The analgesic efficacy of remifentanil for labour. Systematic review of the recent literature.

Although epidural analgesia is still regarded as the gold standard for labour analgesia due to its efficacy, in cases of contraindication, systemic remifentanil is an alternative. Since the first demonstration of the safety of remifentanil in obstetric analgesia in 1996, this has been repeatedly confirmed for both mother and newborn. The aim of this meta-analysis is to evaluate recently published studies (up to December 2014) on the analgesic efficacy of remifentanil during labour (as a Visual Analogue Scale (VAS) decrease in the first hour by 2 or more).



Search of the US National Library of Medicine, National Institutes of Health (www.pubmed.gov), SCOPUS database (www.scopus.com) and Web of Science database (www.webofknowledge.com) using the key words "labour" and "remifentanil". 44 identified articles were included in the review and 15 published randomised controlled studies were incorporated into the meta-analysis. This was based on the fixed model and described by differences in the VAS between t=0 and t=1 hour after remifentanil administration using the 95% confidence interval (CI). The analysis was computed using the Comprehensive meta-analysis version 2.2.064.



The combined data from the meta-analysis showed a statistically significant decrease in VAS in the remifentanil group. From a comparison of the CIs of summary estimates with a cut-off decrease of VAS 2, for the fixed model, there was a statistically significantly greater decrease in VAS than the cut-off. In the systematic review, we describe possible modes of application, dosage and side-effects for mother, fetus/ newborn.



The meta-analysis presented here confirms that remifentanil for labour analgesia is effective but questions remain which can only be answered by further randomized trials.

Related papers:

title: [Peripartum period and hemophilia carriers].
abstract: Women who are carriers for hemophilia are usually considered as safe carriers. However, they can present hemorragic symptoms associated with low factor VIII or IX levels. During pregancy, factor VIII increases whereas factor IX does not. The peripartum period is at risk of increased bleeding in these women. Here are presented reports of clinical data concerning two hemophilia carriers with low factor VIII or IX (30-40%) during the peripartum period. They received remifentanil and ketamine for labor pain management because of contraindication of epidural and spinal analgesia. Delivery occured quickly but they presented immediate moderate postpartum haemorrage. They did not necessitate blood transfusion. The one with hemophilia A received desmopressin just after delivery and the other one received factor IX when she arrived in delivery room. Blood factor VIII or IX has to be assessed in these women with familial history of hemophilia and bleeding. During pregnancy, factor VIII increases and can be assessed many times during pregnancy expecting a level over 50%. Factor IX does not really increase during pregancy and hemorrage can occur. Epidural and spinal anesthesia seem to be contraindicated as far as recommandations are concerned. Coagulation factor substitution is a mean of increasing factor level before these anaesthesias and can be discussed for each case.

title: Intravenous patient-controlled analgesia for labour: a survey of UK practice
abstract: Although regional techniques offer superior analgesia during labour, many women receive other methods of pain relief. Furthermore, there is a specific need for analgesia in a small population of labouring women for whom regional techniques are contraindicated, unavailable or impossible to perform. We surveyed current UK practice of labour analgesia for such patients, with particular reference to the use of intravenous patient-controlled analgesia.  Following approval from the Obstetric Anaesthetists' Association, a questionnaire was sent to the lead anaesthetic consultants of 243 obstetric units in the United Kingdom. The questionnaire evaluated the availability of methods of pain relief other than regional blocks. Information was sought on patient-controlled intravenous analgesia regimens and patient monitoring.  A total of 159 questionnaires were returned giving a response rate of 65.4%. The majority of units that responded (95.5%) used either intramuscular pethidine or diamorphine. Nearly half (49%) offered patient-controlled intravenous analgesia for labour pain. One third of units (36%) had an analgesic protocol for women in whom regional anaesthetic techniques were contraindicated. With patient-controlled intravenous analgesia, remifentanil (34.6%) was the most commonly used opioid for live births while morphine (35.5%) was used more commonly for deliveries involving intrauterine deaths.  The survey demonstrated that, when regional techniques were contraindicated, patient-controlled intravenous opioid analgesia was employed in almost half of the units responding to the questionnaire.

title: [Obstetric analgesia in German clinics. Remifentanil as alternative to regional analgesia].
abstract: Epidural regional analgesia is still recommended as the gold standard for obstetric analgesia due to its high efficacy and less depressing effects to the central nervous system. However, if absolute or relative contraindications for a regional anesthetic technique are present, there is a need for an effective and safe alternative. This survey investigates the current use of intravenous opioids, with a focus on remifentanil as patient-controlled intravenous analgesia (PCIA), in obstetrics in German hospitals.



A questionnaire was sent to 930 anesthesia units. Data were collected and analyzed using SPSS statistical package (PASW Statistics 18.0). The questionnaire requested statistics on births, the existing alternative labor analgesic techniques, intramuscular or intravenous opioids, PCIA or other options. Furthermore, the questions focused on details regarding the use of intravenous opioids in conjunction with PCIA techniques.



Replies were received from 343 anesthetic departments (response rate 37%) and 281 clinics had an obstetric department and were included for further analysis. All clinics provided a 24 h epidural service and the most commonly used opioids were pethidine (19%), meptazinol (17%) and piritramide (16%) for intermittent intravenous/intramuscular administration. Only 0.9% of the clinics offered nitrous oxide as an alternative analgesic technique and 22 (8%) of the responding anesthetic departments offered PCIA. Remifentanil was the most popular choice in conjunction with PCIA (68%) for labor analgesia. Most hospitals offering PCIA continuously monitor oxygen saturation (91%) and the blood pressure (95%), whereas continuous electrocardiograms (18%) and clinical observation of the respiratory frequency (19%) were less commonly reported. However, most clinics offered one-to-one nursing for the parturient using an opioid PCIA.



This survey revealed that pethidine, meptazinol and piritramide are the most common opioids for opioid-based systemic labor pain relief in Germany. If PCIA is offered, remifentanil is the most popular opioid. However, only a few clinics are routinely using PCIA for obstetric analgesia. Furthermore the study showed that the current monitoring standards seem to have room for improvement with respect to safe administration of an opioid PCIA. The safety standards require continuous observation of the oxygen saturation, the possibility for oxygen supply, one-to-one nursing for a close clinical observation of the mother and the presence of an anesthetist during the initial titration phase to safely apply this technique. Applying these safety standards PCIA may prove a useful alternative for central neuraxial labor analgesia in those women who either do not want, cannot have or do not need epidural analgesia.

title: Neonatal depression after obstetrical analgesia with pethidine. the role of the injection‐delivery time interval and of the plasma concentrations of pethidine and norpethidine
abstract: Pethidine (100 mg) was administered i.m. to women in labor at different times before delivery. The interval before respiration in the newborn became sustained was shorter if pethidine was given less than one hour before delivery. The respiratory rate of the newborn increased after naloxone injection in 40 per cent of the cases, mostly when intrauterine exposure to pethidine exceeded one hour. The plasma concentrations of pethidine and norpethidine were measured in mother and newborn. The concentrations in the umbilical vein and artery indicated a continuous net transfer of pethidine from mother to fetus for approximately two hours. This correlates with the clinical finding of maximal neonatal depression 2–3 hours after maternal injection. The concentrations of norpethidine increased with a longer time interval between injection and delivery, but were probably too low to have any effect on the newborn. Neonatal depression seems to be related to the amount of unmetabolized pethidine that has been transferred from mother to fetus but not to norpethidine as had been suspected earlier.

