NoL and BIS Monitoring on Patients Recovery and Safety After Surgery

Study Overview
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Brief Summary
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So far, only vital signs (mostly, blood pressure and heart rate) helped the anesthesiologist to administer hypnotic agents or analgesics. Many devices have offered pain monitoring for anesthetized patients, the most recent being the PMD200 device and its NoL index. The BIS index is widely used for depth of anesthesia monitoring. The hypothesis of this study is that the intraoperative combination of both the NoL and the BIS indices to guide the delivery of opioids and hypotonics respectively, will improve the quality of recovery as well as the safety after anesthesia in ERAS patients undergoing colonic surgery.

Detailed Description
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Hypothesis is that the intraoperative use of the combination of 1) the NoL index (given by the PMD200TM monitor, Medasense LTD inc, Ramat, Israel) to monitor pain levels and to guide opioids' administration during surgery, and 2) the BIS index (Medtronic, St-Laurent, QC, Canada) to monitor the depth of hypnosis during anesthesia and to guide the administration of anesthetic halogenous gases, will improve the quality of recovery as well as the safety after anesthesia in ERAS (Early Rehabilitation After Surgery) patients undergoing colonic surgery under general anesthesia + epidural analgesia. This study will compare a group of patients monitored by the classical monitoring (with anesthesia/analgesia guided by these classical parameters: heart rate, blood pressure; Control C group; no BIS, no NoL) to a group of patients monitored by the same classical monitoring implemented with the NoL/BIS indices (with analgesia/anesthesia guided by these 2 indices; Monitoring M group). The primary objective of the study will be the total consumption of desflurane that is expected to be significantly reduced in the M group. Secondary objectives will be evaluating safety and side effects of anesthesia and opioids and we expect a reduction of the following parameters: time for awakening from anesthesia, time for extubation, time for transfer to PACU, intraoperative opioid consumption, opioid consumption in PACU and for 48h, time for readiness for discharge from PACU, incidence of adverse effects such as: nausea-vomiting / sedation / respiratory depression / itching / dizziness / cognitive dysfunction in PACU and for 48h, satisfaction of the patients at 24 and 48hs, pain scores at rest and at mobilization in PACU, at 24h and 48h. Quality of postoperative recovery after surgery and treatment satisfaction are also expected to be higher in the M group than in the C group.

Official Title
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Evaluation of the Combined Intraoperative Depth of Analgesia (NoL) and Depth of Anesthesia (BIS) Monitoring on the Patients' Recovery and Safety After Surgery: A Pilot Study

Conditions
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Pain, Anesthesia

Intervention / Treatment
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* Device: BIS index/NoL index
* Device: Variation of baseline mean arterial pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA status I, II or III Patients aged 18 years Colo-rectal surgery Duration and type of surgery requiring an epidural analgesia via an epidural catheter placed prior the general anesthesia induction and an arterial line placed after induction of general anesthesia (classical management of ERAS program patients in our center) Exclusion Criteria: chronic arhythmic condition chronic pain Adverse events prompting termination of protocol: Unexpected difficult airway requesting excessive, possibly painful airway manipulations. Unexpected surgical complications requiring strong haemodynamic support (transfusions, volume challenges, vasopressors, inotropic drugs)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control (C Group )<br>Intervention for intraoperative analgesic administration will be based on heart rate and blood pressure variations. Intervention for intraoperative hypnotice/desflurane administration will based on keeping the MAC at 0.8. | Device: Variation of baseline mean arterial pressure<br>* Remifentanil i.v. infusion will be run between 0.03 and 0.15 mcg/kg/min and boluses (0.4mcg/kg) will be given to keep a baseline mean arterial pressure between 10% of variation. Once intubated, the maintenance of anesthesia will be achieved with: desflurane set at 1 MAC to start, then ajusted to 0.8 MAC.<br>|
| Experimental: Monitoring (M Group )<br>Intervention for intraoperative analgesic administration will be based on the NOL index (to keep it below 25). Intervention for the desflurane administration will be based on the BIS index (to keep it between 40-60). | Device: BIS index/NoL index<br>* Remifentanil i.v. infusion will be run between 0.03 and 0.15 mcg/kg/min and boluses (0.4mcg/kg) will be given to keep a NoL index between 10-20. Once intubated, the maintenance of anesthesia will be achieved with: desflurane set at 1 MAC to start, then adapted to the BIS between 45-55.<br>* Other names: PMD200, Bispectral index;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total desflurane consumption | Total consumption and absorption in ml/kg/h of desflurane in group C versus group M | 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hourly desflurane consumption | Consumption and absorption of desflurane in ml/kg/h for each hour of surgery. These data are given by the Drager Perseus A500 ventilator per second during the surgery. | 10 hours | 
| Total remifentanil consumption mcg/h | Total consumption of i.v. remifentanil during surgery and for each hour of surgery | 10 hours | 
| Hypotensive events | Total number of hypotensive events during surgery defined as mean blood pressure below 10% of baseline | 10 hours | 
| Total phenylephrine consumption mcg/h | Total doses of intraoperative infused i.v. phenylephrine and doses per hour | 10 hours | 
| Emergence time (seconds) | Time for awakening (eyes opening) at the end of the surgery, time for extubation, time for transfer to the PACU in seconds | 30 min | 
| Acute pain (NRS scores on scale from 0 to 10) | NRS scale pain score at rest | 48 hours postoperatively | 
| Analgesic requirement (total ml of epidural solution consumption) | cumulative dose over 48hs | 48 hours postoperatively | 
| Nausea and vomiting | on Nausea and vomiting scale from 0 to 4, cumulative scores over 48hours | 48 hours postoperatively | 
| Postoperative sedation | On POSS (postoperative sedation score) scale from 0 to 5, cumulative over 48 hours | 48 hours postoperatively | 
| Postoperative respiratory depression | yes or no (1 or 0) for 48 hours | 48 hours postoperatively | 
| PACU discharge time in minutes | Time for readiness for PACU discharge based on Aldrete scores superior to 9. | 3 hours | 
| Postoperative cognitive dysfunction | Assessment of perioperative cognitive function using the classical MMSE scores over 5 days | 5 days postoperatively | 
| Postoperative delirium | Assessment of perioperative Delirium with NuDESC score over 5 days after surgery | 5 days postoperatively | 
| Postoperative analgesia hydromorphone rescue | Total hydromorphone rescue doses for 5 days, and total epidural doses in ml as continuous infusion + boluses (PCEA) | 5 days postoperatively | 
| Recovery after surgery score on scale QOR15 (scale 0 to 150) | Patients' perceived quality of recovery from anesthesia with QoR-15 | 5 days postoperatively | 
| Postoperative chronic pain (score 0 to 10) | Presence and severity of persistent postoperative pain with DN4 questionnaires | 6 months postoperatively | 
| Postoperative chronic pain (scale 0 to 60) | Presence and severity of persistent postoperative pain SF-MPQ questionnaires | 6 months postoperatively | 
| Mortality | Rate of hospital mortality up to 6 months following surgery | 6 months postoperatively | 
| Readmission | Rate of hospital readmission up to 6 months following surgery | 6 months postoperatively | 
| POCD/POD related inflammatory cytokines | Blood sample will be drawn and cytokines related to POCD/POD will be measured | 24h postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NoL index, Bispectral index, Intraoperative monitoring