Challenges a nd Adva nces in I ntubation : Rapid Se quence Intubation

Sharon Elizabeth Mace, MD, FACEP, FAAPa,b,c,d,*
KEYWORDS  Intubation  Rapid sequence intubation  Endotracheal intubation


Rapid sequence intubation (RSI) is a process whereby pharmacologic agents, specifically a sedative (eg, induction agent) and a neuromuscular blocking agent are administered in rapid succession to facilitate endotracheal intubation.1 RSI in the emergency department (ED) usually is conducted under less than optimal conditions and should be differentiated from rapid sequence induction (also often abbreviated RSI) as practiced by anesthesiologists in a more controlled environment in the operating room to induce anesthesia in patients requiring intubation.2–6 RSI used to secure a definitive airway in the ED frequently involves uncooperative, nonfasted, unstable, critically ill patients. In anesthesia, the goal of rapid sequence induction is to induce anesthesia while using a rapid sequence approach to decrease the possibility of aspiration. With emergency RSI, the goal is to facilitate intubation with the additional benefit of decreasing the risk of aspiration. Although there are no randomized, controlled trials documenting the benefits of RSI,7 and there is controversy regarding various steps in RSI in adult and pediatric patients,8–13 RSI has become standard of care in emergency medicine airway management14–17 and has been advocated in the airway management of intensive care unit or critically ill patients.18 RSI has also been used in the prehospital care setting,14,19,20

Cleveland Clinic Lerner College of Medicine of Case Western Reserve, Cleveland, OH 44195, USA b Observation Unit, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA c Emergency Services Institute, E19, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA d Case Western Reserve University, Metro Health Medical Center, 8500 Metro Health Drive, Cleveland, OH 44109, USA * Emergency Services Institute, E19, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail address: Emerg Med Clin N Am 26 (2008) 1043–1068 doi:10.1016/j.emc.2008.10.002 0733-8627/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved.




although the results have been mixed, especially in trauma patients (most notably in traumatic brain injury patients), such that an expert panel found that ‘‘the existing literature regarding paramedic RSI was inconclusive.’’20 Furthermore, training and experience ‘‘affect performance’’ and that a successful ‘‘paramedic RSI program is dependent on particular emergency medical services (EMS) and trauma system characteristics.’’20

The purpose of RSI is to make emergent intubation easier and safer, thereby increasing the success rate of intubation and decreasing the complications of intubation. The rationale behind RSI is to prevent aspiration and its potential problems, including aspiration pneumonia, and to counteract the increase in systemic arterial blood pressure, heart rate, plasma catecholamine release, intracranial pressure (ICP), and intraocular pressure (IOP) that occurs with endotracheal intubation. Blunting the rise in ICP may be critical in patients with impaired cerebral antoregulation from central nervous system illness/injury. Similarly, avoiding an increase in IOP may be desirable in the patient with glaucoma or an acute eye injury. RSI eliminates the normal protective airway reflexes (such as coughing, gagging, increased secretions, and laryngospasm) that can make intubation more difficult. Use of RSI may limit cervical spine movement, thus, allowing for better control of the cervical spine during intubation with less potential for injury. RSI decreases the trauma to the airway that occurs with intubation. RSI should also decrease or eliminate the discomfort that occurs with intubation and the patient’s recall of the intubation.1 Disadvantages of RSI are (1) the potential for side effects or complications related to the drugs administered for RSI, (2) prolonged intubation leading to hypoxia, and (3) ‘‘emergent’’ or a ‘‘crash’’ airway resulting in a cricothyroidotomy or other ‘‘emergent’’ airway procedure.1

RSI generally consists of seven steps: (1) preparation, (2) preoxygenation, (3) pretreatment, (4) paralysis with induction, (5) protection and positioning, (6) placement of the tube in the trachea, and (7) postintubation management.1,17 These seven steps can be modified when appropriate to fit the clinical situation.21
Step 1—Preparation

Preparation involves having all the necessary equipment and supplies including medications that may be needed for an emergency intubation such as oxygen, suction, bag-valve mask (BVM), laryngoscope and blades, endotracheal (ET) tubes with a stylet with one size larger and smaller than the anticipated ET size, resuscitation equipment, and supplies for rescue maneuvers (eg, laryngeal mask airways [LMA] or cricothyrotomy) in case of a failed intubation according to the Can’t Intubate, Can’t Ventilate American Society of Anesthesiologists (ASA) guidelines.22 The patient should have an intravenous line placed and be put on continuous monitoring to include vital signs (heart rate, respirations, blood pressure, pulse oximetry), cardiac rhythm monitoring, and, preferably, capnography. The mnemonic ‘‘SOAPME’’ is one way to remember the essential equipment needed for intubation: Suction, Oxygen, Airway, Pharmacology, Monitoring, Equipment.23 For the airway, include the ET tubes, laryngoscopes, blades, stylets, and BVM. For pharmacology, select, draw up, and label the appropriate medications (sedative, neuromuscular blocker, ancillary drugs) based on the history, physical

25 Step 2—Preoxygenation Preoxygenation should be occurring during the preparation step. The preparation step is used to ‘‘MAP’’ (Monitor. (up to 5 minutes) should be administered.02 mg/kg (minimum 0. can’t intubate scenario). and (4) atropine is indicated for pediatric patients %10 years old and in patients with significant bradycardia if succinylcholine is given. specifically obese adults or pregnant patients).5 mg/kg. infants and children and patients with an elevated diaphragm. eg. medication administration. a normal child or an obese adult may start to desaturate within 2 minutes. These patients will become hypoxic in a shorter time. The pretreatment phase and preoxygenation phase can (and usually) do occur simultaneously during most instances of RSI in the ED. premedicate with lidocaine. (2) patients with major vessel dissection or rupture or those with significant ischemic heart disease give fentanyl. illnesses. fentanyl 2–3 mcg/kg. The purpose of preoxygenation is to replace the nitrogen in the patient’s functional residual capacity (FRC) with oxygen or ‘‘nitrogen wash-out oxygen wash-in. Medications and their usual dosages that may be given during the pretreatment phase are lidocaine 1. Patient assessment) out a treatment plan for intubation using RSI and a backup contingency plan in case of a failed intubation (can’t ventilate.26 One caveat to remember is that certain patients have a lesser FRC (eg. intubation. In the preoxygenation phase. also preferably with capnography. The clinical indications for these drugs are (1) for patients with elevated ICP and impaired autoregulation: administer lidocaine and fentanyl. For maximal efficacy. although this is not always possible. One caveat to remember is to give fentanyl with caution to any patient in shock (whether compensated or uncompensated) who is dependent on sympathetic drive because of a potential decrease in blood pressure with fentanyl administration. BVM ventilation may be necessary in apneic patients or patients with ineffective spontaneous breathing.1 mg. Assemble. Depending on circumstances. while a normal adult may tolerate up to 5 minutes of apnea before they become significantly hypoxic. (3) adults with significant reactive airway disease. RSI. or rescue airway procedures.’’ ‘‘Denitrogenation’’ can be accomplished in 3 to 5 minutes by having the patient breathe 100% oxygen via a tight-fitting facemask or. Because effective ventilation by the patient is not feasible in many ED patients. with four vital capacity breaths. positive pressure ventilation should be avoided during the preoxygenation step because of a risk for gastric insufflation and possible regurgitation. use of the Sellick procedure with gentle cricoid pressure should be applied in an attempt to limit gastric distention and avoid aspiration during BVM ventilation. Monitoring should include pulse oximetry and cardiac monitoring at a minimum. as long a period of preoxygenation as possible. maximum 0.Rapid Sequence Intubation 1045 examination. if time is an issue. . Patient assessment should be done at this time. replacing the nitrogen reservoir in the lungs with oxygen allows 3 to 5 minutes of apnea without significant hypoxemia in the normoxic adult.24 Assembling adequate personnel needed to assist in the procedure and assigning their roles is also a key component of the preparation phase.5 mg).26 Step 3—Pretreatment Ancillary medications are administered during the pretreatment step to mitigate the negative physiologic responses to intubation. Ideally. and equipment available. In these instances. and atropine 0. or injuries that may negatively affect airway procedures/manipulations. BVM ventilation. the pretreatment drugs should precede the induction agent by 3 minutes. A focused history and physical examination should be done to identify any condition.

