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Pharmacologic Agents Used During Intubation in the ICU

PCCSU Volume 25, Lesson 33


The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. The program provides information on pulmonary, critical care, and sleep medicine issues. CME is no longer available for the PCCSU program.


  • Update your knowledge and understanding of pulmonary medicine topics.
  • Update your knowledge and understanding of critical care medicine topics.
  • Update your knowledge and understanding of sleep medicine topics.
  • Learn clinically useful practice procedures.

CME Availability

Effective July 1, 2013, PCCSU Volume 25 is available for review purposes only.

Effective December 31, 2012, PCCSU Volume 24 is available for review purposes only.

Effective December 31, 2011, PCCU Volume 23 is available for review purposes only. CME credit for this volume is no longer being offered

Effective December 31, 2010, PCCU Volume 22 is available for review purposes only. CME credit for this volume is no longer being offered.

Accreditation Statement

The American College of Chest Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Statement

Credit no longer available as of July 1, 2013.

Disclosure Statement

The American College of Chest Physicians (CHEST) remains strongly committed to providing the best available evidence-based clinical information to participants of this educational activity and requires an open disclosure of any potential conflict of interest identified by our faculty members. It is not the intent of CHEST to eliminate all situations of potential conflict of interest, but rather to enable those who are working with CHEST to recognize situations that may be subject to question by others. All disclosed conflicts of interest are reviewed by the educational activity course director/chair, the Education Committee, or the Conflict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The CHEST educational standards pertaining to conflict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all CHEST CME activities are ensured of independent, objective, scientifically balanced presentations of information. Disclosure of any or no relationships will be made available for all educational activities.

CME Availability

Volume 25 Through June 30, 2013
Volume 24 Through December 31, 2012
Volume 23 Through December 31, 2011
Volume 22 Through December 31, 2010

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PCCSU Volume 25 Editorial Board

Steven A. Sahn, MD, FCCP

Director, Division of Pulmonary and Critical Care Medicine, Allergy, and Clinical Immunology
Medical University of South Carolina
Charleston, SC

Dr. Sahn has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Deputy Editor
Richard A. Matthay, MD, FCCP

Professor of Medicine
Section of Pulmonary and Critical Care Medicine
Yale University School of Medicine
New Haven, CT

Dr. Matthay has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Alejandro C. Arroliga, MD, FCCP
Professor of Medicine
Texas A&M Health Science Center
College of Medicine
Temple, TX

Dr. Arroliga has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Paul D. Blanc, MD, FCCP
Professor of Medicine
University of California, San Francisco
San Francisco, CA

Dr. Blanc has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health, Flight Attendants Medical Research Institute – university grant monies
University of California San Francisco, US Environmental Protection Agency, California Environmental Protection Agency Air Resources Board – consultant fee
Habonim-Dror Foundation Board of Trustees – fiduciary position

Guillermo A. do Pico, MD, FCCP
Professor of Medicine
University of Wisconsin Medical School
Madison, WI

Dr. do Pico has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Ware G. Kuschner, MD, FCCP
Associate Professor of Medicine
Stanford University School of Medicine
Palo Alto, CA

Dr. Kuschner has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Teofilo Lee-Chiong, MD, FCCP
Associate Professor of Medicine
National Jewish Medical Center 
Denver, CO

Dr. Lee-Chiong has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health – grant monies (from sources other than industry)
Covidien, Respironics, Inc. – grant monies (from industry-related sources)
Elsevier – consultant fee

Margaret Pisani, MD, MPH, FCCP
Assistant Professor of Medicine
Yale University School of Medicine 
New Haven, CT

Dr. Pisani has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Stephen I. Rennard, MD, FCCP
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

Dr. Rennard has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

AstraZeneca, Biomark, Centocor, Novartis – grant monies (from industry-related sources)

Almirall, Aradigm, AstraZeneca, Boehringer Ingelheim, Defined Health, Dey Pharma, Eaton Associates, GlaxoSmithKline, Medacrop, Mpex, Novartis, Nycomed, Otsuka, Pfizer, Pulmatrix, Theravance, United Biosource, Uptake Medical, VantagePoint – consultant fee/advisory committee

AstraZeneca, Network for Continuing Medical Education, Novartis, Pfizer, SOMA – speaker bureau

Ex Officio
Gary R. Epler, MD, FCCP

Clinical Associate Professor of Medicine
Harvard Medical School
Brigham & Women's Hospital
Boston, MA

Dr. Epler has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Lilly Rodriguez
ACCP Staff Liaison

By Enrique Diaz-Guzman, MD; Juan Sanchez, MD; and Eduardo Mireles-Cabodevila, MD

Dr. Diaz-Guzman is Associate Professor of the Department of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Dr. Sanchez is Director of the Department of Lung Transplantation and Interventional Pulmonology, Scott & White Healthcare, Temple, Texas. Dr. Mireles-Cabodevila is Clinical Associate of the Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.

