Effects of surgery start time on postoperative cortisol, inflammatory cytokines, and postoperative hospital day in hip surgery: Randomized controlled trial

Abstract

Background: The aim of this study was to compare morning surgery (Group A), characterized by high cortisol levels, with afternoon surgery (Group B), characterized by low cortisol levels, with respect to cortisol, inflammatory cytokines (interleukin [IL]-6, IL-8), and postoperative hospital days (POHD) after hip surgery.

Methods: The study was conducted in a single center, prospective, randomized (1:1) parallel group trial. Patients undergoing total hip replacement or hemiarthroplasty were randomly divided into two groups according to the surgery start time: 8 AM (Group A) or 1-2 PM (Group B). Cortisol and cytokine levels were measured at 7:30 AM on the day of surgery, before induction of anesthesia, and at 6, 12, 24, and 48 hours (h) after surgery. Visual analogue scale (VAS) and POHD were used to evaluate the clinical effect of surgery start time. VAS was measured at 6, 12, 24, and 48 h postoperatively, and POHD was measured at discharge.

Results: In total, 44 patients completed the trial. The postoperative cortisol level was significantly different between the two groups. (24 h, P < .001; 48 h, P < .001). The percentage of patients whose level returned to the initial level was higher in Group B than in Group A (P < .001). Significant differences in IL-6 levels were observed between the two groups at 12, 24, and 48 h after surgery (P = .015; P = .005; P = .002), and in IL-8 levels at 12 and 24 h after surgery (P = .002, P < .001). There was no significant difference between the two groups in VAS and POHD. However, only three patients in Group A were inpatients for more than 3 weeks (P = .233).

Conclusions: Afternoon surgery allowed for more rapid recovery of cortisol to the baseline level than morning surgery, and IL-6 and IL-8 were lower at 1-2 days postoperatively. The results of this study suggest that afternoon surgery may be considered in patients with postoperative delayed wound healing or inflammation because of the difference in cortisol, IL-6 and 8 in according to surgery start time.

Clinical trial registration number: NCT03076827 (ClinicalTRrial.gov).

Figure 1

Flow chart. It shows Flow chart of participants in this randomised trial on the effects of surgery start time (and thus the circadian rhythm of cortisol) on postoperative interleukin-6, interleukin-8, and cortisol levels. Group A had a surgery start time of 8 am and Group B had a surgery start time of 1–2 pm.

Figure 2

Comparison of cortisol levels between the morning and afternoon-surgery groups. Cortisol levels changed over time (P < .001, repeated measure ANOVA) and the degree of change differed between the two groups (^$P < .001, repeated measures ANOVA). Post hoc test was corrected with Bonferroni's method (corrected probability of significance = .05/6 ≒ .008). There were differences between the two groups at 24 h (P < .001, t-test) and 48 h (P < .001, t-test) postoperatively. In 24 h after surgery, Group A (n = 22) was 119.2 μg/dL (SD = 31.3) and Group B (n = 22) was 75.8 μg/dL (SD = 35.1). The difference was 43.4 μg/dL (95% CI, 23.1–63.4, ^∗P < .001). In 48 h after surgery, Group A was 91.7 μg/dL (SD = 19.4) and Group B was 39.7 μg/dL (SD = 15.7). The difference was 52.1 μg/dL (95% CI, 41.3–62.8, ^∗∗P < .001). ANOVA = analysis of variance, BI = before anesthesia induction, CI = confidence interval, SD = standard deviation, 6–48 h, 6–48 h after surgery. Group A had a surgery start time of 8 am and Group B had a surgery start time of 1–2 pm.

Figure 3

The percentage of patients returning to the initial level of cortisol. In Group A (n = 22), 4.5% (^∗, n = 1) of the patients returned to the initial level at 24 h postoperatively and 40.9% (^∗∗, n = 9 of the patients returned to the initial level at 48 h postoperatively. In Group B (n = 22), 59.1% (+, n = 13) of the patients returned to the initial level at 24 h postoperatively and 86.4% (++, n = 19 of the patients returned to the initial level at 48 h postoperatively (P < .001, Log-rank test). All percentages were analyzed by Kaplan–Meier curve analysis. Group A, percentage of return to initial values in the morning surgery group; Group B, percentage of return to initial values in the afternoon surgery group.

Figure 4

Comparison of interleukin-6 (IL-6) levels between the morning and afternoon-surgery groups. Group A (n = 22) and Group B (n = 22) were compared by the Mann–Whitney U test (12 h, ^∗P = .015; 24 h, ^∗∗P = .005; 48 h, ^∗∗∗P = .002). At 12 h after surgery, the median IL-6 level of Group A was 363.4 pg/dL (interquartile range [IQR]: 303.0–485.2 pg/dL) and that of Group B was 270.9 pg/dL (IQR: 252.2–336.7 pg/dL). At 24 h after surgery, the median IL-6 level of Group A was 359.9 pg/dL (IQR: 320.3–749.6 pg/dL) and that of Group B was 232.8 pg/dL (IQR: 171.1–444.4 pg/dL). At 48 h after surgery, the median IL-6 level of Group A was 207.4 pg/dL (IQR: 169.9–271.3 pg/dL) and that of Group B was 123.2 pg/dL (IQR: 73.5–211.6 pg/dL). BI = before anesthetic induction, GA = Group A (morning surgery group), GB = Group B (afternoon surgery group), h = hours, IL = interleukin, IQR = interquartile range.

Figure 5

Comparison of Interleukin-8 (IL-8) levels between the morning and afternoon-surgery groups. Group A (n = 22) and Group B (n = 22) were compared by the Mann–Whitney U test (12 h, ^∗P = .002; 24 h, ^∗∗P < .001). At 12 h after surgery, the median IL-8 level of Group A was 16.3 pg/dL (interquartile range [IQR]: 11.4–23.8 pg/dL) and that of Group B was 11.9 pg/dL (IQR: 9.5–15.1 pg/dL). At 24 h after surgery, the median IL-8 level of Group A was 17.1 pg/dL (IQR: 10.8–21.9 pg/dL) and that of Group B was 10.1 pg/dL (IQR: 8.1–14.3 pg/dL). BI = before anesthetic induction, GA = Group A (morning surgery group), GB = Group B (afternoon surgery group), h = hours, IL = interleukin, IQR = interquartile range.