approximately 45 minutes. (See 'Nondepolarizing agents' above.)

●Reversal of effects with sugammadex – Sugammadex rapidly reverses the neuromuscular blocking effects of rocuronium or vecuronium. For patients undergoing RSI with rocuronium who cannot be intubated and who are anticipated to benefit from reversal of the neuromuscular blockade, we recommend administration of sugammadex, 16 mg/kg IV. Because of the risk of bradycardia and anaphylaxis, full ECG monitoring should be continued during and after administration of sugammadex, and atropine, epinephrine, and other resuscitation drugs should be immediately available. (See 'Sugammadex' above.)