Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

A training plan to implement lung ultrasound for diagnosing pneumonia in children.

BACKGROUND: Lung ultrasound (LUS) for critical patients requires trained operators to perform them, though little information exists on the level of training required for independent practice. The aims were to implement a training plan for diagnosing pneumonia using LUS and to analyze the inter-observer agreement between senior radiologists (SRs) and pediatric intensive care physicians (PICPs). METHODS: Prospective longitudinal and interventional study conducted in the Pediatric Intensive Care Unit of a tertiary hospital. Following a theoretical and practical training plan regarding diagnosing pneumonia using LUS, the concordance between SRs and the PICPs on their LUS reports was analyzed. RESULTS: Nine PICPs were trained and tested on both theoretical and practical LUS knowledge. The mean exam mark was 13.5/15. To evaluate inter-observer agreement, a total of 483 LUS were performed. For interstitial syndrome, the global Kappa coefficient (K) was 0.51 (95% CI 0.43-0.58). Regarding the presence of consolidation, K was 0.67 (95% CI 0.53-0.78), and for the consolidation pattern, K was 0.82 (95% CI 0.79-0.85), showing almost perfect agreement. CONCLUSIONS: Our training plan allowed PICPs to independently perform LUS and might improve pneumonia diagnosis. We found a high inter-observer agreement between PICPs and SRs in detecting the presence and type of consolidation on LUS. IMPACT: Lung ultrasound (LUS) has been proposed as an alternative to diagnose pneumonia in children. However, the adoption of LUS in clinical practice has been slow, and it is not yet included in general clinical guidelines. The results of this study show that the implementation of a LUS training program may improve pneumonia diagnosis in critically ill patients. The training program's design, implementation, and evaluation are described. The high inter-observer agreement between LUS reports from the physicians trained and expert radiologists encourage the use of LUS not only for pneumonia diagnosis, but also for discerning bacterial and viral patterns.

Bronchiolitis, epidemiological changes during the SARS-CoV-2 pandemic.

BACKGROUND: Bronchiolitis is the most common viral infection of the lower respiratory tract in infants under 2 years of age. The aim of this study was to analyze and compare the seasonal bronchiolitis peaks before and during the SARS-CoV-2 pandemic. METHODS: Descriptive, prospective, and observational study. Patients with severe bronchiolitis admitted to the Pediatric Intensive Care Unit (PICU) of a referral tertiary hospital between September 2010 and June 2021 were included. Demographic data were collected. Viral laboratory-confirmation was carried out. Each season was analyzed and compared. The daily average temperature was collected. RESULTS: 1116 patients were recruited, 58.2% of them males. The median age was 49 days. Respiratory syncytial virus (RSV) was isolated in 782 cases (70.1%). In April 2021, the first and only case of bronchiolitis caused by SARS-CoV-2 was identified. The pre- and post-pandemic periods were compared. There were statistically significant differences regarding: age, 47 vs. 73 days (p = 0.006), PICU and hospital length of stay (p = 0.024 and p = 0.001, respectively), and etiology (p = 0.031). The peak for bronchiolitis in 2020 was non-existent before week 52. A delayed peak was seen around week 26/2021. The mean temperature during the epidemic peak was 10ºC for the years of the last decade and is 23ºC for the present season. CONCLUSION: The COVID-19 pandemic outbreak has led to a clearly observable epidemiological change regarding acute bronchiolitis, which should be studied in detail. The influence of the environmental temperature does not seem to determine the viral circulation.

Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU: a multicenter observational retrospective study.

BACKGROUND: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. METHODS: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. RESULTS: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. CONCLUSION: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy.

Mid-regional pro-adrenomedullin for diagnosing evolution after cardiac surgery in newborns: the PRONEW study.

Newborns are the most vulnerable patients after cardiac surgery. Although mortality risk scores before surgery may help predict the risk of poor outcome, new tools are required, and biomarkers could add objective data to these tools. The aim of this study was to assess the ability of mid-regional pro-adrenomedullin (pro-ADM) and pro-atrial natriuretic peptide (pro-ANP) to predict poor outcome after cardiac surgery. This is a pilot diagnostic accuracy study that includes newborns and infants under 2 months admitted to an intensive care unit after cardiac surgery. Pro-ADM and pro-ANP were determined immediately upon admission. Poor outcome was defined as mortality, cardiac arrest, requiring extracorporeal support, requiring renal replacement therapy, or neurological injury. Forty-four patients were included. Twenty-six (59%) had a STAT category of ≥ 4. Ten patients (22.7%) presented a poor outcome, four of whom (9.1%) died. Pro-ADM was higher in patients with poor outcome (p = 0.024) and death (p = 0.012). Pro-ADM showed the best area under curve (AUC) for predicting poor outcome (0.735) and mortality alone (0.869). A pro-ADM of 2 nmol/L had a Sn of 75% and a Sp of 85% for predicting mortality. Pro-ADM > 2 nmol/L was independently associated with poor outcome (OR 5.8) and mortality (OR 14.1). Although higher pro-ANP values were associated with poor outcomes, no cut-off point were found. The combination of STAT ≥ 4 and the biomarkers did not enhance predictive power for poor outcome or mortality.Conclusion: Pro-ADM and pro-ANP determined immediately after surgery could be helpful for stratifying risk of poor outcome and mortality in newborns. What is Known: • Some congenital heart diseases must be corrected/palliated during the first days of life. A useful tool to predict the risk of severe complications has not been proposed. • Most unstable newborns would have higher values of biomarkers such as pro-ADM and pro-ANP related to shock and compensatory actions. What is New: • Pro-ADM and pro-ANP seem to be good biomarkers to predict poor outcome after cardiac surgery. A pro-ADM < 2 nmol/L would imply a low likelihood of a poor outcome. • Deepening the analysis of biomarkers can help in making decisions to prevent/treat complications.

Risk factors and incidence of invasive bacterial infection in severe bronchiolitis: the RICOIB prospective study.

BACKGROUND: Bacterial infection (BI), both community-acquired (CA-BI) and hospital-acquired (HAI), might present as a severe complication in patients with bronchiolitis. This study aimed to describe BI in children with severe bronchiolitis, and to define risk factors for BI. METHODS: This was a prospective, descriptive study that included infants admitted to the pediatric intensive care unit (PICU) due to bronchiolitis between 2011 and 2017. The BROSJOD score was calculated to rate the severity of bronchiolitis. RESULTS: Inclusion of 675 patients, with a median age of 47 days (IQR 25-99). 175 (25.9%) patients developed BI, considered HAI in 36 (20.6%). Patients with BI had higher BROSJOD score, PRISM III, and required invasive mechanical ventilation and inotropic support more frequently (p < 0.001). BI was independently associated with BROSJOD higher than 12 (OR 2.092, 95%CI 1.168-3.748) CA-BI was associated to BROSJOD > 12 (OR 2.435, 95%CI 1.379-4.297) and bacterial co-infection (OR 2.294 95%CI 1.051-5.008). Concerning HAI, an independent association was shown with mechanical ventilation longer than 7 days (OR 5.139 95%CI 1.802-14.652). Infants with BI had longer PICU and hospital stay (p < 0.001), Mortality was higher in patients with HAI. CONCLUSIONS: A quarter of infants with severe bronchiolitis developed BI. A BROSJOD > 12 may alert the presence of CA-BI, especially pneumonia. Patients with BI have higher morbidity and mortality.

New multivariable prediction model PEdiatric SEpsis recognition and stratification (PESERS score) shows excellent discriminatory capacity.

