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Prophylactic norepinephrine combined with 6% hydroxyethyl starch (130/0.4) co-load infusion for preventing postspinal anesthesia hypotension during cesarean section: a randomized, controlled, dose-finding trial

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Abstract

Purpose

Colloid and/or co-load may be more effective than crystalloid for preventing postspinal anesthesia hypotension. We tested five different prophylactic norepinephrine dosages combined with colloid co-load infusion in patients receiving cesarean section and spinal anesthesia.

Methods

Patients were randomly allocated to receive different prophylactic norepinephrine dosages (0 [NE 0 group], 0.025 [NE 25 group], 0.05 [NE 50 group], 0.075 [NE 75 group], or 0.1 [NE 100 group] µg/kg/min) combined with 500 mL 6% hydroxyethyl starch (130/0.4) immediately following spinal anesthesia (n = 35 per group). The primary endpoint was the incidence of postspinal anesthesia hypotension (systolic blood pressure [SBP] < 80% of baseline). Secondary endpoints included severe hypotension, bradycardia, nausea or vomiting, hypertension, SBP stability control versus baseline, the 50% (effective dose, ED50) and 90% (ED90) dose effective for preventing postspinal anesthesia hypotension, Apgar scores, and umbilical cord blood gases.

Results

The incidence of postspinal anesthesia hypotension was 48.6%, 31.3%, 17.1%, 14.3%, and 5.7% in the respective groups. As the prophylactic norepinephrine dosage increased, the incidence of postspinal anesthesia hypotension declined (p < 0.001), and SBP remained stable relative to baseline (median performance error [MDPE], p < 0.001; median absolute performance error [MDAPE], p = 0.001). The ED50 and ED90 values were -0.006 (95% CI -0.046—0.013) and 0.081 (95% CI 0.063—0.119) µg/kg/min. Other endpoints were comparable across the groups.

Conclusion

An initial prophylactic norepinephrine dosage of 0.05 µg/kg/min combined with 500 mL 6% hydroxyethyl starch (130/0.4) co-load infusion was optimal for preventing postspinal anesthesia hypotension during cesarean section.

Trial registration

NCT05133817, registration date: 12 Nov, 2021.

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Acknowledgements

The authors thank Heather L. McConnell, PhD of Houston Methodist Hospital in Houston, Texas, USA for editing assistance.

Funding

This work was funded by the Key Research and Development Program of Ningxia (grant number: 2021BEG03039) and the Ningxia Natural Science Foundation (grant number: 2022AAC03591).

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Author notes

  1. Lei Guo and Xiangsheng Xiong contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, 804S Shengli Street, Yinchuan, 750004, Ningxia, China

    Lei Guo, Rui Qin, Zhenzhou Li, Yongqiang Shi & Yi Chen

  2. Department of Anaesthesiology, The Fifth People’s Hospital of Huaian, Huaian, Jiangsu, China

    Xiangsheng Xiong

  3. Department of Obstetrics, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China

    Wei Xue, Ling He & Shuqin Ma

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Contributions

LG, XSX, ZZL and YC contributed to the analysis of the data. All the authors contributed to the study’s conception and design, writing, review, editing, and final approval of the manuscript.

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Correspondence to Yi Chen.

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Guo, L., Xiong, X., Qin, R. et al. Prophylactic norepinephrine combined with 6% hydroxyethyl starch (130/0.4) co-load infusion for preventing postspinal anesthesia hypotension during cesarean section: a randomized, controlled, dose-finding trial. DARU J Pharm Sci (2023). https://doi.org/10.1007/s40199-023-00479-7

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