Evaluation of the Analgesic Effect of Midazolam and Ketamine as an Additive to Intrathecal Bupivacaine in Patients Undergoing Cesarean Section

Objective :To compare the analgesic effect of intrathecal midazolam and ketamine as an additive to bupivacaine in patients undergoing cesarean section .

Methods:Following Ethics Committee approval and informed patients consent, Ninety patients 18-45 yr old ASA physical status I or II, scheduled for cesarean section under spinal anesthesia, were studied in a prospective, double-blinded, randomized way. The patients were randomly allocated to one of three groups of 30 each. The ketamine group (groupK) received bupivacaine 10mg combined with 0.1 mg/kg ketamine preservative free ,the midazolam group (group M) received bupivacaine 10mg combined with0.02 mg/ kg midazolam and the placebo group (group P) received bupivacaine 10mg combined with 0.5ml distilled water intrathecally . Time to first requirement of analgesic supplement, Sensory block onset time, maximum sensory level , onset of motor block, duration of blockade, hemodynamics variables, the incidence of hypotension, ephedrine requirements, bradycardia ,hypoxemia [Saturation of peripheral oxygen (SpO2)<90], postoperative analgesic requirements and Adverse events, such as sedation, dizziness , Pruritus and postoperative nausea and vomiting were recorded. Patients were instructed preoperatively in the use of the verbal rating scale (VRS) from 0 to 10 (0no pain, 10maximum imaginable pain) for pain assessment. If the VRS exceeded four and the patient requested a supplement analgesic, diclofenac Na supp 100 mg was to be given for post-operative pain relief as needed . For breakthrough pain(VRS >4) if time of administration of diclofenac Na less than 8h,Pethidine 25 mg IV was given.

Study Overview

• Status: Completed
• Conditions: Post Operative Pain
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam; Drug: placebo(distilled water

Detailed Description

The patients were randomly allocated to one of three groups of 30 each. The ketamine group (groupK) received bupivacaine 10mg combined with 0.1 mg/kg ketamine preservative free ,the midazolam group (group M) received bupivacaine 10mg combined with0.02 mg/ kg midazolam and the placebo group (group P) received bupivacaine 10mg combined with 0.5ml distilled water intrathecally .

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Qazvin, Iran, Islamic Republic of
    • Qazvin university of medical science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• patients with American Society of Anesthesiologists(ASA) physical status I and II, undergoing elective cesarean section

Exclusion Criteria:

• significant coexisting disease such as hepato-renal and cardiovascular disease
• any contraindication to regional anesthesia such as local infection or bleeding disorders
• allergy to ketamine or midazolam
• long-term opioid use or a history of chronic pain.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketamine; The ketamine group (groupK) received bupivacaine 10mg combined with 0.1 mg/kg ketamine preservative free intrathecally .	Drug: Ketamine; The ketamine group (groupK) received bupivacaine 10mg combined with 0.1 mg/kg ketamine preservative free intrathecally
Active Comparator: midazolam; The midazolam group (group M) received bupivacaine 10mg combined with0.02 mg/ kg midazolam intrathecally	Drug: Midazolam; The midazolam group (group M) received bupivacaine 10mg combined with0.02 mg/ kg midazolam intrathecally
Placebo Comparator: placebo; The placebo group (group P) received bupivacaine 10mg combined with 0.5ml distilled water intrathecally .	Drug: placebo(distilled water; The placebo group (group P) received bupivacaine 10mg combined with 0.5ml distilled water intrathecally .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative analgesic requirements	postoperative analgesic requirements will be assessed by verbal rating scale (VRS) from 0 to 10 (0no pain, 10maximum imaginable pain).Each administration was initiated by patient request( VRS>4)	24 hours postoperative(Time from the injection of intrathecal anesthetic solution to 24 hours postoperative)
Time to first requirement of analgesic supplement	analgesic administration was initiated by patient request(verbal rating scale[ VRS]>4)	participants will be followed for the duration of 24 hours after intratechal injection (Time from the injection of intrathecal anesthetic solution to first requirement of analgesic supplement will be recorded.)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensory block onset time will be assessed by a pinprick test	The onset of sensory block was defined as the time between the end of injection of the intrathecal anesthetic and the absence of pain at the T10 dermatome	sensory block will be assessed by pinprick test every 10 seconds following intrathecal injection
duration of sensory block will be assessed by a pinprick test	The duration of sensory block was defined as the time for regression from the maximum block height sensory block to T10 dermatom will be assessed by pinprick test every 5 minuts following intrathecal injection	sensory block will be assessed by pinprick test every 5 minuts following intrathecal injection
the onset of motor block will be assessed by the modified Bromage score	The onset of motor block was defined as the time between the end of injection of the intrathecal anesthetic to Bromage block 1	every10 seconds following intrathecal injection
duration of motor block will be assessed by the modified Bromage score	duration of motor block was defined the time from intrathecal injection to Bromage score0	every 5 minutes following intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		5min before the intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		2minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		4minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		6minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		8minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		10 minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		15minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		20 minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		25 minutes after intrathecal injection
hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring		30 minutes after intrathecal injection

Collaborators and Investigators

• Sponsor: Qazvin University Of Medical Sciences
• Investigators: Principal Investigator: Marzieh Beigom Khezri, Qazvin medical science university

Publications and helpful links

General Publications

• Khezri MB, Ghasemi J, Mohammadi N. Evaluation of the analgesic effect of ketamine as an additive to intrathecal bupivacaine in patients undergoing cesarean section. Acta Anaesthesiol Taiwan. 2013 Dec;51(4):155-60. doi: 10.1016/j.aat.2013.12.004. Epub 2014 Jan 21.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 21, 2011
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 28, 2011

Study Record Updates

• Last Update Posted (Estimate): May 17, 2012
• Last Update Submitted That Met QC Criteria: May 16, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: pain; midazolam; ketamine; intrathecal
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: ACTRN12611000729921