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Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.

In a randomised double-blind trial carried out on fit, unpremedicated patients undergoing standard minor operations with early postoperative mobility, using a standard form of anaesthesia, pretreatment with diazepam 0.15 mg/kg or midazolam 0.1 mg/kg failed to reduce significantly the incidence of postoperative muscle pains following suxamethonium 1 mg/kg. By contrast, tubocurarine 0.05 mg/kg proved to be effective as a pretreatment. Neither benzodiazepine influenced the incidence or severity of fasciculations seen with suxamethonium or the duration of neuromuscular block. Tubocurarine virtually abolished visible fasciculation and, in the dose used, reduced the intensity and duration of the neuromuscular block. There were no clinically significant changes in serum potassium, creatinine phosphokinase or aldolase after suxamethonium, although 5 out of 47 showed an atypical rise in creatinine phosphokinase.

Summary We have investigated the possibility of using the pre-operative measurement of cholinesterase activity to predict the postoperative development of myalgia following the administration of suxamethonium. Seventy-seven patients presenting for elective extraction of wisdom teeth were entered in the study. All patients received a standard anaesthetic regimen, including suxamethonium to facilitate tracheal intubation, and standardised postoperative analgesia. Myalgia was assessed postoperatively and no correlation between muscle pains and cholinesterase activity was found.

Summary Mivacurium chloride has been assessed in respect of intubating conditions and neuromuscular effects. The influence of suxamethonium on the onset and duration of subsequently administered mivacurium was also studied. A dose of 0.15 mg.kg−1 of mivacurium was found to provide unacceptable intubating conditions at 2 min in 9/9 patients and further studies were conducted using 0.2 mg.kg−1. Intubating conditions with this dose were acceptable in 65% and 80% of patients at 2 min and 2.5 min respectively. In comparison, intubating conditions were acceptable in 100% of patients at 1 min following 1 mg.kg−1 of suxamethonium. The onset of block occurred in 96 s and 97 s after 0.15 mg.kg−1 and 0.2 mg.kg−1 respectively, and the durations of block in terms of recovery of the first twitch (T1) to 25% and 90% of control, and to recovery of train-of-four ratio to 0.7, were 16.1 and 17.9; 24.1 and 25.8; and 24.2 and 27.0 min respectively with the two doses. The time for the onset of complete block with suxamethonium 1.0 mg.kg−1 was 50 s and the times to 25% and 90% recovery were 9.8 min and 13.3 min. The differences between suxamethonium and both doses of mivacurium were significant (p < 0.05) but there were no significant differences between the two doses of mivacurium in any of the neuromuscular measurements. Prior administration of suxamethonium had no influence on the effects of mivacurium. Cutaneous flushing was observed in 30 out of 75 patients but this was associated with transient hypotension in only two patients. Our results show mivacurium to have a duration of action approximately half that of comparable doses of the intermediate acting relaxants atracurium and vecuronium.

Summary Sixty ASA 1 and 2 children aged between 2 and 16 years who required tracheal intubation as part of anaesthesia for elective surgery were studied. We evaluated intubating conditions, haemodynamic responses and duration of apnoea following propofol 4 mg.kg−1 combined with either remifentanil 1.25 μg.kg−1 (group R), or suxamethonium 1 mg.kg−1 (group S). Tracheal intubation was graded as excellent, good or poor according to ease of laryngoscopy, vocal cord position, coughing, and jaw relaxation and limb movement. Thirty of group S and 28 of group R children were successfully intubated on the first attempt. Overall, intubation conditions were excellent or good in 26/30 (87%) patients in group S and 20/30 (67%) in group R (p

