A hypoperfusion context may aid to interpret hyperlactatemia in sepsis-3 septic shock patients: a proof-of-concept study

Abstract

Background: Persistent hyperlactatemia is particularly difficult to interpret in septic shock. Besides hypoperfusion, adrenergic-driven lactate production and impaired lactate clearance are important contributors. However, clinical recognition of different sources of hyperlactatemia is unfortunately not a common practice and patients are treated with the same strategy despite the risk of over-resuscitation in some. Indeed, pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of fluid overload and vasoactive drugs. We hypothesized that two different clinical patterns can be recognized in septic shock patients through a multimodal perfusion monitoring. Hyperlactatemic patients with a hypoperfusion context probably represent a more severe acute circulatory dysfunction, and the absence of a hypoperfusion context is eventually associated with a good outcome. We performed a retrospective analysis of a database of septic shock patients with persistent hyperlactatemia after initial resuscitation.

Results: We defined hypoperfusion context by the presence of a ScvO₂ < 70%, or a P(cv-a)CO₂ ≥6 mmHg, or a CRT ≥4 s together with hyperlactatemia. Ninety patients were included, of whom seventy exhibited a hypoperfusion-related pattern and 20 did not. Although lactate values were comparable at baseline (4.8 ± 2.8 vs. 4.7 ± 3.7 mmol/L), patients with a hypoperfusion context exhibited a more severe circulatory dysfunction with higher vasopressor requirements, and a trend to longer mechanical ventilation days, ICU stay, and more rescue therapies. Only one of the 20 hyperlactatemic patients without a hypoperfusion context died (5%) compared to 11 of the 70 with hypoperfusion-related hyperlactatemia (16%).

Conclusions: Two different clinical patterns among hyperlactatemic septic shock patients may be identified according to hypoperfusion context. Patients with hyperlactatemia plus low ScvO₂, or high P(cv-a)CO₂, or high CRT values exhibited a more severe circulatory dysfunction. This provides a starting point to launch further prospective studies to confirm if this approach can lead to a more selective resuscitation strategy.

Keywords: Capillary refill time; Central venous oxygen saturation; Central venous-arterial PCO2 gradient; Hyperlactatemia; Hypoperfusion; Resuscitation; Septic shock.

Fig. 1

Severity criteria to compare hyperlactatemic patients without versus with a hypoperfusion context. a Mean norepinephrine doses for both subgroups at baseline, 6 and 24 h. Black boxes describe hypoperfusion-context subgroup; white boxes represent non-hypoperfusion context subgroup. b Comparison of the use of rescue therapy and several outcome parameters between subgroups. HVHF high-volume hemofiltration, Mortality hospital mortality, MV mechanical ventilation, ICU intensive care unit, LOS length of stay

Fig. 2

Distributional figure: the figure displays different plausible allocation of patients under *four* distinctive hypoperfusion-context descriptors and their relationship with outcome in hyperlactatemic septic shock patients. The figure shows the distribution of patients according to the presence of abnormal ScvO₂, CRT, and P(cv-a)CO₂, and its relationship with hospital mortality where white and black circles represent survivors and non-survivors, respectively. a Comparing patients with normal perfusion criteria (bottom) versus those with at least one abnormal criterion (top). b Comparing patients with normal (bottom) versus abnormal ScvO₂ (top). c Comparing patients with normal (bottom) versus abnormal CRT (top). d Comparing patients with normal (bottom) versus abnormal P(cv-a)CO₂ (top). The p values represent the difference in mean lactate values among patients fulfilling or not the descriptors tested. No difference in lactate values was observed when using any of these descriptors although there are trends for difference in survival, especially when using the “at least one abnormal perfusion parameter” criterion as shown in the first column. ScvO ₂ central venous oxygen saturation, CRT capillary refill time, P(cv-a)CO ₂ central venous-to-arterial carbon dioxide difference