timing. This . and C3–C4 in an infant.6 mg/kg 5 0. especially if accidental esophageal intubation occurred.3 mg/kg. The cricoid cartilage is opposite the C4–C5 vertebrae in an adult. The mnemonic ‘‘LOAD’’ has been used to indicate the pretreatment drugs for RSI: L 5 lidocaine.31 Step 5—Protection and Positioning Positioning of the head and neck is essential to achieve the best view of the glottic opening for conventional laryngoscopy by aligning the three axes: oral. assuming there are no contraindications such as known or potential cervical spine injury.30 and nonbarbiturate sedatives (etomidate. misplaced position (avoid applying pressure over the thyroid cartilage or entire larynx which may impede passage of the tube). comorbidity) and the clinician’s experience/training and institutional factors. and incorrect amount of cricoid pressure. the dose would be 10% of the paralyzing dose of rocuronium (10% of 0. The purpose of the defasciculating dose of the ND-NMB is to prevent the fasciculations (and therefore. The applied pressure should be graded and inversely related to the size of the patient with less force in smaller patients. Several caveats regarding the proper technique need to be considered: location. which puts the patient at risk for aspiration. for etomidate the usual dose for procedural sedation is 0. One caveat to remember is that the induction dosages of these sedatives may be different (generally.29 opioids (fentanyl). and laryngeal. Cricoid pressure should be applied as soon as the patient starts to lose consciousness and should be maintained until the correct endotracheal position is verified. Pressure should be gentle but firm enough to compress the esophagus between the cricoid cartilage and the anterior surface of the vertebral body. which includes patient factors (includes cardiorespiratory and neurologic status. to avoid malpositioning the neck.1046 Mace In patients who are receiving succinylcholine as their induction agent and who are at risk for increased ICP. one tenth of the normal paralyzing dose of a nondepolarizing (ND) neuromuscular blocking agent (NMB) can be given 3 minutes before receiving succinylcholine.27 Step 4—Paralysis with Induction Paralysis with induction is achieved by the rapid intravenous administration in quick succession of the induction agent and the NMB.21. The correct performance of the Sellick maneuver involves the use of the thumb and index or middle finger to apply firm downward pressure on the cricoid cartilage anteroposteriorly.31 propofol. thiopental.1 Protection refers to the use of maneuvers to prevent regurgitation of gastric contents with possible aspiration. For example.06 mg/kg). the increase in ICP) that occurs with succinylcholine. allergies. For example. A 5 atropine. which is the application of firm pressure on the cricoid cartilage to avoid passive regurgitation of gastric contents. slightly higher) than the dose used for sedation. Common mistakes include premature release of cricoid pressure. and amount of pressure.32 and the benzodiazepines).33 The dosages and characteristics of these agents and are summarized in Table 1.1 dissociative anesthetics (ketamine). One recommendation in smaller patients is placing the other hand under the neck to avoid changing the neck position while applying cricoid pressure (with the opposite hand). The selection of a specific sedative depends on multiple factors: the clinical scenario. This is achieved via the Sellick maneuver. pharyngeal. and D 5 defasciculation. fentanyl).2 mg/kg and for RSI is 0. This is achieved by extension and elevation of the neck to obtain the ‘‘sniffing the morning air’’ or the ‘‘sipping English tea’’ position.28 Sedatives commonly used for induction during RSI are barbiturates (pentobarbitol. as well as the characteristics of the sedative. and methohexitol). O 5 opioid (specifically.

although there are no data to substantiate this possible complication. can also be administered for pediatric RSI. dexamethasone often is chosen because it does not interfere with the adrenocorticotropin hormone (ACTH) stimulation test.3 mg/kg or 20 mg in a 70-kg adult. an enzyme necessary for adrenal steroid production. it used is less . cricoid pressure should be released immediately because of possible esophageal rupture. which may be needed to later test for adrenal insufficiency. fentanyl (6%).Rapid Sequence Intubation 1047 is assuming there are no contraindications such as cervical spine injury. sometimes with paralysis as well as cardiopulmonary monitoring. Continued sedation and analgesia.31 The usual dose is 0. Barbiturates Thiopental is the most commonly used barbiturate for pediatric RSI6 and may be the most commonly used barbiturate for anesthesia induction. and ketamine (7%). midazolam (16%). the most commonly used sedative for RSI in adults.41 However. hypovolemic patients. the ET tube must be secured. and patients with limited cardiac reserve.6 Etomidate Etomidate. Should vomiting occur. A chest radiograph is done not only to check for proper ET tube placement but also to evaluate the pulmonary status and to monitor for any complications of the intubation and RSI. In any case. and neuromuscular blockade eliminates the possibility of active vomiting. PHARMACOLOGY: SEDATIVE AGENTS FOR RAPID SEQUENCE INTUBATION According to the National Emergency Airway Registry (NEAR) study.6 etomidate was the most commonly used induction agent but was used in less than half the patients (only 42% compared with 69% for all patients). Etomidate does inhibit 11-b-hydroxylase. the most frequently used induction agents were etomidate (69%).40 although this is not the situation with RSI in which a sedative and paralytic generally are coadministered in quick succession.34 followed by thiopental (22%).38 Although either dexamethasone (0.37–39 This has led to the suggestion that a corticosteroid be coadministered when etomidate is given for RSI. Etomidate also decreases ICP and the cerebral metabolic rate.34 Considering just pediatric patients using the NEAR registry.39 Myoclonus is another side effect of etomidate that may interfere with intubation if a paralytic is not used. infusions of etomidate for continued postintubation sedation are contraindicated. although this is probably not clinically significant.35 Transient adrenal suppression has been noted after a single dose of etomidate.1 mg/kg) or hydrocortisone (1–2 mg/kg) may be given. it is time to begin intubation by standard methods. These features are why some clinicians consider it the sedative of choice in a patient who has multiple trauma with both a head injury and hemorrhage or shock.36 Some data indicate that etomidate has a negative impact on patient outcome in critically ill patients with sepsis and septic shock. midazolam (18%). ET tube placement should be confirmed by the usual techniques. which suggests that it may have a neuroprotective effect. It often is used in trauma patients with known or potential bleeding. because it does not have significant cardiovascular effects. is indicated as long as the patient requires advanced airway support. Step 6—Placement of the Endotracheal Tube in the Trachea When the jaw becomes flaccid from the paralytics. Step 7—Postintubation Management After ET tube placement and confirmation. and ketamine (3%).