The use of mini-dose suxamethonium to facilitate the insertion of a laryngeal mask airway was investigated. Sixty patients were assigned randomly in a double-blind manner to receive 0.9% sodium chloride or suxamethonium 0.1 mg.kg−1 intravenously, following intravenous induction with propofol 2.5 mg.kg−1. The laryngeal mask was inserted after the first attempt in 87% of patients. Mini-dose suxamethonium improved the correct positioning of the laryngeal mask during the first attempt (93 vs. 67%, p < 0.02), decreased the incidence of swallowing (p < 0.001), gagging (p < 0.001) and head or limb movement (p < 0.05). Laryngeal mask insertion was graded as easy in 93% of patients who had mini-dose suxamethonium, compared with 60% in the placebo group (p < 0.01). The duration of apnoea between the two groups was not significantly different (0.54 vs. 0.61 min, p = 0.46). The total dose of propofol needed to insert the laryngeal mask was lower in the suxamethonium group (2.57 vs. 3.25 mg.kg−1, p < 0.01) and was associated with less hypotension (p < 0.05). Fasciculation (17%) and mild myalgia (23%) were common despite the small dose of suxamethonium used. In conclusion, mini-dose suxamethonium facilitates laryngeal mask insertion. Myalgia is common and the technique is not recommended for patients who are prone to suxamethonium myalgia.

A prospective study is described of peri-operative dreaming in 144 paediatric patients aged 5-14 years who received suxamethonium for day case surgery. No case of awareness was elicited. One group received pretreatment with 80 micrograms/kg [corrected] tubocurarine. The incidence of dreaming in the 72 patients who were not pretreated was 16.7% compared with 2.8% in the patients pretreated with tubocurarine. This difference is statistically significant. The use of an intermittent suxamethonium technique gives a high incidence of dreaming which may be caused by muscle spindle discharge that produces cerebral arousal. Pretreatment with a non-depolarizing agent decreases this risk of dreaming.

Forty patients without eye disease, undergoing elective nonophthalmic surgery, were studied in a double-blind, randomised, placebo-controlled study evaluating the efficacy of mivacurium pretreatment in attenuating the rise in intra-ocular pressure in response to suxamethonium administration, laryngoscopy and intubation. The patients were randomly allocated to receive either mivacurium 0.02 mg.kg-1 or normal saline as pretreatment 3 min before a rapid sequence induction technique using alfentanil, propofol and suxamethonium. Suxamethonium induced a significant increase in intra-ocular pressure in the control group but not in the mivacurium pretreatment group (mean (SEM) increase = 3.5 (1.2) mmHg vs. 0.4 (0.8) mmHg, p < 0.05). There was a decrease in intra-ocular pressure in both groups after laryngoscopy and intubation with no significant difference between the two groups. These results show that mivacurium pretreatment is effective in preventing the increase in intra-ocular pressure after suxamethonium administration.

A parturient presented for elective caesarean section with a history of multiple spinal operations and scoliosis and a biochemical diagnosis of suxamethonium apnoea. She declined any attempt at regional anaesthesia. We describe the use of a thiopental/remifentanil technique to relax the larynx and provide rapid and excellent conditions for laryngoscopy and tracheal intubation. The parturient awoke following an uneventful caesarean section with excellent pain relief and no recall. The baby had normal Apgar scores and umbilical blood gas measurements.

Summary Tubocurare (0.125 mg.kg-1 or 0.25 mg.kg-1) was injected 10 s before 1 mg.kg-1 suxamethonium in patients anaesthetised with enflurane 1–1.5%. Measurement of electromyographic response was recorded using a 0.2 Hz train-of-four every 20 s. The modified blocks were slower in onset, of lesser intensity, and of shorter duration than that of suxamethonium alone, but were much closer to those of suxamethonium than of tubocurare. However, the train-of-four fade observed during onset of the modified blocks were similar to that of their tubocurare controls and significantly different from the suxamethonium group. We conclude that effective amounts of tubocurare are present in the neuromuscular junction within the 30 s following intravenous injection of the drugs, and this affects the onset of action of the suxamethonium block. The presence of train-of-four fade during a predominantly agonist block is difficult to explain on the basis of diminished acetylcholine release and a postsynaptic site of action of suxamethonium.

