Permissive Hypercapnia Results in Decreased Functional Vessel Density in the Skin of Extremely Low Birth Weight Infants.

BACKGROUND: Ventilator-induced lung injury with subsequent bronchopulmonary dysplasia remains an important issue in the care of extremely low-birth-weight infants. Permissive hypercapnia has been proposed to reduce lung injury. Hypercapnia changes cerebral perfusion, but its influence on the peripheral microcirculation is unknown. METHODS: Data were collected from 12 infants, who were randomized to a permissive high PCO2 target group (HTG) or a control group (CG). Inclusion criteria were birth weight between 400 and 1,000 g, gestational age from 23 to 28 6/7 weeks, intubation during the first 24 h of life, and no malformations. The PCO2 target range was increased stepwise in both groups for weaning and was always 15 mmHg higher in the HTG than in the CG. Skin microvascular parameters were assessed non-invasively with sidestream dark field imaging on the inner side of the right arm every 24 h during the first week of life and on the 14th day of life. RESULTS: Infants in the HTG had significantly higher max. PCO2 exposure, which was associated with a significantly and progressively reduced functional vessel density (FVD, p < 0.01). Moreover, there were significant differences in the diameter distribution over time, with HTG subjects having fewer small vessels but more large vessels. CONCLUSION: High PCO2 levels significantly impaired peripheral microcirculation in preterm infants, as shown by a decreased FVD, presumably secondary to peripheral vasoconstriction. ISRCTN: 56143743.

Microvascular perfusion in cardiac arrest: a review of microcirculatory imaging studies.

Cardiac arrest represents a leading cause of mortality and morbidity in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) increases the chances for a beneficial outcome in victims of refractory cardiac arrest. However, ECPR and post-cardiac arrest care are affected by high mortality rates due to multi-organ failure syndrome, which is closely related to microcirculatory disorders. Therefore, microcirculation represents a key target for therapeutic interventions in post-cardiac arrest patients. However, the evaluation of tissue microcirculatory perfusion is still demanding to perform. Novel videomicroscopic technologies (Orthogonal polarization spectral, Sidestream dark field and Incident dark field imaging) might offer a promising way to perform bedside microcirculatory assessment and therapy monitoring. This review aims to summarise the recent body of knowledge on videomicroscopic imaging in a cardiac arrest setting and to discuss the impact of extracorporeal reperfusion and other therapeutic modalities on microcirculation.

Effect of Pulsatility on Microcirculation in Patients Treated with Extracorporeal Cardiopulmonary Resuscitation: A Pilot Study.

The effect of pulsatile blood flow on microcirculation during extracorporeal cardiopulmonary resuscitation (ECPR) is not elucidated; therefore, we designed an observational study comparing sublingual microcirculation in patients with refractory cardiac arrest (CA) with spontaneously pulsatile or low/nonpulsatile blood flow after treatment with ECPR. Microcirculation was assessed with Sidestream Dark Field technology in 12 patients with CA who were treated with ECPR and 12 healthy control subjects. Microcirculatory images were analyzed offline in a blinded fashion, and consensual parameters were determined for the vessels ≤20 µm. The patients' data, including actual hemodynamic parameters, were documented. Pulsatile blood flow was defined by a pulse pressure (PP) ≥ 15 mm Hg. Compared with the healthy volunteers, the patients who were treated with ECPR exhibited a significantly lower proportion of perfused capillaries (PPC); other microcirculatory parameters did not differ. The groups of patients with pulsatile (n = 7) versus low/nonpulsatile (n = 5) blood flow did not differ in regards to the collected data and hemodynamic variables (except for the PP and ejection fraction of the left ventricle) as well as microcirculatory parameters. In conclusion, microcirculation appeared to be effectively supported by ECPR in our group of patients with CA with the exception of the PPC. We found only nonsignificant contribution of spontaneous pulsatility to extracorporeal membrane oxygenation-generated microcirculatory blood flow.

Microcirculatory blood flow during cardiac arrest and cardiopulmonary resuscitation does not correlate with global hemodynamics: an experimental study.

BACKGROUND: Current research highlights the role of microcirculatory disorders in post-cardiac arrest patients. Affected microcirculation shows not only dissociation from systemic hemodynamics but also strong connection to outcome of these patients. However, only few studies evaluated microcirculation directly during cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of our experimental study in a porcine model was to describe sublingual microcirculatory changes during CA and CPR using recent videomicroscopic technology and provide a comparison to parameters of global hemodynamics. METHODS: Cardiac arrest was induced in 18 female pigs (50 ± 3 kg). After 3 min without treatment, 5 min of mechanical CPR followed. Continuous hemodynamic monitoring including systemic blood pressure and carotid blood flow was performed and blood lactate was measured at the end of baseline and CPR. Sublingual microcirculation was assessed by the Sidestream Dark Field (SDF) technology during baseline, CA and CPR. Following microcirculatory parameters were assessed off-line separately for capillaries (≤20 µm) and other vessels: total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). RESULTS: In comparison to baseline the CA small vessel microcirculation was only partially preserved: TVD 15.64 (13.59-18.48) significantly decreased to 12.51 (10.57-13.98) mm/mm(2), PVD 15.57 (13.56-17.80) to 5.53 (4.17-6.60) mm/mm(2), PPV 99.64 (98.05-100.00) to 38.97 (27.60-46.29) %, MFI 3.00 (3.00-3.08) to 1.29 (1.08-1.58) and HI increased from 0.08 (0.00-0.23) to 1.5 (0.71-2.00), p = 0.0003 for TVD and <0.0001 for others, respectively. Microcirculation during ongoing CPR in small vessels reached 59-85 % of the baseline values: TVD 13.33 (12.11-15.11) mm/mm(2), PVD 9.34 (7.34-11.52) mm/mm(2), PPV 72.34 (54.31-87.87) %, MFI 2.04 (1.58-2.42), HI 0.65 (0.41-1.07). The correlation between microcirculation and global hemodynamic parameters as well as to lactate was only weak to moderate (i.e. Spearman's ρ 0.02-0.51) and after adjustment for multiple correlations it was non-significant. CONCLUSIONS: Sublingual microcirculatory parameters did not correlate with global hemodynamic parameters during simulated porcine model of CA and CPR. SDF imaging provides additional information about tissue perfusion in the course of CPR.

