Critical Care and Mechanical Ventilation Practices Surrounding Liver Transplantation in Children: A Multicenter Collaborative.

OBJECTIVES: We aimed to determine which characteristics and management approaches were associated with postoperative invasive mechanical ventilation (IMV) and with a prolonged course of IMV in children post liver transplant as well as describing the utilization of critical care resources. DESIGN: Retrospective, multicenter, cohort study of children who underwent an isolated liver transplantation between January 2017 and December 2018. SETTING: Twelve U.S., pediatric, liver transplant centers. PATIENTS: Three hundred thirty children post liver transplant admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six patients died in our cohort. The median length of PICU stay was 4.5 days (interquartile range [IQR], 2.9-8.2 d). Most patients were initially monitored with arterial catheters (96%), central venous pressures (95%), and liver ultrasound (93%). Anticoagulation (80%), blood product administration (52.4%), and vasoactive agents (23.0%) were commonly used therapies in the first 7 days. In multivariable logistic regression analysis, age (adjusted odds ratio [aOR] 0.9 [0.86-0.95]), open fascia (aOR 7.0 [95% CI, 2.6-18.9]), large center size (aOR 4.3 [95% CI 2.2-8.3]), and higher Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (aOR 1.04 [95% CI, 1.01-1.06]) were associated with postoperative IMV. In multivariable logistic regression analysis, postoperative day 0 peak inspiratory pressure (PIP) (aOR 1.2 [95% CI, 1.1-1.3]), large center size (aOR 2.9 [95% CI, 1.6-5.4]), and age (aOR 0.89 [95% CI, 0.85-0.95]) were associated with length of IMV greater than 24 hours. Length of IMV greater than 24 hours was associated with bleeding complications ( p = 0.03), infections ( p = 0.03), graft loss ( p = 0.02), and reoperation ( p = 0.03). CONCLUSIONS: Younger age, preoperative hospitalization, large center size, and open fascia are associated with use of IMV, and younger age, large center size, and postoperative day 0 PIP are associated with prolonged IMV on multivariable analysis. Longer IMV is associated with negative outcomes, making it an important clinical marker.

Renal Replacement Therapy Modalities in Critically Ill Children.

OBJECTIVES: The objective of this study is to describe the relative frequency of use of continuous renal replacement therapy, intermittent hemodialysis, and peritoneal dialysis and to analyze characteristics and outcomes of critically ill children receiving renal replacement therapies admitted to PICUs that participate in the Virtual PICU (VPS LLC, Los Angeles, CA) registry. DESIGN: Retrospective, database analysis. SETTING: PICUs that participate in the Virtual PICU (VPS LLC) registry. PATIENTS: Critically ill children admitted to PICUs that participate in the Virtual PICU (VPS LLC) registry and received renal replacement therapy from January 1, 2009, to December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 7,109 cases (53% males) received renal replacement therapy during the study period. The median age was 72.3 months (interquartile range, 8.4-170 mo) and median length of stay was 8.7 days (interquartile range, 3.3-21.2 d). Caucasians comprised 42% of the cohort and blacks and Hispanics were 16% each. Continuous renal replacement therapy was used in 46.5%, hemodialysis in 35.5% and peritoneal dialysis in 18%. Of the 7,109 cases, 1,852 (26%) were postoperative cases (68% cardiac surgical) and 981 (14%) had a diagnosis of cancer. Conventional mechanical ventilation was used in 64%, high-frequency oscillatory ventilation in 12%, noninvasive ventilation in 24%, and extracorporeal membrane oxygenation in 5.8%. The overall mortality was 22.3%. Patients who died were younger 40.8 months (interquartile range, 1.5-159.4 mo) versus 79.9 months (interquartile range, 12.6-171.7 mo), had a longer length of stay 15 days (interquartile range, 7-33 d) versus 7 days (interquartile range, 3-18 d) and higher Pediatric Index of Mortality 2 score -2.84 (interquartile range, -3.5 to -1.7) versus -4.2 (interquartile range, -4.7 to -3.0) (p < 0.05). On multivariate logistic regression analysis, higher mortality was associated with the presence of cancer (32.7%), previous ICU admission (32%), requiring mechanical ventilation (33.7%), receiving high-frequency oscillatory ventilation (67%), or extracorporeal membrane oxygenation (58.4%), admission following cardiac surgical procedure (29.4%), and receiving continuous renal replacement therapy (38.8%), and lower mortality was associated with hemodialysis (9.8%), and peritoneal dialysis (12.3%) (p < 0.0001). CONCLUSIONS: Continuous renal replacement therapy is an increasingly prevalent renal replacement therapy modality used in critically ill children admitted to an ICU. Higher mortality rate with the use of continuous renal replacement therapy should be interpreted with caution.