This study investigates the effect of suxamethonium vs rocuronium on the onset of haemoglobin desaturation during apnoea, following rapid sequence induction of anaesthesia. Sixty patients were randomly allocated to one of three groups. Anaesthesia was induced with lidocaine 1.5 mg.kg(-1), fentanyl 2 microg.kg(-1) and propofol 2 mg.kg(-1), followed by either rocuronium 1 mg.kg(-1) (Group R) or suxamethonium 1.5 mg.kg(-1) (Group S). The third group received propofol 2 mg.kg(-1) and suxamethonium 1.5 mg.kg(-1) only (Group SO). The median (IQR [range]) time to reach S(p)O(2) of 95% was significantly shorter in Group S (358 (311-373 [245-430]) s) [corrected] than in Group R (378 (370-393 [366-420]) s; p = 0.003), and shorter in Group SO (242 (225-258 [189-270]) s) [corrected] than in both Group R (p0.001) and Group S (p0.001). When suxamethonium is administered for rapid sequence induction of anaesthesia, a faster onset of oxygen desaturation is observed during the subsequent apnoea compared with rocuronium. However, time to desaturation is prolonged whenever lidocaine and fentanyl precede suxamethonium.

Upper oesophageal sphincter pressure was recorded with a Dent sleeve in 30 patients breathing nitrous oxide, oxygen and halothane. Twenty-three patients, after thiopentone induction, received suxamethonium and had their trachea intubated either before (group A, n = 11), or after (group B, n = 11), a study period of inhalational anaesthesia. Group C (n = 8) received an inhalational induction. Mean (SD) sphincter pressure after loss of consciousness was 8 (7) mmHg (group A), 6 (5) mmHg (group B) and 24 (13) mmHg (group C) increasing to 19 (7) mmHg in group A immediately after intubation. With an end-tidal halothane concentration of 1.5%, mean sphincter pressure in group B, 16 (7) mmHg, was significantly lower than in group A, 45 (21) mmHg (p < 0.001) and group C, 27 (14) mmHg (p < 0.05). Halothane had no dose-related effect on sphincter pressure. Insertion of a laryngeal mask in group C (n = 7) had no significant effect on sphincter pressure. Induction and maintenance of anaesthesia with halothane, unlike thiopentone or suxamethonium, maintained a degree of upper oesophageal sphincter tone, although three patients in this study had sphincter pressures of less than 10 mmHg and would therefore have been at risk of regurgitation in the presence of gastro-oesophageal reflux.

No drugs in anaesthesia are more problematic than suxamethonium. Yet, no drugs have survived as suxamethonium does in spite of crisis after crisis, and attempt after attempt at its replacement. For decades, suxamethonium has taught us neuromuscular pharmacology and provided us with an encyclopaedia of side effects, while benefiting millions and millions of our anaesthetised patients. With the arrival of sugammadex, it finally appears that suxamethonium can be retired. Suxamethonium has done its job and seen its days! The present review is intended to offer a eulogy for suxamethonium.

Summary An acute episode of a malignant hyperthermia-like syndrome is described which occurred after suxamethonium and isoflurane anaesthesia in a 41-year-old healthy male patient undergoing a minor elective hand operation. Dantrolene therapy rapidly reversed the life-threatening signs. Laboratory results appeared to confirm the suspicion of malignant hyperthermia. However, the in vitro contracture test, which was carried out according to the standards of the European Malignant Hyperthermia Group, was equivocal.

Summary In a double-blind study, 67 young adult patients undergoing anaesthesia for dental extractions were allocated at random to receive either 0.5 mg/kg or 1.5 mg/kg suxamethonium. A greater increase in arterial pressure was seen following induction in the 1.5 mg/kg group, although overall intubating conditions were similar in the two groups. Suxamethonium-associated muscle pains were significantly more common in the group which received the larger dose (p>0.05).

