Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock.

Background: The goal of fluid resuscitation and the use of inotropes in septic shock has traditionally focused on improving blood pressure and cardiac output, without considering the microcirculatory changes. Reaching macrocirculatory goals but with persistent microcirculatory abnormalities (hemodynamic incoherence) in septic shock has been associated with greater organ dysfunction and mortality. The objective of this study was to evaluate the microcirculation (flow and capillary density) and endothelial glycocalyx changes associated with the use of milrinone in children with septic shock, as well as their relationship with clinical variables and organ dysfunction. Methods: A prospective cohort study from February 2022 to January 2023 at a university hospital (Fundación Cardioinfantil-Instituto de Cardiología). Sublingual video microscopy was used to evaluate capillary density, microvascular flow rates and perfused boundary region (PBR-inverse parameter of glycocalyx thickness-abnormal if >2.0 microns). The primary outcome was the association between microcirculation and endothelial glycocalyx changes related to the use of milrinone. Results: A total of 140 children with a median age of two years [interquartile range (IQR) 0.58-12.1] were included. About 57.9% (81/140) of the patients received milrinone infusions. Twenty-four hours after receiving milrinone, the patients maintained functional capillary density (P<0.01) and capillary recruitment capacity (P=0.04) with no changes in capillary blood volume versus those who did not receive milrinone. Children under two years old who received milrinone had better 4-6-micron capillary density than older children [odds ratio (OR) 0.33; 95% confidence interval (95% CI): 0.12-0.89; P=0.02] and less endothelial glycocalyx degradation [adjusted OR (aOR) 0.34 95% CI: 0.11-0.99; P=0.04]. These changes persisted despite elevated ferritin (aOR 0.41; 95% CI: 0.18-0.93; P=0.03). Prolonged capillary refill and elevated lactate were correlated with microcirculation changes in both groups. The patients who died had the highest PBR levels (P=0.04). Conclusions: Children with septic shock who receive milrinone infusions have microcirculation changes compared with those who do not receive them. The group that received milrinone was found to maintain functional capillary density and capillary recruitment capacity and have less endothelial glycocalyx degradation 24 hours after administration. These changes were present despite the inflammatory response and were more significant in those under two years of age.

Association between mechanical ventilation parameters and mortality in children with respiratory failure on ECMO: a systematic review and meta-analysis.

Background: In refractory respiratory failure (RF), extracorporeal membrane oxygenation (ECMO) is a salvage therapy that seeks to reduce lung injury induced by mechanical ventilation. The parameters of optimal mechanical ventilation in children during ECMO are not known. Pulmonary ventilatory management during this therapy may impact mortality. The objective of this study was to evaluate the association between ventilatory parameters in children during ECMO therapy and in-hospital mortality. Methods: A systematic search of PubMed/MEDLINE, Embase, Cochrane, and Google Scholar from January 2013 until May 2022 (PROSPERO 450744), including studies in children with ECMO-supported RF assessing mechanical ventilation parameters, was conducted. Risk of bias was assessed using the Newcastle-Ottawa scale; heterogeneity, with absence <25% and high >75%, was assessed using I2. Sensitivity and subgroup analyses using the Mantel-Haenszel random-effects model were performed to explore the impact of methodological quality on effect size. Results: Six studies were included. The median age was 3.4 years (IQR: 3.2-4.2). Survival in the 28-day studies was 69%. Mechanical ventilation parameters associated with higher mortality were a very low tidal volume ventilation (<4 ml/kg; OR: 4.70; 95% CI: 2.91-7.59; p < 0.01; I2: 38%), high plateau pressure (mean Dif: -0.70 95% CI: -0.18, -0.22; p < 0.01), and high driving pressure (mean Dif: -0.96 95% CI: -1.83, -0.09: p = 0.03). The inspired fraction of oxygen (p = 0.09) and end-expiratory pressure (p = 0.69) were not associated with higher mortality. Patients who survived had less multiple organ failure (p < 0.01). Conclusion: The mechanical ventilation variables associated with higher mortality in children with ECMO-supported respiratory failure are high plateau pressures, high driving pressure and very low tidal volume ventilation. No association between mortality and other parameters of the mechanical ventilator, such as the inspired fraction of oxygen or end-expiratory pressure, was found. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023450744, PROSPERO 2023 (CRD42023450744).

