Perioperative Systemic Lidocaine for Enhanced Bowel Recovery After Bariatric Surgery
Perioperative Systemic Lidocaine for Enhanced Bowel Recovery After Bariatric Surgery
Increasing rates of obesity over the last few decades have led to growing demand for
 bariatric surgery, which may resulted in decreased comorbidities and improved patient
 outcomes. Laparoscopic bariatric surgery has several clinical benefits in terms of improved
 quality of analgesia, reduced pulmonary complications, enhanced recovery of bowel function,
 less immune suppression, and shortened duration of hospital stay than open laparotomies.

 Some investigators reported delayed return of bowel function for approximately two days after
 laparoscopic bariatric surgery, despite it occurred one day earlier than after open
 laparotomy. This potentially can lengthen the duration of hospital stay after bariatric
 procedures. With the impeding cost of health care in the developing countries, safely
 reducing length of stay is essential.

 Other investigators reported early return of bowel movements during the first postoperative
 day in 65% of patients undergoing laparoscopic gastric bypass surgery due to reduced morphine
 use with implementation of a multimodal analgesia strategy including ketorolac, and
 propoxyphene hydrochloride/acetaminophen.

 Lidocaine was investigated in several studies for its use in multi-modal management
 strategies to reduce postoperative pain and opioid use and enhance recovery. A recent
 Cochrane review including 45 trials demonstrated that systemic administration of lidocaine
 was associated with reduced pain scores at most of 'early time points' in patients undergoing
 laparoscopic abdominal surgery (MD -1.14, 95% CI -1.51 to -0.78; low-quality evidence),
 shorter times to first flatus (MD -5.49 hours, 95% CI -7.97 to -3.00; low-quality evidence)
 and first bowel movement (MD -6.12 hours, 95% CI -7.36 to -4.89; low-quality evidence), and
 less risk of paralytic ileus (risk ratio (RR) 0.38, 95% CI 0.15 to 0.99; low-quality
 evidence). However, no evidence of effect was found for lidocaine on shortening the time to
 first defecation. This low-quality evidence may be related to the heterogeneity between the
 studies in respect to the optimal dose, timing and duration of the administration of
 intravenous lidocaine.
Hypothesis

 Recognizing the need for enhanced bowel recovery for patients undergoing laparoscopic
 bariatric surgery, the investigators hypothesize that perioperative administration of low
 rather than high intravenous infusion rates of lidocaine can achieve early postoperative
 restoration of bowel motility at lower plasma levels.

 Up to the best of the investigators' knowledge there is no study addressed the effects of
 perioperative administration of systemic lidocaine on postoperative recovery of bowel
 function in morbidly obese patients undergoing laparoscopic bariatric procedures.

 Aim of the study

 This trial aims to compare the effects of perioperative administration of escalating doses of
 intravenous lidocaine (1.0, 1.5 and 2.0 mg/kg/h) on the perioperative changes in hemodynamic,
 pain scores, and plasma lidocaine concentrations, postoperative recovery of bowel function,
 cumulative morphine use, hospital length of stay, and lidocaine related adverse effects in
 obese patients undergoing laparoscopic bariatric surgeries under general anesthesia.

 Randomization

 Five minutes before induction of general anesthesia, participants will be allocated randomly
 into four groups by drawing sequentially numbered sealed opaque envelopes containing a
 software-generated randomization code to receive an intravenous bolus of 0.1 mL/kg of either
 saline 0.9% or lidocaine 1.5% solution followed by a continuous infusion 0.1 mL/kg/h of
 Saline 0.9% or lidocaine 1%, 1.5% or 2% solution which will be continued for 24 hours after
 surgery. All medications in the study protocol will be based on the dosing body weight [ideal
 body weight (IBW) + 0.4 × (actual body weight-IBW)]. All study solutions looked identical and
 will be prepared by a local pharmacy. All staff in the operating room will be unaware of
 patient allocation group.

 Perioperative management

 An independent anesthesiologist who will not be involved in the study will instruct the
 participants preoperatively about the use of patient controlled analgesia and visual analogue
 scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for worst
 imaginable pain).

 Anesthetic management will be standardized. Oral ranitidine 150 mg and metoclopramide 10 mg
 will be administered the night before and 60 min before arrival in the operating room and
 subcutaneous enoxaparin 60 mg will be administered 12 h before the scheduled operation for
 prophylaxis against deep venous thrombosis.

 Participant's monitoring includes electrocardiography, non-invasive blood pressure, pulse
 oximetry, plethysmography variability index (PVI) and capnography.

 Following pre-oxygenation, in all participants, anesthesia will be induced with fentanyl 2-3
 ug/kg and propofol 1.5-2.5 mg/kg. Rocuronium 0.6 mg/kg will be administered to facilitate
 tracheal intubation. Anesthesia will be initially maintained with 0.7-1.2 minimum alveolar
 concentrations (MAC) of sevoflurane in combination with air (1 L/min) and oxygen (1 L/min)
 mixture to maintain the mean arterial blood pressure (MAP) and heart rate (HR) are ≤20% of
 the baseline values. Fentanyl 0.5 ug/kg increments will be administered when the MAP and HR
 are ≥20% of the baseline values despite a MAC of sevoflurane ≥1.0. Rocuronium 0.1 mg/kg, will
 be used to maintain surgical relaxation.

 Lungs will be initially ventilated in pressure-controlled mode to deliver a tidal volume of 8
 ml/kg of predicted body weight (0.919 × (height in cm - 152.4) + 45.5 for women or 50 for
 men) at an I/E ratio of 1:2 and a positive end-expiratory pressure (PEEP) of 5 cmH2O.
 Respiratory rate will be adjusted to maintain end-tidal carbon dioxide tension (ETCO2)
 between 35 and 40 mm Hg.

