Echocardiography-guided Cirrhosis and Liver Failure-Intensive Care Protocol Sepsis

Summary

* Point-of-care echocardiography is used to guide septic shock resuscitation in patients with severe sepsis in the intensive care unit (ICU), but without systematic evidence for efficacy in critically patients with Cirrhosis and Severe Sepsis.
* Due to portal hypertension, these patients have a hyperdynamic circulation, increased capillary permeability, splanchnic arteriolar vasodilation, reduced effective circulating blood volume and may have latent cirrhotic cardiomyopathy (CCM).
* Hence assessment of volume status and cardiac reserve using conventional central venous pressure (CVP) or mean arterial pressure (MAP) remains difficult.

Novelty:

* In two recent trials, the role of 5% albumin vs PlasmalyteTM (FRISC study)(1) and 20% albumin vs. PlasmalyteTM (ALPS study) (2) were reported as the primary resuscitation fluid. Neither trial showed a clear long term survival benefit of albumin over balanced salt solution (BSS). In fact, the ALPS trial reported that there was increased risk of pulmonary edema with use of 20% albumin as fluid resuscitation.
* A major limitation of such trial data is that the focus is on choice of fluid rather than looking at hemodynamic goals of resuscitation, resulting in protocolized overzealous fluid administration.
* This may result in albumin-related pulmonary edema, and precipitation of overt heart failure in patients with silent CCM.
* POC-Echo-based fluid resuscitation can prevent pulmonary edema and consequently respiratory failure, while ensuring renal and tissue perfusion.
* It is unclear if choice of fluid or appropriate targets of resuscitation drive the survival benefit in the intensive care management of cirrhosis with severe sepsis.

Objectives:

* The investigators will conduct an ICU based randomised controlled feasibility trial comparing two measures of resuscitation: Echocardiography (ECHO) Guided septic shock resuscitation vs. a modified Goal-Directed Fluid Therapy (GDT) as recommended by sepsis guidelines which use protocol fluids.
* The study will validate the role of POC-Echo parameters as volume assessment tools (cardiac index, systemic vascular resistance index) to determine endpoints of fluid resuscitation and need for vasopressors.
* Lastly, the study aims to determine the presence of CCM in this population, and its impact on clinical outcomes.

Methods POC-ECHO will be done within 1 hours of admission to the liver ICU and at 24h, 48 h and 72 hours in patients with cirrhosis with systolic blood pressure of \<90 mmHg or a mean arterial pressure \<65 mmHg. Resuscitation target is maintenance of MAP ≥65 mmHg with use of fluids and/or vasopressors. Clinical, cardiac biomarkers, and survival data based on resuscitation fluids will be prospectively collected. CCM will be defined as per CCM Consortium (2020) criteria.

Expected outcome.

The key questions to be answered in the resuscitation of critically ill patients with cirrhosis and sepsis induced hypotension are:

1. What should be best method of ensuring adequate fluid resuscitation i.e. fluid resuscitation protocol?
2. Which measurable clinical parameter can be used to determine adequacy of fluid resuscitation, and as a predictor of mortality outcomes at 7 and 28 days?
3. Whether early fluid resuscitation translates into better clinical outcome in decreasing duration of hospital and intensive care unit (ICU) stay, prevention of AKI and prevention of secondary sepsis?

Conditions

• Cirrhosis, Liver
• Cirrhotic Cardiomyopathy
• Septic Shock

Interventions

DIAGNOSTIC_TEST

POCUS

* In the Intervention arm (ECHO) arm, we propose a Cardiac ultrasound target-based fluid resuscitation. This incorporates the fluid assessment based on POCUS and myocardial dysfunction based on cardiac ultrasound (cardiac index, myocardial contractility, stroke volume) and portal hypertension-related systemic vasodilation accentuated by sepsis (systemic vascular resistance index or SVRI). * The POCUS -velocity time integral and stroke volume index will be used to determine fluid responsiveness. * If there is an increment in cardiac index by 15% after giving a fluid bolus (i.e. 250-500 ml of BSS in 15min), we can define 'fluid responsiveness' present. * The achievement of lactate clearance, MAP target \>65mmHg and ScV02 \>70% remains similar as the fixed target strategy. The main resuscitation fluid remains 5% albumin in this arm. Albumin infusion will be titrated based on lung ultrasound.

DIAGNOSTIC_TEST

Fixed Resuscitation Strategy based on Target MAP

• Fluid boluses would be administered until a CVP of 8-10 mmHg is achieved and IVC diameter is between 1.8-2 cm with 20-30% collapsibility. Till the central line is placed, the shock index (heart rate/ systolic blood pressure) will be used instead of the CVP. Thus fluids (500 ml crystalloid followed by 5% albumin) will be administered for a shock index ≥1 and till CVP is placed. * When CVP goal is achieved vasopressors will be started to target MAP ≥ 65mmHg. Once MAP target is achieved, ScVO2 ≥70% and lactate clearance \>10% will be targeted. * If ScVO2 is \<70% and lactate clearance is \<10%, noradrenaline will be started and titrated upwards. take it up to a maximum dose. * Second choice of pressor agent will be vasopressin. * Thus. CGDT group targets CVP, MAP\>65 mmHg, followed by ScVO2 ≥70% and lactate clearance in a step wise way.

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-01

Primary Completion

2028-08-30

Completion

2028-12-30

Countries

• India

Study Locations