Gerald A. Gronert

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.

Up-and-down Regulation of Skeletal Muscle Acetylcholine Receptors Effects on Neuromuscular Blockers

Multiple factors alter the interaction of muscle relaxants with the NMJ. This review has focused on the aberrant responses caused principally by alterations in AChRs (table 1). Many pathologic states increase (up-regulate) AChR number. These include upper and lower motor neuron lesions, muscle trauma, burns, and immobilization. Pre- or postjunctional inhibition of neurotransmission by drugs or toxins also up-regulate AChRs. These include alpha- and beta-BT, NDMR, anticonvulsants, and clostridial toxins. We speculate that other bacterial toxins also up-regulate AChR. With proliferation of AChRs, agonist drug dose-response curves are shifted to the left. The exaggerated release of potassium when depolarization occurs with the use of agonists such as SCh and decamethonium can be attributed to the increased number of AChR. Thus, SCh should be avoided in patients who are in the susceptible phase (see section V). In the presence of increased AChR, the requirement for NDMR is markedly increased. Thus, the response to NDMR may be used as an indirect estimator of increased sensitivity to SCh (table 1). The most extensively studied pathologic state in which there is a decrease in AChRs is myasthenia gravis; there is immunologically mediated destruction and/or functional blockade of AChRs. The pathophysiologic and pharmacologic changes in LEMS are quite distinct from those of myasthenia gravis. Decreased AChRs in myasthenia gravis result in resistance to agonists and increased sensitivity to competitive antagonists. In conditioning exercise, the perturbed muscles show sensitivity to NDMR that may be due to decreased AChRs. Chronic elevations of ACh observed with organophosphorus poisoning or chronic use of reversible cholinesterase inhibitors results in down-regulation of AChRs. In this condition, SCh should be avoided because its metabolic breakdown would be impaired; the requirement for NDMR may be decreased. All of the varied responses to SCh and NDMR, which are associated with concomitant changes in AChRs, are analogous to drug-receptor interactions observed in other biologic systems.

Pathophysiology of hyperkalemia induced by succinylcholine.

: SCh is unequivocally contraindicated in the management of patients who have sustainded thermal trauma or direct muscle trauma and those who have neurologic disorders involving motor deficits, including tetanus. The mechanism is clear in some, but not all, of these conditions, and is related to increased chemosensitivity of the muscle membrane due to the development of receptor sites in extrajunctional areas. Though SCh induces a small release of K+ in normal muscle, it produces a potentially lethal efflux in the presence of increased sensitivity. This K+-releasing action of SCh begins about 5 to 15 days after injury and persists for 2 to 3 months in patients who have sustained burns or trauma, and perhaps 3 to 6 months in patients with upper motor neuron lesions.

Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006.

BACKGROUND: We analyzed cases of malignant hyperthermia (MH) reported to the North American MH Registry for clinical characteristics, treatment, and complications. METHODS: Our inclusion criteria were as follows: AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports between January 1, 1987 and December 31, 2006; “very likely” or “almost certain” MH as ranked by the clinical grading scale; United States or Canadian location; and more than one anesthetic drug given. An exclusion criterion was pathology other than MH; for complication analysis, patients with unknown status or minor complications attributable to dantrolene were excluded. Wilcoxon rank sum and Pearson exact &khgr;2 tests were applied. A multivariable model of the risk of complications from MH was created through stepwise selection with fit judged by the Hosmer-Lemeshow statistic. RESULTS: Young males (74.8%) dominated in 286 episodes. A total of 6.5% had an MH family history; 77 of 152 patients with MH reported ≥2 prior unremarkable general anesthetics. In 10 cases, skin liquid crystal temperature did not trend. Frequent initial MH signs were hypercarbia, sinus tachycardia, or masseter spasm. In 63.5%, temperature abnormality (median maximum, 39.1°C) was the first to third sign. Whereas 78.6% presented with both muscular abnormalities and respiratory acidosis, only 26.0% had metabolic acidosis. The median total dantrolene dose was 5.9 mg/kg (first quartile, 3.0 mg/kg; third quartile, 10.0 mg/kg), although 22 patients received no dantrolene and survived. A total of 53.9% received bicarbonate therapy. Complications not including recrudescence, cardiac arrest, or death occurred in 63 of 181 patients (34.8%) with MH. Twenty-one experienced hematologic and/or neurologic complications with a temperature <41.6°C (human critical thermal maximum). The likelihood of any complication increased 2.9 times per 2°C increase in maximum temperature and 1.6 times per 30-minute delay in dantrolene use. CONCLUSION: Elevated temperature may be an early MH sign. Although increased temperature occurs frequently, metabolic acidosis occurs one-third as often. Accurate temperature monitoring during general anesthetics and early dantrolene administration may decrease the 35% MH morbidity rate.

Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: The effects of halothane and dantrolene

Calcium‐induced calcium release and halothane‐induced calcium release from pig sarcoplasmic reticulum (SR) were studied. The SR prepared from pig susceptible to malignant hyperthermia (MH) was shown to release calcium at a much lower level of calcium content than in normal pig SR. The concentration above which halothane can release calcium is 40 μM for both MH‐SR and normal SR, although the latter required a high calcium content to demonstrate the calcium release. Dantrolene was shown to inhibit the halothane‐induced calcium release. Results suggests that SR plays an importnat role in pathogenesis of MH.

Cardiac arrest after succinylcholine: mortality greater with rhabdomyolysis than receptor upregulation.

