Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: A double-blind, randomised clinical trial.

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.

Preemptive Nalbuphine Attenuates Remifentanil-Induced Postoperative Hyperalgesia After Laparoscopic Cholecystectomy: A Prospective Randomized Double-Blind Clinical Trial.

BACKGROUND: Remifentanil-induced hyperalgesia (RIH) is a paradoxical phenomenon that may increase sensitivity to painful stimuli. Nalbuphine, which is both a µ-receptor antagonist and κ-receptor agonist, may affect RIH. The aim of this study was to evaluate the effects of nalbuphine on RIH during laparoscopic cholecystectomy. METHODS: A total of 96 patients were divided into the following four groups: 0.4 µg/kg/min of remifentanil with 0.2 mg/kg of nalbuphine (HRNA), 0.4 µg/kg/min of remifentanil with saline (HRSA), 0.1 µg/kg/min of remifentanil with 0.2 mg/kg of nalbuphine (LRNA), and 0.1 µg/kg/min of remifentanil with saline (LRSA). The pain thresholds of postoperative mechanical hyperalgesia were measured with von Frey filaments. Pain intensity and analgesic consumption were recorded up to 48 h after surgery. RESULTS: Pain thresholds on the inner forearm decreased in the HRSA group compared with the HRNA (P = 0.0167), LRNA (P = 0.0027), and LRSA (P = 0.0318) groups at 24 h after surgery. Pain thresholds on the peri-incisional area decreased in the HRSA group compared with HRNA, LRNA, and LRSA (all P < 0.0001) groups at 24 h after surgery. Patients in the HRNA group showed lower numeric rating scale scores at 1 h (P = 0.0159), 3 h (P = 0.0118), 6 h (P = 0.0213), and 12 h (P = 0.0118) than those in the HRSA group. Postoperative requirement for sufentanil was greater in the HRSA group than the HRNA group during the first 3 h (P = 0.0321) and second 3 h (P = 0.0040). Postoperative sufentanil consumption was also greater in the LRSA group than in the LRNA group during the first 3 h (P = 0.0321) and second 3 h (P = 0.0416). CONCLUSION: Preemptive nalbuphine can ameliorate postoperative hyperalgesia induced by high-dose remifentanil in patients undergoing laparoscopic cholecystectomy.

Pharmacokinetic study and effectiveness evaluation of slow-release PLGA-5-fluorouracil microsphere.

PURPOSE: The aim was to develop a slow-release poly-lactic-co-glycolic acid (PLGA)-5-fluorouracil microsphere, study the pharmacokinetic characteristics as well as to evaluate the effectiveness and safety of this preparation on colorectal tumor in vivo. METHODS: The PLGA-5-fluorouracil microsphere was prepared based on a spray-drying method, and the drug loading of 5-fluorouracil (the percentage of 5-fluorouracil content in the whole microsphere), in vitro 5-fluorouracil release profile and pharmacokinetic characteristics were carried out through high-performance liquid chromatography. The inhibiting effect on tumor growth and safety was examined using in vivo subcutaneously (s.c.) inoculated colorectal tumor models of nude mice. RESULTS: The size of the microsphere was less than 100 µm, drug loading was 20 % and drug release time lasted as long as 30 days. Slow-release PLGA-5-fluorouracil microsphere had longer half-life time (t (1/2)), larger apparent volume of distribution (V ( d )) and smaller area under the curve (AUC) compared with 5-fluorouracil. PLGA-5-fluorouracil microsphere significantly restrained tumor growth and this effect correlated with decreased expression of vascular endothelial growth factor in tumor cells. Body weight measurement and blood analysis did not suggest significant adverse effects on the mice during the study. CONCLUSIONS: The slow-release PLGA-5-fluorouracil microsphere developed here was suitable for regional use; it has pharmacokinetic advantages and appears safe and effective in controlling the tumor growth. This preparation shows promise in reducing local recurrence of colorectal cancer after resection, but needs further investigation.