Intraoperative Lidocaine Infusion vs. Esmolol Infusion for Postoperative Analgesia in Laparoscopic Cholecystectomy

Sponsor

B.P. Koirala Institute of Health Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT02327923

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Gall Stone Disease	Drug: Lidocaine Drug: Esmolol Drug: Paracetamol Drug: Lidocaine Drug: Propofol Drug: Fentanyl Drug: Vecuronium Drug: Atropine Drug: Ephedrine Drug: Morphine Drug: Ketorolac Drug: Ondansetron Drug: Bupivacaine Drug: Tramadol Drug: Neostigmine Drug: Glycopyrrolate	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Intraoperative Lidocaine Infusion vs. Esmolol Infusion for Postoperative Analgesia in Laparoscopic Cholecystectomy: a Randomized Clinical Trial

Actual Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lidocaine Intravenous bolus administration of lidocaine at the time of induction followed by infusion till the last suture.	Drug: Lidocaine 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. Other Names: Lignocaine, Xylocaine Drug: Paracetamol Inj. Paracetamol 1 gm IV at the time of induction Drug: Lidocaine Inj. Xylocaine 2% 3 ml will be infiltrated in skin in all port sites prior to incision. Other Names: Xylocaine Drug: Propofol Inj. Propofol 2- 2.5 mg/kg will be given for induction Drug: Fentanyl Inj fentanyl 1.5mg/kg will be given at the time of induction. Drug: Vecuronium Inj Vecuronium 0.1mg/kg will be given at induction and for maintenance. Drug: Atropine Inj Atropine 0.4 mg IV will be given for bradycardia (HR < 50/min) Drug: Ephedrine Drug: Morphine Drug: Ketorolac Drug: Ondansetron Drug: Bupivacaine Inj. Bupivacaine 0.25% 10 ml will be infiltrated at incision site after closure. Drug: Tramadol Inj tramadol 50 mg IV will be given on SOS basis in ward. Drug: Neostigmine 50 mcg/kg for reversal of residual neuromuscular blockade Drug: Glycopyrrolate 10 mcg/kg with neostigmine
Active Comparator: Esmolol Intravenous bolus administration of esmolol at the time of induction followed by infusion till the last suture.	Drug: Esmolol Esmolol intravenous bolus 0.5 mg/kg at the time of induction followed by infusion @ 5-15 microgram/kg/min till the last suture. Drug: Paracetamol Inj. Paracetamol 1 gm IV at the time of induction Drug: Lidocaine Inj. Xylocaine 2% 3 ml will be infiltrated in skin in all port sites prior to incision. Other Names: Xylocaine Drug: Propofol Inj. Propofol 2- 2.5 mg/kg will be given for induction Drug: Fentanyl Inj fentanyl 1.5mg/kg will be given at the time of induction. Drug: Vecuronium Inj Vecuronium 0.1mg/kg will be given at induction and for maintenance. Drug: Atropine Inj Atropine 0.4 mg IV will be given for bradycardia (HR < 50/min) Drug: Ephedrine Drug: Morphine Drug: Ketorolac Drug: Ondansetron Drug: Bupivacaine Inj. Bupivacaine 0.25% 10 ml will be infiltrated at incision site after closure. Drug: Tramadol Inj tramadol 50 mg IV will be given on SOS basis in ward. Drug: Neostigmine 50 mcg/kg for reversal of residual neuromuscular blockade Drug: Glycopyrrolate 10 mcg/kg with neostigmine

Arm

Intervention/Treatment

Active Comparator: Lidocaine

Intravenous bolus administration of lidocaine at the time of induction followed by infusion till the last suture.

Drug: Lidocaine

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.

Other Names:

Lignocaine, Xylocaine

Drug: Paracetamol

Inj. Paracetamol 1 gm IV at the time of induction

Drug: Lidocaine

Inj. Xylocaine 2% 3 ml will be infiltrated in skin in all port sites prior to incision.

Other Names:

Xylocaine

Drug: Propofol

Inj. Propofol 2- 2.5 mg/kg will be given for induction

Drug: Fentanyl

Inj fentanyl 1.5mg/kg will be given at the time of induction.

