Analgesic therapy improves arterial endothelial function following non-cardiovascular surgery: A randomized, placebo-controlled trial

Abstract

Pain subsequent to non-cardiac surgery may affect the endothelial function, which in turn contributes to myocardial injury (MI). The present study examined whether effective pain control is able to improve the postoperative endothelial function. Patients (n=160) undergoing laparoscopic cholecystectomy were randomly assigned into two groups, treated with tramadol analgesic or saline (placebo) following surgery. On preoperative day 1 (baseline) and postoperatively at 2 h, 1 day and 5 days, pain was assessed on a visual analogue scale (VAS), and B-mode ultrasound was used to measure brachial endothelium-dependent flow-mediated dilation (FMD) and nitroglycerin-induced dilation. At 2 h postoperatively, the FMD in the two groups was significantly lower compared with that at the other three time points (P≤0.005), while VAS was significantly higher (P<0.05). Patients in the tramadol group presented significantly reduced VAS values in comparison with those in the placebo group at 2 h and 1 day postoperatively (P=0.013 and 0.031, respectively), as well as significantly higher FMD at 2 h (6.7±1.5 vs. 6.0±1.7%; P=0.001) and 1 day postoperatively (7.3±1.3 vs. 6.9±1.4%; P=0.03). A VAS score of <5 was independently associated with postoperative FMD of ≥7 (odds ratio, 2.5; 95% confidence interval, 1.0-6.0; P=0.047). Backward multivariate linear regression also demonstrated that FMD was independently correlated with age and VAS score (B=-1.403, P=0.011; B=-0.579, P=0.003). The response to nitroglycerin-induced dilation remained stable in all patients at baseline and at all postoperative time points. In conclusion, analgesic treatment may improve the arterial endothelial function following non-cardiac surgery, which may help prevent postoperative MI.

Keywords: analgesic therapy; endothelial dysfunction; laparoscopic cholecystectomy; myocardial injury; postoperative pain.

Figure 1.

CONSORT flow diagram demonstrating the division of the study participants through each stage of the trial. Two participants in the placebo group were excluded as they had to undergo open cholecystectomy due to dense inflammatory adhesions.

Figure 2.

Comparison of brachial FMD and VAS pain score between patients in the tramadol or placebo group at the baseline and three postoperative time points. (A) Comparison of FMD. ^§P=0.001 and *P=0.015 vs. placebo group. (B) Alterations in the brachial FMD at different time points in the two groups. (C) Comparison of VAS scores in the groups. *P<0.05 vs. placebo group. FMD, flow-mediated dilation; VAS, visual analogue scale.