A Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine.

BACKGROUND: New therapies are created to address specific problems and enjoy popularity as they enter widespread clinical use. Broader use can reveal unknown adverse effects and impact the life cycle significantly. Succinylcholine, a depolarizing neuromuscular blocker, was the product of decades of research surrounding the ancient compound, curare. It was introduced into practice in the 1950s by Burroughs Wellcome and Company (BW Co) and was welcomed due to its rapidly acting muscle relaxation effects. Global clinical use revealed adverse effects, both minor and major, in particular, hyperkalemia and malignant hyperthermia. We investigated when practitioners and the manufacturer became aware of these adverse effects, how information about these side effects was disseminated, and whether the manufacturer met the regulatory requirements of the time, specifically regarding the timely reporting of adverse effects. SOURCES: Primary literature search using online and archived documents was conducted at the Wood Library-Museum of Anesthesiology, Schaumburg, IL. We consulted documents submitted by BW Co to federal authorities, through the Freedom of Information Act (FOIA), Food and Drug Administration (FDA) reports, promotional advertisements, package inserts, published articles, and textbooks. RESULTS: Initial clinical testing in humans in 1952 found no adverse effects on cardiovascular or respiratory systems. Fasciculations and myalgia were early side effects described in case reports in 1952. Large-scale clinical trials in 1953 found abnormally long recovery times among some patients; the discovery of abnormal pseudocholinesterase enzyme activity was not fully demonstrated until the early 1960s. Bradycardia was first reported in 1957 in children, and in 1959 in adults. In 1960, animal studies reported a transient increase in plasma potassium; further experiments in 1969 clearly demonstrated succinylcholine-induced hyperkalemia in burn patients. Malignant hyperthermia was first described in 1966. Similar cases of elevated temperatures and muscle rigidity were described globally but the underlying mechanism was not elucidated until the 1990s. Standard anesthesia textbooks did not report major side effects of succinylcholine until 1960 and included newly documented side effects with each edition. BW Co's packaging contained warnings as early as the 1950s but were later updated in 1962 and beyond to reflect the newly discovered hyperkalemia and malignant hyperthermia. CONCLUSION: Particularly given the regulatory environment of the time, BW Co appropriately reported the adverse effects of succinylcholine after market entry; it updated promotional and packaging material in a timely manner to reflect newly discovered adverse effects. The toxicity, though alarming and put clinicians on alert, did not seem to heavily impact succinylcholine's use, given its various desirable properties. It is still a choice muscle relaxant used today, although there are efforts to develop superior agents to replace succinylcholine.

Succinylcholine Use and Dantrolene Availability for Malignant Hyperthermia Treatment: Database Analyses and Systematic Review.

BACKGROUND: Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. METHODS: The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. RESULTS: Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. CONCLUSIONS: Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.

A 20-Year-Old-Trauma Patient With Suspected Malignant Hyperthermia Following Induction With Succinylcholine: A Case Study.

Malignant hyperthermia (MH) is a life-threatening hypermetabolic state that can occur following induction with depolarizing neuromuscular blockade and volatile anesthesia gases. Because succinylcholine is a common choice for prehospital and emergency department inductions, it is important for staff to be able to recognize and effectively treat an MH crisis. This case study highlights a 20-year-old male trauma patient who presented to a Level I trauma center and was intubated for declining mental status. He developed suspected MH following his anesthetic induction with succinylcholine. The following outlines the case, clinical identification of MH, and treatment.

Prevalence of malignant hyperthermia diagnosis in hospital discharge records in California, Florida, New York, and Wisconsin.