title: Disposition of meperidine and normeperidine following multiple doses during labor. II. Fetus and neonate.
abstract: It has been suggested that continued diffusion gradients from mother to fetus would exist and that both meperidine and normeperidine would accumulate in the fetus following multiple doses of meperidine to the mother during labor. However, no pharmacokinetic data are available. Therefore, the purpose of this study was to document the disposition of meperidine and normeperidine in the fetus and neonate following multiple doses of meperidine to the mother over long time periods. Twelve infants were studied. The results show surprisingly high concentrations of both meperidine and normeperidine in fetal blood at delivery. In addition, the amount of normeperidine increased with time in umbilical cord blood, the ratio of normeperidine to meperidine increased with time, and the umbilical artery-to-vein ratio of meperidine (but not normeperidine) was greater than one following long drug-to-delivery intervals. The data also suggest that with long drug-to-delivery intervals the levels of normeperidine may become clinically important and that the elimination of both compounds by the neonate is prolonged. The study suggests that multiple doses to the mother over long time periods result in maximum accumulation of both meperidine and normeperidine in fetal tissues.

title: Effectiveness of intravenous meperidine for pain relief in the first stage of labour.
abstract: To determine the effectiveness and side effects of intravenous meperidine in labour pain relief.



A double blind, randomized controlled trial was conducted in 84 parturients, using normal saline as control. Visual analogue scale, postpartum parturients' opinion of effectiveness, sedative scores, nausea/vomiting, dizziness, delivery method, Apgar scores, and naloxone prescription were assessed.



There were no statistically significant differences between the mean and median of visual analogue scale of meperidine and control group. In addition, the sedative scores, nausea/vomiting and dizziness in the meperidine group occurred more than those in the control group significantly. Even mean of the pain increment in the meperidine group was less than those in the control group (p < 0.05). The parturients' opinion on the effectiveness of pain relief during labor within 24 hours of the first postpartum day was only 23.80 per cent in the meperidine group, however, it was statistically significantly different when compared to 7.10 per cent in the control group.



Intravenous meperidine exhibited the effectiveness of pain relief of only 23.80 per cent of the subjects, in addition, it may cause many side effects.

title: Lack of analgesic effect of systemically administered morphine or pethidine on labour pain
abstract: severe early onset pre-eclampsia. Magnesium levels were used to add a safety factor when the protocol was formulated in our unit, We find that serum levels of magnesium provide objective data about the therapy and now function more to assess undertreatment than overdose with subsequent adjustment of the infusion rate. We do not find a problem with the processing of the samples. The theoretical problem for the clinician who uses lower limb reflexes to assess toxicity of magnesium still exists when the epidural block may obliterate the tendon the reflexes and confound the diagnosis. The patient was not eclamptic and therefore we do not feel that it is necessary to provide evidence for serum monitoring of magnesium therapy. In fact, since its inception in our unit we have observed only two eclamptic fits in more than 20,000 deliveries. In addition, ldama and Lindow are under the misconception that we performed induction of labour in the reported case. To the contrary, this was a case of induced abortion with synthetic prostaglandins, which do not produce a physiological labour.

title: Preliminary Pharmacokinetics and Pharmacodynamics of an Ultra‐Short‐Acting Opioid: Remifentanil (GI87084B)
abstract: Remifentanil is a newly synthesized 4-anilidopiperidine with an ester side chain susceptible to esterase metabolism. We evaluated the safety, analgesic efficacy, and pharmacokinetics of remifentanil in 48 male volunteers. Volunteers were randomized to receive increasing doses of remifentanil, alfentanil, or placebo. Analgesic efficacy was evaluated by increasing tolerance to a spring-loaded rod measured at the tibia and sternum at multiple time points. Respiratory depression was measured by changes in arterial blood gas tensions and peripheral hemoglobin oxygen saturation. Hemodynamics were continuously monitored by means of an intra-arterial catheter. Both remifentanil and alfentanil produced a dose-dependent increase in analgesia and respiratory depression. Remifentanil was 20 to 30 times more potent (milligram to milligram) than alfentanil when assessed by either analgesic efficacy or respiratory measures. The pharmacokinetics of remifentanil were best described by a biexponential decay curve. Remifentanil had a small volume of distribution of 0.39 (SD, ±0.25) L/kg (alfentanil, 0.52 ± 2 L/kg), with a rapid distribution phase of 0.94 (SD, ±0. 57) min and an extremely short elimination half-life of 9.5 (SD, ±4) min compared with an elimination half-life of alfentanil of 58 (SD, ±7.6) min. The t1/2 ke0 (half-time for equilibration between plasma and the effect compartment) of remifentanil for analgesia was calculated as 1.3 min. Thus, remifentanil appears to have a pharmacologic profile similar to other potent μ agonists, but with exceptionally short-lasting pharmacokinetics, which is likely to make it a very useful opioid for clinical practice.

title: A Comparison of Remifentanil Parturient-Controlled Intravenous Analgesia with Epidural Analgesia: A Meta-Analysis of Randomized Controlled Trials
abstract: Epidural analgesia is generally accepted as the most effective form of pain relief during labor. Remifentanil patient-controlled IV analgesia (PCIA), which is less invasive than epidural analgesia, may be an attractive alternative. In this meta-analysis, we compared the efficacy and safety of the 2 analgesic techniques for labor pain. Databases of PubMed, EMBASE, and Cochrane Library were searched independently by 2 reviewers to retrieve eligible randomized controlled clinical trials. The primary end points were pain scores at 1 and 2 hours, and the secondary end points were nausea, vomiting, pruritus, and umbilical artery pH values. Mean difference (MD) or risk ratio with 95% confidence intervals (CIs) were calculated for each end point. GRADE profiler was applied to assess the quality of evidence. Five eligible trials were retrieved and analyzed. We found that parturients with remifentanil PCIA had higher visual analog scale (10-cm scale) pain scores than those who received epidural analgesia at 1 hour (MD = 1.9 cm; 95% CI, 0.5–3.3; I2 = 94%) and 2 hours (MD = 3.0 cm; 95% CI, 0.7–5.2; I2 = 89%) after initiation of analgesia. There was no statistical difference between epidural analgesia and remifentanil PCIA in the incidence of nausea, vomiting, pruritus, or umbilical artery pH values. However, the CIs are quite wide and contain clinically significant differences. According to GRADE profiler, most end points had moderate quality except that pain scores at 1 hour were of low quality. This meta-analysis suggests that remifentanil PCIA is not superior to epidural analgesia in analgesic efficacy during labor. Given the wide CIs of the pooled results for secondary maternal and neonatal outcomes, definite conclusions cannot be drawn for those outcomes. Further studies are still warranted to validate these conclusions.

title: Comparison of parturient - controlled remifentanil with epidural bupivacain and sufentanil for labour analgesia: randomised controlled trial.
abstract: Epidural analgesia (EA) has significant contraindications including coagulation disorders and parturient refusal. One alternative is intravenous self-administered analgesia using the ultra short-acting opioid remifentanil (rPCA). We compared the efficiency and safety of standard epidural analgesia with parturient-controlled intravenous analgesia using remifentanil as well as personal satisfaction.



We enrolled twelve ASA I classified women with singleton pregnancy who delivered vaginally in the period 3/2010-5/2010 and who received rPCA (n=12) in standard analgesic protocol: 20 µg boluses using PCA pump with a lockout interval of 3 min. The control group consisted of 12 pregnant women who received EA (n=12): 0.125% bupivacaine with sufentanil 0.5 µg/mL in top-up boluses every hour until delivery. Data were acquired from standard Acute Pain Service (APS) form and patient medical records (demographic, labour course parameters), Visual Analogue Scale (VAS), Bromage Scale (BS) and adverse effects of analgesia.



