Morbidity and Mortality report

1
Morbidity and Mortality report

• MICU Bliss 11I
• Veena Panduranga
• Juliana Alvarez-Argote

2
Neuroleptic malignant syndrome
3
Learning Objectives

• Describe a case of neuroleptic malignant syndrome
• Review the pathophysiology, diagnosis, and
  management of neuroleptic malignant syndrome

4
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
5
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
6
Medications associated with NMS
Berman. Neurohospitalist. 2011 January
7
Pathophysiology
Strawn et al. Am J Psychiatry 1646, June 2007
8
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
9
Lab findings

• High CK (rhabdomyolysis)
• Leukocytosis
• Iron deficiency (96)
• Renal failure (from rhabdomyolysis)
• Metabolic acidosis
• EEG non generalized slowing

Berman. Neurohospitalist. 2011 January
10
Diagnosis DSM IV criteria

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

• Muscular rigidity (96)
• Tgt100,4
• Use of neuroleptic medication

• Symptoms not explained by another substance or
  medical condition

Perry and Wilborn. Ann Clin Psychiatry. 2012
11
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

12
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
13
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. 2000 Reulbach et al.
Critical Care 2007
14
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. 2007 Reulbach et
al. Critical Care. 2007

15
Management

• Amantadine anticholinergic
• 100mg PO/NGT q 8h
• Moderate cases
• Dantrolene muscle relaxant, inhibits calcium
  release from sarcoplasmic reticulum
• Severe cases (T gt104, HR gt120)
• 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. 2007 Reulbach et
al. Critical Care. 2007
16
Complications

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

Reulbach et al. Critical Care 2007
17
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
18
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
19
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

20
Thank you!