Intravenous Ketamine Infusion on Postoperative Analgesia of Living Liver Donors

Study Overview
=================
Brief Summary
-----------------
Because of the insufficiency of cadaveric organs and increasing need for organs, the interest in living donor liver transplantation have been greatly increased. The relative reduction of the remaining liver after the operation in Living Liver Donors makes it difficult and compelling to choose a very effective and very safe method in the management of postoperative analgesia. Opioids are the main agents used in the postoperative analgesia of Live Liver Donors. Opioids have serious side effects such as respiratory depression, apnea, circulatory collapse, coma, and death. Both short-term and long-term administration of opioids cause acute opioid-induced hyperalgesia. Ketamine, an NMDA receptor antagonist, has been hypothesized to counter opioid tolerance and NMDA receptor-mediated central sensitization. Various studies and systematic reviews have shown that low-dose ketamine has an opioid-sparing effect in all surgical patients. Although low-dose ketamine has been shown to be beneficial overall in relieving pain, it is unclear whether it has an identified benefit in hepatectomy cases. The aim of this clinical trial was to evaluate the effect of low-dose ketamine administration on postoperative analgesia in living donor liver donors undergoing right hepatectomy procedure.

Detailed Description
-----------------
Liver transplantation is the only treatment for end-stage liver failure. The insufficiency of cadaveric organs and the inability to meet the increasing need for organs with cadaveric transplantations have greatly increased the interest in living donor liver transplantation. The relative reduction of the remaining liver after the operation in Living Liver Donors makes it difficult and compelling to choose a very effective and very safe method in the management of postoperative analgesia. Opioids are the main agents used in the postoperative analgesia of Live Liver Donors. Opioids have serious side effects such as respiratory depression, apnea, circulatory collapse, coma, and death. Both short-term and long-term administration of opioids cause acute opioid-induced hyperalgesia. There is evidence that opioid tolerance can occur in the dorsal root ganglion through N-methyl-D-aspartate (NMDA) receptor activation. Ketamine, an NMDA receptor antagonist, has been hypothesized to counter opioid tolerance and NMDA receptor-mediated central sensitization. Low-dose ketamine is an effective adjuvant in painful orthopedic procedures that reduces pain and opioid need, especially in the first 24 hours after the procedure. Various studies and systematic reviews have shown that low-dose ketamine has an opioid-sparing effect in all surgical patients. Although low-dose ketamine has been shown to be beneficial overall in relieving pain, it is unclear whether it has an identified benefit in hepatectomy cases. The aim of this randomized placebo-controlled clinical trial was to evaluate the effect of low-dose ketamine administration on postoperative analgesia in living donor liver donors undergoing a painful right hepatectomy procedure.

Official Title
-----------------
Effect of Intraoperative Intravenous Ketamine Infusion on Postoperative Analgesia in Right Hepatectomy of Living Liver Donors

Conditions
-----------------
Liver Failure, Liver Transplant; Complications, Post Operative Pain

Intervention / Treatment
-----------------
* Drug: Low dose ketamine infusion
* Drug: 0.9% NaCl infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: living liver donors, aged 16-65 years, who are scheduled for right hepatectomy will be included in the study. Exclusion Criteria: to use opioid medications before surgery, trauma, body mass index (BMI) >35, unstable ischemic heart disease, increased intracranial or intraocular pressure, lactation, to have an allergic to ketamine, morphine, propofol or remifentanil, psychiatric illness, patient-controlled analgesia (PCA) unwillingness or inability to use the device inability to use the numerical rating scale (NRS).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ketamine Group<br>Patients who received low-dose ketamine infusion | Drug: Low dose ketamine infusion<br>* Administering low-dose ketamine infusion to the patient under general anesthesia for Ketamine Group.<br>* Other names: Ketamine;|
| Sham Comparator: Control group<br>Patients who received 0.9% Sodium Chloride Solution, Intravenous, (NaCl) infusion | Drug: 0.9% NaCl infusion<br>* Same dose of 0.9% NaCl infusion as the dose of ketamine for Control Group.<br>* Other names: Saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative opioid consumption | To determine the cumulative opioid consumption at the end of 24 hours in patients who received low-dose ketamine or 0.9% NaCl infusion. | 24 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postop Sedation Score | Postop Sedation Score (0-3): sedation was measured on a scale of 0 to 3 0: fully awake; 1: lightly sedated, rarely sleepy and easily aroused; 2: moderately sedated, often sleepy and easily aroused; 3; severely sedated, sleepy and difficult to wake up | Postoperative 1 hour | 
| postoperative complications | postoperative complications: pruritus, vomiting, hallucination | 24 hour | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Liver, Living liver donor, Transplantation, postoperative pain, ketamine