Analgesic Effect of IntraPeritoneal LIGNOcaine in Gynaecological Open Surgery

Analgesic Effect of IntraPeritoneal LIGNOcaine in Gynaecological Open Surgery: A Double-blinded Randomised Placebo-controlled Trial (IP LIGNO Trial)

The incidence of postoperative pain is highly prevalent among surgical patients. Inadequate postoperative pain control can slow the recovery and it increases the risk of postoperative complications, namely lung collapse and chronic pain. Although morphine is the one of the gold standard analgesia option for postoperative pain, it comes with many unwanted adverse effects, such as severe nausea and vomiting, low blood pressure and dizziness. Thus, multimodal analgesia regime, including local anaesthetic (lignocaine) is strongly advocated for postoperative analgesia.

The normal route of lignocaine is injected into vein for the properties of analgesia and anti-inflammatory. It exerts its effect via the systemic absorption of drugs to block the central neuronal pain transmission. In recent years, studies have demonstrated that instillation of lignocaine inside abdominal cavity can reduce internal organ pain by blocking free nerve ending inside abdomen with minimal systemic absorption of drug and lower complications of systemic toxicity of local anaesthesia as compared to the intravenous route of lignocaine.

Several RCTs showed the beneficial effect of intraperitoneal lignocaine for the reduction of postoperative visceral pain after laparoscopic surgery. However, gynaecological open surgery (cystectomy, hysterectomy) involves greater degree of manipulation and trauma on the internal organs with greater visceral pain, resulting in longer duration of hospitalisation and delayed functional mobility recovery. It is believed that the intraperitoneal lignocaine reduces inflammatory response after surgery and exert analgesia effect by blocking the neural signal transmission at site of tissue injury. Therefore, it is important to conduct this study to examine the analgesic effect of intraperitoneal lignocaine in women undergoing gynaecological open surgery.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain; Gynecologic Disease; Local Anesthetic Systemic Toxicity
• Intervention / Treatment: Drug: Lignocaine; Drug: Normal Saline

Detailed Description

Postoperative pain impedes the progress of recovery and increases the risk of postoperative complications, namely lung atelectasis, incidence of desaturation, pulmonary dysfunction and chronic pain. Although opioid is the one of the gold standard analgesia for postoperative pain, it comes with many unwanted adverse effects, such as respiratory depression, hypotension and incidence of nausea and vomiting. Thus, multimodal analgesia regime, including local anaesthetic is strongly advocated for postoperative analgesia.

Lignocaine is a local anaesthetic agent, which has the properties of analgesia, anti-inflammatory and anti-arrhythmia effect via the blockade of sodium channel receptor in the spinal cord and dorsal root ganglia. The intravenous lignocaine exerts its effect via the systemic absorption of drugs to block the central neuronal transmission. In recent years, studies have demonstrated that intraperitoneal route of lignocaine can reduce visceral pain by inhibiting peritoneal free nerve ending and reduce peripheral neuronal hyper-excitatory of pain signal transmission. It is also believed that intraperitoneal lignocaine is associated with minimal systemic absorption of drug and lower incidence of systemic toxicity local anaesthesia as compared to the intravenous route of lignocaine.

Several randomised controlled trials (RCTs) showed the beneficial effect of intraperitoneal lignocaine for the reduction of postoperative visceral pain after laparoscopic surgery. However, gynaecological open surgery has greater degree of organ manipulation and tissue injury with greater visceral pain, resulting in longer duration of hospitalisation and delayed functional mobility recovery. It is believed that the intraperitoneal lignocaine reduces inflammatory response after surgery and exert analgesia effect by blocking the neural pain signal transmission at site of tissue injury. The dosage of intraperitoneal lignocaine used in the literature ranged from 200-400mg. The serum concentration of intraperitoneal lignocaine was measured, which was associated with a relatively safe serum concentration of lignocaine. Pharmacological studies have showed that the adjuvant dose of adrenaline reduced the systematic absorption of intraperitoneal lignocaine. Therefore, this study is designed to examine the analgesic effect of intraperitoneal lignocaine in gynaecological open surgery. The investigators hypothesised that intraperitoneal lignocaine reduces postoperative pain score at rest and movement in women undergoing gynaecological open surgery.

