Authors

  1. Powell, Nancy D CRNA, DNP
  2. Riddle, Dru CRNA, DNP

Abstract

Review question/objective: In parturients who are in active first and second stages of labor, what is the effect of intravenous patient-controlled analgesia with remifentanil on the level of maternal satisfaction and pain reduction from baseline compared to intravenous fentanyl?

 

Background: Pain during childbirth has been around since the very first birth of a human. The attempts to alleviate pain during childbirth are long standing with efforts made by midwives, obstetrical nurses, obstetricians, and anesthesia providers.

 

Almost all women in labor experience pain at varying degrees which is mediated by uterine activity, cervical dilation, and fetal position. The process of childbirth is categorized into three stages. The first stage of labor is when the cervix slowly dilates, shortens and thins. Pain is usually felt in the abdomen and the lower back with each contraction. The pain typically intensifies as the cervix reaches full dilation and the fetus moves down in the pelvis towards the birth canal. The second stage of labor is when the cervix is fully dilated and effaced (shortened and thinned) and the fetus is pushed through the birth canal. Pain during this stage of labor is intensified further and is usually felt in the lower pelvic and vaginal areas. It then reaches to the perineum as final stretching occurs to accommodate the large head of the fetus. The third stage of labor is when the placenta is delivered and is associated with comparatively little pain.1

 

In recent years, continuous laboring epidural catheters (CLEs) have been a mainstay in the delivery of analgesia for the laboring parturient.2-5 They are the most effective and satisfying analgesic delivery method for the control of pain during labor.6,7 Although a proven, safe and effective method of pain control, CLEs are not an acceptable option for all.8 Many institutions may not have 24 hours a day availability of anesthesia providers to offer this option of pain relief during labor. Some laboring women may have infective processes, coagulopathies, spinal/neurological abnormalities, and other physiologic disorders that are contraindications to the placement of a CLE. Additionally, some women may be too fearful of potential complications while others are physically unable to cooperate for the time it takes to administer the CLE. The fear of potential complications is not unfounded, as the placement of the epidural does not come without risk. Incorrect CLE placement can result in intravascular injection, intraneural injection, or intrathecal injection all of which can have catastrophic consequences.9

 

Before the advent of CLEs, intravenous (IV) narcotics were the backbone of pain management for labor. IV narcotics are still currently in use on a regular basis for women who are in early labor, up to just a few hours before delivery. Narcotics are a powerful class of analgesics with many drugs available that have varying degrees of potency and duration. Commonly used narcotics for labor and delivery include morphine, meperidine, butorphanol, nalbuphine and fentanyl. The choice of which one to use is based on speed of onset, duration of action, associated side effects, provider preference and maternal preference. In spite of well-known sedation properties that exceed its analgesic properties, meperidine continues to be the most commonly used opioid worldwide during labor and delivery.6,8,10-12 This is mostly due to its ease of administration and cost effectiveness.3 In addition to the sedation properties being greater than the analgesic properties, it is well documented in the literature that meperidine causes significant neonatal respiratory depression.8,10,12 With these negative side effects in mind, studies recommend the use of fentanyl as the first line drug to be given for labor analgesia over meperidine.13,14 Fentanyl appears to be a better suited drug for labor, but is still associated with a 44% incidence of a moderately depressed neonate with low Appearance, Pulse, Grimace, Activity and Respiration (APGAR) scores.8 Standard obstetrical practice does not allow administration of either fentanyl or meperidine within two to four hours of delivery or after cervical dilation has reached eight centimeters. This leaves a void in pain relief options for parturients in the later stage of labor and delivery.

 

Patient controlled analgesia (PCA) is a method of drug delivery for pain control that is very familiar to most bedside practitioners. It is a useful strategy for providing pain relief during labor and delivery by establishing plasma levels of narcotics that the parturient can increase quickly and easily as the pain level increases.

