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

• Patients with cirrhosis requiring intensive care for severe sepsis carry a risk of high mortality due to altered hemodynamics with reduced effective arterial volume, portal hypertension, presence of ascites, and risk of complications like acute variceal bleeding (AVB), acute kidney injury (AKI) and circulatory failure(3-5). The main principles for management of severe sepsis include early recognition, control of the source of infection, appropriate and timely administration of antimicrobial agents, and resuscitation with intravenous fluids +/- vasoactive drugs, if needed (6).
• Due to portal hypertension, these patients have a hyperdynamic circulation, increased capillary permeability, splanchnic arteriolar vasodilation, and may have latent cirrhotic cardiomyopathy (CCM) (7). Hence assessment of volume status and cardiac reserve using conventional central venous pressure (CVP) or mean arterial pressure (MAP) remains difficult (8). Although inferior vena cava (IVC) dynamics and IVC collapsibility index are reasonable accurate for ventilated patients, their use in spontaneously breathing subjects or those with tense ascites are not defined(9). Even measures like passive leg raising and Valsalva manoeuvre are difficult to perform in cirrhotic patients with tense ascites.
• Early goal directed therapy (EGDT) improved outcomes in a randomized trial in patients with severe sepsis(10). Thereafter EGDT was incorporated into the 6-hour resuscitation bundle of the surviving sepsis campaign guidelines, but did not incorporate patients with cirrhosis(11-13). Following the early EGDT trials, studies focussed choice of resuscitation fluid i.e., albumin versus normal saline or balanced salt solution (BSS), concerns about potential risks of volume overload and pulmonary edema and lack of generalisability in subsequent trials showed that there was no associated survival benefit with an aggressive fluid protocol(14, 15). In the ALBIOS study, 1818 patients with severe sepsis or septic shock were randomized either to receive 300 ml of 20% albumin plus crystalloid or to receive crystalloid alone initially to achieve the EGDT goals. However, no mortality benefit was demonstrated at 29 or 90 days(16).
• Intravenous albumin improves effective circulatory volume by improving plasma oncotic pressure and expands the total blood volume making it the apparent 'fluid of choice' for resuscitation in cirrhosis. The 5% albumin expands plasma volume by 80% of the administered volume, 20% albumin by 210% and 25% albumin by 260% which is expected to remain in the intravascular compartment longer than balanced salt solutions or normal saline(17). 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 BSS.
• Point-of-care ultrasonography (POCUS), including cardiac ultrasound, is used to assess volume status, and hemodynamic parameters like cardiac output, systemic vascular resistance, cardiac contractility, and pulmonary artery pressure, which aid in the early and accurate diagnosis of heart failure, cirrhotic cardiomyopathy, porto-pulmonary hypertension, hepatopulmonary syndrome, arrhythmia, pulmonary embolism, and ischemic heart disease. This helps determine the ideal amount of fluids, and vasopressors in resuscitation of patients with cirrhosis.

Inclusion criteria

• Critically ill patient with cirrhosis of any etiology
• Sepsis-related Hypotension (MAP <65mmHg or SBP <90mmHg)
• 18-65 yrs of age -

Exclusion criteria

• Already on vasopressors/inotropes
• Severe pre-existing cardiopulmonary disease like porto-pulmonary hypertension (PPH), known coronary artery disease, congenital or valvular heart disease, prosthetic cardiac valves, dilated or restrictive cardiomyopathy.
• Poor chest wall window due to left pleural effusion, left pneumothorax, small intercostal spaces that restrict performance of a POCUS.
• 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
• Previous transjugular intra hepatic portosystemic shunt (TIPS),
• Hepatocellular carcinoma
• Pregnant or lactating women
• Informed consent refused by patient or attendants
• Active COVID-19 infection