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In this study, we compared the effect of isoflurane and desflurane on the posterior tibial somatosensory evoked potential recorded by scalp electrodes during correction of idiopathic scoliosis in pediatric patients. Depth of sedation was controlled by maintaining bispectral index (BIS) at 60 throughout the study. Comparison of patients breathing desflurane and isoflurane showed an evoked cortical amplitude (N37-P45) of 0.53 +/- 0.3 microV versus 1.3 +/- 0.8 microV (P = 0.014), respectively. In addition to this comparison, a crossover design was included whereby the desflurane or isoflurane received in the first part of the study was changed to the other anesthetic. Substituting one anesthetic for another confirmed our initial finding that the cortical evoked amplitude is greater with isoflurane than with desflurane. No differential effect was found between desflurane and isoflurane on the evoked subcortical (N31-P34) amplitude or the P37 latency.

Background: Malignant hyperthermia (MH) is a disorder of skeletal muscle manifested as a life-threatening hypermetabolic crisis in susceptible individuals after exposure to inhalational anesthetics and depolarizing muscle relaxants. Mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) are considered a common cause of the disorder, and, to date, more than 20 RYR1 mutations have been reported in European and Canadian families. Some studies suggest that differences may exist in the frequencies and distribution of mutations in the RYR1 gene between European and North American MH families the frequency and distribution of mutations in the RYR1 gene., Methods: Skeletal muscle samples from 73 unrelated individuals diagnosed as MH susceptible according to the North American MH caffeine-halothane contracture test were studied. Genomic DNA of MH-susceptible patients was investigated by polymerase chain reaction-based restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing analysis. The majority of known RYR1 mutations were analyzed using the restriction fragment length polymorphism method, whereas new mutations were searched by single-strand conformation polymorphism in exons 12, 15, 39, 40, 44, 45, and 46 of the gene., Results: Seven known RYR1 mutations (Arg163Cys, Gly248Arg, Arg614Cys, Val2168Met, Thr2206Met, Gly2434Arg, and Arg2454His) were detected at frequencies of 2.7, 1.4, 1.4, 1.4, 1.4, 5.5, and 4.1%, respectively. In addition, three novel amino acid substitutions (Val2214Ile, Ala2367Thr, and Asp2431Asn) were detected at frequency of 1.4% each. These 10 mutations account for 21.9% of the North American MH-susceptible population., Conclusion: Three novel candidate mutations in the RYR1 gene were identified in these MH patients. The frequency and distribution of RYR1 mutations observed in this North American MH population was markedly different from that previously identified in Europe. Larger-scale studies are necessary to clarify the type and frequency of mutations in RYR1 associated with MH in North American families.

Unlabelled: We studied the neuromuscular blocking effects of rapacuronium (Org 9487) (dose-response curve, onset, and 50% effective dose [ED50] value), and changes in heart rate and blood pressure, as well as evidence of histamine release in neonates, infants, and children in an open-label, randomized, two-center study. Fifteen neonates, 30 infants, and 30 children were studied. Anesthesia was induced and maintained with propofol, nitrous oxide:oxygen (60:40), and fentanyl. Mechanomyographic monitoring of neuromuscular function was performed at the thumb. The potency (ED50) for neonates, infants, and children were 0.32 (95% confidence interval [CI] 0.15-0.61), 0.28 (95% CI 0.11-0.61), and 0.39 (95% CI 0.17-0.85) mg/kg, respectively. Neonates who received 0.3, 0.6, or 0.9 mg/kg Org 9487 developed a maximum T1 twitch depression of 34 +/-28%, 98 +/- 3%, and 99 +/- 2%, respectively. Time-to-peak effect (onset time) for 0.9 mg/kg Org 9487 was 57 +/- 20 s. Maximum percent T1 twitch depression (+/-SD) in infants who received 0.3, 0.6, or 0.9 mg/kg rapacuronium was 41 +/- 34%, 96 +/- 7%, and 100 +/- 1%, respectively. Time-to-peak effect for 0.9 mg/kg Org 9487 was 62 +/- 29 s. In children 0.3, 0.6, and 0.9 mg/kg rapacuronium resulted in an average percent T1 twitch suppression of 29 +/- 23, 83 +/- 11, and 90 +/- 16, respectively. Time-to-peak effect of 0.9 mg/kg Org 9487 was 96 +/- 33 s, respectively. There was no evidence of histamine release or significant changes in heart rate or blood pressure in either group at any dose. Rapacuronium is a low-potency nondepolarizing muscle relaxant with a fast onset of relaxation and minimal cardiovascular effects. Its potency (ED50) is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg). T1 suppression (90% +/- 16) is less and time to peak effect (96 +/- 33 s) is greater (0.9 mg/kg rapacuronium) in children, compared with the combined group of infants and neonates., Implications: This study assesses the potency of rapacuronium (Org 9487) in pediatric patients. The potency of rapacuronium is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg).

