Adverse Effects of Neuromuscular Blockers and Their Antagonists

Abstract

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their unpredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Anaphylaxis during anaesthesia: diagnostic approach

“…All NMBA can elicit anaphylaxis and there is an agreement that the short-acting depolarizing succinylcholine poses the greatest risk, despite its close structural homology to acetylcholine (20,31,32).…”

Adverse reactions to neuromuscular blocking agents

“…It is a rare genetic disorder triggered by exposure to depolarizing NMBAs (succinylcholine) and inhalation of halogenated anesthetics, with a spontaneous mortality rate of 80% [58,59]. In 50% of all cases, the mutation is autosomal dominant, with one of eight potential mutations in the ryanodine receptor.…”

“…Myoglobinemia and increased serum creatinine kinase have been reported following succinylcholine administration, particularly in children [59,62]. The etiology could be the shearing forces set up by asynchronous contractions of adjacent muscle cells following their activation by succinylcholine.…”

“…In certain clinical situations, such as in patients with burns, massive trauma, or acute upper and lower motoneuron disease (eg, spinal cord injury, stroke, demyelinating disease), the resulting hyperkalemia can be severe enough to cause fatal cardiac dysrhythmias and cardiac arrest [25,59].…”

Anaphylaxis to benzalkonium chloride-coated central venous catheter

“…The reported incidence during anesthesia has been variously reported from 1:5,000 to 1:25,000 cases [8]. Anaphylactic shock is associated with a mortality rate of up to 6% [9].…”