STUDY OBJECTIVE: Malignant hyperthermia (MH) is a rare yet potentially fatal pharmacogenetic disorder triggered by exposure to inhalational anesthetics and the depolarizing neuromuscular blocking agent succinylcholine. Epidemiologic data on the geographic variation in MH prevalence is scant. The objective of this study is to examine the prevalence of recorded MH diagnosis in patients discharged from hospitals in four states in the United States. DESIGN: Observational study. SETTING: Healthcare Cost and Utilization Project (HCUP) State Inpatient Database (SID) for California (2011), Florida (2011), New York (2012) and Wisconsin (2012). PATIENTS: A total of 164 hospital discharges that had a recorded diagnosis of MH using the International Classification of Disease, 9th Revision, Clinical Modification code 995.86. METHODS: MH prevalence was assessed by patient demographic and clinical characteristics. MAIN RESULTS: The prevalence of MH per 100,000 hospital discharges ranged from 1.23 (95% Confidence Interval [CI], 0.80-1.66) in New York to 1.91 (95% CI, 1.48-2.34) in California, and the prevalence of MH per 100,000 surgical discharges ranged from 1.47 (95% CI, 0.93-2.02) in New York to 2.86 (95% CI, 2.00-3.71) in Florida. The prevalence of MH in male patients was more than twice the prevalence in female patients. Of the 164 patients with MH diagnosis, 11% were dead on discharge. CONCLUSIONS: There exists a modest variation in the prevalence of recorded MH diagnosis in hospital discharges in California, Florida, New York and Wisconsin. Epidemiologic patterns of MH diagnosis in hospital discharges appear to be similar across the four states. Further research is needed to better understand the geographic variation and contributing factors of MH in different populations.

Succinilcolina vs rocuronio, escogencia clínica mediante un análisis de decisión médica / Succinylcholine vs rocuronium, clnical choice through a medical decision analysis

Objetivo: Realizar un análisis de decisión para escogencia entre succionilcolina y rocuronio en la inducción de secuencia rápida con base en su eficacia y la presentación de eventos adversos. Métodos: Se realizó el análisis de decisión mediante la construcción de árboles de decisiones, con sus respectivos nodos de decisión, oportunidades y utilidades. Los datos fueron tomados de la literatura médica y de una encuesta a profesionales de la anestesia y estudiantes de posgrado en anestesiología; luego éstos fueron procesados por el software Treenage con la realización de los análisis de sensibilidad. Resultados: El árbol de decisión de la literatura médica demuestra un valor esperado para la rama de succionilcolina de 6.50, superior al de la rama de rocuronio, cuyo valor es de 5.22. El árbol de decisión de la encuesta muestra a la succionilcolina como opción a escoger con un valor esperado de 9.08, por encima del valor esperado del rocuronio el cual es de 8.17. Conclusión: La succionilcolina es la mejor escogencia con base en su efectividad clínica para condiciones de intubación traqueal en la inducción de secuencia rápida, y también, es la mejor opción cuando se tienen en cuenta sus efectos adversos.

Objective: To perform a decision analysis for choosing between succinylcholine and rocuronium in a rapid sequence induction situation based on their efficacy and reported adverse effects. Methods: Decision analysis by building decision trees, with their respective decision nodes, opportunities and usefulness was made. The data was taken from the medical literature and a survey performed on anesthesia professionals and anesthesiology residents; then was processed by the Treenage software with sensitivity analysis. Results: The decision tree based on the medical literature shows an expected value for the succinylcholine branch of 6.50, higher than the rocuronium branch with a value of 5.22. The decision tree of the survey shows the succinylcholine as an option to choose with an expected value of 9.08, above the expected value of rocuronium which is 8.17. Conclusion: Succinylcholine is the best choice based on tis clinical effectiveness conditions for tracheal intubation in rapid sequence induction, and it is the best option when consideration its adverse effects.

Malignant hyperthermia: pharmacology of triggering.