Validation of an Ultrasound Cardiac Output Monitor as a Bedside Tool for Pediatric Patients.

The aim of our study was to determine the validity of cardiac output (CO) measurements taken with the ultrasonic cardiac output monitor (USCOM) by comparing to CO measured by pulmonary arterial catheter (PAC) thermodilution during cardiac catheterization. We enrolled thirty-one children (<18 years) undergoing cardiac catheterization in this double-blinded, prospective, observational study. The median CO measured by USCOM was 4.37 L/min (IQR 3.73, 5.60 L/min) compared to 4.28 L/min (IQR 3.52, 5.26 L/min) by PAC thermodilution. The bias (mean difference) between the two methods was 0.2 L/min, and the 95% limits of agreement were -1.2 to 1.6 L/min. The mean percentage error of CO between USCOM and PAC thermodilution was 11%. When excluding a sole outlier, the bias between the two measures decreased to 0.1 L/min (95% limits of agreement -0.6 to 0.9 L/min), and the percentage error was reduced to 8%. The median SVRI measured by USCOM was 22.0 Wood Units (IQR 17.0, 26.8 Wood Units) compared to 22.1 Wood Units (IQR 17.6, 27.4 Wood Units) by PAC thermodilution. Bias (mean difference) between the two methods was -0.6 Wood Units, and the 95% limits of agreement were -8.2 to 6.9 Wood Units. We found that the estimation of CO and by extension SVRI with USCOM is reliable against pulmonary artery catheter thermodilution in children with normal cardiac anatomy. Given the noninvasive nature of USCOM, speed of measurement, and relative ease of use, it may be useful as a bedside tool for pediatric patients.

Impact of Continuous Renal Replacement Therapy Initiation Time, Kidney Injury, and Hypervolemia in Critically Ill Children.

BACKGROUND: The mortality rate of pediatric patients who require continuous renal replacement therapy is approximately 42%, and outcomes vary considerably depending on underlying disease, illness severity, and time of dialysis initiation. Delay in the initiation of such therapy may increase mortality risk, prolong intensive care unit stay, and worsen clinical outcomes. LOCAL PROBLEM: In the pediatric intensive care unit of an urban level I trauma children's hospital, continuous renal replacement therapy initiation times and factors associated with delays in therapy were unknown. METHODS: This quality improvement process involved a retrospective review of data on patients who received continuous dialysis in the pediatric intensive care unit from January 1, 2017, to December 31, 2021. The objectives were to examine the characteristics of the children requiring continuous renal replacement therapy, therapy initiation times, and factors associated with initiation delays that might affect unit length of stay and mortality. RESULTS: During the study period, 175 patients received continuous renal replacement therapy, with an average initiation time of 11.9 hours. Statistically significant associations were found between the degree of fluid overload and mortality (P < .001) and between the presence of acute kidney injury and prolonged length of stay (P = .04). No significant association was found between therapy initiation time and unit length of stay or mortality, although the average initiation time of survivors was 5.9 hours shorter than that of nonsurvivors. CONCLUSION: Future studies are needed to assess real time delays and to evaluate if the implementation of a standardized initiation process decreases initiation time.

Vascular thrombosis after pediatric liver transplantation: Is prevention achievable?

