Case Of Malignant Hyperthermia Research Articles

Malignant Hyperthermia-Associated Diseases: State of the Art Uncertainty

Henry Rosenberg, MD† In one form or another, the following scenario is occurring daily in hospitals throughout the world: a 10-mo-old infant with progressive hypotonia and failure to thrive is scheduled for a surgical muscle biopsy and gastrostomy with general anesthesia. The neurological evaluation reveals a differential diagnosis that may include central white matter disease, metabolic encephalopathy, mitochondrial myopathy, or others. The neurologist recommends a nontriggering general anesthetic in the event that the infant is susceptible to malignant hyperthermia (MH). The anesthesiologist performs an uneventful general anesthetic with total IV anesthesia. Regardless of the results of the muscle biopsy, for each subsequent required anesthetic, a nontriggering technique is performed. What is the likelihood that any of these infants is truly MH-susceptible? This month’s issue of Anesthesia & Analgesia presents a series of articles that helps us answer this question more definitively, though inconclusively, than ever before. As hotline consultants for the Malignant Hyperthermia Association of the United States (MHAUS),* we commonly receive requests to help clinicians by defining the specific disease entities that predispose to MH susceptibility. With the exception of a small number of inherited conditions, the answer is elusive. With all of our knowledge to date on MH, why is this so? Because in clinical medicine, it is extremely difficult to establish definitive causal relationships without prospective randomized controlled trials, and cohort studies are impossible to perform for rare events. Therefore, we are left with a broad generalization derived from case control studies and case reports and series. To complicate matters, these historical reports did not have the benefit of genetic linkage and pedigree analysis which have, in the current era, furthered the definitive diagnosis of various syndromes and their link to MH. The path to this specialized issue on MH-associated diseases began several years ago when we and several other MHAUS hotline consultants hosted a series of panel discussions on MH at the annual meetings of the American Society of Anesthesiologists and the Society for Ambulatory Anesthesia. At the 2006 winter meeting of the Society for Pediatric Anesthesia (SPA), Barbara Brandom, Richard Kaplan, and Ron Litman participated on a panel of challenging pediatric MH cases. The response from the audience was overwhelming and clear: “Tell us who should and who shouldn’t receive a nontriggering technique.” Thus began a 3-yr process that now culminates with the articles presented herein. First, we identified international authoritative experts on each of the broad categories of diseases that have purportedly been linked to MH. Next, we created a partnership between SPA and MHAUS with the purpose of presenting a one-day symposium on MH-related diseases at the 2008 SPA winter meeting.† The organization and implementation of this symposium would not have been possible without the philosophical and financial support of SPA and MHAUS. By all accounts, the symposium was a resounding success. Each of our authorities presented a lecture on a specific category of disease and the From the *Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and †Saint Barnabas Medical Center, Livingston, New Jersey. Accepted for publication May 7, 2009. Address correspondence and reprint requests to Ronald S. Litman, DO, Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia, 34th St. & Civic Center Blvd., Philadelphia, PA 19104. Address e-mail to litmanr@email. chop.edu. Copyright © 2009 International Anesthesia Research Society DOI: 10.1213/ane.0b013e3181ae6b96 *Available at: http://www.mhaus.org. †Available at: http://www.pedsanesthesia.org/meetings/2008winter/spa08_program.pdf.

Administrative Databases: Are They Useful for Clinical Analyses?

