Environmental and genetic factors associated with morphine response in the postoperative period.
OBJECTIVE
The aim of this study was to investigate the respective influence of genetic and nongenetic factors on morphine dose requirements and adverse effects after colorectal surgery.


METHODS
Seventy-four patients who planned to undergo colorectal surgery were included in this pilot study. The cumulative 24-hour postoperative dose of morphine and postoperative nausea or vomiting requiring the antiemetic ondansetron were the 2 clinical end points. The association of patient characteristics, A118G mu-opioid receptor (OPRM1) single-nucleotide polymorphism (SNP); T802C uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) SNP; and 2 adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) (multidrug resistance 1 [MDR1]) exonic SNPs (G2677T/A and C3435T) with study end points was investigated.


RESULTS
Age, creatinine clearance, and the regular use of psychotropic agents were found to be significantly associated with postoperative morphine dose requirements by univariate analysis. Multivariate analysis identified that age (P = .01) and the use of psychotropic agents before surgery (P = .03) were positively associated with a higher rate of morphine consumption. A higher weight (P = .05) and the ABCB1 homozygous GG-CC diplotype (P = .03) were significantly associated with fewer morphine side effects by univariate analysis. The homozygous ABCB1 diplotype (GG-CC) conferred an odds ratio of 0.12 (95% confidence interval, 0.01-0.98) with regard to the use of ondansetron for postoperative nausea or vomiting. Multivariate analysis identified that the ABCB1 GG-CC diplotype was the only borderline-significant (P = .07) predictive factor of morphine side effects.


CONCLUSIONS
Age and prior use of psychotropic agents are associated with postoperative morphine dose requirements. Whether ABCB1 polymorphisms might predict morphine side effects remains to be determined.
Coulbault
Laurent
L
Pharmacology Department, Saint Antoine University of Medicine, University Pierre et Marie Curie, Paris, France.
Beaussier
Marc
M
Verstuyft
Céline
C
Weickmans
Henri
H
Dubert
Liliane
L
Trégouet
David
D
Descot
Christelle
C
Parc
Yann
Y
Lienhart
André
A
Jaillon
Patrice
P
Becquemont
Laurent
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D003107:Colorectal Surgery; D005260:Female; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000473:pathology / Q000517:prevention & control; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D020250:Postoperative Nausea and Vomiting / Q000473:pathology / Q000517:prevention & control; D011184:Postoperative Period; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase