Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery

A Randomized Clinical Trial

Babar A. Khan, MD, MS; Anthony J. Perkins, MS; Noll L. Campbell, PharmD; Sujuan Gao, PhD; Sikandar H. Khan, DO; Sophia Wang, MD; Mikita Fuchita, MD; Daniel J. Weber, MD; Ben L. Zarzaur, MD, MPH; Malaz A. Boustani, MD, MPH; Kenneth Kesler, MD

Disclosures

J Am Geriatr Soc. 2018;66(12):2289-2297. 

In This Article

Results

Of 269 individuals undergoing major thoracic surgery screened from October 2013 to June 2015, 135 were enrolled in the trial. Sixty-eight were randomly assigned to haloperidol and 67 to placebo (Figure 1). Individuals undergoing esophagectomy constituted the largest group (n = 84), with 42 assigned to haloperidol and 42 to placebo (Supplementary Figure S1). There were no differences in baseline participant characteristics between the haloperidol and placebo groups (Table 1) or in the intraoperative and postoperative factors except that more individuals undergoing esophagectomy in the placebo group received propofol (Table 2, Supplementary Table S2 and Supplementary Table S3).

Figure 1.

Flow of participants through study. [Color figure can be viewed at wileyonlinelibrary.com]

Supplementary Figure S1.

Flow of Esophagectomy Participants Through Study

Primary Outcomes

There was no difference in delirium incidence between the haloperidol (22.1%, 15/68) and placebo (28.4%, 19/67) groups (p = .43) (Table 3).

Secondary Outcomes

There were no differences in time to delirium (p = .43) (Figure 2) or median number of delirium days in participants with delirium (haloperidol: median 1 day, interquartile range (IQR) 1–2 days; placebo: 1 day, IQR 1–2 days; p = .71). There was a similar magnitude of reduction in delirium severity scores over time in both groups (Supplementary Figure S2).

Figure 2.

Time to delirium in all participants undergoing thoracic surgery and the subgroup undergoing esophagectomy.

Supplementary Figure S2.

Mean DRS-R-98 Scores over Time by Intervention Group All Patients (Mixed Effect P-value=0.551)

There were no differences in ICU (haloperidol: median 2.2 days, IQR 1–3.3 days; placebo: median 2.3 days, IQR 1–4 days; p = .29) or hospital (haloperidol: median 10 days, IQR 8–11.5 days; placebo: median 10 days, IQR 8–12 days; p = .40) length of stay (Table 3, Supplementary Figure S3). When the analysis was limited to participants with delirium, the haloperidol group had a shorter hospital stay (median 10 days, IQR 8–14 days vs median 11 days, IQR 11–16 days; p = .03) (Supplementary Figure S4).

Supplementary Figure S3.

Time to Discharge All Patients (Wilcoxon P-value=0.405)

Supplementary Figure S4.

Time to Discharge for Delirium Patients Only (Wilcoxon P-value=0.033)

A small subset of participants underwent pre- and postoperative RBANS cognitive assessments (haloperidol, n = 17; placebo, n = 16). Postoperatively, the RBANS percentile change scores improved in the placebo group (haloperidol: median 6, IQR 0–23; placebo: median −9.25, IQR −17.5–0; p = .008).

Esophagectomy Subgroup

Primary Outcome. Delirium incidence was lower in the haloperidol (23.8%, 10/42) than the placebo (40.5%, 17/42) group, but the difference was not statistically significant (p = .16) (Table 3).

Secondary Outcomes. There was no difference in time to delirium between the groups (p = .14) (Figure 2) and no difference in number of days with delirium in participants with delirium (haloperidol: median 1 day, IQR 1–2 days, placebo median 1 day, IQR 1-2 days; p = .70). Delirium severity reduction was similar in both groups (Supplementary Figure S5).

Supplementary Figure S5.

Mean DRS-R-98 Scores over Time by Intervention Group All Esophagectomy Patients (Mixed Effect P-value=0.223)

ICU stay was significantly shorter in the haloperidol (median 2.8 days, IQR 1.1–3.8 days) than the placebo (median 3.1 days, IQR 2.1–5.1 days) group (p = .03) (Table 3). No differences were found in hospital length of stay (haloperidol: median 11 days, IQR 10–12 days; placebo: median 11 days, IQR 10-15 days; p = .25) (Table 3). When the analysis was limited to participants with delirium, the haloperidol group had a trend toward significantly fewer hospital days (haloperidol: median 11 days, IQR 10–14 days; placebo: median 12 days, IQR 11–16 days; p = .06] (Supplementary Figure S6).

Supplementary Figure S6.

Time to Discharge for Delirium Patients Only in the Esophagectomy group (Willcoxon P-value=0.065)

A small subset of participants underwent pre- and postoperative RBANS cognitive assessments (haloperidol, n = 9; placebo, n = 9). Postoperatively, RBANS percentile change scores improved in the placebo group (haloperidol: median 13, IQR 0–24; placebo: median −2, IQR −18–0; p = .05).

Esophagectomy Versus Other Thoracic Surgeries

Individuals undergoing esophagectomy were slightly older (median 62, IQR 53–69 vs median 61 IQR 45–67; p = .16), were more likely to undergo preoperative chemotherapy (75.3% vs 30.0%, p <.001), had greater severity of illness (APACHE 11 score: median 17, IQR 13.5–24.5 vs median 14, IQR 11–20; p = .008), had longer surgeries (median 4.9 hours, IQR 4.1–5.4 hours vs median 2.1 hours, IQR 1.4–3 hours; p <.001), and received a higher intraoperative volume (median 3,000, IQR 2,500–3,775 mL vs median 1,400, IQR 1,000–2,000 mL; p <.001) and more benzodiazepines (diazepam equivalents: median 20 mg, IQR 11.3–62.5 mg vs median 12.5, IQR 5–22.5 mg; p = .003) than those undergoing other thoracic surgeries.

Individuals undergoing esophagectomy had higher delirium incidence (32.1%, 27/84), than those undergoing other thoracic surgeries (13.7%, 7/51) (p = .02), longer duration of mechanical ventilation (median 1 day, IQR 0.4–1.2 days vs median 0.2 days, IQR 0.1–0.8 days; p = .01), and longer ICU (median 2.9 days, IQR 2-4 days vs median 1.1 days, IQR 0–2.2 days; p < .001) and hospital (median 11 days, IQR 10–13 days vs median 7 days, IQR 5–8 days; p < .001) stays and were less likely to be discharged home (84.5% vs 96.1%, p = .048).

Safety

There were no differences in adverse events between the groups (Supplementary Table S4, Supplementary Table S5 and Supplementary Table S6).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....