Opioid Withdrawal Can Cause Fever
Yes, fever is a recognized autonomic manifestation of opioid withdrawal syndrome and occurs as part of the hyperadrenergic state that characterizes this condition. 1, 2
Mechanism and Clinical Presentation
Opioid withdrawal produces fever through autonomic overreactivity resulting from supranormal release of noradrenaline after abrupt discontinuation of exogenous opioids. 1 This autonomic dysfunction manifests alongside CNS irritability and gastrointestinal dysfunction as the three primary domains of opioid withdrawal. 1
Fever is explicitly listed among the established autonomic symptoms of opioid abstinence syndrome by the American Academy of Emergency Medicine and other major medical societies. 2 The complete autonomic symptom cluster includes:
- Fever 1, 2
- Sweating/diaphoresis 1, 2, 3
- Tachycardia 2, 3
- Hypertension 2
- Piloerection (goose-flesh) 2, 3
- Lacrimation and rhinorrhea 2, 3
Temporal Pattern and Clinical Context
Opioid withdrawal symptoms begin 2-3 half-lives after the last dose, peak at approximately 48-72 hours, and typically resolve within 7-14 days. 4 The FDA label for methadone specifically describes fever as occurring during heroin withdrawal, often alternating with chilliness and flushing. 3
In critically ill patients, fever from opioid withdrawal must be distinguished from infectious causes, particularly since withdrawal typically occurs several hours or days after ICU admission when drug history may not be readily available. 1 The American College of Critical Care Medicine recognizes that withdrawal from opiates (including methadone) is associated with fever, often accompanied by tachycardia, diaphoresis, and hyperreflexia. 1
Diagnostic Approach
When evaluating fever in a patient with potential opioid withdrawal:
- Use validated assessment tools like the Clinical Opiate Withdrawal Scale (COWS), which evaluates multiple parameters including autonomic signs, though fever itself is not a scored parameter. 4, 2
- Monitor during the 48-72 hour window when symptom severity typically peaks, as this represents the highest risk period. 4
- Rule out infectious causes systematically, especially in critically ill patients where fever may have multiple etiologies. 1
Special Populations
In neonates with neonatal abstinence syndrome (NAS), fever is a well-documented autonomic sign of opioid withdrawal. 1 The American Academy of Pediatrics explicitly lists fever among the clinical features of neonatal narcotic abstinence syndrome, alongside temperature instability and mottling. 1
In pediatric ICU patients receiving prolonged opioid therapy, fever was observed in >13% of withdrawal observations and correlated significantly with duration of use and total doses administered. 5
Clinical Significance
The fever associated with opioid withdrawal is part of a constellation of symptoms that patients describe as incapacitating and comparable to a moderate to severe flu-like illness. 6, 7 This subjectively severe but objectively mild syndrome drives continued opioid use, as patients go to great lengths to avoid withdrawal symptoms. 6
In trauma ICU patients who developed probable withdrawal syndrome, fever was among the more frequent signs, and these patients spent almost double the time on mechanical ventilation with longer ICU and hospital stays compared to those without withdrawal. 8