Altered Microvascular Reactivity During a Skin Thermal Challenge Is Associated With Organ Dysfunction and Slow Recovery After Cardiac Surgery.

OBJECTIVES: To assess microvascular reactivity during a skin thermal challenge early post-cardiac surgery and its association with outcomes. DESIGN: Noninvasive physiological study. SETTING: Thirty-five-bed department of intensive care. PARTICIPANTS: Patients admitted to the intensive care unit post-cardiac surgery. INTERVENTIONS: Thermal challenge. MEASUREMENTS AND MAIN RESULTS: A total of 46 patients were included; 14 needed vasoactive or ventilatory support for at least 48 hours (slow recovery), and 32 had a more rapid recovery. Skin blood flow (SBF) was measured on the anterior proximal forearm using skin laser Doppler. A thermal challenge was performed by abruptly increasing local skin temperature from 37°C to 43°C while monitoring SBF. The ratio between SBFs at 43°C and 37°C was calculated to measure microvascular reactivity. SBF at 37°C was not significantly different in patients with a slow recovery and those with a rapid recovery, but SBF after 9 minutes at 43°C was lower (48.5 [17.3-69.0] v 85.1 [45.2-125.7], p < 0.01), resulting in a lower SBF ratio (2.8 [1.5-4.7] v 4.8 [3.7-7.8], p < 0.01). Patients with lower SBF ratios were more likely to have dysfunction of at least one organ (assessed using the sequential organ dysfunction score) 48 hours post-cardiac surgery than those with higher ratios: 88% versus 40% versus 27% (p < 0.01), respectively, for the lowest, middle, and highest tertiles of SBF ratio. In multivariable analysis, a lower SBF ratio was an independent risk factor for slow recovery. CONCLUSIONS: Early alterations in microvascular reactivity, evaluated by a skin thermal challenge, are correlated with organ dysfunction. These observations may help in the development of new, simple, noninvasive monitoring systems in postoperative patients.

The Sublingual Microcirculation in Critically Ill Children with Septic Shock Undergoing Hemoadsorption: A Pilot Study.

Background: The importance of perfusion-guided resuscitation in septic shock has recently emerged. We explored whether the use of hemoadsorption led to a potential beneficial role in microvascular alterations in this clinical setting. Methods: A pre-planned secondary analysis of a Phase-II interventional single-arm pilot study (NCT05658588) was carried out, where 17 consecutive septic shock children admitted into PICU were treated with continuous renal replacement therapy (CRRT) and CytoSorb. Thirteen patients were eligible to be investigated with sublingual microcirculation at baseline, 24, 48, 72 and 96 h from the onset of blood purification. Patients achieving a microvascular flow index (MFI) ≥ 2.5 and/or proportion of perfused vessels (PPV) exceeding 90% by 96 h were defined as responders. Results: In 10/13 (77%), there was a significant improvement in MFIs (p = 0.01) and PPVs% (p = 0.04) between baseline and 24 h from the end of treatment. Eight patients displayed a high heterogenicity index (HI > 0.5) during blood purification and among these, five showed an improvement by the end of treatment (HI < 0.5). Conclusions: In this pilot study, we have found a potential association between CytoSorb hemoadsorption and a microcirculation improvement in pediatric patients with septic shock, particularly when this observation has been associated with hemodynamic improvement.

Inhibition of circulating dipeptidyl-peptidase 3 by procizumab in experimental septic shock reduces catecholamine exposure and myocardial injury.

BACKGROUND: Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. METHODS: In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65-75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin-angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. RESULTS: PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. CONCLUSIONS: In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling.

Incoherence between systemic and skin tissue response to transfusion in volume-resuscitated patients withoutacute bleeding.

Alterations in skin blood flow (SBF) may help to detect occult hypoperfusion in critically ill patients after fluid resuscitation. In this study, SBF is globally unaltered by red blood cell transfusion (RBCT) in non-bleeding critically ill patients after initial resuscitation; however, 37.5% of patients showed a significant increase in SBF. No correlation between relative changes in SBF and systemic variables after RBCT was observed.