Intraoperative Lidocaine Infusion vs. Esmolol Infusion for Postoperative Analgesia in Laparoscopic Cholecystectomy
Condition: Gall Stone Disease
MeSH terms: Gallstones; Cholelithiasis; Cholecystolithiasis
Study type: Interventional
Phase: Phase 4

Summary: 
      Comparison of intraoperative infusion of lidocaine and esmolol in the postoperative
      requirement of opioid for postoperative pain management after laparoscopic cholecystectomy to
      decrease opioid related side effects and enhance postoperative recovery with multimodal
      analgesia approach.
    

Detailed description: 
      Postoperative pain after abdominal surgery includes many forms of distress, such as
      spontaneous pain at rest; pain during movement, including that of respiration; and visceral
      pain arising from damage to internal organs during surgery. Acute pain after laparoscopic
      cholecystectomy is complex in nature. The pain pattern does not resemble pain after other
      laparoscopic procedures, suggesting that analgesic treatment might be procedure specific and
      multimodal. Three components have been described: incisional pain as dominant, visceral deep
      pain, and shoulder referred pain. Opioids are most commonly used for postoperative analgesia
      in laparoscopic cholecystectomy. However, they can be associated with many side effects and
      delayed discharge. In addition, opioids do not offer the quality of postoperative pain relief
      that one would expect, probably because of the pain specific to laparoscopic cholecystectomy.
      A single agent is unlikely to treat all three types of pain. Therefore a multimodal approach
      will be required.

      Low-dose IV lidocaine is easy to administer, has well-established analgesic,
      anti-hyperalgesic, and anti-inflammatory effects, and has minimal toxicity in commonly
      studied doses (typically 1.5-3 mg/kg/h). Because postoperative pain is to a large extent an
      inflammatory phenomenon, administration of systemic local anesthetics, which have
      inflammatory modulatory properties, could significantly reduce pain and therefore allow more
      rapid discharge. Lidocaine has an excellent safety record when administered by low-dose
      infusion. In addition, intravenous lidocaine is an effective modality for treating visceral
      pain.

      Esmolol has been proposed as an alternative to intraoperative use of opioids, and found to
      facilitate the fast-tracking process and speed home-readiness of patients undergoing
      outpatient surgery. The various mechanisms of opioids dose sparing with concomitant use of
      β-adrenergic antagonist have been proposed from time to time such as suppression of stress
      hormones and pro-inflammatory cytokines, alteration of hepatic drug metabolism, activation of
      G-coupled proteins in cell membrane, central analgesia and so on but nothing conclusive has
      been established as yet.

      After pre operative evaluation, patients will be premedicated with oral diazepam (0.1-0.2
      mg/kg) at the night before and 2 hours before surgery. Informed consent will be obtained from
      all patients. Patients will be instructed during pre-anaesthetic visit about the use of the
      visual analogue scale (0-10 cm) where 0 is no pain and 10 is worst imaginable excruciating
      pain. They will also be informed that they will be asked their pain (VAS score) with its
      character during first 24 hrs after the surgery.

      Both the patient and the investigator observing the outcome will be blinded about assignment
      of patient group during the study. The investigator will not enter the operating room but
      will be responsible for data collection in post operative period and data analysis. On
      arrival of patients in the preoperative holding area, they will be randomly assigned into any
      of two groups using computer generated random number. Details of group assignment and case
      number will be kept in a set of sealed opaque envelope. The anesthesia staff will open the
      envelope and prepare drugs accordingly. The attending anesthesiologist will not be involved
      in the data collection and analysis, and will follow the standard general anaesthesia
      protocol during the study.

      On arrival to operating room, standard monitoring will be established and baseline heart
      rate, non-invasive B.P, oxygen saturation and bispectral index (BIS) value (Covidien) will be
      recorded. A peripheral vein will be cannulated for administration of IV fluid with 18 G
      cannula Patient will be preoxygenated using 100% oxygen for 3 minutes.

      General anesthesia will be induced with IV fentanyl 1.5 µg/kg , propofol 2-2.5 mg/kg till
      cessation of verbal response and tracheal intubation facilitated with vecuronium 0.1mg/kg IV.
      The lungs will be mechanically ventilated with a 50% mixture of air in oxygen to maintain
      ETCO2 between 35 to 45 mm of Hg. At induction, lidocaine group (L group) patients will
      receive 1.5 mg/kg of lidocaine IV bolus. The lidocaine infusion (B-Braun) of 1.5 mg/kg/h will
      be started immediately after induction of anesthesia. The esmolol group (E group) will
      receive an IV bolus 0.5 mg/kg at induction followed by continuous infusion (B-Braun) of
      esmolol (5-15 μg/kg/min) and titrated to maintain the heart rate within 25% of the baseline
      value. Inj. paracetamol 1 gm IV infusion will be started after induction and given over 15
      min.

