A lactate-targeted resuscitation strategy may be associated with higher mortality in patients with septic shock and normal capillary refill time: a post hoc analysis of the ANDROMEDA-SHOCK study

Abstract

Background: Capillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT-versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset. Results: Patients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%, p = 0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000[500-2000] vs. 500[0-1500], p = 0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19), p = 0.001; and inodilators: 16 (13) vs. 3 (3), p = 0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI[1.5-7.1]); p = 0.003).

Rational Fluid Resuscitation in Sepsis for the Hospitalist

“…14 Importantly, yet another post hoc analysis of the same study demonstrated an association between lactate-based resuscitation and higher mortality if capillary refill time was normal at enrollment. 23 This finding calls into question the current practice of attempting to normalize lactate in patients with sepsis and septic shock, although confirmatory studies are needed. If capillary refill time is chosen as a resuscitation target, it should be performed in a systematic fashion as in the original trial.…”

Management of sepsis and septic shock in the emergency department

“…lactate-targeted resuscitation in terms of mortality in 424 septic shock patients. Even though it failed to reach statistical significance ( p = 0.06), the CRT-targeted strategy was associated to lower mortality at 28 days, which has been recently confirmed by several post-hoc analyses [ 71 – 73 ].…”

What Is the Utility of Measuring Lactate Levels in Patients with Sepsis and Septic Shock?

“…In a Bayesian reanalysis of the trial, there was a beneficial effect of CRT target on 28-day mortality, and in post hoc analysis, among those with normal CRT, those within the lactatetargeted group had higher 28-day mortality (OR: 3.3, 95% CI: 1.5-7.1). 102,103 Patients in the lactate group received more fluid within the first 8 hours (mean difference: þ408 mL, 95% CI: þ110-605 mL, p ¼ 0.01) and had more organ dysfunction at 72 hours (mean SOFA difference: 1.00, 95% CI: 0.02-1.97, p ¼ 0.045).…”