The Antioxidant Effect of Selenium on Succinylcholine-related Myalgia After Adult Sinuscopies: Randomized Controlled Double-Blind Trial.

BACKGROUND: Succinylcholine has a fast onset, short duration of action, and is considered the choice for rapid sequence intubation. However, it produces muscle stiffness and postoperative myalgia (POM) as adverse effects. We hypothesized that the antioxidant selenium might affect POM incidence and severity. OBJECTIVES: The study aimed to investigate the antioxidant effect of selenium (against free radicals' release) in minimizing the frequency of succinylcholine-related POM, measured by the 4-point myalgia score. The severity of fasciculations and the postoperative analgesic profile were recorded. The correlation between fasciculations and POM was also observed. STUDY DESIGN: A prospective randomized controlled double-blind clinical study. SETTING: Assiut University Hospitals. METHODS: The current study included 80 adult patients scheduled for sinuscopies and randomly assigned into 2 equal groups. Two hours before the induction of general anesthesia, patients in the control group received oral placebo tablets, while patients in the selenium group received oral selenium 200 µg. The primary outcome of this trial was the POM score at 24 hours. Secondary outcomes included the intensity of fasciculations, Numeric Rating Scale (NRS), rescue analgesic consumption, and adverse effects of the studied drugs. RESULTS: Myalgia scores were significantly decreased after selenium administration throughout the follow-up period (P = 0.023). No significant difference was reported regarding the incidence or degree of fasciculations (P = 0.511). A mild correlation was noticed between fasciculations and POM with r = 0.176 and P < 0.061. The NRS values were significant between groups at 6 hours after the procedure. There were significant differences (P < 0.05) regarding postoperative supplement analgesia, time to the first rescue analgesia, and the mean total number of analgesic claims. Significant differences were recorded for potassium levels only 30 minutes and creatine kinase levels at 6 and 24 hours postoperatively. LIMITATIONS: This study was applied on a single surgical category and other types of surgical procedures may have an effect on outcomes. Additional larger sample size studies and various doses of selenium may help to validate our results. Selenium is quite a significant element of the enzymatic antioxidant process through glutathione peroxidase. We did not measure the glutathione peroxidase level in blood. CONCLUSIONS: Oral selenium effectively reduced the succinylcholine-induced postoperative myalgia. It prolonged the time to first required analgesia and decreased the analgesic consumption throughout the whole study period without affecting the hemodynamics or any serious adverse effects.

Phenotype and genotype characteristics of 58 patients showing a prolonged effect of succinylcholine: A four-year experience.

INTRODUCTION: This study sought to describe the phenotype and genotype characteristics of patients referred to our laboratory to undergo further assessment due to a suspicion of a prolonged effect of suxamethonium attributed to BChE deficiency. METHODS: All patients referred to our laboratory from January 2016 to December 2019 due to the suspicion of a prolonged effect of suxamethonium were included in this study. The determination of BChE activity and genotyping using complete nucleotide sequencing of the entire complementary DNA-coding region with flanking intron-exon boundaries were completed. RESULTS: During this four-year period, 58 patients were referred to our laboratory for the investigation of prolonged neuromuscular block due to BChE deficiency. Among them, 52 showed a BChE deficiency related to BCHE gene mutations. The most commonly detected genotype was compound homozygous atypical variant (p.Asp98Gly)/homozygous Kalow variant (p.Ala569Thr) (p.[Asp98Gly;Ala567Thr];[p.Asp98Gly;Ala567Thr]). Further, we recorded four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea: p.(Trp205Cys), p.(Leu222His), p.(Glu469Gln), and p.(Lys276Ter). CONCLUSION: During a four-year period, among the 58 patients referred to our laboratory, we have found four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea (p.(Trp205Cys), p.(Leu22His), p.(Glu469Gln), and p.(Lys276Ter)).

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Rocuronium is more hepatotoxic than succinylcholine in vitro.

BACKGROUND: The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. OBJECTIVE: We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. DESIGN: In-vitro study. SETTING: A basic science laboratory, University Hospital Rostock, Germany. MATERIAL/(PATIENTS): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. INTERVENTIONS: After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. MAIN OUTCOME MEASURES: Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. RESULTS: Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. CONCLUSION: An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. TRIAL REGISTRATION: Not suitable.

Reversal of succinylcholine induced apnea with an organophosphate scavenging recombinant butyrylcholinesterase.

