Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic

Mehdi Merouani, Bruno Guignard, François Vincent, Stephen W Borron, Philippe Karoubi, Jean-Philippe Fosse, Yves Cohen, Christophe Clec'h, Eric Vicaut, Carole Marbeuf-Gueye, Frederic Lapostolle, Frederic Adnet, Mehdi Merouani, Bruno Guignard, François Vincent, Stephen W Borron, Philippe Karoubi, Jean-Philippe Fosse, Yves Cohen, Christophe Clec'h, Eric Vicaut, Carole Marbeuf-Gueye, Frederic Lapostolle, Frederic Adnet

Abstract

Introduction: The rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock.

Methods: Septic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation.

Results: Nineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] microg/kg versus 1.4 [0.6 to 2.7] microg/kg; P < 0.01).

Conclusions: Our study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion.

Trial registration: Trial registration: Clinicaltrials.gov NCT00763906.

Figures

Figure 1
Figure 1
Scheme for a fuzzy logic based norepinephrine controller. The monitor was connected to a computer that converted the mean arterial pressure (MAP) and norepinephrine infusion rate into fuzzy datasets and automatically calculated the required change in rate of infusion. MAP level and MAP variation (ΔMAP) – the variables to be controlled – are the outputs of the controlled system, whereas the norepinephrine infusion rate is the input to be adjusted to reach the desired MAP value. The infusion rate changed automatically every 7 minutes after analysis of the MAP and the ΔMAP.
Figure 2
Figure 2
Kaplan-Meier curves demonstrating the probability of being on norepinephrine therapy during the study. Comparisons between the time distribution of both groups were performed by means of the generalized Wicolxon (Breslow) test. Competitive risk analysis was performed when the occurrence of death interacted with the event under study (two patients); P < 0.0001.
Figure 3
Figure 3
Time dependence in norepinephrine infusion rate and mean arterial pressure. (a) Norepinephrine (NE) infusion rate and mean arterial pressure (MAP) over time for a representative patient included in the control group. There is a linear decrease in norepinephrine infusion rate. (b) Norepinephrine infusion rate and MAP over time for a representative patient included in the fuzzy group. The change in norepinephrine infusion rate is more or less sinusoidal.

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