Opioid Abstinence Syndrome

Established Symptoms

The American Academy of Emergency Medicine and other medical societies recognize the following symptoms of opioid abstinence syndrome: gastrointestinal symptoms, such as abdominal cramps, nausea, vomiting, and diarrhea, autonomic symptoms, such as piloerection, sweating, lacrimation, rhinorrhea, tachycardia, hypertension, and fever, musculoskeletal symptoms, such as myalgias, body aches, increased muscle tone, and tremors, and psychological symptoms, such as anxiety, agitation, dysphoria, irritability, insomnia, and intense desire to use opioids 1, 2, 3, 4
The Mayo Clinic Proceedings guidelines describe the symptoms of opioid abstinence syndrome, including gastrointestinal, autonomic, musculoskeletal, and psychological symptoms, with no mention of voice changes 3
The Annual Review of Medicine recommends evaluating patients with opioid abstinence syndrome using validated clinical scales, such as the Clinical Opiate Withdrawal Scale (COWS) and the Subjective Opiate Withdrawal Scale (SOWS), which do not include voice changes as a parameter 4

The Clinical Opiate Withdrawal Scale (COWS) evaluates heart rate, rhinorrhea/lacrimation, gastrointestinal symptoms, tremor, yawning, anxiety, and piloerection, but does not include voice changes 3
The Subjective Opiate Withdrawal Scale (SOWS) includes 16 self-reported symptoms, none of which are related to voice changes 3

The American Academy of Pediatrics and other medical societies recommend that if a patient in opioid abstinence presents with voice changes, an alternative cause unrelated to the abstinence syndrome should be considered, and other conditions such as infection, sepsis, or other pathologies should be ruled out 5, 6
The Annual Review of Medicine describes opioid abstinence syndrome as "subjectively severe but objectively mild" and comparable to a moderate to severe flu-like illness, without including dysphonia or voice changes in its typical presentation 4, 7

The American Academy of Emergency Medicine and other major medical societies list fever as an established autonomic symptom of opioid abstinence syndrome, which occurs due to autonomic overreactivity resulting from supranormal release of noradrenaline after abrupt discontinuation of exogenous opioids 8, 9
Opioid withdrawal produces fever through autonomic overreactivity, manifesting alongside CNS irritability and gastrointestinal dysfunction as the three primary domains of opioid withdrawal 8, 9

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, according to the American College of Critical Care Medicine 10
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 10

In neonates with neonatal abstinence syndrome (NAS), fever is a well-documented autonomic sign of opioid withdrawal, and the American Academy of Pediatrics explicitly lists fever among the clinical features of neonatal narcotic abstinence syndrome, alongside temperature instability and mottling 8, 9

The American Academy of Pediatrics notes that fever from opioid withdrawal typically begins within 24 hours for short-acting opioids like heroin, but can be delayed up to 24-72 hours for methadone, and occasionally may not appear until 5-7 days after the last opioid use 11, 12, 13
For short-acting opioids, withdrawal onset is typically within 24 hours of last use, with symptoms beginning after more than 12 hours since last use 11, 12, 13, 14
The onset of withdrawal for long-acting opioids like methadone is 24-72 hours after last use, with fever possibly not manifesting until this delayed timeframe 11, 12, 13
For patients on methadone maintenance, withdrawal symptoms may not emerge until more than 72 hours after last use 14
The American College of Critical Care Medicine is not cited for a specific fact, however, the timing of withdrawal onset for extended-release formulations like OxyContin is more than 24 hours since last use 14
Peak withdrawal for buprenorphine occurs at 40 hours, with the most severe symptoms at 70 hours 11, 12, 13

Fever occurs due to supranormal release of noradrenaline following abrupt opioid discontinuation, resulting in autonomic overreactivity, which includes increased sweating and diaphoresis, and temperature instability and mottling 11, 12, 15

The American Academy of Pediatrics notes that withdrawal symptoms, including fever, may be delayed until 5-7 days after birth in neonates or last opioid use in adults, often occurring after hospital discharge 11, 12, 13
In neonates exposed to opioids in utero, fever is a well-documented autonomic sign, with the American Academy of Pediatrics explicitly listing it as part of the symptomatology 11, 12, 15

When evaluating for opioid withdrawal fever, it is essential to confirm the time since last opioid use to predict withdrawal onset, as recommended by the Annals of Emergency Medicine 14