Dear Editor, We read with interest the article by Sheng et al, which concluded that prophylactic infusion of metaraminol at 2.00 μg/kg/min is non-inferior to norepinephrine at 0.10 μg/kg/min in terms of neonatal outcomes, as assessed by umbilical arterial pH1. We have several concerns based on the clinical research aspects of this trial. We hope that clarification of these concerns could enhance the interpretation of the study and guide future research efforts. Firstly, the issue of fasting is of concern. The trial required all parturients to fast for ≥8 hours preoperatively without preoperative fluid resuscitation, which is inconsistent with the latest guidelines released by the American Society of Anesthesiologists in 2023 and is not conducive to participant protection2. Moreover, the varying durations of fasting and fluid restriction can result in significant differences in maternal blood volume and vascular tension. These differences may subsequently influence the incidence of hypotension following spinal anesthesia, thereby potentially compromising the reliability of the trial results. Future similar studies should consider shortening the preoperative fasting time in accordance with the guidelines or providing standardized fluid resuscitation to enhance participant comfort and result reliability3. Secondly, the dose of spinal anesthesia drugs warrants discussion. In this study, all parturients were given a single dose of 3 ml of 0.5% hyperbaric ropivacaine for spinal anesthesia, regardless of differences in height and weight. This approach may not be appropriate, especially for shorter subjects, such as those with a height of around 1.4 meters who meet the inclusion criteria4. The dose may affect drug distribution and efficacy, leading to a higher level of neural blockade, which in turn may exacerbate the incidence of hypotension and affect the trial results. Future studies should consider adjusting the drug dose based on height or weight to ensure subject safety and result reliability. Thirdly, the method of assessing the level of blockade is questionable. The trial described that researchers used an 18G blunt needle to perform a cold sensation test along the mid-axillary line, with the highest segment not perceiving cold being considered as the level of blockade. However, it is unclear how the blunt needle was used for the cold sensation test and whether the test assessed pain sensation rather than temperature sensation, which may be a descriptive error. If a cold sensation test is to be conducted, it would be safer and more reasonable to use items such as alcohol swabs. Fourth, the description of hypotension rescue measures is problematic. The trial mentioned that when hypotension or severe hypotension occurred, the metaraminol group was given a single dose of 75 μg of metaraminol, and the norepinephrine group was given a single dose of 6 μg of norepinephrine intravenously until the blood pressure recovered to more than 80% of the baseline. To preserve the double-blind state under anesthesia, it is imperative that the two vasopressor agents attain identical volumes (for instance, 1 ml of metaraminol diluted to a concentration of 75 μg/ml, or 1 ml of norepinephrine diluted to 6 μg/ml)5. However, given the domestic packaging concentrations of metaraminol at 10 mg/ml and norepinephrine at 2 mg/ml, achieving the same volume when withdrawing 75 μg of metaraminol or 6 μg of norepinephrine proves to be unfeasible. The paper only described the dose of the rescue drugs but did not provide detailed information on the concentration and specific operation. Therefore, it is necessary to further clarify how to make the single-dose volume the same to ensure the double-blind state. Finally, we believe that addressing the above issues will enhance the transparency of our research design and facilitate the interpretation of our main findings. We confirm that our article adheres to the TITAN Guidelines 2025, as evidenced by the completed TITAN Guideline Checklist 20256.
Chen et al. (Fri,) studied this question.