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ka Ting Ng, MBChB; Phone Number: +60379492411; Email: katingng1@gmail.com

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 50603
    • Recruiting
    • University of Malaya
    • Contact: Ka Ting Ng, MBChB; Phone Number: +60379492042
    • Principal Investigator: Ka Ting Ng, MBChB
    • Principal Investigator: Pui San Loh, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• all adult women (American Society of Anesthesiologists (ASA) who >18 years old and <60 years old
• gynaecological open surgery with midline or transverse laparotomy incision (below or above umbilicus)

Exclusion Criteria:

• laparoscopic surgery
• allergic to lignocaine
• history of cardiac, vascular or liver disease
• ASA 3-5 or
• body mass index <18/ or >40

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group L; Intraperitoneal lignocaine 200mg/20mls + epinephrine 1:200,000	Drug: Lignocaine; Intraperitoneal lignocaine 200mg/20mls + epinephrine 1:200,000; Other Names: INJECSOL LIG2
Placebo Comparator: Group P; Intraperitoneal 20ml of 0.9% normal saline	Drug: Normal Saline; Intraperitoneal 20ml of 0.9% normal saline; Other Names: B. Braun 0.9% Sodium Chloride Inj. B.P

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain score	At rest and movement (0- no pain, 10- most pain)	1-hour after surgery in the recovery bay
Postoperative pain score	At rest and movement (0- no pain, 10- most pain)	24-hour after surgery in the ward
Postoperative pain score	At rest and movement (0- no pain, 10- most pain)	48-hour after surgery in the ward

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative patient-controlled analgesia morphine consumption	Measured in milligrams	24-hour after surgery in the ward
Postoperative patient-controlled analgesia morphine consumption	Measured in milligrams	48-hour after surgery in the ward
Number of patients requiring rescue analgesia	Number of patients	Throughout in recovery bay after surgery, on average 2-hour after surgery
Postoperative nausea and vomiting	Number of patients	Throughout in the recovery bay after surgery, on average 2-hour after surgery
Adverse events of lignocaine	Central nervous system or cardiovascular side effects- arrhythmias, dizziness or numbness	Throughout the study completion, on average of 48 hours

Collaborators and Investigators

• Sponsor: University of Malaya
• Investigators: Principal Investigator: Pui San Loh, MBBS, University of Malaya; Principal Investigator: Ka Ting Ng, MBChB, University of Malaya

Publications and helpful links

General Publications

• Perniola A, Magnuson A, Axelsson K, Gupta A. Intraperitoneal local anesthetics have predominant local analgesic effect: a randomized, double-blind study. Anesthesiology. 2014 Aug;121(2):352-61. doi: 10.1097/ALN.0000000000000267.
• Williamson KM, Cotton BR, Smith G. Intraperitoneal lignocaine for pain relief after total abdominal hysterectomy. Br J Anaesth. 1997 Jun;78(6):675-7. doi: 10.1093/bja/78.6.675.
• Patel R, Carvalho JC, Downey K, Kanczuk M, Bernstein P, Siddiqui N. Intraperitoneal Instillation of Lidocaine Improves Postoperative Analgesia at Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Trial. Anesth Analg. 2017 Feb;124(2):554-559. doi: 10.1213/ANE.0000000000001799.
• Elhakim M, Elkott M, Ali NM, Tahoun HM. Intraperitoneal lidocaine for postoperative pain after laparoscopy. Acta Anaesthesiol Scand. 2000 Mar;44(3):280-4. doi: 10.1034/j.1399-6576.2000.440310.x.
• Rademaker BM, Kalkman CJ, Odoom JA, de Wit L, Ringers J. Intraperitoneal local anaesthetics after laparoscopic cholecystectomy: effects on postoperative pain, metabolic responses and lung function. Br J Anaesth. 1994 Mar;72(3):263-6. doi: 10.1093/bja/72.3.263.
• Shahin AY, Osman AM. Intraperitoneal lidocaine instillation and postcesarean pain after parietal peritoneal closure: a randomized double blind placebo-controlled trial. Clin J Pain. 2010 Feb;26(2):121-7. doi: 10.1097/AJP.0b013e3181b99ddd.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: May 21, 2023
• First Submitted That Met QC Criteria: May 31, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; Analgesia; Postoperative pain; Lignocaine; Gynaecological
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pain, Postoperative; Genital Diseases, Female; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 1.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No