Objectives: Reliable automated handheld vital microscopy image sequence analysis and the identification of disease states and effects of therapy are prerequisites for the routine use of quantitative sublingual microcirculation measurements at the point-of-care. The present study aimed to clinically validate the recently introduced MicroTools software in a large multicentral database of perioperative and critically ill patients and to use this automatic algorithm to data-mine and identify the sublingual microcirculatory variable changes in response to disease and therapy. Design: Retrospective algorithm-based image analysis and data-mining within a large international database of sublingual capillary microscopy. Algorithm-based analysis was compared with manual analysis for validation. Thereafter, MicroTools was used to identify the functional microcirculatory alterations associated with disease conditions and identify therapeutic options for recruiting functional microcirculatory variables. Setting: Ten perioperative/ICU/volunteer studies in six international teaching hospitals. Patients: The database encompass 267 adult and pediatric patients undergoing surgery, treatment for sepsis, and heart failure in the ICU and healthy volunteers. Interventions: Perioperative and ICU standard of care. Measurements and Main Results: One thousand five hundred twenty-five handheld vital microscopy image sequences containing 149,257 microscopy images were analyzed. 3.89 × 1012 RBC positions were tracked by the algorithm in real time, and offline manual analysis was performed. Good correlation and trending ability were found between manual and automatic total and functional capillary density (r = 0.6–0.8; p < 0.0001). RBC tracking within the database demonstrated changes in functional capillary density and/or RBC velocity in septic shock, heart failure, hypovolemia, obstructive shock, and hemodilution and thus detected the presence of a disease condition. Therapies recruiting the microcirculatory diffusion and convection capacity associated with systemic vasodilation and an increase in cardiac output were separately identified. Conclusions: Algorithm-based analysis of the sublingual microcirculation closely matched manual analysis across a broad spectrum of populations. It successfully identified a methodology to quantify microcirculatory alterations associated with disease and the success of capillary recruitment, improving point-of-care application of microcirculatory-targeted resuscitation procedures.
Assuring adequate tissue oxygenation in the critically ill, but still developing child is challenging. Conventional hemodynamic monitoring techniques fall short in assessing tissue oxygenation as these are directed at the macrocirculation and indirect surrogates of tissue oxygenation. The introduction of handheld vital microscopy (HVM) has allowed for the direct visualization of the microcirculation and with this has offered insight into tissue oxygenation on a microcirculatory level. Since its introduction, technical improvements have been made to HVM, to both hardware and software, and guidelines have been developed through expert consensus on image assessment and analysis. Using HVM, the microcirculation of the skin, the buccal mucosa, and the sublingual mucosa of healthy and (critically) ill neonates and children have been visualized and investigated. Yet, integration of HVM in hemodynamic monitoring has been limited due to technical shortcomings. Only superficial microcirculatory beds can be visualized, inter-observer and intra-observer variabilities are not accounted for and image analysis happens offline and is semi-automated and time-consuming. More importantly, patients need to be cooperative or fully sedated to prevent pressure and movement artifacts, which is often not the case in children. Despite these shortcomings, observational research with HVM in neonates and children has revealed the following: (1) age-related developmental changes in the microcirculation, (2) loss of hemodynamic coherence, i.e., microcirculatory disturbances in the presence of a normal macrocirculation and, (3) microcirculatory disturbances which were independently associated with increased mortality risk. Although these observations underline the importance of microcirculatory monitoring, several steps have to be taken before integration in the decision process during critical care can happen. These steps include technological innovations to ease the use of HVM in the pediatric age group, measuring additional functional parameters of microvascular blood flow and integrated automated analysis software. As a next step, reference values for microcirculatory parameters need to be established, while also accounting for developmental changes. Finally, studies on microcirculatory guided therapies are necessary to assess whether the integration of microcirculatory monitoring will actually improve patient outcome. Nevertheless, HVM remains a promising, non-invasive tool to help physicians assure tissue oxygenation in the critically ill child.
Background The incidence of hemostatic complications in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) is high. The optimal anticoagulation strategy in children undergoing ECMO is unknown. Objectives To study the association between hemostatic complications, coagulation tests, and clinical parameters in pediatric patients undergoing ECMO and their effect on survival. Methods We performed a retrospective cohort study of pediatric patients undergoing centrifugal pump ECMO. Collected data included patient characteristics, risk factors, and coagulation test results. Statistical analysis was done using logistic regression analysis for repeated measurements. Dependent variables were thrombosis and bleeding, independent variables were rotational thromboelastometry (ROTEM), activated partial thromboplastin time (aPTT) and antifactor‐Xa assay (aXa) results, ECMO duration, age <29 days, sepsis and surgery. Results Seventy‐three patients with 623 ECMO days were included. Cumulative incidences of thrombosis and bleeding were 43.5% (95% confidence interval [CI], 26.0%‐59.8%) and 25.4% (95% CI, 13.4%‐39.3%), respectively. A lower maximum clot firmness of intrinsic ROTEM (INTEM; odds ratio [OR], 0.946; 95% CI, 0.920‐0.969), extrinsic ROTEM (OR, 0.945; 95% CI, 0.912‐0.973), and INTEM with heparinase (OR, 0.936; 95% CI, 0.896‐0.968); higher activated partial thromboplastin time aPTT; OR, 1.020; 95% CI, 1.006‐1.024) and age <29 days (OR, 2.900; 95% CI, 1.282‐6.694); surgery (OR, 4.426; 95% CI, 1.543‐12.694); and longer ECMO duration (OR, 1.149; 95% CI, 1.022‐1.292) significantly increased thrombotic risk. Surgery (OR, 2.698; 95% CI, 1.543‐12.694) and age <29 days (OR 2.242, 95% CI 1.282–6.694) were significantly associated with major bleeding. Patients with hemostatic complications had significantly decreased survival to hospital discharge ( P = .009). Conclusion The results of this study help elucidate the role of ROTEM, aPTT, anti–factor Xa, and clinical risk factors in predicting hemostatic complications in pediatric patients undergoing ECMO.
BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly with a mortality of ∼27%. The Congenital Diaphragmatic Hernia Study Group (CDHSG) developed a simple postnatal clinical prediction rule to predict mortality in newborns with CDH. Our aim for this study is to externally validate the CDHSG rule in the European population and to improve its prediction of mortality by adding prenatal variables.
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