Determination of the ED50 and ED95 of intravenous bolus of norepinephrine for the treatment of hypotension during spinal anesthesia for cesarean delivery

Abstract

Norepinephrine is considered as a potential alternative for blood pressure stabilization during spinal anesthesia for cesarean delivery, as it maintains a better maternal heart rate and cardiac output compared with phenylephrine. However, its use as a bolus dose for hypotension treatment remains largely unexplored. Therefore, the present study investigated the ED₅₀ and ED₉₅ of norepinephrine as a bolus for maternal hypotension during cesarean delivery. In the present prospective trial, 42 patients were enrolled for elective delivery under spinal anesthesia. The dose of norepinephrine was decided by the up-and-down sequential allocation method (UDM) with an initial dose of 0.075 µg/kg and a 0.025 µg/kg increment. The 42 patients received a bolus of norepinephrine when systolic blood pressure fell to <80% of baseline. The ED₅₀ was calculated by the sequential method and the probit regression model. The ED₉₅ was then calculated using the probit regression model. The ED₅₀ of norepinephrine, which was determined by the UDM, was 0.067 µg/kg (95% CI, 0.056-0.081). The probit regression model calculated an ED₅₀ of 0.072 µg/kg (95% CI, 0.056-0.088) and an ED₉₅ of 0.121 µg/kg (95% CI, 0.1-0.207). In summary, the present results suggested the ED₅₀ of a bolus norepinephrine for preventing hypotension in elective CD is 0.067 µg/kg (95% CI, 0.056-0.081), with an ED₉₅ of 0.121 µg/kg (95% CI, 0.1-0.207).

Keywords: cesarean section; norepinephrine; spinal anesthesia.

Figure 1.

Flowchart of patient recruitment.

Figure 2.

Sequential test diagram. Scatter plot showing effective, represented by a solid dot, and ineffective, represented by an open dot, doses for all 42 participants. Median effective dosage was 0.067 µg/kg (95% CI, 0.056–0.081).

Figure 3.

Norepinephrine dose-effective probability curve. The dose-response curve identified the relationship between the norepinephrine dosage in the patients and the proportion of patients reporting the effectiveness (defined as the SBP returned to within 95% of the baseline value). The ED₅₀ and ED₉₅ were estimated using probit regression model. SBP, systolic blood pressure.