Clinical trial NCT04011098: Improving Labour Induction Analgesia: Epidural Fentanyl Bolus at Epidural Initiation for Induction of Labour
Official title: Improving Labour Induction Analgesia: a Randomized Control Trial of Single Epidural Fentanyl Bolus at Epidural Initiation for Induction of Labour
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Epidural
Labor Pain
Induction of Labor Affected Fetus / Newborn
Obstetric Anesthesia Problems
Obstetric Pain
Opioid
Keywords: Epidural
Opioids
Fentanyl
Labour Induction
Labour Pain
Obstetric Pain
Induction of Labour
Anesthesia
Obstetric Anesthesia
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
First posted: 2019-07-08
Enrollment: 5
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized control trial (RCT) utilizing parallel groups
Primary purpose: TREATMENT

Brief summary: Labour pain can be intensified for labour inductions and women undergoing inductions often have earlier and more frequent requests for analgesia. Current evidence suggests that epidural analgesia effectively manages pain in labour, but may give rise to adverse effects for both the mother and neonate. Opioids are often added to epidurals to improve the quality of analgesia. Despite reassuring findings regarding epidural opioids, other investigators have found an association between epidural opioids and neonatal respiratory distress, lower Neurological and Adaptive Capacity scores, and reduced rates of breastfeeding. Given the heightened implications for the mother and neonate in situations requiring induction of labour, the desire for a positive outcome whilst still providing adequate maternal analgesia is paramount.

This study thus aims to investigate whether a preliminary epidural Fentanyl bolus at the initiation of the epidural may help to improve analgesia for women undergoing labour inductions for post-term pregnancy in a safe manner. Importantly, the main rationale of this proposed practice being that by achieving adequate epidural analgesia earlier in the labour induction, this may lead to better pain control overall and less overall requirements for epidural PCEA boluses and epidural "top-ups" as the induction progresses.

Detailed description: The pain felt during labour is influenced by many physiological and psychosocial factors and often requires some form of relief. Pain can be intensified for labour inductions as the body's natural pain-relieving endorphins are not readily released in response to the increasingly strong and painful uterine contractions- leading to earlier and more frequent requests for analgesia. Induced labour has also been reported as being significantly longer than spontaneous labour. Current evidence suggests that epidural, combined spinal epidural and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects for both the mother and neonate. Despite this, epidural analgesia is considered the gold standard in the treatment of labor pain and has a role in labour inductions. Opioids are often added to epidurals to improve the quality of analgesia because of their faster onset and superior pain relief. When combined with opioids, lower concentrations of local anesthetic are needed. Such combinations provide adequate analgesic effect while allowing the parturient to maintain maximal motor function.

In studies assessing the safety and efficacy of labour analgesia, neonatal outcome is a primary concern and the use of opioids for labour analgesia is controversial because of the potentially negative effects on neonates. Common indicators of poor neonatal outcomes include a lower Apgar score, a lower Neurological and Adaptive Capacity Score (NACS), and a lower umbilical artery or vein pH value.

Fentanyl is the most widely investigated adjuncts to epidural local anesthetics. Various RCTs comparing epidural local anesthetics with and without fentanyl have found no significant differences in neonatal Apgar scores at one and five minutes between the groups. A recent meta-analysis of twenty-one RCTs involving epidural Fentanyl and Sufentanil concluded that there was no difference in the incidence of Apgar scores \< 7 at one and five minutes, no significant differences in the NACS at two hours and at 24 hours, and no significant differences were found in umbilical cord artery pH between the epidural opioid and control groups. This meta-analysis concluded that the common doses of Fentanyl (total dose of 100-500 mcg) and Sufentanil (total dose of 7.5-30 mcg) used with an epidural/spinal technique are safe for neonates up to 24 hours after delivery. Despite reassuring findings regarding epidural opioids, other investigators have found an association between epidural opioids and neonatal respiratory distress and the use of epidural fentanyl has been associated with a NACS that failed to improve by 24 hours in one study. Furthermore, the use of epidural opioids was associated with reduced rates of breastfeeding in some observational studies, but evidence is unclear and debated.

