A comparison on the effect of remifentanil patient-controlled analgesia versus fentanyl via any delivery method on maternal satisfaction and pain reduction during labor: a systematic review protocol
Authors: Powell Nancy D , Riddle Dru 
Published: December 2014

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.