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December 13, 2023
Patients with opioid addictions are leaving U.S. hospitals against medical advice at a growing rate, researchers at Penn Medicine say. The severity of withdrawal from fentanyl and its mixture with other drugs is fueling the trend.
Hospitals have faced mounting pressure in recent years to find better treatments for patients who are in the throes of opioid withdrawal.
The challenge of safely managing these patients' symptoms is compounded by fentanyl, the synthetic opioid that's now dominant among drug users. Fentanyl is much stronger than heroin, but also shorter-acting. This leads people to inject it more frequently, causing higher rates of infection that require hospital visits.
"Some people are using 10 to 40 bags a day," said Jeanmarie Perrone, the director of Penn Medicine's division of medical toxicology and addiction medicine initiatives. "The doses we're familiar with in a hospital to treat pain would be 10 times higher to treat opioid dependence, maybe 30 times higher. There's a shifting paradigm to educate clinicians that the doses we need have to be much higher than the majority of patients are getting."
An increasing number of patients admitted to U.S. hospitals for opioid use disorder and infections related to drug use are now leaving before they complete their recommended treatments, according to a new study led by Penn Medicine researchers.
One in six patients in these circumstances leave the hospital before their care teams determine it's safe for them to do so. The rate of early discharges increased by more than 50% between 2016 and 2020, with patients most often citing withdrawal and pain.
The study used national data from a range of hospitals to analyze how many patients with opioid addiction left before the third day of treatment, which is usually when withdrawal is most severe.
"The rapid increase in early discharges is alarming," Ashish Thrakar, the study's lead author and an assistant professor of medicine, said in a news release. "In 2016, less than 1 in 10 patients admitted for OUD and injection-related infections left the hospital before their care team considered it safe. What's more, since the study period ended, the COVID-19 pandemic caused the opioid crisis to escalate, underscoring just how urgent it is to understand how we might be able to reverse this trend and get patients the treatment they need."
Overcrowded hospitals have played a role in delaying timely treatment for patients who are in the critical period of withdrawal, Perrone said. But fentanyl also is responsible for increasing the number of patients who need to visit hospitals. And when these patients leave hospitals against medical advice, they face a higher likelihood of death or worsening health conditions that require them to be readmitted for longer stays.
"We're seeing something like a doubling in the rate of complications — specifically infection-related," Perrone said. "More patients with opioid use disorder are being admitted, and some of them require long-term antibiotics like bone infections or heart infections."
Protocols for managing opioid withdrawal often involve replacing a shorter-acting opioid, like fentanyl, with a longer-acting drug like methadone. That can help patients adjust to hospital settings, but many struggle with no-smoking policies and withdrawal symptoms from other drugs they use.
"The average patient that we see coming to the hospital has at least three drugs in their drug screen," Perrone said. "Usually there's some sort of stimulant like cocaine or methamphetamine. There's some sort of opioid and possibly something else."
Fentanyl users frequently are injecting drugs that include the animal sedative xylazine, which took root in Philadelphia and has rapidly spread to other parts of the country in recent years. The tranquilizer is used to prolong the high drug users feel after the effects of fentanyl wear off, but it's been widely associated with dangerous skin wounds that send more people to hospitals with infections. Many patients complain of restlessness, anxiety and pain.
"We're really not sure how much of this is xylazine, how much of it is fentanyl or how much of it is the other drugs," Perrone said. "Certainly in Philadelphia, we hear patients say, 'you know, it's not the fentanyl withdrawal.' They say it's the xylazine withdrawal. When we've looked for an objective, different syndrome of withdrawal, we haven't found it. We are still looking and we expect it might be something different."
As one of the nation's leading health systems, Penn Medicine is better-equipped than most to handle patients suffering from opioid withdrawal. Addiction specialists there have been experimenting with higher doses of methadone and combining that with short-acting opioids to treat fentanyl withdrawal symptoms.
"At a typical small community hospital, they're never going to be comfortable with those doses currently because we've cautioned so much against using opioids," Perrone said. "We all think that's what caused the opioid crisis — too much opioids — so why would you give opioids back to somebody who has this problem? It's paradoxical, but it is what they need until they can be stabilized."
