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 Table of Contents  
REVIEW ARTICLE
Year : 2013  |  Volume : 3  |  Issue : 2  |  Page : 74-76

Remifentanil in labor


1 Department of Clinical Anesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA, USA
2 Department of Anesthesiology and Critical Care Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication19-Dec-2013

Correspondence Address:
Basavana Gouda Goudra
Department of Clinical Anesthesiology and Critical Care, Perelman School of Medicine, Philadelphia, PA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4472.123298

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  Abstract 

Remifentanil is in clinical use for over 15 years. In spite of its unparalleled popularity, largely due to its unique pharmacokinetics, its place in labor analgesia is yet to be determined. Narrow therapeutic window and ability to cause rapid and severe respiratory depression are some of the major setbacks. Need for close monitoring, at least in the initial implementation stage is mandatory. Education of the labor suite nurses along with innovative monitoring technique is needed to realize the full potential of remifentanil in the labor room.

Keywords: Remifentanil labor analgesia, intravenous labor analgesia, obstetric analgesia


How to cite this article:
Goudra BG, Singh PM. Remifentanil in labor. J Obstet Anaesth Crit Care 2013;3:74-6

How to cite this URL:
Goudra BG, Singh PM. Remifentanil in labor. J Obstet Anaesth Crit Care [serial online] 2013 [cited 2019 Dec 6];3:74-6. Available from: http://www.joacc.com/text.asp?2013/3/2/74/123298


  Introduction Top


Epidural analgesia has become the standard for managing labor pain for many decades. However, there are many situations in which epidural is either not available on time, ineffective or contraindicated. Although many alternatives are available, none come close to the efficacy of epidural. [1] In spite of its proven efficacy, obstetrics epidural has its own share of problems. Assisted vaginal birth, hypotension, motor blockade and urinary retention are more frequent with labor epidurals and as a result, cannot be ignored. Entonox seems to be the next preferred option in the United Kingdom. However, for safety reasons, the Federal Drug Administration never approved entonox in the United States. Moreover, the side effects of nitrous oxide - abdominal distension, nausea and drowsiness - are unpleasant and preferably are avoided. None of the non-pharmacological interventions such as hypnosis, biofeedback, intracutaneous or subcutaneous sterile water injection, immersion in water, aromatherapy, acupuncture or acupressure, massage, reflexology and other manual methods such as transcutaneous electrical nerve stimulation, match the quality of pain relief provided by labor epidural. [1] Intravenous opioids are probably the only realistic alternatives, which unfortunately do not come close to epidurals in providing labor pain relief. Pethidine, is still the most popular opioid, which is used worldwide for labor pain. [2] However, the arrival of remifentanil, an ultra-short acting opioid, has opened the door for even more possibilities. Although, remifentanil has been in clinical use for more than 15 years, its place in obstetrics, especially in labor pain management is yet to be clearly defined. With this in mind, an attempt is made to examine its current place in obstetrics armamentarium.


  Pharmacokinetics of Remifentanil Top


The fixed context sensitive half-life of remifentanil is a unique property. It is constant at 2-5 min and is independent of the duration of its infusion. [3],[4],[5] Nonetheless, pharmacokinetic properties in obstetrics that govern the materno-fetal drug transfer need to be understood. [6] The mean ratio of remifentanil from the umbilical vein to the maternal artery was reported to be about 0.88 ± 0.78 by Kan et al., this suggests a significant degree of placental transfer. The doses used in the study of 0.1 mcg/kg/min are unlikely to be exceeded in labor analgesia, even though higher doses may be necessary to provide analgesia for cesarean sections. However, as to be expected (given the nature of metabolism), the drug is metabolized in the fetus with no residual adverse neonatal effects. [3],[4]


  Opioids in Labor Top


Before discussing the role of remifentanil in labor analgesia, it is worth looking briefly at the existing role of opioids in labor. [1],[7] Pethidine, morphine and fentanyl have probably been studied the most. When administered by patient controlled analgesia (PCA), there were no differences between the various opioids in reducing the pain intensity. In one study, morphine and pethidine had no sizable analgesic effect and only sedation was notable. [8] With staff administration, fentanyl was found to be superior to pethidine in reducing the pain intensity. [9] Patient satisfaction was higher with pethidine when compared to that of morphine. Due to the long half-life of the active metabolite norpethidine, neonatal respiratory depression can persist for 3-5 days after birth. [10] Used as a patient controlled intravenous analgesic, pethidine resulted in lower APGAR scores in the neonate. [11] High lipophilicity of sufentanil is a notable disadvantage allowing significant placental transfer. Clearly, a search for an ideal intravenous analgesic to provide labor analgesia persists.


