Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis
CONTEXT:. Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investig...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2023-01-01
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| Series: | Critical Care Explorations |
| Online Access: | http://journals.lww.com/10.1097/CCE.0000000000000849 |
| _version_ | 1797947133322592256 |
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| author | Brittany D. Bissell, PharmD, PhD, FCCM, BCCCP Jamie L. Sturgill, PhD Maria E. C. Bruno, PhD Erick D. Lewis, MS Marlene E. Starr, PhD |
| author_facet | Brittany D. Bissell, PharmD, PhD, FCCM, BCCCP Jamie L. Sturgill, PhD Maria E. C. Bruno, PhD Erick D. Lewis, MS Marlene E. Starr, PhD |
| author_sort | Brittany D. Bissell, PharmD, PhD, FCCM, BCCCP |
| collection | DOAJ |
| description | CONTEXT:. Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.
HYPOTHESIS:. We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.
METHODS AND MODELS:. This was a two-phase preclinical and clinical study. The clinical phase included a subgroup of patients with sepsis from an existing randomized controlled trial while the preclinical phase used a murine model of sepsis with C57BL/6 mice. In the clinical phase, a post hoc analysis was performed in subjects receiving fentanyl versus no opioid receipt. In the preclinical phase, a murine cecal slurry-induced sepsis model followed by secondary infection was used. Mice were randomized to fentanyl versus no fentanyl concomitantly.
RESULTS:. In clinical sepsis, a significant decrease in interleukin-23 (IL-23) level in patients with fentanyl exposure was observed and lower IL-23 was associated with mortality (p < 0.001). Other measured cytokines showed no significant differences. Concomitant fentanyl exposure during murine sepsis was associated with a significantly higher bacterial burden (p < 0.001) after secondary infection; however, immune cell counts and plasma cytokine levels were largely unaffected by fentanyl.
INTERPRETATION AND CONCLUSIONS:. Minimal alterations in cytokines were seen with opioid exposure during clinical sepsis. In a preclinical model, opioid exposure during sepsis was associated with ineffective bacterial clearance upon secondary infection. Further studies are warranted to evaluate the immunomodulatory role of opioids and their implications, especially in the post-sepsis period. |
| first_indexed | 2024-04-10T21:22:59Z |
| format | Article |
| id | doaj.art-9b2ee277cbb44317a67233810c56f88b |
| institution | Directory Open Access Journal |
| issn | 2639-8028 |
| language | English |
| last_indexed | 2024-04-10T21:22:59Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Critical Care Explorations |
| spelling | doaj.art-9b2ee277cbb44317a67233810c56f88b2023-01-20T02:33:54ZengWolters KluwerCritical Care Explorations2639-80282023-01-0151e084910.1097/CCE.0000000000000849202301000-00018Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical SepsisBrittany D. Bissell, PharmD, PhD, FCCM, BCCCP0Jamie L. Sturgill, PhD1Maria E. C. Bruno, PhD2Erick D. Lewis, MS3Marlene E. Starr, PhD41 Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY.2 Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY.3 Department of Surgery, College of Medicine, University of Kentucky, Lexington, KY.3 Department of Surgery, College of Medicine, University of Kentucky, Lexington, KY.3 Department of Surgery, College of Medicine, University of Kentucky, Lexington, KY.CONTEXT:. Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection. HYPOTHESIS:. We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model. METHODS AND MODELS:. This was a two-phase preclinical and clinical study. The clinical phase included a subgroup of patients with sepsis from an existing randomized controlled trial while the preclinical phase used a murine model of sepsis with C57BL/6 mice. In the clinical phase, a post hoc analysis was performed in subjects receiving fentanyl versus no opioid receipt. In the preclinical phase, a murine cecal slurry-induced sepsis model followed by secondary infection was used. Mice were randomized to fentanyl versus no fentanyl concomitantly. RESULTS:. In clinical sepsis, a significant decrease in interleukin-23 (IL-23) level in patients with fentanyl exposure was observed and lower IL-23 was associated with mortality (p < 0.001). Other measured cytokines showed no significant differences. Concomitant fentanyl exposure during murine sepsis was associated with a significantly higher bacterial burden (p < 0.001) after secondary infection; however, immune cell counts and plasma cytokine levels were largely unaffected by fentanyl. INTERPRETATION AND CONCLUSIONS:. Minimal alterations in cytokines were seen with opioid exposure during clinical sepsis. In a preclinical model, opioid exposure during sepsis was associated with ineffective bacterial clearance upon secondary infection. Further studies are warranted to evaluate the immunomodulatory role of opioids and their implications, especially in the post-sepsis period.http://journals.lww.com/10.1097/CCE.0000000000000849 |
| spellingShingle | Brittany D. Bissell, PharmD, PhD, FCCM, BCCCP Jamie L. Sturgill, PhD Maria E. C. Bruno, PhD Erick D. Lewis, MS Marlene E. Starr, PhD Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis Critical Care Explorations |
| title | Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis |
| title_full | Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis |
| title_fullStr | Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis |
| title_full_unstemmed | Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis |
| title_short | Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis |
| title_sort | assessment of opioid induced immunomodulation in experimental and clinical sepsis |
| url | http://journals.lww.com/10.1097/CCE.0000000000000849 |
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