Performance of a closed-loop feedback computer-controlled infusion system for maintaining blood pressure during spinal anaesthesia for caesarean section: a randomized controlled comparison of norepinephrine versus phenylephrine

Abstract

Closed-loop feedback computer-controlled vasopressor infusion has been previously described for maintaining blood pressure during spinal anaesthesia for caesarean section but there are limited data available comparing the relative performance of different vasopressors. The aim of this study was to compare the performance of norepinephrine versus phenylephrine in this system. Data from a randomized, two-arm parallel group, double-blinded controlled trial were reanalyzed. 104 patients scheduled for elective caesarean section under spinal anaesthesia were randomized to receive computer-controlled closed-loop infusion of either norepinephrine 5 µg ml⁻¹ or phenylephrine 100 µg ml⁻¹. This was started immediately after induction of spinal anaesthesia and used an algorithm designed to maintain systolic blood pressure near baseline until fetal delivery. Performance error calculations were used to compare the performance of the two vasopressors. The primary outcome was defined as the median absolute performance error. Median performance error, wobble and divergence were also compared. Median absolute performance error was smaller in the norepinephrine group (median 3.79 [interquartile range 2.82–5.17] %) versus the phenylephrine group (4.70 [3.23–6.57] %, P = 0.028). In addition, median performance error was smaller (0.75 [−1.56–2.52] %) versus 2.61 [0.83–4.57] %, P = 0.002) and wobble was smaller (2.85 [2.07–5.17] %) versus 3.39 [2.62–4.90] %, P = 0.028) in the norepinephrine group versus the phenylephrine group. Divergence was similar between groups. The precision of the control of blood pressure was greater with norepinephrine compared with phenylephrine at the drug concentrations used.

Appendix: Derivation of performance error calculations

1.1 Performance error (PE)

PE was defined as the difference between each measured value of systolic blood pressure (SBP) and the baseline value, expressed as a percentage of the baseline value. For each patient until the time of uterine incision, it was calculated as follows:

$$PEij = \frac{(meaSBPij - tarSBPi)}{tarSBPi} \times 100$$

(1)

where PEij is the percentage performance error for the ith patient at the jth minute, meaSBPij is the measured SBP for the ith patient at the jth minute and tarSBPi is the target SBP (set-point for the closed-loop system) for the ith patient.

1.2 Median performance error (MDPE)

MDPE is a measure of bias and describes whether the measured values for SBP are systematically either above or below the baseline value. For each patient, it was defined as the median of all values of PE and was calculated as follows:

$$MDPEi = {\text{ median}}\left\{ {PEij,\quad j = \, 1, \ldots ,Ni} \right\}$$

(2)

where MDPEi is the median performance error for the ith patient and Ni is the number of values for PE obtained for the ith patient.

1.3 Median absolute performance error (MDAPE)

MDAPE is a measure of inaccuracy and represents an average of the magnitudes of the differences of measured values for SBP above or below the baseline value. For each patient, it was defined as the median of the absolute values of PE (|PE|) and was calculated as follows:

$$MDAPEi = {\text{ median}}\left\{ {|PEij|,\quad j = \, 1, \ldots ,Ni} \right\}$$

(3)

where MDPEi is the median absolute performance error for the ith patient.

1.4 Wobble

Wobble is a measure of the intrasubject variability of PE about MDPE. It was calculated as follows:

$$WOBBLEi = {\text{ median}}\left\{ {|PEij - MDPEi|,\quad j = \, 1, \ldots ,Ni} \right\}$$

(4)

where WOBBLEi is the wobble for the ith patient.

1.5 Divergence

Divergence describes the trend of changes in |PE| with time and is a measure of whether the magnitudes of the differences between measured and target values for SBP increase (positive value for divergence) or decrease (negative value for divergence) with time. It was defined for each patient as the slope of the linear regression equation of the values of |PEij| for that patient against time. It was calculated as follows:

$$DIVERGENCEi = \frac{{Ni\sum\nolimits_{j = 1}^{Ni} {(Tij \times \left| {PEij} \right|) - \sum\nolimits_{j = 1}^{Ni} {Tij \times \sum\nolimits_{j = 1}^{Ni} {\left| {PEij} \right|} } } }}{{Ni\sum\nolimits_{j = 1}^{Ni} {Tij^{2} - \left( {\sum\nolimits_{j = 1}^{Ni} {Tij} } \right)^{2} } }}$$

(5)

where DIVERGENCEi is the divergence for the ith patient and T is time in minutes.