Drs. Diaz-Guzman, Sanchez, and Mireles-Cabodevila have disclosed no significant relationships with the companies/organizations whose products or services may be discussed within this chapter.


  1. Describe the most common pharmacologic agents used during endotracheal intubation in patients who are critically ill.
  2. Understand the pharmacologic differences between different sedative agents.
  3. Discuss the current controversies regarding the use of etomidate.
  4. Examine the role of neuromuscular blockers during rapid sequence intubation.
  5. Understand the population at risk for adverse events of succinylcholine.

Key Words: etomidate; endotracheal intubation; intensive care unit; neuromuscular blocker; sedative

Abbreviations: AGABA = gamma-aminobutyric acid; ICP = intracranial pressure; KETASED = KETAmine SEDation; RSI = rapid sequence induction and intubation; SCh = succinylcholine


Airway management represents one of the most challenging situations in the ICU. Rapid sequence induction and intubation (RSI) is a technique to facilitate tracheal intubation in patients at high risk of aspiration. The goal is to minimize the time between the loss of protective airway reflexes and tracheal intubation. Patients in the ICU frequently experience many complex physiologic derangements that result in cardiorespiratory instability. These present a unique challenge when sedative or paralytic agents are necessary to successfully gain control of the airway. For these reasons, it is of the utmost importance that health-care professionals select the most appropriate combination of drugs to facilitate airway management while still ensuring patient safety. Therefore, health-care professionals must be familiar with and understand the pharmacologic advantages and disadvantages of the agents used to produce analgesia, anesthesia, and neuromuscular blockade during intubation. This review provides a summary of the agents frequently used for airway management in the ICU setting.

The RSI technique may require changes in the sequence of medications administered according to patient condition. Preinduction medications are administered to decrease cough, laryngospasm, and the sympathetic response to intubation. This is followed by an induction medication to create loss of consciousness, muscle relaxation, and the abolition of the airway protection reflexes. During the period of induction, neuromuscular blockers may be administered to enhance intubation conditions. Postintubation medications are directed when maintaining a level of sedation and analgesia in patients who are critically ill, but these are not covered in this article. A protocolized approach to intubation in patients who are critically ill is associated with fewer life-threatening complications.1

Preinduction Agents


Lidocaine is a class 1B antiarrhythmic agent that is frequently used as a topical anesthetic to control the cough reflex during endoscopic procedures. IV administration of lidocaine prior to RSI results in the attenuation of several systemic responses associated with larynx and trachea manipulation.2 An IV dose of 1 or 2 mg/kg given 1 to 5 min prior to intubation is associated with adequate cough control. A recent study evaluated the addition of IV lidocaine to propofol in patients who underwent a laryngeal mask airway insertion. Patients who received lidocaine had lower incidences of coughing, gagging, and laryngospasm.3

Pretreatment with lidocaine has been associated with blunting of hyperadrenergic cardiovascular responses (attenuation of hypertensive and tachycardic responses); however, evidence is limited and some studies have reported no beneficial effects.4 For example, a literature review found that lidocaine produced some benefit in attenuating sympathomimetic effects after intubation in approximately 60% of cases and a reduction in the number of cardiac arrhythmias following intubation, with no cases of lidocaine toxicity or adverse neurologic reaction.2 In addition, lidocaine has been used in patients with head trauma or evidence of increased intracranial pressure (ICP); this is because studies have shown that endotracheal suctioning and laryngeal manipulation cause a significant increase in ICP.5 Whether this is an effect of lidocaine or whether it has any effect on patient outcomes has yet to be determined.5


