Effects of genetic polymorphism of CYP3A4 and CYP3A5 on analgesic efficacy of postoperative intravenous analgesia with sufentanil in patients after laparoscopic surgery

Abstract

Objective To explore the differences of postoperative patient-controlled intravenous analgesia (PCIA) with sufentanil in the patients with different CYP3A4 and CYP3A5 genotypes after laparoscopic surgery. Methods According to CYP3A4 and CYP3A5 genotypes, the population are divided into class Ⅰ (CYP3A4 homozygous mutation, or CYP3A4 heterozygous mutation combined with CYP3A5 homozygous mutation), class Ⅱ (CYP3A4 heterozygous mutation combined with CYP3A5 heterozygous mutation), and class Ⅲ (CYP3A4 wild type, or CYP3A4 heterozygous mutation combined with CYP3A5 wild type). The patients undergoing laparoscopic surgeries in the departments of general surgery and urology of our first affiliated hospital from November 2020 to September 2021 were included in this prospective observational study. Oral swabs were collected for gene detection on CYP3A4 and CYP3A5 during the pre-anesthesia evaluation. According to their genotypes and 1 ∶1 ratio of men and women, they were randomly divided into group A, B and C by the randomized envelope and blind methods, with 30 patients in each group. The gene types of each group would be revealed through 2 steps. All patients in 3 groups received postoperative intravenous analgesia with sufentanil. The data, at 12, 24 and 48 h after surgery were collected as the following: visual analog analgesia score (VAS), Ramsay sedation score, cumulative dose of sufentanil, numbers of analgesic pump compressions, and incidence of postoperative nausea and vomiting. Results A total of 256 oral swab specimens were collected, and 23, 24, and 27 patients in group A, B and C completed the study respectively. After data collection and statistical analysis, the genotype types of the patients in groups A, B and C were disclosed, corresponding to class Ⅰ, Ⅱ and Ⅲ populations respectively. Compared with class Ⅰ, the Ramsay score was significantly increased at 12 h after surgery in the patients from class Ⅲ (P<0.05), and there was no statistically significant difference in Ramsay score among the 3 populations at 24 and 48 h after surgery. There were no statistical differences in the VAS scores, cumulative dosage of sufentanil, number of analgesic pump compressions, and incidence of postoperative nausea and vomiting among the 3 groups 12, 24 and 48 h after surgery. Conclusion Genetic polymorphisms of CYP3A4 and CYP3A5 have no significant effects on analgesic efficacy of postoperative PCIA with sufentanil after laparoscopic surgery

Keywords

• cyp3a4
• cyp3a5
• genetic polymorphism
• sufentanil
• self-control analgesia