Richard F. Kaplan

A Clinical Grading Scale to Predict Malignant Hyperthermia Susceptibility

Background:The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. Methods:Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. Results:This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patients medical condition, anesthetic technique, and surgical procedure. Conclusions:The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. Its use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.

Postoperative malignant hyperthermia: an analysis of cases from the North American Malignant Hyperthermia Registry.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Jaw Relaxation after a Halothane/Succinylcholine Sequence in Children

BackgroundLack of complete jaw relaxation after a halothane-succinylcholine sequence has been described in the literature. To date, however, most existing studies are retrospective, and lack agreement on the magnitude and Incidence of this phenomenon. This prospective study examined the incidence and degree of Incomplete jaw relaxation in 500 children who were given Intravenous succinylcholine during halothane anesthesia. MethodsFive hundred consecutive unmedicated children received a minimum dose of 2 mg/kg Intravenous succlnylcholine after Induction of anesthesia with halothane. The degree of jaw relaxation was assessed 45–60 s later by the same observer using a standardized clinical scale. The degree of relaxation was correlated with the type of surgical procedure, and the presence and intensity of fasciculatlons. ResultsComplete relaxation (mouth opened easily and fully) occurred in 95.4% of study patients. Incomplete relaxation (firm manual separation required to open the mouth fully) was seen in 4.4% of the patients. One child (0.2%) had masseter muscle rigidity (mouth could not be fully opened but intubation possible). There were no Incidents of trismus (teeth clamped shut and intubation via direct visualization impossible). The incidence of incomplete relaxation and masseter muscle rigidity did not correlate with the presence or degree of fasciculations or the type of surgical procedure. There were no clinical signs of a hypermetabolic state or myogloblnuria in any patient. ConclusionsIncomplete jaw relaxation after a halothane-succlnylcholine sequence is not uncommon in children, and is considered a normal response.

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1–12 yr. All received premedication with midazolam, 0.5 mg · kg−1 po and an inhalational induction with up to 3 MAC of either agent in 70% N2O and O2. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg · kg−1) iv. The onset of maximal blockade occurred in 2.4 ± 1.26 (mean ± SD) min with halothane and 1.8 ± 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 ± 2.6, 19.5 ± 4.4, and 24.2 ± 4.8 min) were greater than during halothane anaesthesia (7.2 ± 2.2, 15.0 ± 4.0, 19.2 ± 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T1 > 95%, T4/T1 > 75%) during the surgery which lasted 24–63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary.RésuméL’activité neurobloquante du mivacurium pendant l’anesthésie au sévoflurane ou à l’halothane fait l’objet de cette étude réalisée chez 38 enfants de 1 à 12 ans. Tous ont été prémédiqués au midazolam 0,5 mg · kg−1 et l’anesthésie est induite avec un agent volatil jusqu’à MAC 3 de l’un des agents dans du N2O à 70%. Le nerf cubital était stimulé au poignet au train de quatre aux dix seconds et la force de l’adduction du pouce mesurée avec un transducteur de force Myotrace. L’anesthésie était entretenue avec l’équivalent MAC I d’un des deux agents volatils pendant cinq minutes avant l’administration de mivacurium (0,2 mg · kg−1). Le début du bloc maximum est survenu dans 2,4 ± 1,26 (moyenne ± SD) min avec l’halothane et 1,8 ± 0,54 min avec le sévoflurane (NS). Quatre patients n’ont pas été bloqués à 100% (trois avec l’halothane, un avec le sévoflurane). L’intervalle séparant l’injection à 5; 75, et 95% de la récupération pendant l’anesthésie au sévoflurane (9,8 ± 2,6, 19,5 ± 4,4 et 24,2 ± 4,8 min) a été plus long que pendant l’anesthésie à l’halothane (7,2 ± 2,2, 15,0 ± 4,0, 19,2 ± 4,9 min, respectivement (P < 0,005). An moniteur, chez tous les patients, la fonction neuromusculaire a récupéré spontanément (T1 > 95%, T4/T1 > 75%) au cours de la chirurgie qui a duré de 24–63 min. Tous les patients montraient aussi les signes cliniques d’une récupération complète (par ex., levée de la tête, réflexe pharyngé ou toux). Aucun antagoniste pharmacologique n’a été requis. Il est conclu que le délai jusqu’à la relaxation maximum après une seule dose d’intubation de mivacurium ne diffère pas entre l’anesthésie à l’halothane et l’anesthésie au sévoflurane; les délais de retour à 5, 75 et 95% de la hauteur du twitch sont plus longs pendant l’anesthésie au sévoflurane et il n’est pas nécessaire d’antagoniser le bloc neuromusculaire.

Intramuscular Rocuronium in Infants and Children A Multicenter Study To Evaluate Tracheal Intubating Conditions, Onset, and Duration of Action

BACKGROUND This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia. METHODS Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if <2.5 yr; 0.80% end-tidal concentration if >2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed. RESULTS The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided > or =98% blockade in 7.4+/-3.4 min (in infants) and 8+/-6.3 min (in children). Twenty-five percent recovery occurred in 79+/-26 min (in infants) and in 86+/-22 min (in children). CONCLUSIONS Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary.

