
Demographic Information
The patient is a middle-aged woman (approximate weight: 80 kilograms) with a history of chronic pain management and possible substance use disorder. Her medication history includes previous or ongoing opioid use, and there is reported Kratom use for pain management. No reliable collateral information was available, and the patient's reporting was inconsistent.
Exposure Details
Unclear and conflicting histories complicate the case:
Primary report: The patient consumed a large dose of Kratom for pain relief.
Secondary history: The patient had ceased Kratom use 24 hours before presentation and voluntarily surrendered additional pills from her possession (suggesting intentional discontinuation).
It is also unclear whether she was concurrently taking prescribed opioids, raising the possibility of poly-substance exposure or overlapping withdrawal syndromes.
Given the non-standardization of Kratom formulations and its variable content of mitragynine (a partial μ-opioid receptor agonist), establishing a clear toxicologic dose-response is difficult.
Signs and Symptoms
The clinical presentation is dominated by:
Severe agitation, moaning, non-purposeful movement, and constant discomfort.
Symptoms are not aggressive, but indicate significant CNS dysregulation (moaning, writhing, altered sensorium).
The trajectory is worsening, not improving, which is atypical for simple Kratom withdrawal, where symptoms usually peak by 1–2 days and start to wane.
This constellation may suggest either:
Complicated Kratom withdrawal
Precipitated withdrawal from opioids
Polysubstance withdrawal
A toxic-metabolic encephalopathy or other CNS pathology (less likely given the withdrawal-patterned course and response to supportive meds).
Which of the following are appropriate next steps in her management?
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.
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Authors:
Dr. Omid Mehrpour (MD, FACMT) is a senior medical toxicologist and physician-scientist with over 15 years of clinical and academic experience in emergency medicine and toxicology. He founded Medical Toxicology LLC in Arizona and created several AI-powered tools designed to advance poisoning diagnosis, clinical decision-making, and public health education. Dr. Mehrpour has authored over 250 peer-reviewed publications and is ranked among the top 2% of scientists worldwide. He serves as an associate editor for several leading toxicology journals and holds multiple U.S. patents for AI-based diagnostic systems in toxicology. His work brings together cutting-edge research, digital innovation, and global health advocacy to transform the future of medical toxicology.
References:
Stanciu CN, Gnanasegaram SA, Ahmed S, Penders T. Kratom Withdrawal: A Systematic Review with Case Series. J Psychoactive Drugs. 2019 Jan-Mar;51(1):12-18. doi: 10.1080/02791072.2018.1562133. Epub 2019 Jan 5. PMID: 30614408.