Over the past 50 yr, many drugs have been implicated as triggers of malignant hyperthermia (MH), a potentially fatal pharmacogenetic disorder of skeletal muscle calcium regulation. This review discusses the potent inhalation agents as the principal triggers and evidence that the modern agents, desflurane, sevoflurane, and isoflurane, can cause florid MH reactions in the same way as halothane but also are associated with reactions whose onset is delayed for several hours into anaesthesia. There is evidence that the triggering of MH by drugs is dose-dependent but the minimum dose that will trigger the condition is unknown. This has implications for the preparation of anaesthetic machines when used for known or suspected MH patients. While succinylcholine enhances the response of potent inhalation anaesthetics, its role as an inherent trigger of the condition is controversial. Non-depolarizing neuromuscular blocking drugs appear to protect against the development of MH and this may be by blocking excitation-coupled calcium entry-a recently described route of skeletal muscle calcium entry that may also explain the mechanism of the effect of succinylcholine in MH. Another mechanism for extracellular calcium influx, store-operated calcium entry, is activated in MH muscle and may explain how a triggered reaction is sustained. Finally, reports of drugs that have been implicated as additional triggers of MH over the past 10 yr are discussed.

How much are patients willing to pay to avoid postoperative muscle pain associated with succinylcholine?

STUDY OBJECTIVE: To determine how much money patients are willing to pay to avoid postoperative muscle pains associated with succinylcholine. DESIGN: Observational study with survey instrument. SETTING: University-affiliated metropolitan hospital. PATIENTS: Eighty-eight adult patients, 43 men and 45 women, who were scheduled to undergo surgery with general anesthesia and who completed a preoperative questionnaire (median age range, 41-50 y; median income, US$45,000-60,000). INTERVENTIONS AND MEASUREMENTS: Patients completed a computerized, interactive questionnaire preoperatively. They were asked about demographics and previous experiences with muscle pain and postoperative myalgia. With the use of the willingness-to-pay model, the value that they would be willing to pay for a hypothetical muscle relaxant that avoided postoperative myalgia was determined. MAIN RESULTS: Eighty-nine percent of patients considered avoiding postoperative myalgia as important. Patients were willing to pay a median (interquartile range) of $33 ($19-$50) out of pocket for a muscle relaxant that was not associated with postoperative myalgia, a figure that increased to $40 if the insurance company paid for the drug (P < 0.0001). Willingness to pay was influenced by patients' income but not by prior experience with postoperative myalgia. CONCLUSION: Patients consider avoidance of postoperative myalgia important and are willing to pay $33 out of pocket for a muscle relaxant that is not associated with this side effect.

[Frequency distribution of dibucaine numbers in 24,830 patients]. / Verteilungsmuster der Dibucainzahl bei 24.830 Patientinnen und Patienten.

PURPOSE: Atypical cholinesterase prolongs the duration of neuromuscular blocking drugs such as succinylcholine and mivacurium. Measuring the dibucaine number identifies patients who are at risk. This study shows the frequency distribution of dibucaine numbers routinely measured and discusses avoidable clinical problems and economic implications. METHODS: Dibucaine numbers were measured on a Hitachi 917-analyzer and all dibucaine numbers recorded over a period of 4 years were taken into consideration. Repeat observations were excluded. RESULTS: A total of 24,830 dibucaine numbers were analysed and numbers below 30 were found in 0.07% ( n=18) giving an incidence of 1:1,400. Dibucaine numbers from 30 to 70 were found in 1.23% ( n=306). On the basis of identification of the Dibucaine numbers we could avoid the administration of succinylcholine or mivacurium resulting in a cost reduction of 12,280 Euro offset against the total laboratory costs amounting to 10,470 Euro. CONCLUSIONS: An incidence of 1:1,400 of dibucaine numbers below 30 is higher than documented in the literature. Therefore, routine measurement of dibucaine number is a cost-effective method of identifying patients at increased risk of prolonged neuromuscular blockade due to atypical cholinesterase.

Cost identification analysis for succinylcholine.