The three currently available paper radioallergosorbent tests ('suxamethonium', alcuronium and thiopentone) were evaluated. 'Suxamethonium' radioallergosorbent test (which employs choline conjugated to paper discs) proved to be reliable in the detection of allergy to neuromuscular blockers, which were confirmed as the most common cause of anaphylactic reaction during general anaesthesia. Thiopentone radioallergosorbent test may also be useful, and is recommended in conjunction with 'suxamethonium' radioallergosorbent test in the preliminary investigation of reactions. Patients with positive 'suxamethonium' radioallergosorbent test usually require further testing, including alcuronium radioallergosorbent test, skin testing with a wide range of drug concentrations or leucocyte histamine release test.

The neuromuscular block of successive doses of suxamethonium 100 mg, monitored by electromyography, was investigated in a myasthenic patient (class IIB), undergoing thymectomy. The results suggest that successive doses of suxamethonium in the myasthenic patient are followed by a progressive prolongation of the neuromuscular block. This may be attributed to rapid desensitisation of the myasthenic endplate receptors and the rapid development of phase II block, as evidence by a progressive decrease of the T4/T1 ratio.

The incidence and severity of muscle pains and changes in creatine kinase were assessed following administration of 1 mg.kg-1 suxamethonium either immediately or 2 min after induction of anaesthesia with propofol or thiopentone in patients undergoing elective dental and ophthalmic surgery. The incidence of muscle pains was 35 and 60% respectively in the groups given suxamethonium immediately and 2 min after propofol, and 35 and 55% when given immediately and 2 min after thiopentone, with no statistically significant differences among the groups. Creatine kinase levels increased in all the groups after operation with the least average increase in the group receiving suxamethonium immediately after propofol and the highest increase in the group receiving suxamethonium 2 min after thiopentone. There was no correlation between the incidence and severity of fasciculations, muscle pains and changes in creatine kinase within or between the groups. It is concluded that neither the induction agent nor the time between the induction agent and suxamethonium administration has any significant influence on the incidence of muscle pains or creatine kinase elevation following suxamethonium.

The neuromuscular block of suxamethonium 1.5 mg.kg-1 was investigated in three myasthenic patients (Class IIA), undergoing thymectomy. Two of the patients were receiving pre-operative pyridostigmine therapy. In the three patients, plasma cholinesterase activity was determined on the morning of surgery and was correlated with the neuromuscular response to suxamethonium as monitored by electromyography. The results suggest that the response to suxamethonium in the myasthenic patients can show wide variations according to the level of their plasma cholinesterase activity. The degree and duration of suxamethonium block is inversely related to the plasma cholinesterase activity.

Summary Thirtv patients received topical application of either timolol ophthalmic solution 0.25%, or normal saline, 2 h before elective ophthalmic surgery in a double-blind study. The responses to suxamethonium and tracheal intubation were compared by measuring intra-ocular pressure before induction of anaesthesia, 1 mm after administration of thiopentone 2–4 mg·kg−1 min after administration of suxamethonium 1 mg·kg−1, and I, 2.5 and 5 min after tracheal intubation. There was no significant difference between the groups.

The effect of continuous propofol administration on creatine kinase and suxamethonium-induced postoperative myalgia was evaluated in 50 patients randomised into two groups of 25 patients each. Induction of anaesthesia was identical in all patients. Anaesthesia was maintained with 66% nitrous oxide in oxygen supplemented by either isoflurane 1% or continuous propofol. Creatine kinase was measured before and after operation. Myalgia was evaluated postoperatively by a blinded observer. The median level of myalgia was reduced significantly in the continuous propofol group (p = 0.011). The median creatine kinase value increased significantly in the isoflurane group (from 90 to 160 IU, p = 0.001).

The subject of postoperative myalgia associated with the use of succinylcholine is reviewed. We discuss the mechanisms of succinylcholine-induced myalgia and the techniques available to prevent and treat the myalgia. In situations where patients are at risk of developing myalgia and succinylcholine is the neuromuscular blocker of choice, the use of a combination of techniques may prove to be a useful strategy.

