Remifentanil vs. Combined Spinal-epidural Analgesia for Labor Analgesia and Progress of Labor in Multiparous
Condition: Labor Pain; Labor; Prolonged, Second Stage; Labor; Prolonged, First Stage
MeSH terms: Labor Pain
Study type: Observational

Summary: 
      Remifentanil may be an ideal drug for labor analgesia due to its pharmacodynamic and
      pharmacokinetic profile. As compared to epidural analgesia, it demonstrated satisfactory for
      pain relief at the beginning of labour with a gradual elevation of pain scores as labour
      progresses. However, fast onset and limited time efficacy may render it useful in multiparous
      with a faster labor progression, thus even making it an alternative to single-shot spinal
      analgesia.
    

Detailed description: 
      Introduction:

      Neuraxial analgesia is considered the most effective method of pain relief during labor. When
      unavailable, contraindicated, refused by parturient or discouraged by midwife/obstetrician,
      alternative methods of analgesia are required which should to be effective, without major
      side effects and flexible enough to adapt to variable analgesic requirements during labor.

      Remifentanil may be an ideal drug for labor analgesia due to its pharmacodynamic and
      pharmacokinetic profile. It is an ultra-short-acting µ1-opioid receptor agonist, rapidly
      metabolized by plasma and tissue esterases. It has onset time of 30 to 60 seconds and a peak
      effect at 2,5 min. It rapidly crosses the placenta and it is quickly metabolized by the
      fetus. Several studies which compared remifentanil patient controlled analgesia (PCA) with
      epidural analgesia in nulliparous patients or parturient of mixed parity have demonstrated a
      lower analgesic efficacy of remifentanil. Remifentanil, as compared to epidural analgesia,
      showed a satisfactory for pain relief only at the beginning of labor with a gradual elevation
      of pain scores as labor progressed. However, the fast onset and limited time efficacy may
      render it useful in multiparous with a faster labor progression, thus even making it an
      alternative to single-shot spinal analgesia.

      The anaesthetic technique may also affect the progress of labor. A combined spinal-epidural
      analgesia (CSEA) has been demonstrated to be associated with a greater cervical dilation
      relative to conventional epidural analgesia in nulliparous patients. There are no data on
      labour progression difference as compared to remifentanil PCA in multiparous.

      We therefore conduct the study in multiparous patients to compare remifentanil PCA and CSEA
      with respect to pain relief and the progress of labor.

      Methods:

      Approval for this observational trial was obtained by Republic of Slovenia National Ethical
      Committee (kme.mz@gov.si). Only multiparous fulfilling inclusion criteria will be recruited.
      The parturient requesting remifentanil analgesia will receive remifentanil hydrochloride
      (Ultiva, GlaxoSmithKline, Oslo, Norway) according to the standard operative protocol. Bolus
      doses will be adjusted by anesthesia staff on patient request and side effects (level of
      sedation <3 according to Ramsey scale (scale1-5: 1= alert, 2 = slightly drowsy, 4 = very
      drowsy, 5 = unarousable), respiratory rate (RR)>8 breaths per min, oxygen saturation (SaO2)
      >94%, systolic blood pressure (SBP) > 90 mmHg, heart rate (HR) > 50/min and acceptable
      overall clinical assessment performed by the investigator). Women using remifentanil will
      have one-to-one midwifery care. All midwives will be familiar with the protocol and have
      already received training in this mode of analgesia. Respiratory monitoring will be performed
      throughout the labor only in the remifentanil group using a Capno stream capnograph with an
      oral-nasal cannula, sampling from both the nose and mouth. Supplemental oxygen (2L/min via
      nasal catheter) will be given in all patients. Respiratory monitoring will record continuous
      waveform end-tidal carbon dioxide (ETCO2), SBP, SaO2 and maternal HR. The audible alarms will
      be activated with SaO2<94%, RR<8/min and apnea longer than 20 sec which triggered a staged
      intervention starting with a verbal command and/or light tap on the parturient arm.

      CSEA will be provided on parturient request according to the standard operative protocol.
      Fetal heart rate (FHR) will be monitored to ensure neonatal safety using cardiotocography.

      Data acquisition and retrieval:

      Demographic and medical data will be obtained from personal interviews before analgesia
      initiation and throughout the labor.

      Maternal pain will be evaluated using a 11-point verbal numerical rating scale (NRS), where 0
      is no pain and 10 is the worst imaginable pain. NRS pain scores will be recorded immediately
      before starting PCA (baseline), then every 15 min during the first hour and every 30 min
      thereafter.

      Patient satisfaction with pain relief will be evaluated every 30 minutes after analgesia
      administration and within 24 hours after delivery using a five-point categorical scale
      (1=very good, 2=good, 3=moderate, 4=poor, 5=very poor). At the same time, each parturient
      will be asked if she would choose the same technique for the next delivery and/or recommend
      the same technique to somebody else.

      Non-invasive SBP, maternal HR, SaO2 and sedation score will be recorded before analgesia and
      every 30 min thereafter. The respiratory monitor data will be recorded and adverse
      respiratory events (SaO2<94%, RR<8/min and apnea>20 sec) counted for each woman.

      The number of epidural boluses as well as the total dose of remifentanil will be registered
      automatically in the PCA pump and recorded for each patient. Maternal requests for additional
      analgesia will be manually recorded.

      Data concerning nausea, vomiting and itching will also be collected.

      Oral temperature will be measured both at the onset of analgesia and within 1 hour of
      delivery.

      Data on labor progress (first and second stage labor duration, mean cervical dilation rate)
      and outcome will be recorded for each patient, including the use and maximum dose of oxytocin
      administered, and mode of delivery (spintaneus vaginal, instrumental vaginal, caesarean
      section). Cervical dilation will be assessed by the midwife, and all changes recorded till
      delivery. The time from onset of analgesia until 10-cm cervical dilation will be defined as
      the first stage of labor, while the second stage will be defined as the interval between full
      cervical dilation and delivery of the neonate. The mean cervical dilation rate will be
      defined as 10 minus last cervical examination before analgesia divided by time between
      examinations.

      After delivery, Apgar score at 1 and 5 min,and umbilical artery pH and base excess will be
      abstracted from the medical records.

      Sample size was calculated based on the primary outcome of pain relief during remifentanil
      and CSE analgesia in multiparous measured on an 11 point scale raging from 0 to 10. If the
      true difference between the two studied groups is 1 (on 11 point scale with estimated
      standard deviation of 2,2), we will need to study 77 subjects in each group to be able to
      reject the null hypothesis that the population means of the two groups are not equal with
      probability (power) 0,8. The Type I error probability associated with this test of this null
      hypothesis is 0,05.
    

Intervention name(s): remifentanil; combined spinal-epidural analgesia
Intervention type(s): Drug; Drug
Intervention description(s): Remifentanil PCA will be used to deliver intravenous drug boluses from 20 to 40 micrograms per 2 min lockout interval.; Patient controlled epidural analgesia will be used to deliver epidural boluses of 6-10 ml of 0,1% bupivacaine with 2 micrograms of fentanyl per ml per 15 min lockout interval.
Other intervention name(s): ULTIVA; bupivacaine epidurally
Intervention MeSH terms: Remifentanil; Bupivacaine
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Multiparous
      
Keywords: remifentanil; combined spinal-epidural analgesia; multiparous