Ephedrine for spinal hypotension during elective caesarean section: the final nail in the coffin?

Spinal anaesthesia has become the anaesthetic technique of choice for caesarean delivery, not only to avoid the risk of failed tracheal intubation, but also to facilitate early bonding between the mother and her baby and to improve post-operative analgesia. The practice of spinal anaesthesia should therefore in the first instance be safe for mother and infant, and also comfortable, in that side effects, particularly nausea and vomiting, should be avoided. The controversy concerning the use of the pure direct-acting alpha agonist phenylephrine vs. the mixed direct-/indirect-acting alpha/beta agonist ephedrine for the management of spinal hypotension is approaching resolution. Foetal acidosis, as measured by umbilical cord pH and base deficit, is often quoted as a surrogate marker for neonatal outcome, and there have been several widely cited reviews on this subject. One consensus document has suggested that only very severe acid–base deficits are predictive of cerebral palsy after an acute intrapartum event. However, a recent systematic review concluded that there was a four-fold increase in mortality if pH was less than 7.2. Some studies intimate that some degree of foetal sympathetic activation pre-delivery may have an outcome benefit, and that the search for zero base deficit may be inappropriate. The thorough analysis in Acta Anaesthesiologica Scandinavica this month clearly shows that ephedrine, when used for the treatment of spinal hypotension, is associated with a higher incidence of true foetal acidosis than phenylephrine. A funnel plot conducted by ourselves on the base deficit data found no suggestion of publication bias. Foetal considerations centre around the fact that ephedrine is known to cross the placenta and increase base deficit via an increase in metabolic rate. Although the mechanism of ephedrineassociated acidosis is not related to absolute hypoxia, it could be argued that excessive metabolic stimulation in an already compromised neonate could impair the oxygen supply/demand ratio. A recent investigation showed that ephedrine use is associated with higher lactate, plasma catecholamine concentrations and lower umbilical arterial pH, and a greater base deficit than phenylephrine. In this study, however, large doses of ephedrine (median dose 60 mg pre-delivery) were used by infusion, which some clinicians might regard as excessive. Figure 2 in the current meta-analysis shows a risk ratio of 5.29 for true foetal acidosis for ephedrine compared with phenylephrine. The data shown in Fig. 3 shows that an increased base deficit is significantly associated with ephedrine use, although there is heterogeneity between the studies. This suggests that different doses and dosing regimens may alter the severity of the adverse metabolic effect associated with ephedrine use. In addition, the meta-analysis does not distinguish between studies using ephedrine by bolus vs. infusions. The latter may be associated with tachyphylaxis. Therefore, there is still some doubt as to whether the level of acidosis associated with pre-delivery ephedrine use is of clinical significance when low bolus doses are used in preference to higher dose infusions. There have been only a very limited number of studies on vasopressor use during non-elective caesarean section. One such investigation showed no significant difference in pH and base deficit when comparing the use of the two vasopressors, although cord lactate was significantly higher after ephedrine use.