Efficacy of Intravenous Midazolam-Ketamine Combination Versus Placebo for Prevention of Post-Spinal Shivering in Elective Cesarean Section

NCT07855523 | Not Yet Recruiting Phase 4

• 1 other identifier: Midazolam-Ketamine: Shivering
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

Spinal anesthesia is the preferred anesthetic method for elective cesarean deliveries, but it frequently causes post-spinal shivering. Shivering causes marked maternal discomfort, interferes with clinical monitoring, and increases oxygen consumption and metabolic workload. This study aims to assess whether a prophylactic intravenous combination of low-dose midazolam and low-dose ketamine reduces the occurrence and severity of shivering compared with a placebo in women undergoing elective cesarean delivery under spinal anesthesia. A total of 120 parturients will be randomly assigned into two equal groups:

• Combination Group: Receives intravenous midazolam (0.0375 mg/kg) combined with ketamine (0.25 mg/kg) diluted in 20 mL of 0.9% normal saline.
• Control Group: Receives 20 mL of 0.9% normal saline intravenously as a placebo. In both groups, the intravenous infusion is administered over 10 minutes immediately following delivery of the infant and clamping of the umbilical cord, ensuring no transplacental transfer of the study medications to the newborn. The primary objective is to evaluate the proportion of patients who develop shivering during the first 60 minutes after arrival in the post-anesthesia care unit (PACU). Secondary objectives include shivering severity, the requirement for rescue anti-shivering medication, intraoperative and postoperative sedation levels, hemodynamic stability, body temperature course, potential medication side effects, and maternal satisfaction.

Conditions

Shivering; Post-Spinal Shivering; Hypothermia; Cesarean Section

Keywords

Midazolam; Ketamine; Spinal Anesthesia; Cesarean Delivery; Postanesthetic Shivering; Crossley and Mahajan Scale; Ramsay Sedation Scale

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Post-Spinal Shivering

  Percentage of participants who develop shivering, defined as Grade 2 or higher (visible muscle activity) on the Crossley and Mahajan Shivering Scale.

  Up to 60 minutes after arrival in the post-anesthesia care unit (PACU)

Study Arms (2)

Midazolam-Ketamine Combination Group

EXPERIMENTAL

Patients receive an intravenous infusion of midazolam 0.0375 mg/kg (37.5 µg/kg) combined with ketamine 0.25 mg/kg, diluted in 0.9% sodium chloride to a total volume of 20 mL, administered over 10 minutes immediately after fetal delivery and umbilical cord clamping.

Drug: Midazolam and Ketamine

Placebo Control Group

PLACEBO COMPARATOR

Patients receive 20 mL of 0.9% sodium chloride intravenously over 10 minutes, administered immediately after fetal delivery and umbilical cord clamping.

Drug: 0.9% Sodium Chloride

Interventions

Midazolam and Ketamine DRUG

Patients receive an intravenous infusion containing a combination of midazolam 0.0375 mg/kg (37.5 µg/kg) and ketamine 0.25 mg/kg diluted in 0.9% sodium chloride to a total volume of 20 mL. The infusion is administered over 10 minutes immediately after delivery of the infant and clamping of the umbilical cord.

Midazolam-Ketamine Combination Group

0.9% Sodium Chloride DRUG

Patients receive 20 mL of 0.9% sodium chloride administered intravenously over 10 minutes immediately after delivery of the infant and clamping of the umbilical cord.

Placebo Control Group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women aged 18 to 40 years old.
• American Society of Anesthesiologists (ASA) physical status I or II.
• Singleton pregnancy.
• Term pregnancy (37 to 41 weeks of gestation).
• Scheduled for elective cesarean section under spinal anesthesia.

You may not qualify if:

• Patient refusal.
• Body mass index (BMI) ≥ 40 kg/m².
• Contraindications to spinal anesthesia (e.g., coagulopathy, local infection at the puncture site).
• Known hypersensitivity or allergy to midazolam or ketamine.
• Pre-existing hypertension, pre-eclampsia, or cardiovascular disease.
• Severe cardiovascular, renal, or hepatic dysfunction.
• Neurological or psychiatric disorders (including epilepsy or history of psychosis).
• Baseline (preoperative) body temperature \< 36°C or \> 37.5°C.
• Chronic use of sedatives, opioids, or medications affecting thermoregulation.

Sponsors & Collaborators

• Assiut University: lead

MeSH Terms

Conditions

Hypothermia

Interventions

Midazolam; Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident

Study Record Dates

• First Submitted: September 28, 2026
• First Posted: October 2, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 2, 2026

Record last verified: 2026-09