Background: Vascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric studies are lacking. Methods: This multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications. Results: Within seven postoperative days, 31/331 (9.37%) patients developed intra-abdominal VT. Open fascia occurred more commonly in patients with VT (51.61 vs 23.33%) and remained the only independent risk factor in multivariable analysis (OR = 2.84, p = 0.012). Patients with VT received more blood products (83.87 vs 50.00%), had significantly higher rates of graft loss (22.58 vs 1.33%), infection (50.00 vs 20.60%), and unplanned return to the operating room (70.97 vs 16.44%) compared to those without VT. The risk of bleeding was similar (p = 0.2) between patients on and off anticoagulation. Conclusions: Prophylactic anticoagulation did not increase bleeding complications in this cohort. The only independent factor associated with VT was open fascia, likely a graft/recipient size mismatch surrogate, supporting the need to improve surgical techniques to prevent VT that may not be modifiable with anticoagulation.

A multicenter study of ICU resource utilization in pediatric, adolescent and young adult patients post CAR-T therapy.

Tisagenlecleucel is associated with remarkable outcomes in treating patients up to the age of 25 years with refractory B-cell acute lymphoblastic leukemia (ALL). Yet, due to unique and potentially life-threatening complications, access remains limited to higher-resource and certified centers. Reports of inequity and related disparities in care are emerging. In this multicenter study of ALL patients admitted for anti-leukemia therapy, who required pediatric intensive care (ICU) support (n = 205), patients receiving tisagenlecleucel (n = 39) were compared to those receiving conventional chemotherapy (n = 166). The median time to ICU transfer was 6 (0-43) versus 1 (0-116) days, respectively (p < 0.0001). There was no difference in the use of vasopressor, ionotropic, sedating, and/or paralytic agents between groups, but use of dexamethasone was higher among tisagenlecleucel patients. Patients receiving tisagenlecleucel were more likely to have cardiorespiratory toxicity (p = 0.0002), but there were no differences in diagnostic interventions between both groups and/or differences in ICU length of stay and/or overall hospital survival. Toxicities associated with tisagenlecleucel are generally reversible, and our findings suggest that resource utilization once admitted to the ICU may be similar among patients with ALL receiving tisagenlecleucel versus conventional chemotherapy. As centers consider improved access to care and the feasibility of tisagenlecleucel certification, our study may inform strategic planning.

A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management).

Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO2, inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day ventilator free days. Clinical Trials Registration: NCT03266016.

Definition and global epidemiology of pediatric acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) has been known to occur in children since early descriptions of the disease, but pediatric specific diagnostic criteria were first established in 2015 with the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition of pediatric ARDS (PARDS). There were substantial changes proposed with the PALICC definition, including simplification of radiographic criteria, use of pulse oximetry based metrics to define PARDS, specific criteria for non-invasive ventilation, and the use of oxygenation index (OI) instead of PaO2/FiO2 ratio for those on invasive ventilation. While these changes could potentially result in major changes in the reported incidence and outcome of PARDS, review of the recent literature since publication of the PALICC definitions highlight that major elements regarding the contemporary epidemiology of PARDS have remained stable over the past 20 years. This highlights that the PARDS definition is likely catching up to changes in clinical practice, and suggests that this new definition should be used moving forward as it is more reflective of current practice than historical definitions. However, it is also clear that PARDS severity alone (as measured by the PALICC) criteria insufficiently characterizes the risk for mortality or other important clinical outcomes amongst PARDS patients, although there appears to be some association between PARDS severity and outcome, particularly when hypoxemia is severe.

Cardiac output and systemic vascular resistance: Clinical assessment compared with a noninvasive objective measurement in children with shock.

PURPOSE: To evaluate physician assessment of cardiac output and systemic vascular resistance in patients with shock compared with an ultrasonic cardiac output monitor (USCOM). To explore potential changes in therapy decisions if USCOM data were available using physician intervention answers. STUDY DESIGN: Double-blinded, prospective, observational study in a tertiary hospital pediatric intensive care unit. Forty children (<18years) admitted with shock, requiring ongoing volume resuscitation or inotropic support. Two to 3 physicians clinically assessed cardiac output and systemic vascular resistance, categorizing them as high, normal, or low. An investigator simultaneously measured cardiac index (CI) and systemic vascular resistance index (SVRI) with USCOM categorized as high, normal, or low. RESULTS: Overall agreement between physician and USCOM for CI (48.5% [κ = 0.18]) and SVRI (45.9% [κ = 0.16]) was poor. Interobserver agreement was also poor for CI (58.7% [κ = 0.33]) and SVRI (52.3% [κ = 0.28]). Comparing theoretical physician interventions to "acceptable" or "unacceptable" clinical interventions, based on USCOM measurement, 56 (21%) physician interventions were found to be "unacceptable." CONCLUSIONS: There is poor agreement between physician-assessed CI and SVRI and USCOM, with significant interobserver variability among physicians. Objective measurement of CI and SVRI may reduce variability and improve diagnostic accuracy.