There were no demographic or labour course parameter differences between groups (P>0.05). The differences in VAS decrease (P=0.056) and parturient satisfaction (P=0.24) during the whole analgesia administration were statistically insignificant. The main limitation of the study was small sample and enrolment of healthy singleton pregnant women only.



Remifentanil use in obstetric analgesia is a viable alternative to EA, especially in cases of EA contraindications and parturient disapproval.

title: Intravenous Remifentanil: Placental Transfer, Maternal and Neonatal Effects
abstract: Remifentanil has not been studied in obstetric patients. This study evaluates the placental transfer of remifentanil and the neonatal effects when administered as an intravenous infusion.  Nineteen parturients underwent nonemergent cesarean section with epidural anesthesia and received 0.1 [micro sign]g [middle dot] kg‐1 [middle dot] min‐1 remifentanil intravenously, which was continued until skin closure. Maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood samples were obtained at delivery for analysis of drug concentrations of remifentanil, its metabolite, and blood gases. Maternal vital signs were monitored continuously, and pain and sedation levels were assessed intermittently. Apgar scores were obtained at 1, 5, 10, and 20 min, and Neonatal and Adaptive Capacity Scores were noted 30 and 60 min after delivery. Parturients and newborns were observed for at least 24 h after surgery for side effects.  The means and SDs of UV:MA and UA:UV ratios for remifentanil were 0.88 +/‐ 0.78 and 0.29 +/‐ 0.07, respectively. Mean clearance was 93 ml [middle dot] min‐1 [middle dot] kg‐1. The mean UV:MA and UA:MV ratios for remifentanil acid were 0.56 +/‐ 0.29 and 1.23 +/‐ 0.89, respectively. The mean MA (remifentanil acid):MA (remifentanil) ratio was 2.92 +/‐ 3.65. There were no adverse effects on the neonates, but there was a sedative effect and respiratory depressant effect on the mothers.  Remifentanil crosses the placenta but appears to be rapidly metabolized, redistributed, or both. Maternal sedation and respiratory changes occur, but without adverse neonatal or maternal effects.

title: A Randomized Controlled Trial of the Efficacy and Respiratory Effects of Patient-controlled Intravenous Remifentanil Analgesia and Patient-controlled Epidural Analgesia in Laboring Women
abstract: Safe and effective alternatives are required in labor when epidural analgesia is not appropriate. We hypothesized that patient-controlled IV remifentanil labor analgesia would not be inferior to patient-controlled epidural labor analgesia.This randomized nonblinded controlled noni

title: [French national survey on remifentanil utilisation for obstetrical peridural analgesia].
abstract: The last French survey on alternatives to neuraxial anaesthesia for labour pain was published in 1997. However, intravenous remifentanil has become increasingly used as an option for labour analgesia. We evaluated the use of remifentanil as an alternative to epidural analgesia in level 2 and 3 French maternities in 2009.



This was an internet-based French survey performed in 2009 including all level 2 and 3 maternities. Data recorded were maternity unit characteristic, alternatives to neuraxial analgesia used, and remifentanil administration protocols.



Two hundred and forty maternity units received the survey and 103 responses were completed. A written institutional alternative analgesia protocol for labour pain was present in 78%. Alternative labour analgesia included intermittent nitrous oxide inhalation (58%), intravenous nalbuphine (52%), patient-controlled intravenous administration of remifentanil (52%) and sufentanil (46%). Pethidine administration was reported by one maternity unit (1%). The bolus dose of remifentanil scheduled, and background infusion varied widely between maternity units. The analgesic efficacy of remifentanil used for labour pain was evaluated as moderate (55%) or good (43%). Two serious adverse events were reported.



Intravenous administration of remifentanil was largely reported as an alternative to neuraxial anaesthesia for labour pain. Although remifentanil administration was most often based on a local written protocol, bolus dose and background infusion varied widely between maternity units.

title: Patient-controlled intravenous analgesia as an alternative to epidural analgesia during labor: questioning the use of the short-acting opioid remifentanil. Survey in the French part of Belgium (Wallonia and Brussels).
abstract: Childbirth ranks among the most intense experiences of acute pain. Neuraxial analgesia (i.e. epidural or combined spinal-epidural technique) is the most effective way to relieve that pain but it is contraindicated or impossible to perform for some parturients. We designed a survey of the current use of analgesic alternatives to epidural analgesia (EA) for labor pain, specifically the use of opioid patient-controlled intravenous analgesia (PCIA), in the French part of Belgium (Wallonia and Brussels). A questionnaire was mailed to the departmental chair of the hospitals with an obstetric unit, both in university and non-university centers (total of 53 centers). The questionnaire evaluated the availability of EA, the alternatives used when EA was contraindicated, the use of opioid-based PCIA for labor analgesia as well as opioid preference and doses, and finally the reasons for not using opioid PCIA. The response rate was 67.5% (36 centers). Among the responding hospitals, EA was available for 68% (range 25-85%) of labors and deliveries. When EA was not available or contraindicated, a parenteral opioid (piritramide, tramadol or pethidine) was proposed in 19% (7/36) of the centers, Entonox in 11% (4/36), a pudendal block by obstetricians in 28% (10/36) and non-pharmacologic alternatives (i.e. hypnosis, sophrology, baths and massages) in 19% (7/36). In 28% (10/36) of the centers however, no analgesic alternative was proposed. Opioid PCIA was employed in 36% (13/36) of the centers and for an additional 11% (4/36) only in case of intrauterine death. Remifentanil was the first choice (76.5% of the PCIA), followed by sufentanil (23.5%). Other opioids (piritramide, morphine, fentanyl) and ketamine were also administered by PCIA. Forty-five percents of the centers reported never using opioid PCIA by either lack of knowledge (7%), fear of maternal or fetal side effects (48%) and unability to provide a correct supervision of the parturient during PCIA use (48%), opposition from the pediatricians or obstetricians (17%) or because they considered the technique as ineffective to relieve labor pain (17%). In conclusion, the survey demonstrated that, when EA is contraindicated, systemic opioid administered by PCIA is used in almost half of the centers (47%) and that remifentanil is the first choice, particularly when a live birth is expected.

title: Remifentanil Patient-Controlled Analgesia for Labour: A Complete Audit Cycle
abstract: Remifentanil patient-controlled analgesia (PCA) was introduced to a small maternity unit where an extensive epidural service was difficult to provide. This was a new service and the New Zealand College of Midwives had serious doubts about the efficacy and safety of remifentanil, so auditing its use was important. In a two-stage audit, clinical notes of 244 consecutive remifentanil users were studied between January 2008 and November 2009. We developed a questionnaire to assess the parturients’ satisfaction with remifentanil PCA and designed a proforma to evaluate it against four standards of best practice. During the two audit periods, timely commencement of PCA was achieved in 65% and 82% of cases, respectively. A 70% compliance rate with monitoring standards fell to 10% after the withdrawal of supervision by an acute pain team, but improved to 91% following implementation of regular midwifery training sessions and a redesigned partogram and prescription flowchart. Ninety-four percent of women rated remifentanil PCA as excellent, very good or good. Maternal side-effects were nausea, pruritus and drowsiness. A comparison of Apgar scores of consecutive neonates born by normal vaginal delivery to women receiving no analgesia, with those born to women using remifentanil PCA, demonstrated no difference. As a result of our audit, remifentanil PCA is now viewed by our midwives as an effective and safe method when accompanied by 1:1 care and appropriate monitoring. With our input other maternity units have introduced it, especially where epidural service provision is limited, and for patients in whom epidural analgesia is contraindicated.

