The risk of side effects (particularly sedation and respiratory depression) associated with systemic opioids, traditionally given intramuscularly, led in the 1980s/1990s to the investigation of small, repeated doses of opioid that were self-administered by the patient herself (patient-controlled analgesia, PCA). Originally developed for postoperative analgesia (see Chapter 41, Postoperative analgesia), PCA was extended to administration of opioids in labour. Experience with older opioids (morphine, diamorphine, pethidine) was limited by their slow onset, long duration of action and persistence of side effects, but newer drugs (especially fentanyl and more recently remifentanil) are more suited to the PCA technique and are now in widespread use.
Choice of drug
The ideal drug for PCA in labour would have a very rapid onset, produce intense effective analgesia, and have a rapid offset with no or minimal side effects. Over the years, a succession of drugs and regimens has been used as drugs closer to meeting this ideal have become available:
• Pethidine was the first drug studied for PCA during labour (e.g. 10-20 mg with a lockout of 10 minutes), but is slow in onset and offset, with a risk of cumulation over time (including of its metabolite norpethidine).
• Morphine or diamorphine PCA has received less attention, but is sometimes used in early miscarriage or termination (e.g. 18-22 weeks), when effects on the fetus are no longer a concern.
• Fentanyl became a useful alternative to epidural analgesia in women unable to have the latter for medical reasons (e.g. 20-50 µg bolus with a lockout of 5-6 minutes). Use of fentanyl bolus doses has been reported to cause less neonatal depression than intravenous boluses of pethidine. However, its use has largely been superseded by that of remifentanil.
• Alfentanil, with its rapid onset and offset due to its small volume of distribution and low pKa, may seem well suited for labour analgesia, but there has been no evidence of benefit over the more familiar fentanyl PCA.
• Remifentanil is a very short-acting mu-opioid receptor agonist that is rapidly hydrolysed by red blood cell and tissue esterases and thus is thought to have the characteristics that are ideal for PCA in labour, despite not being licensed for this indication. Furthermore, studies suggest that fetal and neonatal effects are less than with other opioids, since the drug is rapidly metabolised after crossing the placenta. While uterine vein to maternal artery concentration ratio is 0.88, uterine artery to uterine vein concentration ratio is 0.29, illustrating its high placental transfer followed by rapid fetal metabolism and redistribution. Although analgesia is incomplete, there exist two groups of women who might particularly benefit from remifentanil PCA: first, those unable to have an epidural sited for medical reasons; and second, those who do not necessarily want to have an epidural, but who just want analgesia that is more effective than the other methods.
Remifentanil’s analgesic efficacy seems to lie between that of pethidine and neuraxial techniques. Current evidence suggests that remifentanil PCA is associated with improved patient satisfaction and pain scores and decreased conversion to epidural analgesia, in comparison with pethidine. While pain scores are better with epidural analgesia, patient satisfaction appears to be similar.
Regimens used usually include a 20-50 µg bolus with a lockout of 1-3 minutes.
Background infusions are not recommended because of safety concerns (see below).
Side effects
All opioids share the same range of side effects, but common side effects of remifentanil PCA in practice include maternal drowsiness, nausea, pruritus and dizziness. However, the biggest concern is respiratory depression; this may be noted in nearly a third of women using remifentanil PCA. There have been several case reports of cardiac or respiratory arrest and even perimortem caesarean section associated with its use. Problems have been hypothesised to be patient-related (e.g. increased sensitivity), equipment-/administration-related (e.g. a bent arm resulting in a larger bolus dose when unbent), or due to the use of additional parenteral opioids in opioid-naive women. An increased prevalence of respiratory arrest has been noted in women using remifentanil PCA after an intrauterine death; this may be due to altered pharmacokinetics or a tendency to reduced monitoring/observation/presence of staff in these circumstances. It is vital, therefore, that midwifery staff are instructed not to leave a woman alone for a moment if she is receiving remifentanil PCA.
Remifentanil appears to result in fewer problems for the neonate than pethidine. Loss of beat-to-beat variability may be seen with remifentanil use, although this tends to be less marked than with pethidine. The need for neonatal resuscitation appears to be lower with remifentanil.
There may be some benefits of remifentanil PCA over epidural analgesia; the RemiPCA SAFE Network (which has collected data from over 20 hospitals worldwide, although only three from the UK) has noted an association between the use of remifentanil PCA and a lower incidence of pyrexia, a reduced need for oxytocin infusion and a shorter duration of labour than with epidural analgesia.
Management options
For its successful use, there must be locally developed guidelines, appropriate to the obstetric unit, which are strictly adhered to. In addition to careful monitoring of mother and baby, a member of staff who has been trained to observe for possible side effects (e.g. respiratory depression, bradycardia) must be present at all times. Suggested minimum standards for remifentanil PCA include oxygen saturation monitoring with regular documentation of respiratory rate, sedation level and pain scores. A dedicated cannula with an anti-syphon valve should be used. Supplemental oxygen must be administered, and resuscitation drugs and equipment including naloxone and a bag-valve mask must be available.
If a unit plans to use remifentanil PCA, the staff need to be regularly trained and exposed to its use in order to gain familiarity and facilitate safe use.
Key points
• Intravenous PCA is thought to be a more logical and safer method of administering opioids during labour than intramuscular injection.
• Remifentanil PCA provides analgesia that is superior to other opioids, but inferior to neuraxial techniques.
• Remifentanil should only be used if a local protocol is adhered to and appropriate safety precautions are in place.
Further reading
Hinova A, Fernando R. Systemic remifentanil for labor analgesia. Anesth Analg 2009; 109: 1925-9.
Muchatuta NA, Kinsella SM. Remifentanil for labour analgesia: time to draw breath? Anaesthesia 2013; 68: 231-5.
Schnabel A, Hahn N, Broscheit J, et al. Remifentanil for labour analgesia: a meta-analysis of randomised controlled trials. Eur J Anaesthesiol 2012; 29: 177-85.
Van de Velde M, Carvalho B. Remifentanil for labor analgesia: an evidence-based narrative review. Int J Obstet Anesth 2016; 25: 66-74.