Epidemiology and outcomes of children with accidental hypothermia: A propensity-matched study.

BACKGROUND: The purpose of this study was to explore the epidemiology and outcomes of hospitalized children with a diagnosis of accidental hypothermia. METHODS: The 2012 Kids' Inpatient Database, detailing discharge diagnoses in children admitted to US hospitals, was analyzed using International Classification of Diseases, Ninth Revision, Clinical Modification codes to filter out relevant patients. Children ages 1 month to 17 years were included in the analysis. Demographic and outcome variables in the hypothermia group were compared with the rest of the patients. In a separate analysis, children with hypothermia were matched 1:1 using a correlative propensity score using sex, age, hospital region, income quartiles, race, ventilation status, coagulopathy, drowning, and All Patient Refined Diagnosis Related Groups severity score and their outcomes were compared with controls. The sample data were weighted to get a national estimate. RESULTS: Accidental hypothermia was present in 1,028 cases out of 1,915,435 discharges. Children with hypothermia were more likely to be males (54.7% vs. 50.9%; p < 0.05) and infants (32.6% vs. 17.5%); they were less likely to be teens (30% vs. 37.8%). Children with hypothermia were more likely to be admitted in the Southern region (48.3% vs. 38.4%; p < 0.05) and have a higher mortality rate compared to all other discharges (8.5% vs. 0.3%; p < 0.05) or when compared with the matched controls (8.9% vs. 4.4%). CONCLUSIONS: The diagnosis of accidental hypothermia significantly increased mortality in hospitalized children. Interestingly, accidental hypothermia was more common in Southern states compared to the other areas of the United States. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level III.

Tecnica de doble incision para la toma de injerto hueso-tendon-hueso en la reconstruccion del ligamento cruzado anterior. Estudio cadaverico. Correlacion morfologica con las ramas nerviosas pre e infrapatelares / Double incision technique for ACL reconstruction with patellar tendon BTB

Introducción: Una de las complicaciones mas frecuentes en relación con la obtención del injerto patelar mediante la tradicional exposición longitudinal consiste en el compromiso de las denominadas "ramas infrarotulianas del nervio safeno interno". Algunos autores han preconizado la exposición quirúrgica con doble vía (dos longitudinales o dos transversales) refiriendo en tales casos una incidencia menor de dicha complicación. El objetivo del presente trabajo consiste en investigar la relación anatómica de las ramas pre e infrapatelares con una variante técnica de exposición quirúrgica consistente en doble vía, proximal transversal y distal longitudinal. Materiales y metodos: Se practico la disección sistemática de un lote de 20 miembros inferiores de cadáveres de adulto fonnalizados (formol 10 por ciento). En cada caso, en un primer tiempo se practicaron las incisiones tegumentarias : - la incisión proximal fue transversal de ± 25 mm a nivel del polo distal de la rotula ; - la incisión distal fue longitudinal, de ± 25 mm, medial a la tuberosidad anterior de la tibia (TAT). En un segundo tiempo se disecaron las ramas nerviosas pre e infrapatelares registrando su relación anatómica con las incisiones descriptas. Resultados: Por su relación anatómica con el plano profundo, independientemente de su origen, se clasificaron dos grupos de ramas nerviosas: a) prepatelares: superpuestas a la cara anterior de la rótula ; b) infrapatelares: comprendidas entre el polo patelar distal y la TAT. Conclusión: Las observaciones realizadas permiten concluir que la variante técnica descripta implica un riesgo potencial de lesión de las ramas pre e infrapatelares exclusivamente limitado a las variantes anatómicas menos frecuentes según la clasificación de J. Kartus y colaboradores.