The burden of pediatric critical illness among pediatric oncology patients in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Pediatric oncology patients have increased risk for critical illness; outcomes are well described in high-income countries (HICs); however, data is limited for low- and middle-income countries (LMICs). METHODS: We systematically searched PubMed, EMBASE, Web of Science, CINAHL and Global Health databases for articles in 6 languages describing mortality in children with cancer admitted to intensive care units (ICUs) in LMICs. Two investigators independently assessed eligibility, data quality, and extracted data. We pooled ICU mortality estimates using random effect models. RESULTS: Of 3641 studies identified, 22 studies were included, covering 4803 ICU admissions. Overall pooled mortality was 30.3 % [95 % Confidence-interval (CI) 21.7-40.6 %]. Mechanical ventilation [odds ratio (OR) 12.2, 95 %CI:6.2-24.0, p-value<0.001] and vasoactive infusions [OR 6.3 95 %CI:3.3-11.9, p-value<0.001] were associated with ICU mortality. CONCLUSIONS: ICU mortality among pediatric oncology patients in LMICs is similar to that in HICs, however, this review likely underestimates true mortality due to underrepresentation of studies from low-income countries.

Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands: a nationwide prospective observational study (the BRICK study).

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands. Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity. Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25-89). The median length of PICU admission was 5 days (IQR 3-8). The total RSV-related PICU costs are € 3,826,386 in 2021-2022, and € 3,183,888 in 2022-2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection. Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs. Funding: None.

Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes-an international multicentre retrospective study.

Background: Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population. Methods: We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts. Findings: LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p < 0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04-3.34) in the European cohort and 1.6 (1.2-2.2) in the U.S. cohort. Interpretation: We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes. Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Long-term nephrotoxicity in irradiated pediatric kidney tumor survivors: A systematic review.

OBJECTIVE: Nephrotoxicity can occur as a side effect after treatment for kidney tumor in childhood. The use of radiotherapy (RT) has a potential additional effect. METHODS: A systematic electronic literature search that combined childhood kidney cancer with different treatments and nephrotoxicity terms was performed in EMBASE. Studies were included based on the reporting of nephrotoxicity occurrence after treatment for kidney tumor during pediatric age, with 75% of participants being under the age of 25 years at the time of diagnosis, and having been treated with any type of kidney surgery, chemotherapy, and/or RT. RESULTS: A pooled analysis did not show significant difference in estimated glomerular filtration rate between the group of patients who received RT compared with the group treated without RT (SMD -0.11 [95% CI -1.07-0.84] p = .733). CONCLUSION: The current literature suggests that the use of RT does not have a significant impact on the decline of kidney function as independent factor.

Prognostic factors for multi-organ dysfunction in pediatric oncology patients admitted to the pediatric intensive care unit.

Background: Pediatric oncology patients who require admission to the pediatric intensive care unit (PICU) have worse outcomes compared to their non-cancer peers. Although multi-organ dysfunction (MOD) plays a pivotal role in PICU mortality and morbidity, risk factors for MOD have not yet been identified. We aimed to identify risk factors at PICU admission for new or progressive MOD (NPMOD) during the first week of PICU stay. Methods: This retrospective cohort study included all pediatric oncology patients aged 0 to 18 years admitted to the PICU between June 2018 and June 2021. We used the recently published PODIUM criteria for defining multi-organ dysfunction and estimated the association between covariates at PICU baseline and the outcome NPMOD using a multivariable logistic regression model, with PICU admission as unit of study. To study the predictive performance, the model was internally validated by using bootstrap. Results: A total of 761 PICU admissions of 571 patients were included. NPMOD was present in 154 PICU admissions (20%). Patients with NPMOD had a high mortality compared to patients without NPMOD, 14% and 1.0% respectively. Hemato-oncological diagnosis, number of failing organs and unplanned admission were independent risk factors for NPMOD. The prognostic model had an overall good discrimination and calibration. Conclusion: The risk factors at PICU admission for NPMOD may help to identify patients who may benefit from closer monitoring and early interventions. When applying the PODIUM criteria, we found some opportunities for fine-tuning these criteria for pediatric oncology patients, that need to be validated in future studies.