AIM: To develop a quantitative predictive scoring model for the early recognition and assessment of paediatric sepsis. METHODS: Prospective observational study including emergency department and in-hospital febrile patients under 18 years. Sepsis diagnose (Goldstein 2005 definitions) was the main outcome. Variables associated with the outcome were included in a multivariable analysis. Cut-off points, odds ratio and coefficients for the variables kept after the multivariable analysis were identified. The score was obtained from the coefficients, The AUC was obtained from ROC-analysis, and internal validation was performed using k-fold cross-validation. RESULTS: The analysis included 210 patients. 45 variables were evaluated and the bivariate analysis identified 24 variables associated with the outcome. After the multivariable regression, 11 variables were kept and the score was obtained. The model yielded an excellent AUC of 0.886 (95% CI 0.845-0.927), p < 0.001 for sepsis recognition. With a cut-off value of 5 for the score, we obtained a sensitivity of 98%, specificity of 76.7%, positive predictive value of 87.9% and negative predictive value of 93.3%. CONCLUSION: The proposed scoring model for paediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which is of great clinical significance in detecting sepsis early and predicting its severity. Nevertheless external validation is needed before clinical use.

Ethical questions concerning newborn genetic screening.

Newborn screening is a public health strategy used to identify certain diseases in the first days of life and, therefore, facilitate early treatment before the onset of symptoms. The decision of which diseases should be included in a screening goes beyond the medical perspective, including reasons for public health and health economics. There are a number of characteristics to include a disease in the screening, such as that the disorder must be a significant health problem, the natural history of the disease must be well known, a feasible and accurate test must be available, there must be a treatment that is most effective when applied before the onset of clinical symptoms and a health system must be in place that is capable of performing the procedure and subsequent monitoring. Currently, newborn screening programs are currently based on the use of biochemical markers that detect metabolites, hormones or proteins, but recently, the availability of new technology has allowed the possibility of a genetic screening. In addition to technical problems, the possibility of neonatal screening also presents a number of ethical problems. We identified and discussed six areas of particular concern: type of illness, overdiagnosis or overtreatment, information management and informed consent, data confidentiality and protection, justice and legal regulation.

The different manifestations of COVID-19 in adults and children: a cohort study in an intensive care unit.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children. METHODS: This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March-June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes. RESULTS: Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3-41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5-14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5-30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively). CONCLUSIONS: Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.

Use of procalcitonin and C-reactive protein in the diagnosis of bacterial infection in infants with severe bronchiolitis.

The objective was to evaluate the use of procalcitonin (PCT) and C-reactive protein (CRP) for the diagnosis of bacterial infection in bronchiolitis patients. A prospective, single-centre, descriptive, and comparative observational study was carried out on patients with severe bronchiolitis admitted to the paediatric intensive care unit (PICU), from January 2011 to July 2017. Two cohorts were compared: patients with invasive bacterial infection (IBI) and patients with no bacterial infection (NBI). We included 675 patients, 399 of whom were males (59.1%), with median age of 47 days (IQR 25-100.3). Of them, 181 patients were diagnosed with IBI (26.8%). Seventy-two had sepsis (10.7%), 106 had pneumonia (15.7%), and 41 had a urinary tract infection (6.1%). PCT and CRP values were significantly higher in patients with IBI. ROC curves compared the ability of PCT and CRP to diagnose IBI at admission, 24 h, and 48 h. PCT showed a better AUC for diagnosing IBI, with statistically significant differences at all time points (p < 0.001). The best PCT cut-off for IBI diagnosis at admission was 1.4 ng/mL, with a sensitivity of 69% (95% CI 58.4-74.9) and a specificity of 91% (95% CI 88.1-92.5). Procalcitonin showed a better AUC for diagnosing both sepsis and pneumonia, which makes it an excellent predictor.Conclusion: We present PCT as a novel test in comparison with the traditional CRP screening test to discern which bronchiolitis patients have IBI. We highlight the importance of PCT for the diagnosis of pneumonia and sepsis, as it proved to be more sensitive and specific than CRP, with statistically significant differences. What is Known: • Bronchiolitis should be treated with antibiotics only when a bacterial infection is present. • The rate of antibiotic prescription in severe bronchiolitis is extremely high, so diagnostic tools are needed. What is New: • PCT is a good biomarker to discern which bronchiolitis patients have IBI, specially for pneumonia and sepsis diagnoses. It is more sensitive and specific than CRP, with statistically significant differences. • Implementation of PCT cut-off values may prevent unnecessary antibiotic use.

