Safety and Efficacy of Continuous Infusion of Terlipressin With Norepinephrine Versus Norepinephrine Alone in Improving Outcomes of Acute Kidney Injury in Acute on Chronic Liver Failure With Septic Shock

• Aim: To study the safety and efficacy of low-dose continuous infusion of terlipressin with norepinephrine compared to norepinephrine alone in improving outcomes of Acute kidney injury occurring in the context of septic shock in patients with Acute on chronic liver failure. Study population: 1. septic shock with AKI in patients of ACLF Study design: Prospective open labelled randomised controlled study. The study will be conducted in Department of Hepatology ILBS- intensive care unit. At admission: Complete history and physical examination \- Recent Diuretics use \- Loose stools / Recurrent vomiting * Fever, signs of sepsis (Systemic inflammatory response syndrome), shock, respiratory tract infection,spontaneous bacterial peritonitis * Recent contrast use (\< 7 days)/ nephrotoxins use including NSAIDs * Prior renal dysfunction, chronic kudney disease, history of Hemodialysis * History of Hypertension, Diabetes/ renal stones * Baseline workup for Acute on chronic liver failure * Severity of liver disease,AARC-ACLF, MELD score, CTP score (B) Intervention during 0-3 hours (Before randomization) - Pre-randomization interventions: * Withdrawal of diuretics/ Withdrawal of lactulose (in patients with loose stools) * IV hydration with 5 % albumin according to FRISC protocol * Urine output monitoring (catheterize and monitor hourly) ,hourly MAP, Pulse rate * Use of broad-spectrum IV antibiotics promptly within the first hour, in case of suspected/proven sepsis (Avoid nephrotoxic drugs as possible) * Lung ultrasound and IVC (Inferior Vena Cava) measurements will be performed at baseline and hourly for 3 hours. * Fluid boluses will be administered based on IVC measurements and lung ultrasound findings. * Fluid bolus criteria include IVCCI(inferior vena cava collapsibility index) \>40% and an A profile on lung ultrasound. * The stopping rule for fluid boluses is IVCCI \<40% or a B profile on lung ultrasound. * Patients showing improvement within 3 hours will be excluded from further intervention Monitoring • Hemodynamic- MAP,HR, Urine output hourly • Metabolic - lactate, blood sugar, electrolytes • Microbiologic - urine -routine, microscopy and culture, ascitic fluid analysis along with gram stain and c/s in blood culture bottle, sputum or mini BAL -C/s Gram stain. Daily. • Others - daily chest X-ray, Procalcitonin, Cardiac-ECG, 2D echo. Prognostic models: CTP, MELD SOFA daily Stopping Rule • Requirement of Third Vasopressor (Need of Norepinephrine \> 0.5 mcg/kg/min): • If a patient requires norepinephrine at a dose exceeding 0.5 mcg/min, indicating the need for a third vasopressor, this criterion triggers specific actions as per the study protocol. • Threshold (Stopping Rule) for Fluid Boluses: • Fluid boluses will be administered based on IVC and lung ultrasound findings. • The stopping rule for fluid boluses is activated if any of the following criteria are met: • IVC \>25 • IVCCI \<40% • B profile on lung ultrasound • Severe Side Effects or Toxicities (CTAE Grade 4): • If a patient experiences severe side effects or toxicities categorized as CTAE (Common Terminology Criteria for Adverse Events) Grade 4, including arrhythmia, AMI (Acute Myocardial Infarction), cardiomyopathy (as defined later), cyanosis, suspicion or confirmed bowel ischemia, or any other severe adverse event, specific actions or interventions may be required. Salvage group • Patient Unwilling for Further Hospital Stay: • Non responders or when patient in either arm failed • Study will be stopped and management will be done accordingly to guidelines • Adverse effects to terlipressin * Further increase in MAP to be maintained by addition of other ( vasopressors--vasopressin, phenylephrine,steroids) * If the target MAP is not achieved in arm A ,a third vasopressor along with hydrocortisone, Adrenaline and then phenylephrine * If the target MAP is not achieved in arm B, vasopressin along with hydrocortisone, followed by adrenaline and phenylephrine, may be added as a fourth vasopressor. * The indication for start of steroid * Maximum dose of vasopressor in each arm and all patients in salvage arm * Hydrocortisone 100-150mg bolus start followed by 50mg q6hrly and later tapering dose.