Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with piperacillin/tazobactam or cefepime and meropenem.

Piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) and vancomycin (VAN) are commonly used in combination for sepsis. Studies have shown an increased risk of acute kidney injury (AKI) with TZP and VAN compared to FEP or MEM. VAN guidelines recommend area under the curve (AUC) monitoring over trough (Tr) to minimize the risk of AKI. We investigated the association of AKI and MAKE-30 with the two VAN monitoring strategies when used in combination with TZP or FEP/MEM. Adult patients between 2015 and 2019 with VAN > 72 hours were included. Patients with AKI prior to or within 48 hours of VAN or baseline CrCl of ≤30 mL/min were excluded. Four cohorts were defined: FEP/MEM/Tr, FEP/MEM/AUC, TZP/Tr, and TZP/AUC. A Cox Proportional Hazard Model was used to model AKI as a function of the incidence rate of at-risk days, testing monitoring strategy as a treatment effect modification. Multivariable logistic regression was used to model MAKE-30. Overall incidence of AKI was 18.6%; FEP/MEM/Tr = 115 (14.6%), FEP/MEM/AUC = 52 (14.9%), TZP/Tr = 189 (26%), and TZP/AUC = 96 (17.1%) (P < 0.001). Both drug group [(TZP; P = 0.0085)] and monitoring strategy [(Tr; P = 0.0007)] were highly associated with the development of AKI; however, the effect was not modified with interaction term [(TZP*Tr); 0.085)]. The odds of developing MAKE-30 were not different between any group and FEP/MEM/AUC. The effect of VAN/TZP on the development of AKI was not modified by the VAN monitoring strategy (AUC vs trough). MAKE-30 outcomes were not different among the four cohorts.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism.

Progression of Kidney Injury with the Combination of Vancomycin and Piperacillin-Tazobactam or Cefepime in Sepsis-Associated Acute Kidney Injury.

Introduction: The combination of vancomycin/piperacillin-tazobactam is associated with increases in serum creatinine compared to other antibiotic combinations in the treatment of infections for hospitalized patients. However, the available literature is limited to the study of incident acute kidney injury (AKI). The combination has not been evaluated in patients with AKI already present and the degree to which the trajectory of AKI is influenced by this combination is unknown. Methods: This was a single center, retrospective cohort study of adult patients with sepsis and AKI present on admission prescribed a combination of vancomycin with either piperacillin-tazobactam or cefepime within the first 3 days of admission. The primary outcome was maximum serum creatinine observed within days 2-7 of the hospital stay. Subsequent kidney outcomes were evaluated at one week and hospital discharge. Results: Of 480 patients with sepsis and AKI who met inclusion criteria, 288 (60%) received vancomycin/piperacillin-tazobactam, and 192 (40%) received vancomycin/cefepime. Patients were well-matched on clinical factors, including severity of illness, stage of AKI, exposure to other nephrotoxins, and durations of antimicrobial therapy. There were no differences in AKI trajectory during the first week as assessed by maximum serum creatinine (2.1 (1.4-3.5) mg/dl vs. 2.1 (1.4-3.0) mg/dl; p=0.459) and AKI progression (24.0% vs. 23.4%; p=0.895). No differences were observed with other kidney related outcomes, including the need for dialysis (14.6% vs. 13.0%; p=0.628) or major adverse kidney events at hospital discharge (48.3% vs. 47.9%; p=0.941). Conclusions: In patients with sepsis and AKI, the combination of vancomycin/piperacillin-tazobactam compared to vancomycin/cefepime was not associated with higher serum creatinine values or AKI progression in the week following ICU admission.

Narrative Review: Addressing Covid-19 Vaccine Concerns in Special and Vulnerable Populations.

Public health advocates and healthcare professionals (HCPs) have been challenged with vaccine hesitancy and addressing misinformation. In order for HCPs and pharmacists, in particular, to serve as effective stewards of COVID-19 vaccine science in the interest of the public good, it is imperative for HCPs to appreciate the various factors contributing to vaccine hesitancy and vaccine distrust. A PubMed search was performed and relevant articles on COVID-19 vaccine in populations of interest were included. Information from health agencies, such as the Centers for Disease Control and Prevention (CDC) as well as established professional health societies was incorporated for guidance. This review focuses on COVID-19 vaccine concerns in the populations of children, pregnancy and lactation, immunocompromised, and religious and ethnic disparities. We also discuss post emergency use authorization experience with respect to vaccine safety including annotations on Guillain-Barré Syndrome, myocarditis and pericarditis, and thrombosis with thrombocytopenia syndrome.

Cefepime Induced Neurotoxicity Following A Regimen Dose-Adjusted for Renal Function: Case Report and Review of the Literature.

