Patient-controlled continuous epidural analgesia vs intravenous remifentanil infusion for labour anaesthesia
*Joanna Sołek-Pastuszka1, Stanisław Kępiński1, Arystarch Makowski1, Zbigniew Celewicz3, Maciej Żukowski1, Krzysztof Safranow2, Romuald Bohatyrewicz1
1Department of Anaesthesiology and Intensive Therapy, Pomeranian Medical University in Szczecin
2Department of Biochemistry and Chemistry, Pomeranian Medical University in Szczecin
3Department of Maternal-Foetal Medicine, Pomeranian Medical University in Szczecin
Background. Although epidural anaesthesia has become a standard method for labour analgesia all over the world, it is far from being ideal because of side effects and contraindications. Many alternative techniques have therefore been proposed, including the continuous infusion of remifentanil. Encouraged by positive reports, we compared the efficacy of patient-controlled remifentanil infusion (PCA) with patient-controlled continuous epidural analgesia (PCEA).
Methods. Fifty-two ASA I and II parturients were arbitrarily allocated, without randomisation, to two groups to receive PCEA with 0.125% bupivacaine and 0.2 µg kg-1 fentanyl (basic infusion 1 ml h-1, bolus 4 ml, lock-out time 15 min) or remifentanil PCA (0.2 µg kg-1 bolus doses, without basic infusion, lock-out time 2 min). The intensity of pain was assessed using the VAS every 15 min in the PCEA group and every 10 min in the PCA group.
Results. During the first two hours of labour, the VAS score was significantly lower in the PCEA group. Later there was no difference between the groups. The clinical status of the newborns was similar.
Conclusion. The results are difficult to interpret since there was no randomisation and parturients participated in decisions about allocation to one of the study groups. Analgesia provided by remifentanil was assessed as highly acceptable by the patients and the drug can be regarded as a safe alternative to epidural analgesia during labour.
For the majority of women, labour is one of the most positive life experiences; however, 5-7% considers it extremely traumatic, bringing back various unpleasant memories for many months. Up to 38% of those women do not decide to have another baby even 8-10 years after delivery .
Numerous studies using the Visual Analogue Scale (VAS) reveal that 20% of parturients define the labour pain as “unbearable” and 60% as “very strong”. Thus, it seems that with due respect for natural deliveries, effective labour analgesia should be provided to women who experience the most severe pains .
Severe pain has adverse effects on a parturient and foetus. The pain-triggered stress accelerates the basic metabolism of parturients, increases cardiac output and respiration. In extreme cases, reflex hyperventilation results in respiratory alkalosis manifested by maternal symptoms of tetany and foetal cardiac arrhythmias. The stimulation of the sympathetic system and increased levels of endogenous catecholamines cause uterine vasoconstriction, which reduces the maternal-placental flow and may lead to foetal anoxia and acidosis. The catecholamines released impair the uterine contracting function, which prolongs the labour and secondarily worsens the post-delivery neonate status [2, 3].
After some stormy discussions about the efficacy of continuous epidural analgesia (CEA) in the 80-ties and 90ties of the previous century, this type of analgesia has become a widely recognized standard of management in obstetrics and remains the most effective and safest way to relieve labour pain [4, 5]. However, in practice the frequency of CEA use varies. The statistical data show that the use of this method of labour analgesia in the developing counties is minimal; on the other hand, in some private practices, almost all parturients receive CEA. The method in question offers significant benefits – the parturient remains completely conscious throughout the anaesthesia, whose length may be freely prolonged. Moreover, the conversion from the classic variant, i.e. with the arbitrarily fixed speed of infusion, to the patient-controlled epidural analgesia (PCEA) additionally optimizes this method of analgesia.
If epidural analgesia is contraindicated, opioids should be considered . An ideal agent should be safe for both the mother and child, easy to administer, and effective in all stages of labour. As for its pharmacokinetic and pharmacodynamic properties, an ideal agent administered systematically should be characterized by rapid onset of action, quick metabolism and elimination as well as minimal permeability through the placental barrier.
In the early 90-ties, the efficacy of labour pain relief using intramuscular pethidine was studied. The assessment was carried out by the parturient, her partner and nurse. Only the nurses taking care of parturients found this method as satisfactory .
Due to the inconveniences mentioned earlier, the search for a safe labour analgesic has been started . Recently, remifentanil, an opioid of ultra-short action, was recognized the agent meeting the conditions of safety and controlled supply. To verify this hypothesis, a randomized, double-blind study was undertaken in parturients to compare the analgesic effects of intravenous remifentanil and pethidine in patient-controlled analgesia. The study was not completed due to markedly lower Apgar scores in the group receiving pethidine; hence, remifentanil was considered the drug providing good labour analgesia .