  Remifentanil in Labor Analgesia Top


It is clear from the foregoing discussion, that an effective alternative to epidural is needed. It is also clear that none of the opioids in popular use today meet the requirements of an ideal intravenous labor analgesic. One of the first papers to discuss the role of remifentanil as a possible labor analgesic was by Olufolabi et al.[12] They set out to study the safety and efficacy of remifentanil PCA as a labor analgesic in 20 patients. However, the study was stopped at the end of four cases for a variety of reasons. Firstly, the pain relief was inadequate, even with the maximum doses as per the protocol. Moreover, three patients developed oxygen desaturation, including partial respiratory obstruction. Three patients had nausea and vomiting. Facial itching occurred in all of the cases and generalized itching was noted in one patient. These findings were a setback for future use. The authors concluded from the experiences of the four patients that remifentanil is not suitable as a systemic analgesic, despite of its favorable pharmacokinetics. Subsequently, studies that are performed (with increasing experience in use of remifentanil) have been more encouraging. Blair et al., administered remifentanil PCA to 21 women in labor with at least a 3 cm cervical dilation. [13] The protocol allowed for a continuous background infusion of remifentanil, if necessary. A total of 2 out of the 21 patients, analgesia were completely inadequate. Four women had desaturations (>90%) that lasted for more than 15 s. They concluded that remifentanil PCA is most beneficial primarily for multiparous women. A bolus of 0.25-0.5 mcg/kg/min with a lockout of 2 min was concluded to be the effective dose. Some patients found it better than pethidine. However, as a safety measure an anesthetist and an attending mid-wife were present for the duration that the PCA was running.

A further study compared the efficacy of remifentanil with pethidine. [14] In a well-designed randomized trial, 36 women requesting pethidine were allocated into either a pethidine or a remifentanil group. Only women weighing between 50 and 100 kg were included in this study. After a dose finding exercise (5 mcg bolus at each contraction increasing until the contractions were pain free), a PCA regime that allowed 20 mcg bolus with a 3 min lockout was selected. Surprisingly, the lowest oxygen saturation of 89% was recorded in a woman who received pethidine. However, more women using remifentanil had lower saturation levels. Pain relief was significantly better in remifentanil group. The authors concluded that remifentanil is an acceptable alternative to pethidine.

Among the maternal side-effects, mild but statistically significant itching was the most common complication. [15] There was no significant increase in nausea. Cardiovascular instability or respiratory depression was also absent. Although others found some evidence of respiratory depression (one newborn required naloxone), Volikas et al., did not find any abnormality in Apgar scores at 1 and 5 min. [15]

It should be recognized that all the studies were done with an anesthesia provider monitoring the laboring parturient closely. A recent case report highlights the importance of any deviation. [16],[17] The women in this case report suffered from cardiac arrest, from what looked like respiratory depression leading to apnea. Although the women survived with no residual sequel, the authors highlighted the importance of avoiding administration of other opioids concomitantly and starting remifentanil PCA early. Nevertheless, monitoring laboring women receiving remifentanil infusions needs to be close and intensive. Many years ago, remifentanil was described as a drug that was too short acting for its own good. [18] At least in the setting of labor analgesia, it is not only short acting, but also has too narrowed of a therapeutic window to be safe. Monitoring needs to be as intense as in an operating room. As many nurses (called mid-wives in some countries) working in the labor areas are not used to (or understand) such monitoring, alternate and ingenious methods may be necessary. There are drawbacks to using end tidal carbon dioxide as a tool to monitor respiration. For one, the sampling cannula needs to be in an appropriate position for gas sampling. For many nurses, understanding end tidal gas monitoring itself could be a daunting task, though it can be taught and learnt. There are other ways of monitoring respiration. Impedance pneumograms and more recently, acoustic respiratory monitors are found to be reliable in other settings and are ideally suited for the respiratory monitoring of laboring women getting remifentanil. [19] A closed circuit camera system to monitor multiple patient's respirations should be considered, especially if remifentanil PCA can make inroads in an epidural-dominated area.

Finally, technical aspects of the administration have to be addressed meticulously. A dedicated intravenous cannula is mandatory. The remifentanil infusion should not be used in conjunction with any other infusion. The latter practice can potentially allow dangerous doses that can lead to a respiratory arrest.


  Conclusion Top


Clearly, there is a need for a viable alternative to epidural analgesia for labor. Epidural is costly, mainly because of the need of an anesthesiologist to perform and monitor its efficacy. Entonox and pethidine seem to be the only commonly used alternative methods. Entonx is neither very efficacious nor available in all countries. Remifentanil, although pharmacokinetically attractive, is unlikely to fill the void unless measures can be taken to ensure its safe administration. In fact, it could be dangerous in inexperienced hands and unenthusiastic staff. The level of training, motivation and dedication needed is beyond most maternity suites. The one-on-one supervision and monitoring is often difficult to achieve. A change in the culture of labor suites is required in order to make remifentanil an effective analgesic. Multiparous women with an uncomplicated pregnancy and normal expected course of labor might be suitable. In this patient population, advantages of remifentanil might outweigh the drawbacks. With experience, nurses might learn the skills necessary to use remifentanil, thereby avoiding the presence of an anesthesiologist. Then only it can make a significant impact.


  Acknowledgment Top


The authors would like to thank Amit K. Manjunath (premed student, Research Assistant), Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

 
  References Top

1.Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al. Pain management for women in labour: An overview of systematic reviews. Cochrane Database Syst Rev 2012;3:CD009234.  Back to cited text no. 1
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2.Bricker L, Lavender T. Parenteral opioids for labor pain relief: A systematic review. Am J Obstet Gynecol 2002;186:S94-109.  Back to cited text no. 2
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3.Egan TD. Pharmacokinetics and pharmacodynamics of remifentanil: An update in the year 2000. Curr Opin Anaesthesiol 2000;13:449-55.  Back to cited text no. 3
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4.Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, et al. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology 1993;79:881-92.  Back to cited text no. 4
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5.Michelsen LG, Hug CC Jr. The pharmacokinetics of remifentanil. J Clin Anesth 1996;8:679-82.  Back to cited text no. 5
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6.Kan RE, Hughes SC, Rosen MA, Kessin C, Preston PG, Lobo EP. Intravenous remifentanil: Placental transfer, maternal and neonatal effects. Anesthesiology 1998;88:1467-74.  Back to cited text no. 6
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7.Evron S, Ezri T. Options for systemic labor analgesia. Curr Opin Anaesthesiol 2007;20:181-5.  Back to cited text no. 7
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8.Olofsson C, Ekblom A, Ekman-Ordeberg G, Hjelm A, Irestedt L. Lack of analgesic effect of systemically administered morphine or pethidine on labour pain. Br J Obstet Gynaecol 1996;103:968-72.  Back to cited text no. 8
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9.Rayburn WF, Smith CV, Parriott JE, Woods RE. Randomized comparison of meperidine and fentanyl during labor. Obstet Gynecol 1989;74:604-6.  Back to cited text no. 9
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10.Belsey EM, Rosenblatt DB, Lieberman BA, Redshaw M, Caldwell J, Notarianni L, et al. The influence of maternal analgesia on neonatal behaviour: I. Pethidine. Br J Obstet Gynaecol 1981;88:398-406.  Back to cited text no. 10
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11.Volikas I, Male D. A comparison of pethidine and remifentanil patient-controlled analgesia in labour. Int J Obstet Anesth 2001;10:86-90.  Back to cited text no. 11
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12.Olufolabi AJ, Booth JV, Wakeling HG, Glass PS, Penning DH, Reynolds JD. A preliminary investigation of remifentanil as a labor analgesic. Anesth Analg 2000;91:606-8.  Back to cited text no. 12
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13.Blair JM, Hill DA, Fee JP. Patient-controlled analgesia for labour using remifentanil: A feasibility study. Br J Anaesth 2001;87:415-20.  Back to cited text no. 13
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14.Thurlow JA, Laxton CH, Dick A, Waterhouse P, Sherman L, Goodman NW. Remifentanil by patient-controlled analgesia compared with intramuscular meperidine for pain relief in labour. Br J Anaesth 2002;88:374-8.  Back to cited text no. 14
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15.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;95:504-9.  Back to cited text no. 15
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16.Marr R, Hyams J, Bythell V. Cardiac arrest in an obstetric patient using remifentanil patient-controlled analgesia. Anaesthesia 2013;68:283-7.  Back to cited text no. 16
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17.Kranke P, Smith AF. Cardiac arrest and remifentanil PCA. Anaesthesia 2013;68:640.  Back to cited text no. 17
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18.Smith MA, Morgan M. Remifentanil. Anaesthesia 1997;52:291-3.  Back to cited text no. 18
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19.Goudra BG, Penugonda LC, Speck RM, Sinha AC. Comparison of acoustic respiration rate, impedance pneumography and capnometry monitors for respiration rate accuracy and apnea detection during GI endoscopy anesthesia. Open J Anesthesiol 2013;3:74-9.  Back to cited text no. 19
    



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  In this article
Abstract
Introduction
Pharmacokinetics...
Opioids in Labor
Remifentanil in ...
Conclusion
Acknowledgment
References

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