Drug: Vecuronium

Inj Vecuronium 0.1mg/kg will be given at induction and for maintenance.

Drug: Atropine

Inj Atropine 0.4 mg IV will be given for bradycardia (HR < 50/min)

Drug: Ephedrine

Drug: Morphine

Drug: Ketorolac

Drug: Ondansetron

Drug: Bupivacaine

Inj. Bupivacaine 0.25% 10 ml will be infiltrated at incision site after closure.

Drug: Tramadol

Inj tramadol 50 mg IV will be given on SOS basis in ward.

Drug: Neostigmine

50 mcg/kg for reversal of residual neuromuscular blockade

Drug: Glycopyrrolate

10 mcg/kg with neostigmine

Active Comparator: Esmolol

Intravenous bolus administration of esmolol at the time of induction followed by infusion till the last suture.

Drug: Esmolol

Esmolol intravenous bolus 0.5 mg/kg at the time of induction followed by infusion @ 5-15 microgram/kg/min till the last suture.

Drug: Paracetamol

Inj. Paracetamol 1 gm IV at the time of induction

Drug: Lidocaine

Inj. Xylocaine 2% 3 ml will be infiltrated in skin in all port sites prior to incision.

Other Names:

Xylocaine

Drug: Propofol

Inj. Propofol 2- 2.5 mg/kg will be given for induction

Drug: Fentanyl

Inj fentanyl 1.5mg/kg will be given at the time of induction.

Drug: Vecuronium

Inj Vecuronium 0.1mg/kg will be given at induction and for maintenance.

Drug: Atropine

Inj Atropine 0.4 mg IV will be given for bradycardia (HR < 50/min)

Drug: Ephedrine

Drug: Morphine

Drug: Ketorolac

Drug: Ondansetron

Drug: Bupivacaine

Inj. Bupivacaine 0.25% 10 ml will be infiltrated at incision site after closure.

Drug: Tramadol

Inj tramadol 50 mg IV will be given on SOS basis in ward.

Drug: Neostigmine

50 mcg/kg for reversal of residual neuromuscular blockade

Drug: Glycopyrrolate

10 mcg/kg with neostigmine

Outcome Measures

Primary Outcome Measures

Opioid (morphine equivalent) requirement in the first 24 h postoperatively [up to 24 hours postoperatively]
total morphine consumed in the first 24 h postoperatively

Secondary Outcome Measures

Visual analogue scale (VAS) scores for pain severity [up to 24 hours postoperatively]
Pain at rest and with cough or movement using the VAS scale during first 24 h (at PACU and ward). VAS scale consist of a line with 10 cm length, where "0" is no pain and "10" is worst pain patient can imagine.
Incidence of postoperative nausea and vomiting (PONV). [up to 24 hours postoperatively]
Incidence of postoperative nausea and vomiting (PONV) in the first 24 h using PONV scoring.
Time to first voiding [up to first 24 hours postoperatively]
Sedation score using Ramsay Scale. [up to 24 hours postoperatively]
Sedation score using Ramsay Scale during first 24 h postoperatively.
Patient satisfaction following Laparoscopic cholecystectomy [at 24 hours postoperatively]
Patient satisfaction following LC using Likert Satisfaction Scale at 24 h following surgery
Time to first perception of pain [up to 24 hours postoperatively]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult female patients of ASA physical status I or II, between age of 18 to 60 years undergoing elective laparoscopic cholecystectomy under general anaesthesia.

Exclusion Criteria:

Refusal to give consent.
ASA physical status III or more.
Inability to comprehend pain assessment score or severe mental impairment.
Difficult intubation.
Pregnancy.
Morbid obesity.
History of epilepsy.
History of allergy to any drug used in the study.
History of ongoing use of opioids or beta adrenergic receptor antagonists.
Baseline heart rate less than 50 beats per minute.
Presence of pain immediately before surgery.
Chronic pain other than gall stone disease.
Gastrointestinal ulceration, bleeding disorder.
Peritonitis (including previous), perforated gall bladder, severe acute cholecystitis, known to have choledocholithiasis.