 

Remifentanil was first introduced into the United States drug market in 1995 and has slowly found its way into use for labor and delivery. Remifentanil is an ultra short-acting and potent narcotic metabolized by non-specific tissue and plasma esterases. The hydrolysis of the ester link by tissue and plasma esterases affords lack of drug accumulation.15 It has been well documented in the literature that the fast onset and elimination of remifentanil matches well with the onset and duration of contractions during active labor making it an ideal choice for PCA during labor.5,16-18 Rapid elimination permits the titration of an infusion without the concern for prolonged duration of effect or drug accumulation. The safety of mother and neonate are of concern when considering which potent narcotic to administer. Numerous studies have since been published in support of using remifentanil PCA to effectively and safely reduce the pain of labor throughout its duration up to birth.8,10,14,19-26 Favorable neonatal outcomes and proven safety hold far greater implications than maternal efficacy when considering this analgesic for managing labor pain.

 

There is one systematic review published through the International Anesthesia Research Society that compares the effectiveness of pain control of remifentanil during labor to that of meperidine.24 The conclusion of this systematic review revealed remifentanil to be a better analgesic than meperidine and it provided better satisfaction scores. This is not surprising considering the well-known weak analgesic properties of meperidine.

 

There are two studies in the literature comparing the effectiveness of pain reduction and satisfaction of remifentanil and fentanyl during labor.6,12 Each study produced a different conclusion. A systematic review is proposed because of these differences and as a means to focus the body of knowledge concerning this question.

 

Preliminary literature searches have revealed no systematic reviews published comparing remifentanil PCA and fentanyl via any delivery method. Therefore, the purpose of this systematic review is to compare the effectiveness of remifentanil versus fentanyl when used for labor analgesia as measured by maternal satisfaction and reduction in pain score from baseline. The overall intent is to bring together the existing evidence on remifentanil use in labor to provide more insight in choosing the best treatment for intravenous pain management. The results of this systematic review could have an important impact on the decision making process concerning which analgesic to administer during labor. This is important in light of the favorable safety profile of remifentanil when compared to the significant neonatal depression associated with fentanyl. If the systematic review finds that maternal satisfaction and reduction in pain score are better when using remifentanil, a recommended change in practice would be offered which could result in increased safety for the neonate.

 

Article Content

Inclusion criteria

Types of participants

This review will consider studies that include parturients of 18 years and older who are either nulliparous or multiparous, who are of normal term, singleton gestation and deliver in an acute care setting or delivery center.

 

Types of intervention(s)/phenomena of interest

This review will consider studies that evaluate the use of intravenous remifentanil in comparison to intravenous fentanyl during first and second stages of labor.

 

Types of outcomes

This review will consider studies that include the following outcomes measures: level of maternal satisfaction based on subjective rating using a Likert scale or equivalent after delivery and pain score reduction from baseline at various points during labor assessed using a visual analogue scale.

 

Types of studies

This review will consider any existing evidence generated by study designs of prospective randomized controlled trials (RCT) and clinical controlled trials (CCT). In the absence of RCTs and CCTs, observational studies including cohort designs and case controlled designs will be included.

 

Search strategy

The search strategy for this review aims to find both published and unpublished studies in the English language. The timeframe is for studies published between January 1995 and January 2014. Since remifentanil debuted on the drug market in 1995, a search for studies earlier than 1995 presumably will yield no additional studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies.

 

The databases to be searched include:

 

MEDLINE

 

CINAHL

 

EMBASE

 

Clinical Key

 

ProQuest

 

Web of Science

 

The search for unpublished studies will include:

 

MEDNAR

 

New York Academy of Medicine Grey Literature Report

 

ProQuest database for dissertations and theses

 

Initial key words to be used will be:

 

Remifentanil AND patient controlled analgesia AND labor OR labor pain AND fentanyl

 

All studies identified during the databases search will be assessed for relevance to the review based on the information provided in the title, abstract, and descriptor/MeSH terms. A full report will be retrieved for all studies that meet the inclusion criteria. Studies identified from reference list searches will be assessed for relevance based on the study title.

