Malignant Hyperthermia vs. Neuroleptic Malignant Syndrome ========================================================= see also: Serotonin Syndrome Neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) share many clinical features the most prominant of which are hyperthermia and muscular rigdity. However extrapyramidal manifestations are not a feature of MH and the extent of temperature elevation in the latter is, in general, much greater than in NMS. The cause of the temperature elevation is believed to be related to the muscular activity in both cases but the underlying cause of this is different in each case. In MH a defect in muscle calcium tranport is believed to be responsible whereas NMS is probably of central origin and related to hypothalamic dopamine blockage or deficiency. There is *no* overlap in the drugs that cause one syndrome or the other (2). Rare case reports have identified patients who have been diagnosed with both disorders (1). In-vitro tests in patients who have been diagnosed with NMS have failed to identify this group as being at risk for development of MH and thus anesthetic management would not be altered (3). In fact the muscular rigidity and fever associated with NMS has been sucessfully treated with sux (4) although most authors prefer the use of pancuronium (when an NMB is deemed to be indicated) for this purpose. Pseudocholinesterase deficiency will prolong the duration of paralysis in patients given depolarizing NMBs. Even those with normal cholinesterase genotypes exhibit a graded response to sux based upon their baseline levels (5). There is no relation between pseudocholinesterase levels and the development of NMS. H. Louzon MD (1) Kelly D, Brull SJ Neuroleptic malignant syndrome and mivacurium: a safe alternative to succinylcholine? Can J Anaesth 1994 Sep;41(9):845-9 Neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) may have a common pathogenic mechanism; therefore, it has been suggested that known triggering agents for MH (such as succinylcholine) should be avoided in patients with NMS. Electroconvulsive therapy (ECT) continues to play a major therapeutic role in contemporary psychiatry, and succinylcholine has been the muscle relaxant of choice in attenuating violent muscle contractions induced by ECT. Mivacurium is a non-depolarizing muscle relaxant with a relatively rapid onset and a short duration of action, and to date it has been proved safe in MH-susceptible patients. In this case report, following succinylcholine use during ECT, a patient with NMS developed an increase in temperature and serum creatine kinase (CK) level, possibly due to an MH reaction. Since the patient's mental status necessitated further ECT, mivacurium was administered during subsequent treatment and resulted in effective attenuation of muscle contractions without elevation of patient temperature or CK levels. In addition, there was no marked prolongation of the anaesthetic. Mivacurium is a suitable agent for patients with NMS undergoing ECT, as it has not been associated with precipitation of an MH response. (2) Keck PE Jr, Caroff SN, McElroy SL Neuroleptic malignant syndrome and malignant hyperthermia: end of a controversy? J Neuropsychiatry Clin Neurosci 1995 Spring;7(2):135-44 Two primary hypotheses have been proposed to explain the pathophysiology of the neuroleptic malignant syndrome (NMS): 1) that NMS is produced by abrupt and extensive central dopamine receptor blockade by neuroleptics, particularly in nigrostriatal and hypothalamic pathways; and 2) that NMS, like malignant hyperthermia (MH), results from a preexisting defect in skeletal muscle metabolism that is unmasked or provoked by neuroleptic exposure. To evaluate these models, the authors review studies published since 1980 of the clinical features, epidemiology, risk factors, laboratory assessment, and relevant animal models of NMS and MH. Data from these studies suggest that although NMS and MH are clinically similar, they are pharmacologically distinct, implying that cross-reactivity between triggering agents is unlikely to occur. (3) Bello N, Adnet P, Saulnier F, Lestavel P, Adnet-Bonte C, Reyford H, Etchrivi T, Tavernier B, Krivosic-Horber R [Lack of sensitivity to per-anesthetic malignant hyperthermia in 32 patients who developed neuroleptic malignant syndrome] Ann Fr Anesth Reanim 1994;13(5):663-8 The aim of this study was to verify whether a relationship exists between neuroleptic malignant syndrome (NMS) and anaesthetic-induced malignant hyperthermia (MH) or not. The in vitro halothane-caffeine tests were performed on muscle tissue obtained from 32 patients with documented NMS episodes. The diagnosis of NMS relied on Levenson's criteria. The results, expressed in accordance with the criteria of the European MH Group, defined 29 subjects as MH non-susceptible. Three patients were classified as MH equivocal. These findings demonstrate the lack of any link between NMS and MH. Therefore, patients with a history of NMS are not likely to be at risk of developing MH and special measures against MH are not required for anaesthesia in these patients. (4) Morris HH 3d, McCormick WF, Reinarz JA Neuroleptic malignant syndrome. Arch Neurol 1980 Jul;37(7):462-3 The neuroleptic malignant syndrome is an uncommon, severe illness that consists of fever, muscular rigidity, and stupor. Various neuroleptics have been associated with the disease. A detailed neurological, medical, and neuropathological evaluation of this case was performed. Presumably, the syndrome is secondary to biochemical dysfunction of the basal ganglia and possible of the hypothalmus. (5) Vanlinthout LE, van Egmond J, de Boo T, Lerou JG, Wevers RA, Booij LH Factors affecting magnitude and time course of neuromuscular block produced by suxamethonium. Br J Anaesth 1992 Jul;69(1):29-35 This study was designed to identify factors that significantly alter the magnitude and duration of suxamethonium-induced neuromuscular block in patients with an apparently normal genotype for pseudocholinesterase. One hundred and fifty-six adults (ages 18-65 yr) were allocated to 13 subgroups. Patients in each subgroup received suxamethonium 50-2000 micrograms kg-1. The mechanographic response of the adductor pollicis brevis muscle to ulnar nerve stimulation was recorded. The ED50 was found to be 167 micrograms kg-1, ED90 was 316 micrograms kg-1 and ED95 was 392 micrograms kg-1. The duration of action (delta t) was in agreement with earlier published results. The magnitude of block was dose-related and decreased with increasing onset time (ton) and pseudocholinesterase activity (PChA). Neither age nor gender affected the degree of suxamethonium-induced block. Delta t was dose-related, decreased with increasing PChA, and was shorter for women. Age and ton had no effect on delta t.