Endothelial cells (ECs) line the lumen of the entire vascular system and actively regulate blood flow; maintain blood fluidity; control water, solute, and macromolecular transfer between blood and ...tissue; and modulate circulating immune cell recruitment and activation. These vital functions, combined with the broad anatomic distribution of ECs, implicate them in all forms of critical illness. The present article discusses how ECs adapt and break down during the course of critical illness. We first review the biology of ECs, highlighting the vascular segmental differences and their specific roles in the maintenance of homeostasis. We then discuss how ECs acquire new functions to restore local and systemic homeostasis (activation) as well as how breakdowns in EC functions (dysfunction) contribute to local and systemic pathologic responses, with clinical correlations. Lastly, how these processes have been studied in critically ill children is discussed.
An 18-year-old girl with high-risk acute myeloid leukemia developed Streptococcus mitis septic shock and multiorgan dysfunction syndrome, including biventricular failure. Due to the anticipated ...reversibility of her cardiogenic shock, her young age, and her favorable survival chance after an allogeneic hematopoietic stem cell transplant, she was placed on full circulatory support with venoarterial extracorporeal membrane oxygenation as a bridge to her successful hematopoietic stem cell transplantation 2 months later. This highlights the importance of prognostication in patient selection for extracorporeal life support. A multidisciplinary approach is essential to each case until more definite initiation criteria, risk stratification, and treatment protocols are established.
To describe tracheal intubation (TI) practice by Advanced Practice Registered Nurses (APRNs) in North American PICUs, including rates of TI-associated events (TIAEs) from 2015 to 2019.
Retrospective ...study using the National Emergency Airway Registry for Children with all TIs performed in PICU and pediatric cardiac ICU between January 2015 and December 2019. The primary outcome was first attempt TI success rate. Secondary outcomes were TIAEs, severe TIAEs, and hypoxemia.
Critically ill children requiring TI in a PICU or pediatric cardiac ICU.
None.
Among 11,012 TIs, APRNs performed 1,626 (14.7%). Overall, TI by APRNs, compared with other clinicians, occurred less frequently in patients with known difficult airway (11.1% vs. 14.3%; p < 0.001), but more frequently in infants younger than 1 year old (55.9% vs. 44.4%; p < 0.0001), and in patients with cardiac disease (26.3% vs. 15.9%; p < 0.0001).There was lower odds of success in first attempt TI for APRNs vs. other clinicians (adjusted odds ratio, 0.70; 95% CI, 0.62-0.79). We failed to identify a difference in rates of TIAE, severe TIAE, and oxygen desaturation events for TIs by APRNs compared with other clinicians. The TI first attempt success rate improved with APRN experience (< 1 yr: 54.2%, 1-5 yr: 59.4%, 6-10 yr: 67.6%, > 10 yr: 63.1%; p = 0.021).
TI performed by APRNs was associated with lower odds of first attempt success when compared with other ICU clinicians although there was no appreciable difference in procedural adverse events. There appears to be a positive relationship between experience and success rates. These data suggest there is an ongoing need for opportunities to build on TI competency with APRNs.
Tracheal intubation is an important intervention to stabilize critically ill and injured children. Provider training level has been associated with procedural safety and outcomes in the neonatal ...intensive care settings. We hypothesized that tracheal intubation success and adverse tracheal intubation-associated events are correlated with provider training level in the PICU.
A prospective multicenter observational cohort study was performed across 15 PICUs to evaluate tracheal intubation between July 2010 to December 2011. All data were collected by using a standard National Emergency Airway Registry for Children reporting system endorsed as a Quality Improvement project of the Pediatric Acute Lung Injury and Sepsis Investigator network. Outcome measures included first attempt success, overall success, and adverse tracheal intubation-associated events.
Reported were 1265 primary oral intubation encounters by pediatric providers. First and overall attempt success were residents (37%, 51%), fellows (70%, 89%), and attending physicians (72%, 94%). After adjustment for relevant patient factors, fellow provider was associated with a higher rate of first attempt success (odds ratio OR, 4.29; 95% confidence interval CI, 3.24-5.68) and overall success (OR, 9.27; 95% CI, 6.56-13.1) compared with residents. Fellow (versus resident) as first airway provider was associated with fewer tracheal intubation associated events (OR, 0.42; 95% CI, 0.31-0.57).
Across a broad spectrum of PICUs, resident provider tracheal intubation success is low and adverse associated events are high, compared with fellows. More intensive pediatric resident procedural training is necessary before "live" tracheal intubations in the intensive care setting.