Background: The function or expression of subtypes of the sodium ion (Na+) channel is altered in biopsies or cultures of skeletal muscle from many persons who are susceptible to malignant hyperthermia (MH). ATX II, a specific Na+ channel toxin from a sea anemone, causes delayed inactivation of the channel similar to that seen in cell cultures of MH muscle. ATX II was added to skeletal muscle to determine whether altered Na+ channel function could increase the sensitivity of normal skeletal muscle to agents (halothane, caffeine, ryanodine) to which MH muscle is hypersensitive., Methods: Studies were performed of fiber bundles from the vastus lateralis muscle of persons who were deemed not MH susceptible (MH-) or MH susceptible (MH+) according to the MH diagnostic test and of strips of diaphragm muscle from rats. Preparations in a tissue bath containing Krebs solution were connected to a force transducer. ATX II was introduced 5 min before halothane, caffeine, or ryanodine., Results: ATX II increased the magnitude of contracture to halothane in preparations from most MH-, but not MH+, human participants. After ATX II treatment, preparations from 9 of 24 MH- participants generated contractures to halothane, 3%, that were of the same magnitude as those from MH+ participants. Preparations from four of six ATX II-treated healthy participants also gave responses of the same magnitude as those of MH-susceptible participants to a graded halothane challenge (0.5-3%). The contractures to bolus doses of halothane in specimens from male participants were more than three times larger than the contractures in specimens from female participants. In rat muscle, ATX II increased the magnitude of contracture to caffeine (2 mM) and decreased the time to produce a 1-g contracture to ryanodine (1 microM)., Conclusions: ATX II, which causes delayed inactivation of the Na+ channel in cell cultures similar to that reported in cultures of MH+ skeletal muscle, increased the sensitivity of normal muscle to three agents to which MH+ muscle is hypersensitive. The increased sensitivity to halothane, 3%, occurred in most (79%), but not all, MH- participants, and this effect was most evident in male participants. Therefore, abnormal function of the Na+ channel, even if it is a secondary event in MH, may contribute to a positive contracture test result for MH.

Background: Halothane and caffeine diagnostic protocols and an experimental ryanodine test from the North American Malignant Hyperthermia (MH) Group (NAMHG) and the European MH Group (EMHG) have not been compared in the same persons until now., Methods: The outcomes of the NAMHG and EMHG halothane and caffeine contracture tests were compared in 84 persons referred for diagnostic testing. In addition, the authors assessed the experimental ryanodine protocol in 50 of these persons., Results: Although the NAMHG and EMHG halothane protocols are slightly different methodologically, each yielded outcomes in close (84-100%) agreement with diagnoses made by the other protocol. Excluding 23 persons judged to be equivocal (marginally positive responders) by the EMHG protocol resulted in fewer persons classified as normal and MH susceptible (42 and 19, respectively) than those classified by the NAMHG protocol (48 and 34, respectively). For the 61 persons not excluded as equivocal, the diagnoses were identical by both protocols, with the exception of one person who was diagnosed as MH susceptible by the NAMHG protocol and as "normal" by the EMHG protocol. The NAMHG protocol produced only two equivocal diagnoses. Therefore, a normal or MH diagnosis by the NAMHG protocol was frequently associated with an equivocal diagnosis by the EMHG protocol. The time to 0.2-g contracture after the addition of 1 microM ryanodine completely separated populations, which was in agreement with the EMHG protocol and, except for one person, with the NAMHG protocol., Conclusions: Overall, the NAMHG and EMHG protocols and the experimental ryanodine test yielded similar diagnoses. The EMHG protocol reduced the number of marginal responders in the final analysis, which may make the remaining diagnoses slightly more accurate for use in genetic studies.

