Clinical trial NCT03910998: Impact of Intraoperative Deep Neuromuscular Blockade on NOL-guided Opioid Requirement in LSC Colorectal Surgeries
Official title: A Randomized Parallel Design Study to Compare the Impact of Intraoperative Deep Neuromuscular Blockade on Intraoperative NOL-guided Opioid Requirement and Postoperative Early Outcomes in Laparoscopic Colorectal Surgeries
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Laparoscopic Colorectal Surgeries
Keywords: neuromuscular blockade
NOL monitoring
opioid consumption
intraoperative
anesthesia
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
Collaborators: name: Merck Canada Inc.
First posted: 2019-04-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Tow groups of patients. Randomization into group "D" for Deep muscle relaxation vs group "M" for Moderate muscle relaxation according to a randomization list for a total number of 100 patients
Primary purpose: TREATMENT

Brief summary: The aim of the present study is to answer the question whether deep neuromuscular blockade has a clinically significant impact on intra and postoperative pain, opioid requirement and anesthesia related outcomes and side effects for the early phase of recovery (24hs) after colorectal laparoscopic surgery.

Detailed description: Background: For the last decade many studies have reported that intraoperative surgical and anesthesia conditions might have an impact of postoperative pain.

The most recent surgical literature agrees on the fact the IAP should remain under 15mmhg or even 12mmhg during the whole laparoscopic surgery, and many efforts to do so were developed in the most recent years. On the anesthesia side, deep neuromuscular block was associated with better postoperative recovery when looking at pain parameters such as pain scores and opioid requirements. Nevertheless, all these previous studies, even if recent, did not properly evaluate intraoperative pain and did not well control criteria used to guide the administration of intraoperative opioids, one of the main components of anesthesia. Also, lots of these studies did not properly evaluate or control the depth of hypnosis, another main component of anesthesia. Nowadays, new monitors with extremely better sensitivity and specificity are available for each of the anesthesia component. This might completely revisit the previous findings in the literature and offer much better-quality results. Maisonneuve-Rosemont Hospital in Montreal is a unique center that has invested in new monitors to evaluate each of these anesthesia component: BIS index for depth of hypnosis (BIS device, Covidien, Saint-Laurent, Canada), NOL index (PM-200TM device, Medasense LTD, Ramat Gan, Israel) for nociceptive evaluation (intra-operative pain assessment under general anesthesia), and TOF-scan (NMB monitor, Drager, Mississauga, Canada) for quantitative and 3D evaluation of the depth of muscle relaxation.

This study will answer the question whether deep neuromuscular blockade has a clinically significant impact on intra and postoperative pain, opioid requirement and anesthesia related outcomes and side effects for the early phase of recovery (24hs) after colorectal laparoscopic surgery.

This study will be conducted in a single center, and will be an open label, single blinded, randomized controlled study. Type of surgery: laparoscopic colorectal surgery with anesthesia time expected to last more than 120min in ASA 1-3 patients, fully consented for primary colorectal laparoscopic surgery.

The primary objective of the study: To compare total intra-operative remifentanil consumption during anesthesia for laparoscopic colorectal surgery between two groups: Group "D" for Deep muscle relaxation and group "M" for Moderate muscle relaxation. Secondary objectives are listed below. For an expected decrease of 25% in the remifentanil intraoperative consumption per hour of surgery (in mcg) of surgery, with a type I error α = 0.05 (two-tailed), a 90% power, the total sample size needed is 82 (41 per group). To account for an approximative 20% rate of loss to follow-up or missing data due to technical problems, a total of 100 subjects will be recruited.

Study Duration: 24 months. Study Center: Maisonneuve-Rosemont Hospital, CIUSSS de l'Est de l'Ile de Montreal (CEMTL), University of Montreal, Montreal, Quebec, Canada.

Adverse Events: None expected. Subvention: An Independent Investigator Initiated Trial (IIIT) grant application has been accepted by the company Merck (see letter attached) for the sponsoring of this study.

