PICU mortality of children with cancer admitted to pediatric intensive care unit : a systematic review and meta-analysis

Background: Outcomes for children diagnosed with cancer have improved dramatically over the past 20 years. However, although 40% of pediatric cancer patients require at least one intensive care admission throughout their disease course, PICU outcomes and resource utilization by this population have not been rigorously studied in this specific group. Methods: Using a systematic strategy, we searched Medline, Embase, and CINAHL databases for articles describing PICU mortality of pediatric cancer patients admitted to PICU. Two investigators independently applied eligibility criteria, assessed data quality, and extracted data. We pooled PICU mortality estimates using random-effects models and examined mortality trends over time using meta-regression models. Results: Out of 1218 identified manuscripts, 31 studies were included covering 16,853 PICU admissions with the majority being retrospective in nature. Overall pooled weighted mortality was 27.8% (95% confidence interval (CI), 23.7-31.9%). Mortality decreased slightly over time when post-operative patients were excluded. The use of mechanical ventilation (odds ratio (OR): 18.49 [95% CI 13.79-24.78], p < 0.001), inotropic support (OR: 14.05 [95% CI 9.16-21.57], p < 0.001), or continuous renal replacement therapy (OR: 3.24 [95% CI 1.31-8.04], p = 0.01) was significantly associated with PICU mortality. Conclusions: PICU mortality rates of pediatric cancer patients are far higher when compared to current mortality rates of the general PICU population. PICU mortality has remained relatively unchanged over the past decades, a slight decrease was only seen when post-operative patients were excluded. This compared infavorably with the improved mortality seen in adults with cancer admitted to ICU, where research-led improvements have led to the paradigm of unlimited, aggressive ICU management without any limitations on resuscitations status, for a time-limited trial

Organizational characteristics of European pediatric onco-critical care: An international cross-sectional survey

BACKGROUND Intensified treatment protocols have improved survival of pediatric oncology patients. However, these treatment protocols are associated with increased treatment-related morbidity requiring admission to pediatric intensive care unit (PICU). We aimed to describe the organizational characteristics and processes of care for this patient group across PICUs in Europe. METHODS A web-based survey was sent to PICU directors or representative physicians between February and June 2021. RESULTS Responses were obtained from 77 PICUs of 12 European countries. Organizational characteristics were similar across the different countries of Europe. The median number of PICU beds was 12 (IQR 8-16). The majority of the PICUs was staffed by pediatric intensivists and had a 24/7 intensivist coverage. Most PICUs had a nurse-to-patient ratio of 1:1 or 1:2. The median numbers of yearly planned and unplanned PICU admissions of pediatric cancer patients were 20 (IQR 10-45) and 10 (IQR 10-30, respectively. Oncology specific practices within PICU were less common in participating centres. This included implementation of oncology protocols in PICU (30%), daily rounds of PICU physicians on the wards (13%), joint mortality and morbidity meetings or complex patients' discussions (30% and 40%, respectively) and participation of parents during clinical rounds (40%). CONCLUSION Our survey provides an overview on the delivery of critical care for oncology patients in PICU across European countries. Multidisciplinary care for these vulnerable and challenging patients remains complex and challenging. Future studies need to determine the effects of differences in PICU organization and processes of care on patients' outcome

Risk factors for intensive care admission in children with severe acute asthma in the Netherlands:a prospective multicentre study

Rationale: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS). Objectives: To determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections. Methods: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses. Measurements and main results: 110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission. Conclusions: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

The potential of heliox as a therapy for acute respiratory distress syndrome in adults and children: a descriptive review

In neonatal respiratory distress syndrome (RDS) and acute RDS (ARDS) mechanical ventilation is often necessary to manage hypoxia, whilst protecting the lungs through lower volume ventilation and permissive hypercapnia. Mechanical ventilation can, however, induce or aggravate the lung injury caused by the respiratory distress. Helium, in a gas mixture with oxygen (heliox), has a low density and can reduce the flow in narrow airways and allow for lower driving pressures. The aim of this study was to review preclinical and clinical studies of the use of heliox ventilation in acute lung injury associated with respiratory failure. A systematic search was executed in the PubMed and EMBASE databases, with search terms referring to ARDS or an acute lung injury condition associated with respiratory failure and the corresponding intervention. A total of 576 papers were retrieved. After the majority had been excluded 20 papers remained, of which 6 articles described animal models (3 paediatric; 3 adult animal models) and 14 were clinical studies, of which 12 described paediatric patient populations and 2 adult patient populations. In both paediatric and adult animal models, heliox improved gas exchange while allowing for less invasive ventilation in a wide variety of models using different ventilation modes. Clinical studies show a reduction in the work of breathing during heliox ventilation, with a concomitant increase in pH and decrease in PaCO2 levels compared to oxygen ventilation. Although evidence so far is limited, there may be a rationale for heliox ventilation in ARDS as an intervention to improve ventilation and reduce the work of breathin