BACKGROUND: Concerns about the safety of paralytics such as succinylcholine to facilitate endotracheal intubation limit their use in prehospital and emergency department settings. The ability to rapidly reverse paralysis and restore respiratory drive would increase the safety margin of an agent, thus permitting the pursuit of alternative intubation strategies. In particular, patients who carry genetic or acquired deficiency of butyrylcholinesterase, the serum enzyme responsible for succinylcholine hydrolysis, are susceptible to succinylcholine-induced apnea, which manifests as paralysis, lasting hours beyond the normally brief half-life of succinylcholine. We hypothesized that intravenous administration of plant-derived recombinant BChE, which also prevents mortality in nerve agent poisoning, would rapidly reverse the effects of succinylcholine. METHODS: Recombinant butyrylcholinesterase was produced in transgenic plants and purified. Further analysis involved murine and guinea pig models of succinylcholine toxicity. Animals were treated with lethal and sublethal doses of succinylcholine followed by administration of butyrylcholinesterase or vehicle. In both animal models vital signs and overall survival at specified intervals post succinylcholine administration were assessed. RESULTS: Purified plant-derived recombinant human butyrylcholinesterase can hydrolyze succinylcholine in vitro. Challenge of mice with an LD100 of succinylcholine followed by BChE administration resulted in complete prevention of respiratory inhibition and concomitant mortality. Furthermore, experiments in symptomatic guinea pigs demonstrated extremely rapid succinylcholine detoxification with complete amelioration of symptoms and no apparent complications. CONCLUSIONS: Recombinant plant-derived butyrylcholinesterase was capable of counteracting and reversing apnea in two complementary models of lethal succinylcholine toxicity, completely preventing mortality. This study of a protein antidote validates the feasibility of protection and treatment of overdose from succinylcholine as well as other biologically active butyrylcholinesterase substrates.

Skin reactions to intradermal neuromuscular blocking agent injections: a randomized multicenter trial in healthy volunteers.

BACKGROUND: Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs). METHODS: One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs. RESULTS: The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice. CONCLUSION: The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.

Effects of high-dose propofol on succinylcholine-induced fasciculations and myalgia.

BACKGROUND: The purpose of this prospective study was to determine the effects of high-dose propofol on the incidence of fasciculations and myalgia, and to evaluate changes in creatine kinase levels following the administration of succinylcholine in 90 women who underwent laparoscopy. METHODS: Patients were randomly assigned to one of three groups. Induction of anesthesia was performed with thiopentone 5 mg kg(-1) in Group I (n = 30), propofol 2 mg kg(-1) in Group II (n = 30), and propofol 3.5 mg kg(-1) in Group III (n = 30). Then succinylcholine 1 mg kg(-1) was administered to the patients for intubation. RESULTS: Fasciculation was absent in 20% of Group III patients, and no vigorous fasciculation occurred in this group. Furthermore, the severity of fasciculation in Group III was significantly lower than in the other two groups (P = 0.01). Seventy per cent of patients had no myalgia in Group III, 39.2% in Group II and 37% in Group I (P = 0.007). Severity of myalgia was also significantly lower in Group III compared with the other two groups (P = 0.011). Post-operative creatine kinase levels were significantly higher than their baseline values in Groups I and II (P < 0.0001). CONCLUSION: Administration of propofol 3.5 mg kg-1 is effective in reducing fasciculations and myalgia after succinylcholine.

Choice of the muscle relaxant for rapid-sequence induction.

Muscle relaxants are given as part of a rapid-sequence induction to facilitate tracheal intubation. Among all the muscle relaxants available, succinylcholine is the only one with a fast (approximately equal to 1 min) onset and a fast recovery. Therefore it is still the most frequently used muscle relaxant for rapid-sequence induction despite its well-known side-effects. The short duration of action of succinylcholine is, however, no substitute for aggressive airway management in the case of an unexpectedly difficult intubation in order to prevent life-threatening hypoxia. A preoperative assessment of the airway is mandatory in any patient and may indicate the need for using intubation techniques without a muscle relaxant. Rocuronium in large doses (i.e. > or = 1 mg kg-1) is an alternative to succinylcholine in a classical rapid-sequence setting under relatively light anaesthesia. With respect to rapid tracheal intubation, the timing and priming principles offer little advantage over the use of rocuronium in doses of 0.6 mg kg-1 in combination with an appropriate induction technique (i.e. including an opioid) or over the use of larger doses of rocuronium (> or = 1.0 mg kg-1) under relatively light anaesthesia, and may even be potentially harmful. In contrast to rocuronium, the use of rapacuronium in a rapid-sequence setting has been associated with dose-dependent respiratory side-effects that limit its usefulness in doses higher than 1.5 mg kg-1 for this indication.