Introduction: Cefepime induced neurotoxicity (CIN) is commonly associated with renal dysfunction, however CIN can occur in patients with normal renal function or renally dose-adjusted regimens. Few reports of this kind have obtained cefepime concentrations to assist in diagnosis. Patient Case: A 42-year old female with a complex past medical history was transferred to our facility with chief complaint of worsening shock and respiratory failure, and the patient was also noted to be hypernatremic, experiencing diabetic ketoacidosis (DKA), and acute kidney injury (AKI). Her DKA resolved and hypernatremia and AKI began to improve. As a result, cefepime was dose-adjusted for renal function estimated by the Cockcroft-Gault (CG) equation. Her hospital course was complicated by persistent altered mental status (AMS), preventing extubation. Cefepime was discontinued due to concern for CIN, and a concentration was obtained 13-hours after the last dose which was elevated at 49 µg/mL. Two days following cefepime discontinuation, the patient's mental status improved allowing for successful extubation. The patient remained stable and was discharged to an acute care floor and then ultimately back to home. Conclusion: CIN should be part of a wider differential diagnosis for patients experiencing encephalopathy, and inaccurate renal function estimation may be a risk factor for developing CIN. Furthermore, therapeutic drug monitoring (TDM) may serve as an important clinical tool in diagnosing and managing CIN.

Association of Phosphate-Containing versus Phosphate-Free Solutions on Ventilator Days in Patients Requiring Continuous Kidney Replacement Therapy.

BACKGROUND AND OBJECTIVES: Hypophosphatemia is commonly observed in patients receiving continuous KRT. Patients who develop hypophosphatemia may be at risk of respiratory and neuromuscular dysfunction and therefore subject to prolongation of ventilator support. We evaluated the association of phosphate-containing versus phosphate-free continuous KRT solutions with ventilator dependence in critically ill patients receiving continuous KRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a single-center, retrospective, pre-post cohort study of adult patients receiving continuous KRT and mechanical ventilation during their intensive care unit stay. Zero-inflated negative binomial regression with and without propensity score matching was used to model our primary outcome: ventilator-free days at 28 days. Intensive care unit and hospital lengths of stay as well as hospital mortality were analyzed with a t test or a chi-squared test, as appropriate. RESULTS: We identified 992 eligible patients, of whom 649 (65%) received phosphate-containing solutions and 343 (35%) received phosphate-free solutions. In multivariable models, patients receiving phosphate-containing continuous KRT solutions had 12% (95% confidence interval, 0.17 to 0.47) more ventilator-free days at 28 days. Patients exposed to phosphate-containing versus phosphate-free solutions had 17% (95% confidence interval, -0.08 to -0.30) fewer days in the intensive care unit and 20% (95% confidence interval, - 0.12 to -0.32) fewer days in the hospital. Concordant results were observed for ventilator-free days at 28 days in the propensity score matched analysis. There was no difference in hospital mortality between the groups. CONCLUSIONS: The use of phosphate-containing versus phosphate-free continuous KRT solutions was independently associated with fewer ventilator days and shorter stay in the intensive care unit.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Association of Phosphate Containing Solutions with Incident Hypophosphatemia in Critically Ill Patients Requiring Continuous Renal Replacement Therapy.

BACKGROUND: Hypophosphatemia in critically ill patients is a common electrolyte disturbance associated with a myriad of adverse effects. Critically ill patients requiring continuous renal replacement therapy (CRRT) are at high risk of hypophosphatemia and often require phosphate supplementation during therapy. The aim of this study was to evaluate the association of phosphate versus non-phosphate containing CRRT solutions with incident hypophosphatemia in critically ill patients requiring CRRT. MATERIALS AND METHODS: This is a single-center, retrospective, cohort study at a tertiary academic medical center of 1,396 adult patients requiring CRRT during their intensive care unit stay comprising 7,529 (phosphate containing) and 4,821 (non-phosphate containing) cumulative days of CRRT. Multivariable logistic regression was used to model the primary outcome of hypophosphatemia during CRRT according to exposure to phosphate versus non-phosphate containing CRRT solutions. RESULTS: Incident hypophosphatemia during CRRT, serum phosphate <2.5 mg/dL or 0.81 mmol/L, was significantly higher in the non-phosphate versus phosphate containing solution group: 304/489 (62%) versus 175/853 (21%) (p < 0.001). Cumulative phosphate supplementation was also significantly higher in the non-phosphate versus phosphate containing solution group: 79 (IQR: 0-320) versus 0 (0-16) mmol (p < 0.001). Non-phosphate solutions were associated with an 8-fold increase in the incidence of hypophosphatemia (adjusted OR 8.05; 95% CI 5.77, 11.26; p < 0.001). DISCUSSION/CONCLUSIONS: The use of phosphate containing CRRT solutions was independently associated with reduced risk of incident hypophosphatemia and decreased phosphate supplementation during CRRT. Interventional studies to confirm these findings are needed.

