Opioids
Joey Sweeney, PharmD, BCPS
Opioid use, while appropriate in many cases, may be associated with increased morbidity and mortality from infection, suggests a study published in Pharmacotherapy from June 2021. Opioids can reduce the body’s immune response, which is especially relevant during the pandemic for critically ill COVID-19 patients.
The study by Mefford and colleagues summarizes existing studies published between 1947 and 2020. They evaluate the impact of opioid use on immune suppression in critically ill patients and conclude that pharmacists can be opioid stewards by understanding the effect of various opioids on the immune system.
Opioid use for ICU patients
It is known that chronic opioid users—both licit and illicit—have increased rates of bacterial skin and soft tissue infections as well as respiratory, endovascular, and musculoskeletal infections.
In the era of COVID-19, the increased risk of respiratory infections is particularly concerning, the study authors note.
“Critically ill patients at baseline have marked pro-inflammatory systemic responses due to infection, trauma, cardiopulmonary bypass, major surgery, acute respiratory distress syndrome, and more,” the researchers write.
Treating each case on a per-patient basis is a wise choice for clinicians, as a patient’s opioid-use history is just one of the clinically relevant components of their active disease state.
While randomized controlled trials do not exist that address the question of opioid use on clinical outcomes, there have been a few retrospective studies which support the notion that opioid use does reduce clinical outcomes via a likely reduction in immune system response.
Opioid receptors are located on immune cells
Various immune cells express opioid receptors on their cell membranes. Mu, delta, and kappa receptors can be found on macrophages, peripheral mononuclear cells, T cells, B cells, splenocytes, monocyte cell lines, and/or natural killer cells.
The study authors explain that in various animal studies morphine exposure lead to reduced antibody production by B cells in vivo, meaning opioid receptor activation may alter immune response.
Morphine has been shown to inhibit T cells and reduce B cell proliferation in murine models for up to 24 months. These effects haven’t been seen by non-centrally acting opioids such as hydromorphone or oxycodone in a murine model.
The authors do not state how the findings of these animal studies could impact opioid-use decisions within humans.
Morphine: the devil known
Prior research connects morphine to a decrease in NK cell activity within human subjects. In vitro models have shown morphine-induced monocyte apoptosis. Further, morphine reduces both B cells and PBMCs. When macrophages are exposed to morphine ex vivo, phagocytosis is lessened.
Naltrexone diminishes this effect when co-administered. Alarmingly, alveolar macrophage phagocytosis of Streptococcus pneumoniae is inhibited in the presence of morphine. Heroin and methadone have also been shown to exhibit the same effect. Phagocytosis inhibition appears to be dose-dependent. However, the effect of opioid tolerance was not discussed in the study.
Lastly, morphine has been shown to inhibit chemotaxis—the ability of immune cells to be chemically attracted to a threat.
Other opioids: the devil unknown
Morphine is the most studied immune system–altering opioid, followed by fentanyl. However, this does not necessarily mean that other opioids are less impactful to the immune system. Clinicians should be cautious when substituting another opioid if the primary concern is mitigating immune system effects. While the risks of morphine are more well-known, other opioids’ risks on the immune system are simply less known. Trading a devil you know for a devil you don’t is not necessarily a wise clinical decision.
Favorable adjuncts available
Acetaminophen, ketamine, gabapentin, and pregabalin are likely to be immune system–neutral adjuncts that can be used as analgesics for critically ill patients. These agents are unlikely to eliminate the need for opioids for these patients, but they could reduce opioid use.
Aside from all the known benefits of opioid-use reduction in the community, this new research paper shows that it may also positively impact a patient’s ability to fight infections.