Maintenance of maternal blood pressure targets after spinal anaesthesia for caesarean delivery: a reply

We thank Zhao and Huang 1 for their comments on our study 2 and we agree mostly with their points. Although a crystalloid pre-load can counteract the hypovolaemia associated with pre-operative fasting before spinal anaesthesia, it promotes atrial natriuretic peptide release and enhances fluid transfer, leading to peripheral vasodilation and diuretic effects 3. This leads to difficulty in maintaining maternal systolic blood pressure. In contrast, co-loading maintains vascular volume when vasodilation occurs following spinal anaesthesia and prevents excessive fluid transfer 2. The use of a reactive bolus administration of noradrenaline instead of a prophylactic infusion might not reflect standard practice elsewhere. Thus, as the strategy preferred currently for managing maternal blood pressure, the combination of prophylactic vasopressor (either noradrenaline or phenylephrine) with fluid management using co-loading is more conducive to enhancing maternal haemodynamic stability and significantly reducing the incidence of early maternal hypotension after spinal anaesthesia 4. These aspects represent significant design limitations in our study. After applying Bonferroni correction and Holm–Bonferroni correction for multiple comparisons, the proportion of neonatal umbilical artery pH < 7.2 did not show statistical significance and retained statistical significance (p = 0.020), respectively. This was attributed primarily to the low event rate, as there were only 16 (1.4%) cases of rare events in the overall cohort which lacked sufficient statistical power for this secondary analysis. Therefore, the decrease in the incidence of neonatal acidaemia attributable to a higher maternal blood pressure management target should be interpreted with caution. Based on our results, different maternal blood pressure management targets (80% vs. 90%) did not influence neonatal umbilical artery pH. We also agree that further assessment of the impact of maintaining higher maternal blood pressure on neonatal outcome can be conducted with larger sample sizes, using neonatal umbilical artery pH < 7.2 as the primary outcome. Ngan Kee et al. 5 employed the smallest difference of 0.01 of umbilical artery pH in their non-inferiority analysis regarding the application of noradrenaline and phenylephrine on neonatal outcome, which was regarded as the capacity to detect possible minor detrimental effects. Thus, setting a difference of 0.005 for the sample size calculation in our study may be overly stringent and lack clinical significance. By further hypothesising a difference in umbilical artery pH of 0.01, with a statistical power of 90% and a two-sided significance level of 0.05, each group would require a sample size of 526. Considering a 10% dropout rate, 579 patients are needed for the final analysis in each group. The required sample size is close to the previously calculated 600. Nevertheless, it is still not possible to affirm the rationality of the sample size calculation based on a 0.005 difference in umbilical artery pH between the two groups in our study.