To the Editor:— We are pleased that Rosero et al. 1pursued a study of the epidemiology of malignant hyperthermia (MH). We agree with Rosero et al. that reporting to the North American Malignant Hyperthermia Registry may underestimate MH mortality. From the Malignant Hyperthermia Association of the United States Hotline and the American Society of Anesthesiologists Closed Claims Project database we are aware of deaths clearly due to MH that were not reported to the Registry. Reports to the North American Malignant Hyperthermia Registry are voluntary, but provide key details that administrative databases cannot.2†We encourage readers to report suspected MH episodes to the Registry, using forms that are available online at www.mhreg.org.Rosero et al. define MH cases by the hospital discharge diagnosis code of malignant hyperthermia as a result of anesthetics, after excluding other conditions associated with hyperthermia. Did the authors attempt to confirm that the 2,312 MH cases not admitted from another health facility had been exposed to an anesthetic, for example by linking them to surgical or procedural International Classification of Disease, ninth revision (ICD-9) codes? The diagnosis of MH would be more certain if there was some evidence of anesthetic exposure, not just a code.Like any database, the “output” depends on the accuracy of the data entered. The Nationwide Inpatient Sample depends on accurate coding by medical records departments, which in turn are dependent on clinical documentation. The diagnosis of MH requires no supporting evidence to be coded as such. Other studies have shown that incorrect coding and diagnostic inaccuracy can undermine calculations derived from administrative databases.3,4Rosero et al. conclude that the incidence of MH increased from 2000 to 2005. An equally plausible explanation is reporting bias: As coders became aware of the new ICD-9 code for MH, they used it more often. This code (995.86) was approved in 1997, thanks to the efforts of the Malignant Hyperthermia Association of the United States and American Society of Anesthesiologists, and coders may have been unaware of its existence, given the rarity of MH.Finally, we point out an error in Rosero et al. 's paper. The 2007 review by Rosenberg et al. 5did not consider our 2008 report of an MH-associated mortality rate of 1.4% to be “controversial.”2Their review was published almost a year before our paper, making it impossible to cite.*The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States, and Penn State College of Medicine, Hershey, Pennsylvania. mlarach@gmail.com

Increasing the number of diagnostic mutations in malignant hyperthermia

Malignant hyperthermia (MH) is an autosomal dominant disorder characterized by abnormal calcium homeostasis in skeletal muscle in response to triggering agents. Today, genetic investigations on ryanodine receptor type 1 (RYR1) gene and alpha1 subunit of the dihydropyridine receptor (DHPR) (CACNA1S) gene have improved the procedures associated with MH diagnosis. In approximately 50% of MH cases a causative RYR1 mutation was found. Molecular genetic testing based on RYR1 mutations for MH diagnosis is challenging, because the causative mutations, most of which are private, are distributed throughout the RYR1 gene. A more comprehensive genetic testing procedure is needed. Therefore, we aim to expand the genetic information related to MH and to evaluate the effect of mutations on the MH phenotype. Performing an in-depth mutation screening of the RYR1 transcript sequence in 36 unrelated MH susceptible (MHS) patients, we identified 17 novel, five rare, and eight non-disease-causing variants in 23 patients. The 13 remaining MHS patients presented no known variants, neither in RYR1 nor in the CACNA1S binding regions to RYR1. The 17 novel variants were found to affect highly conserved amino acids and were absent in 100 controls. Excellent genotype-phenotype correlations were found by investigating 21 MHS families-a total of 186 individuals. Epstein-Barr virus (EBV) lymphoblastoid cells carrying four of these novel mutations showed abnormal calcium homeostasis. The results of this study contribute to the establishment of a robust genetic testing procedure for MH diagnosis.

Postoperative Malignant Hyperthermia

The initial presentation of malignant hyperthermia (MH) may begin in the postoperative period. However, the maximal latency period between the end of anesthesia care and the onset of postoperative MH is unknown. The authors hypothesized that this latency period is short and is not manifested by hyperthermia as the initial presenting sign. The authors sought to test this hypothesis and to describe the clinical characteristics of postoperative MH by analysis of suspected cases in the North American Malignant Hyperthermia Registry. Of 528 possible or suspected cases of MH in the North American Malignant Hyperthermia Registry, the authors identified 64 possible reports of postoperative MH. The records were reviewed in detail by the authors, each of whom assigned a qualitative score of "likely," "not likely," "not enough information available," or "not applicable" (where MH was not the final definitive diagnosis). Postoperative MH was confirmed after a consensus meeting of the three senior authors who reviewed in detail all possible "likely" cases. The authors identified postoperative MH in 10 subjects. All received volatile agents and 5 also received succinylcholine. All demonstrated signs characteristic of acute MH, including generalized rigidity, hypercapnia and/or tachypnea, tachycardia, and hyperthermia. No subject demonstrated hyperthermia as the presenting sign. The latency period between the anesthesia finish time and the onset of a sign indicative of acute MH ranged from 0 to 40 min. Postoperative MH is uncommon, occurring in 10 of 528 suspected MH cases (1.9%) reported to the North American Malignant Hyperthermia Registry. Postoperative MH began shortly after completion of the anesthetic care. Hyperthermia was not a presenting sign of MH.

