Hemodynamic Phenotype and Capillary Refill Time-targeted Resuscitation Strategy

Summary

Septic shock is associated with a high mortality risk. Fluid overload occurs when fluids are administered to fluid unresponsive patients, but also when inappropriate resuscitation goals are pursued. Alongside, evidence confirms that abnormal peripheral perfusion after resuscitation is associated with increased morbidity and mortality. Targeted resuscitation associates with lower mortality, less organ dysfunction, and less intensity of treatment. Over-resuscitation may contribute to a worse outcome.

Many patients remain hypovolemic after initial resuscitation. Others present very low diastolic arterial pressures (DAP) reflecting profound vasoplegia and may benefit from early norepinephrine (NE) instead of fluids. Administering fluids in this setting could increase the risk of fluid overload. In addition, relevant myocardial dysfunction is present in a significant number of patients. Pulse pressure (PP) and DAP evaluation may help clinicians to individualize initial management sparing unnecessary fluid loading.

Objective: To test if a CRT-targeted resuscitation based on clinical hemodynamic phenotyping can improve a hierarchical clinical outcome - mortality, time to cessation of vital support, and length of hospital stay, all within 28 days - in septic shock patients as compared to usual care.

A2 is a multicenter randomized controlled trial (RCT) comparing a CRT-targeted, hemodynamics-based resuscitation strategy with usual care in patients with early septic shock during a 6 h intervention period. A sample size of 1500 patients was calculated to detect a 6% absolute reduction in mortality in the CRT group, and the win-ratio method will be used to test the superiority in the hierarchical outcomes mentioned above.

The combination of a CRT-targeted strategy with a clinical hemodynamic phenotyping may aid to personalize initial resuscitation with potential additional fluid-sparing effects. To categorize patients at baseline according to PP may conduct patients with low PP (\<40mmHg) to fluid responsiveness (FR) assessment and eventually fluid boluses, while patients with normal PP will be treated according to DAP, adjusting NE when to avoid further fluids loading in patients who normalize CRT.

Fluid resuscitation will be focused on FR+ hypoperfused patients to prevent harmful fluid administration in FR- patients.

Conditions

• Septic Shock

Interventions

OTHER

CRT-targeted strategy associated with a clinical hemodynamic phenotyping to personalize initial resuscitation in septic shock patients

A combination of combine a CRT-targeted strategy with a clinical hemodynamic phenotyping that may aid to personalize initial resuscitation with potential additional fluid-sparing effects.

OTHER

Usual care (UC)

\- Patients allocated to the UC group will be managed by the clinical staff according to usual practice at their sites including decisions about hemodynamic and perfusion monitoring, and all treatments, but should follow general recommendations of the Surviving Sepsis Campaign to avoid extremes of clinical practice. This includes basic hemodynamic targets such as a MAP \>65 mmHg, heart rate (HR) \<120 beats per minute (BPM), arterial oxygen saturation (SaO2) \>94%, Hb \> 7 gr/dl, and the use of NE as the first vasopressor and crystalloids as the fluid of choice.

Sponsors & Collaborators

• Fundacion Clinica Valle del Lili

  collaborator OTHER

• Hospital do Coracao

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• Pontificia Universidad Catolica de Chile

  lead OTHER

Principal Investigators

• Glenn Hernandez, MD, PhD · Pontificia Universidad Catolica de Chile

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-18

Primary Completion

2025-03-30

Completion

2025-06-30

Countries

• Chile

Study Locations