20% Albumin vs. Balanced Salt Solution as Resuscitation Fluid in Cirrhosis With Sepsis Induced Hypotension

Study Overview
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Brief Summary
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Patients with cirrhosis patients have a high incidence of sepsis which can trigger decompensation and may result in prolonged hospital stay and increased mortality. About 30%-50% admissions of patients with cirrhosis have sepsis at presentation and about 15% patients admitted to hospital develop sepsis during the hospital stay . After infection develops, the patient may develop acute kidney injury (AKI), shock, encephalopathy or disseminated intravascular coagulation (DIC) further decreasing the chances of survival. In fact, sepsis in patients with cirrhosis is associated with 15% in-hospital mortality, approximately double that of patients without sepsis. So, sepsis is directly responsible for 30-50% of deaths in cirrhosis . Therefore, it is critical to manage sepsis early and appropriately in cirrhosis to reduce the complications and mortality. Early administration of fluids, source control and empirical antibiotics along with vasopressors if refractory shock are essential components of treatment in all patients with sepsis. Currently, the most accepted strategy for early sepsis management is a combination of early goal directed therapy (EGDT) and physiological parameters, such as urine output, lactate clearance, and administration of antibiotics, within 1 hour of presentation . The use of central venous pressure assessment is fallacious for gauging adequacy of fluid resuscitation in cirrhosis, and the difficulty of performing echocardiographic assessments in the setting of ascites and cirrhotic cardiomyopathy is also well described .

Official Title
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To Compare 20% Albumin vs. Balanced Salt Solution as Resuscitation Fluid and Identify Fluid Responsiveness Criteria in Critically Ill Patients With Cirrhosis With Sepsis Induced Hypotension; a Prospective Randomized Controlled Trial.

Conditions
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Cirrhosis, Liver, Acute-On-Chronic Liver Failure, Shock, Septic, Shock Hypovolemic

Intervention / Treatment
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* Drug: 20% albumin
* Drug: Balanced salt solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical/Imaging or Biopsy proven liver cirrhosis of any etiology who consent for enrolment. Hypotension (Mean arterial pressure <65mmHg or Systolic blood pressure <90mmHg) Aged between18-65 yrs Exclusion Criteria: Already received colloid or more than 2 litres of fluid without baseline echocardiographic assessment. Already on vasopressors/inotropes Severe pre-existing cardiopulmonary disease Acute Respiratory Distress Syndrome (ARDS) Active bleeding like variceal bleed Cerebrovascular events Chronic renal disease - End Stage Renal Disease (ESRD)/ patient on renal replacement therapy Admission to ICU following liver transplantation, burns, cardiac surgery Brain death or likely brain death within 24 hours Previous adverse reaction to human albumin solution Pregnant or lactating women Informed consent refused by patient or attendants

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20% Albumin arm<br>20% Albumin in a dose of 20-40 gm per day as infusion over 12-24 h | Drug: 20% albumin<br>* Albumin arm for resuscitation fluid<br>Drug: Balanced salt solution<br>* Only Balanced salt solution will be used.<br>|
| Active Comparator: Balanced salt solution arm<br>Fluid resuscitation protocol includes use of an immediate 500 ml bolus of crystalloid i.e., balanced salt solution (BSS) or 0.9% normal saline (Rescue phase), followed by 20 ml/kg fluid in the first 6 hours titrated to target MAP of > 65mmHg.The second phase of fluid resuscitation (Optimization phase) will be performed as per IVC targets, attainment of lactate clearance, and LUS score to prevent overload. | Drug: Balanced salt solution<br>* Only Balanced salt solution will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics. | To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension | At enrolment | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics. | To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension | At 6 hours | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics. | To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension | At 24 hours | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess IVC dynamics. | To compare the IVC dynamics in patients with cirrhosis and sepsis induced hypotension | At 48 hours. | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess dynamic changes in cardiac output, stroke volume and E/e' echocardiographic parameters. | To compare the cardiac output in patients with cirrhosis and sepsis induced hypotension | At enrolment | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess dynamic changes in cardiac output, stroke volume and E/e' echocardiographic parameters. | To compare the cardiac output in patients with cirrhosis and sepsis induced hypotension | At 24 hours | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess dynamic changes in cardiac output, stroke volume and E/e' echocardiographic parameters. | To compare the cardiac output in patients with cirrhosis and sepsis induced hypotension | At 48 hours. | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI) | To compare the new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI)in patients with cirrhosis and sepsis induced hypotension | At enrolment | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension and assess new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI) | To compare the new onset of hepatorenal syndrome (HRS) or acute kidney injury (AKI)in patients with cirrhosis and sepsis induced hypotension | At 48 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary marker of AKI (NGal) |  | At enrolment | 
| Change in urinary markers of AKI (NGal) |  | At 24 hours. | 
| Change in urinary markers of AKI(NGal) |  | At 48 hours. | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension., and assess vasopressor requirement | To compare the vasopressor requirement in patients with cirrhosis and sepsis induced hypotension | At enrolment | 
| To compare the efficacy of 20% Albumin vs Plasmalyte in the first 3 -6 hours of volume resuscitation in cirrhosis with sepsis induced hypotension., and assess vasopressor requirement | To compare the vasopressor requirement in patients with cirrhosis and sepsis induced hypotension | At 24 hours |