Malignant hyperthermia developing during esophageal resection in an 82-year-old man

Malignant hyperthermia (MH) is a rare but fatal complication that develops under general anesthesia. Reports on MH in patients over the age of 80 years are unusual. We experienced a case of MH in an 82-year-old patient during esophageal resection. Anesthesia was induced with propofol and succinylcholine, and maintained with sevoflurane. Neither masseter spasm nor rigidity of the limbs was seen during induction. Body temperature (BT) at induction was 36.0 degrees C. Three hours after incision, the level of end-tidal CO2 was elevated to 55 mmHg. We assumed that the rise in end-tidal CO2 had occurred due to secretions in the airway. However, the BT, which had risen at 3 h after incision, continued to rise, and about 60 min later, the BT exceeded 39.0 degrees C. A rise of more than 0.5 degrees C in less than 15 min was seen, and MH was suspected. With dantrolene administration, the BT decreased from 40.9 degrees C at maximum to 37.7 degrees C. With continuous infusion of dantrolene when the patient was transferred to the intensive care unit (ICU), BT remained within the normal range. The next day re-operation was performed, without further complications or recurrence of MH during the postoperative period. Because it is necessary to initiate treatment in the early stage of MH, as soon as possible, although MH prevalence is low in the elderly, it is important to suspect MH when hypercapnia and/or hyperthermia are seen.

Reduced Threshold for Luminal Ca2+ Activation of RyR1 Underlies a Causal Mechanism of Porcine Malignant Hyperthermia

Naturally occurring mutations in the skeletal muscle Ca(2+) release channel/ryanodine receptor RyR1 are linked to malignant hyperthermia (MH), a life-threatening complication of general anesthesia. Although it has long been recognized that MH results from uncontrolled or spontaneous Ca(2+) release from the sarcoplasmic reticulum, how MH RyR1 mutations render the sarcoplasmic reticulum susceptible to volatile anesthetic-induced spontaneous Ca(2+) release is unclear. Here we investigated the impact of the porcine MH mutation, R615C, the human equivalent of which also causes MH, on the intrinsic properties of the RyR1 channel and the propensity for spontaneous Ca(2+) release during store Ca(2+) overload, a process we refer to as store overload-induced Ca(2+) release (SOICR). Single channel analyses revealed that the R615C mutation markedly enhanced the luminal Ca(2+) activation of RyR1. Moreover, HEK293 cells expressing the R615C mutant displayed a reduced threshold for SOICR compared with cells expressing wild type RyR1. Furthermore, the MH-triggering agent, halothane, potentiated the response of RyR1 to luminal Ca(2+) and SOICR. Conversely, dantrolene, an effective treatment for MH, suppressed SOICR in HEK293 cells expressing the R615C mutant, but not in cells expressing an RyR2 mutant. These data suggest that the R615C mutation confers MH susceptibility by reducing the threshold for luminal Ca(2+) activation and SOICR, whereas volatile anesthetics trigger MH by further reducing the threshold, and dantrolene suppresses MH by increasing the SOICR threshold. Together, our data support a view in which altered luminal Ca(2+) regulation of RyR1 represents a primary causal mechanism of MH.

Successful Management of Malignant Hyperthermia During Orthognathic Surgery: A Case Report

Malignant hyperthermia (MH) is a potentially lifethreatening hypermetabolic condition triggered by inhaled halogenated anesthetic agents (eg, halothane, isoflurane, enflurane, desflurane, sevoflurane) or succinylcholine in otherwise normal but genetically susceptible individuals. This disorder was initially de scribed in 1960 by Denborough et al, 2-6 who published the first formal case of MH in an Australian family. MH is inherited as an autosomal dominant disease characterized by uncontrollable skeletal muscle hypermetabolism, rhabdomyolysis, increased oxygen consumption and CO 2 production, tachycardia, hypercapnia, hyperthermia, elevated creatinine kinase, and other features after exposure to a trigger agent. Most MH-susceptible individuals are asymptomatic until they are truly exposed to such an agent. Some genes can counter mutations related to susceptibility to MH; the most widely studied and frequently found of these is the gene for the ryanodine receptor RyR1, located in chromosome 19, which accounts for approximately 50% of the susceptible persons. MH occurs in all ethnic groups, and preva lence varies according to region and age. 2,8 Its exact incidence is unknown but is estimated to be 1:15,000 in children and adolescents and 1:50,000 in adults. The decreased incidence with age may have 2 explanations: a reduced expression of the disease and the death of susceptible individuals before they become adults. 3