Malignant hyperthermia phenotype: hypotension induced by succinylcholine in susceptible swine.

BACKGROUND: Succinylcholine causes immediate and severe arterial hypotension in swine with the malignant hyperthermia phenotype. The underlying mechanisms are unknown. METHODS: Malignant hyperthermia-susceptible (MHS; n = 10) and normal swine (n = 5) were anesthetized with thiopental. The following were monitored: electrocardiogram; arterial blood pressure; pulmonary artery, central venous, and left and right ventricular pressure; cardiac output; end-tidal carbon dioxide; core temperature; peripheral-blood flows; and arterial blood gases. After a control period, 2 mg/kg succinylcholine was given intravenously. Three MHS animals received 1 mg/kg vecuronium and two MHS animals received 2.5 mg/kg dantrolene intravenously. The effects of succinylcholine on left and right ventricular pressure and contractility were analyzed in isolated hearts. The effects of 0.06 mm succinylcholine on isometric tension development were recorded in isolated femoral artery rings. RESULTS: Succinylcholine caused an early, severe decrease in blood pressure, cardiac output, left ventricular pressure, and left ventricular contractility in MHS swine but not in normal swine; no significant differences were found in heart rate, right ventricular parameters, systemic vascular resistance, and preload (pulmonary diastolic pressure, central venous pressure). The succinylcholine-induced hypotension and associated effects were not prevented by dantrolene. However, pretreatment with high-dose vecuronium prevented not only the cardiovascular depression, but also MH. In addition, no phenotypic differences of succinylcholine on contractility or left ventricular pressure were observed in the isolated working hearts. Similary, succinylcholine did not cause a significantly different relaxation in rings in either phenotype. CONCLUSION: Succinylcholine-induced hypotension occurred before muscle hypermetabolism in MHS swine. Succinylcholine had no differential physiologic effects on either the isolated heart or on isolated arteries. This hypotension could not be prevented by dantrolene but was prevented by pretreatment with high-dose vecuronium. Thus, an indirect mechanism such as the release of a cardiac depressant from skeletal muscle may have caused this hypotensive response.

Clinical pharmacology of neuromuscular blocking agents.

The clinical pharmacology of neuromuscular blocking agents is described. During neuromuscular blockade, succinylcholine attaches to receptors in the motor end plate and depolarizes the neuromuscular junction, making the end plate refractory to acetylcholine. The nondepolarizing relaxants have a structure similar to that of succinylcholine and bind to the same receptors. Instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade. As the concentration of nondepolarizing relaxant increases relative to acetylcholine, neuromuscular transmission is compromised. This relationship is used clinically to facilitate recovery from nondepolarizing agents. Succinylcholine is popular because its onset is faster than that of the nondepolarizing relaxants and metabolism by pseudocholinesterase clears it quickly. It is commonly given as an i.v. bolus to facilitate tracheal intubation. The onset of these agents varies widely and is dose dependent. Large doses are usually given to hasten the onset of paralysis; subsequent doses are adjusted according to response. The nondepolarizing agents interact with inhaled anesthetics, magnesium, and many antimicrobials. Drugs like neostigmine, edrophonium, and pyridostigmine antagonize neuromuscular blockade; an anticholinergic drug is typically administered to counteract the cardiovascular effects. The most serious adverse effects of succinylcholine are malignant hyperthermia syndrome, masseter muscle rigidity, and bradycardia. Some nondepolarizing relaxants (atracurium, mivacurium, and pancuronium) are associated with histamine release, occasionally causing serious hypotension and tachycardia. Neuromuscular blocking agents are essential to anesthesia. Older compounds produce greater toxicity than newer compounds, and several of these older compounds therefore are no longer in clinical use.

Continuous propofol administration for suxamethonium-induced postoperative myalgia.

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).

Variation of serum potassium and creatinine phosphokinase levels in suxamethonium-induced muscle relaxation.

