Penn Study Links Medetomidine in Fentanyl to Surge in ICU Withdrawal

The share of patients with opioid use disorder who needed an intensive care sedative just to get through withdrawal rose from just under 6 percent to roughly 32 percent at two Philadelphia hospitals as medetomidine spread through the local fentanyl supply, according to an analysis published September 28 in JAMA Internal Medicine.

The study, led by researchers at the University of Pennsylvania's Perelman School of Medicine, is the first to quantify how much hospital capacity the veterinary tranquilizer is consuming — turning what treatment providers have described anecdotally for two years into a measurable trend line that hospitals and public health agencies can plan against.

What the two hospitals recorded

The research team reviewed records from two Philadelphia hospitals covering January 2020 through September 2025. They focused on patients with opioid use disorder who were treated with dexmedetomidine, an infused sedative that requires intensive care monitoring because it can drive down heart rate and blood pressure, and used receipt of that drug as a marker for severe medetomidine withdrawal.

Medetomidine's arrival in the city's fentanyl supply has been traced anecdotally to mid-2024, so investigators split the data into periods before and after that point. In the pre-medetomidine period, dexmedetomidine was given to just shy of 6 percent of patients with opioid use disorder. In the post-medetomidine period, roughly 20 percent needed it. Over the final three months of the study, the rate climbed to about 32 percent — nearly a third of the patients in front of them.

"You can't address something you can't see," said Tyler Boyce, a fellow in pulmonary and critical care medicine and co-first author of the study. "Showing how an increase in severe withdrawal cases is a reflection of this drug's emergence in the opioid supply will likely prove valuable to hospitals and public health officials trying to appropriately plan responses."

Why this withdrawal behaves differently

Medetomidine is an anesthetic used on large animals, and it is 100 to 200 times more powerful than xylazine — the veterinary sedative it has largely displaced in the illicit opioid supply. Its withdrawal comes on quickly and produces tachycardia, extreme anxiety, nausea and vomiting, with reports of organ damage in severe, untreated cases. Naloxone, the standard overdose reversal medication, does not resolve sedative effects driven by medetomidine because the drug does not act on opioid receptors.

That combination is what pushes patients into critical care. Dexmedetomidine can hold the withdrawal syndrome in check, but it requires continuous monitoring and careful titration, which in practice means an ICU bed.

"Historically, heroin withdrawal without these adulterants could be managed in outpatient or minimally monitored inpatient settings," said Ashish Thakrar, an assistant professor of general internal medicine and the study's other co-first author. "It was striking that, in the last quarter of our study, a third of patients required intensive care unit management for withdrawal from fentanyl mixed with medetomidine. Clinically, we recognize that we are in a new era of withdrawal management."

The findings land roughly a year after federal and municipal health agencies began issuing advisories about the drug. Philadelphia and Baltimore both published warnings in 2026, and CDC surveillance found medetomidine detections had expanded from a handful of states to more than a dozen within two years — a pattern that Baltimore's health department described as a threat that standard overdose response was not built to handle.

The strain shows up in medication use, too

Patients who needed dexmedetomidine were significantly more likely to require other medications and higher doses — evidence, the authors argue, that their severe withdrawal came from medetomidine rather than untreated fentanyl withdrawal alone.

Among patients with medetomidine-related withdrawal, 79 percent received methadone, compared with 50 percent of patients with opioid use disorder who did not need dexmedetomidine. Thirty-six percent received buprenorphine, compared with 26 percent in the comparison group. The dexmedetomidine patients also spent more time in the ICU on average. They tended to be younger than other patients with opioid use disorder and were more likely to be covered by Medicare, a detail that points to patients qualifying through disability rather than age.

"Patients are coming to us very sick, and we have had to rapidly adapt our treatments to serve the patients in front of us," said Margaret Lowenstein, an assistant professor of general internal medicine, research director for the Penn Center for Addiction Medicine and Policy, and the study's senior author. "Understanding the impact of this new adulterant and helping clinicians and hospitals prepare to care for affected patients is critical."

What the authors say is still unknown

The researchers are explicit that the study measures a proxy, not prevalence. Relying on dexmedetomidine administration identifies the most severe cases and almost certainly undercounts patients who were exposed to medetomidine and managed without critical care.

What they want next is a way to identify who is most at risk of the severe withdrawal syndrome, and data that could shape policy — staffing models, withdrawal protocols and hospital capacity planning in markets where the adulterant is now entrenched.

For people in treatment for opioid use disorder, the practical implication is that withdrawal management has become a more resource-intensive undertaking than the standard outpatient taper many programs were designed around. Jails and prisons, which reported their own medetomidine withdrawal crisis earlier this year, face the same arithmetic with fewer clinical resources. People seeking care for opioid addiction can find medication-assisted treatment programs nationwide.