Is OPRM1 genotype a valuable predictor of VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl?

Clinical characteristics

Figure 1 contains the flow chart of the participants. Table 2 describes the baseline characteristics of the subjects, including demographic characteristics and some laboratory test results that may be related to assess the VAS. The clinical and outcome data for subjects were obtained from clinical records. Table 2 describes all patient data, including age, gender, weight, height, fentanyl dosage, operation time, and genotypes of OPRM1 A118G, CYP3A4 *1G, CYP3A5 *3, and COMT Val158Met.

Fig. 1figure 1

The chart of the participants

Table 2 Characteristics of subjects in the research

There was no significant difference in age (59.53 ± 5.87 vs 61.67 ± 4.00), gender, weight (62.23 ± 9.17 vs 64.22 ± 7.60 kg), height (164.80 ± 7.77 vs 162.89 ± 6.53 cm), fentanyl dosage (8.95 ± 2.02 vs 10.21 ± 2.28 μg/kg), operation time (2.33 ± 0.54 vs 2.26 ± 0.33 h), CYP3A4 *1G, CYP3A5 *3 or COMT Val158Met between VAS < 4 and VAS ≥ 4, as shown in Table 2. There was no significant difference in the diameter of tumor (3.99 ± 1.96 vs 3.48 ± 2.12 cm),comorbidity, ASA(I vs II), and tumor location (right/left), as shown in S1.

Among 101 subjects, the number of VAS ≥ 4 and VAS < 4 was significantly different. There was significant difference in OPRM1 genotypes between the two groups. Patients carrying wild gene A had decreased fentanyl sensitivity and were more prone to VAS ≥ 4.

The impact of assessing PACU VAS

The feature selection factors with significant differences in univariate analysis were included in the regression analysis. Based on univariate analysis, multivariate logistic analysis was performed for each factor, including age, sex, weight, height, intraoperative fentanyl dosage, operation duration, OPRM1 A118G、CYP3A4 *1G、CYP3A5 *3 and COMT Val158Met polymorphisms, as shown in Table 3.

Table 3 Risk factors of VAS

Carrying wild gene A was associated with VAS ≥ 4, according to the OPRM1 A118G polymorphism, and was a risk factor for VAS ≥ 4. Further regression analysis showed that without adjusting of confounders, the VAS ≥ 4 in GA and AA-type subjects was 13.73 times higher than that of GG-type subjects. After fully adjusting the confounding factors that may affect PACU VAS, such as age, sex, weight, height, and operation duration, carrying gene A of OPRM1 is a risk factor in VAS ≥ 4. Subjects carrying gene A of OPRM1 were 15.55 times higher than GG-type subjects. After adjusting of age, sex, weight, height, operation duration, and the polymorphisms of CYP3A4*1G, CYP3A5*3, and COMT Val158Met, the probability of VAS ≥ 4 in carrying gene A of OPRM1 subjects was 18.94 times higher than that in GG type subjects, as shown in Table 4.

Table 4 Individual effect of OPRM1 A118G on VAS of PACU

Figure 2 is a diagram of the adjusted effect relationship, which clearly shows that after sequentially adjusting for age, sex, weight, height, intraoperative fentanyl dosage, operation duration and the polymorphisms of CYP3A4 *1G、CYP3A5 *3 and COMT Val158Met, the probability of PACU VAS ≥ 4 in patients carrying gene A of OPRM1 is significantly increased.

Fig. 2figure 2

Adjusted effect relationship diagram between OPRM1 A118G and PACU VAS≥4. Adjusted according to age, sex, weight, height, intraoperative fentanyl dosage, operation duration and the polymorphisms of CYP3A4 *1G、CYP3A5 *3 and COMT Val158Met polymorphisms, the risk of PACU VAS ≥ 4 in the subjects carrying gene A of OPRM1 A118G is significantly increased

Adjusted according to age, sex, weight, height, intraoperative fentanyl dosage, operation duration and the polymorphisms of CYP3A4 *1G, CYP3A5 *3 and COMT Val158Met polymorphisms, the risk of PACU VAS ≥ 4 in the subjects carrying gene A of OPRM1 A118G is significantly increased. In the GG group, the adjusted mean was 0.036,(95%CI: 0.002–0.366); in the GA + AA group, the adjusted mean was 0.468,(95%CI: 0.096–0.879).

Independent effect of OPRM1 A118G gene polymorphism on fentanyl dose in PACU

The polymorphism of OPRM1 A118G was associated with fentanyl dosage during PACU. Carrying A gene is a risk factor for decreased fentanyl sensitivity and increased fentanyl dosage during PACU. Further regression analysis showed that the probability of GA and AA-type subjects receiving high-dose fentanyl was 15.90 times higher than that of GG-type subjects; After adjusting for age, sex, weight, height, intraoperative fentanyl dosage and operation duration, the probability of GA and AA-type subjects was 12.81 times higher than that of GG-type; After fully adjusting for age, sex, weight, height, intraoperative fentanyl dosage, operation duration, and the polymorphisms of CYP3A4 *1G, CYP3A5 *3, COMT Val158Met, the probability of subjects carrying A gene was 14.23 folds higher than that of GG homozygous, as shown in Table 5.

Table 5 Independent effect of OPRM1 A118G polymorphism on fentanyl dose in PACU

The adjusted effect relationship diagram in Fig. 3 clearly shows that after adjusting for age, sex, weight, height, intraoperative fentanyl dosage, operation duration, and the polymorphisms of CYP3A4 *1G, CYP3A5 *3, and COMT Val158Met, the dose of fentanyl in patients carrying gene A of OPRM1 is significantly increased in PACU. In the GG group, the adjusted mean was 43.10 μg(95%CI: 33.82–52.37); in the GA + AA group, the adjusted mean was 59.01 μg(95%CI: 45.36–72.65).

Fig. 3figure 3

Adjusted effect relationship diagram between OPRM1 A118G and PACU fentanyl. Adjusted according to age, sex, weight, height, intraoperative fentanyl dosage, operation duration and the polymorphisms of CYP3A4 *1G、CYP3A5 *3 and COMT Val158Met polymorphisms

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