Dexmedetomine as Adjuvant for Spinal Anesthesia in Elective Cesarian Sections : a Pilot Study

Study Overview
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Brief Summary
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The proposed pilot study is a prospective, randomized, controlled, double-blind, single-center pilot study.The aim of this pilot project is to evaluate the feasibility of a phase III study on the use of dexmedetomidine in intrathecal in the context of elective cesarean section. The target population for the study will be adult pregnant women undergoing elective cesarean section under spinal anesthesia. This study will be carried out at a single site, the CHU Sainte-Justine as part of a research internship as part of the anesthesiology residency program at the University of Montreal.

Detailed Description
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52 patients will be recruted for this study, and will be randomized in two equal groups. All the interventions carried out will be standardized. Medical care for patients will be the same as usual care, except for administration of dexmedetomidine or intrathecal narcotics. In the test group, bupivacaine (12 mg, 1.6 ml) will be injected with 3 mcg of dexemedetomidine. In the second group, bupivacaine (12 mg, 1.6 ml) will be injected with 100 mcg of morphine and 15 mcg of fentanyl with 0.25 ml of normal saline, which corresponds to the standard treatment. The patients will receive standard analgesia, described in the protocol, post-operatively and will also have access to anti-nausea and anti-pruritics. The patient will then be seen the day after surgery to collect her validated self-assessment scales for pain, nausea and vomiting, pruritus, chills and complete her QoR15 questionnaire. This will be collected to establish preliminary data for a second study of non-inferiority for analgesia and gradation of side effects.

Official Title
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Dexmedetomidine Comme Adjuvant à la rachianesthésie Lors de césariennes électives : Une étude Pilote

Conditions
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Analgesia, Analgesics, Opioid, Anesthesia, Obstetrical, Anesthesia, Spinal, Analgesics, Non-Narcotic, Dexmedetomidine, Analgesia, Obstetrical

Intervention / Treatment
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* Drug: Dexmedetomidine 0.004 MG/ML [Precedex]
* Drug: Opioids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient will receive an elective c-section under spinal anesthesia Gestational age > 37 weeks Exclusion Criteria: ASA score ≥ 3 Allergy or contraindication to receiving opioids (morphine or fentanyl) Allergy or contraindication to receiving anti-inflammatory drugs (ketorolac, Naprosyn) Allergy or contraindication to receiving acetaminophen Height <152 cm or> 183 cm Weight <50 or> 110 kg Contraindication to spinal anesthesia Conversion to general anesthesia Combined spinal-epidural anesthesia Inability to give informed consent, either secondary to a mental or physical disability or a significant language barrier (Inability to understand English or French) Need for transfusion or other major complication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot study for a phase 3 study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>Monitoring will be installed upon arrival.Metoclopramide 10 mg IV and Dexamethasone 4 mg will be given for nausea-prophylaxis. Patients may be given ondansetron 4 mg as rescue. Cefazoline 2G or clindamycin 900 mg will be given.A sterile spinal technique will be performed with a 25G Whitacre. Bupivacaine 12 mg (1.6 ml) will be drawn and given, along with dexmedetomidine 3 mcg (0.75 mL) previously blindly prepared for a total of 2.35 ml.Adequate blood pressure will be maintained with phenylephrine infusion or ephedrine IV. Glycopyrrolate 0.2 mg may be given for bradycardia.Once an adequate sensory block is obtained, the obstetrics team can perform the surgery.The patient will receive a dose of ketorolac 30 mg IV before leaving the PACU and then Naproxen 500 mg PO every 12 hours.She will receive acetaminophen 975 mg PO every 6 hours and hydromorphone 2-4 mg PO every 3 hours prn. Patients will also have access to a protocol for treatment of nausea and pruritus. | Drug: Dexmedetomidine 0.004 MG/ML [Precedex]<br>* Injection of 3 mcg of dexmedetomidine and 12 mg of bupivacaine in the intrathecal space to provide spinal anesthesia.<br>|
| Active Comparator: Control group<br>Monitoring will be installed upon arrival.Metoclopramide 10 mg IV and Dexamethasone 4 mg will be given for nausea-prophylaxis. Patients may be given ondansetron 4 mg as rescue. Cefazoline 2G or clindamycin 900 mg will be given.A sterile spinal technique will be performed with a 25G Whitacre. Bupivacaine 12 mg (1.6 ml) will be drawn and given, along with morphine 100 mcg, fentanyl 15 mcg and normal saline 0.25 ml previously blindly prepared for a total of 2.35 ml.Adequate blood pressure will be maintained with phenylephrine infusion or ephedrine IV. Glycopyrrolate 0.2 mg may be given for bradycardia.Once an adequate sensory block is obtained, the obstetrics team can perform the surgery.The patient will receive a dose of ketorolac 30 mg IV before leaving the PACU and then Naproxen 500 mg PO every 12 hours.She will receive acetaminophen 975 mg PO every 6 hours and hydromorphone 2-4 mg PO every 3 hours prn. Patients will also have access to a protocol for treatment of nausea and pruritus. | Drug: Opioids<br>* Injection of 100 mcg of morphine, 15 mcg of fentanyl and 0.25 ml of normal salin (sterile) with 12 mg of bupivacaine in the intrathecal space to provide spinal anesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 3 study feasability | The primary outcome will be to evaluate the phase 3 study feasability through recrutement rates and time needed to recrut a total of 52 patients | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioids consumption | Total morphine equivalent consumed by the patient | 24 hours post-operatively | 
| Pruritus | Self-assessed validated numerical pruritus scale (NPS). Scale between 0 and 10, 10 being the worst symptoms the patient can imagine. | 2, 6, 12 and 24 hours after surgery | 
| Nausea | Absence or presence of nausea / vomiting at 2, 6, 12 and 24 hours after surgery | 2, 6, 12 and 24 hours after surgery | 
| Pain level | Self-assessed validated numerical pain scale (NPS).Scale between 0 and 10, 10 being the worst symptoms the patient can imagine. | 2, 6, 12 and 24 hours after surgery | 
| Quality of recovery and patient's satisfaction | Satisfaction according to the QoR15 questionnaire. Questionnaire containing 15 question to evaluate the quality of recovery in patients after a surgery. | 24 hours after surgery | 
| Nausea | Number of anti-nausea medication doses needed | 24 hours post-operatively |