Procalcitonin (PCT) is increasingly utilized to determine the presence of infection or to guide antibiotic therapy. This review will highlight the diagnostic and prognostic utility of serum PCT in ...children.
Recent studies endorse the use of serum PCT to detect invasive infection, to differentiate sepsis from noninfectious systemic inflammatory response syndrome, and to guide antibiotic therapy. Typical values for maximal sensitivity and specificity are less than 0.5 ng/ml for noninfectious inflammation and greater than 2.0 ng/ml for bacterial sepsis. PCT appears to be a reliable indicator of infection. PCT has performed better than C-reactive protein in some settings, though pediatric comparative data are lacking. PCT may aid in diagnosing infection in challenging patient populations such as those with sickle cell disease, congenital heart defects, neutropenia, and indwelling central venous catheters. Antibiotic therapy tailored to serial PCT measurements may shorten the antibiotic exposure without increasing treatment failure.
PCT is a reliable serum marker for determining the presence or absence of invasive bacterial infection and response to antibiotic therapy. Tailoring antibiotics to PCT levels may reduce the duration of therapy without increasing treatment failure, but more research is needed in children.
Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been ...established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC).
Prospective observational study of children < 5 years old. Patients were classified as non-systemic inflammatory response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock.
Tertiary care pediatric hospitals.
Critically ill children.
None.
Plasma angpt-1 and -2 levels were measured with enzyme-linked immunoassays. Expression of angpt-2 in endothelial cells was assessed with quantitative polymerase chain reaction. Permeability changes in cultured HDMECs were assessed with transendothelial electrical resistance measurements.
Angpt-1 levels were significantly higher in younger children compared with levels found in previous study of older children across disease severity (all P < 0.001). Angpt-2 was significantly higher in this cohort with severe sepsis/septic shock compared with children without SIRS and SIRS/sepsis (all P < 0.003). Angpt-2/1 ratio was also elevated in children with severe sepsis/septic shock but an order of magnitude less than older children (P < 0.02, P = 0.002). Angpt-1 and -2 did not affect basal HDMEC permeability or modulate leak in isolation or in the presence of tumor necrosis factor (TNF).
Angpt-2 levels and the angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal HDMEC permeability alone or modulates TNF induced capillary leak.
Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited.
To estimate population-based MIS-C ...incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years.
This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020.
Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years).
Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections.
In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median interquartile range age, 8 4-13 years; 133 53.6% male; 96 persons 38.7% were Hispanic or Latino; 75 persons 30.2% were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio aIRR, 9.26 95% CI, 6.15-13.93), Hispanic or Latino persons (aIRR, 8.92 95% CI, 6.00-13.26), and Asian or Pacific Islander (aIRR, 2.94 95% CI, 1.49-5.82) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 95% CI, 3.68-8.60), Hispanic or Latino (aIRR, 4.26 95% CI, 2.85-6.38), and Asian or Pacific Islander persons (aIRR, 2.88 95% CI, 1.42-5.83) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 95% CI, 3.7-6.6 children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 95% CI, 4.8-8.3 children per 1 000 000 person-months).
In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.
Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected ...racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities.
This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression.
We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28).
In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.
Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data ...exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events.
We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017.
Forty international PICUs participating in the National Emergency Airway Registry for Children.
Critically ill children 0-17 years old who underwent tracheal intubation in a PICU.
None.
The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock.
Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.
Pediatric severe sepsis is a public health problem with significant morbidities in those who survive. In this article, we aim to present an overview of the important studies highlighting the limited ...data available pertaining to long-term outcomes of survivors of pediatric severe sepsis.
A review of literature available was conducted using PUBMED/Medline on pediatric severe sepsis outcomes. Long-term outcomes and health-related quality of life (HRQL) following severe sepsis was defined as any outcome occurring after discharge from the hospital following an episode of severe sepsis which affected either the survivor or the survivor's family members.
Many children are discharged with worse clinical and functional outcomes, depending on their diagnosis, treatments received, psychological effects, and the impact of their illness on their parents. Additionally, they utilize healthcare services more than their peers and are often readmitted soon after discharge. However, pediatric HRQL studies with worthwhile outcome measures are limited and the current data on pediatric sepsis is mainly retrospective.
There is significant and longstanding morbidity seen in children and their families following a severe sepsis illness. Further prospective data are required to study the long-term outcomes of sepsis in the pediatric population.
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