Use of nondepolarizing neuromuscular blocking agents in mechanically ventilated patients

The pharmacology and history of development of nondepolarizing neuromuscular blocking agents are presented, and the pharmacokinetics and pharmacodynamics of these agents, administration guidelines for mechanically ventilated patients, adverse effects, factors affecting paralysis, and methods for blockade reversal are reviewed. Nondepolarizing neuromuscular blocking agents (tubocurarine, metocurine, pancuronium, vecuronium, and atracurium) are frequently used to induce prolonged pharmacologic paralysis in patients in the intensive-care unit (ICU). These agents are poorly absorbed after oral administration and must be administered by injection, preferably by the i.v. route. Individualized adjustment of the dose is necessary to maintain the desired degree of paralysis. Dosing modifications may be necessary in patients with underlying renal or hepatic diseases and in pediatric and geriatric patients. Patients with thermal burns require larger doses of these drugs than other patients. These agents can cause several important adverse effects, including histamine release, cardiovascular changes, and muscle atrophy. Pathophysiologic variables and drug interactions can affect the degree of paralysis. Generally, patients no longer requiring paralysis in the ICU will be allowed to spontaneously regain muscle function after drug therapy has been discontinued. If the effects of the nondepolarizing neuromuscular blocking agents must be reversed more rapidly, acetylcholinesterase-inhibiting agents such as physostigmine, neostigmine, pyridostigmine, and edrophonium can be used. Nondepolarizing neuromuscular blocking agents can be used to paralyze mechanically ventilated patients, facilitating optimal oxygenation and ventilation.