THIS all began during the World Congress of Anaesthesiologists in Holland in June 1992, at an extramural multinational panel convened to prepare an educational videotape.† Speakers from the United States and Germany described pediatric cases of sudden rhabdomyolysis and hyperkalemic cardiac arrest after administration of succinylcholine. Despite prompt and apparently skilled resuscitation, the mortality rate was 40–55%. This surprising and puzzling mortality rate prompted considerable discussion and, over time, repeated reflection on what might be happening.

Isoflurane and Cerebrospinal Fluid Pressure in Neurosurgical Patients

The effect of isoflurane on cerebrospinal fluid pressure (CSFP) was determined in 20 patients undergoing craniotomy for intracranial supratentorial neoplasm or hematoma. In 15 of these patients, following endotracheal intubation, hyperventilation sufficient to result in Paco2 25–30 torr was begun simultaneously with the introduction of 1 per cent isoflurane. In the remaining five patients ventilation was equivalent, but normocapnia was maintained by adding CO2 to the inspired gases. In the hypocapnic patients CSFPs did not increase above awake values (range 5–45 torr) following isoflurane administration. In the normocapnic patients CSFPs consistently increased. In three of these five patients the increases were precipitous, but were corrected rapidly by establishment of hypocapnia. The authors conclude that the known cerebral vasodilator properties of isoflurance can be countered effectively by hypocapnia. Furthermore, unlike the situation with halothane, it is not necessary to establish hypocapnia prior to introducing isoflurane in order to avoid CSFP increases.

Evaluation of an Ultrasonic Device (doppler) for the Diagnosis of Venous Air Embolism

While being operated on in the upright position, 69 patients were monitored with an ultrasonic device (Doppler) to detect venous air embolism. A right atrial catheter had been inserted previously. Air embolism was suspected or confirmed on 29 occasions in 22 patients. Twenty episodes were signaled by change in the Doppler sounds and confirmed by aspirating air bubbles from the atrium; only one patient developed clinical air embolism. Seven episodes suspected because of characteristic Doppler sound changes were not confirmed by aspirating air or by the development of clinical signs. Two episodes were signaled by the onset of a systolic murmur and confirmed by aspirating air from the atrium; neither was accompanied by changes in Doppler sounds. No patient had complications secondary to air embolism. It is concluded that air embolism is common during operations with the patients upright; that serious sequelae can be minimized by early diagnosis and prompt treatment; and that the Doppler device detects air embolism sensitively but imperfectly.

Internal carotid artery stump pressure and cerebral blood flow during carotid endarterectomy: modification by halothane, enflurane, and innovar.

Carotid endarterectomy requires temporary surgical occlusion of the involved carotid artery. During occlusion, the minimally acceptable (critical) internal carotid artery stump pressure is reported to be 50 torr, whereas for regional cerebral blood flow (rCBF), a critical range is reported to be 18–24 ml/100 g/min. During 90 carotid endarterectomies. rCBF and stump pressure were measured and the EEG continuously monitored. A positive correlation between rCBF and stump pressure (i.e., when both were either above or below their respective critical values) was observed in only 58 percent of the cases. In 28 per cent stump pressures of less than 50 torr were observed despite rCBFs above 24 ml/100 g/min and normal EEGs. In 8 per cent stump pressures were more than 50 torr but rCBFs were less than 18 ml/100 g/min and EEG changes of ischemia were commonly observed. In the remaining 6 per cent rCBFs were marginal (18–24 ml/100 g/min) while stump pressures were more than 50 torr and EEG changes were not observed. The relationship between stump pressure and rCBF was influenced by the anesthetic. In the absence of transient ischemia during occlusion (that is, rCBF > 18 ml/100 g/min), halothane and enflurane anesthesia were associated with significantly higher rCBFs and lower stump pressures than was neuroleptanesthesia. Pre-occlusion and post-occlusion rCBF measurements also demonstrated cerebral vasodilation by halothane and enflurane (halothane > enflurane) and vasoconstriction by neuroleptanesthesia. It is concluded that stump pressure is an unreliable index of CBF during carotid occlusion and that its relationship to CBF is considerably influenced by the anesthetic.

Cardiac Arrests and Deaths Associated with Malignant Hyperthermia in North America from 1987 to 2006 : A Report from The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States

Background:The authors determined associated cardiac arrest and death rates in cases from Canada and the United States as reported to The North American Malignant Hyperthermia (MH) Registry and analyzed factors associated with a higher risk of poor outcomes. Methods:The authors searched the database for AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports with inclusion criteria as follows: event date between January 1, 1987, and December 31, 2006; “very likely” or “almost certain” MH as ranked by MH Clinical Grading Scale; location in Canada or the United States; and one or more anesthetic agents given. The exclusion criterion was a pathologic condition other than MH independently judged by the authors. Severe MH outcomes were analyzed as regards clinical history and presentation, using Wilcoxon rank sum tests for continuous variables and Pearson exact chi-square tests for categorical variables. A Bonferroni correction adjusted for multiple comparisons. Results:Of 291 events, 8 (2.7%) resulted in cardiac arrests and 4 (1.4%) resulted in death. The median age in cases of cardiac arrest/death was 20 yr (range, 2–31 yr). Associated factors were muscular build (odds ratio, 18.7; P = 0.0016) and disseminated intravascular coagulation (odds ratio, 49.7; P < 0.0001). Increased risk of cardiac arrest/death was related to a longer time period between anesthetic induction and maximum end-tidal carbon dioxide (216 vs. 87 min; P = 0.003). Unrelated factors included patient or family history, anesthetic management, and the MH episode. Conclusions:Modern US anesthetic practice did not prevent MH-associated cardiac arrest and death in predominantly young, healthy patients undergoing low- to intermediate-risk surgical procedures.