Evidence for Beneficial Effect of Daily Use of Mechanical Insufflation-Exsufflation in Patients With Neuromuscular Diseases.

BACKGROUND: Daily application of mechanical insufflation-exsufflation (MI-E) is used increasingly in patients with neuromuscular diseases (NMDs) to prevent pulmonary congestion and thereby respiratory tract infections, although its beneficial effect remains uncertain. We, therefore, conducted a systematic review, registered in PROSPERO (CRD42020158278), to compile available evidence for daily MI-E use in subjects with NMDs and stable respiratory condition. METHODS: We performed a systematic comprehensive search of MEDLINE, Embase, CINAHL, and Web of Science up to December 23, 2021. We excluded articles studying the effect of MI-E in case of acute respiratory failure or infections and studies comparing different MI-E devices and settings. Studied outcomes were prevalence and severity of respiratory infections, lung function, respiratory characteristics, and patient satisfaction. We performed a meta-analysis using DerSimonian-Laird random effects model and assessed methodological quality by using the Alberta Heritage Foundation for Medical Research tool. RESULTS: A total of 3,374 records were screened, of which 25 were included, studying 608 subjects. One randomized controlled trial (RCT) found a trend toward reduced duration of respiratory infections compared to air stacking (AS) that was not statistically significant. Long-term effects on pulmonary function tests (PFT) results were reported in one RCT and one retrospective study, with mixed results regarding vital capacity. Most studies compared PFT results before and immediately after MI-E use. Meta-analysis showed an overall beneficial effect of MI-E on cough peak flow (CPF) compared to unassisted CPF (mean difference 91.6 L/min [95% CI 28.3-155.0], P < .001). Subject satisfaction was high, though possibly influenced by major bias. CONCLUSIONS: There is limited evidence available to support beneficial effects of daily use of MI-E in clinically stable subjects with NMDs, with the possible exception of increased CPF immediately after MI-E application. Lack of longitudinal studies preclude conclusions regarding long-term effects. The very limited data comparing MI-E to AS preclude comparisons.

Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study.

BACKGROUND: Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure. METHODS: We included treatment-naïve SMA patients participating in a prospective national cohort study if they required mechanical ventilation because of chronic respiratory failure and if lung function test results were available from the years prior to initiation of ventilation. We analyzed Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV1), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PEmax). We studied the longitudinal course using linear mixed-effects models. We compared patients who electively started mechanical ventilation compared to patients who could not be weaned after acute respiratory failure. RESULTS: We analyzed 385 lung function tests from 38 patients with SMA types 1c-3a. At initiation of ventilation median age was 18.8 years (IQR: 13.2-30.1) and median standardized FVC, FEV1 and PEF were 28.8% (95% CI: 23.5; 34.2), 28.8% (95% CI: 24.0; 33.7) and 30.0% (95% CI: 23.4; 36.7), with an average annual decline of 1.75% (95% CI: 0.86; 2.66), 1.72% (95% CI: 1.04; 2.40) and 1.65% (95% CI: 0.71; 2.59), respectively. Our data did not support the hypothesis of an accelerated decline prior to initiation of mechanical ventilation. Median PEmax was 35.3 cmH2O (95% CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Median FVC, FEV1, PEF and PEmax were lower in patients who electively started mechanical ventilation (p < 0.001). CONCLUSIONS: Patterns of lung function decline cannot predict impending respiratory failure: SMA is characterized by a gradual decline of lung function. We found no evidence for an accelerated deterioration. In addition, PEmax remains low and stable in the years preceding initiation of ventilation. Patients who electively started mechanical ventilation had more restrictive lung function at initiation of ventilation, compared to patients who could not be weaned after surgery or a respiratory tract infection.

Validation of a modified bedside Pediatric Early Warning System score for detection of clinical deterioration in hospitalized pediatric oncology patients: A prospective cohort study.