Pharmacotherapy in Coronavirus Disease 2019 and Risk of Secondary Infections: A Single-Center Case Series and Narrative Review.

Since the onset of the coronavirus disease 2019 pandemic, immune modulators have been considered front-line candidates for the management of patients presenting with clinical symptoms secondary to severe acute respiratory syndrome coronavirus 2 infection. Although heavy emphasis has been placed on early clinical efficacy, we sought to evaluate the impact of pharmacologic approach to coronavirus disease 2019 within the ICU on secondary infections and clinical outcomes. DATA SOURCES: PubMed (inception to March 2021) database search and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to coronavirus disease 2019, management of severe acute respiratory syndrome coronavirus 2-associated respiratory failure, and prevalence of secondary infections with pharmacotherapies were selected. The MeSH terms "COVID-19," "secondary infection," "SARS-CoV-2," "tocilizumab," and "corticosteroids" were used for article identification. Articles were narratively synthesized for this review. DATA SYNTHESIS: Current data surrounding the use of tocilizumab and/or corticosteroids for coronavirus disease 2019 management are limited given the short follow-up period and conflicting results between studies. Further complicating the understanding of immune modulator role is the lack of definitive understanding of clinical impact of the immune response in coronavirus disease 2019. CONCLUSIONS: Based on the current available literature, we suggest prolonged trials and follow-up intervals for those patients managed with immune modulating agents for the management of coronavirus disease 2019.

Comparison of fixed dose versus train-of-four titration of cisatracurium in acute respiratory distress syndrome.

PURPOSE: To compare the ventilatory and clinical outcomes associated with a fixed-dose cisatracurium infusion versus a titrated infusion strategy in patients with Acute Respiratory Distress Syndrome (ARDS). MATERIALS AND METHODS: Single-center, retrospective, cohort study in a medical ICU of a tertiary care academic medical center. Adult patients ≥18 years old with a continuous infusion of cisatracurium for ≥12 h for treatment of ARDS were included. The primary outcome was the PaO2 /FiO2 ratio assessed at 24 and 48 h following cisatracurium initiation. Secondary outcomes included amount of average dose of drug administered, 28-day ventilator-free days, LOS, and hospital mortality. RESULTS: 167 patients were included; median baseline PaO2/FiO2 was 97 (76-146), median SOFA score of 9 (7-11), and ICU mortality was 71/167 (43%). In a mixed-effects model, fixed dose and titrated cisatracurium associated with similar changes in PaO2/FiO2 assessed at 24 and 48 h (p = 0.316). Fixed-dose was associated with a >3-fold increase in drug exposure (average dose 6.4 (5.4-8.0) vs. 2.0 (1.5-2.8) mcg/kg/min; p < 0.001, respectively). No differences were observed in secondary clinical endpoints. CONCLUSION: Fixed-dose cisatracurium was associated with similar ventilatory and clinical outcomes compared to titrated strategy, yet it was associated with a 3-fold increase in dose administered.

How To Prescribe And Troubleshoot Continuous Renal Replacement Therapy: A Case-Based Review.

Continuous RRT (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in patients who are critically ill with AKI in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population, such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk, and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized, or do not have solid evidence-based foundations. In this study, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to patients who are critically ill. Specific focus is on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation, and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves, and is on the basis of step-wise decisions made during the care of this patient, according to the specific patient's needs and the logistics available at the corresponding institution.

Impact of Hyperoncotic Albumin on Duration of Vasopressor Support in Septic Shock: A Propensity Score-Matched Analysis.

BACKGROUND: While albumin has not been shown to reduce mortality in sepsis and septic shock, a tertiary analysis of a large trial suggested that it may reduce the duration of vasopressor use in septic shock. OBJECTIVE: We sought to test if 25% albumin administration was associated with reduced cumulative vasopressor use in septic shock in a real-world setting. METHODS: This was a retrospective, propensity score-matched cohort study of septic shock in which patients receiving albumin were compared with a matched cohort of those not receiving albumin. The primary outcome was days alive and free of vasopressors. RESULTS: The matched cohort included 335 patients who received albumin and 335 who did not. The days alive and free of vasopressors were similar between the albumin and no albumin groups: 17.4 (0-24.8) versus 19.4 (0-25.3); P = 0.160. Similarly, in-hospital mortality was no different between groups (46.9% vs 44.8%; P = 0.587). Receipt of albumin was associated with fewer ventilator-free and intensive care unit (ICU)-free days: 0 (0-19) versus 11 (0-23), P = 0.007, and 0 (0-18) versus 10.6 (0-22.1), P = 0.002, respectively. CONCLUSION AND RELEVANCE: Albumin use in septic shock was not associated with additional days alive and free of vasopressors or in-hospital mortality. The finding of fewer ventilator- and ICU-free days may reflect selection of patients who were critically ill for longer periods of time before or after albumin administration. Additional study is needed to clarify the impact that timing may have on the effectiveness of albumin in septic shock.