Lung ultrasound findings in pediatric patients with COVID-19.

During the pandemic caused by the novel coronavirus (COVID-19), lung ultrasound has been used to diagnose and monitor respiratory condition. The aim of the study was to describe lung ultrasound findings in children with a COVID-19 infection. Patients younger than 18 years old and positive for COVID-19, admitted to pediatric tertiary referral hospital were included. They were divided into two groups depending on the presence of respiratory symptoms. Lung ultrasound results were categorized into four degrees according to Soldati et al. score (J Ultrasound Med 39:1-7, 2020) and it was also described the presence and type of consolidation. Sixteen patients were recruited. The median age was 11 years old (IQR 2.8-12). Four children (25%) required admission to the intensive care unit. Six patients (37.5%) presented with respiratory symptoms. Most of them showed S.score of 2 and subpleural consolidations were observed in four cases (66.6%). Ten patients (62.5%) presented with non-respiratory symptoms, lung ultrasound showed S.score from 0 to 2. Three (30%) were diagnosed of multisystem inflammatory syndrome and lung ultrasounds showed S.score of 2 with bilateral pleural effusion.Conclusions: Children with COVID-19 and respiratory symptoms mostly showed a S.score of 2 and 3 with subpleural consolidations, upon the lung ultrasound assessment. What is Known: • Lung ultrasound is a useful tool for monitoring patients with respiratory symptoms in both adults and children. Lung ultrasounds are altered in adult patients with COVID-19. What is New: • Lung ultrasound might improve COVID-19 assessment, it could be a useful tool to diagnose and monitor patients throughout the COVID-19 pandemic. Even COVID-19 patients with non-respiratory symptoms have lung alterations that are visible on lung ultrasound.

Weaning from neonatal and pediatric ECMO with stand-by cannula.

The precise moment for weaning a patient off extracorporeal membrane oxygenation (ECMO) is not always easy to establish. Also, mechanical causes may obligate to disconnect the patient from the circuit before the optimal weaning off. In these selected cases, the patient can be disconnected from the circuit and the cannula can be left in place (stand-by cannula) until the patient's stability without ECMO is assured. The aim was to describe our experience with the stand-by cannula. Single-institution, long-term retrospective study in a pediatric tertiary care hospital. Neonatal and pediatric patients who were under ECMO and needed stand-by cannula before definitive de-cannulation were included. During 18 years, 166 children required ECMO. In 31 patients (18.7%), stand-by cannula was performed before the weaning off. Twenty patients (64.5%) were newborn. The main reason for requiring ECMO in these newborn was persistent pulmonary hypertension. Eleven patients were pediatric and their main cause for requiring ECMO was cardiogenic shock (six patients, 54.4%). The reasons for requiring stand-by cannula were the uncertainty of a successful weaning off in 17 patients (54.8%), to undergo surgery in 10 patients (32.3%) and to replace the circuit in four cases (12.9%). The median duration of stand-by cannula was 12 h (IQR 6-24). Heparinized saline serum was the main maintenance perfusion (28 patients, 90.3%). Three patients needed to restart support with ECMO. Only one mechanical complication was detected. Stand-by cannula is a safe technique, which allows performing a quick re-entrance on ECMO if the weaning off fails.

Diagnostic and prognostic value of procalcitonin and mid-regional pro-adrenomedullin in septic paediatric patients.

