Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock
Fernando Pálizas, Bernardo Lattanzio, Natalia Durandal, María Eugenia Alonso, J. Duque, Nicolas Falcon, Ruben A. Mesa, Martín Hunter, Mario Omar Pozo, Facundo Gutiérrez, Santiago Sac, Nicole Goette, Sebastián Consalvo, Pilar Zamudio, Gastón Murias, Juan Carlos Pendino, Lisandro Roberto Bettini, Juan Ignacio Ibarzábal, Valentin Torres, Federico Fiorilli, Walter D Sacchi, Valentin Avila, Cecilia Gonzalez, Agustin Traverso, Antonella Lopipi, Giuliana Sterzer, Jesica Rodriguez Louzan, Elisa Estenssoro, Arnaldo Dubín, Glauco Adrieno Westphal, Matheus Liguori, Lucas Tramujas, Bruna Fornazieri Piotto, Marcelo Luz Pereira Romano, Fernando Medrano, Philippe Rola, Ross Prager, John Basmaji, Giorgio Ferri, Leonardo Hernández, Daniel Amigo, Alejandro Barra, Camilo Coba, L A Valdivia, Juan Pablo Valdivia, Edward Petruska, Roselyn Noguera, Cindy Karel Arregoitia-Sarabia, María Alicia Cid, Jaime Tapia, Felipe Anastacio González González, Felipe Morales, Alex Gomez, Carlos Yarur, José Segura, Ruth Rosales, Ronal Pairumani, Carla Araya, E. Canon, Monserrat Vera, Macarena Larroulet, Carlos Gallo, Carlos Mero, Juan Nicolás Medel, Rodrigo Cornejo, Jorge Montoya, Nicolás Carreño, Víctor Illanes, César Cortés, Macarena Amthauer, Cecilia Gonzalez Almonacid, Roy Sandoval, Pedro Javier Castillo Bascur, Renato Andrés Colima Mendoza, Concha Casado, Julio Enrique Morales Valenzuela, Valentina Orellana Naranjo, Carlos Enrique Chavez Medina, Patricio Santiago López Valladares, Pablo Alarcón, Manuel Díaz, Víctor Manuel Vallejos Rubilar, Eduardo Chinchón, Emilio Daniel Valenzuela, Vanessa Oviedo, Ricardo Dias de Castro, Rodrigo Ulloa, Sebastián Morales, Roberto Contreras Aguilera, Roberto Mondaca, Jaime Retamal, Alejandro Bruhn, Pablo Aguilera, Juan Pablo Blanco, César Santis, Roque Basoalto, Paz Uribe Copier, Catalina Godoy Juárez, Mario Bruna, Sebastián Alfaro
Abstract
Importance: The optimal strategy for hemodynamic resuscitation in early septic shock remains uncertain. Objective: To determine the effect of a personalized hemodynamic resuscitation protocol targeting capillary refill time (CRT-PHR) on a hierarchical composite outcome of mortality, duration of vital support, and length of hospital stay. Design, Setting, and Participants: This randomized clinical trial was conducted in 86 centers in 19 countries. Patients within the first 4 hours of septic shock were included between March 2022 and April 2025, with last follow-up in July 2025. Interventions: Patients were randomized to undergo CRT-PHR (n = 720), including assessment of pulse pressure, diastolic arterial pressure, fluid responsiveness, and bedside echocardiography, to tailor fluids, vasopressors, and inotropes, vs usual care (n = 747). Main Outcomes and Measures: The primary outcome was a hierarchical composite of mortality, duration of vital support (vasoactives, mechanical ventilation, and kidney replacement therapy), and length of hospital stay assessed at 28 days. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy and stratified by median APACHE (Acute Physiology and Chronic Health Evaluation) II score at admission. Secondary outcomes were mortality, vital support-free days, and length of hospital stay at 28 days. Results: From 1501 randomized patients, 1467 were included in the primary analysis (mean age, 66 [17] years; 43.3% female). There were 131 131 wins (48.9%) in the CRT-PHR group vs 112 787 (42.1%) in the usual care group for the hierarchical composite primary outcome, with a win ratio of 1.16 (95% CI, 1.02-1.33; P = .04). Individual wins for death were 19.1% vs 17.8%; duration of vital support, 26.4% vs 21.1%; and length of hospital stay, 3.4% vs 3.2% in the intervention vs usual care groups, respectively. Conclusions and Relevance: Among patients with early septic shock, a personalized hemodynamic resuscitation protocol targeting capillary refill time was superior to usual care for the primary composite outcome, primarily due to a lower duration of vital support. Trial Registration: ClinicalTrials.gov Identifier: NCT05057611.