Effects of Ondansetron on Hemodynamics in Cesarean Section Under Spinal Anesthesia
Condition: Ondansetron; Cesarean Section; Spinal Anesthesia; Hemodynamics
Study type: Interventional
Phase: Phase 4

Summary: 
      BACKGROUND:

      Spinal anesthesia (SA) induced maternal hypotension is the most frequent and troublesome
      complication in cesarean section (CS), compromising both maternal and neonatal well-being.
      Many strategies have been used to prevent its occurrence but no single technique has been
      confirmed to be completely effective. the investigators hypothesized that ondansetron, a
      serotonin-receptor-antagonist, could have beneficial effects on maternal hemodynamics during
      CS under SA.

      METHODS:

      In this prospective double-blind placebo-controlled study, one hundred healthy parturients
      were randomized to receive either 8 mg of intravenous ondansetron (group O) or the same
      volume of saline (group S), 5 minutes prior to the induction of SA. All women received a
      coloading volume of 500 ml of saline. Maternal hemodynamics: blood pressure, heart rate and
      cardiac output (CO) were measured with a non-invasive device based on pulse wave transit
      time: the esCCO device Nihon Kohden hemodynamic monitor. Ephedrine was administered to treat
      hypotension (systolic blood pressure less than 80% of baseline).
    

Detailed description: 
      1. Type of the study:

           After institutional ethical committee approval, we conducted a prospective double-blind,
           placebo-controlled, randomized study, at the department of anesthesiology of the
           Mahdia's university hospital, from August to November 2017.

        2. Inclusion criteria:

           Parturients eligible for the present study are women who:

           are scheduled for elective cesarean section under spinal anesthesia. aged between 20 to
           40 years. are with an American Society of Anesthesiologist (ASA) physical status of I-II
           are with a normal liver and renal function and fetal screening, and with no medical
           history of heart disease.

           are with a single fetus.

        3. Protocol description:

      3.1. Pre-operative time: A pre-anesthetic consultation, carried out at least 48 hours before
      the surgical procedure, made it possible to define eligible women for our study, to inform
      the parturients about the nature and the progress of the protocol and to collect their
      consent. Women were fasted for 6 hours before surgery and did not receive any premedication.
      In the morning of the intervention, a preoperative visit allowed us to check the application
      of instructions and the absence of intercurrent event.

      3.2. per-operative time:

      Randomization was performed at the entrance to the operating room after verification of the
      inclusion and exclusion criteria. All participants were randomly assigned to one of two
      groups according to a randomization table.

      In the operating room, baseline values of noninvasive blood pressure (BP), electrocardiogram
      (ECG), and pulse oximetry (SPO2) were recorded using a Nihon Kohden monitor which also
      allowed a continuous non-invasive estimation of cardiac output (esCCO), based on pulse wave
      transit time (PWTT) which is automatically computed from pulse Oximetry waveform and
      electrocardiogram signals. After inputting the date of birth, sex, weight and height, the
      monitor was calibrated by the heart rate, pulse pressure, and PWTT.

      Peripheral venous access was secured with an 18-gauge canula. An anesthesia nurse ; not
      included in the analysis ;verified the allocation and prepared the appropriate dose of
      Ondansetron (8 mg) with 0.9% saline solution to a total volume of 10 ml or a placebo of 0.9%
      saline solution10 ml. The syringes had no identifying markers indicating group allocation.
      The nurse injected the contents of the syringe intravenously over 60 s, 5 min before the
      lumbar puncture was performed. The anesthetist caring for the woman was blinded to group
      allocation.

      Spinal anesthesia was induced in the sitting position at the L3-4 or L4-5 interspace, with a
      25-gauge spinal needle pencil point. We administered 10 mg of 0.5% hyperbaric Bupivacaine,
      with 5ɤof Sufentanil and 100ɤof morphine. After injection, patients were immediately placed
      supine with 15 degrees left tilt. All women were rapidly coloaded with 500 ml of 0.9% saline
      solution.

      Hemodynamic data were recorded at 2-min interval in the first 15-min and then every 5-min
      until the end of the procedure.

      Sensory block height level was checked by assessing the perception of coldness using an
      alcohol swab, and motor block using Bromage scale.

      Supplemental oxygen was administered via nasal canula at 2L/min. Maintenance fluids (10 ml/kg
      in the first one hour and 5ml/kg in the subsequent hours) were given at room temperature.
      Oxytocin was given following delivery of the fetus (5 IU directly and 10 IU in 250 ml of
      Glucose solution 5%). Antibioprophylaxis using 2g of Cefazolin was administered
      intravenously, in case of allergy, we used Clindamycin.

      Neonatal Apgar score was noted at 1 and 5min after delivery.

      Hypotension was defined as a decrease in systolic blood pressure (SBP)> 25% of baseline, and
      severe hypotension was defined as SBP< 80 mmHg. Treatment was initiated with intravenous
      Ephedrine 9 mg. More bolus of Ephedrine can be required.

      Bradycardia, defined as a decrease in heart rate (HR) to less than 50 beats/min, was treated
      with intravenous atropine 0.5 mg.

      Tachycardia was defined as HR >120 beats/min. Low flow was defined as a decrease in cardiac
      output (CO) > 15% from baseline.

      3.3. Post-operative time:

      After surgery, all parturients were transferred to the post-intervention monitoring room.

      Standard monitoring of all parturients systematically included heart rate (HR), non invasive
      blood pressure (NIBP), respiratory frequency (RR), uterine globe tonus, bleeding, diuresis
      and temperature.

      A glucose solution 5 % infusion enriched with electrolytes and comprising 20 IU of Oxytocin
      was instituted at a rate of 2 liters to 3l/24 h depending on the weight of the parturient.

      The protocol of postoperative analgesia is ensured by the administration of Paracetamol in
      slow intravenous infusion at the dose of 1gevery 6 hours and Nefopam at the dose of 20 mg in
      slow infusion of 30 min every 8 hours. The postoperative prescription included also for all
      parturients Enoxaparin-based thrombophylaxis for 7 days.
    

Intervention name(s): Ondansetron 8Mg/4mL Injection
Intervention type(s): Drug
Intervention description(s): investigators administrated intravenously Ondansetron 8 mg 5 minutes before spinal anesthesia.
Other intervention name(s): OD-C/S
Intervention MeSH terms: Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Ondansetron group (group O): 8mg(10 ml) of Ondansetron administrated 5 minutes before spinal anesthesia control group (group C): saline solution 0,9%(10ml)
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Prevention