Oxford Meeting - November 2002

Opioids in the Delivery Room

Dr J Blair

Pethidine has recently been shown to lack analgesic effect by Olofsson et al [1] and produces severe maternal sedation. As with all lipid soluble opioids it rapidly crosses the placenta. Neonatal neurobehavioural depression and impaired sucking and feeding are seen for at least 48 hours if pethidine is given IM around 3 hours before delivery. Pethidine PCA has been investigated but higher total doses than the IM regimen, concerns regarding norpethidine, and a failure to show a consistent reduction in pain scores lead to pethidine pca remaining unpopular. Fentanyl also has been tried in PCA form but there was concern that fentanyl may accumulate in the fetus, especially in the presence of fetal distress with acidosis. One of the few studies of fentanyl PCA [2] found reduced neonatal oxygen saturation compared to an epidural control group. The 1990' s saw the introduction of a new opioid: remifentanil. The unique pharmacokinetic profile seemed to offer the "rapid onset! offset" that mirrored contraction pain. In addition there was no problem with accumulation during a long labour as the context sensitive half time was demonstrated at around 3 minutes. Preliminary studies of paediatric pharmacokinetics showed that the adult profile was also seen in young children [3].

A feasibility study for remifentanil PCA with escalating bolus doses of remifentanil from 0.25 mcg kg-l to 1 mcg kg-I, with and without a background infusion of up to 0.05 mcg kg/min was completed [4]. Each bolus dose at each level was available for 15 minutes after which time the parturient was asked to record the level of pain experienced during the proceeding contractions. The dose was steadily increased until effective pain relief was reached or an adverse effect occurred. The first parturient to use the remifentanil PCA contracted at the rate of 1 contraction every 2 minutes and the 3 minute lockout time was therefore shown to be too long. We therefore studied the next 20 women using a lockout time of 2 minutes.

13 of the 21 women, 62%, continued to use the remifentanil PCA up to delivery. Baseline median pain scores were high with a median value of 8cm. After 15 minutes median pain scores had reduced to 6cm. Median pain scores at delivery for those using remifentanil PCA rose to 8 cm. Sedation and satisfaction scores were significantly higher and anxiety scores were significantly reduced at bolus dose 0.5 mcg/kg compared to baseline levels. 

Median apgar scores for the babies born with the mother using the PCA were 8 and 9 at 1 and 5 minutes respectively and the mean cord pH was 7.34. No baby required naloxone to establish spontaneous breathing. We concluded that at doses up to 0.5 mcg/kg, without a background infusion and with a 2 minute lock-out time, remifentanil appeared to be safe and effective in reducing pain scores for contractions during active labour. We then compared remifentanil with pethidine, the current popular opioid [5]. This study was double-blinded, randomised and had similar inclusion criteria to those of the first feasibility study. Before starting the PCA the pain of the contractions and all other parameters were recorded as a baseline and were repeated at 30 minute intervals. Continuous SaO2 monitoring was performed and the cardiotocograph or CTG was recorded for a minimum of one hour after starting the PCA. At delivery APGAR scores at 1, 5 and 10 minutes were recorded, cord blood was taken for blood gas analysis and a Neurologic and Adaptive Capacity Score or NACS was recorded at 30 minutes and 120 minutes after delivery. The mother was asked for overall average pain and satisfaction with analgesia scores at 2 hours after delivery. More women chose to continue using remifentanil than pethidine pca for delivery although this difference was not statistically significant. There were no significant differences between pain scores between the two groups although pain scores in the pethidine group continued to rise whilst those in the remifentanil group remained constant. Satisfaction scores were significantly higher with remifentanil and sedation scores also tended to be higher although this was not statistically significant. Overall pain scores again tended to be lower for remifentanil and overall satisfaction with analgesia was significantly higher with remifentanil. Women spent an average of 2 minutes an hour below SaO2 90% for remifentanil and 1.5 minutes an hour below SaO2 90% for pethidine. Fewer CTG traces deteriorated in the remifentanil group. NACS scores again tended to favour remifentanil. APGAR scores were similar with median scores of 8 at one minute however the minimum scores were 6 for remifentanil but only 4 for pethidine. Apgar scores at 5 minutes showed median scores of 9 in both groups however the minimum scores were 8 for remifentanil but only 6 for pethidine. All scores were at least 9 by 10 minutes.

Reductions in pain scores were disappointing with remifentanil in the second study, however women were more satisfied with the analgesia they received from remifentanil. Other studies that have since been published show that remifentanil is capable of reducing pain scores. With regard to maternal safety, concerns centre on possible respiratory depression and vomiting. With regard to fetal well being and neonatal outcome we feel our two studies are reassuring. Remifentanil certainly has a better profile than pethidine. In conclusion then, remifentanil PCA is capable of reducing pain scores in labour and has a better fetal profile than pethidine. Maternal side effects remain the main cause for concern and mothers must be monitored closely. Perhaps the time has come to abandon the 60 year old 1M pethidine injection in labour and move on into the 21st century?

1. Olofsson C, Ekblom A, Ekman-Ordeberg G, Hjelm A, Irestedt L. Lack of analgesic effect of systemically administered morphine or pethidine on labour pain. Br J Obstet Gynaecol1996; 103 :968- 72

2. Nikkola EM, Ekblad UU, KerPO.lntravenous Fentanyl PCA during labour. Can J Anaesth 1997; 44: 248-55

3. Kan RE et al.lntravenous remifentanil. Placental transfer, maternal and neonatal effects. Anesth 1998;88:1467-74

4. Blair JM, Hill DA, Fee JPH. Patient-controlled analgesia for labour using remifentanil: a feasibility study. Br J Anaesth 2001; 87: 415-20

5. Blair JM, Dobson GT, Hill DA, JPH Fee. Patient-controlled analgesia for labour: a comparison of pethidine with remifentanil. Anesth 2001; 95:AI063