title: Remifentanil patient-controlled analgesia for labour: optimizing drug delivery regimens
abstract: PurposeA pilot study was undertaken to compare the efficacy of two regimens of intravenous patient-controlled analgesia (PCA) with remifentanil for labour analgesia.MethodsTwenty term parturients requesting labour analgesia were randomized to receive one of two regimens of intravenous remifentanil. The initial settings in both groups consisted of an infusion of 0.025 μg·kg-1·min-1, a PCA bolus of 0.25 μg·kg-1 and a lockout interval of two minutes. In Group A, the infusion was increased in a stepwise manner from 0.025 to 0.05, 0.075 and 0.1 μg·kg-1·min-1 as required; the bolus was kept constant at 0.25 μg·kg-1. In Group B, the bolus was increased from 0.25 to 0.5, 0.75 and 1 μg·kg-1 as necessary; the infusion was kept constant at 0.025 μg·kg-1·min-1. Maternal pain, satisfaction and sedation scores, remifentanil requirement, and side effects were recorded.ResultsMean pain and patient satisfaction scores, and cumulative doses of remifentanil were similar in the two groups. The overall incidence of side effects was greater in Group B (P = 0.0007), with drowsiness observed in 100% of patients, as compared to 30% in Group A (P = 0.003). The minimum oxygen saturation levels were 94.3% ± 2.6% and 92.2% ± 3.8% in Groups A and B respectively (P = 0.19).ConclusionsAlthough pain and satisfaction scores were similar in both groups, the regimen used in Group A was associated with fewer side effects compared to the Group B dosing regimen. This pilot study suggests that remifentanil intravenous PCA is efficacious for labour analgesia as a bolus of 0.25 μg·kg-1, with a lockout interval of two minutes and continuous infusion of 0.025-0.1 μg·kg-1·min-1. The potential for respiratory depression mandates close respiratory monitoring. Large-scale trials to evaluate safety issues are warranted.RésuméObjectifUne étude pilote a été entreprise afin de comparer l’efficacité de deux régimes intraveineux d’analgésie contrôlée par le patient (ACP) avec du rémifentanil pour le travail obstétrical.MéthodeVingt parturientes à terme demandant une analgésie pour le travail ont été randomisées à recevoir l’un de deux régimes de rémifentanil intraveineux. Les réglages de base dans les deux groupes consistaient en une perfusion de 0,025 μg·kg-1 ·min-1, un bolus ACP de 0,25 μg·kg-1 et un intervalle d’interdiction de deux minutes. Dans le groupe A, la perfusion a été augmentée par paliers de 0,025 à 0,05, 0,075 et 0,1 μg·kg-1 ·min-1 au besoin; le bolus a été maintenu constant à 0,25 μg·k-1. Dans le groupe B, le bolus a été augmenté de 0,25 à 0,5, 0,75 et 1 μg·kg-1 au besoin; la perfusion a été maintenue constante à 0,025 μg·kg-1·min-1. Les douleurs maternelles, les scores de satisfaction et de sédation, les besoins en rémifentanil et les effets secondaires ont été enregistrés.RésultatLes scores moyens de douleur et de satisfaction des patientes ainsi que les doses cumulatives de rémifentanil ont atteint des résultats similaires dans les deux groupes. L’incidence totale d’effets secondaires était plus élevée dans le groupe B(P = 0,007), avec des cas de somnolence chez 100 % des patientes comparativement à 30 % dans le groupe A (P = 0,003). Le minimum de saturation en oxygène était de 94,3 % ± 2,6% et 92,2 % ± 3,8 % dans les groupes A et B respectivement (P = 0,19).ConclusionBien que les scores de douleur et de satisfaction étaient similaires dans les deux groupes, le régime utilisé par le groupe A a été associé à moins d’effets secondaires que le régime de dosage du groupe B. Cette étude pilote suggère que l’ACP intraveineuse au rémifentanil est efficace pour l’analgésie pour le travail en bolus de 0,25 μg·kg-1, avec un intervalle d’interdiction de deux minutes et une perfusion continue de 0,025 - 0,1 μg·kg-1 ·min-1. Toutefois, un monitorage respiratoire attentif est nécessaire en raison du potentiel de développement de dépressions respiratoires. Des essais à grande échelle pour évaluer les questions d’innocuité sont requis.

title: Patient-controlled intravenous analgesia with remifentanil in nulliparous subjects in labor
abstract: in this study we controlled the efficiency and safety of using remifentanil combined with two different supplementary background infusions for labor analgesia in nulliparous patients.  60 subjects were allocated to two groups. After programming the patient-controlled analgesia device to deliver a fixed load and demand doses of intravenous remifentanil for all subjects, group r (n = 30) received a background infusion of remifentanil 0.1 μg/kg/min and group R (n = 30) received a supplementary infusion of remifentanil 0.15 μg/kg/min. Visual analogue scale for analgesia, hemodynamic parameters, sedation scales and fetal heart rates were recorded at the 5th, 10th, 20th and 30th min of the study and measurements continued every 15 min during 90 min of labor and delivery. Side effects, Apgar and satisfaction scores were obtained for every subject.  visual analogue scale scores of group R were significantly lower than those of group r throughout labor and delivery (p < 0.05). Hemodynamic parameters and fetal heart rates of the two groups were not different (p > 0.05). Most subjects were awake and only nausea was obtained (p > 0.05). The increase in the Apgar and satisfaction scores was not statistically significant (p > 0.05).  it was determined that remifentanil with a 15-μg demand dose and 0.15 μg/kg/min supplementary continuous infusion is an effective choice for patient-controlled analgesia during labor in nulliparous subjects.

title: Patient controlled analgesia for labour: a comparison of remifentanil with pethidine *
abstract: We compared the analgesic efficacy and safety of remifentanil and pethidine via patient controlled analgesia for women in established uncomplicated labour. Women received either remifentanil 40 μg with a 2‐min lockout (n = 20) or pethidine 15 mg with a 10‐min lockout (n = 19). Visual analogue scores for pain during the study and for overall pain were similar for both groups (mean (SD) 6.4 (1.5) cm for remifentanil and 6.9 (1.7) cm for pethidine). The area under the curve for visual analogue scores of satisfaction with analgesia was higher for remifentanil than for pethidine (p = 0.001). Maternal arterial oxygen saturation was similar in both groups. Neurologic and Adaptive Capacity Scores at 30 min were higher for remifentanil than for pethidine (median (interquartile range [range]) 36 (34.5–37 [32–39]) vs 34 (33–35 [30–35]), respectively; p = 0.003).

title: Obstetric analgesia: a comparison of patient-controlled meperidine, remifentanil, and fentanyl in labour.
abstract: To compare the analgesic efficacy of remifentanil with meperidine and fentanyl in a patient-controlled setting (patient-controlled analgesia, PCA).



Parturients (n=159) were randomly assigned to receive remifentanil (n=52), meperidine (n=53), or fentanyl (n=54). Pain scores and an observer sedation scores were assessed hourly. Fetal outcome was evaluated with Apgar score, cord blood gas analysis and the Neurologic and Adaptive Capacity Score.



