Acknowledgements. »Supported by the Canadian Institutes of Health Research, Natural Sciences and. Engineering Research Council of Canada, Fraser Health ...
Response to noxious stimuli in closed-loop controlled propofol anesthesia with target controlled infusion of remifentanil Matthias Görges1, Klaske van Heusden1, Nicholas West2, Aryannah Umedaly2, Christian L Petersen2, Guy A Dumont1, J Mark Ansermino2, and Richard N Merchant2 Departments of 1Electrical & Computer Engineering, and 2Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, Vancouver, BC, Canada
Background
Results
» Closed-loop controlled anesthesia can
effectively control drug administration during induction and maintenance of anesthesia1.
» Problem: Its effectiveness in minimizing
physiological responses to specific noxious stimuli is not understood.
» Study Aim: Evaluate, in adults, the
Δ WAV
CNS
20 10
Methods
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» Induction: Anesthesia was induced using
closed-loop propofol (target WAVCNS of 50) and a target-controlled open-loop remifentanil infusion (estimated effect site concentration3 of 2-5 ng/ml at the anesthetists’ discretion).
» Intubation: The subjects’ airway was
instrumented at a time deemed appropriate by the anesthetist. Rocuronium was given prior to intubation in 25 subjects.
» Measurement: Heart rate (HR), non-invasive systolic blood pressure (SYS), depth of hypnosis (WAVCNS), and times of intubation and procedure start were recorded.
References » [1] Anesth Analg. 2013 doi: 10.1213/ANE.0b013e3182973687, [2] Paediatr Anaesth 2013;23(8):712-9, [3] Anesthesiology. 1997;86(1):10-23, [4] Anesthesiology. 1998;88(5):1170-82.
Δ SYS [mmHg]
30
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board approval with written informed consent for 35 ASA I-III subjects (13 female); » median age (range) 63 (39-82) years; » body mass index of 28 (18-34) kg/m2.
Δ HR [bpm]
Table 1: Predicted effect site concentrations (Ce) Median (range)
Propofol4 Ce [μg/ml]
Remifentanil3 Ce [ng/ml]
Intubation Start of Procedure
5.47 (3.21-8.31) 2.62 (1.47-7.04)
2.02 (2.00-6.03) 3.02 (2.00-6.82)
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performance of a closed-loop propofol infusion system2, using NeuroSENSE (NeuroWave Systems Inc, Cleveland, OH) EEG feedback, in providing adequate anesthesia to block responses to stimuli from endotracheal intubation and skin incision.
» Sample: Health Canada and research ethics
[−]
50
» Stimulus Response: Figure 1 shows WAVCNS, HR and SYS values
measured one minute before the stimulus, at the time the stimulus was marked, and 5 minutes after the stimulus for all subjects.
0
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Discussion
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» Intubation Response: Intubation at a median WAVCNS index of 51
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0 2 Intubation
4
Δ WAV
[−]
CNS
0
2 4 Time [min]
0
2
4
Δ HR [bpm]
Δ SYS [mmHg]
50
(range 27-82) resulted in a small HR increase (median 8 bpm), followed by a rapid return to baseline. SYS remained unchanged during intubation, followed by a median decrease of 14 mmHg 5 min after intubation, which coincided with a median drop in WAVCNS index by 18 – this overshoot was likely amplified by response to stimulation and consequent loss of this stimulation.
» Skin Incision Response: HR and SYS response to procedure start
40
showed small increases of 2 bpm and 8 mmHg respectively, indicating the closed-loop system successfully controlled anesthetic depth to reduce the subjects’ response to this strong stimulus.
30 20
» Mitigation strategies: » An additional remifentanil bolus or delayed time to intubation may
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»
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» Future work: Anesthetic phase based adaptation / prediction of patient stimulation to guide controller response.
−40 −50 0 2 Procedure Start
be needed to mitigate the HR response to intubation and to reduce the overshoot. Closed loop control of remifentanil may be needed to adequately respond to fast changes in WAVCNS.
4
0
2 4 Time [min]
0
2
4
Figure 1: Stimulation response data for intubation (top) and start of procedure (bottom). The data was adjusted to zero at the time of the stimulus, and population percentile values (5%, 25%, 50%, 75%, and 95%) overlaid as black lines.
Acknowledgements » Supported by the Canadian Institutes of Health Research, Natural Sciences and
Engineering Research Council of Canada, Fraser Health, and a Canadian Institutes of Health Research Postdoctoral Fellowship [M. Görges]. The authors would like to thank all participating subjects and anesthesiologists.
