Role of Branched-chain Amino Acids Infusion as Adjunct Therapy Post Liver Surgery for Patients in Intensive Care Unit

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the impact of intravenous BCAAs infusion as adjunct therapy post liver surgery in intensive care unit (ICU).

Detailed Description
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Patients will be enrolled in the study&randomly assigned in a 1:1 manner to receive either intravenous (IV) BCAAs in a dose of 0.5-1gm/Kg/day for at least 48hours up to maximum 5 days immediately post-operative or placebo (sterile normal saline in a volume equal to the study drug). All demographic data will be obtained including the patients' age, sex, weight,associated co-morbidities (diabetes mellitus & hypertension), the presence of chronic liver disease (CLD), Child-Pugh score, Sequential Organ Failure Assessment (SOFA), the type of liver surgery, & nutritional status according to nutritional risk screening 2002 (NRS 2002); well-nourished if NRS 2002 < 3 while malnourished if NRS 2002 ≥ 3 prior BCAAs infusion. Vital signs including the heart rate, mean arterial pressure (MAP), central venous pressure (CVP), arterial oxygen saturation (SaO2), insulin requirements, urine volume & fluid balance will be recorded on admission (day 0), then will be followed up and recorded at regular intervals during treatment on 1, 3, 5 &7days. Laboratory investigations including the complete blood profile (white blood cells, band%, lymphocytes), prothrombin time (PT), liver enzymes; Aspartate aminotransferase (AST), Alanine aminotransferase (ALT),serum bilirubin, serum albumin, C-reactive protein (CRP)& kidney functions will be recorded at randomization as a baseline (day 0)& will be assessed on day 0,1, 3, 5 & 7 of the study. Thirty-day survival & infectious morbidity will be followed by phone calls to the patient or one of his/her first-degree relatives.

Official Title
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Role of Branched-chain Amino Acids Infusion as Adjunct Therapy Post Liver Surgery for Patients in Intensive Care Unit

Conditions
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Liver Function Post BCAA Infusion

Intervention / Treatment
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* Drug: BCAA preparation Intravenous infusion
* Drug: sterile normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects are adults aged between 18& 75years who are admitted to the ICU of National Hepatology & Tropical Medicine Research Institute (NHTMRI) post liver surgery e.g. hepatocellular carcinoma, liver hemangioma, hydatid resection, segmentectomy, partial hepatectomy as in donor for living donated liver transplant. Exclusion Criteria: if pregnant. hemodynamic instability requiring circulatory support. need for dose of BCAAs > 1gm/Kg/day or < 0.5 gm/Kg/day. severe malnutrition; body mass index (BMI < 16).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study<br> | Drug: BCAA preparation Intravenous infusion<br>* BCAA IVi in a dose 0.5-1 gm/Kg/day for 2-5 days post liver surgery versus sterile normal saline in a volume equal to the study drug<br>|
| Placebo Comparator: control<br> | Drug: sterile normal saline<br>* sterile normal saline in a volume equal to the study drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect on liver function tests | improvement of liver function tests, AsT | within one week post liver surgery | 
| effect on liver function tests | improvement of ALT | within one week post liver surgery | 
| effect on liver function tests | Improvement of total bilirubin | within one week post surgery | 
| effect on liver function tests | improvement of alkaline phosphatase | within one week post surgery | 
| effect on liver function tests | improvement of prothrombin time | within one week post surgery | 
| Child-Pugh score post-surgery. | Improvement with BCAA infusion | within one week post surgery | 
| SOFA score post-surgery | improvement with BCAA infusion | within one week post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day infectious morbidity Infectious morbidity | occurrence of infections post surgery | 30 days post surgery | 
| non infectious morbidity | occurrence of hepatic encephalopathy, ruptured esophageal varices, ascites requiring diuretic agent for control, wound dehiscence, intra-abdominal bleeding, intestinal obstruction, renal failure, pleural effusion, need mechanical ventilation, blood sugar control & nutritional status change. | 30 days | 
| ICU stay. length of ICU stay, length of hospital stay & 28day mortality. length of ICU stay, length of hospital stay & 28day mortality. length of ICU stay, length of hospital stay & 28day mortality. | Length of ICU stay in days | within two weeks post surgery | 
| Hospital stay. length of ICU stay, length of hospital stay & 28day mortality. length of ICU stay, length of hospital stay & 28day mortality. length of ICU stay, length of hospital stay & 28day mortality. | Length of hospital stay in days | within two weeks post surgery | 
| mortality | 28-day mortality | 28 day |