Improving Labour Induction Analgesia: Epidural Fentanyl Bolus at Epidural Initiation for Induction of Labour

Labor Pain Clinical Trial

Official title:

Improving Labour Induction Analgesia: a Randomized Control Trial of Single Epidural Fentanyl Bolus at Epidural Initiation for Induction of Labour

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04011098
• Other study ID #: Bio 18-73
• Status: Terminated
• Phase: Phase 1
• Start date: July 1, 2019
• Est. completion date: November 2, 2020

Study information

• Verified date: November 2020
• Source: University of Saskatchewan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: November 2, 2020
• Est. primary completion date: November 2, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Epidural
• Induction of Labor Affected Fetus / Newborn
• Labor Pain
• Obstetric Anesthesia Problems
• Obstetric Pain
• Opioid

Intervention

Drug:
• Epidural Fentanyl Bolus
Fentanyl bolus refers to the provision of a 2 ml bolus of epidural Fentanyl (50 mcg/ml; therefore a total dose of 100 mcg) after epidural placement, followed by a standard care infusion of epidural local anesthetic/opioids, with a PCEA pump for subsequent analgesia (0.08% Bupivicaine with 2 mcg/ml Fentanyl Solution).
• Standard Epidural Group
The Control group will receive a 2 ml bolus of standard epidural mix solution (0.08% Bupivicaine with 2 mcg/ml Fentanyl) after epidural placement followed by standard care infusion of the same solution, with a PCEA pump for subsequent analgesia.

Locations

Country	Name	City	State
Canada	Royal University Hospital	Saskatoon	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
University of Saskatchewan

Country where clinical trial is conducted

Canada, 

References & Publications (20)

Anim-Somuah M, Smyth RM, Jones L. Epidural versus non-epidural or no analgesia in labour. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD000331. doi: 10.1002/14651858.CD000331.pub3. Review. Update in: Cochrane Database Syst Rev. 2018 May 21;5:CD000331. — View Citation

Beilin Y, Bodian CA, Weiser J, Hossain S, Arnold I, Feierman DE, Martin G, Holzman I. Effect of labor epidural analgesia with and without fentanyl on infant breast-feeding: a prospective, randomized, double-blind study. Anesthesiology. 2005 Dec;103(6):1211-7. — View Citation

Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, Jordan S, Lavender T, Neilson JP. Pain management for women in labour: an overview of systematic reviews. Cochrane Database Syst Rev. 2012 Mar 14;(3):CD009234. doi: 10.1002/14651858.CD009234.pub2. Review. — View Citation

Jordan S, Emery S, Bradshaw C, Watkins A, Friswell W. The impact of intrapartum analgesia on infant feeding. BJOG. 2005 Jul;112(7):927-34. — View Citation

Kumar M, Paes B. Epidural opioid analgesia and neonatal respiratory depression. J Perinatol. 2003 Jul-Aug;23(5):425-7. — View Citation

Lee BB, Ngan Kee WD, Lau WM, Wong AS. Epidural infusions for labor analgesia: a comparison of 0.2% ropivacaine, 0.1% ropivacaine, and 0.1% ropivacaine with fentanyl. Reg Anesth Pain Med. 2002 Jan-Feb;27(1):31-6. — View Citation

Loftus JR, Hill H, Cohen SE. Placental transfer and neonatal effects of epidural sufentanil and fentanyl administered with bupivacaine during labor. Anesthesiology. 1995 Aug;83(2):300-8. — View Citation

Lowe NK. The nature of labor pain. Am J Obstet Gynecol. 2002 May;186(5 Suppl Nature):S16-24. Review. — View Citation

Melzack R. The myth of painless childbirth (the John J. Bonica lecture). Pain. 1984 Aug;19(4):321-37. Review. — View Citation

Nikkola EM, Jahnukainen TJ, Ekblad UU, Kero PO, Salonen MA. Neonatal monitoring after maternal fentanyl analgesia in labor. J Clin Monit Comput. 2000;16(8):597-608. — View Citation

Poma S, Scudeller L, Gardella B, Broglia F, Ciceri M, Fuardo M, Pellicori S, Repossi F, Zizzi S, Noli S, Delmonte MP, Iotti GA. Outcomes of induced versus spontaneous labor. J Matern Fetal Neonatal Med. 2017 May;30(10):1133-1138. doi: 10.1080/14767058.2016.1205028. Epub 2016 Jul 13. — View Citation

Rayburn WF. Minimizing the risks from elective induction of labor. J Reprod Med. 2007 Aug;52(8):671-6. Review. — View Citation

Reynolds F. Labour analgesia and the baby: good news is no news. Int J Obstet Anesth. 2011 Jan;20(1):38-50. doi: 10.1016/j.ijoa.2010.08.004. Epub 2010 Dec 13. Review. — View Citation

Ruban P, Sia AT, Chong JL. The effect of adding fentanyl to ropivacaine 0.125% on patient-controlled epidural analgesia during labour. Anaesth Intensive Care. 2000 Oct;28(5):517-21. — View Citation

Russell R. The effects of regional analgesia on the progress of labour and delivery. Br J Anaesth. 2000 Jun;84(6):709-12. — View Citation

Siddik-Sayyid SM, Taha SK, Azar MS, Hakki MA, Yaman RA, Baraka AS, Aouad MT. Comparison of three doses of epidural fentanyl followed by bupivacaine and fentanyl for labor analgesia. Acta Anaesthesiol Scand. 2008 Oct;52(9):1285-90. doi: 10.1111/j.1399-6576.2008.01765.x. — View Citation