Summary A period of apnoea lasting 480 minutes following suxamethonium in a 6-week-old male infant is described. Neuromuscular function recovered following the administration of fresh frozen plasma. The infant was found to be homozygous for atypical cholinesterase (E1a E1a). This is believed to be the youngest reported case of suxamethonium apnoea.

A cumulative dose followed by an infusion was used to determine the dose response to suxamethonium in a patient with diagnosed myasthenia gravis who was in true remission (asymptomatic while receiving no therapy). The ED50 and ED90 values for suxamethonium were 0.08 mg/kg and 0.20 mg/kg, and an infusion rate of 3.2 mg/kg/hour was required to maintain a 90-95% depression of the single twitch response as monitored by integrated electromyography. These values are within the range for normal patients, and we conclude that myasthenic patients during a true remission may not demonstrate resistance to suxamethonium.

Sixty ASA physical status I and II, premedicated patients were administered propofol 2 mg x kg-1 and remifentanil 2 microg x kg-1 (group R), alfentanil 50 microg x kg-1 (group A) or suxamethonium 1 mg x kg-1 (group S) as a rapid bolus. One minute after study drug administration, tracheal intubation was performed. Intubation conditions were then scored. Excellent or good conditions were observed in only 35% in group R compared with groups S and A (100% and 85%, respectively; p0.001). The haemodynamic response to tracheal intubation was blunted in groups R and A compared with group S (p0.001). The mean heart rate in groups R and A was significantly lower than group S (p0.001). We conclude that remifentanil 2 microg x kg-1 given as a rapid bolus will not produce intubating conditions as good as those obtained with alfentanil 50 microg x kg-1 or suxamethonium 1 mg x kg-1 if administered after propofol 2 mg x kg-1.

A fit 36-year-old parturient received a general anaesthetic for manual removal of a retained placenta. She underwent rapid sequence induction of anaesthesia with suxamethonium, shortly followed by 10 mg of mivacurium. One hour later she had failed to establish adequate ventilation despite administration of drugs to reverse neuromuscular blockade. A provisional diagnosis of suxamethonium-related apnoea was made and her lungs were ventilated overnight on the Intensive Care Unit. Plasma cholinesterase levels at the time were reduced to one-third of normal, with normal dibucaine and fluoride numbers. One month later her levels were back within the reference range.

This study was designed to compare the tracheal intubating conditions during a rapid sequence induction of anaesthesia using rocuronium 0.6 (n = 61) or 1.0 mg.kg-1 (n = 130) or suxamethonium 1.0 mg.kg-1 (n = 127) as the neuromuscular blocking drugs. Anaesthesia was induced with fentanyl 1-2 micrograms.kg-1 and thiopentone 5 mg.kg-1 (median dose) and intubating conditions were assessed 60s after the administration of the neuromuscular blocking drug by an observer unaware of which drug had been given. Intubating conditions were graded on a three-point scale as excellent, good or poor, the first two being considered clinically acceptable. The study was carried out in two parts. At the end of the first part a comparison between the two doses of rocuronium was carried out when at least 50 patients had been enrolled in each group. The results showed the intubating conditions to be significantly superior with the 1.0 mg.kg-1 dose of rocuronium (p < 0.01). Final comparison between the 1.0 mg.kg-1 doses of rocuronium and suxamethonium showed no significant difference in the incidence of acceptable intubations (96 and 97%, respectively). The incidence of excellent grade of intubations was, however, significantly higher with suxamethonium (80% vs. 65%; p = 0.02). It is concluded that rocuronium 1.0 mg.kg-1 can be used as an alternative to suxamethonium 1.0 mg.kg-1 as part of a rapid sequence induction provided there is no anticipated difficulty in intubation. The clinical duration of this dose of rocuronium is, however, 50-60 min.