Anesth Analg 2001;92:1358-1359
© 2001 International Anesthesia Research Society
LETTERS
A Preliminary Investigation of Remifentanil as a Labor Analgesic
Srinivasan Dhileepan, FRCA, and
Richard G. W. Stacey, FRCA
Kingston HospitalKingston-upon-ThamesSurrey, UK
To The Editor: We read with interest the article by Olufolabi et al. (1) and wish to challenge their assertion that the use of remifentanil may be inappropriate for labor analgesia.
For the past 2-1/2 yr at Kingston hospital, we have used remifentanil for labor analgesia in cases in which regional analgesia is contraindicated (2). We find it extremely effective. We wish to suggest some reasons why our experience is different.
The authors’ maximum dose allowed was only 0.5 µg/kg per bolus. We start at this dose and increase by 50% if analgesia becomes insufficient. Several patients have had 1 µg/kg bolus doses toward the end of labor without the side effects encountered in this study. From the graphically represented consumption data presented for the four patients, it appears that the first patient used between 1.75–2.5 µg · kg-1 · h-1 and the other three patients received between 3–8 µg · kg-1 · h-1. The median consumption of remifentanil by patients at Kingston hospital has been 7 µg · kg-1 · h-1 (range, 5–17 µg · kg-1 · h-1). We feel that the authors did not increase the dose sufficiently to match the increasing pain as labor progresses. It is likely that the difference in consumption and our willingness to increase the dose are responsible for the difference in efficacy, rather than tolerance to the effects of remifentanil. Another contributing factor might be the administration of the drug by a third party.
This adds a communication lag to the inevitable delivery and onset delays. We have observed that when patients first start on the regimen it is difficult to provide analgesia in the early phase of the contraction. With tutoring, the patient can learn to anticipate the next contraction and to make an early effective demand. This learning is only possible if the contractions are regular and is unlikely with third party administration.
A third factor to explain the better performance may be the use of a 50:50 mix of oxygen and N2O (Entonox) as an adjunct when needed. We use oximetry throughout the infusion, and we have not observed any episodes of desaturation with this balanced approach.
In summary, we feel that the regimen failed because of inadequate dosing compounded by the delays associated with third-party administration. Patient-controlled analgesia when used for postoperative pain relief is very dependent on the size of the bolus (3), tending to fail if the bolus is too small or too large. It is likely that the same holds true for its use in labor analgesia. Because remifentanil does not accumulate in the fetus (4), the dose can be increased sufficiently to achieve analgesia. We therefore stress the need for a flexible approach with a cautious start, adequate monitoring, and a willingness to increase the dose to one that remains effective as labor progresses.
References
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Olufolabi AJ, Booth JV, Wakeling HG, et al. A preliminary investigation of remifentanil as labor analgesic. Anesth Analg 2000; 91: 606–8.[Abstract/Free Full Text]
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Jones R, Pegrum A, Stacey RGW. Patient-controlled analgesia using remifentanil in the parturient with thrombocytopenia. Anaesthesia 1999; 54: 461–5.[Web of Science][Medline]
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Owen H, Plummer JL, Armstrong I, Mather LE, Cousins MJ. Variables of patient-controlled analgesia. 1. Bolus size. Anaesthesia 1989; 44: 7–10.[Web of Science][Medline]
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Kan RE, Hughes SC, Rosen MA, et al. Intravenous remifentanil. Placental transfer, maternal and neonatal effects. Anesthesiology 1998; 88: 1467–74.[Web of Science][Medline]
Response
James D. Reynolds, PhD,
John V. Booth, MB, ChB, FRCA, and
Adeyemi J. Olufolabi, MB, ChB, FRCA
Division of Women’s AnesthesiaDepartment of AnesthesiologyDuke University Medical CenterDurham, NC
In Response: Drs. Lavand’homme, Veyckemans, and Roelants (1) have chosen to employ a remifentanil infusion combination of continual plus on-patient-demand boluses. We selected bolus administration (2) by itself because we wished to focus on remifentanil’s unique pharmacokinetics (i.e., rapid metabolic inactivation). With this dosing method, we hoped to produce an analgesic effect only when it was required. A continual infusion protocol, although seemingly effective in their hands, no longer provides a clear distinction between remifentanil and other opioids used as systemic labor analgesics (3). This was a distinction we were specifically trying to exploit by utilizing bolus deliveries at the onset of a uterine contraction.