hypovolemia Causes histamine release Porphyria - Avoid intra-arterial injection (can cause gangrene). Used in patients with [ ICP if hemodynamically stable Side Effects Can cause myoclonic movements Precautions.5 Use with cause in asthmatics or if hypotensive - . Avoid extravasation (causes tissue necrosis). Thiopental 3–4 Negative CV effects. causes tissue necrosis Avoid intra-arterial injection (can cause gangrene). Barbiturate. Use with caution if in septic shock and sepsis and consider giving corticosteroid Reversal Agent Comment Myoclonic movements may make intubation difficult if NMB not given Barbiturates. hemorrhaic patients. especially if head injury and hemorrhage Induction agent (sedative).3 (usual 70 kg Adult dose 5 100 mg) Indication Induction agent (sedative). Contraindication Adrenal insufficiency. Often used in hypovolemic. Used in patients with [ ICP if hemodynamically stable Induction agent (sedative). Methohexital 1–1. Avoid extravasation. Use low doses cautiously if CV disease. shock.1048 Mace Table 1 Medications for rapid-sequence intubation Sedatives Etomidate Dose (IV) (mg/kg) for Intubation 0. and in trauma patients.

5 Induction agent (sedative). hypoxia. [ IOP. EDTA - Abbreviation: CV. significant CV disease Ultra short acting.5 (Y dose with age) Induction agent (sedative) Allergy to egg.0 (Y dose if used with benzodiazepine or thiopental) 0. hypotension. Rapid Sequence Intubation 1049 . soybean oil. hemorrhage. bradycardia. CV disease Consider alternatives if [ ICP. [ IOP may cause emergence reaction Minimal CV effects unless hypovolemic - Use with atropine if age %10 years or significant bradycardia Dose varies widely. Negative CV effects limits its use in man ED-RSI patients Benzodiazepine. apnea. cardiovascular. renal failure. [ BP. shock Induction agent (sedative) Sympathomimetic effects [ ICP. in elderly. apnea. Often used if hypovolemic.5–1. Midazolam Flumazenil Propofol 1–2.Ketamine 0. liver disease. paradoxical agitation Hypotension. [ HR Respiratory depression.5–2. Y dose if given with opioids. Use cautiously if volume depletion.

However. especially in head injured or hypovolemic patients. is contraindicated in patients with ICP. so it is critical that thiopental be given intravenously as a dilute solution while being careful to avoid any tissue infiltration. However. in patients with underlying cardiovascular disease. rapid administration) respiratory depression of the central nervous system (CNS) that can cause apnea. several untoward effects may occur. Ketamine’s sympathomimetic effects.43 Ketamine is probably the sedative of choice for asthmatic patients for many reasons. if possible.1050 Mace commonly than etomidate for ED RSI.and rate-related (eg. Ketamine. and cardiac output. Thiopental decreases both cerebral blood flow and the metabolic demands of the brain. these sympathomimetic effects are undesirable in patients who already have significant hypertension or tachycardia. laryngospasm. patients with preexisting cardiovascular disease may also experience hypotension when given thiopental. cough. The conclusion is to avoid using thiopental. exerts its effects by interrupting the connection between the thalamo-neocortical tracts and the limbic system. dehydration.29 Thiopental has some respiratory side effects. or head trauma. pericarditis. especially during airway manipulation: catecholamine release causing systemic or intracranial hypertension. when hypotension occurs. It has a dose. hemorrhage. patients who are hypovolemic or in shock or who are already tachycardic may not be capable of further compensatory heart rate increases and can experience a drop in blood pressure with thiopental administration. relieves bronchospasm by dilating bronchial smooth muscle and stimulating the pulmonary b receptors. Similarly. it has an additional advantage in that it also has analgesic properties. which makes it an ideal sedative agent in patients with known increased ICP or patients with head injury who are hemodynamically stable. through the release of endogenous catecholamines. Unlike all the other sedatives.42 This French study compared the cerebral hemodynamics of ketamine combined with midazolam and found no significant difference in ICP or cerebral perfusion pressure when compared with midazolamsufentanil. therefore. hypovolemia.27 Tissue necrosis can occur with intraarterial injection or extravasation. This makes ketamine an excellent sedative in patients who are hypotensive. and bronchospasm. cause an increase in heart rate. at least partly because many ED RSI patients are hemodynamically unstable. With ‘‘light’’ anesthesia. This . especially if secondary to shock. <6 months) was a contraindication to the use of ketamine. hypotension with associated hypoperfusion can occur in patients who are hypovolemic or have myocardial depression.30 Ketamine also causes an increase in ICP by both an increase in systemic blood pressure and cerebral vasodilatation and. a recent study indicates that ketamine is safe and effective even in neonates. there is a compensatory baroreceptor mediated reflex tachycardia. a dissociative anesthetic. it has been recommended to coadminister an analgesic (such as fentanyl) especially in head-injured patients. especially in asthmatic patients. Generally. blood pressure. or shock or limit thiopental to small frequent doses (1–3 mg/kg) while carefully monitoring blood pressure. an intracranial mass. although a recent study has challenged this contraindication.29. Unfortunately.41 To mitigate or avoid these negative effects. or tamponade. Thus. Ketamine increases tracheobronchial/oropharyngeal secretions. high dose. acting via a centrally mediated mechanism.42 It has previously been thought that young age (eg.41 Ketamine Ketamine. an intracerebral hemorrhage. Thiopental has negative cardiovascular effects: myocardial depression and peripheral vasodilatation.