Simkin P, Bolding A. Update on nonpharmacologic approaches to relieve labor pain and prevent suffering. J Midwifery Womens Health. 2004 Nov-Dec;49(6):489-504. Review. — View Citation

Torvaldsen S, Roberts CL, Simpson JM, Thompson JF, Ellwood DA. Intrapartum epidural analgesia and breastfeeding: a prospective cohort study. Int Breastfeed J. 2006 Dec 11;1:24. — View Citation

Wang K, Cao L, Deng Q, Sun LQ, Gu TY, Song J, Qi DY. The effects of epidural/spinal opioids in labour analgesia on neonatal outcomes: a meta-analysis of randomized controlled trials. Can J Anaesth. 2014 Aug;61(8):695-709. doi: 10.1007/s12630-014-0185-y. Epub 2014 Jul 11. — View Citation

Wilson MJ, MacArthur C, Cooper GM, Bick D, Moore PA, Shennan A; COMET Study Group UK. Epidural analgesia and breastfeeding: a randomised controlled trial of epidural techniques with and without fentanyl and a non-epidural comparison group. Anaesthesia. 2010 Feb;65(2):145-53. doi: 10.1111/j.1365-2044.2009.06136.x. Epub 2009 Nov 12. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Labour analgesia quality: Change in verbal rating pain scale (VRS) after epidural placement	Quality of labour analgesia/pain scores will be assessed by the verbal rating pain scale (VRS) with a minimum score of 0 indicating "No Pain" and a maximum score of 10 indicating "Worst Possible Pain". Higher values closer to 10 indicate worse pain/poor analgesia. A score of 2 is indicative of "mild pain", a score of 4 is indicative of "moderate pain", a score of 6 is indicated of "severe pain", and a score of 8 is indicative of "very severe pain".; 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.	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	Total epidural opioid consumption	Total opioid consumption will be measured by reviewing the epidural pump and adding together the total opioid infused and number PCEA or documented epidural "top-ups" or boluses.	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.
Secondary	Incidence of failed/incomplete epidurals	Patient charts will be reviewed to look for any signs of a failed or incomplete/inadequate epidural (i.e. need to re-do epidural, concerns regarding incomplete block, need for multiple top-ups).	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.
Secondary	Neonatal well-being: Presence or Absence of Fetal Heart Tracing Abnormalities	Neonatal well-being will be assessed by monitoring for concerns charted about Fetal Heart Tracings. Specifically, patient charts will be reviewed to assess for concerns regarding early decelerations, late decelerations, and variable decelerations. The amount of decelerations will also be documented (if applicable).	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.
Secondary	Neonatal well-being: Apgar scores	Neonatal well-being will be assessed by recording Apgar scores at 1 minute following fetal delivery, and at 5 minutes following fetal delivery. The maximum and most reassuring Apgar score is 10 which indicates a neonate that is active, has a heart rate over 100 beats per minute, has a prompt response to stimulation, appears pink/well oxygenated and has a vigorous cry. In general, Apgar scores of 7 or higher are typically considered normal for a neonate and neonates with scores above 7 are unlikely to require resuscitative intervention.; Any Apgar score below 7 is abnormal and should alert the care team of the possible need for resuscitative intervention. A score of 4-6 is below normal and means the neonate will likely need medical intervention or resuscitation. Apgar scores of 1-3 are critically low and indicative of a need for resuscitative intervention and intensive care.	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.
Secondary	Neonatal well-being: Umbilical artery pH value	Neonatal well-being will be assessed by recording and documenting the umbilical artery vein pH lab value drawn at the time of fetal delivery/birth. A umbilical artery pH value < 7.0 will be considered as abnormal and indicative of pathologic fetal acidemia.	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.
Secondary	Neonatal well-being: Breast-feeding quality	Neonatal well-being will be assessed by reviewing postpartum patient charts to look for any documented consults to breastfeeding consultant (i.e. "yes" or "no" regarding the need for breastfeeding consultant). The number of breastfeeding consults will also be documented (if applicable).	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.
Secondary	Maternal well-being: Respiratory Rate	Maternal well-being will be assessed by recording and documenting the maternal respiratory rate at specific intervals (see Time Frame below). A respiratory rate less than 12 will be considered as abnormal and bradypneic. A respiratory rate greater than 25 will be considered as abnormal and tachypneic.	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
Secondary	Maternal well-being: Heart Rate	Maternal well-being will be assessed by recording and documenting the maternal heart rate at specific intervals (see Time Frame below). A heart rate less than 60 beats per minute will be considered as abnormal and bradycardic. A heart rate greater than 110 beats per minute will be considered as abnormal and tachycardic.	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
Secondary	Maternal well-being: Blood pressure	Maternal well-being will be assessed by recording and documenting the maternal blood pressure at specific intervals (see Time Frame below). Both systolic and diastolic blood pressures will be recorded. A systolic blood pressure less than 95 mmHg or a diastolic blood pressure less than 55 mmHg will be considered as abnormal and hypotensive. A systolic blood pressure greater than 140 mmHg or a diastolic blood pressure greater than 95 mmHg will be considered as abnormal and hypertensive.	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
Secondary	Maternal well-being: Oxygen Saturation (SpO2)	Maternal well-being will be assessed by recording and documenting the maternal oxygen saturation at specific intervals (see Time Frame below). A maternal oxygen saturation less than 94% will be considered as abnormal and indicative of hypoxia.	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