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Opioid Use Disorder Plays Significant Role in Many Sepsis Cases

Analysis  |  By Christopher Cheney  
   January 26, 2022

About 30,000 to 40,000 opioid use disorder patients are hospitalized with sepsis each year.

The Sepsis Alliance is highlighting the intersection of sepsis and opioid use disorders.

Sepsis develops in response to infection, and can lead to tissue damage, organ failure, and death. Sepsis is the leading cause of in-hospital death in the United States. More than 1.7 million Americans are diagnosed with sepsis annually.

On Jan. 27, the Sepsis Alliance Institute is hosting a webinar on the intersection of sepsis and opioid use disorder. The webinar features Chanu Rhee, MD, MPH, associate hospital epidemiologist at Brigham and Women's Hospital and assistant professor of population medicine at Harvard Medical School, and Simeon Kimmel, MD, MA, attending physician at Boston Medical Center and assistant professor of medicine at Boston University School of Medicine.

Rhee and Kimmel were interviewed recently by HealthLeaders. The following transcript of that conversation has been edited for brevity and clarity.

HealthLeaders: How prevalent are sepsis cases among people afflicted with opioid use disorder?

Chanu Rhee: You need to have the denominator—how many people have opioid use disorders. In 2018, the Centers for Disease Control and Prevention (CDC) estimated that about 2 million people in the United States had opioid use disorders. We also know how many adults are hospitalized with sepsis each year, which is about 1.7 million adults. In a paper that Dr. Kimmel and I published recently in Critical Care Medicine, we found that about 2% of hospitalized sepsis patients had opioid use disorder.

With those numbers, we can do some math. There are 1.7 million adults with sepsis each year, and 2% of those patients have opioid use disorder, so we are talking about 30,000 to 40,000 opioid use disorder patients who are hospitalized with sepsis each year.

HL: What are the primary elements of the intersection of sepsis and opioid use disorder?

Simeon Kimmel: Many people with opioid use disorder are using injection opioids. When somebody injects an opioid, there is penetration of the skin barrier with a needle, which introduces the risk of infection. That can be the result of bacteria that are living on the skin, bacteria on the injection equipment such as the syringe, or the substance that is being injected can be contaminated with bacteria. Especially in the era of fentanyl, which has contaminated the injection opioid supply, fentanyl is a shorter-acting opioid that requires more frequent injections. What we are seeing is that people are injecting very frequently, which leads to an increased risk of skin and soft tissue infection. We see blood stream infections, where bacteria get into the blood and infect the heart valves, bones, and joints—we see septic arthritis. We also see lung infections and other kinds of infections related to this dynamic.

Opioid use can lead to overdose, which can lead to the risk of developing aspiration and pneumonias. There is some evidence that suggests that opioid use itself may have some effects on the immune system that can predispose people to developing infections such as lung infections.

Rhee: Even with oral opioid use, overdose can lead to pneumonia, and pneumonia is a common cause of sepsis.

HL: What are the primary signs that someone afflicted with opioid use disorder is also developing sepsis?

Rhee: The signs of sepsis are generally the same for people with opioid use disorder as for people in the general public. There can be confusion, disorientation, shortness of breath, high heart rates, fever, shivering, extreme discomfort, and clammy or sweaty skin. A lot of these signs can overlap with the signs of opioid withdrawal, which can make it very hard to tell an individual is developing sepsis versus having withdrawal. This can be a challenge for patients and healthcare providers.

For healthcare providers trying to identify sepsis in opioid disorder patients, you need to look for signs that might localize specific infections such as cough and shortness of breath. If a chest X-ray is taken, providers should look for pneumonia. Providers should look for redness and signs of infection at injection sites to be on the lookout for skin and soft tissue infections. Providers should look at vital signs for low blood pressure, high heart rates, and low oxygen saturation. Providers should look at laboratory data such as white blood cell counts.

