2.1

Participants

This study is a randomized, double-blind clinical trial, with two intervention groups and a parallel design which is registered in Iranian Registry of Clinical Trials (IRCT20160825029520N2). The trial was conducted and reported following the CONSORT (Consolidated Standards of Reporting Trials) guidelines to ensure transparency and accuracy in reporting.

The inclusion criteria for this study were as follows: no history of psychiatric illness, no use of alpha-receptor antagonist drugs, no history of allergy to the studied drugs, age between 18 and 45 years, being classified as ASA II by the American Society of Anesthesiology, and undergoing elective surgery. Initially, 96 pregnant women referred to Neyshabur Hakim Hospital for cesarean deliverys met these criteria. However, six patients were excluded due to reasons such as failure of spinal anesthesia, unwillingness to continue the intervention, the need for misoprostol, or the requirement for additional anesthesia following the spinal procedure. Consequently, 90 participants were ultimately included in the study and were randomly assigned to three groups. The study was approved by the Ethics Committee of Neyshabur University of Medical Sciences (IR.NUMS.REC.1397.008), and informed consent was obtained from all participants.

2.2

Procedure

After final IRCT registration, recruitment commenced. The participants were randomly allocated to three groups: dexmedetomidine (group D), magnesium sulfate (group M), and control (group C). In order to ensure randomization and a balanced sample size in each group, the block randomization method was used with a block size of six. Using the results obtained from the studies of Moeen and Faiz, ^, and considering the significance level of 0.05 and the power of 0.95, the number of samples for each group was estimated at 30. A demographic questionnaire was completed for each participant by the researcher. In the operating room, venous puncture was performed with an 18-gauge cannula. Before spinal, all participants received preload (8cc/kg) and maintenance (10cc/kg/hr) normal saline with the same temperature as the operating room. A standard monitoring including monitoring of noninvasive blood pressure, pulse oximeter, heart rate, and electrocardiograph was applied for each patient. Spinal anesthesia was performed at the L3-L4 or L4-L5 subarachnoid space with a 22-gauge Quincke needle while the patient was sitting. In the dexmedetomidine group (group D), 5 micrograms of dexmedetomidine (Precedex; Hospira, LakeForest, IL, USA) plus 12.5 mg bupivacaine 0.5 % (MYLAN, Saint-priest, France), in the magnesium sulfate group (M group) 25 mg of magnesium sulfate (Samen Daru, Iran) plus 12.5 mg of bupivacaine 0.5 % (MYLAN, Saint-priest, France), and in the control group (group C) 12.5 mg of bupivacaine plus 1 mL of 0.9 % normal saline was injected. After spinal anesthesia by an anesthesiologist (not involved in data collection), the patients were placed in supine position and under 6 lit/min oxygen therapy through a face mask. The temperature of the operating and recovery room was maintained between 24 and 26 °c. Physiological symptoms were recorded in the checklist by a research associate (blinded to the treatment group). Shivering intensity was evaluated by Tsai and Chu method (0= no shivering, 4= most shivering). Physiological symptoms, the shivering intensity were recorded every 5 min. And we reported before and 20, 45, 55, and 65 min after spinal anesthesia. Central temperature was measured through the tympanic membrane using an electronic tympanic thermometer device. Also, physiological symptoms including non-invasive blood pressure (SBP, [CR]

1 Systolic blood pressure

2 Diastolic blood pressure

3 Saturation of Peripheral Oxygen

2.3

Statistical analysis

Statistical analysis was conducted independently for three groups: placebo, dexmedetomidine and magnesium sulfate group. The continuous variables were expressed as median (interquartile range [IQR]) due to the asymmetric nature and were summarized by number and percentages for qualitative variables. Differences in characteristics among three groups were assessed using Chi-squared and Fisher’s exact test for categorical variables. For quantitative variables, analysis of variance (ANOVA (or alternative non-parametric tests such as Kruskal-Wallis were employed. The physiological symptoms of the patients were documented at specific time intervals and then compared among the groups. The repeated measures proportional odds logistic regression was fitted using the generalized estimating equations (GEE) method to assess the severity of shiver. The shivering level before cesarean delivery was adjusted in the model. For a more detailed analysis of the effect of the groups under study, two separate models were fitted. In the first model, the effect of both time and groups on severity of shivering was investigated. In the second model, a logistic regression was fitted, taking in account that the patient had experienced shivering at least once during one of the measurement intervals. Pairwise comparisons were performed for each model using with Tukey’s test. The statistical analysis was performed using statistical software R version 4.3.1 for Windows. A two-sided P-value of <0.05 was considered statistically significant.