Opioid withdrawal manifesting with delirium

Dear Editor,

Patients undergoing opioid withdrawal commonly exhibit severe muscle spasms, musculoskeletal pain, autonomic symptoms, apprehension, restlessness, sleeplessness, and thermal discomfort. The impact of opioids, such as oxycodone and heroin, on µ-opiate receptors in the ventral tegmental area (VTA) results in decreased activity of inhibitory GABA inter-neurons. This, in turn, leads to an augmented release of dopamine in the forebrain regions. The reduction in dopamine neuron firing and release in efferent targets like the nucleus accumbens is considered a primary factor in the emergence of affective withdrawal symptoms, including anxiety, dysphoria, depression, and irritability.[1] The withdrawal process from chronic opioid use exposes the neural adaptations the brain undergoes to maintain equilibrium in the presence of the drug. Consequently, neural circuits regulating various functions, from gastrointestinal to affective states, become immediately imbalanced, giving rise to opioid withdrawal syndrome.[1] Opioid withdrawal delirium is classified in DSM-5 under “Neurocognitive disorders”.[2] Complications of opioid withdrawal are infrequent in the absence of coexisting medical conditions.[3] However, symptoms like persistent vomiting and diarrhea during opioid withdrawal may lead to dehydration, electrolyte imbalance, and, ultimately, heart failure with fatal consequences.[4]

A 24-year-old male was brought to the emergency department of a tertiary care hospital with a history of reduced social interaction, restlessness, irritability, and poor sleep since 5 days. Detailed history revealed use of opioids in the form of brown sugar (heroin) since past 01 month. Last opioid consumption was 4 days prior to initial presentation. Initial examination revealed opioid withdrawal features in the form dilated pupils, restlessness, muscle pain, rhinorrhea, yawning, piloerection, and tachycardia. MSE revealed an anxious looking individual with irritable affect. He was oriented to time, place, and person; attention was arousable; and concentration was well sustained. The Clinical Opiate Withdrawal Scale (COWS) score was 18. Urine drug screen was positive for opioids. He was admitted for detoxification and initially managed symptomatically. Within 06 hours of admission, he developed features of delirium. Corroborative history from multiple sources revealed no history of fever, head injury, seizures, or other psycho-active substance use. Additionally, there were no past or family histories of psychiatric or neurological illness. Laboratory evaluation (including biochemical, electrolytes, and metabolic) revealed no abnormality. NCCT head revealed no significant abnormality.

In view of temporal association with opioid withdrawal symptoms and onset of delirium, a diagnosis of opioid withdrawal state with delirium was established (ICD-10, F11.3). The delirium was initially managed with inj lorazepam and inj haloperidol for behavioral control. However, hallucinatory and aggressive behavior persisted; the Richmond Agitation-Sedation Score was +3. The patient was transferred to the ICU and managed with midazolam infusion at 2 mg/hour and dexmedetomidine infusion at 32 mcg/hour in consultation with a neurophysician and intensivist. Behavioral control was achieved within 3–4 hours, and he recovered from delirium in the next 24 hours. The benzodiazepines were gradually tapered off over the next 7 days. He was put on Tab Naltrexone 50 mg/day, motivation enhancement therapy, relapse prevention training, and network therapy. He remained abstinent during 01-month and 03-month follow-ups.

The index case consumed opioids with a short duration of action, resulting in a brief yet intense withdrawal syndrome. Typically, milder withdrawal features are observed when substances with longer durations of action are used.[1] In the present case, delirium manifested 4 days after the cessation of brown sugar usage, with no evidence of toxemia or pyrexia. Complications such as convulsions and delirium are uncommon in opioid withdrawal,[3] and the literature on this subject is scarce. A comparative study involving 136 opioid users in India and Nepal by Aich et al.[5] identified seven cases of opioid withdrawal delirium. Given the potential for complications like delirium during the management of opioid withdrawal, vigilant and continuous monitoring is imperative.

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