27 Atropine is used for RSI because it causes an increase in heart rate.1 mg and a maximum of 0. and hiccups. better amnesia. The advantages of propofol are its very quick . coughing. Small doses of midazolam have been given for the treatment of emergence reactions. the consensus is that it is still useful in selected patients.2. As with all sedatives. GABA is an inhibitory neurotransmitter. The excess secretions may. Ketamine. in the elderly.44 Glycopyrollate is the antimuscarinic drug of choice for procedural sedation because it has a greater antisialagogue effect and fewer side effects (less tachycardia.27 Ketamine has respiratory/cardiovascular stability and maintains airway reflexes. This opens a chloride channel causing hyperpolarization of the neuronal cell membrane.33 Other advantages of midazolam versus diazepam include fewer adverse effects. atropine crosses the blood–brain barrier (glycopyrollate does not so it has no CNS side effects) and may increase the incidence of emergence reactions. while paradoxically increasing the incidence of emergence reactions in a subset of patients. The antagonist. including midazolam. and lorazepam. This teaching has been challenged recently by several studies that reported the prophylactic administration of benzodiazepine did not decrease the incidence of emergence reactions28. can be used in patients with coronary artery disease. and no CNS side effects). positive nitroglycerin-like effect in patients with heart failure (decreases the increased ventricular filling pressure).1. midazolam) with ketamine will prevent emergence reactions.02 mg/kg intravenously with a minimum of 0. and anticonvulsant properties.33 All of the benzodiazepines. and seizure treatment. Other uncommon side effects are paradoxical agitation. Advantages of the benzodiazepines include minimal cardiovascular effects (unless the patient is hypovolemic). or significant heart disease. is associated with an occasional emergence reaction. an analog of phencyclidine (PCP). Fortunately. muscle relaxant. vomiting. patients with renal failure. It has no analgesic effects. and its amnestic effects are variable. which is desirable when offsetting the bradycardic effects of succinylcholine during RSI. have sedative.Rapid Sequence Intubation 1051 may have a positive effect by decreasing mucus plugging in some cases.45 Benzodiazepines Midazolam is the most commonly used benzodiazepine for RSI and ED sedation primarily because it has a rapid onset and short duration.27. hypnotic. fewer dysrhythmias.46 but actually increased the risk of respiratory depression and prolonged recovery. Traditional teaching is that coadministration of a benzodiazepam (eg. thereby blocking neuronal depolarization or activation. or severe hepatic disease. rare instances of apnea and laryngospasm have been reported.5 to 1. amnestic.27. Benzodiazepines bind to a specific benzodiazepine receptor site on the GABA (gamma-aminobutyric acid) receptor.1.0 mg. interfere with visualization of the airway during laryngoscopy. can reverse the effects of the benzodiazepines. pretreatment with atropine (preferred for RSI) or glycopyrollate (preferred for sedation) prevents excess secretions.01 to 0.44 In addition. and greater potency. however. The main disadvantage of the benzodiazepines is that they can cause respiratory depression and apnea.44 Although the routine use of atropine has been questioned.44 The dose of atropine for RSI is 0. flumazenil. diazepam. so its use should probably be avoided in psychotic patients.33 Propofol Propofol is an ultra–short-acting sedative hypnotic agent. anxiolytic.45. The benzodiazepine dosage for RSI and sedation varies widely and should be decreased when given along with opioids.

hypoxia and apnea. 1 and 2). the dense bar areas (Ach from the vesicles is released into the synaptic cleft through the neural membrane adjacent to the dense bars). bradycardia. 2). which is an invagination of the sarcolemma (see Figs.32 Because of these side effects/complications its use as a sedative for RSI is limited in many ED patients. The motor end plate refers to the complex of branching nerve terminals that invaginate into (but actually lie outside) the sarcolemma. hypotension. Propofol also has negative cardiovascular effects so it should be used with caution in patients with volume depletion. The ionosphere component extends through the postsynaptic neural membrane to the interior of the postsynaptic membrane. Cleveland.) . Mace. or cardiovascular disease. a protein particle located on the postsynaptic myocyte membrane has two parts: a binding component and an ionophore component. although higher doses may be needed in pediatric patients and lower doses in geriatric patients. The binding component projects outward from the postsynaptic myocyte membrane into the synaptic space where it binds the neurotransmitter Ach. It also has antiemetic properties. and mitochondria (which supply the adenosine triphosphate [ATP]that acts as the energy source for the synthesis of Ach) (Fig.32 so it should be administered slowly. Motor end plate of the neuromuscular junction. MD. 3). and Dave Schumick of the Cleveland Clinic Center for Medical Art and Photography. A single terminal branch of the nerve axon lies in the synaptic gutter or synaptic trough. as well as other ions) through the membrane (Fig. with permission. (Courtesy of Sharon E. Fig. Anatomy The neuromuscular or myoneural junction is the junction between the nerve fiber ending or nerve terminal. and the interposed synaptic cleft (synaptic space). OH. can be used in malignant hypothermia patients. 1) Subneural clefts are folds of the muscle cell (myocyte) membrane.38 PATHOPHYSIOLOGY A discussion of the anatomy and physiology of the neuromuscular junction is valuable in understanding how the neuromuscular blockers work. Structures found in the nerve terminal include synaptic vesicles containing the neurotransmitter Ach. the muscle fiber including the muscle fiber membrane or sarcolemma. voltage gated calcium channels (which are protein particles that penetrate the neural membrane). and the dosage is unchanged for patients with renal or liver disease. 4). which markedly increase the surface area at which the synaptic neurotransmitter Ach can act (Fig. The nicotinic receptor.32 Side effects include hypotension. (Fig. The ionosphere may serve as an ion channel that permits the movement of ions (in this case primarily sodium ions. 1.1052 Mace onset and short duration.

3. The calcium ions bind with ‘‘release sites’’ that are unique protein molecules on the inner surface of the presynaptic neural membranes. the calcium ion channels open. With nerve stimulation. This altered protein molecule on the nicotinic skeletal muscle receptor increases the permeability of the skeletal myocyte cell to various ions (sodium. increasing the neural membrane permeability to calcium. which permits the vesicles to release the neurotransmitter Ach into the synaptic space (Fig. MD. potassium. 4). Neuromuscular junction shows nerve axon terminal in synaptic trough. and the interposed synaptic space. thereby releasing Ach into the synaptic space (synaptic cleft). OH. with permission. 5). and Dave Schumick of the Cleveland Clinic Center for Medical Art and Photography. and calcium) with an influx of sodium into the skeletal myocyte (see Fig. Mace. When the action potential depolarizes the presynaptic membranes. Ach then diffuses across the synaptic cleft to the motor endplate. chloride. allowing calcium ions to stream into the presynaptic nerve ending. the sarcolemma with subneural clefts. Cleveland. Cleveland.) Neurotransmitter: Acetylcholine Acetylcholine (Ach).Rapid Sequence Intubation 1053 Fig. (Courtesy of Sharon E. Attachment of Ach to the nicotinic receptors on the skeletal muscle leads to a conformational change in the nicotinic receptor. Mace. 2. is released from the ending of preganglionic and postganglionic parasympathetic nerves and preganglionic sympathetic nerves.) . the impulse reaches the nerve ending causing the Ach vesicles to travel to the nerve surface and rupture. (Courtesy of Sharon E. Structures in the neromuscular junction. The coupling of the calcium ion to the specific protein molecule opens the release sites. Exocytosis is the process whereby the Ach containing vesicles fuse with the nerve terminal membrane and release their Ach. the neurotransmitter at cholinergic synapses. with permission. MD. Ach is synthesized from choline and acetic acid in the nerve and packaged in vesicles. OH. and Dave Schumick of the Cleveland Clinic Center for Medical Art and Photography. This produces a large positive potential charge within the skeletal Fig.