Development, implementation and outcomes of a quality assurance system for the provision of continuous renal replacement therapy in the intensive care unit.

Critically ill patients with requirement of continuous renal replacement therapy (CRRT) represent a growing intensive care unit (ICU) population. Optimal CRRT delivery demands continuous communication between stakeholders, iterative adjustment of therapy, and quality assurance systems. This Quality Improvement (QI) study reports the development, implementation and outcomes of a quality assurance system to support the provision of CRRT in the ICU. This study was carried out at the University of Kentucky Medical Center between September 2016 and June 2019. We implemented a quality assurance system using a step-wise approach based on the (a) assembly of a multidisciplinary team, (b) standardization of the CRRT protocol, (c) creation of electronic CRRT flowsheets, (d) selection, monitoring and reporting of quality metrics of CRRT deliverables, and (e) enhancement of education. We examined 34-month data comprising 1185 adult patients on CRRT (~ 7420 patient-days of CRRT) and tracked selected QI outcomes/metrics of CRRT delivery. As a result of the QI interventions, we increased the number of multidisciplinary experts in the CRRT team and ensured a continuum of education to health care professionals. We maximized to 100% the use of continuous veno-venous hemodiafiltration and doubled the percentage of patients using regional citrate anticoagulation. The delivered CRRT effluent dose (~ 30 ml/kg/h) and the delivered/prescribed effluent dose ratio (~ 0.89) remained stable within the study period. The average filter life increased from 26 to 31 h (p = 0.020), reducing the mean utilization of filters per patient from 3.56 to 2.67 (p = 0.054) despite similar CRRT duration and mortality rates. The number of CRRT access alarms per treatment day was reduced by 43%. The improvement in filter utilization translated into ~ 20,000 USD gross savings in filter cost per 100-patient receiving CRRT. We satisfactorily developed and implemented a quality assurance system for the provision of CRRT in the ICU that enabled sustainable tracking of CRRT deliverables and reduced filter resource utilization at our institution.

Acute skeletal muscle wasting and dysfunction predict physical disability at hospital discharge in patients with critical illness.

BACKGROUND: Patients surviving critical illness develop muscle weakness and impairments in physical function; however, the relationship between early skeletal muscle alterations and physical function at hospital discharge remains unclear. The primary purpose of this study was to determine whether changes in muscle size, strength and power assessed in the intensive care unit (ICU) predict physical function at hospital discharge. METHODS: Study design is a single-center, prospective, observational study in patients admitted to the medicine or cardiothoracic ICU with diagnosis of sepsis or acute respiratory failure. Rectus femoris (RF) and tibialis anterior (TA) muscle ultrasound images were obtained day one of ICU admission, repeated serially and assessed for muscle cross-sectional area (CSA), layer thickness (mT) and echointensity (EI). Muscle strength, as measured by Medical Research Council-sum score, and muscle power (lower-extremity leg press) were assessed prior to ICU discharge. Physical function was assessed with performance on 5-times sit-to-stand (5STS) at hospital discharge. RESULTS: Forty-one patients with median age of 61 years (IQR 55-68), 56% male and sequential organ failure assessment score of 8.1 ± 4.8 were enrolled. RF muscle CSA decreased significantly a median percent change of 18.5% from day 1 to 7 (F = 26.6, p = 0.0253). RF EI increased at a mean percent change of 10.5 ± 21% in the first 7 days (F = 3.28, p = 0.081). At hospital discharge 25.7% of patients (9/35) met criteria for ICU-acquired weakness. Change in RF EI in first 7 days of ICU admission and muscle power measured prior to ICU were strong predictors of ICU-AW at hospital discharge (AUC = 0.912). Muscle power at ICU discharge, age and ICU length of stay were predictive of performance on 5STS at hospital discharge. CONCLUSION: ICU-assessed muscle alterations, specifically RF EI and muscle power, are predictors of diagnosis of ICU-AW and physical function assessed by 5x-STS at hospital discharge in patients surviving critical illness.

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19.

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.

Impact of protocolized diuresis for de-resuscitation in the intensive care unit.

OBJECTIVE: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill. METHODS: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria. RESULTS: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR - 2257 (- 5676-920) mL vs 265 (- 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated. CONCLUSIONS: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.