Neuromuscular Blockers
Pharmacology
Neuromuscular blocking agents produce skeletal muscle paralysis by inhibiting the action of acetylcholine at the neuromuscular junction. Depolarizing agents (succinylcholine; Table III–10) depolarize the motor end plate and block recovery; transient muscle fasciculations occur with the initial depolarization. Nondepolarizing agents (atracurium, pancuronium, and others; see Table III–10) competitively block the action of acetylcholine at the motor end plate, preventing depolarization. Therefore, with nondepolarizing agents, no initial muscle fasciculations occur and a flaccid paralysis is produced.
The neuromuscular blockers produce complete muscle paralysis with no depression of CNS function (they are positively charged and water-soluble compounds that do not cross the brain-blood barrier rapidly). Thus, patients who are conscious will remain awake but be unable to move, and patients with status epilepticus may continue to have seizure activity despite paralysis. Furthermore, the neuromuscular blockers do not relieve pain or anxiety and have no sedative effects.
Succinylcholine produces the most rapid onset of neuromuscular blockade. After intravenous administration, total paralysis ensues within 30–60 seconds and lasts 10–20 minutes. It is hydrolyzed rapidly by pseudocholinesterase, an enzyme present in the vascular compartment but not at the neuromuscular junction (NMJ). Therefore, a relatively small fraction of the administered dose reaches the site of action, and diffusion from the NMJ back into the intravascular space determines metabolism. Larger (1.5 mg/kg IV in adults) rather than smaller doses should be used for rapid-sequence intubation (RSI).
Rocuronium, a nondepolarizing agent, also has a rapid onset of effect. However, the duration of the blockade (22–94 minutes) is considerably longer than that of succinylcholine. Sugammadex, a specific and rapid reversal agent for rocuronium, has been approved for use in the United Kingdom, Sweden, Germany, and Finland, but at the time of this writing it has not been approved in the United States.
The onset and duration of several other neuromuscular blockers are described in Table III–10.
Table III-10 Selected Neuromuscular Blockers
Table III-10 Selected Neuromuscular Blockers
Drug
Onset
Durationa
Dose (All Intravenous)
Depolarizing
Succinylcholine
0.5–1 min
2–3 min
0.6 mg/kgb (children: 1 mg/kgc) over 10–20 seconds; repeat as needed.
Nondepolarizing
Atracurium
3–5 min
20–45 min
0.4–0.5 mg/kg (children <2 years: 0.3–0.4 mg/kg).
Cisatracurium
1.5–2 min
55–61 min
0.15–0.2 mg/kg (children 2–12 years: 0.1 mg/kg), then 1–3 mcg/kg/min to maintain blockade.
Doxacurium
5–7 min
56–160 min
0.05–0.08 mg/kg (children: 0.03–0.05 mg/kg), then 0.005–0.01 mg/kg every 30–45 minutes to maintain blockade (children may require more frequent dosing).
Mivacurium
2–4 min
13–23 min
0.15–0.25 mg/kg (children: 0.2 mg/kg), then 0.1 mg/kg every 15 minutes or by continuous infusion; start with 0.01 mg/kg/min and maintain with average adult dose of 0.006–0.007 mg/kg/min (children: 0.014 mg/kg/min).
Pancuronium
2–3 min
35–45 min
0.06–0.1 mg/kg; then 0.01–0.02 mg/kg every 20–40 minutes as needed to maintain blockade.
Pipecuronium
3–5 min
17–175 min
0.05–0.1 mg/kg (adjust for renal function); then 0.01–0.015 mg/kg every 17–175 minutes (children may be less sensitive and require more frequent dosing).
Rocuronium
0.5–3 min
22–94 min
0.6–1 mg/kg; then 0.01 mg/kg/min to maintain blockade.
Vecuronium
1–2 min
25–40 min
For children older than 1 year and adults: 0.08- to 0.1-mg/kg bolus, then 0.01–0.02 mg/kg every 10–20 minutes to maintain blockade.
Indications
Neuromuscular blockers are used to abolish excessive muscular activity, rigidity, or peripheral seizure activity when continued muscle activity may produce or aggravate rhabdomyolysis, mechanical injury, or hyperthermia. They are also employed when excessive muscular movement may place the patient (or others) at risk for injury.
Drug overdoses involving stimulants (eg, amphetamines, cocaine, phencyclidine, monoamine oxidase inhibitors) or strychnine.
Tetanus. Nondepolarizing agents should be chosen because infection with Clostridium species can predispose patients to pathologic hyperkalemia induced by the use of succinylcholine.
Hyperthermia associated with muscle rigidity or hyperactivity (eg, status epilepticus, neuroleptic malignant syndrome, or serotonin syndrome (See Altered Mental Status)). Note: In susceptible patients, malignant hyperthermia (See Hyperthermia) can be triggered by succinylcholine (see below). Once it develops, neither depolarizing nor nondepolarizing agents will be effective for malignant hyperthermia. In fact, inability to induce paralysis with these agents should suggest the diagnosis of malignant hyperthermia.
In intubated patients, partial or complete neuromuscular blockade may facilitate improved patient-ventilator synchrony, enhanced gas exchange, and lowered risk for barotrauma.
Suspected or verified cervical spine injury, or any setting in which there is increased intracranial pressure (eg, intracranial hemorrhage, hepatic encephalopathy). Note: Succinylcholine can cause an increase in intracranial pressure, and in this setting agents intended to blunt the increase may be administered before administration of the paralytic (see Item V.C below).
Paralytic agents can also be used to treat acute laryngospasm.
Although they are not always needed for orotracheal intubation, neuromuscular blockers can provide prompt paralysis, offering the intubator a superior view of laryngeal structures to facilitate accurate placement of the endotracheal tube. The preferred agents for this purpose, succinylcholine and rocuronium, both have a rapid onset and minimal cardiovascular effects.
Contraindications
Lack of preparedness or inability to intubate the trachea and ventilate the patient after total paralysis ensues. Proper equipment and trained personnel must be assembled before the drug is given.
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