It is always a challenge looking for the warning signs of sepsis. There is no one perfect or sensitive sign. You have to put things together in a constellation of symptoms and signs to get a diagnosis. It can be particularly challenging in patients with opioid use disorder.

HL: What are the key data points that demonstrate the epidemiology of sepsis in opioid-related hospitalizations?

Rhee: In a recent paper, we sought to describe the epidemiology of hospitalized patients with sepsis and opioid use disorders. We looked at a couple million patients who were hospitalized at 373 hospitals between 2009 and 2015. We identified sepsis using CDC surveillance criteria. We identified patients with opioid-related hospitalizations using previously validated diagnosis codes as well as inpatient prescriptions for buprenorphine. The bottom line is we found sepsis was present in about 6% of opioid-related hospitalizations. Conversely, opioid use disorders were present in about 2% of sepsis hospitalizations.

In terms of the burden and the mortality, we found that patients with opioid use disorders who had sepsis had lower short-term mortality rates compared to sepsis patients without opioid use disorders. This was a trend that persisted even after risk adjustment.

Over half of patients who had opioid-related hospitalizations who ended up dying during their hospitalization had sepsis. That was higher than the mortality rate for non-opioid-related hospitalizations—about a third of those patients had sepsis. This data suggests that sepsis is a major contributor to death in patients with opioid-related hospitalizations.

Finally, the prevalence of opioid use disorders among hospitalized patients, and especially among patients with sepsis, rose during the study period from 2009 to 2015. It increased 41% among all hospitalizations, and when we looked at sepsis hospitalizations, it increased by 77%. It became a bigger and bigger problem over time.

HL: How can sepsis be prevented in people afflicted by opioid use disorder?

Kimmel: There are several important steps. The first is that people with opioid use disorder need to have access to supplies to inject substances as safely as possible. That means access to alcohol swabs to be able to clean their skin and access to sterile injection equipment.

Second, there needs to be education for people with opioid use disorder to understand that they should seek care early for their infections.

Third, we need to improve the care of people in the hospital, so people feel comfortable coming to the hospital when they are sick. I take care of a lot of people with opioid use disorder in a drop-in clinic, and I spend a lot of time helping people understand the risks and benefits from their perspective of coming to the hospital because there is fear of being in the hospital such as fear of experiencing withdrawal symptoms.

Fourth, we need to improve access for treatment of opioid use disorders. There has been a lot of progress over the past few years around increasing low-barrier access to buprenorphine and improving access to methadone, which are evidence-based medications that reduce the risk of developing sepsis.

HL: Can you offer other insights about the intersection of sepsis and opioid use disorder?

Kimmel: There is a growing recognition of the importance of training clinicians to be able to treat opioid use disorder. Increasingly, there are systems in place to improve the treatment of opioid use disorder in the hospital. There has been development of addiction consult services. There are a growing number of infectious disease doctors who also are dually trained in addiction medicine. These are encouraging developments in terms of normalizing and improving the treatment of opioid use disorder.

Rhee: The intersection of sepsis and opioid use disorder highlights an important message around sepsis in general. There is so much focus on early recognition and treatment of sepsis in the hospital, which is perfectly important and makes a lot of sense. However, we are not focusing on what causes sepsis to develop in healthy people or people without underlying issues. Opioid use disorder is the perfect example of an issue that leads relatively healthy people to develop sepsis. There is only so much we can do to address sepsis once someone is in the hospital—we need to get upstream on the factors that predispose people to sepsis.

Christopher Cheney is the CMO editor at HealthLeaders.


People who inject opioids are at risk of infections that can lead to sepsis, including skin infections, soft tissue infections, and blood stream infections.

Even people who use oral opioids can develop sepsis because overdoses can lead to pneumonia, and pneumonia is a common cause of sepsis.

Diagnosing sepsis in an opioid use disorder patient can be difficult because the signs of sepsis are similar to the symptoms of opioid withdrawal.

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