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Surgical Technique or Genomics? Predictors of Post-operative Morphine Consumption

Surgical Technique or Genomics? Predictors of Post-operative Morphine Consumption. Dr. Keith Candiotti Department of Anesthesiology University of Miami. Rationale.

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Surgical Technique or Genomics? Predictors of Post-operative Morphine Consumption

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  1. Surgical Technique or Genomics?Predictors of Post-operative Morphine Consumption Dr. Keith Candiotti Department of Anesthesiology University of Miami

  2. Rationale • Several studies investigating postoperative pain and convalescence have shown laparoscopy to be superior compared to open nephrectomy. • Our recent study has shown that the Interleukin-1 receptor antagonist (IL-1Ra) polymorphism has a significant impact on postoperative morphine consumption. • This present study was designed to evaluate if genomics (IL-1) or surgical technique was a better predictor of postoperative morphine consumption.

  3. IL-1Ra Association with Morphine Use • The cytokine interleukin-1 (IL-1) acts as a major initial inducer of a proinflammatory state. • Two structurally different forms (IL- 1αand IL-1β) exist, both of which bind to the same receptor protein (IL-1R). • The IL-1-receptor antagonist (IL-1Ra) binds to this same receptor but does not initiate signal transduction, thus acting as an antagonist to both IL-1α and IL-1β

  4. IL-1Ra Association with Morphine Use • IL-1β mediated induction of cyclooxygenase-2 (COX-2) in the central nervous system elevates PGE2 levels in the CSF and contributes to inflammatory pain hypersensitivity . • Additionally, it has been demonstrated that IL-1β induces substance P release from primary afferent neurons through the COX-2 system • Recently, it has been demonstrated that the IL-1Ra variants decrease the expression of IL-1β.

  5. IL-1Ra Association with Morphine Use • The IL-1*1 genotype (wildtype) is associated with “regular” expression of IL-1 and thus proinflammatory. • IL-1*2 (probably *3) are associated with a down regulation of IL-1 and reduced inflammation. • Peak of IL-1 is at around 24 hours post-op. • Previous reports showed some association with opioid use but were not conclusive.

  6. Study Design • 80 patients undergoing nephrectomies were enrolled. • Standardized anesthetic protocol was utilized. • Patients were followed for 72 hours • All patients were on Morphine PCA for at least 48 hours. • Patients reported VAS pain scores for 0-72 hours. • Data was separated based on surgery incision type.

  7. * ** Morphine Consumption at Each 12 Hours Postoperatively * ** Postoperative Time (hrs) *p=0.002; **p=0.002 between two groups

  8. * Pain Scores Postoperatively * Postoperative Time (hrs) * P=0.010

  9. 24 H Morphine Consumption in the IL-1 Ra Polymorphism A vs. C p=.03 B vs. D p=.04 B vs. C p=.5 N=29 Morphine Consumption mg

  10. Conclusions • Postoperative pain is multifactorial. • Based on the current surgical literature incision type is a major predictor of postoperative pain. • Polymorphisms in certain genes have been linked with morphine consumption and postoperative pain (CYP2D6, IL-1, ABCB1, Mu-receptor variants. • Based on our preliminary data genomics (IL-1) MAY play as great a role in postoperative pain as surgical incision type.

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