 All operations will be performed by the same surgeons. During CO2 pneumoperitoneum, the
 intra-abdominal pressure will be maintained at 12-14 mm Hg.

 Participants position will be changed from supine to a 40° reverse Trendelenburg position.

 During the operation, intraoperative fluid management was guided by a goal directed therapy
 algorithm using the PVI to guide fluid responsiveness. Hemodynamic control is standardized
 according to the investigators' protocol. Hypotension (defined as MAP value <25% of the
 baseline value on two consecutive readings within 3 min), not responding to decrease the
 sevoflurane MAC to 0.7 and a 5 ml/kg mL Ringer lactate or Acetate bolus over 5 min, will be
 treated with intravenous boluses of ephedrine, 3 mg or norepinephrine, 5 ug IV. Hypertension
 (defined as >20% increase in mean baseline MAP) will be treated by deepening anesthesia and
 administering doses of fentanyl, or labetalol, 20 mg. Tachycardia (defined as >20% increase
 in mean baseline HR) will be treated with esmolol, 20 mg. Bradycardia (HR <45) persisting for
 >2 min will be treated with glycopyrrolate, 0.2 mg IV, boluses.

 Intravenous ondansetron, 4 mg IV, will be given for all participants for prevention of
 postoperative nausea and vomiting. Before wound closure, bupivacaine 0.25% will be
 infiltrated at all portals, and residual neuromuscular block will be antagonized with
 neostigmine, 50 µg/kg IV, and glycopyrrolate, 10 µg/kg IV. After completing surgery,
 sevoflurane will be discontinued and infusion of study medication will be continued for 24 h
 after the wound closure. Times from discontinuation of sevoflurane to eye opening, obeying
 simple commands (e.g., open mouth, squeeze hand) and tracheal extubation will be recorded.

 Postoperative analgesic regime will be standardized in all participants including 30 mg of
 intravenous ketorolac every 6 h and paracetamol 1 g IV every 6 h and rescue doses of
 intravenous meperidine 25 mg. Participants will be discharged from the post-anesthesia care
 unit when they have a modified Aldrete score levels.

 Intravenous fluids will run at 40 mL/h on the night of surgery and will be discontinued 24 h
 after surgery. Little attention is paid to urine output or oliguria in the absence of
 abnormal vital signs. Strict parameters for fluid boluses the night of surgery are in place
 based on hypotension and tachycardia. Active bedside mobilisation will be enforced for the
 first time the evening after surgery and assisted ambulation the morning after surgery at
 least twice a day.

 Criteria for hospital discharge are as follows: absence of nausea and vomiting in the last 24
 h, return of bowel function (daily defecation) and toleration of full diet, no to minimal
 pain (VAS less than 4), afebrile and no surgically associated morbidity (fever, wound
 dehiscence, wound infection, anastomotic leak, abscess). These variables will be recorded by
 a blind assessor to the allocation, every day at 10:00, 14:00 and 18:00 h. Patients ready for
 discharge after 14:00 h will be discharged on the following morning. All drains have to be
 removed before discharge.

 Blindness

 All staff in the operating room will be unaware of patient allocation group. Patients will be
 unaware about their allocation group. All study solutions looked identical and will be
 prepared by a local pharmacy.

 Caregivers: An independent anesthesiologist who will not be involved in the study will
 instruct the patients preoperatively about the use of patient controlled analgesia and visual
 analogue scale to assess the severity of postoperative pain (0 mm for no pain and100 mm for
 worst imaginable pain) and will give the anesthetics and will be instructed to avoid using
 local anesthetics. An independent investigator involved in the assessment of the data and
 participants will be blind to the group assignment.

 Statistical analysis:

 Data will be tested for normality using the KolmogorovSmirnov test. Repeated-measures
 analysis of variance will be used for serial changes in the continuous data at different
 times after administration of study solution and the differences will be then corrected by
 post-hoc Bonferroni correction test. Fisher's exact test will be used for categorical data.
 Kruskal-Wallis one-way ANOVA and post-hoc Wilcoxon rank sum t-tests will be used for
 comparisons of the non-continuous data. Categorical data will be expressed as number (%),
 ordinal data will be expressed as median [range] and continuous data will be expressed as
 mean ± SD. A value of P<0.05 is considered to represent statistical significance.

 Power analysis and sample size calculation:

 Based on a previous study, the time to the return of bowel movements after laparoscopic
 bariatric surgery was normally distributed with a mean of 70 hours and a standard deviation
 of 22 hours. An a priori analysis indicated that 45 patients in each group would be
 sufficient to detect a 20% reduction in mean time to return of bowel movements, with a type I
 error of 0.005 (0.05/10 possible comparisons) and a power of 80%. The investigators added 15%
 more patients to account for drop-outs during the study.
Inclusion Criteria:

 -  Obese patients with a body mass index equal or greater than 35 kg/m2.

 -  American Society of Anesthesiologists (ASA) II-III

 -  Patients scheduled for laparoscopic bariatric surgery under general anesthesia

 Exclusion Criteria:

 -  History of significant cardiac disease.

 -  History of significant respiratory disease.

 -  History of significant hepatic disease.

 -  History of significant renal diseases.

 -  History of an atrio-ventricular block grade II to III.

 -  Long QT syndrome.

 -  Pre-existing disorder of the gastrointestinal tract.

 -  Patients with history of alcohol or drug abuse.

 -  Allergy to amide local anesthetics.

 -  History of epilepsy.

 -  Pregnancy.

 -  Patients receiving cardiovascular medications.

 -  Patients receiving steroids.

 -  Patients receiving an opioid analgesic medication within 24 h before the operation.

 -  Conversion from a laparoscopic to an open laparotomy.