Surgery‐induced inflammation reduces morphine distribution into cerebrospinal fluid

Abstract

ObjectiveTo determine the effects of surgery‐induced inflammation on morphine distribution across blood‐brain barrier (BBB)MethodsBlood and cerebrospinal fluid (CSF) concentrations of morphine were measured in adult patients undergoing aortic aneurism surgery with (n=12) and without (n=13) cardiopulmonary bypass (CPB). Morphine concentrations were determined by mass‐spectrometry. A Q‐plex cytokine ELISA was used to measure plasma and CSF cytokines.ResultsThe surgical inflammatory response was characterized by increased plasma concentrations IL‐6, a known regulator of BBB drug transporters. The plasma area under the curve from 0 to 24 h (AUC0–24h) of interleukin‐6 (IL‐6) was significantly higher (p=0.02) in the CBP (7900±8180 pg/ml h) versus the non‐CPB (1690±1680 pg/ml h) group, indicating that individuals receiving CPB had a more robust inflammatory response. The CSF to plasma AUC0–24h ratio of morphine in the CPB versus non‐CPB groups was 1.06±0.57 and 2.51±2.08 (p=0.03), respectively, indicating that less morphine penetrated into the brain following CPB when a larger inflammatory response was present.ConclusionCSF morphine exposure is lower in individuals undergoing aortic aneurism with CPB. This effect may be due to IL‐6‐mediated changes in blood‐brain barrier drug uptake or efflux transporter function.The HSFC, PEF and CAS funded the project.

Putative Involvement of Cytokine Modulation in the Development of Perioperative Neurocognitive Disorders

“… Vasunilashorn et al 2021 68 29 Knee or hip total arthroplasty Spinal Elective Nil Before surgery and 1-month after surgery IL-6, CHI3L1, CRP In serum samples there was a significant increase in IL-6 at 1 month. Wang et al 2013 91 36 Aortic aneurysm surgery ± cardiopulmonary bypass Spinal Elective Nil Pre-incision, wound closure and every 4 hours for up to 5 days after surgery IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IFN-γ and TNF-α Plasma IL-6 levels were higher in the patient group which underwent cardiopulmonary bypass. Note : A table summarising studies which have investigated cytokine changes in cerebrospinal fluid and blood both before and after an operation.…”