Correct Answer: E (A, B, D)

Rationale:

• A. Suboxone 16 mg: Higher dose avoids precipitated withdrawal in partial agonist cases and serves diagnostic/therapeutic roles.

• B. Phenobarbital: Broad CNS suppressant—valuable if withdrawal is severe or non-opioid mediated.

• D. Toxicology screen: Critical due to unreliable history, potential Kratom-opioid overlap.

• C is incorrect: Lower buprenorphine doses paradoxically increase the risk of precipitated withdrawal due to partial agonism.

Diagnostic Journey

The team faces a significant diagnostic challenge due to:

• Lack of consistent history.

• Lack of a known timeline of the last opioid or Kratom use.

• Presence of physical signs consistent with opioid withdrawal, but also movement disorders, which are less typical for opioid withdrawal alone.

Considerations:

• Kratom withdrawal is opioid-like but can be more idiosyncratic, with tremors, insomnia, emotional lability, and motor restlessness.

• Symptoms can mimic serotonin syndrome or catatonia, but without hyperreflexia/clonus or lead-pipe rigidity.

Hospital Presentation

The patient was:

• Uncontrolled, requiring midazolam drip for sedation.

• Unable to swallow, precluding oral/sub-lingual therapies initially.

• Demonstrated progressive symptoms overnight, pointing away from a self-limited course and toward either untreated withdrawal or continued toxic effect.

Initial Treatment Approaches

Therapies under consideration:

• Midazolam drip for symptom control.

• Avoidance of premature Suboxone to prevent precipitated withdrawal, given the unknown opioid load.

• Phenobarbital is a general CNS depressant and anticonvulsant agent to manage movement abnormalities and agitation.

• A potential test dose of Suboxone (buprenorphine-naloxone) is considered for a treatment trial if opioids are believed to be involved, aiming to mitigate withdrawal via partial agonism at μ-opioid receptors.

Laboratory Findings Overview

Not explicitly detailed in the transcript, but for full context, assume the following relevant labs were obtained or are pending:

• Comprehensive toxicology screen: including synthetic opioids, Kratom alkaloids (if available), benzodiazepines, and antidepressants.

• CBC, CMP, lactate, ammonia, and creatinine kinase to rule out metabolic derangement or rhabdomyolysis.

• Arterial blood gas (ABG) if altered mentation persists.

Management Strategy Development

Decision made:

• Initiate Suboxone at 16 mg, sublingually, despite inability to swallow (as it's absorbed via mucosa).

  • This is a higher dose strategy, as lower doses are paradoxically more likely to precipitate withdrawal.

  • If precipitated withdrawal occurs, the plan includes supportive therapy with benzodiazepines, ondansetron, and additional Suboxone (to outcompete full agonist activity and stabilize receptor occupancy).

• If Suboxone fails, shift to:

  • Phenobarbital loading dose: 10 milligrams per kilogram (approx. 600 mg), aiming for plasma levels of 15–20 micrograms per milliliter.

  • Continue benzodiazepines for sedation and withdrawal management as needed.

Laboratory Trends Analysis

To be monitored:

• If Suboxone improves symptoms, opioid withdrawal becomes the most likely diagnosis.

• Improvement in heart rate, BP, and mental status post-buprenorphine would indicate successful receptor occupancy.

• If worsening occurs post-Suboxone, suspect precipitated withdrawal or non-opioid pathology.

• Labs may show improving CK levels, electrolytes, and acid-base status if restlessness and rhabdomyolysis are mitigated.

Prognosis Evaluation

Prognosis hinges on:

• Responsiveness to Suboxone (suggests straightforward withdrawal).

• Lack of complications such as rhabdomyolysis, aspiration pneumonia, or prolonged delirium.

• Full resolution of motor symptoms and mental status without persistent agitation or autonomic instability.

If Suboxone works, it's a Good prognosis.
If not, Prolonged ICU-level care may be required with the barbiturate-based supportive regimen.

Conclusion and Takeaways

This case exemplifies the diagnostic complexity when facing withdrawal syndromes from non-traditional opioids like Kratom, especially in the context of polypharmacy, unreliable history, and confounding movement symptoms.

Recent literature, including the systematic review and case series by Stanciu et al. (2019), underscores that Kratom withdrawal can occur independently of traditional opioid use and mimic—but also diverge from—classic opioid withdrawal presentations. Their findings emphasize a range of symptoms such as delusions, hallucinations, and neuromotor agitation, which may mirror our patient’s atypical course. This supports the clinical decision to approach Kratom withdrawal using opioid withdrawal frameworks, including buprenorphine initiation, while remaining alert to idiosyncratic symptoms that may require adjunctive agents like phenobarbital.

Key Lessons:

• High-dose Suboxone (16 mg) is safer than low-dose in unclear withdrawal scenarios to avoid precipitated withdrawal.

• Phenobarbital is a valuable adjunct for uncontrolled withdrawal with CNS excitability when standard regimens fail.

• Early and clear toxicology testing and clinical response to therapy remain crucial for diagnosis in unreliable historians.

Preventative Measures:

• Improved regulation and public education on Kratom.

• Clear protocols for managing withdrawal from novel or mixed opioid agonists.

• Monitoring for unusual presentations of withdrawal syndromes to avoid misclassification as behavioral or psychiatric agitation.