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© 2002 International Anesthesia Research Society
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Abstract |
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IMPLICATIONS: A 34-h remifentanil infusion was administered for labor analgesia in a patient with thrombocytopenia and renal insufficiency. Compared with other opioids, remifentanil may produce fewer cumulative effects during prolonged infusion because of its unique metabolism.
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Introduction |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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There are few options for labor pain management when regional analgesia is contraindicated. IV fentanyl or meperidine provides moderate analgesia, but side effects may occur after multiple doses (1,2). Like other µ-opioid receptor agonists, remifentanil produces analgesia, but it is uniquely metabolized by nonspecific esterases. We describe a 34-h IV remifentanil infusion for labor analgesia in a patient with severe antiphospholipid antibody syndrome, thrombocytopenia, renal insufficiency, and preeclampsia.
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Case Report |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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A 33-yr-old, 120-kg, G8P0 was admitted at 33 wk gestational age for severe epigastric pain. The patient had been diagnosed with antiphospholipid antibody syndrome and required heparin and aspirin throughout her pregnancy. On admission, laboratory studies revealed a positive antiplatelet immunoglobulin G antibody titer, a 64-s partial thromboplastin time, and 52 x 109/L platelets. Prednisone was initiated for presumed autoimmune thrombocytopenia. After 5 days, platelets decreased to 32 x 109/L, serum creatinine increased to 1.4 mg/dL, and labile hypertension developed. Liver enzymes and abdominal ultrasound were normal, but the decision was made to proceed with delivery because of deterioration in the maternal status.
The anesthesiology staff was consulted for pain management. After discussion with the patient, a continuous remifentanil infusion was initiated with a computerized syringe pump (Baxter PCA1; Baxter Health Care Corp., Deerfield, IL). Monitoring included noninvasive blood pressure, pulse oximetry, and capnography. Two 18-gauge peripheral IV catheters were placed: one for oxytocin, magnesium sulfate, and maintenance fluid administration and the other solely for remifentanil to prevent an accidental overdose with concomitant drug administration. Supplemental oxygen was administered by nasal cannula at 4 L/min, and a labor nurse was continuously present. End-tidal carbon dioxide was measured through a nasal cannula prong by introducing a truncated 14-gauge IV catheter connected by tubing to a capnograph, as previously described (3).
The initial remifentanil infusion, 0.05 µg · kg-1 · min-1, completely relieved the epigastric pain. With labor induction, however, the infusion was maintained between 0.1 and 0.13 µg · kg-1 · min-1 for 18 h. At this rate, the patient had mild discomfort with and slept between uterine contractions, being easily aroused except once, when she became somnolent with 9 breaths/min and an end-tidal carbon dioxide of 42 mm Hg. The infusion was decreased, and the patient awoke within 1–2 min. After 18 h, the patient’s cervix was dilated 3 cm, and she complained of increasing pain. The infusion was increased to 0.15–0.20 µg · kg-1 · min-1 and was maintained for an additional 15 h during active labor. Throughout, labor vital signs remained stable, with blood pressure 150–160/80–90 mm Hg, heart rate 80–90 bpm, 10–20 breaths/min, oxygen saturation 97%–99%, and end-tidal carbon dioxide 27–34 mm Hg. At one brief interval, when the medication pump became empty, the patient reported a verbal pain score of 10 of 10 (verbal pain scale, 0 = no pain, 10 = maximum pain) with contractions. Resuming the infusion decreased the verbal pain score to 4 of 10 throughout labor.
Thirty-three hours after the infusion was initiated, the patient’s cervix was completely dilated. The second stage of labor lasted 17 min. The infusion was decreased to 0.15 µg · kg-1 · min-1 1 min before spontaneous delivery and terminated 30 min later, after episiotomy repair. The male infant (2160 g) had Apgar scores of 5 and 7 at 1 and 5 min, respectively. Umbilical arterial and venous pH were 7.16 and 7.22, respectively, consistent with a mild acidosis. For several hours before delivery, the fetal heart rate tracing had deep variable decelerations, and a nuchal cord was evident at delivery. Newborn resuscitation consisted of nasopharyngeal suctioning and brief positive-pressure ventilation. Naloxone and subsequent oxygen were withheld, because respirations were adequate and the infant’s condition improved.
The remifentanil infusion lasted 34 h, and a total of 18 mg was administered. The infusion ranged from 0.05 to 0.2 µg · kg-1 · min-1. Although she was not completely pain free, the patient, her family, and the obstetric team were pleased with the degree of analgesia provided for labor.
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Discussion |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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There are three reports of remifentanil use during labor and no controlled studies (4–6). Thurlow and Waterhouse (4) used a 20-µg patient-controlled remifentanil bolus every three minutes in two laboring patients with thrombocytopenia. The infusion was three hours or less, and the individual dose did not exceed 1 mg. In another study, three patients self-administered remifentanil boluses (0.5–1.0 µg/kg) as needed every two minutes (5). Consumption ranged from 2.6 to 5.1 mg over 4 to 12 hours (average 426–1050 µg/h), and one patient experienced sedation and fetal bradycardia with 75-µg boluses (5). In the third study, intermittent remifentanil boluses were administered to four patients in labor (6). The first patient experienced inadequate analgesia by patient-controlled boluses (0.25 µg/kg) because of the small dose used and the five-minute lockout interval programmed into the infusion device. For this reason, the remaining three patients received remifentanil boluses (up to 0.5 µg/kg) by an anesthesiologist at the onset of each contraction. For each patient, pain initially decreased, but as labor progressed, analgesia was insufficient. When the remifentanil dose was increased, sedation and vomiting became problematic; thus, remifentanil was discontinued after two or three hours (6).