OH. Cleveland. Mace. Nicotinic receptors on the sarcolemma in the open and closed states. and Dave Schumick of the Cleveland Clinic Center for Medical Art and Photography. 6). binding to the nicotinic receptor. The release of Ach from the nicotinic receptor on the skeletal myocyte ends depolarization. referred to as the ‘‘end plate potential. Under normal circumstances. 5). OH. release into synaptic space. exocytosis.’’ The end plate potential creates an action potential that travels along the skeletal myocyte membrane causing muscle contraction (Fig.) myocyte. Mace. Ach can either diffuse back into the nerve ending or be broken down by the acetylcholinesterase enzyme into choline and acetic acid (see Fig. Cleveland. (Courtesy of Sharon E. and Dave Schumick of the Cleveland Clinic Center for Medical Art and Photography. with permission. 5. MD. (Courtesy of Sharon E.) . 4. Acetylcholine in the neuromuscular junction: synthesis.1054 Mace Fig. large amounts of the enzyme acetylcholinesterase are found in the synaptic space. and inactivation. Fig. MD. with permission.

an abrupt increase of greater than 20 to 30 millivolts causes further opening of additional sodium channels. 139.Rapid Sequence Intubation 1055 Fig. Mace. MD. 6. Patients given an NMB may be aware of their environment. (A) Effect of Curare. In addition. (B) Normal. and tachycardia. with permission. (C) Effect of Botulinum toxin. which results in blocking the action of Ach in opening the sodium ion channels. will be insufficient to cause an action potential in the skeletal muscle fiber membrane. the physician must be prepared for a difficult or failed airway with the possibility that a surgical airway may be necessary if the patient cannot be oxygenated or ventilated adequately with a bag-valve mask or extraglottic device. Textbook of physiology. This is what happens with various drugs or toxins. 6). 6th edition p. The threshold potential of about À50 millivolts is indicated by the dashed line. A weak local end plate potential. (Modified from Guyton AG. the patient may be aware of and remember the intubation. . First. especially if there is the potential for a difficult or failed airway. NEUROMUSCULAR BLOCKERS Definition Neuromuscular blocking agents (NMBs) are substances that paralyze skeletal muscles by blocking nerve impulse transmission at the neuromuscular or myoneural (muscle-nerve) junction. Skeletal muscle end plate potential. whereas conversely increasing the resting membrane potential to a more negative number makes the neuron less excitable (see Fig. However. allowing for an action potential in the skeletal muscle fiber membrane. including painful stimuli. The botulinum toxin prevents depolarization by decreasing the amount of Ach released by the nerve terminals. which is considered inhumane. less than 20 to 30 millivolts. There are several critical factors to remember with RSI. Failure to sedate the patient allows the possibility of negative physiologic responses to airway manipulation such as increased ICP. Cleveland. with permission. For example.) The Flow of Ions and the Action Potential Physiologically. even though they are unable to respond. Assessment of the airway. whenever an NMB is used. Concomitant sedative use limits or helps avoid these adverse physiologic responses to airway manipulation and may even result in a better view of the airway during laryngoscopy. and Dave Schumick of the Cleveland Clinic Center for Medical Art and Photography. The flow of ions is important. Courtesy of Sharon E. because decreasing the resting membrane potential voltage to a less negative value increases neural excitability leading to depolarization when the threshold (about 50 millivolts in skeletal muscle) is reached. OH. a sedative is coadministered with the NMB. should be done before administering an NMB. hypertension. the drug curare competes with Ach for the nicotinic receptor sites on the skeletal muscle. editor.

which prevents muscle contraction.6.34 Sch is the prototype of the depolarizing agents. because there is minimal if any pseudocholinesterase at the neuromuscular junction. has been used in innumerable patients since its introduction as an NMB in 1952.5 to 2. The neuromuscular block/motor paralysis is terminated when the NMB (eg.0 mg/kg in an adult)47 and not 1 mg/kg as stated in some . not just at the neuromuscular junction. Ach and all NMBs are quaternary ammonium compounds.6 Pharmacology All NMBs are structurally similar to the neurotransmitter Ach. Sch) unbinds from the AchR and diffuses back into the circulation where it is hydrolyzed by plasma cholinesterase. Sch’s short duration of action is caused by the rapid hydrolysis by plasma cholinesterase both before Sch reaches and after Sch leaves the neuromuscular junction. with vecuronium used in 7%.5 mg/kg (or about 100 mg in a 70-kg adult)1 (some experts suggest 1. DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS Succinylcholine Succinylcholine (Sch) is the only depolarizing agent currently available in the United States. It is preferable to overestimate rather than underestimate the dose because an insufficient dose may make it difficult to intubate if the patient is not adequately paralyzed. This nonspecific action at sites throughout the body. Depolarizing agents mimic the action of Ach. Do not underdose the drug. Nondepolarizing agents work by competitive inhibition to block Ach’s action at the neuromuscular junction to prevent depolarization. helps explain some of their side effects. Dosing of Succinylcholine There are some ‘‘pearls’’ regarding Sch dosing. Because its chemical structure (eg.5-mg/kg intravenous dose. Use the total body weight (not the lean weight) even in the morbidly obese or pregnant patient. eg. According to the NEAR registry. quaternary ammonium compound) is similar to that of Ach. it binds to the acetylcholine receptor (AchR) on the motor end plate and depolarizes the postjunctional neuromuscular membrane. the preferred dose is 1. succinylcholine (90%) was also the most commonly used NMB. The major advantages of Sch are its rapid onset with complete motor paralysis occurring within 45 to 60 seconds and short duration of action lasting only 6 to 10 minutes when given in the recommended 1. rocuronium (12%). nicotinic (ganglionic) and muscarinic autonomic sites. the most frequently used NMBs were succinylcholine (82%).1056 Mace NMBs are depolarizing or nondepolarizing. Transient fasciculations (caused by initial depolarization) are followed by blockade of neuromuscular transmission with motor paralysis when Sch is given. and is the most commonly used NMB for ED RSI. and rocuronium in 2%. Some Ach may diffuse back into the nerve terminal.34 For pediatric patients only. They case a sustained depolarization of the neuromuscular junction. although the majority of Ach is hydrolyzed by plasma cholinesterase. Muscle contraction will not reoccur until the neuromuscular junction returns to the resting state and then is depolarized again. resulting in continuous stimulation of the motor end plate AchRs. Plasma cholinesterase (also referred to as ‘‘pseudocholinesterase’’ or ‘‘butylcholinesterase’’) rapidly hydrolyses Sch to succinylmonocholine (a very weak NMB) and choline. and vecuronium (5%). the positive charges of these compounds at the nitrogen atom account for their attraction to the cholinergic nicotinic (ionotropic) receptors at the neuromuscular junction and at other nicotinic receptor sites throughout the body. Thus.

