Intravenous anesthetics play an important role in airway management. They permit rapid induction of anesthesia and facilitate securing of the airway with an ETT with minimal stress to the patient. The ideal medication would provide amnesia, analgesia, and muscle relaxation. In addition, the ideal medication would have minimal effect on the patient's hemodynamics, preventing both hypotension due to sedation and analgesia and hypertension from the stimulation of laryngoscopy. Unfortunately, no one medication encompasses all of these properties. Instead, a balanced approach with a combination of medications is utilized. In elective intubations, the availability of time and the presence of an empty stomach allow for premedication; this is followed by an induction agent, which provides unconsciousness, and then a paralytic to help facilitate intubation. In emergent intubations, premedication may not be possible due to the lack of time or a contraindication to its use such as a full stomach. The hemodynamics of the patient may limit the amount of induction agent utilized; those who are particularly tenuous may not tolerate any induction agent. If paralysis is required, only fast acting paralytics will be of benefit during an emergent intubation. Common medication dosages are listed in Table 17–3.
Table 17–3Common endotracheal intubation medication indications and dosages. ||Download (.pdf) Table 17–3 Common endotracheal intubation medication indications and dosages.
|Indication ||Medication Class ||IV dose ||Onset |
< 30 s
GABA receptor agonist
NMDA receptor antagonist
Midazolam is a fast-acting intravenous benzodiazepine that allows for anxiolysis and anterograde amnesia by crossing the brain blood barrier and activating the gamma-butyric acid (GABA) receptor complex. The acidic nature of the intravenous preparation keeps midazolam in solution; however, exposure to the pH of the blood causes a structural change making midazolam extremely lipophilic. Hepatic metabolism results in formation of an active metabolite (1-hydroxymidazolam), which is renally cleared and may contribute to prolonged sedation with extended infusions. The short duration of action is aided by its lipophilicity, which promotes rapid redistribution from the brain to inactive tissue sites, such as fat and skeletal muscle. Side effects include respiratory depression, especially when given in conjunction with an opioid.21
Fentanyl is a synthetic centrally acting opioid agonist that is structurally related to meperidine. It is approximately 100 times more potent than morphine. The rapid onset of action is attributed to its high lipophilicity, which also leads to its short duration of action by redistribution. Hepatic metabolism results in an inactive metabolite. Side effects include respiratory depression, especially when given with a benzodiazepine, and chest wall rigidity at high doses.21
Lidocaine is an amide local anesthetic that is capable of suppressing the sympathetic response to intubation by inhibiting the gag and cough reflex. Blunting the sympathetic response can limit the rise in blood pressure due to manipulation of the airway during intubation and can prevent an increase in intracranial pressure (ICP) in a patient with known or presumed head injury.21
Propofol is an alkylphenol compound that is insoluble in water, and therefore, must be administered as an emulsion, containing soybean oil, glycerol, and egg lecithin. The rapid onset of action is attributed to its high lipophilicity. The short duration of action is primarily due to redistribution from highly perfused compartments such as the brain to the poorly perfused compartments such as skeletal muscle. In addition to its hypnotic properties, propofol is both a respiratory and cardiac depressant. Hypotension following induction is primarily due to vasodilation; however, the baroreceptor response is also attenuated preventing an adequate increase in heart rate to compensate for the decrease in blood pressure.22 Hypotension following emergent intubation in critically ill patients is a strong predictor of mortality.23 As a result, propofol should be used with caution if at all in hypotensive patients requiring emergent intubation. Hypotension should be immediately treated with a vasopressor, such as phenylephrine (IV dose 50-200 mcg).
Etomidate is a carboxylated imidazole that acts as a hypnotic by inhibiting the GABA receptors of the reticular activating system. Etomidate is poorly soluble in water and therefore is administered in a 35% propylene glycol solution. Onset of action is similar to propofol with a duration of effect of 3 to 12 minutes. Unlike propofol, etomidate has minimal effects on myocardial contractility and cardiac output resulting in less hypotension.21 Myoclonus caused by a disinhibitory effect on the central nervous system is characteristic. A single induction dose of etomidate causes adrenal suppression by inhibiting the activity of 11-β-hydroxylase, an enzyme required for cortisol and aldosterone synthesis.24,25 Subgroup analysis in the Corticus trial indicated a decreased responsiveness to cortisol and increased mortality in septic patients who received etomidate.26 In summary, etomidate is an attractive induction agent in hemodynamically unstable patients; however, recent studies demonstrating adrenal suppression and increased mortality in septic patients has called its use into question.