Given the heightened implications for the mother and neonate in situations requiring induction of labour, the desire for a positive outcome whilst still providing adequate maternal analgesia is paramount. This study thus aims to investigate whether a preliminary epidural Fentanyl bolus at the initiation of the epidural may help to improve analgesia for women undergoing labour inductions for post-term pregnancy in a safe manner. Importantly, the main rationale of this proposed practice being that by achieving adequate epidural analgesia earlier in the labour induction, this may lead to better pain control overall and less overall requirements for epidural PCEA boluses and epidural "top-ups" as the induction progresses.

Eligibility criteria: Inclusion Criteria:

* Healthy parturients
* Parturients presenting for labour induction for post-term pregnancy (i.e. pregnancy beyond 42 weeks gestational age)
* Parturients who have had an uncomplicated pregnancy

Exclusion Criteria:

* Parturients presenting for induction of labour for pre-labour (premature) rupture of membranes
* Parturients presenting for induction of labour for hypertensive disorders of pregnancy \[including preeclampsia, eclampsia, HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets)\]
* Parturients with maternal diabetes
* Fetal growth restriction
* Multiple gestation pregnancy
* Known or suspected Chorioamnionitis
* Known or suspected Abruptio placentae
* Oligohydramnios
* Parturients with cholestasis of pregnancy
* Known alloimmunization with fetal effects.
* Parturients with other chronic medical conditions or any complications related to pregnancy
* Participants who lack capacity to consent on their own behalf

Primary outcomes:
measure: Labour analgesia quality: Change in verbal rating pain scale (VRS) after epidural placement
timeFrame: Verbal rating pain scale will be assessed 1) Prior to epidural placement, 2) 20 minutes after epidural placement, 3) 60 minutes after epidural placement, and 4) 120 minutes after epidural placement
Secondary outcomes:
measure: Total epidural opioid consumption
timeFrame: Total epidural opioid consumption will be summed following fetal delivery and discontinuation of the epidural infusion. The aim will be to collect this data within 24 hours of fetal delivery via chart review.
measure: Incidence of failed/incomplete epidurals
timeFrame: Incidence of failed/incomplete epidurals will be determined following fetal delivery and once all chart documents are available for review. The aim will be to collect this data within 24 hours of fetal delivery via chart review.
measure: Neonatal well-being: Presence or Absence of Fetal Heart Tracing Abnormalities
timeFrame: Fetal Heart Tracing abnormalities will be assessed and summed following fetal delivery and once chart documents/fetal heart tracing strips are all available. The aim will be to collect this data within 24 hours of fetal delivery via chart review.
measure: Neonatal well-being: Apgar scores
timeFrame: Apgar scores will be recorded at 1 minute following fetal delivery and at 5 minutes following fetal delivery. The aim will be to collect this data within 24 hours of fetal delivery via chart review.
measure: Neonatal well-being: Umbilical artery pH value
timeFrame: Neonatal well-being will be assessed by recording the umbilical artery pH lab value at the time of fetal delivery/birth. The aim will be to collect this data within 24 hours of fetal delivery via chart review.
measure: Neonatal well-being: Breast-feeding quality
timeFrame: Neonatal breast-feeding quality will assessed and documented following fetal delivery and once all chart documents are available for review. The aim will be to collect this data within 48 hours of fetal delivery via chart review.
measure: Maternal well-being: Respiratory Rate
timeFrame: Maternal respiratory rate will be assessed 1) Prior to epidural placement, 2) Every 5 minutes after epidural placement until 20 minutes after epidural placement, 3) 60 minutes after epidural placement, and 4) 120 minutes after epidural placement
measure: Maternal well-being: Heart Rate
timeFrame: Maternal heart rate will be assessed 1) Prior to epidural placement, 2) Every 5 minutes after epidural placement until 20 minutes after epidural placement, 3) 60 minutes after epidural placement, and 4) 120 minutes after epidural placement
measure: Maternal well-being: Blood pressure
timeFrame: Maternal blood pressure will be assessed 1) Prior to epidural placement, 2) Every 5 minutes after epidural placement until 20 minutes after epidural placement, 3) 60 minutes after epidural placement, and 4) 120 minutes after epidural placement
measure: Maternal well-being: Oxygen Saturation (SpO2)
timeFrame: Maternal oxygen saturation will be assessed 1) Prior to epidural placement, 2) Every 5 minutes after epidural placement until 20 minutes after epidural placement, 3) 60 minutes after epidural placement, and 4) 120 minutes after epidural placement
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: U of S Department of Anesthesiology, Perioperative Medicine and Pain Management
name: Harry Neveling, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
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