Background and Rationale Sepsis affects 20 to 30 million people globally each year, with an estimated 48.9 million cases in 2017. Despite medical advances, it still carries a high risk of death. Since sepsis progresses rapidly, early treatment is essential. This includes not only starting antibiotics quickly but also managing fluid levels effectively. Research suggests that in sepsis, fluid problems are often due to poor distribution in the body rather than an actual lack of fluids.
Currently, fluid and blood pressure management is often based only on monitoring arterial pressure, which may not provide a full picture of what's happening in the patient's circulatory system. More advanced indicators like Stroke Volume, Cardiac Output, and Peripheral Vascular Resistance can offer better guidance to optimize treatment and improve outcomes.
New non-invasive devices such as NICaS (Non-Invasive Cardiac System) make it easier and faster to monitor these values. NICaS uses electrical impedance technology and is approved by both the FDA and CE. It is easy to use, does not require specialized training, and allows for a more personalized and accurate treatment approach by tracking key heart and circulation parameters in real time.
Primary Objective
The main goal of this study is to compare two treatment strategies for patients with sepsis admitted to medical wards, and see which one leads to better survival:
* Fluid and/or vasopressor therapy guided by non-invasive hemodynamic monitoring (using NICaS), based on values like Stroke Volume, Cardiac Power Index, and Peripheral Vascular Resistance. * Standard fluid therapy based on the international Surviving Sepsis Campaign (SSC) guidelines.
Secondary Objectives
* Use of vasopressors: Check which strategy leads to less frequent use of vasopressor drugs and shorter treatment duration with them. * Kidney function: See which method is linked to fewer cases needing dialysis or kidney support. * Timing of vasopressors: Understand if giving vasopressors earlier leads to better short- and mid-term outcomes, such as lower death rates after 30 days, fewer ICU admissions, and shorter hospital stays. * Albumin levels and circulation: Track how blood albumin levels change with circulation status, to see if there's a link with fluid leakage (capillary leak) and risk of death. * Fluid balance: Analyze how fluid gains and losses relate to changes in heart and circulation measurements. * Microcirculation: Test if adding signs of small vessel (microcirculation) issues to the main heart and blood flow indicators improves predictions of how patients will do. * Prediction scores: Investigate whether combining NICaS readings with common scoring systems like SOFA or APACHE helps doctors predict patient outcomes more accurately. * Time to stability: Compare how quickly patients in each treatment group recover to a stable condition. According to Rosenthal and Kavic's criteria, a patient is considered stable when: -Their illness is improving -There's low risk of getting worse again - Organ support is stable - There's little chance of new problems arising - There are no major complications.
Conclusion This study aims to evaluate whether a more personalized approach using real-time, non-invasive hemodynamic monitoring can lead to better outcomes in septic patients compared to standard care. If successful, this method could help reduce deaths, complications, and treatment costs in sepsis management.
Provision of specific informed consent;
Confirmed or suspected diagnosis of sepsis, defined according to the latest SSC guidelines as: "the presence of a clear or suspected infection with life-threatening organ dysfunction caused by a dysregulated host response to infection indicated by a SOFA (Sequential Organ Failure Assessment) score ≥ 2";
Patients of both sexes, aged 18 years or older;
Patients evaluated in the Emergency Department for suspected infection requiring hospital admission, at the General Medicine ward of Ospedale Alto Vicentino in Santorso (VI, Italy) or the Emergency Medicine ward of the Policlinico Universitario of Pisa (Italy).
Stay in the Emergency Department of more than six hours, considered as the time between ED admission and ward admission;
Administration of more than 1000 cc of crystalloid therapy in the three hours prior to patient arrival in the ward;
Any admission from a facility or ward other than the Emergency Department;
Sepsis related to an ongoing hospital stay or any sepsis not fitting the definition of community-acquired infection;
Parallel
non-invasive hemodynamic assessment
Diagnostic testPatients will be evaluated with non-invasive hemodynamic monitoring using NICaS, measuring cardiac index, stroke volume, cardiac power, vascular resistance, and total body water. A fluid challenge (10 ml/kg crystalloids in 20 minutes) will assess fluid responsiveness. Patients with \>15% stroke volume increase ("fluid responders") will continue hydration therapy per guidelines. Those with ≤15% increase or altered hemodynamics ("fluid non-responders") will start vasopressor treatment. Hemodynamic monitoring repeats every 3 hours for 12 hours to guide therapy adjustments aiming to optimize key parameters (CI, SV, CPI, SVRI). All treatments, fluid balances, and vital signs are recorded systematically.
Treatment per SSC Guidelines
Other interventionPatients receive fluid resuscitation with 30 ml/kg crystalloids over 3 hours. Fluid responsiveness is assessed by blood pressure increase and urine output. Fluid responders (MAP \>65 mmHg and urine output \>1 ml/kg/h) continue maintenance fluids (1-2 ml/kg/h), adjusted by the physician. Non-fluid responders (MAP ≤65 mmHg or urine output \<1 ml/kg/h) start vasopressors to maintain MAP \>65 mmHg, with dosage and fluid therapy managed by the physician. All therapy changes are recorded.
All-cause mortality at 30 days
The primary endpoint of the study will be all-cause mortality at 30 days from hospital admission. Patient survival will be determined using one of the following methods: review of medical records, phone calls to the patient or their designated contact, or to the healthcare facility.
Need for organ support
Proportion of participants who require initiation of mechanical ventilation and/or renal replacement therapy after study enrollment during the hospitalization period.
Days free of organ support
defined as a patient alive and without assisted breathing, new invasive renal replacement therapy, or use of vasopressors (excluding vasopressor use before 48 hours). Each day a patient is alive and free of organ support counts as a day alive and free of organ support.
Hours free of renal replacement therapy
the number of hours between enrollment and the start of renal replacement therapy. If a decision is made to initiate palliative care instead of renal replacement therapy, the hours counted will be from enrollment until the decision to start palliative care.
Initiation of vasopressor therapy
Proportion of participants requiring initiation of vasopressor therapy after study enrollment. The use of vasopressors will be recorded during the hospitalization period, including the type of vasopressor and the time of initiation.
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Regione del Veneto - AULSS n. 7 Pedemontana
Lead sponsor
University Hospital of Pisa
Collaborator