BACKGROUND: Hospitalized pediatric oncology patients are at risk of severe clinical deterioration. Yet Pediatric Early Warning System (PEWS) scores have not been prospectively validated in these patients. We aimed to determine the predictive performance of the modified BedsidePEWS score for unplanned pediatric intensive care unit (PICU) admission and cardiopulmonary resuscitation (CPR) in this patient population. METHODS: We performed a prospective cohort study in an 80-bed pediatric oncology hospital in the Netherlands, where care has been nationally centralized. All hospitalized pediatric oncology patients aged 0-18 years were eligible for inclusion. A Cox proportional hazard model was estimated to study the association between BedsidePEWS score and unplanned PICU admissions or CPR. The predictive performance of the model was internally validated by bootstrapping. RESULTS: A total of 1137 patients were included. During the study, 103 patients experienced 127 unplanned PICU admissions and three CPRs. The hazard ratio for unplanned PICU admission or CPR was 1.65 (95% confidence interval [CI]: 1.59-1.72) for each point increase in the modified BedsidePEWS score. The discriminative ability was moderate (D-index close to 0 and a C-index of 0.83 [95% CI: 0.79-0.90]). Positive and negative predictive values of modified BedsidePEWS score at the widely used cutoff of 8, at which escalation of care is required, were 1.4% and 99.9%, respectively. CONCLUSION: The modified BedsidePEWS score is significantly associated with requirement of PICU transfer or CPR. In pediatric oncology patients, this PEWS score may aid in clinical decision-making for timing of PICU transfer.

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.

Short-term effect of air stacking and mechanical insufflation-exsufflation on lung function in patients with neuromuscular diseases.

Air stacking (AS) and mechanical insufflation-exsufflation (MI-E) aim to increase cough efficacy by augmenting inspiratory lung volumes in patients with neuromuscular diseases (NMDs). We studied the short-term effect of AS and MI-E on lung function. We prospectively included NMD patients familiar with daily AS or MI-E use. Studied outcomes were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) prior to, immediately after, and up to 2 h after treatment. Paired sample T-test and Wilcoxon signed-rank test was used. Sixty-seven patients participated. We observed increased FVC and FEV1 immediately after AS with a mean difference of respectively 0.090 L (95% CI 0.045; 0.135, p < .001) and 0.073 L (95% CI 0.017; 0.128, p = .012). Increased FVC immediately after MI-E (mean difference 0.059 L (95% CI 0.010; 0.109, p = .021) persisted 1 hour (mean difference 0.079 L (95% CI 0.034; 0.125, p = .003). The effect of treatment was more pronounced in patients diagnosed with Spinal Muscular Atrophy, compared to patients with Duchenne muscular dystrophy. AS and MI-E improved FVC immediately after treatment, which persisted 1 h after MI-E. There is insufficient evidence that short-lasting increases in FVC would explain the possible beneficial effect of AS and MI-E.

Oscillometry: A substitute of spirometry in children with neuromuscular diseases?

INTRODUCTION: Spirometry plays an important role in the assessment of possible respiratory failure in children with neuromuscular diseases (NMDs). However, obtaining reliable spirometry results is a major challenge. We studied the relation between oscillometry and spirometry results. Oscillometry is an easy, noninvasive method to measure respiratory resistance R and reactance X. We hypothesized an increased R and reduced X in patients with more reduced lung function. METHODS: In this prospective single-center study, we included all children with NMDs able to perform spirometry. We consecutively measured R and X at 5, 11, and 19 Hz and (forced) vital capacity, peak expiratory flow. Spearman correlation coefficients and positive and negative predictive values were calculated. Regression curves were estimated. RESULTS: We included 148 patients, median age 13 years (interquartile range: 8-16). A negative correlation was found between R and spirometry outcomes (Spearman correlation coefficient [ρ]: -0.5 to -0.6, p < 0.001). A positive correlation was found between X (i.e., less negative outcomes) and spirometry outcomes (ρ: 0.4-0.6, p < 0.001). Highest correlation was found at lower frequencies. Regression analysis showed a nonlinear relation. Measurement of inspiratory and expiratory R and X did not provide added value. Positive predictive values of 80%-85% were found for z-scores of R measured at 5 Hz versus (F)VC ≤ 60%. CONCLUSION: We found a nonlinear relation between oscillometry and spirometry results with increased R and reduced X in patients with more restrictive lung function decline. Given the difficulties with performing spirometry, oscillometry may be a promising substitute.

