Fluid Management and Individualized Resuscitation in Sepsis

Inclusion Criteria: * Adult patients (≥ 18 years of age); * Referred to internal medicine, nephrology, geriatric medicine, oncology, hematology, lung medicine, rheumatology, gastrointestinal / liver medicine, urology, or emergency medicine (non-trauma); * Confirmed or suspected infection according to the physician's judgement upon arrival to the ED, based the presence of an acute phase response not due to an alternative non-infectious cause (i.e., body temperature \< 36°C or \>38°C, leukocyte count \> 12 x109/L or C-reactive protein \> 50 mg/L), and/or on symptoms suggestive for an infection (e.g. productive cough, dyspnea, dysuria, pollakisuria, abdominal pain, erythema) * Need for hemodynamic resuscitation, based on any of the following (first measurement at ED arrival \[triage\]): * Mean arterial pressure (MAP) \< 70 mmHg * Systolic blood pressure (SBP) \< 90 mmHg or a SBP decrease \>40 mmHg * Lactate \> 4.0 mmol/L * Shock index\* \> 0.9 * Enrolled in study within one hour after ED arrival Exclusion Criteria: * Primary diagnosis of: acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, drug overdose, or injury from burn or trauma, diabetic ketoacidosis, hyper-osmolarity syndrome, pancreatitis * Known aortic insufficiency, aortic abnormalities, or intraventricular heart defect, such as ventral septal defect or atrial septal defect * Known advanced heart failure - meaning NYHA IV functional class HF, on waiting list for heart transplant, LVAD recipient or chronic inotrope use. * Known end-stage kidney disease (dialysis-dependent CKD stage 5 or eGFR \<15 mL/min/1.73 m²) * Decompensated liver cirrhosis at ED admission (e.g., ascites, hepatic encephalopathy, or variceal bleeding) * Hemodynamic instability due to active bleeding * Patient has received \>1 liter of IV fluid prior to study randomization * Requires immediate surgery * Transfer from another hospital after initiation of therapy (a.o. referred by another hospital ICU) or another in-hospital setting * Pregnant women * Trauma patients * Suspected intra-abdominal hypertension, based on the presence of portal hypertension (i.e. presence of ascites due to liver cirrhosis, esophageal varices or as measured by Doppler ultrasound) * Inability to obtain IV access * Patient uncouples from treatment algorithm * Patient should be excluded based on the opinion of the Clinician/Investigator * Not able to commence treatment protocol within 1 hour after randomization * Potential ICU-admission unwanted by advanced care directive (e.g., limited life expectancy)