UNLABELLED: The cost of a dose of succinylcholine from society's perspective equals the acquisition cost of the drug plus the cost of its adverse outcomes. We hypothesized that although the acquisition cost of succinylcholine is minimal, the true cost would be much larger. We reviewed the medical literature to identify the total cost of a dose of succinylcholine when administered for nonemergency purposes according to manufacturers' guidelines (i.e., to adults only). We found that 88% of the cost per dose of succinylcholine was for the chance of dying or sustaining permanent brain injury from anaphylactic or anaphylactoid reactions to succinylcholine. Consequently, the estimated cost per dose of succinylcholine was sensitive to the incidence of anaphylactic or anaphylactoid reactions to succinylcholine, the risk of severe injury from anaphylactic or anaphylactoid reactions, and the financial value of unforeseen instant death or permanent brain injury. The range for the cost per dose of succinylcholine was thus large, $9 to $93. Our best estimate of the cost per dose was $37. We conclude that the true cost per dose of succinylcholine from society's perspective is more than 20 times the acquisition cost. However, a precise costing requires better knowledge of the incidence and consequences of anaphylactic or anaphylactoid reactions to succinylcholine. IMPLICATIONS: The true cost of succinylcholine is more than 20 times the acquisition cost of the drug. The estimated cost is very sensitive to the risk and cost of patients dying or sustaining brain injury from anaphylactic or anaphylactoid reactions to succinylcholine.

[Anesthetic complications. The incidence of severe anesthetic complications in patients and families with progressive muscular dystrophy of the Duchenne and Becker types]. / Narkosezwischenfälle. Inzidenz schwerer Narkosezwischenfälle bei Patienten und in Familien mit progressiven Muskeldystrophien vom Typ Duchenne und Becker.

UNLABELLED: During the last 30 years a great number of case reports presented severe anaesthetic complications with sudden cardiac arrest in patients with muscular dystrophies, mostly unsuspected at the time of the event. As succinylcholine was involved in the majority of the intractable incidents with lethal outcome the Food and Drug Administration (FDA) of the United States recommended a warning of the administration of succinylcholine in young children and adolescents in 1992 and an extensive international discussion on the routine use of succinylcholine in paediatric anaesthesia. Epidemiological studies on this issue are rare. We projected an inquiry about the incidence rate and type of severe anaesthetic complications in an utmost large number of patients and families with Duchenne (DMD) and Becker type (BMD) muscular dystrophy. METHODS: With the approval of the ethic committee of the university Witten/Herdecke and informed consent of the participants we investigated all patients and families who were diagnosed, controlled and treated for DMD or BMD as inpatients or outpatients in a "Muscle Centre" since 1983. The questionnaire asked for the number of patients per family, classification of the disease DMD or BMD, number and date of anaesthetics in the patients and eventual complications, anaesthetics and eventual complications in the parents, siblings and relatives and the occurrence of malignant hyperthermia (MH) in the family or relatives. Statistical assessments were done by Fisher's exact test for stratified 2 x 2 tables and Zelen's test for homogeneity of odds ratios. RESULTS: 200 out of 224 questionnaires could be evaluated. The diagnosis was confirmed by molecular genetic and immunohistochemical investigations. In 147 families it turned out to be DMD, in 53 families BMD. The 212 male and 9 female patients in the 200 families were given 444 anaesthetics. Sudden cardiac arrest occurred in 6 patients, all successfully resuscitated. Nine less severe incidents consisted of fever, symptoms of rhabdomyolysis (CK-elevation, dark coloured urine, hyperkalemia) and masseter spasm. The statistical assessment revealed that the occurrence of an event was highly dependent whether the diagnosis of muscular dystrophy was established or not (p < 0.0001, Fisher's exact test). All six cardiac arrests occurred in the 45 families with undiagnosed disease and no event happened in the 134 families with already known DMD/BMD. There was evidence that the number of anaesthetics without prior establishment of the diagnosis decreased after 1992 (p = 0.004, Fisher's exact test). CONCLUSIONS: Our results demonstrate that severe incidents and cardiac arrests occurred only in young children with undiagnosed DMD or BMD who received inhalational agents and succinylcholine. A cardiac arrest in 6 out of 200 families was found much more frequently than in the normal paediatric population (about 1:1000 to 1:3000). The decrease of events after 1992 (warning of the FDA) and disappearance of sudden cardiac arrests in our group of patients might be due to the world wide discussion on routine use of succinylcholine in children or the much earlier establishment of the diagnosis in our population. An early diagnosis of DMD and BMD and the avoidance of the triggering agents succinylcholine and volatile anaesthetics can reduce the risk of severe anaesthetic complications.

