Neuroleptic Malignant Syndrome
Transcription
Neuroleptic Malignant Syndrome
12/20/2010 Neuroleptic Malignant Syndrome Disclaimer NEITHER THE PUBLISHER NOR THE AUTHORS ASSUME ANY LIABILITY FOR Anoop Bhagat ANY INJURY AND OR DAMAGE TO Medicine/Psychiatry PERSONS OR PROPERTY ARISING FROM Resident Objectives THIS WEBSITE AND ITS CONTENT. Introduction Life threatening and potentially fatal. Identifying Neuroleptic Malignant Syndrome Pathophysiology of Neuroleptic Malignant Syndrome Treatment of Neuroleptic Malignant Syndrome Legal aspects Idiosyncratic reaction to a neuroleptic medication. Delay and Colleagues ‘akinetic hypertonic syndrome’ After introduction of neuroleptics in 1960 Typical and Atypical Antipsychotics 1 12/20/2010 Associated Medications Most often seen with the typical high potency neuroleptic agents Reported also with : - low potency neuroleptic agents - atypical antipsychotic agents - antiemetic agents Antiparkinson medication withdrawal Epidemiology Epidemiology Incidence Agency for Healthcare Research and Quality - 2000 – 2075 cases - 2001 – 2444 cases - 2002 – 1835 cases Risk factors Most frequently older antipsychotics Duration of treatment Keck and associates No geographic variation Pre-morbid Psychomotor agitation No racial variation Higher in males Higher doses of neuroleptics with greater rates of dose increase Less than 40 years of age Higher number of intramuscular injections Elderly and children Concurrent use of lithium 0.02 to 2.4 percent 2 12/20/2010 Risk Factors Mortality Simultaneous use of 2 or more neuroleptics 10 – 20 % Encephalitis, Encephalitis AIDS increase susceptibility Decreased over the past 2 decades Dehydration Maybe due to the awareness of the syndrome High serum creatinine kinase Higher mortality with medical complications Iron defeciency and substance abuse Neuroleptic Malignant Syndrome Pathogenesis Detection of Suspected Neuroleptic Malignant Syndrome DVD/VHS Trailer Central dopamine blockade theory. 2 Major Theories. Theories Neuroleptic induced muscle toxicity. 3 12/20/2010 Central Dopamine Blockade Theory Dopamine Activity Thermoregulation Suggested by Henderson and Wooten Hypothalamus Impaired heat dissipation Corpus Striatum Muscle rigidity Spinal cord Autonomic disturbances Low CSF dopamine metabolite Pathophysiology Neuroleptic Induced Muscle Toxicity Calcium ion transport Increased contractility Hyperthermia Muscle cell breakdown Dantrolene 4 12/20/2010 Genetics Clinical Manifestations Mental status change - 82 % of patients Familial clusters D2 receptor gene Reduced function of dopamine receptors Inherited changes Muscular rigidity - lead pipe rigidity Hyperthermia - 87 % of patients Autonomic instability - 88% of patients Atypical Manifestations Atypical antipsychotics Conventional antipsychotics Varied presentation Criteria A Development of severe muscle rigidity Development of elevated temperature Associated with neuroleptic medication use DSM V 5 12/20/2010 Criteria B Criteria C Two or more of the following: 1. diaphoresis 2. dysphagia 3. tremor 4. incontinence 5. changes in the level of conciousness ranging from confusion to coma The symptoms in Criteria A and B are not due to another substance (eg. Phencyclidine) or a neurological or other general medical condition (eg. Viral encephalitis). 6. mutism 7. tachycardia 8. elevated or labile blood pressure 9. leukocytosis 10. Laboratory evidence of muscle injury (eg. Elevated CPK) Criteria D Dysautonomic syndromes Serotonin syndrome The symptoms in Criteria A and B are not better accounted for by a mental disorder (eg. Mood disorder with catatonic features). M li th th i Malignant hyperthermia Malignant catatonia Central anticholinergic syndrome and other drug related syndromes 6 12/20/2010 Serotonin Syndrome NMS vs. Serotonin Syndrome Detailed history of medication use Use of Serotonin Specific Reuptake Inhibitors Medication dose adjustment Shivering Symptom onset Hyperreflexia Neuromuscular Myoclonus Rhabdomyolysis Ataxia Metabolic Acidosis GI