This randomized, double-blind, placebo-controlled, single-center clinical research was approved by Ethics Committee of Affiliated Hospital of Nantong University and all the participants have signed informed consents. This trial was performed between April 2019 to September 2019 and adheres to CONSORT guidelines. The ethical processes of the research conformed to the “Declaration of Helsinki”. The study was registered in chictr.org.cn on 11 March 2019 (registration number: ChiCTR1900021810), and the full trial protocol can be accessed at chictr.org.cn.
Sixty-one patients undergoing selective gynecological laparoscopy surgery with general anesthesia were enrolled in the study. Inclusion criteria were patients aged from 18-60 years old, American Society of Anesthesiology (ASA) status I-II. Exclusion criteria were pregnancy, malignant tumor, arrhythmia, hypertension, any kinds of medication, allergic to DEX or any drugs used during this study and other situations unsuitable for the research. Exclusion criteria during surgery were operation time less than 40min or more than 3 hours, changes of operative procedure and blood loss more than 400ml.
Study groups and randomization
Patients were randomly allocated to DEX group (group D) or normal saline group (group N) in a
1:1 ratio by random figure table provided by an independent statistician. The random numbers were placed in the envelopes and sealed, which were opened right before anesthesia induction. Study drugs were prepared by a nurse who was independent of data collection. The anesthesiologists and patients were blinded to treatment group allocation. DEX was infused at 0.5ug/kg/h in group D since induction of anesthesia and was stopped before skin suture. Patients in group N received normal saline infusion at the same rate.
All patients were administered with a unified anesthetic induction: midazolam 2mg, propofol bolus of 1.5mg/kg, sufentanil bolus of 0.5ug/kg and cisatracurium 0.2mg/kg. Anesthesia was maintained with sevoflurane, propofol, remifentanil and cisatracurium. Infusion rate of propofol and remifentanil was adjusted according to bispectral index (BIS). Fluctuation range of blood pressure(BP) and heart rate(HR) was between ±20% of the basic value. Hypotension (systolic blood pressure decreased to 80% of the basic value or was lower than 90mmHg) was treated with ephedrine and bradycardia (HR decreased to 80% of the basic value or was lower than 50bpm) was treated with atropine. The BIS values was controlled between 40 and 60 and the end-tidal CO2 pressure was maintained at 35-45mmHg.Forced-air warming blankets were used during anesthesia. Azazetron was routinely used for all patients before extubation. Patients were given a patient-controlled intravenous analgesia (PCIA) pump with the formulation of sufentanil and azazetron once all the anesthetics were stopped.
BP and HR were recorded before induction, at extubation (T0), 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),7(T7),8(T8),12(T9),24(T10), and 48(T11) hours after operation. NRS scores were recorded 1(T1), 2(T2), 3(T3) ,4(T4), ,8(T8),12(T9),24(T10) hours after operation. OAA/S scores were recorded at 10-min intervals for the first hour after extubation. Time to extubation (TE) was defined as the time from the cessation of all the anesthetics to extubation. Adverse events include hypertension, hypotension, tachycardia, bradycardia, respiratory depression, postoperative nausea and vomiting(PONV), shiver and pruritus.
Sample size was calculated according to preliminary data based on HR at the first hour after surgery, α = 0.05 , β = 0.20 and missing rate of 0.1. Minimum sample size was estimated 15 for each group, and we expanded the sample size to 30 for each group. Continuous data are presented as medians with 25–75% interquartile ranges. Continuous data were compared using Student’s t-test. For categorical data, Pearson’s chi-square test with Fisher’s exact test was used. A two-sided P value less than 0.05 was considered statistically significant.