Opioid agents provide analgesia and decrease the sympathetic tone, thus resulting in attenuation of the hemodynamic responses to laryngeal stimulation. Among commonly used agents, fentanyl and its derivatives are preferred to morphine due to their more rapid onset of action and shorter duration. The administration of opioids prior to intubation results in a reduction in blood pressure and heart rate (blunting hemodynamic response to intubation), although higher doses may be associated with hypotension, apnea, and chest wall rigidity.6 The administration of 2 to 3 mcg/kg of fentanyl given 2 min prior to intubation results in blunting of the hypertensive response, but it has little impact on reflex tachycardia.7 Similarly, other opiates, such as sufentanil, alfentanil, and remifentanil, attenuate the hemodynamic responses to rapid sequence intubation.8

Induction Agents


Etomidate is a short-acting IV anesthetic agent used for induction of anesthesia. It is frequently used by intensivists for inducing anesthesia, particularly in patients with hemodynamic instability. Etomidate causes less hypotension in patients with cardiovascular disease; thus, many health-care professionals prefer it for airway management in patients who are critically ill.9 In recent years, there has been extensive debate about its use in patients with sepsis and those who are critically ill. Etomidate suppresses the production of cortisol, and data suggest worse outcomes in patients with sepsis.10 Some authors have proposed abandoning the use of this agent in patients who are critically ill.11

Mechanism of Action: Etomidate is a carboxylated imidazole that affects gamma-aminobutyric acid (GABA) receptors that contain beta-3 subunits. It causes anesthesia and amnesia. It has no analgesic properties.

Pharmacokinetics: The onset of action of etomidate is 30 to 60 s, with a peak effect at 1 min. Its duration of action lasts 3 to 5 min. Seventy-six percent is bound to protein. It has an elimination half-life of 2.5 h.

Pharmacodynamics: There is hepatic and plasma metabolism within hours. It has no active metabolite.

Dosing: Etomidate is dosed at 0.2 to 0.6 mg/kg.

Contraindications: Its use is contraindicated in patients who experience hypersensitivity to its formula.

Effects in Patients Who Are Critically Ill: Etomidate suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11-beta-hydroxylase.12 Continuous infusion of etomidate for sedating patients with trauma who are critically ill has resulted in increased mortality that is associated with adrenocortical dysfunction.13 The use of a single dose of etomidate during RSI results in the suppression of cortisol levels up to 48 to 72 h in patients who are critically ill, and this has prompted some to suggest that the use of etomidate in patients with septic shock should be discouraged. Moreover, a subset analysis of the Corticosteroid Therapy of Septic Shock trial10 suggested that patients with septic shock who received etomidate for RSI had a higher mortality compared with patients who did not receive etomidate. By contrast, a retrospective study of 113 patients diagnosed with sepsis reported that the use of a single dose of etomidate for RSI was not associated with increased mortality, but it instead resulted in more frequent use of corticosteroids following intubation.14 Two recent meta-analyses found no effect or negative effects of etomidate on mortality.15,16 In the KETAmine SEDation (KETASED) trial,17 which is a randomized trial that compared ketamine with etomidate, 86% of patients receiving etomidate had adrenal insufficiency compared with 48% of patients receiving ketamine (P < .001). The researchers found no difference in morbidity or mortality among the groups. At this time, there is evidence that etomidate causes suppression of the adrenal axis, which may lead to alterations in patient physiology; yet, there is not enough evidence to firmly conclude that the use of a single dose of etomidate for RSI is associated with increased mortality in patients who are critically ill.


Benzodiazepines have been the mainstay for sedation in the critical care setting for several years. The familiarity with their use in sedation of patients who are critically ill, in managing acute agitation, and their relatively safe profile make them a frequently used class of medications. During RSI, paralytic and sedative agents are concurrently or sequentially administered. Thus, the induction agent must have a rapid onset to achieve sedation before the onset of paralysis. For this reason, the benzodiazepine of choice is the one with the fastest onset. Midazolam is a frequent option for inducing endotracheal intubation in the prehospital, ED, and critical care settings.

Mechanism of Action: Midazolam is a high-affinity agonist of the GABA receptor. It stimulates the GABA receptor complex to produce anxiolysis, hypnosis, muscle relaxation, and amnesia.

