Dennis Goodstein

Objectives: Medetomidine, a veterinary alpha-2-adrenergic agonist, has emerged as a dominant adulterant in the Philadelphia illicit opioid supply, producing a severe withdrawal syndrome requiring significant inpatient support. We developed an intravenous dexmedetomidine protocol for intermediate care units (IMCU) and describe the safety and feasibility of delivering this care outside the intensive care unit (ICU). Methods: A retrospective descriptive analysis of patients who received dexmedetomidine under an IMCU orderset for alpha-2 withdrawal was conducted at two urban medical centers in Philadelphia, PA, from April 2024 to February 2026. Encounters were classified as protocol-concordant or protocol-discordant by dosing and level of support; the concordant cohort was primary. Variables included demographics and addiction consult status. Outcomes included length of stay (hospital and IMCU), ICU admission, rapid response team activation, intubation, and discharge disposition. Results: Of 487 encounters, 449 (92.2%) were protocol-concordant and 38 (7.8%) protocol-discordant. All subsequent results describe the protocol-concordant cohort (n=449) unless otherwise noted. The cohort was predominantly male (58.1%) with a mean age of 41.8 years. Median hospital stay was 6.0 days and median IMCU stay was 2.2 days. ICU admission was not required in 50.1% of encounters. Rapid response team activation occurred in 38 encounters (8.5%), the majority for escalating withdrawal management. Patient-directed discharge occurred in 41.4% of encounters. Conclusions: An IMCU dexmedetomidine protocol deployed across seven monitored units at 2 hospitals offers a replicable framework for managing medetomidine withdrawal while potentially mitigating critical care capacity challenges. Identified opportunities include modification of titration and dosing strategies and further investment in addiction consult infrastructure.

Purpose of Review: Medetomidine is a veterinary α2-adrenergic agonist that has been an adulterant of illicitly manufactured opioids since 2022. We review its pharmacology, detection, intoxication, withdrawal, and management, and assess why severe withdrawal has emerged in some regions but not others. Recent Findings: Medetomidine has spread through North American drug markets yet evades most toxicology testing. Roughly two hundred times more potent than xylazine, with greater α2 selectivity and imidazoline-1 activity, it causes intoxication resembling other α2 agonists: sedation and bradycardia. The dominant clinical problem is withdrawal: autonomic dysregulation, intractable vomiting, and encephalopathy frequently requiring intensive care. Treatment requires multimodal α2-agonist therapy, often escalating to parenteral dexmedetomidine. Where it is established, withdrawal encounters and hospital admissions have risen. Summary: We hypothesize that both local prevalence and drug concentration determine where withdrawal appears. This syndrome exposes gaps in both assessment and treatment; prospective multicenter research, a validated withdrawal instrument, and integrated addiction-critical care models are needed.

Background: Rib fractures in the elderly are associated with pulmonary complications and mortality. The erector spinae plane (ESP) block might reduce pain and improve pulmonary function. Lidocaine infusions offer a non-invasive alternative delivery of local anesthetic. This pilot study was designed to inform the design of a future large trial. Methods: Patients ≥ 55 years of age with at least three unilateral rib fractures were randomly assigned to an ESP catheter, lidocaine infusion, or multimodal analgesia alone. Baseline measurements included the Duke Activity Status Index (DASI) score. Pain, opioid use, adverse effects, vital capacity, delirium, and sedation were assessed for 72 hours. Primary outcomes were average pain ratings and opioid consumption. Pulmonary complications, opioid use, functional status, and safety outcomes were assessed to determine feasibility of a definitive trial. Results: Twenty-four patients were included in analyses. Demographics and injury severity were similar. The recruitment rate was 2.4 patients per month with two patients withdrawals. The mean ± SD pain ratings did not differ between ESP, lidocaine, and control groups, respectively (day 1: (4.9 ± 3.1 versus 5.8 ± 3.1 versus 5.6 ± 3.3); day 2: (4.4 ± 3.3 versus 5.4 ± 3.0 versus 7.4 ± 2.6); and day 3: (4.4 ± 2.1 versus 5.8 ± 2.6 versus 5.2 ± 3.5; p=0.70). Median [IQR] opioid consumption did not differ between the same groups, respectively (25.0 [66.8] versus 26.7 [89.2] versus 20.0 [101.4]; p=0.68). Three lidocaine patients experienced possible local anesthetic systemic toxicity (LAST) despite our conservative dosing protocol. Two patients died before the 30-day assessments. Pneumonia occurred more frequently in controls and could be a future 4 primary outcome for a definitive trial, which would require enrolling 11 patients per month over three years. Delirium occurred less frequently in ESP patients. Conclusions: Analgesia was comparable between groups. While this study does not rule out a modest early analgesic benefit of ESP block or lidocaine infusion, pulmonary complications or delirium may be the preferred endpoint. Possible LAST symptoms occurred in three lidocaine patients despite conservative dosing and should be systematically assessed in future trials, especially in the elderly.

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as “kratom” or “7-OH,” despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal symptoms after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal in the absence of other opioid use. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg × 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of suspected MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings.

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as "kratom" or "7-OH," despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg x 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings.

Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention.

Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention.

Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 samples). Importantly, 32% of medetomidine exposures would have been missed without enzymatic pre-treatment. Patients exhibited two distinct clinical phenotypes: intoxication, characterized primarily by sedation; bradycardia; and often hypotension, and withdrawal, presenting with life-threatening tachycardia; hypertension and often encephalopathy. Notably, clinical phenotype correlated with urinary concentrations of 3-OH-M but not xylazine. These findings underscore the critical need for heightened clinical awareness and need for contemporaneous toxicologic screening mechanisms for medetomidine exposure, emphasizing its distinct clinical presentations and the potential public health implications posed by its widespread adulteration in illicit opioids.