Another challenge facing many hospitals, in Philadelphia and elsewhere, is the lack of available addiction specialists or consult services that can quickly begin working with patients. Due to high patient volumes for all kinds of issues, many of those with opioid withdrawal end up waiting multiple days in the emergency department before they can be seen by a specialist.
"There are more patients vying for the same number of people who have the ability to treat them well," Perrone said.
The effects of the pandemic — particularly the housing crisis — also have made it harder for patients to stick around in hospitals when they're in withdrawal.
"People are more opioid dependent. They're losing more things like their housing and relationships," Perrone said. "As housing becomes a factor, it requires them to be in the hospital because they can't get home care and other things. It's an even bigger change to be in a hospital when you're living outside."
Last year, Philadelphia recorded its highest death toll from drug overdoses. More than 80% of the city's 1,413 fatal overdoses were attributed to opioids — particularly fentanyl, which made up 96% of opioid-related deaths.
Fatal overdoses among Black and Hispanic people increased by 87% and 43%, respectively, from 2018 to 2022, the health department's annual report said. Most of this surge has been attributed to opioids mixed with stimulants, suggesting fentanyl increasingly is present in street drugs.
"The drugs that individuals are using have changed over the past decade, and how we treat them should change, too," M. Kit Delgadio, the senior author of the hospital study and director of Penn Medicine's Nudge Unit, which uses behavioral science to enhance patient outcomes, said in a news release.
In recent years, Perrone and her Penn Medicine colleagues have developed innovative protocols to treat patients who come to the hospital for complications related to opioid use.
Three emergency departments at Penn Medicine hospitals have a program that starts patients on buprenorphine — another drug used to treat opioid withdrawal — so that they don't need to be admitted. They can directly start treatment and get connected with a primary care doctor who can help tailor an addiction treatment plan. Patients don't need to have insurance or IDs to get this help.
Buprenorphine is one of the two drugs used in Suboxone, which is often given to patients to manage opioid dependence. The potency of fentanyl has made it more difficult for clinicians to safely prescribe Suboxone, because it may exacerbate symptoms if taken too early during withdrawal.
"In the fentanyl era, people feel withdrawal symptoms earlier and think they're ready for a dose of Suboxone, but in fact sometimes they have to wait 24 hours or even longer before they can take suboxone safely without getting worsening symptoms," Perrone said.
Buprenorphine can be used to treat withdrawal symptoms and pain. Another advantage is that it can be injected as a long-acting source of relief that helps patients after they leave the hospital. Suboxone is taken orally and may be more readily abandoned once patients are discharged.
"We know that people do really well if they have a long-acting injectable on-board," Perrone said. "Then they don't have a change of heart on day two without taking their Suboxone. We're experimenting with ways of getting people into treatment that we call low-barrier access. The emergency department is the most available 24/7 pathway."
Because so many patients enter the hospital with multiple drugs in their systems, finding the right combination of withdrawal treatments is a balancing act.
"I do think that there are still a lot of symptoms that are hard to manage because we just don't have a good recipe right now," Perrone said.
Beyond the challenge of treating physical symptoms, there are other emotional and behavioral factors that make it difficult for people stay at hospitals when they're in withdrawal. Perrone said hospitals would benefit from having more robust peer support staff.
"Using more peers on a daily basis to really sit with patients and visit them, building relationships could help," Perrone said. "I think all of the hospitals are using them in some capacity, but probably not not enough for the growing volume."
The authors of the study, which was published this month in the Journal of the American Medical Association, suggested hospitals could be incentivized to reduce early discharges. They also believe hospitals should be better integrated with addiction consult services, which are proven to reduce early discharges by efficiently lining patients up with specialized care.
"Withdrawal symptoms from fentanyl are more difficult to manage than from other opioids like heroin and oxycodone," Thakrar said. "This study illustrates why we need more research on how to manage individuals withdrawing from fentanyl and other substances in the unregulated drug supply."