Patient safety in South Africa: PICU adverse event registration*

Adverse event registration is a means to improve patient safety in a PICU. So far it has been used in European and North American countries mainly. We studied adverse events in a South African setting with the aims to 1) assess rates and types of adverse events with two different registration methods and 2) describe characteristics of patients experiencing adverse events. This study consisted of 1) a retrospective audit of randomly selected patient records and 2) a prospective observational study of real-time registration of AEs during ward rounds. Adverse events were identified using the Child Health Corporation of America - Pediatric Pharmacy Advocacy Group PICU trigger tool. A multidisciplinary 20 bed PICU at the Red Cross War Memorial Children's Hospital in Cape Town. The retrospective section of the study involved 80 randomly selected patients who had been discharged from the PICU, and the prospective study involved patients who were present in the PICU between March and June 2012. None. The retrospective audit identified 260 adverse events in 61 patients (50.8 per 100 patient days). Nineteen patients (24%) did not have any adverse events. Catheter complications, hypoglycemia, and endotracheal tube malpositioning requiring repositioning were most frequent. Prospective registration during 58 ward rounds revealed 272 adverse events in 236 patients (27.2 per 100 patient days), particularly catheter complications, nosocomial infection, and surgical complications. Hundred thirty-two patients of the total 236 patients (56%) did not experience an adverse event. Patients experiencing adverse events underwent mechanical ventilation significantly more frequently. Length of stay was significantly associated with number of adverse events. The trigger tool method identifies a higher adverse event rate compared with real-time registration. Each method has a unique contribution to yield types of adverse event

FiO2 predicts outcome in infants with respiratory syncytial virus-induced acute respiratory distress syndrome

Respiratory syncytial virus (RSV) infection can progress to acute respiratory distress syndrome (ARDS) in infants. ARDS is a life-threatening condition that is characterized by severe hypoxemia, defined as PaO(2)/FiO(2) ratio <300 mmHg. This ratio is used in many trials as the sole oxygenation criterion for ARDS. Recently, however, it has been shown in adults with ARDS that FiO(2), independently of the PaO(2)/FiO(2) ratio predicts mortality. Because epidemiology and outcome of ARDS differ strongly between children and adults, we determined if FiO(2) on admission (baseline FiO(2)) independently predicted the duration of mechanical ventilation (MV) and length of stay (LOS) in the pediatric intensive care unit (PICU) in infants with RSV-induced ARDS. Retrospective observational study. A 14-bed pediatric intensive care unit. One hundred twenty-nine mechanically ventilated infants with RSV-induced ARDS. None. Independent predictors for outcome, including baseline FiO(2) and PEEP, were analyzed using the cox regression model. Endpoints were duration of MV and LOS in the PICU. A higher baseline FiO(2) was independently associated with a longer duration of MV (HR 0.12, CI 0.02-0.87, P = 0.036) and increased LOS in the PICU (HR 0.09, CI 0.01-0.57, P = 0.023). Neither baseline PEEP nor PaO(2)/FiO(2) ratio correlated with outcome. FiO(2) level independently predicted outcome in infants with RSV-induced ARDS, whereas both PEEP and the PaO(2)/FiO(2) ratio did not. This suggests that FiO(2) should be taken into account in defining disease severity in infants with RSV-induced ARD

Pediatric acute respiratory distress syndrome: fluid management in the PICU

The administration of an appropriate volume of intravenous fluids, while avoiding fluid overload, is a major challenge in the pediatric intensive care unit. Despite our efforts, fluid overload is a very common clinical observation in critically ill children, in particular in those with pediatric acute respiratory distress syndrome (PARDS). Patients with ARDS have widespread damage of the alveolar capillary barrier, potentially making them vulnerable to fluid overload with the development of pulmonary edema leading to prolonged course of disease. Indeed, studies in adults with ARDS have shown that an increased cumulative fluid balance is associated with adverse outcome. However, age-related differences in the development and consequences of fluid overload in ARDS may exist due to disparities in immunologic response and body water distribution. This systematic review summarizes the current literature on fluid imbalance and management in PARDS, with special emphasis on potential differences with adult patients. It discusses the adverse effects associated with fluid overload and the corresponding possible pathophysiological mechanisms of its development. Our intent is to provide an incentive to develop age-specific fluid management protocols to improve PARDS outcomes