Ketamine is a phencyclidine derivative that causes a dose-dependent state of “dissociative anesthesia” that produces both amnesia and analgesia. Ketamine interacts with a variety of receptors. Its amnestic property is likely due to the inhibition of the N-methyl-d-aspartate (NMDA) complex. Stimulation of the sympathetic nervous system causes an increase in heart rate, myocardial contractility, and mean arterial blood pressure, making it an ideal agent in hemodynamically compromised patients.27 The mechanism of this indirect stimulatory effect is via inhibition of norepinephrine reuptake. The direct myocardial depressant effect of ketamine may be unmasked in patients with poor catecholamine stores such as the chronically or severely critically ill patient. Stimulation of the sympathetic nervous system will also result in increased cerebral oxygen consumption, cerebral blood flow, and ICP making it a poor choice in patients with suspected head injury and elevated ICP. Ketamine is infamous for its ability to cause hallucinations; however, the coadministration of a benzodiazepine can usually attenuate this effect.28
Succinylcholine (SCh) is a depolarizing neuromuscular blocking drug (NMBD) that has a fast onset time and short duration of action, making it ideal for rapid sequence induction (RSI). Structurally, SCh is related to acetylcholine (ACh) and functions by binding to the ACh receptor on the motor end plate, resulting in continued depolarization of the receptor and subsequent skeletal muscle paralysis. The onset of paralysis is typically preceded by fasciculations, which are caused by transient generalized skeletal muscle contractions. Normal muscle function does not return until the receptor is allowed to repolarize to its resting state, which occurs after metabolism of SCh by pseudocholinesterase. Pseudocholinesterase metabolizes SCh at such a high rate that only a small portion of the injected dose reaches the motor end plate. Altered pseudocholinesterase function can result in paralysis lasting 6 to 8 hours after a single dose. A relative decrease in pseudocholinesterase levels in patients with liver disease, kidney disease, anemia, pregnancy, and cocaine and amphetamine abuse has a minimal clinical effect and no alteration in the dose of SCh is required.29
Certain adverse effects may prevent SCh from being utilized as a RSI paralytic. On average, the serum potassium level increases 0.5 mEq/L following administration of SCh. If a paralytic is required in a patient with symptomatic hyperkalemia, an alternative medication should be considered; however, renal failure in a patient with normal potassium levels is not a contraindication to the administration of SCh.30 Severe hyperkalemia causing cardiac arrest has been documented in patients with disorders of the nervous system (eg, spinal cord transection, amyotrophic lateral sclerosis, Guillain-Barre, etc) or extensive burn injury. Approximately 5 to 15 days after an acute injury, the body produces extrajunctional ACh receptors (ie, outside of the motor end plate) that may cause excessive potassium release following administration of SCh. This phenomenon puts patients at increased risk of hyperkalemic cardiac arrest. Nonetheless, it is generally considered safe to administer SCh within 24 hours of the acute injury nerve injury or stroke.31 Hyperkalemia may also occur in patients with disorders of the musculoskeletal system, such as Duchenne muscular dystrophy, and SCh should be avoided in such patients. The increase in potassium level after SCh administration has been associated with length of stay in the ICU, which acts a surrogate marker for immobility. The risk of acute hyperkalemia (≥ 6.5 mEq/L) is highly significant after 16 days in the ICU.32
The administration of SCh increases intraocular pressure (IOP) by 5 to 10 mm Hg for 2 to 6 minutes.33 In patients with open eye injuries, the concern that increased IOP will cause extrusion of intraocular contents has limited the use of SCh in these patients. Nonetheless, there has never been a reported case of this occurring in the literature. The effect of SCh on ICP is controversial. Studies demonstrating a modest increase in ICP after SCh administration are inconsistent.34 SCh may act as a trigger for malignant hyperthermia, a life-threatening complication resulting in high fever, muscle rigidity, rhabdomyolysis, and renal failure, which requires immediate treatment with dantrolene. Fortunately, the incidence of malignant hyperthermia after administration of SCh is rare. While SCh may cause a number of potential adverse side effects, no medication has been able to match its fast onset time and short duration to replace it as the paralytic of choice during an emergent intubation.
Rocuronium is a nondepolarizing NMBD that causes paralysis by antagonism of the ACh receptor. The onset of action is slightly slower than that of SCh at a rapid sequence intubating dose of 1.2 mg/kg (normal intubating dose 0.6 mg/kg), but faster than the other nondepolarizing NMBDs. The major concern with rocuronium is its prolonged duration of action of approximately 1 hour. If a patient needs to be woken up due to difficulty in intubating or ventilating, they will not be able to regain spontaneous respiration for a prolonged period of time. Sugammadex is a specific reversal agent for rocuronium, preventing its interaction with the ACh receptor, and reverses paralysis within 3 minutes of administraion.35 Sugammadex is currently not available in the United States due to Food and Drug Administration concerns regarding hypersensitivity and allergic reactions.