In recent years, numerous reports about intravenous remifentanil for labour analgesia were published [10, 11, 12, 13]. Therefore, we decided to compare this method with PCEA.
The study included parturients requesting analgesia and qualified for natural deliveries. Before analgesia, patients were informed about the available methods of analgesia; their detailed medical histories were taken concerning the clinical status, coexisting diseases and course of pregnancy. Parturients participated in decision making about analgesia based on the information provided. Additionally, prior to analgesia each patient was instructed how to operate the PCEA pump. The anaesthetist was present in the delivery room throughout the labour.
Patients were allocated to two groups: group I – parturients obtaining PCEA, and group II – those receiving patient-controlled intravenous remifentanil infusions (PCA).
Group II included patients with contraindications for epidural analgesia, with no such contraindications yet without consent or once intravenous analgesia was preferred, and cases in which the catheter insertion to the epidural space failed.
Patients were provided with complete information about the techniques of analgesia, and the procedure chosen was administered once the written consent was obtained. Analgesia was initiated in the first stage of labour depending on the severity of pain. In the PCEA group, the administration of the agent was started at the maximum cervical dilation of 5-6 cm for primiparas and 3-5 cm for multiparas. In group I, the degree of motor block was assessed using the Bromage scale; in group II, the level of sedation was assessed every 15 min according to the Ramsay scale.
In group I, the epidural catheter was inserted at the L3-L4 or L2-L3 level to the depth of 2-3 cm. Proper placement was confirmed by the lack of subarachnoid anaesthesia symptoms after the test dose of 5% lidocaine, i.e. 2 mL.
Agents were administered to the epidural catheter using the following regimen:
- first, 10 mL of 0.125% bupivacaine with adrenaline and addition of 0.1 mg of fentanyl,
- after 30 min, the infusion of 0.125% bupivacaine with adrenaline and fentanyl was started at the speed of 1-1 using the PCEA pump,
- the supplementary dose from the PCEA pump „on request” was 4 mL whereas the minimum interval between doses – 15 min,
- if analgesia was insufficient, the additional 5 mL of 0.25% bupivacaine with adrenaline was considered.
The group II patients were anesthetized with patient-controlled intravenous infusions of remifentanil, without the basic infusion according to the following protocol:
- during analgesia the continuous infusion of crystalloids was used at the speed of about 70-100 mL h-1,
- a single dose of remifentanil was 0.2 mg kg-1 and was triggered by a parturient. The minimum interval between successive doses was 2 min. The parturient decided about the onset of supply.
If analgesia remained insufficient, the anaesthetist could increase a single dose of remifentanil by 0.2 mg kg-1 every 10 min until the maximum dose of 0.8 mg kg-1.
Patients assessed the severity of pain according to VAS immediately before anaesthesia (VAS 0), 15 min after anaesthesia and further every 15 min in group I or every 10 min in group II until delivery (final VAS). The VAS values at successive hours (VAS 1, VAS 2, VAS 3, etc.) were recorded as means of repeated measurements in a given time interval.
The anaesthesia charts contained demographic data of patients, obstetric data (including the onset of delivery, duration of individual stages and mode of delivery), and vital parameters – HR, SAP/DAP, SpO2, motor block levels according to the Bromage scale (group I), sedation levels according to the Ramsay scale (group II), and adverse events observed.
The results were statistically analysed. The significance of intergroup differences in individual parameters was assessed using the non-parametric Mann-Whitney U test since the distribution of variables was often non-normal (which was verified with the Shapiro-Wilk test). For nominal variables, the significance of intragroup differences was analysed using the Fisher test. The power of correlation was measured with the Spearman nonparametric coefficient of rank correlation. The findings were presented as a mean and standard deviation. P<0.05 was considered as significant.
The anaesthetic procedures were carried out in 52 women, both primiparas and multiparas fulfilling the ASA I-II criteria. The characteristics of the population are presented in Table 1.
Prior to anaesthesia, the group I patients (n=26) assessed the severity of pain according to VAS as significantly higher compared to the group II patients (n-26); yet, a few group II women, who seemed to suffer much and requested analgesia, scored their pain as VAS 3-4. During one hour of analgesia, pain sensations markedly decreased in the epidural analgesia group and the VAS scores at 1 and 2 h of analgesia were substantially lower than in the remifentanil group. At successive labour hours, the intergroup differences in pain were no longer significant (Table 2).
Moreover, in group II, the subjectively perceived duration of uterine contractions was found shorter (on average about 20-30 sec) although according to cardiotocographic recordings, the contractions were longer.