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

OBJECTIVES: To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. DESIGN: A single-center prospective cohort study from January to December 2021. SETTING: Twelve medical-surgical PICU beds at a university hospital. PATIENTS: Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. CONCLUSIONS: Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.

Association Between Serum Lactate and Unsatisfactory Outcomes in Critically Ill Children in the Immediate Post-operative Period of Liver Transplantation.

OBJECTIVES: Serum lactate is a useful biomarker of tissue perfusion in critically ill patients. We evaluated the behavior of serum lactate in children in the pediatric intensive care unit (PICU) immediately after liver transplantation and its association with surgical complications, graft dysfunction and 90-day mortality. MATERIALS AND METHODS: A prospective observational study carried out between November 2009 and December 2019. Multidisciplinary PICU at the University Children's Hospital, Fundación Cardioinfantil-IC, Bogotá, Colombia. MEASUREMENTS AND MAIN RESULTS: Patients between 1 month and 18 years of age who were in the immediate post-operative period following living-donor or cadaveric liver transplantation were included. A total of 145 patients with a median age of 14 months (IQR 8-60) met the inclusion criteria. Biliary atresia was the main diagnosis in 56.5% of the cases. A serum lactate level > 3.0 mmol/L on admission to the PICU was associated with biliary complications (AUC 0.73 95% CI 0.54-0.93; p = 0.05) and mortality (AUC 0.72 95% CI 0.63-0.8; p = 0.01). A lactate level > 2 mmol/L after 6 h in the PICU was associated with mortality (AUC 0.70 95% CI 0.54-0.83; p = 0.02). Higher lactate levels and lack of clearance were associated with the presence of tardus et parvus waveforms (p = 0.001) on liver Doppler, primary dysfunction (p < 0.001), arterial thrombosis (p < 0.001) and neurological complications (p = 0.04). There was an inverse correlation between admission lactate and the volume of fluids administered during surgery (rho = 0.36; p < 0.001). A total procedure time > 350 min, along with a vasopressor score > 7 and elevated lactate, were associated with worse outcomes (p < 0.001). CONCLUSIONS: In post-operative pediatric liver transplant patients, the level of serum lactate is associated with post-operative surgical complications and mortality.

Correlation between Arterial Lactate and Central Venous Lactate in Children with Sepsis.

Introduction. Lactate is an important indicator of tissue perfusion. The objective of this study is to evaluate if there are significant differences between the arterial and central venous measurement of lactate in pediatric patients with sepsis and/or septic shock. Methods. Longitudinal retrospective observational study. Forty-two patients were included between the age of 1 month and 17 years, with a diagnosis of sepsis and septic shock, who were admitted to the intensive care unit of a university referral hospital. The lactate value obtained from an arterial blood sample and a central venous blood sample drawn simultaneously, and within 24 hours of admission to the unit, was recorded. Results. The median age was 2.3 years (RIC 0,3-15), with a predominance of males (71.4%), having a 2.5 : 1 ratio to females. Most of the patients had septic shock (78.5%) of pulmonary origin (50.0%), followed by those of gastrointestinal origin (26.1%). Using Spearman's Rho, a 0.872 (p < 0.001) correlation was found between arterial and venous lactate, which did not vary when adjusted for age (p < 0.05) and the use of vasoactive drugs (p < 0.05). Conclusion. There is a good correlation between arterial and venous lactate in pediatric patients with sepsis and septic shock, which is not affected by demographic variables or type of vasoactive support.

Adaptive support ventilation: State of the art review.

Mechanical ventilation is one of the most commonly applied interventions in intensive care units. Despite its life-saving role, it can be a risky procedure for the patient if not applied appropriately. To decrease risks, new ventilator modes continue to be developed in an attempt to improve patient outcomes. Advances in ventilator modes include closed-loop systems that facilitate ventilator manipulation of variables based on measured respiratory parameters. Adaptive support ventilation (ASV) is a positive pressure mode of mechanical ventilation that is closed-loop controlled, and automatically adjust based on the patient's requirements. In order to deliver safe and appropriate patient care, clinicians need to achieve a thorough understanding of this mode, including its effects on underlying respiratory mechanics. This article will discuss ASV while emphasizing appropriate ventilator settings, their advantages and disadvantages, their particular effects on oxygenation and ventilation, and the monitoring priorities for clinicians.