Pharmacokinetics: Its time to onset is 20 to 60 s, and its duration of action is 15 to 30 min. The elimination half-life of midazolam is 3 h, but it is unpredictably prolonged because the length of the infusion increases. This effect is more evident in patients with cirrhosis, heart failure, or advanced age, as well as in those who are obese. The volume of distribution will increase with heart failure and renal failure. Approximately 95% of midazolam is bound by protein.18

Pharmacodynamics: Hepatic hydroxylation occurs through the cytochrome P450 isoenzyme 3A4. Midazolam is an active metabolite alpha-1-hydroxymidazolam with a half-life of approximately 1 h. Excretion after hepatic glucuronide conjugation occurs through renal glomerular filtration and tubular secretion. Its metabolism is affected by inhibitors of the cytochrome P450 enzyme (eg, cimetidine, macrolides, diltiazem).18

Dosing: The dosing of midazolam for intubation use is 0.1 to 0.2 mg/kg.

Contraindications: Midazolam is contraindicated for the concurrent use of potent inhibitors of cytochrome P450 3A4.

Effects in Patients Who Are Critically Ill: In patients undergoing surgery with left ventricular dysfunction (ejection fraction < 45%), preoperatively induced midazolam caused a 36% reduction in the cardiac index and a 21% reduction in mean arterial pressure19; however, these results were similar to the effects of propofol, thiopental, and etomidate. In the ED setting, midazolam has shown hemodynamic stability as well as significant decreases in blood pressure levels. These effects are likely to be related to the dose used.20 A review of a multicenter ED intubation registry revealed that midazolam was used alone as an induction agent in 16% of the cases, with a mean dose of 0.05 mg/kg, which is below the recommended dose for induction.21


Propofol is frequently used as an IV anesthetic for induction and sedation in the critical care setting. In a French multicenter trial,22 propofol was used as an induction agent for 14% of the intubations. Its rapid onset makes it ideal for RSI. However, in those who are critically ill, the hemodynamic effects of propofol, particularly after bolus administration, may limit the scenarios in which it can be used. Propofol reduces airway resistance, possibly making it the agent of choice for patients with bronchospasm.23

Mechanism of Action: Propofol is a 2,6-diisopropylphenol and a lipid-soluble phenolic derivative (alkylphenol) that acts in the GABA receptor. It reduces airway resistance and produces sedation, amnesia, and laryngeal and muscle relaxation.24 Propofol also maintains or decreases ICP. Its effects are increased when it is used with opiates.25

Pharmacokinetics: The time to onset of propofol is 9 to 40 s, and its duration of action is 10 to 15 min. Its elimination half-life is 30 to 60 min, but it is unpredictably long when used during prolonged infusion and in patients who are obese. Its distribution volume is decreased in patients who are elderly but is increased with prolonged infusions (> 10 days). Ninety-nine percent is bound by protein.25

Pharmacodynamics: Propofol is hepatically and extrahepatically metabolized. It contains no active metabolites. Excretion of propofol after hepatic glucuronide conjugation is mainly renal. There is no dose adjustment for patients with hepatic or renal impairment.25

Dosing: Intubation dosing of propofol is 1 to 3 mg/kg.

Contraindications: Propofol is contraindicated in people with allergies to soy, eggs, or peanuts (propofol is diluted on soy oil, so there is a potential for cross reaction).

Effects in Patients Who Are Critically Ill: Hypotension is more common with propofol use; it may be dose dependent, and it is more pronounced when administered as a bolus. Propofol causes a dose-dependent decrease in heart rate, stroke volume, and systemic vascular resistance, which may be more pronounced in patients diagnosed with sepsis.26 In patients undergoing surgery with left ventricular dysfunction (ejection fraction < 45%), a preoperative induction with propofol caused a 38% reduction in the cardiac index and a 32% reduction in mean arterial pressure19; however, these results were similar to the effects of midazolam, thiopental, and etomidate. No study has evaluated endotracheal intubation in the emergency department setting or in patients who are critically ill or hemodynamically unstable.


Ketamine is a derivative of phencyclidine with a rapid onset of action. It is a dissociative anesthetic that is a potent amnestic, analgesic, and sympathomimetic agent. Ketamine is widely used in the ED setting for the sedation of pediatric patients and has recently been considered a safe alternative for emergency endotracheal intubation in the critically ill population given its lack of association with adrenal insufficiency as demonstrated with etomidate. The anesthetic state induced by ketamine resembles a cataleptic state. The patient often has his or her eyes open with nystagmus while the corneal and light reflexes remain intact; however, the patient is completely unaware of the environment. Patients awakened while on ketamine may experience emergence phenomena characterized by hallucinations, delirium, and vivid dreams. These emergence phenomena are not expected in patients who continue to receive other types of sedatives needed for support by mechanical ventilation.