Suxamethonium-induced rhabdomyolysis in a healthy middle-aged man.

A 43-year-old man developed rhabdomyolysis after uvulo- palatopharyngoplasty. After induction with thiopentone and suxamethonium the anesthesia was maintained with halothane. The patient responded to treatment and made an uneventful recovery. In earlier reports of rhabdomyolysis after general anaesthesia with halothane and suxamethonium almost all the patients had malignant hyperthermia (MH) or muscular dystrophy. About 50% of malignant hyperthermia patients carry a mutation in the RYR1 gene. Our patient did not have mutations in the four MH-associated genes tested, but the total amount of different mutations is by now about twenty. Therefore, despite these negative tests rhabdomyolysis may be a sign of subclinical malignant hyperthermia which cannot be ruled out by our investigations. This rare case of rhabdomyolysis in a healthy man suggests careful monitoring of the patient when-ever suxamethonium is used.

Relative efficiency of succinylcholine, xylazine, and carfentanil/xylazine mixtures to immobilize free-ranging moose.

We compared the efficiency of succinylcholine chloride, xylazine hydrochloride and carfentanil/xylazine mixtures in immobilizing 364 free-ranging moose (Alces alces) between 1987 and 1997 in Québec (Canada). With succinylcholine chloride (0.070, 0.062, 0.051 mg/kg of estimated body weight for calves, juveniles and adults), 63% of the 252 immobilization attempts led to complete immobilization and marking, whereas 7% of the darted animals died of respiratory paralysis during handling. The moose took an average of 13 min to lay down after darting (down time). Injection of xylazine (3.67-4.22 mg/kg) permitted sedation (the animal laid down but got up again when approached) or complete immobilization in 78% of the 40 darted adult moose, the mean down time being 8.7 min. No mortality was noted with this drug but 58% of the marked animals were only sedated. The use of RX821002A (0.058 mg/kg) as an antagonist, permitted a mean recovery time of 2.8 min after intravenous injection. With the carfentanil/xylazine mixtures (0.0071 and 0.181 mg/kg), 96% of the immobilization trials (n = 72) led to complete (88%) or partial (8%) immobilization, but 6% of the moose died several days after capture. The mean down time was 6.6 min, and injection of naltrexone (0.709 mg/kg) antagonized the effect of the immobilizing agent within 3.7 min. The respiratory rate was higher (P < 0.05) among moose immobilized with xylazine (35/min) than among those immobilized with carfentanil/xylazine mixtures (19/min) but this variation could be related to a longer pursuit time (z = 3.60; P < 0.01) and higher stress levels during handling. Rectal temperature also was higher with xylazine but the difference was small (39.7 vs. 39.3, P = 0.03) and did not differ significantly between the sexes (P > 0.05). Considering loss of materials and helicopter flight time due to non-successful marking trials, carfentanil/xylazine mixtures were the least expensive ($333 Cdn/animal).

Malignant hyperthermia induced by general anesthesia for bone marrow harvesting.

We present a case of a bone marrow donor who developed rhabdomyolysis, acute renal failure and pulmonary edema following an apparently uneventful general anesthesia for bone marrow harvesting. Because malignant hyperthermia (MH) was suspected, he was treated with dantrolene, fluid loading, and continuous hemodiafiltration along with symptomatic supportive care. He made a full recovery and was discharged 3 weeks after harvest. Although the incidence of MH is low, marrow donation involves the risks of anesthesia as is seen in this case. Close monitoring is required to prevent life-threatening complications associated with the bone marrow harvesting procedure.

