Intraoperative Lidocaine and Combined With Ketamine on Opioid After Bariatric Surgery

Study Overview
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Brief Summary
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The most effective long-term treatment for obesity is bariatric surgery, however, postoperative pain control is challenging in these group of population. Opioid-sparing technique with multimodal analgesia is recommended but the evidence supported is still limited. Multimodal analgesia, particularly lidocaine and ketamine, has been used effectively in various type of surgery. However, the evidence supported their use in obese patients undergoing bariatric surgery is limited.

Detailed Description
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The prevalence of obesity and associated diseases have been increasing in recent decades. From 1980 to 2013, the number of adults with BMI more than 25 kg/m2 increased from 28.8% to 36.9% in men, and from 29.8% to 38% in women. According to World Health Organization (WHO), the prevalence of overweight among adults in Thailand in 2016 was 32.6%, markedly increased from 2011 which was 23.9%. To date, the most effective long-term treatment for obesity is bariatric surgery because of significantly reducing body fat, the development of new obesity-related conditions, and overall mortality. However, postoperative complications, particularly respiratory complication, are concerned because obesity is associated with respiratory compromise and sleep-disordered breathing. The 2016 guideline for perioperative care in bariatric surgery developed by enhanced recovery after surgery (ERAS) society state that, regarding to current evidence, there is no specific anesthetic agents or techniques for bariatric surgery, however, multimodal analgesia should be used to reduce opioid consumption and opioid-related complications such as respiratory depression, postoperative nausea and vomiting and ileus. Moreover, several studies supported opioid-sparing technique to avoid respiratory complications. Intravenous lidocaine is widely used to reduce postoperative pain and to reduce perioperative opioid as a multimodal analgesia. From Cochrane review, perioperative lidocaine can decrease pain at rest, postoperative ileus and postoperative nausea and vomiting in elective and urgent surgery. Few trials in obese patients underwent laparoscopic bariatric surgery found that lidocaine infusion can decrease opioid consumption. However, the supported evidence is still limit. Ketamine has been used for postoperative analgesia as well, as an effective adjunct to decrease opioid consumption in various types of surgery, including open bariatric surgery. Moreover, the recent retrospective study (Tovikkai P, in press) found that there was a positive interaction between intraoperative lidocaine infusion and ketamine for decreasing opioid consumption in obese patients underwent laparoscopic bariatric surgery. However, the benefit of lidocaine and ketamine for postoperative pain in obese patients underwent laparoscopic bariatric surgery is still debated. Therefore, we designed this study to examine the effect of intraoperative lidocaine infusion and intraoperative lidocaine infusion combined with intraoperative low-dose ketamine infusion on opioid consumption in obese patients undergoing laparoscopic bariatric surgery.

Official Title
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The Effect of Intraoperative Lidocaine Infusion and Intraoperative Lidocaine Combined With Ketamine Infusion on Opioid Consumption After Laparoscopic Bariatric Surgery: A Randomized Controlled Trial

Conditions
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Laparoscopic Bariatric Surgery

Intervention / Treatment
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* Drug: Lidocaine Hydrochloride
* Drug: Ketamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults patients age older than 18 years. Body mass index more than 30 kg/m2. Scheduled for laparoscopic bariatric surgery, including laparoscopic sleeve gastrectomy, robotic-assisted laparoscopic sleeve gastrectomy, laparoscopic Roux-en-Y gastric bypass surgery or robotic-assisted laparoscopic gastric bypass. Exclusion Criteria: Patient refusal. Inability to communicate or read in Thai language. Allergic to lidocaine or ketamine. History of opioid use within 2 weeks before surgery Cardiovascular disorder, including high grade atrioventricular block (second degree or third degree), history of coronary artery disease, poor controlled hypertension. History of stroke, intracranial hemorrhage or intracranial mass Cognitive impairment Schizophrenia or history of antipsychotic drugs Pregnant or breast-feeding patients Conversion to open surgery

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Lidocaine and Ketamine<br>Participants in this arm will receive intra-operative lidocaine and ketamine infusion as adjunctive drugs for pain control. All medication is dosed based on calculated lean body weight (LBW) by Janmahasatian formula. | Drug: Lidocaine Hydrochloride<br>* lidocaine will be given 1.5 mg/kg bolus at induction then 2mg/kg/hr until the end of surgery.<br>* Other names: Li;Drug: Ketamine<br>* Ketamine will be given 0.35 mg/kg bolus at induction then 0.2 mg/kg/hr until the end of surgery.<br>* Other names: Ke;|
| Active Comparator: Lidocaine<br>Participants in this arm will receive only intra-operative ketamine infusion as adjunctive drugs for pain control. All medication is dosed based on calculated lean body weight (LBW) by Janmahasatian formula. | Drug: Lidocaine Hydrochloride<br>* lidocaine will be given 1.5 mg/kg bolus at induction then 2mg/kg/hr until the end of surgery.<br>* Other names: Li;Drug: Placebo<br>* Normal saline will be given with the same rate of lidocaine or ketamine.<br>* Other names: Normal Saline;|
| Placebo Comparator: Placebo<br>Participants in this arm will receive normal saline, same volume as lidocaine and ketamine. | Drug: Placebo<br>* Normal saline will be given with the same rate of lidocaine or ketamine.<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid consumption | Opioid consumption at 24 hr post-operation using Morphine Milligram equivalents(MME) | 24-hour | 
| Score of post-extubation cough | post-extubation cough graded by care giver using modified Minogue scales, which defined grade1 as no coughing or muscular stiffness, grade 2 as coughing once or twice, or transient cough response to removal of tracheal tube that resolved with extubation, grade 3 as ≤ 3 coughs lasting 1-2 seconds, or total duration of coughing last ≤ 5 seconds and grade 4 as ≥ 4 coughs with each lasting > 2 seconds, total duration of coughing last > 5 seconds. | up to 24 hours (at extubation period after surgery finished) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| operative time | time since incision started until the last suture done recorded in minutes. | intraoperative (since the incision started until finished the last suture) | 
| anesthetic time | time since anesthetic started until finished and patient out of room recorded in minutes. | intraoperative (since anesthetic started until patient out of the operating room) | 
| the length of hospital stay | time since admission until discharge recorded in hours. | until 30-day postoperation | 
| numbers of participants with postoperative complications | cardiac arrhythmia, myocardial infarction, respiratory compromised, reintubation, readmission. | until 30-day postoperation | 
| Score of sore throat | sore throat score grading by self-assessment score, which defined grade 0 as no sore throat, grade 1 as minimal sore throat, grade 2 as moderate sore throat and grade 3 as severe sore throat. | assess at 24-hour post-operation |