Preliminary risk-benefit analysis of ropivacaine in labour and following surgery

Abstract

Ropivacaine is a new, long-acting local anaesthetic, prepared as a single enantiomer (the S form). Ropivacaine has a pKa of 8.07, a protein binding of approximately 94%, but a lower lipid solubility than bupivacaine. Extensive animal toxicological studies have shown a lower propensity for cardiotoxicity with ropivacaine than with bupivacaine. Studies in sheep have shown that the systemic toxicity of ropivacaine is not enhanced by gestation. Studies in human male volunteers have shown that ropivacaine is associated with at least 25% less CNS and cardiovascular adverse effects than bupivacaine following use of intravenous infusions of either drug at a rate of 10 mg/min, to a maximum dose of 150 to 250 mg. With its lower toxicity, especially cardiovascular toxicity, and less intense motor blockade, ropivacaine may have advantages over bupivacaine in epidural pain relief during labour. In general, comparative studies have shown ropivacaine and bupivacaine to have similar efficacy, but ropivacaine has a greater degree of separation between motor and sensory blockade than bupivacaine when it given epidurally for epidural pain relief during labour (as intermittent doses or continuous infusion) or for caesarean section. A significantly lower rate of instrumental deliveries and significantly higher neurological and adaptive capacity scores in neonates at 24 hours were noted for following epidural relief during labour with ropivacaine in a meta-analysis of 6 studies comparing this agent with bupivacaine. Ropivacaine is also of great interest when used as an epidural infusion for postoperative analgesia. There are a few studies evaluating epidural infusions of ropivacaine 0.1%, 0.2% or 0.3% (10 ml/h for 21 hours) after upper or lower abdominal or orthopaedic surgery, and epidural infusion of ropivacaine 0.2% (6 to 14 ml/h) after orthopaedic surgery. The studies show that ropivacaine provides postoperative pain relief in a dose-related manner with minimal or a low degree of dose-related motor blockade. Recommended doses of ropivacaine given epidurally to control postsurgical pain or labour pain are 20 to 40 mg as a bolus with 20 to 30 mg as a top-up with an interval > or = 30 minutes. Alternatively, ropivacaine 2 mg/ml (0.2%) can be given as a continuous epidural infusion at a rate of 6 to 14 ml/h (lumbar) or 4 to 8 ml/h (thoracic). Epidural ropivacaine 0.2% provides a good level of analgesia with minimal motor block, but the effects of a combination of ropivacaine and an opioid administered epidurally could have potential and need to be investigated. Preoperative or postoperative subcutaneous wound infiltration, during cholecystectomy or hernia repair, with ropivacaine 100 to 175 mg has been shown to be more effective than placebo and as effective as bupivacaine in reducing wound pain. The adverse effects associated with epidural administration of ropivacaine include hypotension, nausea, bradycardia, transient paraesthesia, back pain, urinary retention and fever. In comparative studies of ropivacaine and bupivacaine, the 2 drugs appear to be associated with a similar incidence of similar types of adverse effects excluding cardiovascular and CNS toxicities which are lower with ropivacaine. In conclusion, ropivacaine is effective for pain relief during labour and in the postoperative period. Ropivacaine is associated with less cardiovascular and CNS toxicity than bupivacaine and provides a greater degree of dissociation between sensory and motor effects producing less intense motor blockade and more rapid recovery to full patient mobilisation.