Malignant Hyperthermia in a Patient with Partially Accommodative Esotropia

Purpose: Malignant hyperthermia is hypermetabolic disorder of skeletal muscle that manifests during general anesthesia. Strabismus and ptosis are important risk factors in ophthalmology field for malignant hyperthermia. We report a case of malignant hyperthermia in patient with partially accommodative esotropia. Case summary: A 6-year-old patient was supposed to undergo a surgical correction for 20 prism diopters of right esotropia after correction of hypermetropia. Because the patient showed tachycardia and hyperthermia just after inhalation of sevoflurane, we interrupted general anesthesia and cancelled the surgery. The patient was transferred to the intensive care unit. In this case, no significant familial and past histories were found. Intractable tachycardia and hyperthermia that had not responded to conservative management improved after two administration of dantrolene sodium. The patient was returned to the ward three days later. As the patient showed no other complication, he was discharged. Conclusions: In malignant hyperthermia, early diagnosis, appropriate management, and prompt administration of dantrolene sodium are important factors for better prognosis. Preoperatively, full explanation of possible complication and history taking are needed. Careful observation is necessary during anesthesia and surgery. J Korean Ophthalmol Soc 49(8):1356-1359, 2008

Identification of Risk Factors for Exertional Heat Illness: A Brief Commentary on Genetic Testing

This commentary discusses known links between Exertional Heat Illness (EHI), Malignant Hyperthermia (MH), and other hereditary diseases of muscle. Genetic and functional testing is also evaluated as measures of fitness to return to duty/play. Reviews and research articles from Sports Medicine, Applied Physiology, and Anesthesiology. Detailed comparisons of existing literature regarding clinical cases of EHI and MH and the potential utility of genetic testing, specifically the ryanodine receptor (RYR1) gene and other genes related to disorders of skeletal muscle. EHI is a complex disorder wherein physiological, environmental, and hereditary factors interact to endanger an individual's ability to maintain thermal homeostasis. Individuals' genetic background is likely to play an important role, particularly when EHI recurs. Recurrent EHI has been associated with MH and other genetic disorders, highlighting the importance of identification and exclusion of individuals with known high risk factors.

Malignant Hyperthermia in China

Malignant hyperthermia has rarely been reported in China. We report the first case of malignant hyperthermia, verified by caffeine-halothane contracture test and genetic testing, in a Chinese patient.

Negative Arterial to End-Tidal Carbon Dioxide Gradient: An Additional Sign of Malignant Hyperthermia During Desflurane Anesthesia

Widespread use of desflurane anesthesia has changed the clinical presentation of malignant hyperthermia (MH). Delayed onset of MH symptoms has been reported previously. A negative gradient between arterial to end-tidal CO2 ([a-ET]Pco2) was observed during anesthesia in pregnant patients and infants and has been associated with increased CO2 production, increased cardiac output, reduced functional residual capacity, and low lung compliance. The same conditions exist in cases of MH crisis. We describe an unusual case of MH in which a negative value of (a-ET) Pco2 gradient has been used as diagnostic and monitoring tool.

Malignant hyperthermia genetic testing in North America Working Group Meeting. Bethesda, Maryland. September 4-5, 2002.

Malignant hyperthermia genetic testing in North America Working Group Meeting. Bethesda, Maryland. September 4-5, 2002.

A Case of Malignant Hyperthermia during General Anesthesia with Sevoflurane: A case report

We experienced a malignant hyperthermia in 24-year-old male with sevoflurane during the mandibular prognathism surgery. The malignant hyperthermia emerged 150 minutes after induction of general anesthesia using propofol, rocuronium, sevoflurane, and .Sevoflurane has been reported that it can induce delayed onset of malignant hyperthermia under absence of succinylcholine. The prognosis of malignant hyperthermia is determined by early recognition, vigorous treatment and the time of dantrolene injection. In our case, when we suspected episode, all anesthetics were stopped and dantrolene injection was immediately given intravenously. The patient recovered normal temperature and consciousness without any complication.

Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?

Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Although genetically heterogeneous, mutations in the RYR1 gene (19q13.1) are associated with the majority of reported MH cases. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. We have therefore assessed the prevalence of 15 RYR1 mutations currently used in the genetic diagnosis of MH in a sample of over 500 unrelated European MH susceptible individuals and have recorded the frequency of RYR1 genotype/IVCT phenotype discordance. RYR1 mutations were detected in up to approximately 30% of families investigated. Phenotype/genotype discordance in a single individual was observed in 10 out of 196 mutation-positive families. In five families a mutation-positive/IVCT-negative individual was observed, and in the other five families a mutation-negative/IVCT-positive individual was observed. These data represent the most comprehensive assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis and highlight the possible limitations of MH screening methods. The implications for genetic diagnosis are discussed.

Two case of malignant hyperthermia with hemofiltration

Two case of malignant hyperthermia with hemofiltration

Fatal malignant hyperthermia—delayed onset and atypical course

A case of malignant hyperthermia (mh) in a 27-year-old man is described. In a first anaesthesia using isoflurane and succinylcholine, the end-tidal CO 2 rose from 39 to 49 mmHg 2.75 h post-intubation and the body temperature rose to 39.8 °C 14 h post-intubation but was normal again the next day. In a second anaesthesia using the same medication, the maximal end-tidal CO 2 was 44 mmHg and the body temperature rose to 39 °C after 9 h. After 4 days, the fever rose to 40 °C, and to 42 °C when death occurred 10 days after the second anaesthesia. Masseter spasms or muscle rigidity were never present. According to the death certificate, death was due to multi-organ failure from sepsis. At autopsy, the skeletal muscles were pale and oedematous. Histology demonstrated focal necroses in the skeletal muscles, shock kidneys with myoglobin excretion and myoglobin clots in small blood vessels of the lungs. Hence, the postmortem diagnosis “malignant hyperthermia” was established but accusations of medical maltreatment were rejected because of the atypical and protracted clinical course and because uncharacteristic signs of malignant hyperthermia were attributable to the clinically suspected sepsis.

Mutations in the RYR1 gene in Italian patients at risk for Malignant Hyperthermia: evidence for a cluster of novel mutations in the C-terminal region

Mutations in the ryanodine receptor type 1 (RYR1) gene are associated with Malignant Hyperthermia (MH) and Central Core Disease (CCD). We report here on the molecular analysis of the RYR1 gene in Italian families referred as potential cases of MH or in patients with CCD or multicore/minicore myopathy. Of a total of 20 individuals with mutations in the RYR1 gene, 14 were part of a group of 47 MH susceptible (MHS) patients, 4 of 34 individuals diagnosed as MH equivocal (MHE), and 2 were patients diagnosed with minicore myopathy and CCD, respectively. Mutations were found to segregate with the MHS or MHE phenotype within the families of the probands. A discordance between phenotype and genotype was observed in a family where a mutation detected in an MHS proband was also found in the father who had been diagnosed MH normal (MHN) at the IVCT. In addition to known mutations, seven novel mutations were found, five of which occurred in exons encoding the C-terminal region of RYR1. These results indicate that the C-terminal region of RYR1 represents an additional hot spot for mutations in patients with MH, similar to what has been reported for patients with CCD.

Prevention and treatment of malignant hyperthermia in certified training hospitals in Japan: a questionnaire.

To assess the preparedness of hospitals in Japan for cases of malignant hyperthermia (MH). A survey was sent to 884 training hospitals certified by the Japan Society of Anesthesiologists (JSA) in June and July 2000. Useful answers were received from 431 (48.8%) institutions. For general anesthesia, inhalation anesthetics were widely used in 283 (65.7%) hospitals, and succinylcholine was the most commonly used muscle relaxant, which was used in 270 hospitals (62.5%). For patient monitoring, 422 (97.9%) hospitals used a pulse oximeter for all general anesthesia cases. A capnogram was used in 152 (35.3%) hospitals, and continuous body temperature was measured in 128 (29.7%). Two hundred and eighty-eight (66.8%) hospitals had more than six vials of dantrolene prepared for use, whereas 13 (3.0%) had none. The results of the survey revealed that some hospitals had inadequate monitoring methods and a lack of prepared dantrolene for cases of MH under general anesthesia. We recommend that essential monitors be deployed and adequate preparations of dantrolene be maintained for effective early diagnosis and treatment of MH.

