Severe abnormalities in microvascular perfused vessel density are associated to organ dysfunctions and mortality and can be predicted by hyperlactatemia and norepinephrine requirements in septic shock patients
Introduction
Microcirculatory perfusion has been the subject of extensive research over the last decade, especially in the context of sepsis [1], [2], [3], [4]. Several sublingual microcirculatory abnormalities have been described and linked to morbidity and mortality in septic shock patients [1], [3], [5]. More recent research has been focused on potential therapies to improve microcirculatory flow with some promising results [6], [7], [8], [9], [10], [11]. However, there are still fundamental aspects that need to be resolved before launching major controlled clinical trials. First, although several indices to evaluate sublingual microcirculation have been proposed [5], the clinical relevance of individual microcirculatory parameters is far from being well established [1], [2], [3], [4]. This is particularly true for perfused vessel density (PVD), a parameter representing functional capillary density. Second, no severity staging has been proposed or validated for any of these microcirculatory indices. Third, the relationship between systemic hemodynamics, global perfusion parameters, and microcirculatory derangements is still controversial [6], [8], [12], [13], [14], and as a consequence, it is not clear if macrohemodynamic or perfusion parameters can predict the status of microcirculatory perfusion.
As a matter of fact, a significant correlation between systemic hemodynamic parameters and microcirculatory indices was observed in septic shock patients early on after emergency hospital admission [12]. Nevertheless, this finding has not been reproduced in intensive care unit (ICU)–based studies [1], [6]. In the same line, the relationship between microcirculatory derangements and metabolic perfusion-related parameters is controversial. Although some studies report parallel changes in microcirculatory flow and lactate during septic shock resuscitation [6], [11], others have failed to find any correlation [13]. Therefore, from a bedside perspective, it is hard to identify which septic shock patients are more likely to present a microvascular dysfunction and thus constitute better candidates for microcirculatory assessment and for potential inclusion in clinical trials.
To address these uncertainties, we conducted a clinical study in a large multicenter cohort of patients with septic shock. Our aims were to determine the general relationship of PVD to mortality and organ dysfunctions and to explore if patients in the lowest quartile of distribution for this parameter presented a higher risk of bad outcome. In addition, we wanted to identify systemic hemodynamic and perfusion variables that enhance the probability of finding a severe underlying microvascular dysfunction.
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Setting
We conducted a retrospective, cross-sectional study in 3 academic centers (Chile, Argentina, and The Netherlands). Septic shock patients [15] enrolled in 7 prospective studies evaluating microcirculation in different settings were considered for inclusion [4], [7], [9], [10], [13], [16], [17]. Although the main objectives of these studies were markedly different, they shared the following aspects: (1) local institutional review boards approval with informed consent requirement (except in study
Results
One hundred twenty-two patients were included (age, 65 years [18-84]; APACHE II score, 21 [18-25]; basal SOFA score 10 [7-12]; 24-hour SOFA score 9 [7-11]; hospital mortality, 33%). Main septic sources were abdominal 44%, respiratory 29%, urinary tract 10%, and catheter related 5%. Microcirculatory assessment was performed in all cases during the first 12 hours after shock onset. Hemodynamic and perfusion parameters during microcirculatory assessment were the following: MAP, 67 (61-72) mm Hg;
Discussion
Perfused vessel density was significantly related to organ dysfunctions and mortality in our cohort of septic shock patients, but this effect was largely explained by patients exhibiting more severe microcirculatory abnormalities as represented by the lowest quartile of distribution for PVD. The presence of hyperlactatemia and high NE requirements increased the odds of finding a severe underlying microvascular dysfunction during a sublingual microcirculatory assessment.
A recent consensus
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