Intramuscular rapacuronium in infants and children: a comparative multicenter study to confirm the efficacy and safety of the age-related tracheal intubating doses of intramuscular rapacuronium (ORG 9487) in two groups of pediatric subjects.

BackgroundThis multicenter, assessor, blinded, randomized study was conducted to confirm and extend a pilot study in which intramuscular rapacuronium was given to infants and children to confirm efficacy and to evaluate tracheal intubating conditions. MethodsNinety-six pediatric patients were studied in two groups: infants aged 1 to 12 months (n = 46) and children aged 1 to 3 yr (n = 50). Infants received 2.8 mg/kg and children 4.8 mg/kg of intramuscular rapacuronium during 1 minimum alveolar concentration halothane anesthesia. These two groups were studied in three subgroups, depending on the time (1.5, 3, or 4 min) at which tracheal intubation was attempted after the administration of intramuscular rapacuronium into the deltoid muscle. Neuromuscular data collected included onset time, duration of action, and recovery data during train-of-four stimulation at 0.1 Hz. Data were analyzed by the Cochran-Mantel-Haenszel procedure. ResultsThe tracheal intubating conditions were deemed acceptable in 17, 36, and 64% of infants and 20, 47, and 71% of children at 1.5, 3, or 4 min, respectively. The mean values for % of control twitch height (T1) 2 min after rapacuronium in both groups were similar. The mean (SD) time required to achieve more than or equal to 95% twitch depression in infants was 6.0 (3.7) versus 5.5 (3.8) min in children. ConclusionsOnly 27% of patients achieved clinically acceptable tracheal intubating conditions at 1.5 or 3 min after administration of 2.8 mg/kg and 4.8 mg/kg rapacuronium during 1 minimum alveolar concentration halothane anesthesia. Tracheal intubation conditions at 4 min were acceptable in 69% of subjects. The duration of action of 4.8 mg/kg of rapacuronium in children was longer than 2.8 mg/kg of rapacuronium in infants.

Halothane-induced ATP Depletion in Platelets from Patients Susceptible to Malignant Hyperthermia and from Controls

Since the cellular defect of malignant hyperthermia (MH) may occur in tissues other than muscle and since platelets share certain contractile characteristics with muscle cells, testing platelets has been suggested as a way to diagnose susceptibility to MH. In analogy to the in vitro depletion of muscle adenosine triphosphate (ATP), the authors compared platelet basal nucleotide levels and halothane-induced depletion of ATP from 10 MH-susceptible patients and from 12 unrelated nonsusceptible controls. A rapid and simple isocratic high-pressure liquid chromatography technique was used to analyze acid-extracted platelet nucleotides. Halothane added to platelet-rich plasma at 37°C significantly decreased ATP in platelets in a dose-dependent as well as a time-dependent manner. In contrast, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were not changed significantly. Other volatile anesthetic agents also depleted ATP in platelets. Although ATP in platelets exposed to halothane was depleted significantly, there was no difference between platelets from MH-susceptible patients and non-susceptible controls. Therefore, halothane-induced ATP depletion in platelets is not a reliable test for diagnosing MH susceptibility.

Sedation for Diagnostic and Therapeutic Procedures Outside the Operating Room

Abstract Sedation of children for tests and procedures represents a significant portion of the care that pediatric anesthesiologists provide. At the same time, other pediatric subspecialists also provide sedation services for which pediatric anesthesiologists provide back-up and oversight. The manner in which sedation is divided between anesthesiologists and other specialists is not consistent between institutions and must be decided based on patient need and the availability of individuals who are qualified to provide sedation. To aid in standardization, sedation guidelines have been promulgated by multiple organizations with the objective of bringing the same rigorous standards for evaluation, monitoring, documentation, and quality improvement to the practice of sedation that has characterized anesthesiology care. Sedation outcomes are generally improved when this care is provided in an organized system of care in which the sedation providers, administrators, nurses, and technical support have well understood protocols for scheduling cases, induction/maintenance of sedation, and recovery/discharge. The unique challenge of sedation lies in providing safe and effective service while working in a multitude of locations, each with unique challenges. Sedation providers must be aware of the requirements of each venue such as the pain and repeated procedures that characterize oncology procedures or the strong magnetic field of the MRI scanner. Care must be designed that meets the needs of the patient and the individual who is performing the procedure. In order to optimize sedation provision, an extensive knowledge of the pharmacokinetics and pharmacodynamics of the sedative and analgesic agents is critical.

Repeat episodes of severe muscle rigidity in a child receiving sevoflurane

We report on a patient who developed two episodes of severe muscle rigidity, increased endtidal CO2 and increased creatine phosphate kinase associated with sevoflurane anesthesia. Dysrhythmias and hyperthermia were not observed and dantrolene was not administered. Genetic testing for the 17 known mutations associated with malignant hyperthermia (MH) was negative. Although we cannot rule out MH or other neuromuscular diseases we suggest that this rare event may be a direct effect of sevoflurane.

Juvenile hyaline fibromatosis: anesthetic management

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disease with incomplete penetrance. Difficulty with intubation of the trachea may be caused by gingival hypertrophy and tempromandibular joint and cervical spine contractures