Did Anesthetics Trigger Cardiac Arrests in Patients with Occult Myopathies?

Children’s Hospital and Regional Medical Center, Seattle, Washington, and University of Washington School of Medicine, Seattle, Washington. jmorra@chmc.orgIn Reply:—Dr. Larach et al. have reported that of the 25 cardiac arrest patients reported to The North American Malignant Hyperthermia (MH) Registry and MH Association of the United States Hotline from 1990–1993, 48% showed evidence for a previously unrecognized myopathy, and 32% had hyperkalemia-associated arrests. In contrast, 6.7% (10/150) of the Pediatric Perioperative Cardiac Arrest Registry patients were hyperkalemic at the time of arrest. All but one of these cases was associated with either massive transfusion (n = 5), reperfusion after liver transplant (n = 2), or renal insufficiency (n = 2). In one patient, succinylcholine administration resulted in hyperkalemia and cardiac arrest. This was a patient with severe neurologic deterioration from subacute sclerosing panencephalitis. No laboratory data or muscle biopsy data were provided to confirm the presence of a myopathy. The same was true for the 3 children found to have cardiomyopathy and for the 18 children whose arrest was assumed to be cardiovascular in origin but could not have a specific cause assigned.The fact that fewer hyperkalemia-associated arrests have been reported to the Pediatric Perioperative Cardiac Arrest Registry than to The North American MH Registry is not surprising, given the different focus and entry criteria of the two registries. In fact, no cases of MH have been reported to the Pediatric Perioperative Cardiac Arrest Registry, perhaps because we have become more knowledgeable about MH prevention and therapy such that few MH-susceptible patients progress to cardiac arrest. In addition, the decreasing use of succinylcholine during the past decade as faster-acting nondepolarizing relaxants have become available may have resulted in the diagnosis of fewer patients with occult myopathy or MH susceptibility.We agree with Dr. Larach et al. that more information is required. As suggested in Dr. Rothstein’s editorial, 1this sort of information can come only with a prospective multicenter epidemiologic study of anesthesia-related cardiac arrest.Dr. Cote argues that we should not condemn halothane because it remains the most widely used anesthetic agent for children around the world, has a long track record of safety, and is inexpensive relative to other agents, such as sevoflurane. His points are well-taken. However, pediatric anesthesiologists recognize that halothane can cause bradycardia and hypotension in their patients, occasionally to the degree that cardiopulmonary resuscitation is required. The impact of halothane on heart rate, blood pressure, and cardiac output has been well-documented in many animal 2–4and human 5–7studies. Recently, studies comparing the cardiovascular responses in newborns, infants, and children to whom either halothane or sevoflurane was administered have suggested important differences, particularly with respect to heart rate and cardiac contractility and output. 8–10As Dr. Cote points out, another important difference between these two agents is that it is possible to deliver roughly twice the number of minimum alveolar concentration multiples of halothane than of sevoflurane.Halothane continues to be a frequently used agent in our institution, as in other institutions around the world that care for children. We hope that information provided by the Pediatric Perioperative Cardiac Arrest Registry about halothane’s role in contributing to occasional cardiac arrest will improve the safety of its use. As an example, the use of controlled ventilation was an associated factor in approximately half of the patients in which halothane-related cardiovascular depression caused cardiac arrest; the remainder had arrests during spontaneous or assisted ventilation. Thus, the classic teaching that spontaneously breathing patients do not have arrests caused by inhalation agent–induced cardiovascular depression is not always true.As anesthetic agents with the promise of improved efficacy or fewer side effects become available, we would be remiss not to compare them with the gold standard. We do not know whether sevoflurane is associated with less risk compared with halothane, but there is reason to think this might be so. At the moment, each of us must apply an incomplete data set to our practices. Cost is certainly an issue and may be the decisive issue if sevoflurane is unaffordable. Those of us with the luxury of choice are charged with analyzing our outcomes as rigorously as possible and making the information available to others.

Malignant Hyperthermia In The Indian Subcontinent: Non-availability Of Dantrolene - A Cause For Concern?

We report the first case of malignant hyperthermia from the Indian sub-continent and raise the issue of non-availability of dantrolene in a country, where this clinical entity was thought not to exist.