 

Assessment of methodological quality

Quantitative papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to discussion and inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I ). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

 

Data collection

Quantitative data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II ). The data extracted will include specific details about the interventions, populations study methods, and outcomes of significance to the review question and specific objectives. For studies where there is missing or unclear data, an attempt will be made to contact primary authors for information.

 

Data synthesis

Quantitative papers will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Odds ratio (for categorical data) and weighted mean differences (for continuous data) and the 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square. Where statistical pooling is not possible, the findings will be presented in narrative form.

 

Conflicts of interest

No conflicts of interest exist.

 

References

 

1. Datta S, Bhavani SK, Scott S. Obstetric anesthesia handbook. 5th ed. New York: Springer Science+Business Media; 2010. [Context Link]

 

2. Hill D. Remifentanil patient-controlled analgesia should be routinely available for use in labour. Int J Obstet Anesth. 2008;17(4):336-9. [Context Link]

 

3. Ryan A. Labour analgesia guidelines for obstetrical practice reproductive care program of Nova Scotia [Internet]. Nova Scotia: [publisher unknown]; 2005 [updated 2005 Oct; cited 2013 Nov]. [Context Link]

 

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16. Ng TK, Cheng BC, Chan WS, Lam KK, Chan MT. A double-blind randomised comparison of intravenous patient-controlled remifentanil with intramuscular pethidine for labour analgesia. Anaesthesia. 2011; 66(9):796-801. [Context Link]

 

17. Volmanen PV, Akural EI, Raudaskoski T, Ranta P, Tekay A, Ohtonen P, et al. Timing of intravenous patient-controlled remifentanil bolus during early labour. Acta Anaesthesiol Scand. 2011;55(4):486-94. [Context Link]

 

18. Xu S, Shen X, Guo X, Shen R, Wang F. Effectiveness of remifentanil for labor pain control: a systematic review and meta-analysis. HealthMED. 2012; 6(7):2407-18. [Context Link]

 

19. Anderson D. A review of systemic opioids commonly used for labor pain relief. J Midwifery Womens Health. 2011; 56(3):222-39. [Context Link]

 

20. D'Onofrio P, Novelli AMM, Mecacci F, Scarselli G. The efficacy and safety of continuous intravenous administration of remifentanil for birth pain relief: an open study of 205 parturients. Anesth Analg. 2009;109(6):1922-4. [Context Link]

 

21. Hill D. The Use of Remifentanil in Obstetrics. Anesthesiology Clinics. 2008; 26(1):169-82. [Context Link]

 

22. Jost A, Ban B, Kamenik M. Modified patient-controlled remifentanil bolus delivery regimen for labour pain. Anaesthesia. 2013; 68(3):245-52. [Context Link]

 

23. Kan RE, Hughes SC, Rosen MA, Kessin C, Preston PG, Lobo EP. Intravenous remifentanil: placental transfer, maternal and neonatal effects. Anesthesiol. 1998; 88(6):1467-74. [Context Link]

 

24. Leong WL, Sng BL, Sia AT. A comparison between remifentanil and meperidine for labor analgesia: a systematic review. Anesth Analg. 2011; 113(4):818-25. [Context Link]

 

25. Shen MK, Wu ZF, Zhu AB, He LL, Shen XF, Yang JJ, et al. Remifentanil for labour analgesia: a double-blinded, randomised controlled trial of maternal and neonatal effects of patient-controlled analgesia versus continuous infusion. Anaesthesia. 2013; 68(3):236-44. [Context Link]

 

26. Volikas I, Butwick A, Wilkinson C, Pleming A, Nicholson G. Maternal and neonatal side-effects of remifentanil patient-controlled analgesia in labour. Br J Anaesth. 2005; 95(4):504-9. [Context Link]

Appendix I: Appraisal instruments

 

MAStARI appraisal instrument[Context Link]

Appendix II: Data extraction instruments

 

MAStARI data extraction instrument[Context Link]

 

Keywords: fentanyl; labor; labor pain; patient controlled analgesia; remifentanil