      Anesthesia will be maintained in all groups with isoflurane adjusted upto 2.5% to maintain
      MAP within 20% of baseline and BIS value between 50 to 60. An orogastric tube will be
      inserted in every patient before surgical incision. No supplemental opioids will be used
      during surgery. Supplemental neuromuscular blockade will be achieved with vecuronium IV bolus
      doses after observing curare notch in capnometry. Inj. ketorolac 30 mg IV and ondansetron 4mg
      (0.1mg/kg) IV will be given after removal of gall bladder. Any episode of intraoperative
      hypotension (MAP lower than 65 mm Hg) and bradycardia (heart rate < 50 bpm) will be treated
      with ephedrine 5 mg and atropine 0.4 mg IV respectively.

      Patient position and monitoring

      Hasson surgical technique will be used. Each port site will be infiltrated with 3ml of 2%
      lidocaine before incision. Pneumoperitoneum will be achieved with carbon dioxide. Patients
      will be positioned in 30 degrees reverse trendelenburg position and tilted toward the left
      slowly. Non-invasive blood pressure assessment, oximetry, ECG and end tidal CO2 will be
      continually monitored during the anesthesia. During pneumoperitoneum, controlled ventilation
      will be adjusted to maintain ETC02 between 35 to 45 mm of Hg. Intra-abdominal pressure will
      be kept below 15 mm of Hg during laparoscopy.

      At the end of surgery, patients will be returned to a supine position and the carbon dioxide
      left in the peritoneal cavity will be expelled by slow abdominal decompression. Isoflurane
      will be discontinued after the last skin suture, and the lignocaine or esmolol infusions will
      also be stopped at completion of surgery. 10 ml of 0.25% Bupivacaine will be infiltrated in
      the incision site.

      Residual neuromuscular block will be reversed with neostigmine 0.05 mg/kg IV and
      glycopyrrolate 0.01 mg/kg IV. Thorough gastric and oropharyngeal suctioning will be done.
      Then, orogastric tube will be removed before endotracheal extubation. Trachea will be
      extubated on the operating table. Then, the patient will be transferred to the postanesthesia
      care unit.

      Postoperative Care and observation In PACU, non-invasive blood pressure, heart rate,
      respiration, and temperature will be monitored by nurses unaware of the study. Pain at
      awakening will be noted using VAS scale. Pain including its character will be assessed at
      rest and on movement by a VAS every 30 min by the investigator and by nurses on SOS basis on
      patient's request. If the VAS for pain is more than 3 at rest, morphine 1 mg IV and Tramadol
      50 mg IV will be administered in PACU and in ward respectively and repeated on SOS basis. It
      will be stopped if any adverse effects noticed which will include increased sleepiness,
      respiratory depression (SPO2 < 90%, R.R < 8 per minute). Metoclopramide 10 mg IV will be
      administered for grade 3 & 4 PONV.

      In the investigators institution, no step-down high dependency unit is available and patients
      will be transferred to ward directly from the PACU and following outcome parameters will be
      observed at 2, 6, 8, 12 and 24 h after surgery.
    

Intervention name(s): Lidocaine; Esmolol; Paracetamol; Lidocaine; Propofol; Fentanyl; Vecuronium; Atropine; Ephedrine; Morphine; Ketorolac; Ondansetron; Bupivacaine; Tramadol; Neostigmine; Glycopyrrolate
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Lidocaine intravenous 1.5mg/kg IV bolus at the time of induction followed by IV infusion @ 1.5 mg/kg/hr till the last suture.; Esmolol intravenous bolus 0.5 mg/kg at the time of induction followed by infusion @ 5-15 microgram/kg/min till the last suture.; Inj. Paracetamol 1 gm IV at the time of induction; Inj. Xylocaine 2% 3 ml will be infiltrated in skin in all port sites prior to incision.; Inj. Propofol 2- 2.5 mg/kg will be given for induction; Inj fentanyl 1.5mg/kg will be given at the time of induction.; Inj Vecuronium 0.1mg/kg will be given at induction and for maintenance.; Inj Atropine 0.4 mg IV will be given for bradycardia (HR < 50/min); Inj. Bupivacaine 0.25% 10 ml will be infiltrated at incision site after closure.; Inj tramadol 50 mg IV will be given on SOS basis in ward.; 50 mcg/kg for reversal of residual neuromuscular blockade; 10 mcg/kg with neostigmine
Other intervention name(s): Lignocaine, Xylocaine; Xylocaine
Intervention MeSH terms: Ketorolac; Lidocaine; Atropine; Ephedrine; Fentanyl; Glycopyrrolate; Morphine; Tramadol; Ondansetron; Bupivacaine; Propofol; Neostigmine; Vecuronium Bromide; Esmolol
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Laparoscopic cholecystectomy; lidocaine infusion; Esmolol infusion; Postoperative opioid consumption; Multimodal analgesia