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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
marzieh beigom khezri, Qazvin University Of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01404442
First received: July 21, 2011
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Post Operative Pain
Drug: placebo(distilled water
Drug: Ketamine
Drug: Midazolam
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by Qazvin University Of Medical Sciences:

Primary Outcome Measures:
  • Time to first requirement of analgesic supplement [ Time Frame: 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.) ] [ Designated as safety issue: Yes ]
    analgesic administration was initiated by patient request(verbal rating scale[ VRS]>4)

  • Postoperative analgesic requirements [ Time Frame: 24 hours postoperative(Time from the injection of intrathecal anesthetic solution to 24 hours postoperative) ] [ Designated as safety issue: Yes ]
    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)


Secondary Outcome Measures:
  • Sensory block onset time will be assessed by a pinprick test [ Time Frame: sensory block will be assessed by pinprick test every 10 seconds following intrathecal injection ] [ Designated as safety issue: Yes ]
    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

  • duration of sensory block will be assessed by a pinprick test [ Time Frame: sensory block will be assessed by pinprick test every 5 minuts following intrathecal injection ] [ Designated as safety issue: Yes ]
    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

  • the onset of motor block will be assessed by the modified Bromage score [ Time Frame: every10 seconds following intrathecal injection ] [ Designated as safety issue: Yes ]
    The onset of motor block was defined as the time between the end of injection of the intrathecal anesthetic to Bromage block 1

  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 5min before the intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 2minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 4minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 6minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 8minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 10 minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 15minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 20 minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 25 minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • hemodynamic variables are assessed by noninvasive automatic blood pressure measurement and electrocardiogram monitoring [ Time Frame: 30 minutes after intrathecal injection ] [ Designated as safety issue: Yes ]
  • duration of motor block will be assessed by the modified Bromage score [ Time Frame: every 5 minutes following intrathecal injection ] [ Designated as safety issue: Yes ]
    duration of motor block was defined the time from intrathecal injection to Bromage score0


Enrollment: 90
Study Start Date: May 2011
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 .

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 .

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01404442

Locations
Iran, Islamic Republic of
Qazvin university of medical science
Qazvin, Iran, Islamic Republic of
Sponsors and Collaborators
Qazvin University Of Medical Sciences
Investigators
Principal Investigator: Marzieh Beigom Khezri Qazvin medical science university
  More Information

No publications provided by Qazvin University Of Medical Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: marzieh beigom khezri, Assistant professor, Qazvin University Of Medical Sciences
ClinicalTrials.gov Identifier: NCT01404442     History of Changes
Other Study ID Numbers: ACTRN12611000729921
Study First Received: July 21, 2011
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Qazvin University Of Medical Sciences:
midazolam
ketamine
intrathecal
pain

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Bupivacaine
Ketamine
Midazolam
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Hypnotics and Sedatives

ClinicalTrials.gov processed this record on July 23, 2014