Popular depolarising muscle relaxant, suxamethonium (succinylcholine chloride), produces fasciculation in group of muscles and 'after pain'. Mode of its action is neuromuscular blockage. It also may be associated with muscle fibre injury and altered membrane permeability. These may cause rise of serum K+ and creatinine phosphokinase (CPK) levels. But use of diazepam either during or as pretreatment may reduce the fasciculation, 'after pain' and rise of K+ and CPK levels. Present study was undertaken to show whether any correlation of the degree of fasciculation and postsuxamethonium myalgia is present or not and whether diazepam has any role in reducing muscle injury and in turn reducing the levels of serum K+ and CPK.

Pharmacodynamics of high-dose vecuronium in children during balanced anesthesia.

To compare the speed of onset, intubating conditions, duration of action, and recovery from neuromuscular blockade with vecuronium to those with succinylcholine, 40 ASA physical status 1 or 2 children (ages 2-9 yr) were studied during N2O-O2-opioid anesthesia. Each child was randomly assigned to receive a bolus dose of one of the following muscle relaxants: succinylcholine 2.0 mg/kg (n = 10), vecuronium 0.1 mg/kg (n = 10), vecuronium 0.2 mg/kg (n = 10), or vecuronium 0.4 mg/kg (n = 10). The evoked electromyogram of the abductor digiti minimi to train-of-four stimulation was monitored. We found that with succinylcholine, the time to 95% twitch depression (speed of onset, mean +/- SD), 24 +/- 7 s, was significantly less than that with each dose of vecuronium: 0.1 mg/kg, 83 +/- 21 s; 0.2 mg/kg, 58 +/- 17 s; and 0.4 mg/kg, 39 +/- 11 s, respectively (P less than 0.05). The time to laryngoscopy and intubation did not differ significantly between succinylcholine (48 +/- 10 s) and vecuronium 0.4 mg/kg (57 +/- 13 s); however, both were significantly less than than with vecuronium 0.1 and 0.2 mg/kg (P less than 0.005). The intubating conditions were excellent in 100% of patients. The duration of action was least with succinylcholine (5.7 +/- 1.5 min) and increased with increasing doses of vecuronium: 0.1 mg/kg, 23.9 +/- 5.1 min; 0.2 mg/kg, 55.2 +/- 11.6 min; and 0.4 mg/kg, 74.6 +/- 9.9 min, respectively (P less than 0.001). The recovery index was most rapid with succinylcholine (1.6 +/- 0.4 min) and was slowest with vecuronium 0.4 mg/kg (22.6 +/- 2.1 min) (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Complications during anaesthesia in patients with Duchenne's muscular dystrophy (a retrospective study)

The purpose of this retrospective study was to estimate the frequency and severity of anaesthetic complications in patients with Duchenne's muscular dystrophy (DMD). Forty-four boys with DMD were exposed to anaesthesia and surgery 84 times during a period of 22 years (1965-86). The procedures took place at 15 different hospitals. Retrospective examination of the case records showed: 19 cases with local analgesia without any complications, and 18 of 65 general anaesthetics with minor or more serious complications. In ten cases an increase in body temperature above 37.5 degrees C was seen, five had abdominal pain and dark-coloured urine after surgery, and three had a critical perioperative course with a resemblance to malignant hyperthermia. The complications were almost exclusively related to the use of succinylcholine. The use of succinylcholine was dispersed through all ages. Three out of the eight patients with severe complications occurred 1.5, 2.5 and 4 years before the neuromuscular disease was diagnosed. Thus an unusual course of anaesthesia in male children calls for further investigation. Although it has been stated before that succinylcholine is contraindicated in patients with Duchenne's muscular dystrophy, the drug continues to be used.

Myalgia in outpatient surgery: comparison of atracurium and succinylcholine.