The clinical presentation generally includes muscle rigidity (especially masseter stiffness).47 Administer Sch as a rapid bolus followed by a 20 to 30 cc saline flush to avoid incomplete paralysis.27 Repeat doses or prolonged use of Sch is to be avoided for several reasons. Sch may increase the serum potassium up to 0. It is thought to be caused by an abnormal ryanodine receptor causing marked leakage of calcium from the sarcoplasmic reticulum of skeletal muscle cells resulting in extremely high intracellular calcium levels. especially certain inhalational anesthetics (such as halothane. Refrigeration lowers the drug’s degradation rate so that it maintains 90% activity for up to 90 days. electrolyte abnormalities. Unfortunately. Repeat dosing or prolonged use of Sch potentiates its effects at the sympathetic ganglia and vagal effects. such as a patient with rhabdomyolysis or patients with chronic skeletal muscle disease in whom there is ‘‘up-regulation’’ from increased sensitization of extrajunctional AchR . sympathetic hyperactivity with hyperthermia (up to 113 F). and sinus tachycardia. whereby the neuromuscular membrane returns to the resting state and becomes resistant to further depolarization with Sch can also occur with repeat doses of Sch. although the dose is increased to 2 mg/kg to reach and activate the remaining AchRs unaffected by the disease. dysrhythmias.5 mEq/L because of depolarization of the myocytes (skeletal muscle cells). increased CO2 production.21. Hyperkalemia Even in ‘‘normal’’ patients. This is one reason some experts recommend atropine pretreatment in infants/small children. the mortality rate has decreased from 70% to less than 10%. disseminated intravascular coagulation. Sch can be used in patients with myasthenia gravis. Thus. sevoflurane. 4-mg/kg dose in a rare life-threatening situation in which there is inability to obtain venous access. Malignant Hypothermia Malignant hyperthermia is a rare genetic myopathetic disorder precipitated by multiple drugs. especially if the drug is not refrigerated. because Sch degrades gradually at room temperature. The recommended Sch dose in infants (including neonates) is 2 mg/kg based on their higher volume of distribution. there is a functional decrease in AchRs at the neuromuscular junction secondary to an antibody-mediated autoimmune destruction of the AchRs. With intensive medical therapy including dantrolene sodium. the rise has no clinical significance except in patients with a predisposition to hyperkalemia. hypotension/shock. Complications that can occur include rhabdomyolysis. The negative muscarinic effects from vagal stimulation may lead to bradycardia and hypotension even at recommended doses. Symptoms generally begin within an hour of the drug or anesthetic administration but may be delayed for hours. Be careful to check the expiration date on the drug vial. Desensitization blockage. anyone with significant bradycardia. acidosis. Succinylcholine Contraindications The absolute contraindications to Sch are (1) a history of malignant hyperthermia in the patient or family and (2) patients at high risk of severe hyperkalemia. In patients with myasthenia gravis. and death. desiflurane.Rapid Sequence Intubation 1057 references. a history is often not available. with RSI in the ED.47 and some even recommend up to 3 mg/kg in newborns. and those receiving multiple doses of Sch. any history of malignant hyperthermia in the patient or any family member is an absolute contraindication to Sch. Sch has been given intramuscularly in a 3. isoflurane) and Sch.

Bradycardia Bradycardia after Sch administration most frequently occurs in infants and children because of the vagal predominance of their autonomic nervous system but can also occur in patients of any age with repeated Sch doses. anemia. minimizes or eliminates this bradycardia response. most patients with renal failure undergo successful RSI with Sch without any untoward cardiovascular events. and muscular dystrophies. because the Sch interacts with the unstable muscle membrane of the myopathic cells causing rhabomyolysis and hyperkalemia. With rhabdomyolysis. causes hyperkalemia because the abnormal upregulated AchRs have low conductance and prolonged ion channel opening times that lead to an increase in potassium. so the risk of life-threatening hyperkalemia does not start until days (usually 3–5 days) after the injury or illness onset. there is no supportive evidence for this. eg. Prolonged Neuromuscular Blockade Any factor that inhibits the breakdown of Sch will prolong neuromuscular blockade and paralysis. the destruction of myocytes secondary to tissue injury releases potassium from the cells causing the serum potassium level to increase. Various genetic variants of pseudocholinesterase exist including one disorder with defective pseudocholinesterase in which individuals receiving Sch remain paralyzed for up to 6 to 8 hours after a single dose of Sch. Sch also should not be used in patients with myopathies. Thus. The extrajunctional AchR sensitization becomes clinically significant 4 to 5 days after injury or illness onset. various malignancies. multiple sclerosis. even years (3 or more years) after an acute injury or a progressive disease. pregnancy.47 However. The hyperkalemic response to Sch has also been reported in patients in the intensive care unit with life-threatening infections. An abnormal form or a decrease in pseudocholinesterase (either acquired or congenital) leads to prolonged paralysis from delayed degradation of Sch. However. motor neuron injury. Sch is not recommended for patients with known hyperkalemia because of concern that even the ‘‘usual’’ potassium increase of 0. Sch should be avoided in patients with ECG changes of hyperkalemia. Such susceptibility is not present immediately after the onset of neuromuscular disease or after a traumatic injury but can develop within 4 to 5 days and last indefinitely. increased age.5 mE/L may precipitate fatal dysrhythmias in a patient with existing significant hyperkalemia and acidosis. Duchene muscular dystrophy or Becker muscular dystrophy. Decreased pseudocholinesterase levels can also occur secondary to various acquired disorders: liver disease.02 mg/kg. Up-regulation usually occurs within 3 to 5 days and lasts indefinitely. Patients with extensive muscle wasting from denervating neuromuscular diseases include patients with a spinal cord injury. renal failure. The second mechanism. Although the longstanding tenet has been to avoid Sch in patients in chronic renal failure who have normokalemia. Pretreatment with atropine. up-regulation. immediately after their injury or disease onset. chronic cocaine use. this finding has little . This is important because Sch can be used in the acute trauma patient. connective tissue disease. the acute stroke or head injured patient. and organophosphate poisoning. Hyperkalemia can occur whenever there is massive tissue destruction or severe muscular wasting. especially if there is disuse atrophy and chemical denervation of the Ach receptors. Giving defasciculating doses of nonpolarizing NMBAs does not affect the hyperkalemic response. stroke. or a patient with neuromuscular disease.1058 Mace in muscle. including Duchene muscular dystrophy.47 In reality. 0.

myoglobinemia. Some experts have recommended the use of Sch even in patients with an open globe injury if there is a need for emergent securing of the airway. Defasciculation can be accomplished by pretreatment with lidocaine at 1. and increased cardiac output (increased oxygen consumption and increased carbon dioxide production). Some researches have noted small increases in ICP (range.5 mg/kg or 10% of the intubating dose of a nondepolarizing NMB. Fasciculations do not occur with the ND-NMBs. it may occur in isolation. the nondepolarizing NMB prevents Ach from access to the nicotinic receptor. although the additional time and steps associated with such pretreatment may be impractical and time consuming in an airway emergency.49 Fasciculations Fasciculations are involuntary. They are caused by the depolarization of Ach receptors. unsynchronized muscle contractions. More importantly. . increased creatinine kinase. Sch has been used safely and effectively in patients with penetrating eye injuries during RSI anesthesia. small. by itself. which causes a conformational change in the AchR receptor resulting in depolarizination of the neuromuscular junction. initiates an action potential. there has been no evidence of neurologic deterioration secondary to the transient ICP increase associated with Sch. whereas other studies have shown no increase. However. thereby preventing muscle contraction. Increased Intracranial Pressure The effect of Sch on ICP has been debated with various studies noting conflicting results. Fasciculations have various negative effects: myalgias. although a cricothyrotomy has been necessary in rare cases. which also likely results in a greater increase in IOP).1% of patients after Sch administration. Management includes giving a standard dose of a ND-NMB. citing the greater risk from allowing the negative side effects of an uncontrolled intubation (including hypoxia and coughing or vomiting. increased catecholamines (with secondary increased blood pressure and heart rate).001% to 0. and likely clinically insignificant transient increases in ICP with Sch. in turn. which is propagated to all of the muscles supplied by the nerve. Unlike Sch. 5–10 mm Hg). Pretreatment with a nondepolarizing NMB prevents the increase in ICP.Rapid Sequence Intubation 1059 clinical significance because even large decreases in pseudocholinesterase activity cause small increments in the duration of neuromuscular paralysis after Sch administration because baseline pseudocholinesterase levels are quite high. cause some paralysis.48. This. It has been associated with malignant hyperthermia.47 Increased Intraocular Pressure Sch can increase the IOP by 6 to 8 mm Hg. The extensive experience with Sch in the clinical setting of patients with acute intracerebral pathology documenting its safety and efficacy coupled with the dangers of a failed airway with secondary cerebral insult from hypoxia obviates against these theoretical. Trismus Masseter muscle spasm (trismus) occurs in 0. and the suggested pretreatment dose of a nondepolarizing NMB may. The transient small increases in cerebral blood flow and ICP that occur with Sch may be caused by fasciculations. NONDEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS Nondepolarizing (ND) NMBs competitively block Ach transmission at the postjunctional cholinergic nicotinic receptors.

