The goal of this clinical trial is to find out if a personalized treatment approach can improve care for people with sepsis in the emergency department (ED).
Sepsis is a life-threatening condition that happens when the body has an uncontrolled response to an infection. This can lead to low blood pressure, organ failure, and death if not treated quickly. Right now, most people with sepsis receive a standard amount of fluids to raise their blood pressure. But this one-size-fits-all approach can lead to fluid overload and other complications. Because each person responds differently, this study will test whether a more personalized treatment-based on how the heart responds to fluids-can lead to safer and more effective care.
The study will include 188 adults who come to the ED at the University Medical Centre Groningen (UMCG) with suspected sepsis in need of hemodynamic resuscitation. Everyone in the study will receive fluids to support their blood pressure.
Participants will be randomly assigned to one of two groups:
* Personalized treatment group: Fluids and vasopressors (medications that raise blood pressure) will be given based on how the heart responds to each fluid dose. This response is measured using a non-invasive monitor that tracks stroke volume index (ΔSVI)-a measure of how much blood the heart pumps. * Standard care group: Fluids will be given based on current guidelines (30 milliliters per kilogram of body weight), as decided by the treating doctor.
Researchers will compare how much fluid is given during the first 3 hours of care. They will also look at:
* When and how much vasopressor medicine is used * How well blood pressure and circulation respond * Signs of organ recovery or damage * How long participants stay in the hospital * Any problems or side effects during treatment
The researchers hope that this personalized approach will lead to using less fluid, starting vasopressors earlier, and helping people with sepsis recover more safely and quickly.
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)
Mean arterial pressure (MAP) < 70 mmHg
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)
Parallel
Personalized SV-guided resuscitation
Other interventionParticipants will receive an IV fluid bolus directly after inclusion. Next, measurement of the cardiac output change in response to the fluid bolus by the Starling SV will be used to determine fluid responsiveness. Vital parameters and fluid responsiveness will be used to guide hemodynamic resuscitation, consisting of IV fluids and/or vasopressors, during the first 3 hours.
Standard Care Resuscitation
Other interventionIn the control group, IV fluid and vasopressor administration will be determined at the discretion of the physician and in accordance with currently available guidelines (e.g. Sepsis Surviving Campaign).
The volume of IV fluids in ml administered within the first three hours after study enrolment.
The primary endpoint is the volume of IV fluids in ml administered within the first three hours after study enrolment.
Length-of-stay in hospital/intensive care unit (ICU)
Length-of-stay in hospital and on intensive care unit (ICU) in days
New onset organ failure
Any of the following within 48 hours: * Rise in Sequential Organ Failure Assessment (SOFA) score of at least 2 * Organ support (i.e. vasopressor use \[non-\]invasive mechanical ventilation, acute dialysis, ECMO)
Fluid balance
Net fluid balance calculated as the total volume of fluids administered (intravenous and oral, including prehospital) minus the total volume of fluid output (urine and other measurable losses) within the first three hours after ED presentation
Fluid resuscitation
Volume of IV fluid resusciation within 7 days
Cost-effectiveness
Evaluation of cost-effectiveness based on hospital length of stay, requirement for advanced care, and costs associated with diagnostic and monitoring measurements.
Starling SV monitor trends
Continuous monitoring and recording of stroke volume index (SVI), cardiac index (CI), and total peripheral resistance index (TPRI) trends using the Starling SV device throughout the fluid resuscitation period in the intervention group.
Hemodynamic parameter trends
Measurement of hemodynamic parameters, including systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, lactate levels, and capillary refill time, during resuscitation period, recorded up to three hours after arrival at the emergency department.
Photoplethysmographic (PPG) waveform trends
Measurement of photoplethysmography (PPG) waveform features, including systolic and diastolic peak amplitudes, pulse interval and perfusion index, recorded continuously during the emergency department stay, up to three hours after arrival.
Click on the lead sponsor to view all of their trials.
