Ketamine, Lidocaine and Combination for Postoperative Analgesia in Open Liver Resection

Study Overview
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Brief Summary
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Lidocaine and ketamine both are being used for perioperative analgesia. Perioperative lidocaine infusion has been shown to reduce postoperative pain and opioid consumption. Perioperative low dose Ketamine has shown improved postoperative pain and reduced opioid usage. We therefore tested the hypothesis that the combination would provide better analgesia in the milieu of intrathecal morphine.

Detailed Description
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All study participants were monitored according to American Society of Anesthesiologists guidelines. All received intrathecal morphine (300 to 400 mcg) at L3-4 interspace via 25 G Whitacre needle. Participants were then randomized (computer generated) into one of four groups. General anesthesia was induced and endotracheal intubation was done. Immediately, after intubation, Lidocaine group (L) received a Lidocaine infusion at 0.33 mg/kg/h. The Ketamine group (K) received a ketamine infusion at 70 mcg/Kg/h. The Lidocaine-Ketamine group (LK) received a Lidocaine infusion at 0.33 mg/kg/h plus a Ketamine infusion at 70 mcg/Kg/h. The control group (P) received a normal saline infusion to keep the blind. The infusions were stopped approximately 30-45 minute before the completion of surgery. All participants received a hydromorphone patient-controlled analgesia (PCA) via a pump. All were given acetaminophen 650 mg every 6 hrs for 4 days. Postoperatively, participants were monitored for nausea, vomiting, sedation, respiratory depression, light-headedness, perioral numbness, pruritus, disturbed dreams and hallucinations. Postoperative Hydromorphone consumption for the first, second and third day was recorded from the chart maintained by acute pain service team who were blinded to the group assignment. After the operation, study participants were interviewed at regular intervals by a blinded investigator about their current pain level, as well as satisfaction with pain management. They were also be questioned regarding the presence and severity of opioid-related side effects (nausea, vomiting, sedation, respiratory depression and, pruritus) and light-headedness, perioral numbness, disturbed dreams and hallucinations. Hospital charts were reviewed and data collected to analyze time to request for additional analgesia and total consumption of opioids, non-opioid analgesics, anti-emetics, and antipruritics within the first 72 hours postoperatively.

Official Title
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Ketamine, Lidocaine and Combination for Postoperative Analgesia in Open Liver Resection: A Prospective, Randomized, Four-arm, Double Blind, Placebo Controlled Trial

Conditions
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Hepatectomy

Intervention / Treatment
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* Drug: Lidocaine
* Drug: Ketamine
* Drug: Lidocaine+ketamine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA physical status 2-4 Elective major liver resection Signed informed consent Exclusion Criteria: ICU admission after surgery tracheal extubation not planned after surgery language barrier mental impairment severe coagulopathy chronic pain or opioid dependance or both alcohol/substance abuse allergy to the study drugs refusal for spinal infection at site of spinal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Lidocaine, ketamine, combination and placebo are being evaluated for treating postoperative pain in major liver resection
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine<br>This group will receive lidocaine infusion perioperatively | Drug: Lidocaine<br>* This group will receive lidocaine infusion<br>* Other names: Lidocaine infusion;|
| Experimental: Ketamine<br>This group will receive ketamine infusion perioperatively | Drug: Ketamine<br>* This group will receive Ketamine infusion<br>* Other names: Ketamine infusion;|
| Experimental: Lidocaine+ketamine<br>This group will receive a combination of lidocaine and ketamine infusion, perioperatively | Drug: Lidocaine+ketamine<br>* This group will receive mixture of ketamine and lidocaine infusion<br>* Other names: Xylocaine;|
| Placebo Comparator: placebo<br>This group will receive saline infusion as placebo perioperatively | Drug: Saline<br>* This group will receive saline infusion<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 | Total milligrams of opioids consumed would be measured | 24 hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid consumption | Total milligrams of opioids consumed would be measured. Higher opioid consumption indicates worse pain control. | 48 hrs | 
| Opioid related side effects | Questions regarding all opioid related side effects will be asked. These will include inquiry regarding nausea, vomiting, hallucinations, sedation, respiratory depression, pruritus | 72 hrs | 
| Chronic pain | Incidence of chronic pain at 6 weeks will be noted by a numerical rating scale of 1-10 where 0 would be no pain at all and 10 would be worst possible pain. This is standard pain assessment tool. Lower numbers indication better outcomes. | 6 weeks | 
| Patient satisfaction | Patient satisfaction will be noted using a numeric rating scale; where 0 will be completely unsatisfied and 10 will be completely satisfied. Higher values depict better satisfaction and better outcomes. | 72 hrs | 
| Chronic pain | Incidence of chronic pain at 12 weeks will be noted by a numerical rating scale of 1-10 where 0 would be no pain at all and 10 would be worst possible pain. This is standard pain assessment tool. Lower numbers indication better outcomes. | 12 weeks | 
| Opioid consumption | Total milligrams of opioids consumed would be measured. Higher opioid consumption indicates worse pain control. | 72 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lidocaine, Ketamine, postoperative analgesia