Pharmacogenetic Aspects of Postoperative Anesthesia with Ketoprofen in Cardiac Surgery Patients

Abstract

Aim. Evaluation of the effect of polymorphisms of the CYP2D6, CYP2C8 genes on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.Material and methods. The study included 90 patients with an established diagnosis of coronary artery disease and postoperative period after cardiac surgery. Patients received ketoprofen 100 mg intramuscularly 2 times a day for 5 days. The intensity of pain was rated by Numeric Rating Scale. The severity of dyspepsia was assessed by the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. DNA was isolated from venous blood using an automated system. Single nucleotide polymorphisms CYP2C8 (C>T) rs11572080, CYP2D6*4 (1846G>A) rs3892097 were determined by the real-time polymerase chain reaction method.Results. In patients with genotypes GA and GG for the allelic variant CYP2D6*4, significant differences in the intensity of pain syndrome were found on days 4 and 5 of the postoperative period: 3,91±2,17 and 4,95±1,8 points (p=0,04), 3,52±1,95 and 4,5±1,7 points (p=0,04) in patients with GA and GG genotypes on days 4 and 5, respectively. In patients with the CT genotype for the CYP2C8 rs11572080, the severity of dyspepsia by GSRS was significantly higher than in patients with the CC genotype: 22,67±7,64 and 18,97±4,25 points, respectively.Conclusion. Patients with the GA genotype for the CYP2D6*4 allelic variant showed a lower intensity of pain syndrome than the GG genotype. In patients with the CT genotype for the CYP2C8 rs11572080, higher dyspepsia was revealed than in the CC genotype.

Keywords

• postoperative analgesia
• cardiac surgery
• pharmacogenetics
• ketoprofen