Early diagnosis of sepsis and its severity stratification at admission is critical to improve patient outcomes and to ensure the optimal use of health care resources. In order to assess the diagnostic potential of mid-regional pro-adrenomedullin (MR-proADM) in septic paediatric patients in comparison with procalcitonin (PCT), and to evaluate the usefulness of a single early determination of MR-proADM as a stratification and severity prediction tool, a prospective observational study was conducted. Seventy-three paediatric patients with a suspicion of sepsis were included. A single blood test was carried out at initial time to analyse infection biomarkers. PCT values were significantly higher in septic patients in comparison with non-septic patients (p = 0.03) with an AUC of 0.748 (p = 0.003). Levels of MR-proADM significantly increased in patients with severe sepsis (p = 0.048), with an AUC of 0.729 (p = 0.013). MR-proADM showed a positive correlation with pSOFA, PRISM III, and PELOD-2 severity scores. Levels of MR-proADM were significantly higher in patients who required vasoactive drugs (p = 0.02) or presented renal dysfunction (p = 0.004).Conclusion: PCT appeared to be superior to MR-proADM in diagnosing sepsis. Determining MR-proADM plasma levels at the initial phase of sepsis could be a useful tool for sepsis stratification and morbidity prediction before organ failure occurs. The present results need to be assessed with larger sample size studies.What is Known:•CRP and PCT are already included in clinical practice to assess sepsis and estimate disease severity, although their sensitivity and specificity are lower than desired.•ADM is a protein that has immune and vascular modulation actions, and its blood levels are increased in adult and paediatric sepsis.•ADM is a promising tool for early diagnosis and prognostic assessment in adult sepsis.What is New:•PCT appeared to be superior to MR-proADM in diagnosing paediatric sepsis.•MR-proADM plasma levels could be a useful tool for paediatric sepsis stratification and morbidity prediction.

Procalcitonin-guided protocol decreased the antibiotic use in paediatric patients with severe bronchiolitis.

AIM: Our aim was to determine the effectiveness and safety of a procalcitonin-guided protocol to decrease antibiotic use in infants with severe bronchiolitis. METHODS: This prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin-guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010-2014 and 366 in 2015-2017. RESULTS: We recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0-100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol. CONCLUSION: The implementation of a procalcitonin-guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.

End-of-life care in a pediatric intensive care unit: the impact of the development of a palliative care unit.

BACKGROUND: The purpose of this paper is to describe how end-of-life care is managed when life-support limitation is decided in a Pediatric Intensive Care Unit and to analyze the influence of the further development of the Palliative Care Unit. METHODS: A 15-year retrospective study of children who died after life-support limitation was initiated in a pediatric intensive care unit. Patients were divided into two groups, pre- and post-palliative care unit development. Epidemiological and clinical data, the decision-making process, and the approach were analyzed. Data was obtained from patient medical records. RESULTS: One hundred seventy-five patients were included. The main reason for admission was respiratory failure (86/175). A previous pathology was present in 152 patients (61/152 were neurological issues). The medical team and family participated together in the decision-making in 145 cases (82.8%). The family made the request in 10 cases (9 vs. 1, p = 0.019). Withdrawal was the main life-support limitation (113/175), followed by withholding life-sustaining treatments (37/175). Withdrawal was more frequent in the post-palliative group (57.4% vs. 74.3%, p = 0.031). In absolute numbers, respiratory support was the main type of support withdrawn. CONCLUSIONS: The main cause of life-support limitation was the unfavourable evolution of the underlying pathology. Families were involved in the decision-making process in a high percentage of the cases. The development of the Palliative Care Unit changed life-support limitation in our unit, with differences detected in the type of patient and in the strategy used. Increased confidence among intensivists when providing end-of-life care, and the availability of a Palliative Care Unit may contribute to improvements in the quality of end-of-life care.

Venoarterial extracorporeal membrane oxygenation support for neonatal and pediatric refractory septic shock: more than 15 years of learning.