Comparative trials of Sch with rocuronium found that Sch (1 mg/kg) resulted in superior intubation conditions when compared with rocuronium (0.50 The clinical duration (in minutes) for the NMB are ultra short acting. and 3) as a pretreatment agent to lessen or eliminate the fasciculations and their side effects (eg. priming has risks (including aspiration). and cisatracurium). Specific Nondepolarizing Neuromuscular Blocking Agents The medical use of ND-NMBs originated from the use of curare as the poison in the arrows of South American Indians.6–1.51.34 and is the drug of choice for RSI in the ED1 and anesthesia. pipecuronium. Most ND-NMBs are classified according to chemical class: steroids (aminosteroids). The doses and classes of some of the commonly used ND-NMBs are given in Table 2. such as d-tubocurarine. 2) to maintain postintubation paralysis (remember that repeated doses of Sch should be avoided.50 If Sch cannot be used and intubation in less than 90 seconds is needed. less than 10. and there are side effects. myalgias and increased IOP. especially various plants growing in several jungle regions throughout the world. or long acting.52 Another recent study also noted . vecuronium.1060 Mace Some ultra short ND NMBs are undergoing research.50 Indications for Nondepolarizing Neuromuscular Blocking Agents The ND-NMBs are used: 1) for muscle relaxation if Sch is contraindicated or unavailable. alcuronium.34 Sch’s advantages include rapid onset and offset (eg. or according to onset or duration of action: ultra short acting.50 The high dose regimen for RSI is preferred over the ‘‘priming technique.15 mg/kg/dose) as a second choice. metacurine.6 mg/kg). and long acting. were originally isolated from various naturally occurring sources. benzylisoquinolinium. d-tubocurarine. doubling the dose of rocuronium from 0. Nondepolarizing Versus Depolarizing Agent for Rapid Sequence Intubation Sch is still the most commonly used NMB in ED-RSI6. short acting. Some of the ND-NMBs. intragastric pressure [IGP]) associated with Sch use. profound depth of neuromuscular blockade. rocuronium (0.51. intermediate. 10 to 20. inability to secure the airway with the possibility of a difficult or failed airway.2 mg/kg dose) is the most commonly used paralytic agents for RSI because of its rapid onset and short duration with vecuronium (0. Currently. intermediate acting include vecuronium. ICP. although several ND-NMBs are being developed and tested. atracurium.2 mg/kg shortens the onset of complete neuromuscular blockade from about 1. doxacurium. greater than 50. which are preferred. rocuronium. 89 seconds) to 1 minute (mean. and better intubating conditions. The contraindication for the use of ND-NMBs is the same as for a depolarizing NMB. then the higher doses of the NDNMB can be used. there are no clinically approved ultra–short-acting ND-NMB blockers. 20 to 50. and long-acting include pancuronium. The older NMBs such as tubocurarine have a higher incidence of hypotension and cardiovascular side effects secondary to histamine release than the newer NMBs (for example. 10% of the intubating dose) is given 2 to 4 minutes before the second large dose for tracheal intubation for several reasons: intubating conditions are less optimal than with Sch. short acting. 55 seconds).50 Of the ND-NMBs. and cisatracurium. However. intermediate. the only ultra short NMB available in the United States is the depolarizing NMB. Sch. Short-acting ND-NMBs include rapacuronium and mivacurium.5 minutes (mean. rocuronium. and gallamine. short duration of action). if possible). a low dose of rocuronium was used. or others. but they are not yet clinically available.6 mg/kg to 1.52 However.’’ whereby a small subparalyzing dose of the ND-NMB (eg.50 Currently.

another step. and uncomfortable visual disturbances for the patient with partial neuromuscular block.55–57 Some experts anticipate that the availability of a reversal agent for the ND-NMB will expand the use of nondepolarizing NMBs. MODIFICATION OF RAPID-SEQUENCE INTUBATION ‘‘Facilitated intubation’’ refers to the use of a sedative only (without a paralytic) to pharmacologically assist with intubation. Rocuronium is the most commonly used ND-NMB because of its rapid onset. approved by the US Food and Drug Administration) in the near future. The Future of Rapid-Sequence Intubation There is a new reversal agent.50 A drug familiar to emergency medicine.57 and overall greatly decrease the use of Sch. It most often is used for neurosurgical patients with an increase intracranial pressure and is synergistic with fentanyl.’’54 Use of Nondepolarizing Neuromuscular Blocking Agents as Pretreatment The ND-NMBs in a dose that is approximately 10% of the intubating dose can be used as a pretreatment for Sch to prevent fasciculations and their side effects. also referred to as ‘‘pharmacologically assisted intubation. the ND-NMB is generally administered 2 minutes before giving the intubating dose of Sch. There is a danger of aspiration. there are several confounding issues to consider. dexmedetomidine. more importantly.53 A Cochrane meta-analysis concluded ‘‘succinylcholine created superior intubation conditions to rocuronium when comparing both excellent and clinically acceptable intubating conditions. specifically rocuronium (in a 1. and additional time to the process. Lidocaine is effective in minimizing or preventing the fasciculations with their side effects that occur after Sch administration.21 Timing or the use of a small subparalyzing dose of a NDNMB has several problems as well.’’ has been recommended by some clinicians in specific circumstances because it does not involve neuromuscular blockade. Facilitated intubation. Some advocate the avoidance of a neuromuscular paralysis and the use of sedation alone (‘‘facilitated intubation’’) in clinical scenarios in which a difficult airway is anticipated. there are limited data regarding its use for RSI in the ED.6 mg/kg was used) with no difference in the incidence of adverse airway effects. difficulty swallowing. and it can be given 1. Although defasciculation is achieved.2 mg/kg dose) for RSI. Giving ND-NMB increases the muscle’s resistance to Sch’s action such that increasing the Sch dose by 50% is recommended. sugammadex.5 to 3 minutes before the induction of anesthesia. which is anticipated to be clinically available (eg. Perhaps.5 mg/kg of lidocaine. can be used as an alternative to ND-NMB for priming before Sch administration. Some clinicians also use fasciculations as a clue to when neuromuscular blockade has occurred.21 . and conditions are ready for ET tube placement.Rapid Sequence Intubation 1061 similar results with Sch (1 mg/kg) providing superior intubation conditions when compared with rocuronium (again. In clinical practice. Use of a ND-NMB may result in less favorable conditions for tracheal intubation and slow the onset of Sch. Currently. The dose is 1. Use of a defasciculating dose of ND-NMB adds another drug to RSI (with the additional risk of possible side effects/complications and drug errors). but there are no data available regarding its use for RSI in the ED.58 There is also a newer sedative. a lower dose 0. which has been used in the operating room. lidocaine. for the emergent intubation in the ED is the extra time (about 2 or more minutes) added to the procedure before intubation occurs.59 Esmolol has also been used as a preinduction agent for RSI.