Mechanism of Action: Ketamine works at many receptors and has a wide range of effects. It causes anesthesia and neuroinhibition by a noncompetitive antagonism of the N-methyl-D-aspartate receptor. Analgesic effects are mediated by the stimulation of opioid receptors. Ketamine also causes sympathetic activation by mediating the release of catecholamine (maintaining sympathetic activity).27

Pharmacokinetics: The onset of action for ketamine is 45 to 60 s. Its duration of action is 10 to 20 min at an IV dose of 2 mg/kg.

Pharmacodynamics: It is hepatically metabolized to norketamine that is metabolically active.27

Dosing: Ketamine is dosed at 0.5 to 2.0 mg/kg.

Contraindications: Ketamine is contraindicated in patients with hypertension and in those who are hypersensitive to the formula.

Effects in Patients Who Are Critically Ill: The KETASED trial17 randomized patients who were critically ill to etomidate or ketamine for rapid sequence intubation. There were no differences in intubation conditions or severity of organ dysfunction as measured by the Sequential Organ Failure Assessment score; however, the incidence of adrenal insufficiency was higher in the etomidate group. There was no difference between groups in terms of hemodynamic parameters, oxygen saturation, and overall morbidity and mortality outcomes.

The use of ketamine in the setting of elevated ICP has been controversial.28 Ketamine increases cerebral blood flow and metabolism in spontaneously breathing volunteers; however, during controlled ventilation and sedation, it does not increase ICP.29 Evidence that ketamine raises ICP is weak. It can possibly be used for RSI in patients who are hemodynamically unstable and are suspected to have elevated ICP.

The respiratory effects of ketamine include preservation of respiratory drive, bronchodilation, and a lack of inhibition of hypoxic pulmonary vasoconstriction; these effects make it an alternative option for RSI in patients with asthma or exacerbations due to chronic obstructive pulmonary disease.


Dexmedetomidine is an alpha-2 adrenoceptor agonist used for continuous IV sedation in patients who are intubated and those who are not. Dexmedetomidine has a unique respiratory-sparing effect, and it causes sedation, anxiolysis, hypnosis, analgesia, and amnesia. Case reports and randomized trials have described its use as an adjuvant in fiberoptic intubation for patients with difficult airways who are awake and undergoing elective intubation.30,31

Mechanism of Action: Dexmedetomidine is an alpha-2 adrenoceptor agonist that produces sedation, anxiolysis, analgesia, amnesia, and sedation (but with easy patient arousal and cooperation). It also reduces salivary secretions and does not depress the respiratory rate. Administration of high-dose boluses of dexmedetomidine may result in a biphasic hemodynamic response, which is first characterized by bradycardia and hypertension secondary to the initial stimulation of peripheral alpha-2B vascular receptors, then followed by central sympatholysis and a dose-dependent decrease in cardiac output, heart rate, and blood pressure.32

Pharmacokinetics: The onset of action is 5 to 10 min with a duration of action lasting 60 to 120 min. The half-life of dexmedetomidine is 6 min, with a terminal elimination half-life of 2 h. It is 94% protein bound.

Pharmacodynamics: It is hepatically metabolized via N-glucuronidation, N-methylation, and cytochrome CYP2A6. Dexmedetomidine has no active metabolites. No dose adjustment is given for renal impairment. A dose reduction is given to patients with hepatic impairment. It is excreted into urine and feces.

Dosing: Dexmedetomidine is dosed as a bolus of 1 mcg/kg then infused at 0.2 to 0.7 mcg/kg/h.

Contraindications: Dexmedetomidine is contraindicated in patients with allergy, hemodynamic instability, heart block, bradycardia, or left ventricular dysfunction.

