Nociception During Anesthesia in Patients Taking ß1-adrenergic Antagonist Chronic Treatment Clinical Trial
Official title:
Impact of Chronic Treatment by β1-adrenergic Antagonists on Nociceptive-Level (NOL) Index Variation After a Standardized Noxious Stimulus Under General Anesthesia: An Observational Study
The aim of the present study is to investigate the effect of chronic treatment with β1-adrenergic antagonist on the NOL index variation, the heart rate variation and the mean blood pressure variation after a standardized noxious stimulus.
Hypothesis: We hypothesize that the NOL values variations obtained in response to a
standardized noxious stimulus under general anesthesia in a group of patients chronically
treated with β1-adrenergic antagonists, will be similar to the NOL values variations
previously obtained in response to a similar standardized noxious stimulus and previously
reported in a group of patients without any β1-adrenergic antagonist.
Background: The Pain Monitoring Device (PMD200TM) monitor (Medasense Biometrics Ltd., Ramat
Gan, Israel) uses the Nociception Level (NOL) index, a multiple parameter-derived index that
has recently shown a good sensitivity and specificity to detect noxious stimuli. The NOL
index variations of the latest version of the PMD200TM has shown better sensitivity and
specificity to detect standardized noxious stimulus than heart rate or blood pressure
variation in a population without any β1-adrenergic antagonist treatment. β1-adrenergic
antagonist treatment was so far a limitation to the use of the NOL index. Indeed,
β1-adrenergic antagonists have a depressive action on the heart rate, including limitation of
the heart rate variability after a noxious stimulus. Because heart rate and its variability
are parameters which are part of the parameters combined to build the NOL index, chronic
treatment with β1-adrenergic antagonist could alter the ability of the NOL index to detect
noxious stimulus. However, Edry R. (Edry R, 2017) assessed the impact of chronic treatment
with β1-adrenergic antagonist on NOL index variation after noxious stimuli in a pilot study
(9 patients under chronic treatment with β1-adrenergic antagonist and under general
anesthesia) and didn't show any influence of this treatment on the NOL index variation. But
this study was not large enough and did not fully answered the question whether chronic
treatment with β1-adrenergic antagonist might impact NOL ability to detect precise and
standardized stimulus and to compare the results to those in patients without this type of
chronic medication.
Objectives:
Primary objective:
To explore the NOL variation in a group of patients under chronic treatment with
β1-adrenergic antagonists submitted to standardized noxious stimulus under general
anesthesia.
Secondary objectives:
Secondary outcome [1] To explore the heart rate variation and the mean blood pressure
variation in a group of patients under chronic treatment with β1-adrenergic antagonists
submitted to standardized noxious stimulus under general anesthesia.
Secondary outcome [2] To compare the heart rate variation and the mean blood pressure
variation in a group of patients under chronic treatment with β1-adrenergic antagonists
submitted to standardized noxious stimulus under general anesthesia to a control group of
patients without any β1-adrenergic antagonist chronic treatment; results gathered from a
previous study (Renaud-Roy E, 2019), exposed to the same noxious stimulus and under the same
anesthesia conditions.
Secondary outcome [3] To explore the ability of the NOL index, the heart rate and the mean
blood pressure to discriminate between noxious and non-noxious states in a group of patients
with β1-adrenergic antagonist chronic treatment submitted to standardized noxious stimulus
under general anesthesia. To determine sensitivity and specificity (ROC curve and AUC of ROC)
for each parameter: HR, MAP, NOL index.
Secondary outcome [4] To evaluate the NOL index, the heart rate and the mean blood pressure
variations after tracheal intubation in patients with β1-adrenergic antagonist chronic
treatment.
Methods:
Adult patients undergoing general anesthesia for any types of surgery and who have been
chronically treated with β1-adrenergic antagonists for at least three months prior to surgery
will be enrolled to reach a total of patients with full analysis of data of n=25. All
patients will be consented prior to the surgery. Induction of anesthesia will be standardized
for all patients and based on their adjusted body weight calculated before induction, with:
IV midazolam (0.02mg/kg), IV propofol (1.5-2mg.kg-1), IV remifentanil (1mcg.kg-1 followed by
a continuous infusion of 0.05 µg.kg-1.min-1), IV rocuronium (0.6 to 1mg.kg-1). Depth of
anesthesia with desflurane will be maintained and monitored with the BIS index kept between
40 and 60. Intubation will be performed 3 minutes after the intravenous administration of the
propofol, remifentanil and rocuronium boluses. The end of the bolus of remifentanil (given
1mcg/kg; adjusted body weight) will be the start of the 3 min period to wait before
proceeding with the tracheal intubation. Three minutes after intubation, the remifentanil
infusion will be decreased to 0.005 µg.kg-1.min-1 to reduce the risk of developing
hypotensive events and to prepare the patient for the standardized noxious stimulus of the
study protocol realized under very low doses of opioids under desflurane hypnosis with BIS
40-60.
At least 10 min after the post-intubation decrease of the remifentanil infusion rate, the OR
team will stop any physical contact/stimulation of the patient allowing at least a 3-minutes
rest period under stable anesthesia. Baseline mean arterial blood pressure (MAP) and heart
rate (HR) will be defined for the rest of the study as the mean of 3 measures in the 3
minutes during this "no pain - no touching" evaluation period to get baselines values of all
the study parameters. If necessary, phenylephrine will be given to keep a MAP > 65 mmHg.
At this point, the standardized electrical (tetanic) stimulation will be applied on the area
of the ulnar nerve at the wrist level, at a frequency of 100 Hz and a current of 70 mA for a
duration of 30 seconds, followed by 3 minutes of observation period without any other
stimulation of the patient by the anesthesia or the surgical team (EZstimII, Model ES400,
Life-Tech, Stafford, Tx, USA). At the end of the observation period, the study is
discontinued and the anesthesia will be conducted at the discretion of the anesthesiologist
in charge of the patient.
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