effects Malignant Hyperthermia Rare genetic disorder Associated with anesthetic agents Hyperthermia Muscle rigidity Dysautonomia Muscle contracture testing Malignant Catatonia Behavioral prodrome Psychosis, agitation, catatonic excitement Dystonic posturing, waxy flexibility, stereotyped repetitive movements Impossible to differentiate in 22% of patients Laboratory values are typically normal 7 12/20/2010 Catatonia Anticholinergic Syndrome Dry skin, decreased sweating, mydriasis, dry mouth http://www.youtube.com/watch?v=zAEJ-Jvndms Less severe elevated body temperature and encephalopathy Creatinine kinase levels not elevated Diaphoresis and rigidity are absent Other Drugs Differential Diagnosis Cocaine and ecstasy Increased physical exertion Rigidity is not common 8 12/20/2010 Investigations Imaging Complete blood count (CBC) Blood cultures Comprehensive metabolic profile Creatinine kinase level Urine myoglobin level CXR CT Head Lumbar Puncture Arterial blood gas (ABG) level INR Serum and urine drug screening (eg, salicylates, cocaine, amphetamines) Laboratory Abnormalities Elevated serum CK Leukocytosis Liver transaminases Acute renal failure Histology Muscle Biopsy - Controversial - Grossly swollen - Edematous - Necrosis 9 12/20/2010 Histology NMS Complications Rhabdomyolysis Acute renal failure Thromboembolism Acute respiratory failure Seizures DIC Hepatic failure Sepsis Prognosis Management Resolution in 2 weeks Prolonged course Prompt recognition - Depot antipsychotics Immediate discontinuation of the neuroleptic - Structural brain disease Intensive supportive care and medical monitoring Sequelae Treatment of comorbid medical illness 10 12/20/2010 Supportive Measures Pharmacotherapy Reduce body temperature. Treat suspected or secondary infections with empiric antibiotics. Consider intubation for patients with excessive salivation, swallowing dysfunction, coma, hypoxemia, acidosis, and severe rigidity with hyperthermia. Rapid peripheral muscle relaxation Dantrolene Dopamine agonists Combined therapy Aggressive hydration Hemodynamic monitoring. Sedate the patient. Dantrolene Dopamine Agonists Muscle relaxant Inhibits calcium ion release Recommended R d d ffor severe hyperthermia h th i Bromocriptine 25 mg/d PO initially Amantadine gradually increase to tid/qid Levodopa and carbidopa not to exceed 400 mg/d 11 12/20/2010 ECT and NMS Post NMS Neuroleptic Use Wait at least 2 weeks Alternative to oral treatment Reasonable treatment option 6-10 treatments Hydration NMS Sequelae Cerebellar neuronal degeneration Lithium Dysarthria Difficulties comprehending commands Attention problems Abnormalities in her muscle tone, power, reflexes, gait, co-ordination and sensory function Cerebellar gait ataxia Use lower potency antipsychotics Start low and go slow with titration Avoid concomitant lithium use Avoid dehydration Monitor for NMS NMS in Children and Adolescents Dr. Neuhut et al Published cases over an 18 year period Increased creatinine kinase, fever, tachycardia, rigidity, altered mental state Prompt management NMS symptoms resolved No reported deaths 12 12/20/2010 Legal Aspects Legal Aspects Discontinue neuroleptic promptly. Use of dantrolene or bromocriptine Seek appropriate consultation. Risk factors Transfer to higher level of care. Informed consent Document differential diagnosis. Psychoeducation Document treatment plan. Inform the family. Resources Resources National Organization for Rare Disorders Neuroleptic Malignant Syndrome Information Services (NORD) NMSIS [email protected] 888-667-8367 www.rarediseases.org www.nmsis.org Tel: 203-744-0100 13 12/20/2010 References References Heiman-Patterson TD. Neuroleptic malignant syndrome and malignant hyperthermia. Important issues for the medical consultant. Med Clin North Am. Mar 1993;77(2):477-92. Lazarus A, Mann SC, Caroff SN. The Neuroleptic Malignant Syndrome and Related Conditions. Washington, DC: American Psychiatric Press; 1989. Castillo E, Rubin RT, Holsboer-Trachsler E: Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome. American Journal of Psychiatry 146:324-328, 1989 Nierenberg D, Disch M, Manheimer E, Patterson J, Ross J, Silvestri G, et al. Facilitating prompt diagnosis and treatment of the neuroleptic malignant syndrome. Clin Pharmacol Ther. Nov 1991;50(5 Pt 1):580-6. Levenson JL: Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome (ltr). American Journal of Psychiatry 146:1241, 1989 Shalev A, Hermesh H, Munitz H: The role of external heat load in triggering the neuroleptic malignant syndrome. American Journal of Psychiatry 145:110-111, 1988 Reulbach U, Dütsch C, Biermann T, Sperling W, Thuerauf N, Kornhuber J, et al. Managing an effective treatment for neuroleptic malignant syndrome. syndrome Crit Care. Care 2007;11(1):R4. 2007;11(1):R4 Sachdev P, Mason C, Hadzi-Pavlovic D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry. Aug 1997;154(8):1156-8. Stoudemire A, Luther JS: Neuroleptic malignant syndrome and neuroleptic-induced neuroleptic induced catatonia: differential diagnosis and treatment. International Journal of Psychiatry in Medicine 14:57-63, 1984 Shiloh R, Valevski A, Bodinger L, Misgav S, Aizenberg D, Dorfman-Etrog P, et al. Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients. Int Clin Psychopharmacol. May 2003;18(3):147-9. Scheftner WA, Shulman RB: Treatment choice in neuroleptic malignant syndrome. Convulsive Therapy 8:267-279, 1992 Davis JM, Janicak PG, Sakkas P, et al: Electroconvulsive therapy in the treatment of the neuroleptic malignant syndrome. Convulsive Therapy 7:111-120, 1991 Gold R, Lenox RH: Is there a rationale for iron supplementation in the treatment of akathisia? A review of the evidence. Journal of Clinical Psychiatry 56:476-483, 1995 Pelonero AL, Levenson JL, Silverman JJ: Neuroleptic therapy following neuroleptic malignant syndrome. Psychosomatics 26:946-948, 1985 Delay J, Pichot P, Lemperiere T, et al: Un neuroleptique majeur non phenothiazine et non reserpine, l'haloperidol, dans le traitement des psychoses [Haloperidol, a nonphenothiazine, nonreserpine neuroleptic for the treatment of psychosis]. Annales Medico-Psychologiques 118:145-152, 1960 References Croarkin PE, Emslie GJ, Mayes TL. Neuroleptic malignant syndrome associated with atypical antipsychotics in pediatric patients: a review of published cases. J Clin Psychiatry. Jul 2008;69(7):1157-65. Deuschl G, Oepen G, Hermle L. Neuroleptic malignant syndrome: observations on altered consciousness. Pharmacopsychiatry. Jul 1987;20(4):168-70. Dickey W. The neuroleptic malignant syndrome. Prog Neurobiol. 1991;36(5):425-36. Gurrera RJ, Chang SS, Romero JA. A comparison of diagnostic criteria for neuroleptic malignant syndrome. J Clin Psychiatry. Feb 1992;53(2):56-62. Hammerman S, S Lam C C, Caroff SN. SN Neuroleptic malignant syndrome and aripiprazole. aripiprazole Journal of the American Academy of Child and Adolescent Psychiatry. June 2006;45 (6):639-41. Kaplan HI, Sadock BJ, Grebb JA. Kaplan and Sadock's Synopsis of Psychiatry. Philadelphia, Pa: Lippincott, Williams, & Wilkins; 1994:1913, 2004-2005. Kaufman KR, Levitt MJ, Schiltz JF, Sunderram J. Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis. Ann Clin Psychiatry. JulSep 2006;18(3):201-4. Keck PE Jr, Caroff SN, McElroy SL. Neuroleptic malignant syndrome and malignant hyperthermia: end of a controversy?. J Neuropsychiatry Clin Neurosci. Spring 1995;7(2):135-44. Keck PE Jr, Pope HG Jr, McElroy SL. Declining frequency of neuroleptic malignant syndrome in a hospital population. Am J Psychiatry. Jul 1991;148(7):880-2. Klein JP, Fiedler U, Appel H. Massive creatine kinase elevations with quetiapine: report of two cases. Pharmacopsychiatry. 2006;39(1):39-40. [email protected] bh t@ t d Thank You 14
Similar documents
Neuroleptic Malignant Syndrome - The Association of Physicians of
– Elevated or labile blood pressure (BP) – Tachycardia – Incontinence – Dysphagia – Mutism – Tremor – Changes in the level of consciousness ranging from confusion to coma – Leukocytosis – Labora...
More information