Effects in Patients Who Are Critically Ill: The effects of dexmedetomidine as an induction agent for endotracheal intubation in patients who are critically ill have not yet been studied. The main concern is the hemodynamic profile of dexmedetomidine. In case reports and randomized control trials on elective intubation for critical airways, dexmedetomidine consistently demonstrates the onset of hypotension and bradycardia, which, in some instances, required pharmacologic intervention (vasopressors).30,31

Paralytic Agents

The use of paralytic agents is controversial.33 It is worth noting that intubation conditions in a patient who is paralyzed are easier to achieve and the incidence of complications may be decreased.34 Yet, the loss of spontaneous ventilation may become a life-threatening event in patients with difficult airways, severe metabolic disturbances, or hemodynamic instability. Many of the intubations in the ED and critical care settings are performed in emergent situations and in a relatively or fully uncontrolled setting (as compared with an operating room); further, the health-care professional in the critical care setting may be in training, someone who is not an anesthesiologist, or he or she may have limited resources or training on difficult airway management. To complicate matters, the agent with the most favorable half-life, succinylcholine (SCh), has several contraindications and warnings for its use due to deadly complications. Other paralytic agents have prolonged durations of action, which may potentially leave a patient with no airway but spontaneously breathing, or in a catastrophic “no airway and no breathing” scenario. The development of sugammadex (which is currently only available in Europe), an agent that reverses the neuromuscular blockade of rocuronium and vecuronium, may change the horizon of paralytic agent use in the critical care setting.

Several methods of paralytic administration have been previously described.33 The use of such agents is dependent on practice, circumstance, and training. The use of newer paralytic drugs has also changed practice. Here we describe the four most common methods:

1. Rapid Sequence Intubation: Most commonly, the paralytic drug is immediately administered after the induction dose. However, the practice may have changed, and the majority of health-care professionals may wait until the patient has lost consciousness.35

2. Precurarization: It is common practice to provide tubocurarine or a nondepolarizing paralytic (10% of the dose) 2 to 3 min before administering a paralytic drug.36 The goal is to reduce muscle fasciculation. A total of 3 min must elapse between the defasciculating dose and SCh, which may not be feasible in a patient who is critically ill. Furthermore, the effects on the critically ill population have not been described.

3. Priming: In this technique, an initial dose of a nondepolarizing paralytic (10% to 25% of the dose) is followed by the remaining paralytic agent dose. This achieves a faster onset of paralysis as well as better intubation conditions. However, this may cause respiratory depression or aspiration. There is no consensus on doses, timing, medications or data in the critical care setting.

4. Timing: In this technique, a single bolus of a nondepolarizing paralytic agent is given and is followed by an induction dose once there is clinical evidence of weakness (ptosis or arm weakness).33

In the critical care setting, the optimal paralytic agent should have the fastest onset of action and the shortest duration; it should also provide good to excellent intubation conditions and have only minimal adverse events. SCh meets the first three goals; however, it fails on the fourth goal. Nondepolarizing agents have a safer profile, but their longer durations of action have kept them off the list for RSI in patients who are unstable. The most appropriate nondepolarizing agent in this setting is rocuronium.


SCh is the most frequently used paralytic agent during rapid sequence intubation in the ED and critical care settings.22 It is the only depolarizing neuromuscular-blocking agent available for clinical use.

Mechanism of Action: It consists of two molecules of acetylcholine linked together, which cause depolarization of the neuromuscular endplate. It stimulates all cholinergic receptors. SCh will bind to the postsynaptic acetylcholine receptors of the motor endplate. The depolarization avoids the postjunctional membrane to respond to any release of acetylcholine. Muscle paralysis ensues until the SCh unbinds from the acetylcholine receptor and is hydrolyzed by pseudocholinesterase.37

Pharmacokinetics: The time to onset of SCh is 30 to 60 s, and its duration of action is 6 to 10 min.

Pharmacodynamics: Immediate hydrolysis occurs through plasma pseudocholinesterase. SCh has no active metabolites. There is no dose adjustment for patients with hepatic or renal impairment.

Dosing: SCh is dosed at 0.6, 1, or 1.5 mg/kg of total body weight.

Contraindications: SCh is contraindicated in patients with allergy and in those with a personal or family history of malignant hyperthermia or are at risk of hyperkalemia (underlying hyperkalemia, chronic renal failure rhabdomyolysis, and metabolic acidosis). SCh may cause an increase in intraocular and intragastric pressures, pulmonary edema, arrhythmia, and bradycardia.24

In patients whose muscle activity has decreased, acetylcholine receptors are not stimulated, which may lead the receptors to upregulate (proliferate). Upregulation of the acetylcholine receptor happens along the muscle membrane.37 Since the effect of SCh is systemic, the receptors will depolarize and cause a massive leak of cellular potassium. Upregulation of the receptor can be seen in chronic conditions where it is usually permanent, but it also can be seen days (2 to 3 days) after the onset of the condition and remain for many months or years. The conditions in which acetylcholine receptor upregulation is expected include major burns (> 48 h), major trauma (> 48 h), stroke (> 48 h), bed immobility (> 5 days), muscular dystrophy or myopathies (eg, critical care neuromyopathy), and denervation syndromes (eg, spinal cord injury, amyotrophic lateral sclerosis).

