Adverse effects of nondepolarising neuromuscular blocking agents. Incidence, prevention and management.

Nondepolarising muscle relaxants block neuromuscular transmission, acting as antagonists of the nicotinic receptors at the neuromuscular junction. Their undesired effects are frequently caused by interaction with acetylcholine receptors outside this junction, and autonomic cardiovascular effects may result. Other adverse effects include anaphylactic or anaphylactoid reactions, and histamine release. Various disease states may present specific considerations in the use of nondepolarising muscle relaxants. Although many complications of these drugs (such as prolonged block or resistance) are easily treated, others may necessitate immediate intervention and vigorous therapy. Careful selection of an appropriate relaxant for a particular patient will usually prevent the occurrence of complications.

Adverse effects of depolarising neuromuscular blocking agents. Incidence, prevention and management.

Muscle relaxants block neuromuscular transmission, acting at nicotinic acetylcholine receptors of the neuromuscular junction. Suxamethonium (succinylcholine) is a depolarising agent, whereas all other relaxants in clinical use are nondepolarising. The desired neuromuscular block results from the structural similarity of muscle relaxants to acetylcholine, enabling the interaction with receptors at the neuromuscular junction. Adverse effects of suxamethonium are generally related to its agonist mode of action. Autonomic cardiovascular effects may result. Other adverse effects include anaphylactic or anaphylactoid reactions, and histamine release. Various disease states may present specific considerations in the use of muscle relaxants. Although many complications of muscle relaxants (such as prolonged block or resistance) are easily treated, others may require immediate intervention and vigorous therapy. Careful selection of appropriate relaxants for particular patients will usually prevent the occurrence of complications.

A defasciculating dose of d-tubocurarine causes resistance to succinylcholine.

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).

Sensitivity to vecuronium in myasthenia gravis: a dose-response study.

A cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle were used to determine the potency of vecuronium in 20 normal patients and in ten patients with myasthenia gravis under thiamylal, N2O, O2, fentanyl anaesthesia. The mean (+/- SEM) values for ED50, ED90, and ED95 in the normal patients were 19 +/- 1, 31 +/- 1 and 36 +/- 2 micrograms.kg-1, respectively. Myasthenic patients showed increased sensitivity to vecuronium, the mean values for ED50, ED90, and ED95 were 10 +/- 2, 17 +/- 2 and 20 +/- 3 micrograms.kg-1, being 50, 55 and 56 per cent of normal, respectively. We did not demonstrate a difference in sensitivity to vecuronium between those myasthenic patients who received pyridostigmine preoperatively and those who did not, nor among those chronically treated with corticosteroids, compared with those who were not.