Objective: To assess the clinical use of the Dynamic Objective Risk Assessment (DORA) severity of illness score in a site remote from its development., Design: Prospective chart review., Setting: Tertiary referral pediatric intensive care unit (PICU)., Patients: One hundred sixty consecutive admissions involving 621 patient days., Interventions: None., Measurements and Main Results: Pediatric Risk of Mortality (PRISM) scores were collected daily for all PICU patient days. Collection of data was performed by a physician not directly involved in the ordering of vital signs or laboratory data. The daily DORA score was calculated from the previous day's PRISM score and the admission PRISM score according to a previously described formula. The DORA score determines the patient's risk of mortality for the next 24 hrs. Also documented were the tests not ordered for each patient day. The sensitivity and specificity of the DORA score in our patient population were very similar to that previously reported using the previously described 1% cutoff for predicted mortality. We also noted that the tests ordered were related to the physician's perception of the patient's degree of sickness, and were themselves predictive of outcome., Conclusion: An outcome scoring system created in one group of PICUs can be applied to patients in another PICU remote from where the scoring system was developed with similar ability to predict outcome.

Background: The abundance of a specific sodium channel subunit (SkM2) appeared to be altered in vitro in cell cultures from persons susceptible to malignant hyperthermia. This study sought to determine whether these findings are artifacts of cell culture or whether they may be relevant to malignant hyperthermia., Methods: Regulation of transcript levels of SkM2, a specific sodium channel alpha-subunit, was determined by mRNA analysis. Functional SkM2 protein was estimated in biopsy sections of vastus lateralis muscle by inhibiting the directly elicited muscle twitch by tetrodotoxin, which can differentiate at least three sodium currents in skeletal muscle., Results: The transcript levels of SkM2 were depressed by 115-fold in six of seven persons susceptible to malignant hyperthermia; and the functional expression of the SkM2 protein, based on the tetrodotoxin sensitivity of the directly elicited twitch, was decreased by at least fourfold in muscle from persons susceptible to malignant hyperthermia compared with persons who were not susceptible., Conclusions: As in previous studies in cell culture, altered mRNA and/or the functional expression of a specific subunit of the sodium channel (SkM2) was found in biopsy sections of muscle from all 12 persons examined who were susceptible to malignant hyperthermia but in none of the 16 nonsusceptible participants. Human malignant hyperthermia is a heterogeneous disorder, and the down-regulation of SkM2 may be involved in the final common pathway through which mutations in any one of several proteins, including the ryanodine receptor, could render a person susceptible.

Background: Succinylcholine-induced masseter muscle rigidity (MMR) is a potentially life-threatening complication of anesthesia and is closely correlated with the heterogeneous disorder malignant hyperthermia (MH) susceptibility. MMR also is identified with a variety of neuromuscular disorders, including the myotonias, that are associated with abnormal in vitro contracture test (IVCT) results. Recently, mutations in the adult skeletal muscle sodium channel alpha-subunit gene (SCN4A) have been shown to cause generalized nondystrophic myotonias, some of which are associated with mild nonspecific symptoms. The purpose of the current investigation was to begin to evaluate the molecular genetic relationship between known mutations in the SCN4A gene, MMR, and the results of the IVCT used to diagnose MH-susceptibility., Methods: A single extended pedigree of 16 individuals was ascertained through a proband who experienced MMR and whole-body rigidity after succinylcholine administration. Subsequently, four individuals were shown to have a mild form of myotonia on clinical and laboratory examination. IVCT was carried out according to standardized protocols. Mutations in the SCN4A gene were sought in exons 22 and 24 using single-strand conformational analyses. Variability in the SCN4A gene sequence was confirmed by direct DNA sequence analyses., Results: Four individuals with myotonia were shown to carry a guanine-to-cytosine mutation at nucleotide position 3917 of the reported SCN4A sequence. This DNA mutation was coinherited with MMR and an abnormal IVCT result in this family. Previous studies have demonstrated that the glycine1306-to-alanine substitution is associated with a mild clinical syndrome referred to as myotonia fluctuans., Conclusions: The current report provides direct evidence that succinylcholine-induced MMR, whole-body rigidity, and an abnormal IVCT result are associated with a mutation in the SCN4A gene.