Effects in Patients Who Are Critically Ill: SCh is extensively used in the critical care setting. Numerous reports in the literature are available about its adverse events.33 A recent meta-analysis demonstrated that SCh creates better intubation conditions than rocuronium.38


Rocuronium is a steroidal, nondepolarizing neuromuscular-blocking agent that is similar in structure to vecuronium; however, it is less potent (more than six times) and has a faster onset of action. These characteristics have made it a therapeutic option for intubation with RSI. Health-care professionals should remain aware that the duration of action of rocuronium is 30 min or more, a fact that underscores the need for knowledge of airway management, difficult intubation, and rescue techniques.

Mechanism of Action: Rocuronium blocks the binding of acetylcholine to receptors on the motor endplate.

Pharmacokinetics: The time to onset of rocuronium is 30 to 60 s, and its duration of action is 30 to 75 min (the larger the dose, the longer the duration of action). In patients who are critically ill, the volume of distribution may be larger and they may have a lower plasma clearance; however, upregulation of the receptors makes it difficult to predict the kinetics of rocuronium.

Pharmacodynamics: The metabolism of rocuronium is minimally hepatic and it has a weakly active metabolite. It is excreted by the liver and found in urine. Its half-life is 60 to 70 min. It is 30% protein bound. Elimination is prolonged in renal impairment, but there is no alteration in effect. Clearance is prolonged in severe liver diseases, and this may prolong the paralytic effect.

Dosing: The dosing of rocuronium is 0.6 to 1.2 mg/kg of total body weight.

Contraindications: Rocuronium is contraindicated in patients with allergy. Elimination and effects may be prolonged.

Effects in Patients Who Are Critically Ill: A Cochrane review38 found that SCh was superior to rocuronium in creating optimal intubation conditions; however, the studies reviewed were focused on the operating room setting rather than on patients who were critically ill. In an ED retrospective study, rocuronium was compared with SCh in patients sedated with etomidate. No significant difference was found in first-attempt success, and no data were provided on hemodynamic or airway complications.39


The reversal of pharmacologic paralysis is often performed with a combination of neostigmine and glycopyrrolate in the operating room. This combination relies on the inhibition of acetylcholinesterase and the blockade of muscarinic receptors. Sugammadex has known cardiovascular adverse events, tachyarrhythmia or bradyarrhythmia, hypotension, seizures, and hyperperistalsis, among others. It also has a slow reversal time. A new agent for the reversal of paralysis from steroidal nondepolarizing neuromuscular blockers has been approved for use in Europe; however, it has not been approved by the US Food and Drug Administration for use in the United States. 40

Mechanism of Action: The mechanism of action of sugammadex is its modified cyclic oligosaccharide that traps aminosteroidal, nondepolarizing neuromuscular-blocking agents. The complex has tight bonds and effectively reduces the paralytic agent-free levels, thus leading to a reversal of paralysis. It binds to rocuronium with the highest affinity, followed by vecuronium, and has low affinity for pancuronium.

Pharmacokinetics: Its onset of action is 2 to 5 min.

Pharmacodynamics: Sugammadex has no metabolism. Its half-life is approximately 2.2 h. The sugammadex-paralytic complex is eliminated by urine. It may bind to contraceptive steroids, thus decreasing their effectiveness. In patients taking fusidic acid, flucloxacillin, or toremifene, sugammadex may delay the time to paralytic reversal or cause paralysis to reoccur. It is not bound to proteins and it has no active metabolites. When sugammadex is excreted in urine, it remains unchanged.40

Dosing: Sugammadex is administered 3 min following rocuronium and dosed at 16 mg/kg.

Contraindications: Sugammadex has caused hypersensitivity reactions and anaphylaxis. When low doses or long-acting agents are used, sugammadex may cause recurarization, which is a return to a neuromuscular blockade.

Effects in Patients Who Are Critically Ill: Sugammadex has not been studied in this population.

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