Can Haldol Cause Hyperthermia?
Yes, haloperidol (Haldol) can cause hyperthermia through two distinct mechanisms: neuroleptic malignant syndrome (NMS) and simple drug-induced hyperthermia, both of which are potentially life-threatening and require immediate discontinuation of the medication. 1
Mechanisms of Haloperidol-Induced Hyperthermia
Neuroleptic Malignant Syndrome (NMS)
NMS is the most serious hyperthermic complication of haloperidol and manifests as a potentially fatal symptom complex. 1
Clinical features include hyperpyrexia (high fever), muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmias). 1
Elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure are additional signs that may develop. 1
Haloperidol is among the most frequently reported drugs causing NMS in the ICU setting, particularly among the butyrophenone class of antipsychotics. 2
The mechanism involves central dopaminergic blockade that initiates muscle contraction, distinguishing it from malignant hyperthermia which has a peripheral muscle mechanism. 2
NMS is not dose-related and can begin within hours of therapy initiation or after months of treatment. 3
Simple Drug-Induced Hyperthermia
Hyperpyrexia and heat stroke not associated with the full NMS symptom complex have also been reported with haloperidol. 1
This represents a hypersensitivity reaction where fever develops through dysregulation of hypothalamic temperature control. 2
The lag time between initiating haloperidol and fever development averages 21 days (median 8 days), though it can occur at any point. 2
Fever typically resolves 1-3 days after discontinuation but may take up to 7 days. 2
Diagnostic Approach
When evaluating hyperthermia in a patient on haloperidol, you must differentiate between NMS, simple drug fever, and infectious causes.
Key Distinguishing Features for NMS:
- Muscle rigidity is the hallmark finding that distinguishes NMS from simple drug fever. 1
- Elevated creatine phosphokinase levels indicate muscle breakdown. 1
- Autonomic instability with fluctuating vital signs. 1
- Altered mental status including catatonic signs. 1
Key Features for Simple Drug Fever:
- Fever without muscle rigidity or significant autonomic dysfunction. 2
- Temporal relationship to haloperidol administration is the primary diagnostic criterion. 2
- Rash and eosinophilia are uncommon and should not be relied upon for diagnosis. 2
Rule Out Infection:
- Complete infectious workup is mandatory as infection remains a common cause of fever in hospitalized patients. 2
- The diagnosis of drug-induced fever is established by temporal relationship and exclusion of other causes. 2
Immediate Management
For Suspected NMS:
Immediate discontinuation of haloperidol is the first and most critical step. 1
Provide intensive symptomatic treatment and medical monitoring, typically in an ICU setting. 1
Treat any concomitant serious medical problems for which specific treatments are available. 1
Consider benzodiazepines for agitation and muscle activity. 4
Manage hyperthermia with external cooling measures. 4
Treat dehydration and elevated creatine kinase with IV fluids to prevent renal failure from rhabdomyolysis. 4
Dantrolene has been utilized successfully based on the hypothesis that NMS shares similarities with malignant hyperthermia. 3
Bromocriptine and amantadine (dopaminergic agonists) have shown benefits by counteracting the dopaminergic blockade. 3
For Simple Drug-Induced Fever:
Discontinue haloperidol immediately. 2
Provide supportive care with antipyretics and hydration. 4
Monitor for at least 24-48 hours after discontinuation to ensure resolution of symptoms. 4
Critical Pitfalls to Avoid
Do not continue haloperidol if drug-induced hyperthermia is suspected—discontinuation is the definitive treatment. 2, 4
Do not assume fever is always infectious in origin when a patient is on haloperidol; consider drug-induced causes early. 2
Do not overlook the possibility of NMS, which requires immediate intensive care intervention as it can be life-threatening. 4, 1
Do not delay treatment of suspected NMS while awaiting confirmatory laboratory results—clinical suspicion warrants immediate action. 4
Do not rechallenge patients who experienced NMS with the same antipsychotic, as recurrences have been reported. 1
Do not rechallenge patients who experienced anaphylaxis or toxic epidermal necrolysis with haloperidol. 2
Special Considerations
Patients with underlying myopathies (such as central core disease) may be at increased risk for hyperthermic reactions to haloperidol. 5
Thermoregulation may be impaired in patients on antipsychotics, resulting in significant hyperthermia that can potentiate other complications including cerebrovascular accidents. 6
If antipsychotic treatment is required after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered with close monitoring, as recurrences have been reported. 1