Pro-atrial natriuretic peptide and proadrenomedullin before cardiac surgery in children. Can we predict the future?

Introduction and objective: Pro-atrial natriuretic peptide (proANP) and pro-adrenomedullin (proADM) levels increase in acute heart failure and sepsis. After cardiac surgery, children may require increased support in the intensive care unit and may develop complications. The aim of this study was to evaluate the utility of proANP and proADM values, determined prior to cardiac surgery, for predicting the need for increased respiratory or inotropic support during the post-operative period. Methods: This was a prospective study in children. Biomarkers were analyzed before surgery using a single blood test. The primary endpoints were the need for greater respiratory and/or inotropic support during the post-operative period. Secondary endpoints were the relationship between these biomarkers and complications after surgery. Results: One hundred thirteen patients were included. ProANP and proADM were higher in children who required greater respiratory and inotropic support, especially proANP; for increased respiratory support, 578.9 vs. 106.6 pmol/L (p = 0.004), and for increased inotropic support, 1938 vs. 110.4 pmol/L (p = 0.002). ProANP had a greater AUC than proADM for predicting increased respiratory support after surgery: 0.791 vs. 0.724. A possible cut-off point for proANP could be ≥ 325 pmol/L (sensitivity = 66.7% and specificity = 88.8%). In the multivariate analysis, the logarithmic transformation of proANP was independently associated with the need for increased respiratory support (OR = 3.575). Patients who presented a poor outcome after cardiac surgery also had higher biomarker values (proADM, p = 0.013; proANP, p = 0.001). Conclusions: Elevated proANP before cardiac surgery may identify which children will need more respiratory and inotropic support during the post-operative period

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 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 12 may alert the presence of CA-BI, especially pneumonia. Patients with BI have higher morbidity and mortality

Prognostic value of biomarkers after cardiopulmonary bypass in pediatrics: The prospective PANCAP study

Objective:To assess the usefulness of procalcitonin, pro-adrenomedullin and pro-atrial natriuretic peptide as predictors of need for mechanical ventilation and postoperative complications (need for inotropic support and bacterial infection) in critically ill pediatric patients after cardiopulmonary bypass. Design:A prospective, observational study Setting: Pediatric intensive care unit. Patients: Patients under 18 years old admitted after cardiopulmonary bypass. Measuraments and main results: Serum levels of procalcitonin, pro-adrenomedullin and pro-atrial natriuretic peptide were determined immediately after bypass and at 24-36 hours. Their values were correlated with the need for mechanical ventilation, inotropic support and bacterial infection. One hundred eleven patients were recruited. Septal defects (30.6%) and cardiac valve disease (17.1%) were the most frequent pathologies. 40.7% required mechanical ventilation, 94.6% inotropic support and 15.3% presented invasive bacterial infections. Pro-adrenomedullin and pro-atrial natriuretic peptide showed significant high values in patients needing mechanical ventilation. Cut-off values higher than 1.22 nmol/L and 215.3 pmol/L, respectively for each biomarker, may indicate need for mechanical ventilation with an AUC of 0.721 and 0.746 at admission and 0.738 and 0.753 at 24-36 hours, respectively but without statistical differences. Pro-adrenomedullin and procalcitonin showed statistically significant high values in patients with bacterial infections. Conclusions: After bypass, pro-adrenomedullin and pro-atrial natriuretic peptide are suitable biomarkers to predict the need for mechanical ventilation. Physicians should be alert if the values of these markers are high so as not to progress to early extubation. Procalcitonin is useful for predicting bacterial infection. This is a preliminary study and more clinical studies should be done to confirm the value of pro-adrenomedullin and pro-atrial natriuretic peptide as biomarkers after cardiopulmonary bypass

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 limitationis 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 lifesustaining 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

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

Procalcitonin to stop antibiotics after cardiovascular surgery in a pediatric intensive care unit-The PROSACAB study.