Background: Controversy exists regarding the definition of masseter muscle rigidity (MMR) and anesthetic management after MMR. This study reports current anesthetic management after MMR, estimates the incidence of clinical malignant hyperthermia (MH) in patients with MMR, and is the first to evaluate the coincidence of MMR with malignant hyperthermia susceptibility (MHS) according to the 1987 North American Malignant Hyperthermia Group protocol., Methods: Practicing anesthesiologists referred pediatric patients for biopsy between 1986 and 1991 based on evidence of MMR after succinylcholine (1975-1991). The clinical scenario was described as MMR alone or MMR followed by signs of MH, including arterial CO2 tension > 50 mmHg, arterial pH < or = 7.25, and base deficit > 8. Patients had caffeine-halothane muscle contracture testing to determine MHS., Results: Seventy patients (50 boys and 20 girls) were evaluated. Eighty-three percent (58 of 70) of anesthetics were halothane-succinylcholine. In 68% (48 of 70) of cases, the anesthetic was discontinued, whereas anesthesia was continued with nontriggering agents in 11% (8 of 70) and with triggering agents in 13% (9 of 70). Fifty-nine percent (41 of 70) of patients were diagnosed as MHS by muscle biopsy. In 7% (5 of 70) of patients, clinical MH developed within 10 min of MMR., Conclusions: This study, by using the current North American Malignant Hyperthermia Group protocol, reaffirms the high incidence (59%, 41 of 70) of MHS associated with MMR as confirmed by muscle biopsy. Of the MHS patients, 5 developed signs of clinical MH. Most anesthesiologists in this study, when confronted with MMR, discontinued anesthesia. Because of the potential lethality of MH and the > 50% concordance between MMR and MHS, the most conservative course of action after MMR is to discontinue the anesthetic and observe the patient for clinical evidence of MH. An acceptable alternative, depending on the urgency of the surgery, would be to continue anesthesia with nontriggering agents for MH, with appropriate monitoring.

Opioids are known to affect the MAC of inhalational anesthetics. We have determined the interaction between fentanyl and desflurane, following a bolus injection of fentanyl at induction in 134 adult patients. Five groups of patients were studied. Four groups received desflurane or isoflurane in oxygen with either fentanyl 3 or 6 micrograms/kg and thiopental 2-5 mg/kg given as a bolus injection at the time of induction. An additional group received desflurane in oxygen alone. Groups were stratified by age. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. The MAC desflurane in oxygen was 6.3% (5.3-7.6%, 95% confidence interval [CI]). Fentanyl 3 micrograms/kg produced a fentanyl plasma concentration of 0.78 +/- 0.53 ng/ml at skin incision and resulted in a MAC for desflurane of 2.6% (2.0-3.2%, 95% CI) %. Fentanyl 6 micrograms/kg produced a fentanyl plasma concentration of 1.72 +/- 0.76 ng/ml at skin incision and resulted in a MAC for desflurane of 2.1% (1.5-2.6%, 95% CI). To compare recovery times to eye-opening and response to commands, patients were grouped according to the plasma fentanyl concentrations at the time of awaking. Recovery was faster in patients who received desflurane than in those who received isoflurane. The authors conclude that the MAC of desflurane is significantly reduced 25 min following a single dose of 3 micrograms/kg of fentanyl and that increasing the fentanyl dose to 6 micrograms/kg produces little further decrease in MAC. Desflurane is also associated with faster recovery from anesthesia than is isoflurane.

Three doses of ocfentanil (1, 3, and 5 micrograms/kg), a new narcotic, were compared with fentanyl (5 micrograms/kg) as a supplement to general anesthesia. Sixty adult ASA I-III patients undergoing elective surgery were studied. The drugs were given as a bolus injection during induction of anesthesia in a double-blind manner. With the stimulus of tracheal intubation, systolic arterial blood pressure increased (mean +/- SE) from 127 +/- 6.9 to 183 +/- 7.4 mm Hg and heart rate increased from 82.1 +/- 4.8 to 104 +/- 6.4 beats/min in patients who had received 1 microgram/kg of ocfentanil intravenously. In comparison to patients who received 1 microgram/kg of ocfentanil, the increases in heart rate and systolic arterial blood pressure at the time of tracheal intubation were less with 3 and 5 micrograms/kg of ocfentanil and 5 micrograms/kg of fentanyl (P less than 0.05). At incision, heart rate decreased after the intravenous administration of 5 micrograms/kg of ocfentanil when compared with patients who received 1 microgram/kg of ocfentanil. There were differences between study groups in the mild increase in arterial blood pressure observed at incision. The authors conclude that ocfentanil and fentanyl appear to be similar in action, with 3 micrograms/kg of ocfentanil being approximately equivalent in effect to 5 micrograms/kg of fentanyl.