The objective of the study was to report our institutional experience in the management of children and newborns with refractory septic shock who required venoarterial extracorporeal membrane oxygenation (VA ECMO) treatment, and to identify patient-and infection-related factors associated with mortality. This is a retrospective case series in an intensive care unit of a tertiary pediatric center. Inclusion criteria were patients ≤ 18 years old who underwent a VA ECMO due to a refractory septic shock due to circulatory collapse. Patient conditions and support immediately before ECMO, analytical and hemodynamic parameter evolution during ECMO, and post-canulation outcome data were collected. Twenty-one patients were included, 13 of them (65%) male. Nine were pediatric and 12 were newborns. Median septic shock duration prior to ECMO was 29.5 h (IQR, 20-46). Eleven patients (52.4%) suffered cardiac arrest (CA). Neonatal patients had worse Sepsis Organ Failure Assessment (SOFA) score, Oxygenation Index and PaO2/FiO2 ratio, blood gas analysis, lactate levels, and left ventricular ejection fraction compared to pediatric patients. Survival was 33.3% among pediatric patients (60% if we exclude pneumococcal cases) and 50% among newborns. Hours of sepsis evolution and mean airway pressure (MAP) prior to ECMO were significantly higher in the non-survivor group. CA was not a predictor of mortality. Streptococcus pneumoniae infection was a mortality risk factor. There was an improvement in survival during the second period, from 14.3 to 57.2%, related to shorter sepsis evolution before ECMO placement, better candidate selection, and greater ECMO support once the patient was placed. CONCLUSION: Patients with refractory septic shock should be transferred precociously to a referral ECMO center. However, therapy should be used with caution in patients with vasoplegic pattern shock or S. pneumoniae sepsis. What is Known: • Children with refractory septic shock have significant mortality rates, and although ECMO is recommended, overall survival is low. • There are no studies regarding characteristics of infections as predictors of pediatric survival in ECMO. What is New: • Septic children should be transferred precociously to referral ECMO centers during the first hours if patients do not respond to conventional therapy. • Treatment should be used with caution in patients with vasoplegic pattern shock or S. pneumoniae sepsis.

Clinical, biochemical and microbiological factors associated with the prognosis of pneumococcal meningitis in children.

BACKGROUND: Pneumococcal meningitis (PM) has a high morbidity and mortality. The aim of the study was to evaluate what factors are related to a poor PM prognosis. METHODS: Prospective observational study conducted on patients admitted to the Pediatric Intensive Care Unit in a tertiary hospital with a diagnosis of PM (January 2000 to December 2013). Clinical, biochemical and microbiological data were recorded. Variable outcome was classified into good or poor (neurological handicap or death). A multivariate logistic regression was performed based on the univariate analysis of significant data. RESULTS: A total of 88 patients were included. Clinical variables statistically significant for a poor outcome were younger age (p=.008), lengthy fever (p=.016), sepsis (p=.010), lower Glasgow Score (p<.001), higher score on Pediatric Risk Mortality Score (p=0.010) and Sequential Organ Failure Assessment (SOFA) (p<.001), longer mechanical ventilation (p=.004), and inotropic support (p=.008) requirements. Statistically significant biochemical variables were higher level of C-reactive protein (p<.001) and procalcitonin (p=.014) at admission, low cerebrospinal (CSF) pleocytosis (p=.003), higher level of protein in CSF (p=.031), and severe hypoglycorrhachia (p=.002). In multivariate analysis, independent indicators of poor outcome were age less than 2 years (p=.011), high score on SOFA (p=.030), low Glasgow Score (p=.042), and severe hypoglycorrhachia (p=.009). CONCLUSIONS: Patients younger than 2 years of age, with depressed consciousness at admission, especially when longer mechanical ventilation is required, are at high risk of a poor outcome.

Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial.

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. CLINICAL TRIAL REGISTRATION: NCT04217980.

The reuse of genetic information in research and informed consent.

Important advances in genetics research have been made in recent years. Such advances have facilitated the availability of huge amounts of genetic information that could potentially be reused beyond the original purpose for which such information was obtained. Any such reuse must meet certain ethical criteria to ensure that the dignity, integrity, and autonomy of the individual from whom that information was obtained are protected. The aim of this paper is to reflect on these criteria through a critical analysis of the literature. To guarantee these values, ethical criteria need to be established in several respects. For instance, the question must be posed whether the information requires special attention and protection (so-called genetic exceptionalism). Another aspect to bear in mind is the most appropriate type of consent to be given by the person involved, on the one hand favouring research and the reuse of genetic information while on the other protecting the autonomy of that person. Finally, there is a need to determine what protection such reuse should have in order to avoid detrimental consequences and protect the rights of the individual. The main conclusions are that genetic information requires special care and protection (genetic exceptionalism) and that broad consent is the most practical and trustworthy type of consent for the reuse of genetic information.