The Effect of Dexmedetomidine on Intraoperative Blood Glucose Homeostasis

Secondary Analysis of a Randomized Controlled Trial

Chun-Jing Li; Bo-Jie Wang; Dong-Liang Mu; Dong-Xin Wang


BMC Anesthesiol. 2021;21(139) 

In This Article

Materials and Methods

This was secondary analysis of a randomized controlled trial which was approved by Clinical Research Ethics Committee of Peking University First Hospital (2015–987) and registered with Chinese Clinical Trial Registry on December 1, 2015 (, registration number ChiCTR-IPR-15007654).[23] Written informed consents were obtained from all patients or their legal representatives in original trial. Present study was carried out in accordance with CONSORT 2010 guidelines and Declaration of Helsinki.

Participants and Baseline Data Collection

Elderly (age ≥ 60 years) patients who underwent selective major non-cardiac surgery with expected duration ≥ 2 h under general anaesthesia were included. Patients who met any of the following criteria were excluded: (1) history of psychiatric disease, i.e., schizophrenia, epilepsy or Parkinson's disease; (2) visual, hearing, language or other barrier that impeded communication and preoperative delirium assessment; (3) history of traumatic brain injury or neurosurgery; (4) severe bradycardia (heart rate less than 40 beats per minute), sick sinus syndrome, or atrioventricular block of degree 2 or above without pacemaker; (5) severe hepatic dysfunction (Child–Pugh grade C); (6) renal failure (requirement of renal replacement therapy); (7) neurosurgery.

Randomization and Allocation

In this two-armed parallel study, patients were randomized to dexmedetomidine group and control group in a ratio of 1:1. Random numbers were generated by using SAS statistical package version 9.3 (SAS Institute, Cary, NC, USA) with a block size of 4.


Opaque envelopes were used to seal random number and kept by a study coordinator who was not involved in patient recruitment, data collection, perioperative care and postoperative follow-up.

Study drugs were prepared by the coordinator according to the randomization results. The study drugs, either 200 μg (2 ml) dexmedetomidine or 2 ml normal saline, were diluted into 50 ml with normal saline (with a final concentration of 4 μg/ml for dexmedetomidine). All study drugs were colourless solution provided in syringes of the same size and brand.

Blinding method of randomization and study drug were masked from patients, investigators who performed data collection and postoperative follow-up, and related healthcare providers. Blinding was maintained throughout the study period.

To ensure patients' safety, the group allocation could be unmasked in the occurrence of severe adverse events or any unexpected deterioration in the patient's clinical status. These situations were documented in the case report forms.

Intervention, Anaesthesia and Perioperative Care

For patients in dexmedetomidine group, a loading dose of dexmedetomidine (0.15 ml/kg, i.e., 0.6 μg/kg) was administered during a 10-min period before anaesthesia induction and then was followed by a continuous infusion at a rate of 0.125 ml/kg/hr (i.e., 0.5 μg/kg/hr) till 1 h before the end of surgery. For patients in control group, volume-matched normal saline was administered at the same rate for the same duration.

To ensure patient's safety, study drug infusion could be slowed down or stopped by the attending anaesthesiologists in the following conditions: (1) severe bradycardia or hypotension which did not improve after routine treatment; (2) new onset atrioventricular block which did not improve after routine treatment; or (3) other conditions that anaesthesiologists considered necessary. Reasons that led to any protocol deviations were recorded. These patients were included in the intention-to-treat analysis but excluded from the per-protocol analysis.

Anesthesia induction and maintenance were administrated with propofol and sufentanil as well as inhalation of a 1:1 nitrous oxide-oxygen mixture. The aim of anesthesia depth was to maintain Bispectral index (BIS) value between 40 and 60. Non-depolarizing neuromuscular blocking drugs (i.e., rocuronium) were administered for muscle relaxation. Fluid infusion and blood transfusion were performed according to routine practice. Blood pressure was maintained within 20% from baseline and nasopharyngeal temperature between 36.0 and 37.0 °C.

All patients were transferred to the post-anaesthesia care unit (PACU) or the intensive care unit (ICU) before being sent back to general wards. Patient-controlled intravenous analgesia (PCIA) was provided for postoperative analgesia.

Outcome Assessment

Primary Outcome. Primary outcome was the incidence of intraoperative hyperglycaemia. In consistence with consensuses, hyperglycaemia was defined as serum blood glucose higher than 10 mmol/L at any time during surgery.[24,25]

Blood glucose values were read from arterial blood gas analyser (GEM® Premier 3000, Instrumentation Laboratory, MA, USA). Blood samples were obtained from intra-arterial lines before beginning of surgery and then at 1-h interval till the end of surgery. All patients received at least two arterial blood gas testes during surgery.

Secondary Outcome. Secondary endpoints included glycemic variation and risk factors of intraoperative hyperglycemia. Glycemic variation was defined as the difference between the highest and lowest perioperative glucose levels during surgery.[26]

Baseline and intraoperative variables were analyzed to identify risk factors of hyperglycemia by univariate and multivariable logistic regression analysis.

Statistical Analysis

Sample Size Calculation. Sample size calculation in previous study was based on the hypothesis that intraoperative dexmedetomidine could decrease the incidence of postoperative delirium (309 patients in dexmedetomidine group and 310 patients in control group).[23] As a secondary analysis, we planned to investigate the effect of dexmedetomidine on intraoperative hyperglycemia. Thus, we excluded patients without record of intraoperative blood glucose record. We finally enrolled 303 patients in dexmedetomidine group and 306 patients in control group.

Outcome Analysis. The normality of continuous data was tested in prior. Continuous data with normal distribution were compared with the independent sample T-test. Continuous data with non-normal distribution were compared with the independent sample Mann–Whitney U test. Categorical data were compared with the Chi-squared test.

For primary outcome, the incidence of intraoperative hyperglycemia was presented as number (percentage). Estimated effect size was reported in the form of relative risk (RR) with 95% confidence interval (CI) both in intention-to-treat analysis and per protocol analysis. Subgroup analyses were also tested based on age, sex, history of diabetics, site of surgery and type of surgery.

The incidence of glycemic variation was presented in number (percentage) and analysed by Chi-squared test. Univariate analysis was firstly used to analyse the underlying relationship between baseline and intra-operative variables and hyperglycemia. Variables with P < 0.1 were entered multivariate analysis to identify independent risk factors of hyperglycemia. Intervention with dexmedetomidine was compulsorily analysed in univariate and multivariable analysis.

Statistical analyses were done with SPSS 14.0 (SPSS, Inc., Chicago, IL) and SAS 9.3 (SAS Institute, Cary, NC, USA). All tests were two tailed and P value less than 0.05 was considered as statistically significant.