The predictive performance and impact of pediatric early warning systems in hospitalized pediatric oncology patients-A systematic review.

Pediatric early warning systems (PEWS) arewidely used to identify clinically deteriorating patients. Hospitalized pediatric oncology patients are particularly prone to clinical deterioration. We assessed the PEWS performance to predict early clinical deterioration and the effect of PEWS implementation on patient outcomes in pediatric oncology patients. PubMED, EMBASE, and CINAHL databases were systematically searched from inception up to March 2020. Quality assessment was performed using the Prediction model study Risk-Of-Bias Assessment Tool (PROBAST) and the Cochrane Risk-of-Bias Tool. Nine studies were included. Due to heterogeneity of study designs, outcome measures, and diversity of PEWS, it was not possible to conduct a meta-analysis. Although the studies reported high sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC) of PEWS detecting inpatient deterioration, overall risk of bias of the studies was high. This review highlights limited evidence on the predictive performance of PEWS for clinical deterioration and the effect of PEWS implementation.

Short-term effect and effect on rate of lung function decline after surgery for neuromuscular or syndromic scoliosis.

INTRODUCTION: Understanding the impact of scoliosis surgery on lung function is important for counseling patients about risks and benefits of surgery. We prospectively compared the trends in lung function test (LFT) results before and after scoliosis surgery in children with neuromuscular diseases or dysmorphic syndromes. We hypothesized a stabilization. METHODS: We prospectively included children with neuromuscular or syndromic scoliosis able to perform LFTs. We studied (forced) vital capacity ([F]VC), ratio of forced expiratory volume in 1 s (FEV1 ) and FVC, and peak expiratory flow (PEF). Preoperative LFT results were compared with results 3-4 months after surgery. The mean monthly change in LFT results up to 2 years after surgery was compared with the preoperative natural history using linear mixed-effects models. RESULTS: We included 43 patients. No significant change was observed in absolute values of (F)VC, FEV1 /FVC, and PEF before and after surgery. In 23 neuromuscular patients median standardized VC, FVC, and PEF decreased significantly after surgery from 43% to 33%, 42% to 31%, and 51% to 40%, respectively. In 20 syndromic patients, median FVC decreased from 68% to 65%. The monthly rate of change in FVC did not change significantly in both groups with a mean difference of 0.18% (95% CI: -0.27, -0.61) and -0.44% (95% CI: -1.05, 0.16). CONCLUSION: No stabilization of lung function 3-4 months after scoliosis surgery was observed in children with neuromuscular and syndromic scoliosis with restrictive lung function disease. The effect on the rate of lung function decline remains inconclusive.

Natural history of respiratory muscle strength in spinal muscular atrophy: a prospective national cohort study.

BACKGROUND: Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life. METHODS: We measured maximal expiratory and inspiratory pressure (PEmax and PImax), Sniff Nasal inspiratory pressure (SNIP), peak expiratory flow (PEF), and peak cough flow (PCF) in treatment-naïve patients with SMA. We used mixed-models to analyze natural history patterns. RESULTS: We included 2172 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. All outcomes were lower in the more severe phenotypes. Significant differences in PEF were present between SMA types from early ages onwards. PEF decline was linear (1-2%/year). PEF reached values below 80% during early childhood in types 1c-2, and during adolescence in type 3a. PEmax and PImax were severely lowered in most patients throughout life, with PEmax values abnormally low (i.e. < 80 cmH2O) in virtually all patients. The PEmax/PImax ratio was < 1 throughout life in all SMA types, indicating that expiratory muscles were most affected. All but SMA type 3b patients had a lowered PCF. Patients with types 2b and 3a had PCF levels between 160 and 270 L/min, those with type 2a around 160 L/min and patients with type 1c well below 160 L/min. Finally, SNIP was low in nearly all patients, most pronounced in more severely affected patients. CONCLUSIONS: There are clear differences in respiratory muscle strength and its progressive decline between SMA types. We observed lower outcomes in more severe SMA types. Particularly PEF may be a suitable outcome measure for the follow-up of respiratory strength in patients with SMA. PEF declines in a rather linear pattern in all SMA types, with clear differences at baseline. These natural history data may serve as a reference for longer-term treatment efficacy assessments.

