Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial

Eduardo Kattan, Gustavo A Ospina-Tascón, Jean-Louis Teboul, Ricardo Castro, Maurizio Cecconi, Giorgio Ferri, Jan Bakker, Glenn Hernández, ANDROMEDA-SHOCK Investigators, Glenn Hernandez, Gustavo Ospina-Tascón, Lucas Petri Damiani, Elisa Estenssoro, Arnaldo Dubin, Javier Hurtado, Gilberto Friedman, Ricardo Castro, Leyla Alegría, Jean-Louis Teboul, Maurizio Cecconi, Giorgio Ferri, Manuel Jibaja, Ronald Pairumani, Paula Fernández, Diego Barahona, Alexandre Biasi Cavalcanti, Jan Bakker, Glenn Hernandez, Leyla Alegría, Giorgio Ferri, Nicolás Rodriguez, Patricia Holger, Natalia Soto, Mario Pozo, Jan Bakker, Deborah Cook, Jean-Louis Vincent, Bryan P Kavanagh, Phil Dellinger, Wim Rietdijk, Eduardo Kattan, Gustavo A Ospina-Tascón, Jean-Louis Teboul, Ricardo Castro, Maurizio Cecconi, Giorgio Ferri, Jan Bakker, Glenn Hernández, ANDROMEDA-SHOCK Investigators, Glenn Hernandez, Gustavo Ospina-Tascón, Lucas Petri Damiani, Elisa Estenssoro, Arnaldo Dubin, Javier Hurtado, Gilberto Friedman, Ricardo Castro, Leyla Alegría, Jean-Louis Teboul, Maurizio Cecconi, Giorgio Ferri, Manuel Jibaja, Ronald Pairumani, Paula Fernández, Diego Barahona, Alexandre Biasi Cavalcanti, Jan Bakker, Glenn Hernandez, Leyla Alegría, Giorgio Ferri, Nicolás Rodriguez, Patricia Holger, Natalia Soto, Mario Pozo, Jan Bakker, Deborah Cook, Jean-Louis Vincent, Bryan P Kavanagh, Phil Dellinger, Wim Rietdijk

Abstract

Background: Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR-) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes.

Methods: ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR- subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality.

Results: FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 [0-500] vs. 1500 [1000-2500] mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR- patients was found, including 24-h SOFA score (9 [5-12] vs. 8 [5-11], p = 0.4), need for MV (78% vs. 72%, p = 0.16), need for RRT (18% vs. 21%, p = 0.7), ICU-LOS (6 [3-11] vs. 6 [3-16] days, p = 0.2), and 28-day mortality (40% vs. 36%, p = 0.5). Only thirteen patients remained fluid responsive along the intervention period.

Conclusions: Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients.

Trial registration: ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.

Keywords: Early resuscitation; Fluid overload; Fluid responsiveness; Septic shock.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Achievement of resuscitation endpoints during the intervention period according to fluid responsiveness status at baseline. FR+, fluid responsive; FR−, non-fluid responsive
Fig. 2
Fig. 2
a, b Evolution of fluid responsiveness during protocolized resuscitation, according to fluid responsiveness status at baseline

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