Pain scores decreased in all groups, the decrease varying from mild to moderate, average pain scores remaining above 4.5 cm in all groups. Remifentanil PCA was associated with the greatest decrease in pain scores, but the difference was significant only at 1 h. Pain scores returned towards baseline over time; 3 h after the initiation of treatment, pain scores no longer differed significantly from baseline values in any of the groups. Significantly more parturients receiving meperidine crossed over to epidural analgesia. Overall satisfaction scores were higher with remifentanil, but remifentanil produced more sedation and itching. More periods of desaturation (Sa(o(2)) <95%) were observed during administration of remifentanil and fentanyl. There were no significant differences in fetal outcome between the three groups.



The efficacy of meperidine, fentanyl, and remifentanil PCA for labour analgesia varied from mild to moderate. Remifentanil PCA provided better analgesia than meperidine and fentanyl PCA, but only during the first hour of treatment. In all groups, pain scores returned to pre-treatment values within 3 h after the initiation of treatment.

title: A randomised comparison of intravenous remifentanil patient-controlled analgesia with epidural ropivacaine/sufentanil during labour.
abstract: The μ-opioid agonist remifentanil has a rapid onset and offset and a short half-life making it an attractive option for intravenous patient-controlled labour analgesia. We aimed to compare the efficacy of intravenous remifentanil patient-controlled analgesia with epidural ropivacaine/sufentanil during labour.



Parturients were randomly assigned to receive intravenous patient-controlled analgesia with remifentanil (n=10) or epidural analgesia (n=10). Pain and satisfaction scores were assessed every hour by means of visual analogue scale, together with an observer sedation score. Side effects and neonatal outcome were noted.



After one hour, visual analogue pain scores had decreased significantly in both groups (remifentanil: -3.8 ± 2.6, P<0.01; epidural -6.7 ± 2.0, P<0.01). The decrease in pain scores in the epidural group was significantly greater than the remifentanil group at all time intervals. The decrease in pain scores was sustained in the epidural group whereas in the remifentanil group pain scores increased over time. Oxygen saturation was significantly lower in the remifentanil group after one hour of treatment compared to the epidural group (95.2 ± 2.4% vs. 99.0 ± 1.1%, P<0.01). Patient satisfaction scores during and after delivery were similar in both groups. No differences were found in neonatal outcome.



In the 20 patients recruited to this study, pain relief in labour with epidural ropivacaine/sufentanil was more effective than with intravenous remifentanil patient-controlled analgesia.

title: Labor analgesia in preeclampsia: remifentanil patient controlled intravenous analgesia versus epidural analgesia.
abstract: Epidural analgesia is considered to be the preferred method of labor analgesia in preeclamptic patients. Systemic opioids are another good effective, easy to administer alternative but may cause maternal and fetal respiratory depression. Remifentanil's rapid onset and offset of effects, should make it an ideal drug for the intermittent painful contraction during labor.  30 preeclamptic patients were randomly assigned to one of two equal groups; Epidural Group: received epidural analgesia according to a standardized protocol using bupivacaine plus fentanyl. REMIFENTANIL GROUP: PCA was set up to deliver remlfentanil 0.5 microg/kg as a loading bolus infused over 20 seconds, lockout time of 5 minutes, PCA bolus of 0.25 microg/kg, continuous background infusion of 0.05 microg/kg/min, and maximum dose is 3 mg in 4 hours. Women were advised to start the PCA bolus when they feel the signs of a coming uterine contraction.



All women demonstrated a significant decrease in VAS score in the first hour after administration of analgesia (P < 0.05). Analgesic quality as regard Visual Analog Pain Scores, sedation score, and post-delivery patient satisfaction in both groups, are comparable (P > 0.05). PCA remifentanil infusion until time of delivery produce no observable maternal, fetal or neonatal side effects (P < 0.05).



PCA intravenous remifentanil is an effective option for pain relief with minimal maternal and neonatal side effects in labor for preeclamptic patients with contraindications to epidural analgesia or requesting opioid analgesia.

title: The effects of remifentanil or acetaminophen with epidural ropivacaine on body temperature during labor
abstract: PurposeEpidural analgesia is associated with hyperthermia during labor and presumably causes it, although no convincing mechanism has been postulated. It seems likely that fever associated with pyrogenic factors related to labor is suppressed by opioids, whereas it is expressed normally in patients given epidural analgesia. We examined this hypothesis and the possible etiology of temperature elevation in labor.MethodsIn this prospective, randomized, controlled study, we assessed 201 parturients during spontaneous labor. Analgesia was randomly provided with one of four treatment groups: (1) epidural ropivacaine alone, (2) IV remifentanil alone, (3) epidural ropivacaine plus IV remifentanil, and (4) epidural ropivacaine plus IV acetaminophen. At randomization, patients were normothermic. Intrapartum hyperthermia (≥38°C) was correlated to the analgesic technique.ResultsThe maximum increase in oral temperature was greatest in the ropivacaine group (0.7 ± 0.6°C) and least in the remifentanil group (0.3 ± 0.4°C; P = 0.013). The percentage of patients who became hyperthermic (≥38°C) during the first 6 h of labor was greatest in the ropivacaine group (14%) and least in the remifentanil-alone group (2%), but the difference was not statistically significant. The maximum forearm-finger gradients were lower (less vasoconstriction) in the remifentanil group when compared to the gradients in patients with epidural analgesia (1.4 ± 1.8 vs 3.0 ± 1.7, respectively; P < 0.001).ConclusionOur results are consistent with the theory that low-dose opioids inhibit fever in patients not given epidural analgesia. However, in view of the negative results, the hypothesis of epidural-induced hyperthermia may be questionable.

title: Remifentanil: A Novel Systemic Analgesic for Labor Pain
abstract: In a double-blind, randomized, controlled clinical trial, we compared the analgesic effect of remifentanil in patient-controlled IV analgesia (PCIA) during labor and delivery with the effect of an IV infusion of meperidine. Eighty-eight healthy term parturients who requested IV analgesia for labor pain were enrolled in the study and were randomly assigned to receive either increasing doses (0.27–0.93 &mgr;g/kg per bolus) of PCIA remifentanil (n = 43) or an IV infusion of meperidine 150 mg (range, 75–200 mg) per patient (n = 45). Remifentanil by the PCIA device was more effective and reliable analgesia for labor and delivery than IV infusion of meperidine. The visual analog score was lower (35.8 ± 10.2 versus 58.8 ± 12.8; P < 0.001) and the patient satisfaction score higher (3.9 ± 0.6 versus 1.9 ± 0.4; P < 0.001), with less of a sedative effect (1.2 ± 0.1 versus 2.9 ± 0.1; P < 0.001) and less hemoglobin desaturation (97.5% ± 1.0 versus 94.2% ± 1.5; P < 0.007). The percentage of analgesia failure (the rate of crossover from opiate to epidural analgesia) was less for remifentanil compared with meperidine (10.8% versus 38.8%; P < 0.007). There were no significant differences between groups in the mode of delivery or neonatal outcome. There were fewer nonreassuring abnormal fetal heart rate patterns, i.e., higher variability and reactivity with fewer decelerations, under remifentanil therapy as compared with meperidine (P < 0.001). In conclusion, an intermittent incremental regimen with repeated small-dose PCIA boluses of remifentanil provided effective and reliable analgesia during labor and delivery.