Introduction and objective: Children admitted to the pediatric intensive care unit after cardiovascular surgery usually require treatment with antibiotics due to suspicion of infection. The aim of this study was to assess the effectiveness of procalcitonin in decreasing the duration of antibiotic treatment in children after cardiovascular surgery. Methods: Prospective, interventional study carried out in a pediatric intensive care unit. Included patients under 18 years old admitted after cardiopulmonary bypass. Two groups were compared, depending on the implementation of the PCT-guided protocol to stop or de-escalate the antibiotic treatment (Group 1, 2011-2013 and group 2, 2014-2018). This new protocol was based on the decrease of the PCT value by 20% or 50% with respect to the maximum value of PCT. Primary endpoints were mortality, stewardship indication, duration of antibiotic treatment, and antibiotic-free days. Results: 886 patients were recruited. There were 226 suspicions of infection (25.5%), and they were confirmed in 38 cases (16.8%). The global rate of infections was 4.3%. 102 patients received broad-spectrum antibiotic (4.7±1.7 days in group 1, 3.9±1 days in group 2 with p = 0.160). The rate of de-escalation was higher in group 2 (30/62, 48.4%) than in group 1 (24/92, 26.1%) with p = 0.004. A reduction of 1.1 days of antibiotic treatment (group 1, 7.7±2.2 and group 2, 6.7±2.2, with p = 0.005) and 2 more antibiotic free-days free in PICU in group 2 were observed (p = 0.001), without adverse outcomes. Conclusions: Procalcitonin-guided protocol for stewardship after cardiac surgery seems to be safe and useful to decrease the antibiotic exposure. This protocol could help to reduce the duration of broad-spectrum antibiotics and the duration of antibiotics in total, without developing complications or adverse effects

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. Methods The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). Results 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). Conclusions The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually

Disseny i validació d’una eina pel reconeixement i estratificació precoç de la sèpsia i xoc sèptic en pediatria