The newborns were observed by the team of neonatologists. The only significant difference was found in SAP values at 1h. In newborns of mothers anaesthetized with remifentanil its mean value was 62 mm Hg whereas in those whose mothers were anaesthetized epidurally – 71mm Hg. It should be stressed, however, that both values were within normal limits 51-72 mm Hg.
Explicit interpretation of the findings is hindered by the fact that patients were not randomly chosen and co-decided about the method of analgesia used. Moreover, it is likely that in parturients who demonstrated more strongly their suffering, the epidural analgesia was administered more often. This enabled fast onset of the analgesia procedure.
However, continuous epidural analgesia is associated with potential adverse effects, such as arterial hypotension caused by sympathetic block, loss of natural tissue tone of the pelvic fundus and abnormal engagement of the foetus head or post-puncture syndrome (with back, nape, head, stomach, or peritoneal pains, dysuria [14, 15] as well as neurologic deficits in the form of disaesthesia).
The prolongation of first and second period of labour and increased incidence of Caesarean sections following CEA were widely discussed. The classic study by Chestnut and colleagues  concerning various concentrations of bupivacaine and bupivacaine with fentanyl revealed that epidural analgesia did not affect the duration of the second period of labour, incidence of instrumental deliveries or of Caesarean sections. The authors of other studies, however, agree that CEA significantly increases the requirements for oxytocin, slightly prolongs the second period of labour and increases the risk of its instrumental completion .
It is still disputed what the optimal timing of CEA is in relation to the labour period and uterine cervical dilation. The majority of reports document shorter labours in parturients with analgesia at the dilation of 4 cm or less [17, 18, 19].
There are also some reports demonstrating higher efficacy of epidural analgesia in the early period of labour, i.e at cervical dilation of 2 cm. The authors stress high efficiency, about threefold lower requirements for local anaesthetics in the first period of labour and more dynamic course of delivery . Moreover, the addition of an opioid reduces local anaesthetic demands. Thus, in practice lower concentrations of local anaesthetics are used, which weakens motor block at comparable levels of analgesia; this, in turn, helps in rotation of the foetus head in the birth canal and reduces the risk of instrumental delivery .
Compared to the classic method, PCEA optimizes labour epidural analgesia providing much better stabilization of circulation in parturients, lower consumption of drugs, hence lower risks of adverse events, higher chances of ambulation during the first labour period and definitely higher satisfaction of patients, who can individually adjust the dose of drugs according to demands .
Higher decreases in pain sensations following PCEA observed in our study most likely resulted from occurrence of immediate sympathetic block. However, further reduction in pain differences between groups is difficult to account for. It is worth stressing that the majority of remifentanil patients, despite slightly lower efficacy of analgesia, declared their willingness to undergo similar management during next deliveries.
Numerous studies attempting to use various methods and drugs of effective labour analgesia have been and are being carried out, which indicates that a single, effective and fully safe method of labour analgesia is lacking.
Intramuscular pethidine used routinely in maternity units is far from being an ideal opioid. It is administered in an uncontrollable manner and the highest level in foetal blood is observed at 2-3 h after its intramuscular administration. In natural deliveries, it is difficult to anticipate the time of labour, thus it is possible to extract the newborn at the peak pethidine level in maternal blood, which may result in respiratory depression of the neonate. Moreover, it should be stressed that the active pethidine-norpethidine metabolite exerts depressive effects on the newborn respiratory system. The half-life of petidine in neonates is 15-23 h, whereas that of norpethidine – even 20-60 h .
The neonatal observations show that newborns of mothers who received pethidine are less active and may develop respiratory problems. Mothers, on the other hand, may be at risk of such side effects of pethidine as nausea, vomiting, drowsiness, disorders of balance or respiratory disturbances and depression . Furthermore, satisfactory decreases in pain during the first and second period of labour were reported only by 60% of patients receiving i.m. pethidine. In the CEA group, this percentage was 88% .
Our study shows that patient-controlled analgesia with intravenous remifentanil infusions is an effective and safe alternative to epidural labour analgesia enabling to avoid limitations and typical complications of central blockade. However, proper monitoring of parturients should be provided to prevent possible respiratory depression.
The pharmacokinetic and pharmacodynamic properties of remifentanil make it almost an ideal agent for labour analgesia. The use of remifentanil may become a new way of effective labour pain management in parturients and provision of safety for newborns . The authors of the present study are planning further, randomized studies regarding applications of remifentanil PCA with the basic infusion option.
1. Intravenous remifentanil patient-controlled analgesia in labour is a safe alternative to continuous epidural analgesia.
2. Intravenous remifentanil patient-controlled analgesia in labour is slightly less effective in the first two hours of labour yet further analgesia is comparable to continuous epidural analgesia.
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