title: Neuraxial analgesia versus intravenous remifentanil for pain relief in early labor in nulliparous women
abstract: ObjectiveTo assess if there is a difference in duration of labor, the mode of delivery, average Visual Analog Scale (VAS) pain scores, maternal overall satisfaction with analgesia, side effects and neonatal outcomes in nulliparous women who received early labor analgesia with either epidural, patient-controlled IV analgesia (PCIA) with remifentanil or combined spinal–epidural (CSE) techniques.Study designThis is a prospective randomized interventional study.Subjects and methodsThe study included 1,140 healthy nulliparous women (with term, singleton pregnancies) early in labor, requesting labor analgesia, during the period from September 2009 to August 2011 at TAIBA Hospital in Kuwait. The participants were randomized to receive either epidural analgesia (Group I), or PCIA with remifentanil (Group II) or CSE analgesia (Group III). The primary outcome was the rate of cesarean delivery.ResultsCSE analgesia was associated with a statistically highly significant decrease in labor duration (from analgesia to vaginal delivery), duration of latent and active phases of the first stage, and duration of the second stage of labor, average VAS pain scores, and a highest maternal overall satisfaction score with analgesia (P < 0.01) as compared to epidural analgesia or PCIA with remifentanil.ConclusionIn terms of labor duration, average VAS pain scores, and maternal overall satisfaction score with analgesia, CSE analgesia is superior to that provided by epidural analgesia or PCIA with remifentanil for pain relief in early labor in nulliparous women. However, there were no differences in the mode of delivery, side effects or neonatal outcomes between the three techniques.

title: A double‐blind randomised comparison of intravenous patient‐controlled remifentanil with intramuscular pethidine for labour analgesia *
abstract: In a prospective, double‐blind, randomised controlled trial, we compared the efficacy of patient‐controlled analgesia using remifentanil (25–30 μg per bolus) with intramuscular pethidine (50–75 mg) for labour analgesia in 69 parturients. Parturients receiving patient‐controlled analgesia reported less pain than those receiving intramuscular pethidine throughout the study period (p < 0.001), with maximal reduction in visual analogue pain score at 2 h after commencement of analgesia (mean (SD) 20 (17) in the patient‐controlled analgesia group and 36 (22) in the intramuscular pethidine group. The median (95% CI) time to the first request for rescue analgesics was significantly longer with patient‐controlled analgesia (8.0 (6.8–9.2) h) compared with intramuscular pethidine (4.9 (3.8–5.4) h, p < 0.001). Maternal satisfaction scores were also higher with remifentanil compared with intramuscular pethidine (p= 0.001). There was no report of sedation, aponea or oxygen desaturation in either group, and Apgar scores were similar between groups. We conclude that patient‐controlled analgesia with remifentanil provides better labour analgesia and maternal satisfaction than intramuscular pethidine. At this dose, maternal and fetal side effects were uncommon.

title: Remifentanil by patient-controlled analgesia compared with intramuscular meperidine for pain relief in labour.
abstract: The pharmacokinetics of remifentanil suggests that it may be suitable for analgesia during labour.



In an open pilot study, 36 women requesting meperidine for analgesia were recruited early in labour and randomized to receive either meperidine i.m. or remifentanil given as patient-controlled analgesia (PCA). Pain severity, sedation and anxiety were assessed with visual analogue scales and overall effective analgesia was assessed by the woman and midwife.



The pain scores were lower in the remifentanil group: median pain score at 60 min was 72 mm for meperidine and 48 mm for remifentanil (P=0.004) and median maximum pain score during the first 2 h was 82.5 mm for the meperidine group and 66.5 mm for the remifentanil group (P=0.009). Both the midwives' and the women's assessments of overall effective analgesia were higher in the remifentanil group [Likert scale (5 = excellent to 1 = poor): chi2=12.10, P=0.002 for mothers' assessment; chi2=12.80, P=0.002 for midwives' assessment].



In this pilot study, remifentanil by PCA gave better pain relief to mothers in labour than intramuscular meperidine. However, remifentanil is a potent respiratory depressant and adequate continuous monitoring is necessary.

title: Labour analgesia: a randomised, controlled trial comparing intravenous remifentanil and epidural analgesia with ropivacaine and fentanyl
abstract: To compare the analgesic efficacy and side-effects of remifentanil intravenous patient-controlled analgesia (IVPCA) with walking epidural analgesia (EDA) during labour.  Thirty-nine parturient patients of mixed parity, with normal singleton pregnancies, were randomised to receive either remifentanil IVPCA (RA group) or EDA (EA group). The epidural solution contained ropivacaine 1 mg ml−1 and fentanyl 2 &mgr;g ml−1, and the initial dose was 10 ml h−1. Starting bolus of remifentanil was 0.15 &mgr;g kg−1, with subsequent steps of 0.15 &mgr;g kg−1. Lock-out time was 2 min, bolus infusion speed 2 ml min−1 (100 &mgr;g min−1) and there was no background infusion. Visual analogue scale was used for pain assessment. Maternal heart rate, blood pressure, oxygen saturation, respiratory rate, sedation, nausea/vomiting, itching, satisfaction and fetal/neonatal outcome were recorded.  Thirty-seven parturient patients were analysed. Both treatments provided good analgesia, but with higher pain scores in the RA group. Pain reduction at the end of first and during second stage and maximum pain reduction were similar (RA/EA group): 27/26 (P = 0.920), 31/29 (P = 0.909) and 61/59 (P = 0.855), respectively. Maternal satisfaction was similar. Two parturients receiving remifentanil (6%) converted to epidural, one because of inadequate analgesia. Remifentanil produced more maternal sedation, desaturation (SaO2 < 92%) and need for supplemental oxygen. Neonatal outcome was reassuring. Highest mean total dose of remifentanil was 0.70 &mgr;g kg−1 (range 0.30–1.05).  Remifentanil IVPCA and epidural provided effective analgesia, with high maternal satisfaction scores and reassuring neonatal outcome. Remifentanil produced more maternal sedation and oxygen desaturation. Close monitoring is, therefore, mandatory.

title: A comparison of pethidine and remifentanil patient-controlled analgesia in labour.
abstract: We conducted a double-blind randomised controlled trial comparing the efficacy of analgesia during labour of remifentanil and pethidine. Nine women were randomised to receive an i.v. bolus of remifentanil 0.5 microg.kg(-1)with a lockout period of 2 min and eight women were randomised to receive a bolus of pethidine 10 mg with a lockout period of 5 min. A visual analogue scale (VAS) scoring system was used to assess the level of pain hourly throughout the first and second stages of labour and a score was recorded within half an hour of delivery for the level of pain overall throughout labour (post delivery score). The study was terminated after 17 subjects, on agreement with the local ethics committee, due to concern with the poor Apgar scores in the pethidine group. With the data available, we demonstrated significantly lower mean hourly and post delivery VAS scores for pain in the remifentanil group (P < 0.05). The 1 and 5 min Apgar scores were significantly lower in the pethidine group compared with the remifentanil group (P < 0.05). This preliminary study suggests that remifentanil may have a use as patient-controlled analgesia for women in labour.

title: Comparison of remifentanil and nitrous oxide in labour analgesia
abstract: We compared the efficacy and side‐effects of remifentanil with those of nitrous oxide during the first stage of labour.

title: Intravenous remifentanil vs. epidural levobupivacaine with fentanyl for pain relief in early labour: a randomised, controlled, double‐blinded study
abstract: We hypothesised that intravenous patient‐controlled analgesia (IV PCA) with remifentanil could provide as satisfactory pain relief for labour as epidural analgesia.