We studied 60 outpatients randomly divided into two groups. Anesthesia was induced with fentanyl 1.5 micrograms.kg-1 plus thiopentone 5-7 mg.kg-1. Patients in Group I were intubated with the aid of succinylcholine 1.5 mg.kg-1 after pre-treatment with d-tubocurarine 0.05 mg.kg-1. Group II received atracurium 350 micrograms.kg-1 three minutes after a priming dose of 50 micrograms.kg-1. Anesthesia was maintained with isoflurane 1-2 per cent in a mixture of nitrous oxide 60 per cent and oxygen 40 per cent. No supplemental doses of fentanyl or atracurium were given. Intubation conditions were satisfactory for all patients in both groups. There was no significant difference in intubation score between the two groups. The incidence of myalgia was 76 per cent in the succinylcholine group compared to 23 per cent in the atracurium group (p less than 0.005). Fifty per cent of the patients in the succinylcholine group had myalgia necessitating bed rest or analgesics compared to 23 per cent in the atracurium group (p less than 0.05). We conclude that atracurium is a suitable neuromuscular relaxant for outpatient surgery and that myalgia is a major morbidity factor in this population that can be reduced by the use of atracurium instead of succinylcholine.

Side effects and changes in pulmonary function after fixed dose precurarization with alcuronium, pancuronium or vecuronium.

On hundred and sixty premedicated patients undergoing surgery were assessed for changes in pulmonary function and signs of partial neuromuscular blockade following precurarization with a fixed dose of alcuronium 2 mg, pancuronium 1 mg or vecuronium 1 mg, and the efficacy of the drugs in the prevention of suxamethonium-associated side effects was compared. In this respect, no differences were observed between the three drugs. Pretreatment with alcuronium and pancuronium was followed by small decreases in pulmonary function. Statistically significant changes were seen only when vecuronium 1 mg was used as the fixed-dose precurarization agent.

["Self-taming": an alternative to the prevention of succinylcholine-induced pain]. / "Self-taming": Eine Alternative zur Prophylaxe des durch Succinylcholin induzierten Schmerzes.

Muscle pain associated with single-bolus administration of suxamethonium is reported to be one of the common complications of this technique. Since suxamethonium is the most commonly used relaxant in our department and priming with nondepolarizing muscle relaxants is also reported to be linked with complications, while the literature concerning this problem is very contradictory, we wondered if the so-called "self-taming" method represents an alternative to pretreatment with nondepolarizing muscle relaxants. One hundred thirty-two patients (69 male, 63 female) were randomly allocated to three groups. Anesthesia was induced with thiopentone 7 mg/kg body weight. Group 1 (n = 44) was pretreated with 2 mg pancuronium bromide 3 min prior to full relaxation with suxamethonium 1.5 mg/kg. Group 2 (n = 43) received no pretreatment. Group 3 (n = 45) received 4 mg suxamethonium i.v. after induction. One minute later the remaining dose of suxamethonium was applied ("self-taming"). Muscle fasciculation and postoperative myalgia were verified by means of a score. Neuromuscular transmission was recorded on a monitor after controlled train-of-four stimulus and time of onset of neuromuscular blockade was measured. With regard to muscle fasciculation, postoperative pain, and onset of neuromuscular blockade, "self-taming" with suxamethonium yielded results identical to pretreatment with pancuronium bromide. It may therefore be considered as an alternative to pretreatment with nondepolarizing muscle relaxants.

Clinical pharmacology of muscle relaxants in patients with burns.

Pathophysiologic changes accompanying burn trauma can alter the pharmacokinetics and pharmacodynamic responses to neuromuscular relaxants. Pathophysiologic changes that can potentially affect kinetics in the hypermetabolic phase of burn injury include increased hepatic blood flow, increased glomerular filtration, and increased protein binding. Except for D-tubocurarine, the pharmacokinetics of neuromuscular relaxants relative to burn trauma have not been studied. The unbound volume of distribution, clearance, and half-life of D-tubocurarine were not significantly different from controls, but the plasma binding and renal elimination at 24 hours was increased in burn patients. The aberrant pharmacodynamic responses to neuromuscular relaxants in burn patients include the potential for lethal hyperkalemia with the administration of depolarizing relaxant, succinylcholine, and a 2.5- to 5.0-fold increase in the dose or plasma concentration requirement for nondepolarizing relaxant, including D-tubocurarine, metocurine, pancuronium, and atracurium. The altered pharmacodynamic responses are probably related to an increase in nicotinic acetylcholine receptor number. An alternative to succinylcholine to produce rapid-onset neuromuscular paralysis include the administration of 3XED95 doses of pancuronium and metocurine in combination (but recovery from paralysis is prolonged). Vecuronium and atracurium have good cardiovascular stability and faster recovery times even in high dosages in healthy patients, but the pharmacokinetics and pharmacodynamics of these drugs in patients with burns have not been fully characterized.