Analgesic Effect of IntraPeritoneal LIGNOcaine in Gynaecological Open Surgery

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Postoperative Pain, Gynecologic Disease, Local Anesthetic Systemic Toxicity

Intervention / Treatment
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* Drug: Lignocaine
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgery, Lignocaine, Postoperative pain, Analgesia, Gynaecological