title: A Comparison Between Remifentanil and Meperidine for Labor Analgesia: A Systematic Review
abstract: Remifentanil is an ultrashort-acting opioid with favorable pharmacokinetic properties that make it suitable as a labor analgesic. Although it crosses the placenta freely, it is eliminated quickly in the neonate by rapid metabolism and redistribution. We aimed to determine whether remifentanil compared with meperidine is effective in reducing pain scores in laboring parturients. Other effects on the mother, the labor process, and the neonate were also examined. MEDLINE, CINAHL, Embase, Cochrane CENTRAL, and Maternity and Infant Care databases were searched without language restriction using multiple keywords for labor analgesia, remifentanil, and meperidine. Published abstracts from 5 key research meetings and references from retrieved articles were examined for additional studies. Randomized controlled trials in laboring parturients comparing remifentanil with meperidine were selected. Risk of bias was assessed using criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed for adequacy of sequence generation, allocation concealment, blinding, and completeness of follow-up. Data were extracted from each study using a standardized data collection form. The primary outcome was reduction in pain scores (visual analog scale [VAS], 0–100 mm). We also evaluated maternal side effects (sedation, oxygen desaturation, and bradypnea) and effects on the neonate (Apgar scores, umbilical cord pH, and Neurologic and Adaptive Capacity Scores). Seven studies (349 patients) were identified for inclusion; only 3 studies were suitable for quantitative synthesis in a meta-analysis (233 patients). We found that remifentanil reduces the mean VAS score at 1 hour by 25 mm more than meperidine (P < 0.001) (95% confidence interval = 19–31 mm). Limited conclusions can be made regarding the side-effect profile of remifentanil because of insufficient data. Compared with meperidine, remifentanil is superior in reducing mean VAS scores for labor pain after 1 hour.

title: Remifentanil in obstetrics
abstract: The present study summarizes the knowledge to date of the use of remifentanil in obstetric anaesthesia and analgesia.  Modest labour analgesia, particularly for the first stage, can be achieved using a patient-controlled analgesia bolus of 40 μg with a 2-min lockout. Neonatal effects are minimal; however, maternal desaturation is a possibility and requires one-to-one supervision and appropriate monitoring. Background infusions can improve analgesia, but maternal desaturation or even apnoea is more likely. Remifentanil is effective at obtunding responses to airway manipulation and surgery under general anaesthesia. Neonatal effects are more pronounced and 50% of neonates may need assisted ventilation, and occasionally naloxone.  Remifentanil has a place in obstetric anaesthesia and analgesia. Further studies are needed to confirm if background infusions are safe in addition to patient-controlled analgesia. Studies are needed to establish a dose range under general anaesthesia that prevents neonatal respiratory depression at birth.

title: Alternatives to neuraxial analgesia for labor
abstract: Although millions of parturients profit from neuraxial analgesia for labor, there are far more of those who do not have this choice for one reason or another. They need alternative ways to relieve labor pain. Recent findings Paracervical block gives less efficient analgesia compared with single-shot spinal in a sample of multiparae at active labor but is associated with better umbilical artery pH. Use of a neurostimulator may increase success in pudendal block. It is possible to reduce nitrous oxide occupational exposure by a developed scavenging system. Intravenous remifentanil gives less efficient pain relief than epidural analgesia. The maternal satisfaction, however, may be comparable.  Paracervical block with modern technique is a viable option for selected cases. It is rapid and does not affect the course of labor, but its efficacy is only modest. Pudendal block can be used in the second stage of labor or for episiotomy tear repair and pain. Intravenous remifentanil is currently becoming an established method, although its safety is still an issue. Nitrous oxide is a useful method to be used alone or together with the other methods.

title: Maternal and neonatal side-effects of remifentanil patient-controlled analgesia in labour.
abstract: Remifentanil has been suggested as an ideal opioid for patient-controlled analgesia (PCA) in labour, but the safety profile has not been established. The aims of this preliminary prospective observational study were to investigate the maternal side-effects and early neonatal effects, and to assess the placental transfer of remifentanil PCA during labour.



Women with no known obstetric complications or contraindication to remifentanil were recruited (n=50). Remifentanil was administered at a bolus dose of 0.5 microg kg(-1) and a lockout period of 2 min. A visual analogue scale was used to assess pain, nausea and itching. Maternal observations were recorded hourly and fetal heart rate trace was assessed every 2 h. Umbilical cord gases, 1 and 5 min Apgar scores and neurological evaluation of the neonate were recorded. Maternal venous blood and umbilical artery and vein cord blood samples were collected for analysis of remifentanil concentration.



Fifty women enrolled in the study (24 multiparous, 26 primiparous). There was no evidence of cardiovascular instability or respiratory depression. Pain scores decreased significantly, but there was no significant change in nausea after initiating the PCA. A statistically significant increase in itching was found to be clinically mild and 22 women were slightly drowsy (95% confidence interval [CI], 30-58.7%) but alert to voice. Ten fetal heart rate traces demonstrated changes in the first 20 min, but did not require intervention (95% CI, 10-33.7%). The median 1 and 5 min Apgar scores were 9. The mean umbilical cord gases and neurological examination were within normal limits. Maternal vein and umbilical vein cord samples demonstrated placental transfer of remifentanil, and small amounts were detected in umbilical artery samples.



At the bolus dose used remifentanil PCA has an acceptable level of maternal side-effects and minimal effect on the neonate. Remifentanil crosses the placenta and appears to be either rapidly metabolized or redistributed in the neonate.

title: Patient-controlled analgesia for labour using remifentanil: a feasibility study.
abstract: We have investigated the efficacy and safety of remifentanil in a patient-controlled analgesia device for labour in 21 women. Remifentanil was available in increasing doses (bolus doses 0.25-1.0 microg x kg(-1)) with and without a background infusion (0.025-0.05 microg x kg(-1) x min(-1)). A lockout time of 2 min was used. Thirteen out of 21 (62%) women chose to continue using remifentanil up to and during delivery. Nineteen out of 21 (90%) achieved a reduction in pain score from baseline. Using a VAS of 0-10 cm the median maximum reduction in pain score was 3 cm (range 0-8 cm). There was a significant reduction (P<0.05) from baseline pain scores (median= 8 cm) to scores at bolus doses in the range 0.25-0.5 microg x kg(-1) (median=5 cm). There were no significant reductions in the fetal heart rate. Apgar scores and cord blood gas analyses remained within normal limits. We conclude that a remifentanil patient-controlled analgesia system (bolus doses 0.25-0.5 microg x kg(-1), without a background infusion) may safely provide worthwhile, although incomplete, analgesia for labour.

title: Remifentanil in Obstetric Analgesia: A Dose-Finding Study
abstract: IV patient-controlled analgesia (PCA) with remifentanil is a new approach in systemic opioid analgesia during labor. We determined the minimum effective dose of IV remifentanil by increasing the PCA bolus from 0.2 &mgr;g/kg with 0.2 &mgr;g/kg increments during a 60-min study period until the analgesia was considered adequate by the parturient. Twenty healthy parturients with singleton pregnancies participated in the study during the first stage of labor. Remifentanil hydrochloride was given IV via PCA over 1 min with a lockout time of 1 min. The parturient started the PCA bolus at the first subjective sign of uterine contraction. All 17 patients who completed the study reached adequate pain relief. The median effective PCA bolus was 0.4 &mgr;g/kg and consumption was 0.066 &mgr;g · kg−1 · min−1, with wide individual variation (0.2–0.8 &mgr;g/kg and 0.027–0.207 &mgr;g · kg−1 · min−1, respectively). The pain scores were reduced by a median of 4.2 (25th–75th percentiles, 3.1–5.2;P < 0.001) on an 11-point numeric scale. Although there was a wide individual variation in the dose required, remifentanil seems effective for labor analgesia. However, maternal oxygen desaturation, sedation, and reduced fetal heart rate beat-to-beat variability were observed frequently. There was wide individual variation in the dose required for effective labor analgesia. Potentially serious side effects, which were observed frequently during remifentanil analgesia, may limit remifentanil’s use in obstetrics.

