Hyperbaric Bupivacaine Versus Hyperbaric Prilocaine 2% for Cesarean Section Under Spinal Anesthesia

Study Overview
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Brief Summary
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Over the past 15 years, cesarean delivery is most commonly performed under spinal anesthesia using hyperbaric bupivacaine which provides an adequate sensory and motor block. Despite effective surgical anesthesia, bupivacaine is associated with long duration motor block and dose-dependent maternal hypotension potentially harmful for the fetus. Prilocaine with its new 2% hyperbaric formulation (HP), developed recently, showed rapid onset of action and faster regression of motor block compared to other local anesthetics without noteworthy side-effects when used intrathecally. The aim of this randomized, multicenter, powered clinical trial is to investigate whether HP may be an efficient alternative to hyperbaric bupivacaine for scheduled caesarean delivery under spinal anesthesia, with more rapid rehabilitation and less adverse effects. Our hypothesis is that hyperbaric prilocaine offers shorter motor block and more rapid rehabilitation than bupivacaine.

Official Title
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Hyperbaric Bupivacaine Versus Hyperbaric Prilocaine 2% for Cesarean Section Under Spinal Anesthesia: a Randomised Clinical Trial

Conditions
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Pregnant Women, Pain, Hypotension

Intervention / Treatment
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* Drug: Hyperbaric bupivacaine
* Drug: Hyperbaric prilocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : American Society of Anesthesiologists physical status (ASA) < III Age 18-40 year Body Weight <110 kg Height between 160 and 175 cm Gestational age>37 SA Elective cesarean delivery Singleton pregnancy Non complicated pregnancy Signed informed consent obtained prior to any study specific assessments and procedures Exclusion Criteria: Twin pregnancy History of 2 cesarean section or more Diabetes and gestational diabetes Placenta praevia Congenital foetal abnormality Intrauterine growth retardation Patient in labour Membrane rupture Known allergy to local anaesthetics Standard contraindications to neuraxial block. Disagreement of the patient Neurological impairment Gestational low blood pressure Pre eclampsia and eclampsia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Hyperbaric bupivacaine<br>Hyperbaric bupivacaine 0.5% will be administered at the dose of 10 mg intrathecally associated with 100 µg of morphine and 2.5 µg of sufentanyl. | Drug: Hyperbaric bupivacaine<br>* The dose of 10 mg of hyperbaric bupivacaine will be administered to one of two groups intrathecally and the quality of sensory and motor block as well as side-effects will be observed at precise time points.<br>* Other names: Marcaine;|
| Active Comparator: Hyperbaric prilocaine<br>Hyperbaric prilocaine 2% will be administered at the dose of 50 mg intrathecally associated with 100 µg of morphine and 2.5 µg of sufentanyl. | Drug: Hyperbaric prilocaine<br>* The dose of 50 mg of hyperbaric prilocaine will be administered to one of two groups intrathecally and the quality of sensory and motor block as well as side-effects will be observed at precise time points.<br>* Other names: Tachipri;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Regression of Motor Block | Time to regression of motor block is the time between maximal blockade (score 1, as evaluated by the Modified Bromage scale), and no blockade (score 6). Degree of motor blockade is assessed before and 10, 15, 20 minutes after spinal anesthesia, then every 15 minutes until the end of surgery, and thereafter, every 30 minutes until complete regression of motor block | until complete regression of motor block (up to 4 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Successful Anesthesia (Successful Sensory Block) | Time between spinal injection and reached bilateral T4 sensory level. | From spinal injection of the local anesthetic to bilateral T4 level (average 20 minutes) | 
| Number of Participants Per Maximal Level of Sensory Block Attained After Spinal Anesthesia | Level of Sensory block is assessed as loss of sensation to cold, and represents the dermatomal level under which anesthesia is effective. It is measured every 2 minutes after spinal anesthesia during 15 minutes, then every 5 minutes until the end of surgery, thereafter, once 30 minutes until total regression of sensory block (T12-S1). A dermatome is the area of skin that is supplied by a single spinal nerve - Dermatome levels : C5-C8 for Cervical levels and T1-T4 for Thoracic levels. To perform cesarean section loss of cold sensation at a dermatome of at least T4 has to be obtained. The results are expressed as the number of patients reaching each dermatomal level from T4 and above (see below) as maximal sensory level, this is a usual outcome used to evaluate the quality of anesthesia. | until complete release of sensory block (T12-S1) (average 4 hours) | 
