Fluid Intolerance Signals as Safety Limits to Prevent Fluid-induced Harm During Septic Shock Resuscitation

Обзор

The goal of this multicentric randomized controlled trial is to compare, in septic shock patients who require further fluid resuscitation, two strategies of administering fluids. The intervention group will integrate fluid intolerance signals to the decision making process, while the control group will follow standard of care, for a 6 hour study protocol. The main question it aims to answer is 1. To compare the effect of both resuscitation strategies on fluid-induced harm, assessed by the change in pulmonary, cardiac, and renal function biomarkers during the study period. 2. To assess the safety of both resuscitation strategies on hypoperfusion resolution, measured by the improvement of capillary refill time (CRT) and lactate during the study period. 3. To determine the dynamics of the different fluid intolerance signals

Подробное описание

Fluids are the first-line hemodynamic therapy during septic shock resuscitation, restoring tissue perfusion by effectively increasing cardiac output and oxygen delivery. Nevertheless, resuscitation fluids can be seen as a double-edged sword since they have a narrow therapeutic index. In the one hand, insufficient fluid administration can perpetuate hypoperfusion, leading to irreversible tissue hypoxia, while excessive fluid administration can lead to fluid-induced harm. The extreme scenario of this condition, fluid overload, has been consistently associated with worse clinical outcomes, including increased risks of prolonged mechanical ventilation, acute kidney injury and mortality. As an eminently retrospective diagnosis, it may underestimate the importance of timely recognition of fluid-induced harm during the resuscitation period and could shift clinicians' efforts to treatment rather than prevention. Thus, identifying organ-specific venous congestion signals early on during the resuscitation process is desirable and could avoid these adverse outcomes. Recent studies have shown that venous congestion signals are present even during the first day of ICU admission.

The investigators hypothesized that in critically ill patients with septic shock, a fluid resuscitation strategy that integrates fluid intolerance signals as safety limits will prevent fluid-induced harm, without compromising hypoperfusion resolution, compared to a standard resuscitation strategy.

To confirm this hypothesis, the investigators propose a multicenter prospective randomized controlled study in 62 critically ill patients with septic shock, comparing two strategies for conducting fluid resuscitation, aiming to decrease fluid-induced harm. One strategy will follow the standard of care, while the other will rest on real-time ultrasound-based monitoring of fluid intolerance signals. The latter approach will allow clinicians to limit fluid administration when potentially deleterious signals appear. The impact of both strategies on fluid-induced harm will be assessed by the evolution of key organ function biomarkers, namely lungs, heart, and kidneys during the 6-hour study period. Perfusion dynamics will be assessed by capillary refill time and arterial lactate kinetics during the study period. Patients will receive general monitoring and management according to ICU standards. Patients will be followed-up for 28 days for other relevant outcomes.

Вмешательства

• Другое Intervention resuscitation
  In fluid responsive patients, fluid intolerance will be checked. Lung Ultrasound (LUS): Anterior LUS with 4-point assessment at each hemithorax. Min:0 and a max:24. Low risk: \< 10; intermediate risk: 10-14 or delta of 2 points. High risk: \>14, or an increase \>4 from baseline. VExUS: Low risk: Grade 0-1. Intermediate risk: 2. High risk: 3 E/e' ratio: Low risk: \<8. Intermediate risk: 8-13. High risk \>14. Central venous pressure (CVP): Low risk \<12 mmHg. Intermediate risk: 12-15 mmHg or a d
• Другое Standard of Care resuscitation
  In fluid responsive patients, fluid challenges of 500 ml of balanced crystalloid will be performed in 30 minutes. After a fluid challenge, peripheral perfusion status and fluid responsiveness will be re-measured. If the patient persists with hypoperfusion, successive fluid challenges will be performed until hypoperfusion resolves or the patient becomes fluid unresponsive. If hypoperfusion signals persists and the patient becomes fluid unresponsive, alternative resuscitation interventions will be

Первичные конечные точки

• Delta of PaO2: fraction of inspired oxygen (FiO2) ratio between 0-6 hours [Срок оценки: 6 hours]

Вторичные конечные точки (5)

• Delta of proBNP between 0-6 hours [Срок оценки: 6 hours]
• Delta of plasma neutrophil gelatinase-associated lipocalin (NGAL) between 0-6 hours [Срок оценки: 6 hours]
• Delta of creatinine between 0-6 hours [Срок оценки: 6 hours]
• Delta of capillary refill time between 0-6 hours [Срок оценки: 6 hours]
• Delta of arterial lactate between 0-6 hours [Срок оценки: 6 hours]

Критерии участия

Критерии включения

• Diagnosed or suspected septic shock
• < 24 hours since diagnosis
• Hypoperfusion signal (altered arterial lactate or CRT) that requires further resuscitation
• Mechanical ventilation
• Positive fluid responsiveness status

Критерии исключения

• Pregnancy
• Do-not-resuscitate status
• Acute coronary syndrome
• Active bleeding
• Severe concomitant acute respiratory distress syndrome (ARDS) (PaO2:FiO2 ratio < 100)
• Anticipated surgery, prone positioning, or renal replacement therapy in the next 6 hours
• Refractory shock according to attending physician
• BMI > 40.
• Inadequate echocardiographic window

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Чили · 3 центра

• Hospital Biprovincial Quillota-Petorca — Quillota
• Hospital Barros Luco — Santiago
• Hospital Clinico UC Christus — Santiago

Публикации

• Munoz F, Born P, Bruna M, Ulloa R, Gonzalez C, Philp V, Mondaca R, Blanco JP, Valenzuela ED, Retamal J, Miralles F, Wendel-Garcia PD, Ospina-Tascon GA, Castro R, Rola P, Bakker J, Hernandez G, Kattan E. Coexistence of a fluid responsive state and venous congestion signals in critically ill patients: a multicenter observational proof-of-concept study. Crit Care. 2024 Feb 19;28(1):52. doi: 10.1186/s PMID 38374167
• Kenny JS, Prager R, Rola P, Haycock K, Basmaji J, Hernandez G. Unifying Fluid Responsiveness and Tolerance With Physiology: A Dynamic Interpretation of the Diamond-Forrester Classification. Crit Care Explor. 2023 Dec 12;5(12):e1022. doi: 10.1097/CCE.0000000000001022. eCollection 2023 Dec. PMID 38094087
• Kattan E, Castro R, Miralles-Aguiar F, Hernandez G, Rola P. The emerging concept of fluid tolerance: A position paper. J Crit Care. 2022 Oct;71:154070. doi: 10.1016/j.jcrc.2022.154070. Epub 2022 Jun 2. PMID 35660844
• Kattan E, Ospina-Tascon GA, Teboul JL, Castro R, Cecconi M, Ferri G, Bakker J, Hernandez G; ANDROMEDA-SHOCK Investigators. Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial. Crit Care. 2020 Jan 23;24(1):23. doi: 10.1186/s13054-020-2732-y. PMID 31973735
• Zampieri FG, Damiani LP, Bakker J, Ospina-Tascon GA, Castro R, Cavalcanti AB, Hernandez G. Effects of a Resuscitation Strategy Targeting Peripheral Perfusion Status versus Serum Lactate Levels among Patients with Septic Shock. A Bayesian Reanalysis of the ANDROMEDA-SHOCK Trial. Am J Respir Crit Care Med. 2020 Feb 15;201(4):423-429. doi: 10.1164/rccm.201905-0968OC. PMID 31574228
• Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Fr PMID 30772908
• Bagshaw SM, Brophy PD, Cruz D, Ronco C. Fluid balance as a biomarker: impact of fluid overload on outcome in critically ill patients with acute kidney injury. Crit Care. 2008;12(4):169. doi: 10.1186/cc6948. Epub 2008 Jul 24. PMID 18671831

Идентификаторы

NCT: NCT06568744 · 220607015 · 1230475

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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