The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery

Abstract

Background: Surgery induces a variety of metabolic, endocrine, and immune changes collectively known as the "stress response," which may often lead to prolonged postoperative convalescence. Anesthetic management may modulate this physiological response, thus affecting the postoperative course. We hypothesized that the intraoperative administration of dexmedetomidine (DEX), a sympatholytic agent, would reduce the stress response and improve the quality of recovery in patients undergoing major surgery.

Methods: We conducted a prospective randomized double-blinded study of 54 patients undergoing multilevel spinal fusion. Anesthesia was maintained using either propofol/fentanyl/dexmedetomidine (PFD) or propofol/fentanyl/placebo-saline (PFS). The quality of recovery (a primary endpoint) was assessed using a 40-item quality of recovery questionnaire and a 9-question Fatigue Severity Scores. The tests were carried out preoperatively on postoperative days (POD) 1, 2, 3, and 30. Blood samples were collected at baseline, in the postanesthesia care unit, and at POD 1 and were analyzed for levels of cortisol, C-reactive proteins (CRP), and cytokines interleukin (IL)-1α, IL-1β, IL-1ra, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α. Data were analyzed using SPSS software (version 18) using a multivariate and mixed model approach to test for the effect of surgery and drug group. Pairwise comparisons were assessed by means of the t test or rank tests after correcting for multiple comparisons.

Results: The global 40-item quality of recovery questionnaire scores showed a significant effect of time (F(4,114)=22.63, P<0.001) and drug (F(1,51)=4.368, P=0.042), with average scores decreasing to lower values on POD 1 (163.63±2.47) and POD 2 (170.94±2.38) compared with baseline (180.56±1.588, mean±SE, 2-tailed t tests, P<0.001). By POD 3, scores were significantly lower (-13.74 point difference, P=0.005) in the PFS group (169.3±3.87) than in the PFD group (183.04±2.76). All patients reported significantly higher levels of fatigue postoperatively, but intergroup difference in Fatigue Severity Scores was detected on POD 3 only, with scores in the PFS group higher than in the PFD group (50.0±4.0 vs. 36.3±4.9, P=0.035). In both groups, plasma cortisol levels were highest in the postanesthesia care unit, whereas CRP levels were elevated on POD 1. DEX significantly reduced the levels of cortisol, but not those of CRP. Levels of cytokines IL-6, IL-8, and IL-10 were significantly higher immediately after surgery and at POD 1. Plasma levels of other cytokines were not affected by surgery. DEX delayed postoperative rise in IL-10 but not in IL-6 or IL-8.

Conclusions: DEX infusion during multilevel spinal fusions moderately improved the quality of recovery and possibly reduced fatigue in the early postoperative period. Moreover, it reduced plasma levels of cortisol and IL-10 in comparison with the control group. Our sample size was not sufficient to detect differences either in the incidence of complications or in clinically relevant outcomes.

Figure 1

Changes in global QoR40 Scores over time. Scores showed a significant effect of time, (p < 0.001), and drug (p = 0.042). Scores were significantly lower in the PFS group than in PFD group on POD 3 (p=0.005).

Figure 2

Changes in Fatigue Severity Scores over time. Score showed a significant effect of time (surgery) (p<0.001). Patients in the PFD group had numerically lower scores at every post surgical evaluation and were significantly lower on POD 3 by pairwise comparison PFD-PFS on POD2=−13.7, p=0.035).

Figure 3

Figures 3a and 3b. Plasma concentrations of cortisol and CRP preoperatively (BSL), immediately after surgery (PACU) and on postoperative day 1 (POD1). Cortisol levels were significantly higher in the PACU for the PFS group than in the PFD cohort (p=0.031). At POD1 mean CRP values were significantly greater than at the baseline (p=0.026), but without a significant difference between groups.

Figure 3

Figures 3a and 3b. Plasma concentrations of cortisol and CRP preoperatively (BSL), immediately after surgery (PACU) and on postoperative day 1 (POD1). Cortisol levels were significantly higher in the PACU for the PFS group than in the PFD cohort (p=0.031). At POD1 mean CRP values were significantly greater than at the baseline (p=0.026), but without a significant difference between groups.