Surgical Technique or Genomics Predictors of Postoperative Morphine Consumption

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

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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- 1a and
  IL-1ß) 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-1a and IL-1ß

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IL-1Ra Association with Morphine Use

• IL-1ß 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-1ß 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-1ß.
  

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IL-1Ra Association with Morphine Use

• The IL-11 genotype (wildtype) is associated with
  regular expression of IL-1? and thus
  proinflammatory.
• IL-12 (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.

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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.

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Morphine Consumption at Each 12 Hours
Postoperatively


Postoperative Time (hrs)
p0.002 p0.002 between two groups
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Pain Scores Postoperatively

Postoperative Time (hrs)
P0.010
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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
N29
Morphine Consumption mg
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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.