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.

[The effect of muscle relaxants on masseter tone. An experimental study in an MH-susceptible swine model]. / Zur Wirkung von Muskelrelaxanzien auf den Massetertonus. Eine experimentelle Studie am MH-disponierten Schweinemodell.

Malignant hyperthermia (MH) may occur, when a genetically predisposed individual or pig (MHS) is exposed to triggering agents. The increase in free, ionized sarcoplasmic calcium inducing the vicious circle of MH is believed to result from calcium-induced release with volatile anaesthetics, and from depolarization-induced calcium release with succinylcholine (SCH). The administration of SCH to susceptible humans or pigs frequently produces an increase in masticatory muscle tone. This hitherto ill-defined phenomenon is referred to as "masseter spasm" (MS). We have attempted to elucidate the pathophysiology of MS in a porcine model. METHODS. After the protocol had been approved by the state authorities, 6 MHS pigs were investigated. The pigs were mixed breeds (German Landrace and Dutch Pietrain) and were 9 +/- 1 weeks old with an average body weight of 25.5 kg. Premedication consisted of intramuscular injection of azaperone, 7.5 mg.kg-1. Anaesthesia was induced with piritramide, 1.2 mg.kg-1, administered via a cannulated ear vein. Subsequent to laryngoscopic endotracheal intubation, neuromuscular blockade was achieved with 4 mg pancuronium. Ventilation was set at 12 breaths per minute and adjusted to maintain an end-tidal CO2 concentration of 4.7% by adapting the tidal volume (PhysioFlex). Anaesthesia was maintained with piritramide, 2.25 mg.kg-1.h-1, pancuronium, 0.4 mg.kg-1.h-1, and N2O (60% in O2). Instrumentation included an arterial line, a central venous line, and a fiberoptic pulmonary artery catheter (Oximetrix). Masticatory muscle tone (MMT) was assessed with an intermolar balloon, connected to a pressure transducer and calibrated to zero prior to SCH administration. As a reference variable for effects produced by SCH, intraocular pressure (IOP) was measured manometrically in the anterior chamber. After stabilization of haemodynamic variables, the neuromuscular blockade was allowed to wear off. After recovery of the evoked masseter electromyogram, a paralyzing dose of pancuronium was administered (0.5 mg.kg-1). When paralysis was complete, SCH was administered (1.5 mg.kg-1), followed a few minutes later by dantrolene infusion (5 mg.kg-1 over 10 min). RESULTS. The administration of SCH was followed by clinically unequivocal MH episodes in all pigs, indicated by an increase in oxygen uptake (VO2; PhysioFlex; Fig. 1) and end-tidal CO2 concentration and a decrease in oxygen saturation of mixed venous blood (svO2; Fig. 2). Despite complete neuromuscular blockade (monitored with EMG), SCH produced an increase in MMT in all pigs which was reversed by dantrolene (Fig. 3). The time course of MMT paralleled that of IOP, suggesting a similar underlying mechanism. DISCUSSION. Succinylcholine is a trigger of MH in susceptible individuals; onset of the syndrome may be associated with "masseter spasm". SCH increases extraocular muscle tone, probably by means of stimulating multiply innervated fibers; the resulting IOP increase is not prevented by competitive neuromuscular blockade. The existence of multiple innervated fibers has also been shown in muscle spindles in the deep layers of the masseter, with their stimulation resulting in elevation of the jaw. We speculate that the increases in MMT and IOP observed in this study reflect the same process, i.e. a motor response, initiated by SCH-induced stimulation of the intramyocellular contractile system of multiply innervated muscle fibers, that is independent of neuromuscular transmission. Triggering of MH with SCH despite complete neuromuscular blockage suggests a mechanism other than depolarization-induced calcium increase. And, for the semantics, according to neurological terminology MS should be referred to as contracture not as spasm.