Paediatric Acute Respiratory Distress Syndrome Neuromuscular Blockade study (PAN-study): a phase IV randomised controlled trial of early neuromuscular blockade in moderate-to-severe paediatric acute respiratory distress syndrome.

BACKGROUND: Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40-50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU). METHODS: This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02902055 . Registered on September 15, 2016.

Role of extracorporeal membrane oxygenation in pediatric cancer patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in pediatric patients with underlying malignancies remains controversial. However, in an era in which the survival rates for children with malignancies have increased significantly and several recent reports have demonstrated effective ECMO use in children with cancer, we aimed to estimate the outcome and complications of ECMO treatment in these children. METHODS: We searched MEDLINE, Embase and CINAHL databases for studies on the use ECMO in pediatric patients with an underlying malignancy from inception to September 2020. This review was conducted in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Included studies were evaluated for quality using the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses (DerSimonian and Laird) were performed. The primary outcomes were mortality during ECMO or hospital mortality. RESULTS: Thirteen retrospective, observational cohort studies were included, most of moderate quality (625 patients). The commonest indication for ECMO was severe respiratory failure (92%). Pooled mortality during ECMO was 55% (95% confidence interval [CI], 47-63%) and pooled hospital mortality was 60% (95% CI 54-67%). Although heterogeneity among the included studies was low, confidence intervals were large. In addition, the majority of the data were derived from registries with overlapping patients which were excluded for the meta-analyses to prevent resampling of the same participants across the included studies. Finally, there was a lack of consistent complications reporting among the studies. CONCLUSION: Significantly higher mortalities than in general PICU patients was reported with the use of ECMO in children with malignancies. Although these results need to be interpreted with caution due to the lack of granular data, they suggest that ECMO appears to represents a viable rescue option for selected patients with underlying malignancies. There is an urgent need for additional data to define patients for whom ECMO may provide benefit or harm.

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.

Identifying the critically ill paediatric oncology patient: a study protocol for a prospective observational cohort study for validation of a modified Bedside Paediatric Early Warning System score in hospitalised paediatric oncology patients.

INTRODUCTION: Hospitalised paediatric oncology patients are at risk to develop acute complications. Early identification of clinical deterioration enabling adequate escalation of care remains challenging. Various Paediatric Early Warning Systems (PEWSs) have been evaluated, also in paediatric oncology patients but mostly in retrospective or case-control study designs. This study protocol encompasses the first prospective cohort with the aim of evaluating the predictive performance of a modified Bedside PEWS score for non-elective paediatric intensive care unit (PICU) admission or cardiopulmonary resuscitation in hospitalised paediatric oncology patients. METHODS AND ANALYSIS: A prospective cohort study will be conducted at the 80-bed Dutch paediatric oncology hospital, where all national paediatric oncology care has been centralised, directly connected to a shared 22-bed PICU. All patients between 1 February 2019 and 1 February 2021 admitted to the inpatient nursing wards, aged 0-18 years, with an International Classification of Diseases for Oncology (ICD-O) diagnosis of paediatric malignancy will be eligible. A Cox proportional hazard regression model will be used to estimate the association between the modified Bedside PEWS and time to non-elective PICU transfer or cardiopulmonary arrest. Predictive performance (discrimination and calibration) will be assessed internally using resampling validation. To account for multiple occurrences of the event of interest within each patient, the unit of study is a single uninterrupted ward admission (a clinical episode). ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional ethical review board of our hospital (MEC protocol number 16-572/C). We adapted our enrolment procedure to General Data Protection Regulation compliance. Results will be disseminated at scientific conferences, regional educational sessions and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL8957).