[cat] La sèpsia és encara freqüent i difícil de detectar a l’inici d’un síndrome febril. Per tant cal seguir endavant amb la recerca en sistemes de detecció, diagnòstic i pronòstic. Des de la implementació de l’eina de cribratge actual, el Codi Sèpsia, s’ha incrementat la consciència de la sèpsia entre el personal sanitari amb el conseqüent augment de detecció i inici precoç del tractament. Tot i així, la quantificació i ponderació de les variables que inclou, fa aquest codi més objectiu i facilita també la seva adhesió com a eina automàtica en el sistema sanitari informatitzat. Un cop feta la validació externa, aquest model predictiu es proposarà com a nova eina de cribratge. Davant un pacient febril amb un cribratge positiu per sèpsia, s’ha d’ampliar l’estudi per poder confirmar el diagnòstic i estratificar la gravetat. Durant les últimes dècades, s’han identificat una gran varietat de biomarcadors en sèpsia i infecció bacteriana. Alguns d’ells, com el percentatge de neutròfils immadurs i la proteïna C reactiva, relacionats amb inflamació, la procalcitonina, relacionada amb inflamació durant infecció bacteriana o el lactat com a marcador d’estrés oxidatiu, han estat ben estudiats i se’n coneixen els avantatges i limitacions. L’adrenomedulina, és un biomarcador més recent amb efecte vasodilatador, metabòlic i immune, i s’han relacionat principalment amb el pronòstic de pacients adults sèptics. En pediatria, la seva elevació sembla estar relacionada amb el pronòstic dels pacients sèptics, més que amb el diagnòstic. La sèpsia és una síndrome sense una prova de diagnòstic estàndard validada, i la seva identificació recau en els criteris diagnòstics de les diferents definicions que han anat apareixent al llarg dels anys i que recullen característiques que poden ser identificades i mesurades en pacients. L’última actualització de les definicions i criteris diagnòstics en pediatria va ser l’any 2005 a la Conferència Internacional de Consens sobre la Sèpsia Pediàtrica. Aquets estan basats en els criteris de resposta inflamatòria sistèmica i no inclouen biomarcadors analítics. Per altre banda, el pronòstic de la sèpsia, i del pacient crític pediàtric en general, ha estat clàssicament assessorat per escores o escales de gravetat. Les més conegudes i utilitzades son el PRISM III, PELOD-2 i recentment el pSOFA. Aquestes escales de puntuació són adaptacions de models per pacients adults, prediuen la mortalitat però no altres tipus de morbiditats, utilitzen dades de les primeres 24 hores d’ingrés que indiquen fallida orgànica, i estan dissenyades per avaluar poblacions i no pacients individuals. Per afrontar el repte del diagnòstic de sèpsia i la seva estratificació o predicció del pronòstic precoç, és necessari l’anàlisi de la combinació ideal de constants vitals, signes clínics i biomarcadors en sang tant aviat com es sospiti la sèpsia. A la tesi es proposa l’escala de puntuació PESERS (PEdiatric SEpsis Recognition and Stratification score) per assolir aquest objectiu. De la mateixa manera que és difícil predir l’evolució a sèpsia d’un pacient febril en un primer moment, també és difícil, una vegada arribat al punt de la fallida multiorgànica, identificar els pacients amb capacitat de revertir la situació amb tècniques de suport “convencional” d’aquells que requeriran tècniques més invasives com l’oxigenació per membrada extracorpòria. Durant els últims anys la supervivència dels pacients sèptics pediàtrics sotmesos a ECMO ha augmentat. En el nostre centre aquesta millora s’ha relacionat amb una evolució més curta de la sèpsia abans d’iniciar la ECMO i el major suport un cop iniciada aquesta teràpia.[eng] Since the implementation of the current screening tool, the Sepsis Code, awareness of sepsis has increased among healthcare personnel, and detection and early initiation of treatment have increased. Nevertheless, the quantification of the variables’ weights makes this code more objective and also facilitates its use as an automatic tool in the computerized healthcare system. During the last decades, a wide variety of biomarkers have been identified in sepsis and bacterial infection. Adrenomedullin is a recent biomarker with a vasodilator, metabolic and immune effect, and has been mainly related to the prognosis of septic adult patients. In paediatrics, its elevation seems to be related to the prognosis of septic patients, rather than to the diagnosis. Sepsis is a syndrome without a validated standard diagnostic test, and its identification lays on the diagnostic criteria of the different definitions that have appeared over the years. The last update of the definitions and diagnostic criteria in paediatrics was in 2005, and do not include analytical biomarkers. On the other hand, the prognosis of sepsis has classically been assessed by scores or severity scales such as PRISM III, PELOD-2 or pSOFA. These scoring scales are adaptations of models for adult patients, predict mortality but not other types of morbidities, and are designed to evaluate populations and not individual patients. To face the challenge of sepsis diagnosis and its early stratification, it is necessary to analyze the ideal combination of vital signs, clinical signs and blood biomarkers as soon as sepsis is suspected. PESERS score scale (PEdiatric SEpsis Recognition and Stratification score) is proposed in this thesis to achieve this goal. It is also difficult, once the point of multi-organ failure has been reached, to identify patients with the ability to reverse the situation with “conventional” supportive techniques of those which will require more invasive techniques such as extracorporeal membrane oxygenation. Over the last few years the survival of pediatric septic patients undergoing ECMO has increased. In our centre this improvement has been related to a shorter evolution of sepsis before starting ECMO and greater support once this therapy has started

A Review of Adrenomedullin in Pediatric Patients: A Useful Biomarker

Adrenomedullin has several properties. It acts as a potent vasodilator, has natriuretic effects, and reduces endothelial permeability. It also plays a role in initiating the early hyperdynamic phase of sepsis. Since its discovery, many articles have been published studying the uses and benefits of this biomarker. The aim of this review is to determine the usefulness of adrenomedullin in pediatric patients. Relevant studies covering adrenomedullin in pediatrics (&lt;18 years) and published up until August 2021 were identified through a search of MEDLINE, PubMed, Embase, Web of Science, Scopus, and Cochrane. Seventy studies were included in the present review, most of them with a low level of evidence (IV to VI). Research on adrenomedullin has primarily been related to infection and the cardiovascular field. The performance of adrenomedullin to quantify infection in children seems satisfactory, especially in sepsis. In congenital heart disease, this biomarker seems to be a useful indicator before, during, and after cardiopulmonary bypass. Adrenomedullin seems to be useful in the pediatric population for a large variety of pathologies, especially regarding infection and cardiovascular conditions. However, it should be used in combination with other biomarkers and clinical or analytical variables, rather than as a single tool