Clinical trial NCT02963337: Remifentanil vs. Combined Spinal-epidural Analgesia for Labor Analgesia and Progress of Labor in Multiparous
Official title: Pain Relief and Progress of Labour With Remifentanil Patient-controlled Analgesia Versus Combined Spinal-epidural Analgesia in Multiparous Women: a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Labor Pain
Labor; Prolonged, Second Stage
Labor; Prolonged, First Stage
Keywords: remifentanil
combined spinal-epidural analgesia
multiparous
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2016-11-15
Enrollment: 162
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Multiparous

Brief 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.

Eligibility criteria: Inclusion Criteria:

* patients' request for pain relief
* ASA physical status 1-3
* uncomplicated singleton pregnancy with cefalic presentation
* gestation age \> 37 weeks
* regular uterine contractions
* cervical dilation 2-5 cm
* anticipated vaginal delivery
* fetus without suspected abnormality and normal CTG

Exclusion Criteria:

* contraindications for remifentanil usage
* contraindications for CSE

Primary outcomes:
measure: Pain relief with remifentanil or CSE in multiparous women
timeFrame: two years
Secondary outcomes:
measure: Patient satisfaction with pain relief
timeFrame: two years
measure: Duration of first and second stage of labor
timeFrame: one year
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana, Ljubljana, Slovenia
Study officials:
affiliation: University Medical Centre
name: Vesna Novak Jankovic, Professor
role: STUDY_CHAIR
References:
citation: Douma MR, Middeldorp JM, Verwey RA, Dahan A, Stienstra R. A randomised comparison of intravenous remifentanil patient-controlled analgesia with epidural ropivacaine/sufentanil during labour. Int J Obstet Anesth. 2011 Apr;20(2):118-23. doi: 10.1016/j.ijoa.2010.11.009. Epub 2011 Mar 3.
citation: Blajic I, Zagar T, Semrl N, Umek N, Lucovnik M, Stopar Pintaric T. Analgesic efficacy of remifentanil patient-controlled analgesia versus combined spinal-epidural technique in multiparous women during labour. Ginekol Pol. 2021;92(11):797-803. doi: 10.5603/GP.a2021.0053. Epub 2021 Apr 29.