The depolarization of the motor end-plate receptors produced by suxamethonium (either directly or via repetitive discharge generation by the motor nerve terminals) (40) results in generalized and desynchronized contraction of skeletal muscle fibers. These fasciculations result in aching muscle pain (in up to 90% of patients), most commonly in the neck, pectoral region, shoulders, and back. The pain is most often experienced the day after operation and is worse in ambulatory patients. It is more common in women than in men. Children, elderly patients, athletes, and pregnant women (41) complain less often. Africans also seem to be less susceptible (42).
The cause of the pain is unknown, although there are many hypotheses such as damage to muscle (43,44) resulting from asynchronous contractions of adjacent muscle fibers (45), irreversible damage to muscle spindles (46), potassium flux (47), lactic acid (48), serotonin (49), calcium influx-associated damage to muscle spindles (50), and prostaglandins (51,52). The pain appears not to be related to the extent or intensity of the observed fascicu-lations.
Various preventive measures have been recommended, but none is effective in all cases. One reliable method is the injection of a small non-paralysing dose of a non-depolarizing neuromuscular blocker 2-3 minutes before the injection of suxamethonium (53-57) in preventing fasciculations, but the patient must be carefully observed, since an unexpected degree of paralysis occasionally ensues (SEDA-6,130).
Other measures, much disputed, include the prior injection of diazepam (58,59), procaine or lidocaine (57), vitamin C, suxamethonium itself (10 mg), and aspirin (51,52). The combined use of atracurium 0.05 mg/kg and lidocaine 1.5 mg/kg reduced the incidence of postoperative myalgia to 5% compared with 75% in controls (57). Thiopental, injected immediately beforehand, is also said to have some effect, as is giving the suxamethonium slowly.
Rarely, on injecting suxamethonium, contracture, instead of the usual relaxation, of skeletal muscles ensues. In denervated muscles the postulated mechanism is direct activation of the contractile mechanism by suxametho-nium because of the widespread chemosensitivity of the muscle fiber membranes.
Paradoxical contracture is most often associated with myo-tonia dystrophica and myotonia congenita. A myotonic reaction has also been reported in a patient with hyperkalemic periodic paralysis (60). Suxamethonium is therefore contra-indicated in these conditions, even though normal responses are sometimes seen. Contracture has also been reported as a result of denervation in Pancoast's syndrome and after plexus injuries and, rarely, in patients with amyotrophic lateral sclerosis or multiple sclerosis (61-63).
Failure of relaxation and generalized muscular rigidity after suxamethonium is sometimes also seen in patients who develop the syndrome of malignant hyperthermia. Isolated masseter muscle rigidity can occur after the administration of suxamethonium, being reported particularly in children given both suxamethonium and halothane. Most experts define masseter muscle rigidity as a major increase in masseter muscle tone severe enough to make mouth opening impossible and to prevent laryngoscopy and endotracheal intubation. Referring to the high incidence of positive results with halothane-caffeine contracture testing, some believe that up to 50% of patients with masseter muscle rigidity are susceptible to malignant hyperthermia (64-67). Others are not convinced of such a high degree of correlation (68) and hold that divers other factors are responsible for the majority of cases (69-71). While severe masseter muscle rigidity is rare (72), smaller increases in jaw tension of about 60 seconds duration occur almost invariably after suxamethonium administration (73,74). Such increases in masseter muscle tone can be attenuated by using propofol as an induction agent and by precurarization, that is pre-treatment with a small dose of a non-depolarizing muscle relaxant (74) This might be important during rapid sequence induction of anesthesia.
A hypothesis has been offered to explain muscle hyper-excitability in response to suxamethonium (75). Voltage clamp experiments on alpha subunits of human muscle sodium channels, heterologously expressed in HEK 293 cells, showed that succinic acid, a metabolite of suxamethonium, shifted steady-state activation in the direction of more negative membrane potentials. The EC50 for this effect was 0.39mmol/l. This might lead to muscle hyperexcitability in vivo. Clearly, it is not currently possible to claim any direct clinical implications of this study, but two facts should be considered. After the administration of a routine dose of suxamethonium, blood concentrations of 0.17mmol/l have been reported (76) Thus, equimolar concentrations of succinic acid are to be expected, given that cholinesterase activity is not impaired. Moreover, succinic acid is a citric acid cycle intermediate, ubiquitous in body tissues. In conditions of ischemia and hypoxia, tissue and serum concentrations of succinic acid increase up to 0.2 mmol/l (77,78). Thus, the administration of suxamethonium to a hypoxic patient may well lead to succinic acid concentrations that affect muscle sodium channel excitability in vitro.
Myoglobinuria (79) and raised serum creatine kinase activity (44) have been reported after suxamethonium and appear to be evidence of muscle damage, probably resulting from fasciculation. Repeated bolus doses of suxamethonium result in higher plasma myoglobin concentrations (80) and creatine kinase activities (44). Myoglobinemia seems to be much more common in children than in adults (SEDA-10,107) (SEDA-11,121) (81) and is more marked when halothane is used (82). On occasion, myoglobinuria results in renal insufficiency (83-88).
There is an association between (latent) muscular dystrophy (usually of the Duchenne or Becker type) and the production of rhabdomyolysis by suxametho-nium (84,85,89,90). Suxamethonium can cause excessive muscle damage in these patients, as manifested not only by severe myoglobinemia and raised serum creatine kinase activity but also by acute exacerbation of muscle weakness postoperatively (SEDA-11, 121) (7,29,84,91,92). Massive potassium release can result in hyperkalemic cardiac arrest. Such patients may also develop features suggestive of the syndrome of malignant hyperthermia (93,94). Suxamethonium should not be used in patients with Duchenne muscular dystrophy or who have a family history suspect for the condition.
Prolonged paralysis can result from idiosyncrasy, overdose, or reduced or abnormal plasma cholinesterase activity. There are geographical and racial differences in sensitivity to suxamethonium (SEDA-6, 129) (95,96); some of these differences arise from dietary and other environmental factors and others result from variations in plasma cholinesterase genotypes. Genotypically normal patients may be paralysed by a usual (1 mg/kg) dose of suxamethonium for as short a time as 2 minutes or (rarely) as long as 20 minutes, and the duration in general inversely reflects plasma cholinesterase activity (97).
Prolonged paralysis after suxamethonium has also been reported in von Recklinghausen's disease (98), but resistance to suxamethonium has also been seen (4).
Was this article helpful?