Opioids in the management of pain during delivery

Abstract

Labour and delivery involve severe pain for most women. The goal for pain treatment in obstetrics is to provide effective and safe analgesia during all phases of delivery. The ideal method for pain relief during delivery is not yet available. This thesis aims at studying some aspects of opioids in obstetric pain treatment with respect to analgesic efficacy and side-effects, and to analyse pain during delivery from a neurobiological perspective. The analgesic effect of systemically given opioids was studied in a dose-response and in a prospective randomised and double-blind fashion. A lack of clinically significant analgesic effect was observed despite pronounced sedation. The results are interpreted to suggest that visceral pain during active labour is poorly responsive to systemically given opioids. Epidural analgesia (EDA) only using local anaesthetics is a most effective technique for pain relief during labour but is considered to increase the frequency of instrumental deliveries (vacuum extraction and Caesarean section). In a prospective, controlled randomised study in 1000 parturients during active labour, a 50% reduction of bupivacaine, but with addition of the lipophilic opioid sufentanil to sustain analgesia, the frequency of instrumental delivery was significantly reduced. The addition of sufentanil to EDA did not increase the risk of post-partum urinary retention.

The anaesthetic quality during Caesarean section was studied, using a randomised and double-blind technique, in 100 parturients receiving either epidural or subarachnoidal anaesthesia with bupivacaine. In half of the patients the lipophilic opioid fentanyl was added. Intraoperative pain and discomfort did not differ significantly between the groups, indicating that an adequate dose of a local anaesthetic (bupivacaine) is of major importance when using either of the two regional anaesthetic techniques. No clinically significant effect of adding fentanyl was observed with respect to postoperative pain. The theoretical additive or synergistic effect of fentanyl, was possibly "masked" by adequate dosage of local anaesthetic. The concentration of the excitatory amino acid aspartate was significantly increased in cerebrospinal fluid during active labour but unexpectedely the concentration of nitrate (reflecting nitric oxide) was significantly lower than in controls. No effect was seen on concentrations of substance P, substance P-endopeptidase or met-enchephalin. Our results suggest that excitatory amino acids and nitric oxide are of importance in spinal nociception and visceral pain during active labour.

In conclusion, we suggest that systemic opioids, still one of the most widely used methods for "analgesia" in obstetrics, should not be administered for analgesia during labour. The epidural technique can be significantly improved with respect to the frequency of instrumental deliveries by reducing the amount of local anaesthetic and by adding a lipophilic opioid. Thereby the use of epidural analgesia could be increased in order to meet the demands from parturients in pain. Anaesthetic quality during Caesarean section using regional techniques is primarily determined by the amount of local anaesthetic used. Knowledge of the mechanisms of excitatory amino acids more detailed may permit the development of new and improved pain control strategies during labour.