Assessing the Cardiac Safety of a Multimodal Protocol for 'Tranq Dope' Withdrawal: A Retrospective QTc Analysis

BACKGROUND: "Tranq dope"-fentanyl adulterated with xylazine-has complicated the management of opioid withdrawal in emergency departments (EDs). A novel withdrawal protocol was implemented to address these challenges, utilizing concurrent agents to intentionally synergize and potentiate effects. Questions remain about the safety of its components, some of which may prolong the QT interval. METHODS: We conducted a retrospective cohort study of adult ED patients with suspected fentanyl/xylazine exposure treated utilizing novel protocol across two urban hospitals in Philadelphia, PA between September 2022 and October 2024. Patients with both pre- and post-treatment electrocardiograms (ECGs) were included. QTc intervals were reviewed by an experienced cardiac electrophysiologist. The primary outcome was QTc change after treatment exposure. Secondary outcomes included symptom improvement (measured by Clinical Opiate Withdrawal Scale [COWS]), medication-specific QTc effects, adverse events, and hospital disposition. RESULTS: 1375 patients received protocol medications. 284 had pre- and post-treatment ECGs. Mean age 39 years; 62.3 % male. Nearly all tested positive for fentanyl (98.5 %), most cocaine (63.8 %). Mean QTc changed from 457 ms (pre) to 456 ms post-treatment. No protocol medication was associated with QTc prolongation. Vancomycin (+13 ms), ondansetron (+16 ms), and methadone (+15 ms) were independently associated with QTc increase in adjusted models. COWS scores improved significantly (mean reduction 10 points, p < 0.001), and no life-threatening arrhythmias were observed. CONCLUSION: The use of a multi-agent 'tranq dope' withdrawal protocol was not associated with serious adverse events. Pre and post-treatment QTc were variable but overall effects were neutral. These findings suggest these treatments can be used in those at risk, or with known QTc prolongation, though more study is needed to confirm findings.