Jun Hu1, Mudan Zhu, Zongbin Gao, Shihao Zhao, Xiaomei Feng, Jinbao Chen, Ye Zhang, Mervyn Maze. 1. From the Department of Anaesthesiology, The Second Hospital of Anhui Medical University, and Key Laboratory of Anaesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei (JH, YZ), Department of Anaesthesiology, Tongling People's Hospital of Anhui Medical University, Tongling, Anhui, China (MZ, ZG, SZ, JC), Department of Anaesthesiology, University of Utah, Salt Lake City, Utah (XF) and Department of Anaesthesia and Perioperative Care and Centre for Cerebrovascular Research, University of California, San Francisco, San Francisco, California, USA (XF, MM).
Abstract
BACKGROUND: Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce. OBJECTIVE: To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Single-centre, tertiary care hospital, November 2016 to September 2018. PATIENTS: Eligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90). INTERVENTIONS: Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 μg kg-1), over 15 min, followed by a continuous infusion at a rate of 0.1 μg kg-1 h-1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol. OUTCOME MEASURES: The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile. RESULTS: All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P < 0.0001). CONCLUSION: Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881.
BACKGROUND: Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce. OBJECTIVE: To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Single-centre, tertiary care hospital, November 2016 to September 2018. PATIENTS: Eligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90). INTERVENTIONS: Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 μg kg-1), over 15 min, followed by a continuous infusion at a rate of 0.1 μg kg-1 h-1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol. OUTCOME MEASURES: The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile. RESULTS: All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P < 0.0001). CONCLUSION: Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881.