The effect of red blood cell transfusion on the microcirculation of anemic children.

UNLABELLED: Red blood cell transfusion can improve but also might temporarily reduce the microcirculation. The buccal microcirculation was visualized and total vessel density (TVD) determined with sidestream dark field imaging in 19 pediatric anemic (Hb 7.2 g/dL, 95 % CI 6.5-7.9) oncology or hematology patients receiving red blood cell transfusions (Tx) and in 18 age-matched healthy non-anemic controls. After transfusion, Hb (8.0 g/dL, 95 % CI 7.3-8.6) and TVD increased (14.7 ± 1.7 versus 16.6 ± 2.0 mm/mm(2)) significantly with a concomitant decrease in RBC velocity in medium-sized vessels (pre-Tx 711 ± 199 versus post-Tx 627 ± 163 µm/s). Compared to the controls, pre-Tx TVD (17.5 ± 1.3 mm/mm(2)) was lower and RBC velocity (476 ± 77 µm/s) was significantly higher. After transfusion, TVD and RBC velocity remained significantly lower and higher, respectively. In a subgroup, analysis of the transfused children with infection of TVD at baseline was lower with a larger increase after transfusion compared to anemic children without infection (ΔTVD 3.4 ± 2.6 versus ΔTVD 1.3 ± 1.5 mm/mm(2)). CONCLUSION: With the rise of hemoglobin after transfusion, significant improvements of tissue perfusion were demonstrated but differences to non-anemic controls persisted. In particular, the microcirculation of anemic oncology patients with infection improved after transfusion. WHAT IS KNOWN: • Transfusions can improve but also temporarily reduce the microcirculation. • In neonates, transfusion significantly increases total vessel density. What is New: • Pretransfusion, the microcirculation of the anemic children differed significantly from the controls. • After transfusion, the microcirculation improved but still differed from the controls. • These changes were most profound in anemic patients with concurrent infection, therefore transfusion threshholds might need to be higher.

Early microvascular changes with loss of the glycocalyx in children with type 1 diabetes.

OBJECTIVE: To evaluate the microcirculation of children with type 1 diabetes mellitus who demonstrate no clinical signs of diabetic microangiopathy for the presence of microvascular alterations and glycocalyx perturbation. STUDY DESIGN: Images of sublingual vessels were obtained in 14 children with diabetes (ages 12.8 ± 2.8 years, diabetes duration 6.7 ± 4.3 years) and 14 control patients (ages 11.8 ± 2.8 years) by the use of sidestream dark field imaging and analyzed for total vessel density, vessel surface coverage, vessel diameter distribution, mean flow index, and glycocalyx thickness. Wilcoxon rank sum test and Pearson correlation were used for statistical analysis. RESULTS: We observed profound microcirculatory changes in children with diabetes compared with control patients, with a significant reduction of glycocalyx thickness (0.38 µm vs 0.60 µm; P = .013), which was inversely correlated with blood glucose levels (r = -0.55; P = .003). Furthermore, the percentage of large vessels (>20 µm diameter) was significantly increased (11% vs 6%; P = .023) at the expense of capillaries (<10 µm diameter) with consequent increase in total vessel surface coverage (30% vs 26.0%; P = .041). No differences were seen in total vessel density and mean flow index. CONCLUSIONS: Microvascular alterations, including changes in microvessel distribution and loss of the glycocalyx, can be detected in children with type 1 diabetes mellitus before clinically apparent vascular complications. Our results disclose the glycocalyx as a possible monitoring measurement for earlier detection of diabetic microangiopathy and may provide a basis for new therapeutic strategies aiming at protection or restoration of the glycocalyx.

Microcirculatory mechanisms in postnatal hypotension affecting premature infants.

BACKGROUND: Hypotension remains a common complication in preterm infants and is associated with high neonatal morbidity and mortality. The underlying mechanisms are still not fully understood. We studied the microcirculation in extremely low birth weight infants to understand the relationship between blood pressure and skin perfusion. METHODS: In 21 patients (gestational age <30 wk, birth weight <1,225 g), functional vessel density (FVD) and diameter distribution were obtained prospectively by side stream dark-field imaging at the right arm in the first 48 h after birth. Infants with blood pressure below gestational age and receiving catecholamines were defined as hypotensive as compared with the remaining normotensive control group. RESULTS: In the first 6 h after birth, FVD was significantly higher in the hypotensive group than in the control group. After 12 h, there were no significant differences in either blood pressure or FVD between the two groups. FVD did not change significantly during the observation period in either group. CONCLUSION: Hypotensive infants have a higher FVD, possibly due to loss of microvascular tone leading to vasodilation and flow redistribution. However, the link between blood pressure and perfusion remains unclear, and no definitive correlation could be found.