Impact of Protocolized De-resuscitation with Frusemide/Renal Replacement Therapy Compared with Standard Intervention in Critically Ill Patients on Mortality in A Tertiary Care Hospital

BACKGROUND: A positive cumulative fluid balance in critically ill patients has been associated with poor clinical outcomes, and is independently associated with organ dysfunction and an increased risk of death.1 The impact that a stringent removal of excess fluid, after initial hemodynamic stabilization, has on intensive care unit (ICU) outcome may be compared with that of a more conservative fluid management protocol. This study was undertaken with the aim of studying the impact of protocolized deresuscitation during the first week in ICU patients and its impact on the 28-day mortality. METHODS: The study was conducted at a tertiary care, referral ICU for a period of one year from January 2023 to January 2024. Baseline demographics such as age, sex, diagnosis, APACHE II scores, comorbid conditions, cardiac ejection fraction (EF), case distribution, post-operative status, need for vasopressors and re-admission to ICU were taken. The inclusion criteria were all adult ICU patients >18 years of age with at least 2 days of ICU admission, while patients excluded were those who did not consent for the study, length of ICU stay <2 days, lactates>4, patients requiring norepinephrine/epinephrine> 0.2 mcg/kg/min/& >1 vasopressor in use and patients with subarachnoid haemorrhage. Patients were assigned to either standard care – at the discretion of physician or to the protocolized diuresis with frusemide, starting from the next day after achieving stabilization, for a period up to 48 hours. The frusemide protocol involved a 0.5 mg/kg bolus followed by infusion at 2.5 mg/hour, or haemodialysis, to target a negative or neutral balance, or fluid accumulation state in the 1st week. Primary outcome measured was 28-day mortality. Secondary outcomes included were ICU mortality, mechanical ventilator days, ICU length of stay (ICU-LOS), hospital – LOS, New adverse effects – hypernatremia, metabolic alkalosis and new AKI. RESULTS: Out of the 200 patients, 102 were included in the protocolized deresuscitation group and 98 were included in standard care group. Baseline parameters did show statistical significance in terms of age, overload states, comorbidities like diabetes, HTN, CKD and cardiac disease. A regression analysis for the confounding factors among baseline parameters found association of elevated left ventricular filling pressure (LVFP) with mortality and urosepsis with 28-day mortality. There was no difference in 28-day mortality between the two groups (22% versus 19%, p = 0.845) or ICU mortality (10.8% versus 12.8%, p=0.667). Among secondary outcomes, the ICU – LOS was 5.0 days ([4.0-8.0], p value = 0.43) days for both the groups. The hospital LOS was found to have median [IQR] of 8[7.0-11.0] days and 8[6.0-11.3] days respectively. The need for mechanical ventilation and vasopressor was significantly higher in standard care [22.5% and 43.6%] compared to protocolized deresuscitation group [37.3% and 59.1%], respectively, (p = 0.002) in both cases. Among the secondary outcomes, the standard care group had a more positive fluid balance at stabilization (2908 mL vs 1220, p <0.001) as well as at ICU discharge (4646 mL vs -250 mL, p <0.001). Among the adverse effects, there was no worsening of lactates, hypernatremia, and metabolic alkalosis. New onset of AKI was noted more in protocolized deresuscitation group (15.7% vs 6.4%, p = 0.39). Hypokalemia was found in a greater number of patients in the protocolized deresuscitation group (11% versus 4%) versus standard care group. Among the CKD subgroup, there was a significant difference in the 28-day mortality between CKD positive and negative patients (52% versus 13.3%, p= 0.015) but the secondary outcomes did not differ. CONCLUSION: This study aimed to see was whether deresuscitation in a protocol format with targeted neutral to negative balance may impact clinical outcomes in all subsets of ICU patients. There was no difference in 28-day mortality or ICU mortality between the protocolized deresuscitation and standard care group. This differs from certain other studies where the mortality increased with increase in cumulative balance by day 7.2 Larger studies are needed to corroborate these findings.