Recovery and psychomotor performance were studied in 80 ASA physical status I-III adult patients undergoing outpatient surgery. Patients were divided into four equal groups: thiopental induction of anesthesia followed by desflurane in nitrous oxide and oxygen (Th-DES-N2O/O2), thiopental induction of anesthesia followed by isoflurane in nitrous oxide and oxygen (Th-ISO-N2O/O2), thiopental induction of anesthesia followed by desflurane in oxygen (Th-DES-O2), and desflurane inhaled induction followed by desflurane in oxygen (DES-DES-O2). Patients were excluded from analysis if they required opioids or antiemetics postoperatively. The use of desflurane was associated with more rapid awakening compared with isoflurane (time to eye opening 9.45 +/- 0.67 min [Th-DES-N2O/O2] and 13.8 +/- 1.59 min [Th-ISO-N2O/O2], P less than 0.05). Psychomotor performance was measured using the choice reaction time and critical flicker fusion threshold. At 30 min after discontinuing anesthesia, five patients in the Th-ISO-N2O/O2 group and one patient in the Th-DES-N2O/O2 group were too sleepy to perform psychomotor tests. In addition, five patients who received Th-DES-O2 and one patient who received the inhaled induction and maintenance of anesthesia with desflurane in oxygen were too sleepy to perform tests at 30 min. Patients receiving Th-DES-N2O/O2 showed less impairment of choice reaction time than those receiving Th-ISO-N2O/O2. Critical flicker fusion threshold, however, showed no difference between groups. The use of thiopental was associated with delayed recovery. Compared with isoflurane, desflurane anesthesia is associated with more rapid initial awakening and less impairment of choice reaction time.

Anesthetic management and outcome were examined in patients with negative in vitro contracture tests for malignant hyperthermia (MH). Contracture testing was performed in a standardized fashion using 3% halothane alone and incremental doses of caffeine alone. Medical records were examined for 54 anesthetic exposures in 42 MH(-) patients who had received anesthesia since their MH testing. Sixteen patients received anesthesia with known MH triggering agents on 23 occasions, all without incident. In six MH(-) patients with previous masseter muscle rigidity, no adverse reactions occurred in response to volatile anesthetic agents. Succinylcholine was avoided in these patients. Eleven MH(-) patients were managed as if MH-susceptible, although it was known that these patients had tested MH(-). Two of these patients also receive prophylactic iv dantrolene. These results suggest that "triggering" anesthetic agents may be safely administered to patients who test MH(-) by in vitro contracture testing. However, until the anesthetic experience of larger numbers of MH(-) patients is known, these results should be interpreted cautiously.

Caffeine and halothane contracture testing is widely used to detect malignant hyperthermia (MH) susceptibility. The accuracy and reliability of the 3% halothane test and the incremental caffeine test, as recommended by the North American MH Group, were assessed in 11 swine (five MHS, six control). Nine swine were tested twice, 4-6 weeks apart. Accuracy of the in vitro diagnosis was also assessed by in vivo anesthetic challenge. Of all muscle bundles from MH-susceptible swine, 65% reacted positively to 3% halothane and 70% to 2 mM caffeine. Only 35% had a positive caffeine-specific concentration, and 25% developed an increase in baseline tension greater than or equal to 7% at 2 mM caffeine. However, when only the most positive response to 3% halothane or to 2 mM caffeine was used (a minimum of three fresh muscle strips is recommended), these two tests were highly sensitive and specific. In control swine one of 30 muscle bundles reacted positively to 3% halothane. A positive caffeine-specific concentration developed in one of 25 control muscle bundles exposed to caffeine. The variability in the results of these tests mandated that at least three muscle bundles be used for each test. Nonviable muscle bundles could not be relied upon to provide accurate results. In this porcine model, MH susceptibility could be detected by performing the Caffeine Halothane Contracture Test (CHCT) according to the guidelines of the North American MH Group. However, only the 3% halothane test and the response to 2 mM caffeine produced adequate diagnostic results in this breed of swine.

Previous studies in cat, rat, and swine have implicated fiber type as influencing the halothane and caffeine contracture test used to diagnose malignant hyperthermia (MH). The authors performed fiber type analysis using myosin ATPase stains on 31 fascicles of skeletal muscle from nine patients following contracture testing. There was no significant difference in fiber type composition between fascicles from MH negative (n = 5) and MH positive (n = 4) patients. Furthermore, examining each of the 31 fascicles, the authors found no correlation (P greater than .05) of contracture magnitude with percentage of either Type I or Type II fibers using the Pearson Product-Moment correlation calculation. The authors conclude that fiber type composition does not influence contracture test results in human biopsies.

