Opioids and the Risk of Infection: A Critical Appraisal of the Pharmacologic and Clinical Evidence

ABSTRACT

Introduction: There are concerns that opioids may be associated with an increased risk of infection. This safety issue is alarming given the widespread use of opioids in pain management.

Areas covered: In this review, we summarize the pharmacologic aspects of opioids related to the immune system and to the assumed pathophysiology of opioid-related infections. We also synthesize and critically appraise the available clinical evidence on the potential association between the use of opioids and the risk of infection. PubMed was searched from inception to 1 February 2019 for all articles published in English with terms corresponding to ‘opioids’ and ‘infections’.

Expert opinion: Morphine appears to suppress the immune system via affecting cells of the innate and the adaptive immunity as well as via modulating the hypothalamic-pituitary-adrenal axis. However, knowledge gaps exist regarding the immune-related pharmacology of non-morphine opioids. Observational studies have suggested an increased risk of infections associated with the use of opioids. However, methodological limitations such as confounding by indication due to the choice of non-use as comparator render the interpretation of most of these studies difficult. Thus, further efforts in preclinical research and well-conducted observational studies are needed to provide more robust evidence in this regard.

KEYWORDS:

• Opioids
• pharmacoepidemiology
• pharmacology
• morphine

Article highlights

• Preclinical studies have suggested that morphine may suppress the immune system by affecting cells of the innate and adaptive immunity or by modulating the hypothalamic-pituitary-adrenal axis.

• The immune-related effects of morphine seem to depend on timing, species under study, duration of treatment, and dose.

• Important knowledge gaps exist regarding the immune-related pharmacology of non-morphine opioids.

• Several observational studies have indicated that opioids may be associated with an increased risk of infections, particularly pneumonia.

• Interpretability of most observational studies is limited due to methodological limitations such as confounding by indication, and non-immune related mechanisms such as sedation could also account for the risk of respiratory infections.

• Further studies are needed to better characterize the immunosuppressive potential of opioids and particularly of non-morphine compounds.

This box summarizes the key points contained in the article.

Acknowledgments

FK is the recipient of a Doctoral award from the Fonds de recherche du Québec - santé (FRQS; Quebec Foundation for Health Research). SK is the recipient of a Kuok Scholarship from the Rossy Cancer Network. FK and SK are recipients of a training award from the Canadian Institutes for Health Research Drug Safety and Effectiveness Training Program. KBF holds a salary support award from the FRQS and a William Dawson Scholar award from McGill University.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

There was no funding for this study.