Supported by the Canadian Institutes of Health Research, Natural Sciences and. Engineering Research Council of Canada, Fraser Health, and a Canadian ...
Response to noxious stimuli during closed-loop controlled propofol anesthesia at different remifentanil effect site concentrations Matthias Görges1 , Klaske van Heusden1, Nicholas West2 , Sonia Brodie2 , Aryannah Umedaly2, Christian L Petersen2, Guy A Dumont1 , J Mark Ansermino 2, and Richard N Merchant2 1 2
Departments of Electrical & Computer Engineering, and Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, Vancouver, BC, Canada
Background
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Methods
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Health Canada and research ethics board approval with written informed consent were obtained.
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Induction: Anesthesia was induced using closed-loop propofol (target WAVCNS of 50) and a target-controlled open-loop remifentanil infusion (CeRemi of 2-6 ng/ml at the anesthetists’ discretion) or closed-loop remifentanil infusion (baseline Remi infusion of 0.1 mcg/kg/min).
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Intubation: Laryngoscopy at a time deemed appropriate by anesthesiologist; median 5.5 (2.8-11.5) min. Rocuronium given prior to intubation in 31 subjects.
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Measurements: Heart rate (HR), noninvasive systolic blood pressure (SYS), depth of hypnosis (WAVCNS), and times of intubation and skin incision.
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Data Split: CeRemi more or less than 3.1 ng/ml at the time of stimulation.
Results
»Sample: 79 ASA I-III subjects » 33 females » median age (range) 61 (22-82) years » body mass index of 28 (18-42) kg/m2 » 25 cases with closed-loop Remi infusion
Table 1: Predicted effect site concentrations (Ce) Median (range)
Ce Prop 5 [μg/ml]
Ce Remi 3 [ng/ml]
Intubation Procedure start
5.14 (2.43-8.31) 2.51 (1.45-8.23)
3.03 (2.00-6.15) 3.93 (2.00-9.67)
Δ WAV [−]
Δ HR [bpm]
Δ SYS [mmHg]
50
50
50
0
0
0
−50 50
0
2
4
0
−50
−50 50
0
2
4
0
0
2 4 Time [min]
−50
−50 50
0
2
2 4 Time [min]
−50
0
2 4 Time [min]
Δ HR [bpm]
Δ SYS [mmHg]
50
50
50
0
0
0
−50
4
0
0
Δ WAV [−]
CeRemi >= 3.1 ng/ml
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Results
Past experience: Speculated that, at time of intubation, a higher remifentanil effect site concentration3 (CeRemi) reduces heart rate response to intubation2. Literature: CeRemi of 3 ng/ml, with propofol effect site concentration (CeProp) of 3 μg/ml, has a high probability for successful intubation4. Study Aim: Evaluate, if a CeRemi of at least 3.1 ng/ml would be associated with less somatic response to these stimuli.
50
CeRemi < 3.1 ng/ml
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CeRemi >= 3.1 ng/ml
Closed-loop controlled anesthesia has been shown to effectively control drug administration during induction and maintenance of anesthesia1. We are currently evaluating a closed-loop propofol infusion system, which uses NeuroSENSE (NeuroWave Systems Inc, Cleveland, OH) EEG feedback, for administering anesthesia in adult patients. Feedback systems do not anticipate intense stimulation, like intubation or skin incision.
CeRemi < 3.1 ng/ml
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0
2
4
−50 50
0
−50
0
2
4
0
0
2 4 Time [min]
−50
−50 50
0
2
4
0
0
2 4 Time [min]
−50
0
2 4 Time [min]
Figure 1: Response to intubation (left subplot) and skin incision (right subplot), split by CeRemi greater than 3.1 ng/ml (top row; n=42 for intubation, n=51 for skin incision) and lower than 3.1 ng/ml (bottom row; n=35 for intubation, n=24 for skin incision). Data are scaled to zero at the time of the stimulus, to show relative changes, with population percentile values (5%, 50%, and 95%) overlaid as black lines
Discussion »
Higher CeRemi has only a minor effect on intubation response » Median HR increase reduced by 1 bpm » Median SYS increase reduced by 1.5 mmHg » Reduced WAVCNS overshoot by 2 units at 5 min » Higher CeRemi reduces HR and WAVCNS variability after skin incision » Limitations: Timing and WAVCNS at intubation are different between patients. CeRemi is likely not in steady state and may not reflect the patient’s kinetics. » Future work: Evaluate performance of closed-loop control of analgesia?
A cknowledgements » 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.
References
» [1 ] An est h An alg . 2 0 1 3 ;1 1 7 (5 ):1 1 3 0 -3 8 » [2 ] Proc 2 0 1 3 ISAP An n Mt g ;2 0 1 3 ; A2 2 » [3 ] An est h esiolog y. 1 9 9 7 ;8 6 (1 ):1 0 -2 3 » [4 ] An est h esiolog y. 2 0 0 4 ;1 0 0 (6 ):1 3 7 3 -8 1 » [5 ] An est h esiolog y. 1 9 9 8 ;8 8 (5 ):1 1 7 0 -8 2