Seventy-seven patients who developed masseter muscle rigidity (MMR) after receiving succinylcholine to facilitate tracheal intubation were evaluated for malignant hyperthermia (MH) susceptibility by in vitro halothane and caffeine contracture tests. Thirty-nine patients were diagnosed as MH-susceptible. Neither age, sex, nor type of surgery or anesthesia distinguished MH-susceptible from nonsusceptible patients. Two susceptible and two nonsusceptible patients had evidence of a myopathy. Fifty-two patients had serum creatine phosphokinase (CPK) levels measured in the perioperative period. Although all values were above normal, CPK values equal to or greater than 20,000 IU within 24 hr of trismus (in the absence of myopathy) were observed in six of 30 patients diagnosed as MH-susceptible, but were found in none of the nonsusceptible patients. Considering the high percentage of patients exhibiting MMR that are indeed susceptible to MH (approximately 50%) compared to estimates of MH in the population as a whole (approximately 0.005%), MMR should be considered a presumptive sign of MH. Perioperative CPK values greater than 20,000 IU are highly suggestive of MH susceptibility. Patients exhibiting MMR should be evaluated for MH susceptibility and myopathies. Succinylcholine should be avoided for subsequent anesthetics in patients with a history of MMR.

This study examines in vitro the contractures induced by halothane and succinylcholine in skeletal muscle taken as biopsy specimens from 42 patients referred to the authors' laboratory for diagnosis of malignant hyperthermia (MH) susceptibility. In addition, possible differences between the response of preparations from these same patients with and without a history of masseter muscle rigidity following succinylcholine (SCh) administration were determined to investigate the in vitro relationship of masseter muscle rigidity to MH. Halothane 3%-induced contractures in preparations from MH susceptibles were similar, whether the group had a history of masseter muscle rigidity (1.15 +/- 0.18 g; n = 10) or not (1.02 +/- 0.21 g; n = 14). Halothane did not induce significant contractures in those diagnosed as normals. Succinylcholine alone did not elicit contractures from preparations derived from MH susceptibles or nonsusceptibles. Succinylcholine induced significant contractures in all preparations preexposed to halothane. Preparations from MH-negative patients with a history of masseter muscle rigidity were rendered sensitive to halothane (contractures of 1.17 +/- 0.30 g; n = 4) when SCh was present. In contrast, halothane added in the presence of SCh did not induce contractures to the same extent in preparations from MH-negative patients without a history of masseter muscle rigidity. This is the first reported in vitro method by which to examine the clinically troublesome interaction between SCh and halothane. This approach also may prove to be important in further investigations of the relationship between masseter muscle rigidity and MH.

The relationship between neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) was investigated using the in vitro skeletal muscle contracture test to screen for MH-susceptibility in NMS patients. The maximum contracture tension which developed following exposure to halothane (1-3%), and incremental doses of fluphenazine (0.2-25.6 mM) was measured in muscle obtained from seven NMS, six MH, and six control patients. Comparison of the cumulative responses to fluphenazine revealed no significant differences among the groups. However, the response (mean +/- SEM) to halothane in the NMS group (1.7 +/- 0.7 g), which was similar to the response in the MH group (1.5 +/- 0.2 g), was significantly greater than the response found in controls (0.2 +/- 0.1 g). In addition, five of seven NMS patients could be diagnosed as MH-susceptible, based on the development of muscle contractures greater than 0.7 g in response to 1-3% halothane. In contrast, none of the controls were MH-susceptible. These findings appear to correlate with clinical evidence suggesting an association between NMS and MH.

The fragility of erythrocytes from 21 patients undergoing in vitro skeletal muscle contracture testing for malignant hyperthermia (MH) susceptibility was examined. Osmotic fragility was determined by the degree of hemolysis in buffered saline solutions of decreasing osmotic strength. Halothane-induced fragility was determined in an isotonic solution containing increasing percentages of halothane saturated solution. The effects of six different incubation conditions prior to performing fragility tests were examined in an attempt to optimize discrimination of MH susceptible patients, including the following: 1) no preincubation; 2) 24-hr incubation at 4 degrees C; 3) 72-hr incubation at 4 degrees C; 4) 24-hr incubation at 37 degrees C; 5) 24-hr incubation at 22 degrees C with plasma from an MH-susceptible patient; and 6) 24-hr incubation at 22 degrees C with plasma from a normal patient. Despite examining six different incubating conditions and the two methods of hemolysis induction, no differences in erythrocyte fragility were detected between patients diagnosed as MH susceptible or normal. Erythrocyte fragility testing is not useful for diagnosing MH susceptibility.