Drs. Dhileepan and Stacey did bolus dose with remifentanil, apparently to good effect in three patients (4), but their suggestion that we should have continued to increase our dose in the face of maternal desaturation and nausea/vomiting seems a bit sophistic. In addition, their decision to include Entonox, with its potential to produce hypoventilation and hypoxemia (5), may warrant closer scrutiny (i.e., more patients studied) because of remifentanil’s own respiratory depressant actions.
Neither research groups’ more positive experience with this drug changes the fact that the four patients we studied withdrew because of the presence of opioid-related side effects in the absence of adequate pain control (2). However, one must always recognize the hazards of extrapolating results from small sample sizes. There are several issues regarding the use of remifentanil as a labor analgesic that cannot be addressed by our abbreviated study, by Dr. Lavand’homme et al.’s and Drs. Dhileepan and Stacey’s preliminary work, or by the case reports and abstracts cited in their letters, be they available before or after our communication was accepted for publication. Such issues include the rapid development of tolerance (6), the higher levels of remifentanil required by women (7), the severity of respiratory depression, the occurrence of side effects (contrary to what the first letter implies, the cited two abstracts do not report the incidence of nausea and vomiting), and the recent suggestion that remifentanil might be an inappropriate drug for providing "conscious sedation during painful procedures" (8).
An additional issue to consider is patient satisfaction. A parturient presented with the Hobson’s choice of remifentanil or nothing will no doubt have a different perspective of her labor analgesia than one for whom regional anesthesia is available. For the former situation it would appear that the most appropriate answer would come from a comparative study between remifentanil and fentanyl where all patients have been made aware that this is the only avenue of pain relief available to them. In the meantime, primum non nocere. As such, we currently have no plans to further utilize remifentanil on our labor and delivery floor. As this would not appear to be the case for Drs. Lavand’homme, Veyckemans, and Roelants, nor for Drs. Dhileepan and Stacey, we look forward to reading their completed studies in which some of the issues listed above will hopefully be expounded upon.
References
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Roelants F, De Frannceschi E, Lavand’homme P. Patient-controlled intravenous analgesia (PCIA) using remifentanil (R) for labor analgesia [abstract]. Anesthesiology 2000; 92: A63.
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Olufolabi AJ, Booth JV, Wakeling HG, et al. Preliminary investigation of remifentanil as a labor analgesic. Anesth Analg 2000; 91: 606–8.
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Nikkola EM, Ekkbblad UU, Kero PO, et al. Intravenous fentanyl PCA during labor. Can J Anaesth 1997; 44: 1248–55.[Web of Science][Medline]
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Jones R, Pegrum A, Stacey RGW. Patient-controlled analgesia using remifentanil in the parturient with thrombocytopenia. Anaesthesia 1999; 54: 461–5.
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Northwood D, Sapsford DJ, Jones JG, et al. Nitrous oxide sedation causes post-hyperventilation apnoea. Br J Anaesth 1991; 67: 7–12.[Abstract/Free Full Text]
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Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg 1998; 86: 1307–11.[Abstract]
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Drover DR, Lemmens HJM. Population pharmacodynamics and pharmacokinetics of remifentanil as a supplement to nitrous oxide anesthesia for elective abdominal surgery. Anesthesiology 1998; 89: 869–77.[Web of Science][Medline]
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Litman RS. Conscious sedation with remifentanil during painful medical procedures. J Pain Symp Manag 2000; 19: 468–71.
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