Clinical trial NCT03410836: Impact of Intravenous Lidocaine During Colorectal Surgery on Pain and Immune Functions
Official title: Impact of Intraoperative Intravenous Lidocaine Administered During Laparoscopic Colorectal Surgery on Remifentanil Consumption, Postoperative Pain and Immune Cell Activity: A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Intravenous Lidocaine and Immunity
Keywords: lidocaine
colorectal cancer
laparoscopy surgery
anesthesia
inflammation
cytokine
post-operative immunosuppression
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
Collaborators: name: Foundation of Anesthesia and Resuscitation of Quebec
First posted: 2018-01-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups of patients. Randomization into the treatment group or placebo group according to a randomization list for a total number of patients of 60.
Primary purpose: TREATMENT

Brief summary: This study evaluates the impact of intraoperative intravenous lidocaine administered during laparoscopic colorectal surgery on the intraoperative remifentanil consumption as well as postoperative pain and opioid requirements. It will evaluate immune cell activity for 48hours after surgical stress and general anesthesia with or without intravenous lidocaine.

Detailed description: Hypothesis: We hypothesize that the intravenous lidocaine (IVL) versus placebo administered during laparoscopic colorectal surgery will allow for: a reduction in intraoperative remifentanil consumption, an improvement in patients' early rehabilitation after surgery, and an enhancement of the immune profile of our patients through an increase in the balance Th1/Th2 and cellular immunity.

Background: so far, IVL was shown to have several properties: analgesic, anti-inflammatory, and anti-hyperalgesic. Its effects on rehabilitation and pain are still controversial except for abdominal surgery. To date, no study evaluated the impact of IVL in colorectal surgery on intraoperative consumption of remifentanil. Postoperative immune suppression is multifactorial and depends on the surgical traumatism, but also on the doses of opioids given during anesthesia. No study evaluated in colorectal surgery the impact of IVL on postoperative cellular immunity and on the risk of cancer recurrence.

Specific Objectives: primary objective: to reduce by 30% the consumption of remifentanil in the IVL group versus the placebo group; secondary objectives: to evaluate the quality of recovery from anesthesia in the OR (awakening and extubation time), in the PACU and on the wards (pain scores, opioid consumption with patient controlled analgesia (PCA), postoperative nausea and vomiting (PONV), transit recovery time, time in PACU and time in hospital), and to evaluate the postoperative inflammatory parameters and adaptative immune functions (Th1/Th2) until postoperative 48h.

Methods: 60 adult patients ASA 1-3 scheduled for elective laparoscopic colorectal surgery will be included in this randomized controlled trial. Randomisation will be into group Control (C) and Lidocaine (IVL). Anesthesia and monitoring will be standardized and accompanied with the monitoring of the depth of anesthesia (BISpectral index, Medtronic) and the depth of analgesia (NoL index, Medasense LTD, recorded on an observational manner). IVL group will blindly be administered intravenous 1.5 mg/kg lidocaine bolus and then 1.5 mg/kg/h until the end of the surgery as previously described. C group will receive the same amount (ml) of placebo. Statistics: a preliminary analysis (idem group C) showed that the total amount of remifentanil given for this type of surgery was 2481+/-985 mcg (duration 141+/-30Min). Considering that we wish to reduce by 30% the remifentanil consumption in the group IVL, the number of patients to be included per group is 30 (alpha 0.05 and beta 20%).

Significance/Importance: this study will evaluate the impact of IVL on intraoperative consumption of remifentanil but also on immune functions after surgery in order to reduce the risk of cancer recurrence. If this study brings positive results, this will lead to a significant change in clinical practice of anesthesia. This is a pilot study on the immune functions, but this might bring very strong results to ask for future grants on the impact of IVL on cancer recurrence.

Study Design: Prospective, randomized controlled study. Subject Population: Adult patients scheduled to undergo elective laparoscopic colorectal surgery under general anesthesia.

Sample Size: 60 patients will be evaluated in this study. Study Duration: 1 year. Study Center: Maisonneuve-Rosemont Hospital, CIUSSS de l'Est de l'Ile de Montreal, Montreal, Quebec, Canada.

Adverse Events: None expected.

Eligibility criteria: Inclusion Criteria:

* ASA status I, II or III
* Patients older than 18 years
* Colonic surgery
* Classical management of ERAS program patients in our center

Exclusion Criteria:

* Arrhythmia, abnormal electrocardiographic , antiarrhythmic therapy
* Immunosuppressive treatments, corticosteroids or long-term NSAIDs (multiple weekly doses) or during preoperative 48 hours
* conversion intraoperative of a laparoscopic surgical technique to a laparotomy technique
* Pregnant women
* Inability to complete the questions related to this study
* Inability to use hydromorphone postoperative PCA
* Intolerance or allergy to lidocaine, hydromorphone or any other drug that is included in the protocol for perioperative management

Unexpected events leading to the exclusion:

* Difficult unplanned intubation
* Surgical complication requiring aggressive haemodynamic support (vasopressors, inotropes, transfusion)

Primary outcomes:
measure: Reduction of total intraoperative remifentanil consumption by 30% in the intravenous lidocaine ("IVL") group compared with the control group ("C"). Total consumption of remifentanil in mcg.
timeFrame: Intra-operative, 5 hours
Secondary outcomes:
measure: Evaluation of the number of remifentanil boluses given intraoperatively (n)
timeFrame: T0 to end of surgery, 5 hours
measure: Assessment of total consumption of inhaled anesthetic desflurane in ml
timeFrame: intra-operative
measure: Evaluation of time for extubation
timeFrame: post-operative 1 hour
measure: Evaluation of the hydromorphone dose in mg used in the post-operative care unit (PACU) titration
timeFrame: in recovery room, 3 hours
measure: Evaluation of the nausea and vomiting scores, 0 to 3 scale
timeFrame: 48 hours
measure: Evaluation of the length of stay in the recovery room based on the Aldrete scores (Score from 0 to 9)
timeFrame: in recovery room, 3 hours
measure: total hydromorphone consumption (mg) after PACU, on wards
timeFrame: 48 hours
measure: Evaluation of the satisfaction of the patient scale 0 to 100 (%)
timeFrame: 48 hours postoperatively
measure: Assessment of total hospital duration of stay in hours
timeFrame: 7 days postoperatively
measure: Evaluation of the time in hours required for the emission of a first gas in hours
timeFrame: 5 days postoperatively
measure: Assessment of rehabilitation scores and cognitive functions
timeFrame: 2 days
measure: Assessment of cytokines in plasma
timeFrame: 48 hours
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont, CIUSSS de l'Est de l'Ile de Montréal
state: Quebec
Study officials:
affiliation: CIUSSS Est de l'ile de Montreal
name: Philippe Richebé, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: