Morbidity and Mortality report

MICU Bliss 11I

Veena Panduranga

Juliana Alvarez-Argote

Neuroleptic malignant syndrome

Learning Objectives

Describe a case of neuroleptic malignant syndrome

Review the pathophysiology, diagnosis, and management of neuroleptic malignant syndrome

Overview

Life-threatening, idiosyncratic reaction to medications affecting central dopaminergic neurotransmission.

Early recognition is critical to prevent morbidity and death

First reported case in 1956 with chlorpromazine

Berman. Neurohospitalist. 2011 January

Overview

Dopamine depletion Dopamine receptor blockers:

Virtually all antipsychotics, including atypical antipsychotics

Cessation of dopaminergic medications: levodopa, amantadine, tolcapone

Incidence: 0.02% to 2% of pts on neuroleptics

Adnet et al. Br J Anaest. 2000

Medications associated with NMS

Berman. Neurohospitalist. 2011 January

Pathophysiology

Strawn et al. Am J Psychiatry 164:6, June 2007

Clinical presentation

Within 2 weeks after exposure Most cases hours to days after exposure Muscular rigidity followed by hyperthermia in several

hours, along with wide range of altered mental status Drowsiness, agitation, confusion, delirium, coma

Autonomic dysfunction: labile BP, tachypnea, tachycardia, sialorrhea, diaphoresis, flushing, skin pallor, incontinence

Berman. Neurohospitalist. 2011 January

Lab findings

High CK (rhabdomyolysis) Leukocytosis Iron deficiency (96%) Renal failure (from

rhabdomyolysis) Metabolic acidosis EEG: non generalized slowing

Berman. Neurohospitalist. 2011 January

Diagnosis: DSM IV criteria:

Muscular rigidity (96%) T>100,4 Use of neuroleptic

medication

Two or more of: Diaphoresis Dysphagia Tremor Incontinence (54%) AMS Mutism (96%) Tachycardia Labile BP (40%) Leukocytosis Elevated CK (91%)

Symptoms not explained by another substance or medical condition

Perry and Wilborn. Ann Clin Psychiatry. 2012

Diagnosis

DSM IV criteria: Severe muscular rigidity and high temperature,

associated with use of neuroleptic medication Two or more of: diaphoresis, dysphagia, tremor,

incontinence, AMS, mutism, tachycardia, labile BP, leukocytosis, elevated CK

Symptoms not explained by another substance or medical condition

Differential diagnosis Heat stroke:

flaccid extremities, abrupt onset, hypotension, dry skin CNS infection:

Prodrome symptoms, meningismus, CSF labs Serotoninergic sd.

Absence of high CK, leukocytosis, presence of GI symptoms (n/v/d) Lethal catatonia:

Psychosis for weeks prior to presentation Malignant hyperthermia:

History of depolarizing muscle relaxants or inhaled anesthetics Cocaine intoxication Alcohol w/d

Strawn et al. Am J Psychiatry. 2007

Management Neurologic emergency

Many will need ICU level of care Stop neuroleptic Restart dopaminergic meds in withdrawal

(levodopa) Aggressive hydration (if high CK, AKI) Control temperature Bicarb for AKI Cardio respiratory support

Adnet et al. Br J Anaest. 2000Reulbach et al. Critical Care 2007

Management Bromocriptine: dopaminergic

PO or NGT 2.5mg BID or TID increase up to 45mg/d Monitor liver function

Benzodiazepines: Reasonable first line 1-2mg IV/IM q 4-6h Mild/moderate cases or primarily catatonic symptoms

Strawn et al. Am J Psychiatry. 2007Reulbach et al. Critical Care. 2007

Management Amantadine: anticholinergic

100mg PO/NGT q 8h Moderate cases

Dantrolene: muscle relaxant, inhibits calcium release from sarcoplasmic reticulum Severe cases (T >104, HR >120) 2.5mg/Kg + 1mg/Kg q 6h IV Increase up to 10mg/Kg/d Stop once symptoms resolving (resp

failure/hepatotoxicity) ECT:

Cases with no response to medications/supportive care

Strawn et al. Am J Psychiatry. 2007Reulbach et al. Critical Care. 2007

Complications

Renal failure DIC Rhabdomyolysis MI Asp. PNA Seizures, arrhythmias (lyte abnormalities)

Reulbach et al. Critical Care 2007

When to restart neuroleptics

Wait 2 weeks for PO antipsychotics Wait 5 weeks for depot forms Change neuroleptic med Switch from typical to atypical Start at low doses, titrate slowly

Neuroleptic Malignant Syndrome Information Service. 2011. http://www.nmsis.org

Prognosis

Mortality ~40% before 1984 Mortality greatly reduced (~10%) when recognized

and treated early

Recurrence of NMS in 30-50% cases after restarting neuroleptics

Complete recovery in first 2 days to 2 weeks Mortality 2/2 arrhythmia, DIC, renal or CV

complications

Bottoni. Hospital physician. 2002

Take home points… NMS is a rare but severe reaction to dopamine blocking agents or

withdrawal to dopaminergic agents Early recognition is critical in preventing significant morbidity and

mortality Main manifestations are muscular rigidity, hyperthermia and

history of medication intake or abrupt cessation Main management consists of stopping offending agent/restarting

dopaminergic, aggressive hydration and temperature control Medications for NMS treatment include benzos, dantrolene, Many will require ICU level 2/2 cardiorespiratory decompensation

Thank you!