5 mg 0. Allergy Naloxone. CAD Pediatric patients %10 yrs.02 Minimum 0.1062 Mace Table 2 Additional medications for rapid sequence intubation Drug (Pretreatment Drugs) Lidocainea Dose (IV) (mg/kg)* for Intubation 1. major vessel dissection/rupture.1 mg Maximum 0. Patients with significant bradycardia Side Effects May cause hypotension May cause hypotension Precautions Contraindications Allergy Reversal Agent Comments Often used with fentanyl for [ ICP Fentanyla (an opioid) 2–3 mcg/kg Avoid bolus injection to avoid chest wall/ masseter rigidity. bradycardia.5 Indication [ ICP.06 (1/10th of paralyzing dose) May cause tachycardia. Naltrexone Often used with lidocaine for [ ICP Atropine 0. hypertension Rocuronium (Defasculating dose of ND-NMB)b [ ICP [ IOP May cause incomplete paralysis Sugammadex (not yet available)c .06 (may cause paralysis). adults with reactive airway disease [ ICP. Allergy Avoid if patient has significant tachycardia or hypertension Avoid doses >0.

1.Neuromuscular Blocking Agents Succinylcholine Adult 1. patients with pseudocholinesterase inhibitors Contraindication malignant hyperthermia. Reversal Agents Depolarization of motor end plate at myoneural junction. Allergy Allergy Mechanism of Action. Duration 6–10 minutes Rocuronium 0. Onset 30-60 sec. Intermediate acting High dose. Sugammadex.6–1.2 mg/kg has a shortened onset but long duration Blocks acetylcholine from binding to receptors. nonacute (>4–5 days) burn patients or neuromuscular disease patients (may cause hyperkalemia). Avoid repeat doses/ prolonged use Depolarizing neuromuscular blocker. (not yet available)c Onset high dose 1 min.0 1. Duration 20 min (continued on next page) Rapid Sequence Intubation 1063 .5 (some recommend 2 in adults). patients with known severe hyperkalemia. Newborns 3. No reversal agent Use with atropine if age %10 years or significant bradycardia.2 high dose Nondepolarizing neuromuscular block. [ dose to 2 myasthenia gravis patients. Infants 2. Short acting Bradycardia in children (pretreat with atropine) use with caution if [ ICP/IOP/IGP. Low dose 11⁄2 min.

Intermediate acting Side Effects Onset 2. CAD.1 Precautions Contraindications Allergy Indication Nondepolarizing neuromuscular blocker.1064 Mace Table 2 (continued) Drug (Neuromuscular Blocking Agents) Vecuroniumd Dose (IV) (mg/kg)* for Intubation 0.1 Nondepolarizing neuromuscular blocker. Abbreviations: ICP. (not yet available)c Blocks acetylcholine from binding to receptors. Duration 60–100 min. which can reverse the ND-NMBs. IOP. anticipated to be available in the near future. Reversal Agent Blocks acetylcholine from binding to receptors. doses for intubation are generally higher than for procedural sedation. Duration. b Lidocaine also prevents fasciculations with succinylcholine so a defasciculating dose of ND-NMB may be unnecessary if lidocaine is given.5–3 min. CV. Sugammadex. a Coadministration of lidocaine and fentanyl may have a synergistic effect. d The ND-NMBs that have a longer duration (specifically. Long acting Onset 2–3 min. blood pressure. intracranial pressure. c Sugammadex is a new reversal agent. coronary artery disease. Not all the available drugs are listed. cardiovascular. nondepolarizing. intraocular pressure. 20–40 min. HR. heart rate. IGP. Long duration Note: Doses are in mg/kg except for fentanyl. which is in mcg/kg. neuromuscular blocker. Sugammadex (not yet available)c Comments Slow onset. intragastric pressure. NMB. but the more commonly used drugs are given. Long duration Pancuroniumd 0. vecuronium and pancuronium) are not commonly used for RSI in the ED because of their long duration. . ND. BP. Allergy Slow onset.

paralysis with induction.20(5):339–44.75:541–3. and episodes of clenched jaws and orofacial muscle spasm. RSI has higher success rates than facilitated intubation. 2. Hedges JR. REFERENCES 1.6 SUMMARY RSI is the process involving administration of a sedative (eg. editors.62 When comparing successful rates of intubation.. 100–14 [Chapter 5].complications and survival. Chest 1979. 44%. The purpose of RSI is to make emergent intubation easier and safer. using 0. 2004. Possible disadvantages are complications from the additional drugs. New York: McGraw-Hill Co.61 The conclusion was that facilitated intubation (etomidate only) had a decreased rate of success when compared with RSI (etomidate 1 succinylcholine). Taryle DA. A prehospital study of facilitated intubation using midazolam alone noted a successful intubation rate of only 62. For ED intubations. which is less than the usual success rate for prehospital RSI. In: Roberts JR.60 A later study from the same investigators (an air medical transport service) prospectively compared facilitated intubation using etomidate versus RSI using etomidate and succinylcholine. Philadelphia: Saunder. protection and positioning.5%. 47%. Murphy MF. 4. Pretreatment in rapid sequence intubation: indicated or contraindicated? CJEM 2006. sedative only. Campbell S. 4th edition. Chandler JE. pretreatment. Pediatric rapid sequence intubation: a review. Walls RM. Good JT Jr. p. and laryngoscopic conditions using several scoring systems was significantly more difficult for the facilitated intubation (etomidate only) versus RSI. Rapid sequence intubation. the first attempt intubation success rates were RSI. Murphy MF.60–62 Proponents of facilitated intubation suggest that there may be clinical scenarios in which paralysis is not an option.34 For pediatric patients. RSI remains the standard of care in emergency medicine airway management.34 The successful intubation rate for first attempt was RSI 5 85%. Pediatr Emerg Care 2004. and sedative only (no NMB) 5 76%.Rapid Sequence Intubation 1065 For facilitated intubation. In: Mace SE. Schrexnayder SM. et al. however. Pain management and sedation emergency department management. MacQuarrie K.6. Emergency room intubations .3 mg/kg of etomidate as their sedative without any NMB reported an 89% rate of successful intubation. The successful rate for first intubation was RSI 5 91%. difficult intubation in 16%. The procedure of RSI generally consists of seven steps: preparation. The results were: 63% (15 of 24) of the facilitated intubation (etomidate only) group received additional medications versus 4% (1 of 25) in the RSI group. Kovacs G. based on these studies. the results of the NEAR studies confirm the superiority of RSI over facilitated intubation. preoxygenation. Ducharme J. Hopson LR. . thereby increasing the success rate of intubation while decreasing the complications. induction agent) followed almost immediately by a NMB to facilitate endotracheal intubation. and sedative only (no NMB) 5 88%. p. Pharmacologic adjuncts to intubation. Dronen SC. A study in the prehospital air medical setting. placement of the endotracheal tube. 78%. 3. Bledsoe GH. 5. prolonged intubation with hypoxia. Controversy has arisen regarding various steps in RSI. and precipitating an emergent or crash airway. and post intubation management. editors. Clinical procedures in emergency medicine. the most common sedative used has been etomidate.8(4):243–4. although midazolam has also bee used. and no medication. 2006. 211–8 [Chapter 28].

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