title: Pharmacogenetics-guided analgesics in major abdominal surgery: Further benefits within an enhanced recovery protocol.
abstract: OBJECTIVE
  Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects). The purpose of this study was to perform the first assessment of the impact of a pharmacogenetics (PGx) guided selection of analgesics following major abdominal surgery within an ERP.
  
  
  METHODS
  A consecutive series of open and laparoscopic colorectal resections or major ventral hernia repair (PGx group) had a guided analgesic protocol based upon assessment of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1 genes. Study patients were compared to a recent historical series of patients (H group) managed using our well validated ERP. The primary outcome measure was the Overall Benefit of Analgesia Score (OBAS). Pain scores were also assessed.
  
  
  RESULTS
  The data demonstrated a similar mix of procedures and gender between groups and more than half of the PGx group had revised analgesia from the standard ERP. The PGx group demonstrated significantly lower OBAS scores (p = 0.0.1) from POD1 (3.8 vs 5.4) through POD 5 (3.0 vs 4.5) Analgesia was also superior for the PGx group from POD1 through POD 5 (p = 0.04).
  
  
  CONCLUSIONS
  Pharmacogenetics guidance resulted in frequent modifications of the analgesic program, resulting in excellent analgesia with a 50% reduction in narcotic consumption, and a reduced incidence of analgesic related side effects compared to our standard ERP. These data suggest further improvement in ERP resulting from a patient centric analgesic, reduced narcotic regimen which provides early and durable pain control with fewer narcotic related side effects.
authors.affiliation: University of Texas Medical Branch at Galveston, Galveston, TX, United States. Electronic address: ajsenago@utmb.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Senagore
authors.affiliation: Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Champagne
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, University Hospitals-Case Medical Center, Cleveland, OH, United States.
authors.forename: Eslam
authors.initials: E
authors.lastname: Dosokey
authors.affiliation: University Hospitals of Cleveland, Cleveland, OH, United States.
authors.forename: Justin
authors.initials: J
authors.lastname: Brady
authors.affiliation: Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Steele
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, University Hospitals-Case Medical Center, Cleveland, OH, United States.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Reynolds
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, University Hospitals-Case Medical Center, Cleveland, OH, United States.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Stein
authors.affiliation: Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: Conor P
authors.initials: CP
authors.lastname: Delaney
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000700:Analgesics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003106:Colon / Q000601:surgery; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006555:Hernia, Ventral / Q000601:surgery; D065386:Historically Controlled Study; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D010597:Pharmacogenetics; D057285:Precision Medicine; D017450:Receptors, Opioid, mu / Q000235:genetics; D012007:Rectum / Q000601:surgery; D064232:Visual Analog Scale
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000700:Analgesics; D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D003577:Cytochrome P-450 Enzyme System; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1; Enhanced recovery; Overall Benefit of Analgesia Score (OBAS); Pharmacogenetic testing