LAUSR

As many of us enter the hottest months of the summer, this month’s issue of Shock beckons with its characteristic mix of clinical and translational studies on injury, shock, resuscitation, and sepsis. Readers are invited to enjoy a cool drink while perusing a new review article, five clinical science papers, and 10 basic science articles. As much as we like to believe that what we do in practice at the bedside has a profound and positive impact on patients’ outcomes, there comes a time to challenge the status quo. Potter et al. (1) do just that in their systematic review on the impact of vasoactive medications on microcirculatory blood flow. The authors remind us that the pathophysiology of sepsis is deranged microvascular flow, yet what we see and treat is frequently the macrovascular hemodynamic parameters of cardiac index (CI), mean arterial pressure (MAP), and end organ function such as urine output. The group from the UK pools together the available literature on the effects of vasodilators, inotropes, vasopressors, and immunomodulatory drugs on the microvasculature as measured by orthogonal polarization spectral, sidestream dark field (SDF), and incident dark field imaging. They lament the low quality of published data by GRADE methodology and note the significant risk for heterogeneity and bias in the pooled studies. These limitations lead them to conclude that despite improvements in macrocirculatory parameters by multiple drugs, the only (weak) available evidence suggests vasopressors might provide benefit for patients with chronic hypertension when the infusion is used to restore MAP to baseline. The authors implore us to consider the reasons why current data is lacking—failure to have consensus on outcomes measures and definitions, lack of study of drugs at various ranges and dosing regimens, and the timing of first administration of trial drugs. The authors are to be applauded for suggesting where we should focus our attention—on the study of pharmacotherapies to augment the microcirculation (levosimendan and nitroglycerin), and also for providing recommendations to improve study methodology. The first clinical science article by Kawamoto et al. (2) invites us to join them in exploring how plasma extracellular vesicle (EV) expression of integrins and programmed cell death-1 (PD-1) ligands may differ in patients with systemic inflammatory response syndrome (SIRS) and sepsis compared with healthy controls. Further, the authors aim to bring benchto-bedside with the correlation of their findings to the clinical