| Time to Resolution of Sensory Block | Evaluation at every 2 minutes after spinal anesthesia during 15 minutes, then every 5 minutes until the end of surgery, and thereafter, every 30 minutes until total regression of sensory block (T12-S1). | until complete release of sensory block (T12-S1) (average 4 hours) | 
| Time to Motor Block Onset | Time of installation of the motor block (time between spinal injection and maximum motor block of 1, as evaluated by the Modified Bromage scale). Degree of motor blockade is assessed before and 10, 15, 20 minutes after spinal anesthesia | From spinal injection of the local anesthetic to bilateral T4 level and during surgery (average 1 hour) | 
| Number of Patients With Hypotension and Use of Vasopressors | Arterial blood pressure will be measured at every 1 minute during the first 15 minutes, then at every 2.5 minutes until the end of surgery, and at every 20 minutes in the Post Anesthesia Care Unit (PACU). A low blood pressure (hypotension) is defined as a systolic blood pressure lower than 20% or more than the basal blood pressure (Systolic blood pressure before spinal anesthesia) | up to 2 hours after surgery | 
| Number of Participants With Urinary Retention | All parturients will be questioned and examined for urinary retention (yes or no) | up to 4 hours after surgery | 
| Time to First Walk | Time for the patients to be able to walk in their room then in the hallway without any assistance for the first time. | up to 24h after surgery | 
| Maternal Satisfaction Assessed by Visual Analogic Scale (VASS) | All patients will be asked to rate their satisfaction about anesthetic technique during surgery and in the arrival in the Post Anesthesia Care Unit (PACU). Satisfaction evaluated by Visual analog scale (0 cm= very unsatisfied and 10cm = very satisfied) | up to 24 hours after surgery | 
| Maternal Rehabilitation Assessed by Visual Analogic Scale (VASR) | Maternal rehabilitation is evaluated at postoperative Day1, postoperative Day 2 and postoperative Day 3. Evaluation by Visual analog scale (0 cm= very poor and 10cm = excellent) | up to 72 hours after surgery | 
| Number of Participants With Adverse Events (Nausea, Vomiting, Pruritis, Headache) | Evaluation from 15 minutes after spinal injection to the end of surgery, then every 4 hours for 24 hours, then once a day for 3 days (score 0=no symptom; 1=symptom with no necessary treatment; 2=symptom present and treated) | up to 72 hours after surgery | 
| Number of Participants With Transient Neurologic Symptoms (TNS) | Evaluation of apparition of TNS at postoperative Day 1, postoperative Day 2, postoperative Day 3 and postoperative Day 15. TNS are defined as pain and/or dysesthesia occurred after complete release of sensory block at the gluteal level, at the thighs and at the legs. | up to 15 Days after surgery | 
| Pain as Assessed by Visual Analogue Scale | Pain levels will be determined at incision, baby delivery, peritoneal and skin closure, every 5 minutes during surgery, and thereafter every 4 hours for 24 hours. Visual analog pain score (scale = 0 no pain; 10 = worst pain imaginable). Patient will receive additional analgesic treatment above VAS>3. | up to 24 hours after surgery | 
| Newborn Apgar Score | Newborn Apgar score assessed at 1, 5, 10 minutes after baby extraction. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from 0 to 2, then summing up the five values thus obtained. The overall resulting score ranges from 0 to 10 ( 0-3 : severely depressed, 4-6 : Moderately depressed and 7-10 : Excellent condition). The five criteria are summarized using words chosen to form an abbreviation (Appearance, Pulse, Grimace, Activity, Respiration). | up to 10 minutes after baby extraction | 
| Newborn Methemoglobinemia (MetHb) | Newborn Methemoglobinemia (MetHb) will be assessed at delivery by cordal blood sample, as a routine control in obstetrics, and expressed as a percentage of total hemoglobinemia. Methemoglobinemia (MetHb) is a blood disorder in which an abnormal amount of methemoglobin (hemoglobin in the form metalloprotein) is produced. This specific type of of Hemoglobin carries oxygen through your blood but doesn't release it to the cells. | average 1 hour | 
| Newborn Umbilical pH | Newborn umbilical pH will be assessed at delivery by cordal blood sample, as a routine control, and expressed as standard value | average 1 hour | 
| Time of Surgery | Time between incision and end of surgery | average 1 hour | 
| Time From Spinal Injection to Baby Delivery | Time between spinal injection and baby delivery | average 1 hour | 
| Time From Baby Delivery to End of Surgery | Time between baby delivery, and the end of surgery | average 1 hour | 
| Total Blood Loss | Total blood loss (milliliters) during surgery | average 1 hour | 
| Obstetrician Satisfaction | Satisfaction ranged between 1 (totally unsatisfied) to 4 (totally satisfied) assessed at the end of surgery | average 1 hour | 
| Midwife Satisfaction | Satisfaction ranged between 1 (totally unsatisfied) to 4 (totally satisfied) assessed at postoperative Day 3 | 72 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cesarean delivery, Spinal anesthesia, Local anesthetics