In this report, a continuous infusion was used because of the patient’s constant epigastric pain. In addition, there is evidence suggesting that continuous infusions may produce less sedation than larger intermittent boluses (7). A 1 µg/kg remifentanil bolus will provide intense analgesia by one minute, but the drug effects can last for three minutes, explaining why sedation can occur between uterine contractions (8). In our patient, analgesia was maintained during contractions without excess sedation between contractions. A continuous infusion with a small intermittent bolus may represent another dosing alternative, but in this case it was not considered because the continuous infusion was sufficient. Although other opioids could have been administered, remifentanil was selected for use in this case because of the patient’s worsening renal function and the possibility of a prolonged infusion.
Remifentanil is metabolized by nonspecific tissue esterases independent of renal function. The major metabolite is remifentanil acid, an opioid agonist 1:2000–1:4000 less potent than remifentanil (9). Unlike the parent compound, remifentanil acid depends on renal excretion (10). We were concerned that remifentanil acid might accumulate over time and potentiate the effects of remifentanil. Studies in patients with renal failure, however, have shown that at recommended doses, remifentanil acid is unlikely to reach clinically significant concentrations even after prolonged infusion (10).
IV opioid infusions during labor may produce maternal and neonatal respiratory depression. To reduce this risk, we measured maternal oxygen saturation and end-tidal carbon dioxide, and a labor nurse remained with the patient. Remifentanil-related respiratory depression can resolve quickly and spontaneously, as occurred in our patient, but it must be recognized and the dose decreased to prevent maternal and fetal compromise. The neonatal depression at delivery may have been associated with remifentanil. Remifentanil readily crosses the placenta (umbilical venous/maternal blood ratio 0.88 ± 0.78) but is quickly metabolized or redistributed by the fetus (umbilical artery/umbilical vein ratio 0.29 ± 0.07) (11). In this case, the rapid metabolism of remifentanil prevented the need for naloxone, but it may be preferable to discontinue remifentanil 15 minutes before delivery to minimize the incidence of newborn respiratory depression.
In summary, in this case remifentanil provided adequate labor analgesia for 34 hours. IV remifentanil may be appropriate for labor analgesia when regional anesthesia is contraindicated; however, it is not approved for obstetric use, and controlled studies should be performed before this technique is recommended.
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References |
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TopAbstractIntroductionCase ReportDiscussionReferences |
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- Rayburn WF, Smith CV, Parriott JE, Woods RE. Randomized comparison of meperidine and fentanyl during labor. Obstet Gynecol 1989; 74: 604–6.[Web of Science][Medline]
- Morley-Forster PK, Weberpals J. Neonatal effects of patient-controlled analgesia using fentanyl in labor. Int J Obstet Anesth 1998; 7: 103–7.[Medline]
- Gallacher BP. The measurement of end tidal carbon dioxide concentrations using modified nasal prongs in ophthalmologic patients under regional anesthesia. Reg Anesth 1991; 16: 189.
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Thurlow JA, Waterhouse P. Patient-controlled analgesia in labour using remifentanil in two parturients with platelet abnormalities. Br J Anaesth 2000; 84: 411–3.
[Abstract/Free Full Text] - Jones R, Pegrum A, Stacey RG. Patient-controlled analgesia using remifentanil in the parturient with thrombocytopaenia. Anaesthesia 1999; 54: 461–5.[Web of Science][Medline]
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Olufolabi AJ, Booth JV, Wakeling HG, et al. A preliminary investigation of remifentanil as a labor analgesic. Anesth Analg 2000; 91: 606–8.
[Abstract/Free Full Text] - Rosow CE. An overview of remifentanil. Anesth Analg 1999; 89 (Suppl 4): S1–3.
- Glass PSA, Gan TJ, Howell S. A review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesth Analg 1999; 89 (Suppl 4): S7–14.
- Buerkle H, Wilhelm W. Remifentanil for gynaecological and obstetric procedures. Curr Opin Anaesthesiol 2000; 13: 271–5.[Medline]
- Hoke JF, Shlugman D, Dershwitz M, et al. Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers. Anesthesiology 1997; 87: 533–41.[Web of Science][Medline]
- 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]
This article has been cited by other articles:
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  J. Waring, S. K. Mahboobi, K. Tyagaraj, and D. Eddi Use of Remifentanil for Labor Analgesia: The Good and the Bad Anesth. Analg., June 1, 2007; 104(6): 1616 - 1617. [Full Text] [PDF]
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T. A. Saunders and P. S.A. Glass A Trial of Labor For Remifentanil Anesth. Analg., April 1, 2002; 94(4): 771 - 773. [Full Text] [PDF]
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