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

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 28day 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 nonfluid 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.

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina

“…10 Hospital Misericordia, Córdoba, Argentina. 11 Sanatorio de la Trinidad Mitre, Buenos Aires, Argentina. 12 Hospital Lagomaggiore, Mendoza, Argentina.…”

“…These tests anticipate that a fluid challenge will result in an increase of cardiac output > 15%, without the risk of volume overload. Although a recent study showed its feasibility during the early resuscitation of septic shock [11], the approach is still scarcely used to assess the appropriateness of a fluid challenge [12].…”

Terms, Definitions, Nomenclature, and Routes of Fluid Administration

“…The ability for hemodynamic parameters to improve in response to a fluid challenge or bolus ( 51 , 62 ). There is some variability in the specific parameters and magnitude of change that are considered consistent with a positive response.…”

“…There is some variability in the specific parameters and magnitude of change that are considered consistent with a positive response. However, many definitions consolidate around an increase in cardiac output ( 51 , 62 ) or stroke volume ( 52 , 54 ) by at least 10–15% from baseline following administration of a fluid bolus that is delivered over <15 ( 51 , 52 ) or 30 min ( 53 ). Others consider a patient to be fluid responsive if there is a significant change in one or more of the following: increase in mean arterial pressure of more than 10 mm Hg, decrease in heart rate of more than 10 BPM, increase in central venous pressure (>2 cm H 2 O) or an increase urine output ( 53 , 63 ).…”

“…The administration of intravenous fluids to reverse life-threatening tissue hypoperfusion ( 31 , 62 ). Synonym: volume resuscitation .…”