Last reviewed: 8 Nov 2021
Last updated: 05 May 2020



History and exam

Key diagnostic factors

  • agitation, irrationality, restlessness, sometimes aggressive behavior
  • hyperthermia >100°F (>38°C) but <103°F (<39.5°C)
  • hyperthermia >103°F (>39.5°C)
  • seizures
  • diaphoresis, flushed facial skin
  • tachycardia and palpitations
  • traumatic injury
  • headache
  • serotonin drug interaction
  • hypertension
  • hyperreflexia and clonus
  • chest pain
  • cardiac arrhythmia

Other diagnostic factors

  • history of hepatitis B or C, HIV
  • tremor, repetitive movements
  • disorientation, confusion, delirium
  • malnutrition
  • superficial venous abnormalities
  • rapid speech, pacing, trismus
  • hallucinations or delusions
  • tremor, hypertonicity, or muscle rigidity
  • paranoia, hypervigilance, or psychosis
  • mydriasis
  • history of heart disease
  • tachypnea
  • dyspnea
  • lack of thirst
  • abdominal pain
  • positive Babinski reflex
  • focal neurologic signs, papilledema

Risk factors

  • high ambient temperature
  • volume depletion
  • exercise and sweating
  • excessive alcohol intake
  • polydrug usage
  • anxiety and depression
  • history of behavioral disturbance
  • history of delinquency or crime
  • ADHD
  • attendance at dance club or rave party
  • history of drug misuse for more than 1 year
  • genetic predilection

Diagnostic investigations

1st investigations to order

  • serum glucose
  • serum electrolytes
  • serum creatinine, BUN
  • ABG
  • serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase
  • serum prothrombin time, PTT, INR
  • urinalysis
  • urine toxicology screen
  • serum alcohol level
  • serum creatine kinase
  • serum troponin
  • ECG
  • CXR

Investigations to consider

  • serum D-dimer
  • abdominal x-ray
  • CT of the head
  • MRI of the head
  • cerebral angiography

Treatment algorithm



John R. Richards, MD, FAAEM, FRSM


Department of Emergency Medicine

University of California, Davis Medical Center




JRR is an author of a number of references cited in this topic.


Dr John R. Richards would like to gratefully acknowledge Dr Alison Jones, a previous contributor to this topic. AJ is an author of a number of references cited in this topic.

Peer reviewers

Andrew Stolbach, MD

Assistant Professor

Department of Emergency Medicine

Johns Hopkins University Hospital




AS declares that he has no competing interests.

Richard J. Geller, MD, MPH, FACP

Associate Clinical Professor of Medicine

University of California San Francisco School of Medicine

San Francisco



RJG declares that he has no competing interests.

David Wood, BSc, MB ChB, MD, MRCP

Consultant Physician and Clinical Toxicologist

Guy's and St Thomas' Poisons Unit




DW is an author of a reference cited in this topic.

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