title: Knowledge-Assisted Sequential Pattern Analysis With Heuristic Parameter Tuning for Labor Contraction Prediction
abstract: The optimal dosing regimen of remifentanil for relieving labor pain should achieve maximal efficacy during contractions and little effect between contractions. Toward such a need, we propose a knowledge-assisted sequential pattern analysis with heuristic parameter tuning to predict the changes in intrauterine pressure, which indicates the occurrence of labor contractions. This enables giving the drug shortly before each contraction starts. A sequential association rule mining based patient selection strategy is designed to dynamically select data for training regression models. A novel heuristic parameter tuning method is proposed to decide the appropriate value ranges and searching strategies for both the regularization factor and the Gaussian kernel parameter of least-squares support vector machine with radial basis function (RBF) kernel, which is used as the regression model for time series prediction. The parameter tuning method utilizes information extracted from the training dataset, and it is adaptive to the characteristics of time series. The promising experimental results show that the proposed framework is able to achieve the lowest prediction errors as compared to some existing methods.

title: Respiratory arrest in an obstetric patient using remifentanil patient‐controlled analgesia *
abstract: Remifentanil patient‐controlled analgesia is well established in many centres and provides satisfactory pain relief for many women in labour. We describe a patient using remifentanil patient‐controlled analgesia who suffered a respiratory arrest requiring a brief period of ventilation. In our institution, remifentanil patient‐controlled analgesia has been offered to women in labour since 2009. Up to this point, we had not observed any critical incidents in over 130 patients using this mode of analgesia in our labour suite.

title: Maternal and Neonatal Effects of Remifentanil at Induction of General Anesthesia for Cesarean Delivery: A Randomized, Double-blind, Controlled Trial
abstract: Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study. In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 &mgr;g/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil. The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, −17 to 31] mmHg) compared with the control group (42 [6–73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23–45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23). A single bolus of 1 &mgr;g/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

title: The Pharmacodynamic Effect of a Remifentanil Bolus on Ventilatory Control
abstract: In doses typically administered during conscious sedation, remifentanil may be associated with ventilatory depression. However, the time course of ventilatory depression after an initial dose of remifentanil has not been determined previously.  In eight healthy volunteers, the authors determined the time course of the ventilatory response to carbon dioxide using the dual isohypercapnic technique. Subjects breathed via mask from a to-and-fro circuit with variable carbon dioxide absorption, allowing the authors to maintain end-tidal pressure of carbon dioxide (PETCO2) at approximately 46 or 56 mmHg (alternate subjects). After 6 min of equilibration, subjects received 0.5 &mgr;g/kg remifentanil over 5 s, and minute ventilation (&OV0312;E) was recorded during the next 20 min. Two hours later, the study was repeated using the other carbon dioxide tension (56 or 46 mmHg). The &OV0312;E data were used to construct two-point carbon dioxide response curves at 30-s intervals after remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (keo), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration–response curve (&ggr;).  The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l · min−1 · mmHg−1 [−0.12 to 0.66] 2 min after remifentanil (P < 0.001); within 5 min, it recovered to approximately 0.6l · min−1 · mmHg−1, and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mmHg (&OV0312;E50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P < 0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of &OV0312;E50 included keo = 0.24 min−1 (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and &ggr; = 1.74.  After administration of 0.5 &mgr;g/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.

title: Timing of intravenous patient‐controlled remifentanil bolus during early labour
abstract: Remifentanil labour analgesia is superior to nitrous oxide but less potent than epidural analgesia. The short onset and offset times of effect suggest that the timing of the bolus in the contraction cycle could have importance. We hypothesised that administering a remifentanil bolus during contraction pause would improve analgesia in early labour.

title: The effects of Entonox and epidural analgesia on arterial oxygen saturation of women in labour
abstract: The arterial oxygen saturation of 40 mothers in the first stage of labour was monitored using pulse oximetry. Half the mothers received epidural analgesia and the rest inhaled Entonox for pain relief. Eight mothers in the Entonox group and six in the epidural group had at least one episode of significant hypoxia (saturation < 90%). There was little difference in the number of hypoxic episodes experienced by either group (29 in the Entonox and 21 in the epidural) although their mean duration and severity was greater in the Entonox group. Women in labour who inhale Entonox have an appreciable incidence of arterial desaturation. Epidural analgesia reduces the severity of hypoxic episodes although it does not eliminate them.

title: Maternal hypoxaemia during labour and delivery: the influence of analgesia and effect on neonatal outcome
abstract: The effect of analgesia on the incidence of hypoxaemia was assessed in an unrandomised trial in 51 parturients from the last hour of the first stage of labour until delivery. Women were retrospectively divided into four groups: no analgesia, pethidine with intermittent Entonox, extradural bupivacaine (either infusion of 0.125% or top‐ups of 10ml of 0.25%): and extradural infusion of 0.1% bupivacaine with 2 μg.ml ‐1fentanyl. The lowest median incidence of desaturation (Spo2< 94%) was in the extradural bupivacaine group: 0 min.h‐1 in the last hour of the first stage and 0.1 min.h‐1 in the second stage. The incidence was significantly lower than in the pethidine I Entonox group (1.4min.h‐1) in the last hour of the first stage (p < 0.001) and the extradural bupivacaine /fentanyl group (0.9 min.h‐1 and no analgesia group (3min.h‐1) in the second stage (p < 0.05 in both cases). There was no correlation between maternal oxygenation during the second stage and measures of neonatal outcome including Apgar score and umbilical artery and vein blood gases.

title: Must we press on until a young mother dies? Remifentanil patient controlled analgesia in labour may not be suited as a “poor man’s epidural”
abstract: BackgroundThe epidural route is still considered the gold standard for labour analgesia, although it is not without serious consequences when incorrect placement goes unrecognized, e.g. in case of intravascular, intrathecal and subdural placements. Until now there has not been a viable alternative to epidural analgesia especially in view of the neonatal outcome and the need for respiratory support when long-acting opioids are used via the parenteral route. Pethidine and meptazinol are far from ideal having been described as providing rather sedation than analgesia, affecting the cardiotocograph (CTG), causing fetal acidosis and having active metabolites with prolonged half-lives especially in the neonate. Despite these obvious shortcomings, intramuscular and intravenously administered pethidine and comparable substances are still frequently used in delivery units.Since the end of the 90ths remifentanil administered in a patient-controlled mode (PCA) had been reported as a useful alternative for labour analgesia in those women who either don’t want, can’t have or don’t need epidural analgesia.DiscussionIn view of the need for conversion to central neuraxial blocks and the analgesic effect remifentanil has been demonstrated to be superior to pethidine. Despite being less effective in terms of the resulting pain scores, clinical studies suggest that the satisfaction with analgesia may be comparable to that obtained with epidural analgesia. Owing to this fact, remifentanil has gained a place in modern labour analgesia in many institutions.However, the fact that remifentanil may cause harm should not be forgotten when the use of this potent mu-agonist is considered for the use in labouring women. In the setting of one-to-one midwifery care, appropriate monitoring and providing that enough experience exists with this potent opioid and the treatment of potential complications, remifentanil PCA is a useful option in addition to epidural analgesia and other central neuraxial blocks. Already described serious consequences should remind us not refer to remifentanil PCA as a “poor man’s epidural” and to safely administer remifentanil with an appropriate indication.SummaryTherefore, the authors conclude that economic considerations and potential cost-savings in conjunction with remifentanil PCA may not be appropriate main endpoints when studying this valuable method for labour analgesia.