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Abstract
Background and Aims Acute post-operative pain remains a significant challenge despite multi-modal analgesia approach and novel analgesic pathways may improve upon existing strategies. The endocannabinoid pathway may facilitate analgesia, but there is limited data regarding the impact of surgery and existing therapeutics on the endocannabinoid pathway during the perioperative time period. The specific aims of the study were to 1) measure the inter-individual variability of blood endocannabinoid levels in patients scheduled for elective total knee arthroplasty, 2) determine the effect of oral acetaminophen on blood endocannabinoid levels, and 3) determine the effect of surgery on blood endocannabinoid levels.
Methods The study protocol was approved by the Mayo Clinic IRB and patients provided informed consent. 23 adult patients undergoing elective total knee arthroplasty were enrolled in a prospective observational cohort study and provided venous blood samples at three time points (before surgery, before surgery after intravenous acetaminophen, and 24 hours postoperative). We measured endocannabinoid levels at each time point using a validated liquid chromatograph/mass spectrometry assay. We analyzed the data using a mixed methods linear regression model with the subject as a random effect and each time point as a fixed effect. We considered a p value < 0.05 significant. (Figure 1)
Results Two endocannabinoids differed significantly after exposure to acetaminophen (O-AEA and 14,15-EET-EA). Nine markers were different after exposure to surgery and perioperative management (O-AEA, LEA, DH-g-LEA, DEA, 2-AG, AEA, 14,15-EET-EA, OLA, PEA). Figure 1
Conclusions Acetaminophen and surgery have an impact on endogenous endocannabinoid blood levels, which presents a novel therapeutic target for perioperative analgesia.