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Pancuronium
See also Neuromuscular blocking drugs, non-depolarizing
General information
Pancuronium bromide is a non-depolarizing muscle relaxant [ ] with two quaternary ammonium groups on a steroid (androstane) skeleton. It is about 5–7 times as potent as d -tubocurarine. Protein binding occurs to both albumins and globulins, probably only to a relatively slight extent (10–20%), although reports vary from 10% to 90%. In contrast to most other non-depolarizing relaxants, pancuronium is metabolized at about 10–20%. Deacetylation in the liver probably accounts for the greater part of this biotransformation. The major metabolites are 3-monohydroxypancuronium, 17-monohydroxypancuronium, and (3,17)-dihydroxypancuronium; they are active pharmacologically, 3-monohydroxypancuronium being half as potent and the other two having 2% of the potency of pancuronium. About 40–50% of a dose is normally excreted in the urine and 5–10% in the bile over 24 hours as pancuronium plus its metabolites.
Pancuronium is reported to inhibit plasma cholinesterase [ ] and this may be partly why the action of suxamethonium, given after a small dose of pancuronium, is prolonged. It also weakly inhibits acetylcholinesterase.
For tracheal intubation the usual dose is 0.1 mg/kg. When given after suxamethonium, 0.05 mg/kg is sufficient for good abdominal relaxation. Further doses of about one-quarter to one-third of the initial dose are given at intervals of 30–40 minutes to maintain relaxation. Reversal is easily achieved with neostigmine, provided there is some spontaneous return of neuromuscular transmission beforehand. If the evoked twitch height is less than 10% of the control value, there can be difficulty in reversing the blockade; this applies to all non-depolarizing relaxants, except perhaps vecuronium and atracurium.
The onset time for complete neuromuscular blockade is similar to that of d -tubocurarine and other non-depolarizing agents, namely 2–4 minutes. However, this is to some extent dose-dependent, and because of the relative lack of cardiovascular effects and histamine release, pancuronium can safely be given in higher dosages, thus producing good intubation conditions within 2 minutes. The dose of d -tubocurarine required to achieve similar conditions in 2 minutes would result in hypotension. As with d -tubocurarine, repeated doses can lead to accumulation and prolonged blockade.
In burned patients resistance to the neuromuscular blocking action of pancuronium may be encountered [ ], as with other non-depolarizing relaxants.
Patients in whom pancuronium bromide is of value [ ] include:
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patients with hypoxemia resisting mechanical ventilation and so cardiovascularly unstable that the use of sedatives is precluded;
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patients with bronchospasm unresponsive to conventional therapy;
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patients with severe tetanus or poisoning when muscle spasm prohibits adequate ventilation;
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patients with status epilepticus unable to maintain their own ventilation;
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shivering patients in whom metabolic demands for oxygen should be reduced;
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patients requiring tracheal intubation in whom suxamethonium is contraindicated.
Organs and systems
Cardiovascular
Cardiovascular adverse effects are minimal with pancuronium. Ganglion blockade does not occur. Slight dose-dependent rises in heart rate, blood pressure, and cardiac output are common [ ], but are often masked by the actions of other co-administered agents, such as fentanyl or halothane, which cause bradycardia or hypotension. These adverse effects of pancuronium are thus often beneficial and can be deliberately harnessed. Several mechanisms contribute: vagal blockade via selective blockade of cardiac muscarinic receptors [ ], release of noradrenaline from adrenergic nerve endings [ ], increased blood catecholamine concentrations [ ], inhibition of neuronal catecholamine reuptake [ ], and direct effects on myocardial contractility [ ]. These have been reviewed [ ].
Occasionally nodal rhythm, atrioventricular dissociation, and tachydysrhythmias (such as ventricular extra beats or even bigeminy) develop, but these usually occur in association with halothane.
Supraventricular tachycardia has been reported after pancuronium 8 mg in a patient taking aminophylline 800 mg/day [ ].
Nodal rhythm can occur after injection of pancuronium. This dysrhythmia and bradycardia appear to be more common when neostigmine (plus atropine) is given for reversal of pancuronium-induced neuromuscular blockade than for reversal of d -tubocurarine or alcuronium [ ]; cholinesterase inhibition by pancuronium may contribute to the bradycardia in these circumstances.
Nervous system
Accidental injection into the cerebrospinal fluid of 4 mg of pancuronium resulted in generalized hypotonia, weakness, and hypoventilation [ ]. Neostigmine given intravenously led to prompt recovery.
Sensory systems
Neonates with congenital diaphragmatic hernia often develop respiratory failure. To facilitate mechanical ventilation, neuromuscular blocking agents may be used. Sensorineural hearing loss can occur in survivors, with a reported incidence of up to 60%. It has been associated with the use of pancuronium. In a historical cohort study of 37 survivors of congenital diaphragmatic hernia, children with hearing loss had received significantly higher doses of pancuronium during respiratory failure than children without hearing loss [ ]. In addition, the cumulative dose of pancuronium correlated with the intensity of hearing loss in decibels. There were no differences with regard to oxygenation and ventilation parameters or to the cumulative dose of aminoglycosides, vancomycin, or furosemide, but children with hearing loss had received a higher cumulative dose of etacrynic acid. The authors admitted that the retrospective study design and the small sample size demanded cautious interpretation of their observations. For the time being, this report is not reason enough to avoid pancuronium if neuromuscular blockade is required. However, it should be remembered that the risk of severe neuromuscular disturbances associated with long-term administration of neuromuscular blocking agents militates against the routine use of these drugs in patients in intensive care, both children and adults. If muscle relaxants are given in this setting for more than a few hours, their effect should be monitored by a peripheral nerve stimulator to avoid overdose and drug accumulation. This may prove technically difficult in neonates.
Liver
Significant hyperbilirubinemia has been reported to occur more frequently in critically ill neonates given pancuronium than in a control group [ ]. The hyperbilirubinemia increased in the 4 days after withdrawal of pancuronium, whereas during the administration period the hyperbilirubinemia was less in the pancuronium group.
Autacoids
Histamine release and bronchospasm are relatively rare with pancuronium but have been reported [ ].
Body temperature
Malignant hyperthermia, possibly triggered by pancuronium, has been described [ ], although pancuronium is generally considered to be safe in patients who are susceptible to the syndrome [ ].
Second-generation effects
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