Eligibility criteria: Inclusion Criteria:

* ASA1-3 patients,
* fully consented,
* primary colorectal laparoscopic surgery and no previous laparotomy for the last 5 years
* BMI \< 35,
* Age \> 18yo,
* no allergy to any of the medications used in this study.

Exclusion Criteria:

* history of coronary artery disease
* serious cardiac arrhythmia (including atrial fibrillation)
* history of substance abuse
* chronic use of psychotropic and/or opioid drugs
* use of drugs that act on the autonomic nervous system (including β-blockers)
* history of psychiatric diseases with the need of medication
* allergy to any drug used in the study protocol
* refusal of the patient for participation in the study

Primary outcomes:
measure: Total intra-operative remifentanil consumption during surgery in mcg/kg/h
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
Secondary outcomes:
measure: Number of IV boluses and increases of remifentanil infusion, number, no unit
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Number of times NOL index passes over the threshold of 25, number, no unit
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Area Under the Curve (AUCs) whenever the NOL is above 25, no unit
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Total intraoperative time from T0 until Tend with NOL above 25 in minutes
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Intraoperative level of intra-abdominal pressure (IAP) in mmHg
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Abdominal insufflation duration in minutes
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Time for awakening and extubation in seconds
timeFrame: Intra-operative (from T0 incision until Tend = start dressing)
measure: Pain score at rest on a scale from 0 to 10
timeFrame: every 15 minutes until discharge from PACU, up to 3 hours
measure: Pain score at coughing/mobilization on a scale from 0 to 10
timeFrame: every 15 minutes until discharge from PACU, up to 3 hours
measure: Pain score at the shoulder on a scale from 0 to 10
timeFrame: every 15 minutes until discharge from PACU, up to 3 hours
measure: Postoperative Hydromorphone consumption in mg in Postoperative Care Unit (PACU)
timeFrame: every 15 minutes until discharge from PACU, up to 3 hours
measure: Pain score at rest at 8hs on a scale from 0 to 10
timeFrame: 8 hours after surgery in hospital
measure: Pain score at coughing/mobilization at 8hs on a scale from 0 to 10
timeFrame: 8 hours after surgery in hospital
measure: Pain score at rest at 16hs on a scale from 0 to 10
timeFrame: 16 hours after surgery in hospital
measure: Pain score at coughing/mobilization at 16hs on a scale from 0 to 10
timeFrame: 16 hours after surgery in hospital
measure: Pain score at rest at 24hs on a scale from 0 to 10
timeFrame: 24 hours after surgery in hospital
measure: Pain score at coughing/mobilization at 24hs on a scale from 0 to 10
timeFrame: 24 hours after surgery in hospital
measure: Amount of opioids received in 24h as Patient Controlled Analgesia in mg
timeFrame: 24 hours after surgery in hospital
measure: Recovery score QOR15 questionnaire (150 points maximum for this questionnaire)
timeFrame: 24 hours after surgery in hospital
measure: POSS postoperative Sedation score in PACU on a scale from 1 to 4
timeFrame: every 30 minutes from T0 = arrival in PACU until discharge from PACU, up to 3 hours
measure: postoperative nausea and vomiting score in PACU on a scale from 0 to 3
timeFrame: every 30 minutes from T0 = arrival in PACU until discharge from PACU, up to 3 hours
measure: postoperative Aldrete score in PACU on a scale from 5 to 15
timeFrame: every 30 minutes from T0 = arrival in PACU until discharge from PACU, up to 3 hours
Other outcomes:
Locations:
city: Montréal-Est
country: Canada
facility: Hopital Maisonneuve Rosemont, CIUSSS de l'Est de l'Ile de Montréal
state: Quebec
Study officials:
affiliation: CIUSSS Est de l'île de Montréal
name: Philippe PR Richebé, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: