Abstract
BackgroundPersistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates.ResultsForty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375–2625] vs. 1500 [1000–2000], p = 0.3), or balances (982[249–2833] vs. 15,800 [740–6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed.ConclusionsCRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion.Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018)
Highlights
Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved
Sample size calculation After a thorough literature review, we found only one pilot study comparing peripheral perfusion vs. standard care based resuscitation in septic shock patients [10], showing that the former resulted in significantly less resuscitation fluids at 6 h (4227 ± 1081 ml vs. 6069 ± 1715 ml)
Time from septic shock diagnosis to protocol start was similar in both arms (CRT-T, 4 [2,3,4,5,6,7,8,9] h vs. LAC-T, 5 [2,3,4,5,6] h; p = 0.9)
Summary
Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. Hyperlactatemia is a non-specific marker of hypoperfusion, since other pathogenic mechanisms such as sustained hyperadrenergia and impaired hepatic clearance may contribute to increased serum lactate levels [1, 3, 4] This may have relevant clinical implications, since if non-hypoperfusion-related sources predominate, increased serum lactate levels This may have relevant clinical implications, since if non-hypoperfusion-related sources predominate, pursuing lactate as a target may lead to fluid overload, potentially increasing mortality or morbidity [5,6,7]. ANDROMEDASHOCK results should be confirmed by future major trials, but in the meantime, many non-resolved issues could be addressed by smaller randomized controlled trials including the effect of both strategies on organ perfusion
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