Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial

Background: 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. Therefore, pursuing lactate normalization may lead to the risk of fuid overload. Peripheral perfusion, assessed by the capillary refll time (CRT), could be an efective 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) fuid resuscitation strategy on fuid balances within 24 h of septic shock diagnosis. In addi‑ tion, we compared the efects of both strategies on organ dysfunction, regional and microcirculatory fow, and tissue hypoxia surrogates. Results: Forty-two fuid-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-disap‑ pearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content diference ratio; and lactate/pyruvate ratio. There was no diference between CRT-T vs. LAC-T in 6 h-fuid 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 predefned perfusion target (62 vs. 24, p=0.03). No signifcant diferences in perfusion-related variables or hypoxia surrogates were observed. Conclusions: CRT-targeted fuid resuscitation was not superior to a lactate-targeted one on fuid administration or balances. However, it was associated with comparable efects on regional and microcirculatory fow parameters and hypoxia surrogates, and a faster achievement of the predefned resuscitation target. Our data suggest that stopping fuids in patients with CRT≤3 s appears as safe in terms of tissue perfusion.

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