Modulació de la resposta inflamatòria sistèmica en nens críticament malalts després de la suplementació parenteral amb glutamina

En condicions d’estrès pot existir un dèficit relatiu de glutamina (Gln). Aquesta actua com a font energètica i en la protecció cel·lular, activant l’expressió de les “Heat Shock Proteins” (HSP). Disminucions en la seva concentració mitja provoquen una alteració en la regulació inflamatòria. La seva suplementació estimula mecanismes de mort bacteriana i disminueix l’explosió citotòxica. OBJECTIUS: Determinar la resposta inflamatòria en els pacients pediàtrics suplementats amb Gln parenteral respecte els que reben nutrició estàndard. Valorar la morbi-mortalitat. METODOLOGIA: Estudi prospectiu, a doble cec i aleatoritzat amb blocs balancejats. Es van recollir mostres analítiques i dades de la història clínica dels pacients ingressats en la Unitat de Cures Intensives Pediàtriques (UCIP) de l’Hospital Sant Joan de Déu de Barcelona. Criteris d’inclusió: pacients (1 mes – 14 anys), que van requerir nutrició parenteral (NPT), afectes d’infeccions sistèmiques o focals greus, i post operats cirurgia major abdominal. Criteris d’exclusió: pacients amb patologia prèvia de base i derivats d’altres centres amb evolució clínica de més de 48 h. Aleatorització en dos grups: Grup 1 o grup experimental al que es va administrar una solució d’aminoàcids (Aminopaed® o Vamin®) i es va suplementar amb Gln (Dipeptiven®), anomenat NPS + Gln. Grup 2 o grup control al que es va administrar una solució d’aminoàcids(Aminopaed® o Vamin®) no suplementada, anomenat NPS. Es van recollir 73 pacients en cada grup. Les variables a estudi van ser: edat; sexe; Pediatric Risk Score of Mortality II (PRISM-II) a l’ingrés; malaltia actual; nivells de limfòcits CD4, CD8 i CD4/CD8; valors d’interleuquines (IL) IL-6, IL-10 i de HSP-70 a les 0 hores (h) a les 48h al cinquè dia; i presència de sobre infecció, fallida multi orgànica i mortalitat. RESULTATS: Els nivells de Gln no van mostrar diferències entre els grups. El dia 5, els pacients del grup experimental presentaren nivells d’HSP-70 significativament superiors que el grup control (68,6 vs 5,4, p = 0,014). En tots dos grups, els nivells d’IL-6 van tenir un descens significatiu des de el dia 0 al dia (NPS: 42,24 vs 9,39, p < 0,001; NPS + Gln: 35,20 vs 13,80, p<0,001), però tan sols en el grup experimental va existir un descens significatiu entre el dia 2 i el dia 5 (13,80 vs 10,55, p = 0,013). Els nivells d’IL-10 no van variar durant les visites excepte en el grup control entre el dia 0 i el dia 2 (9,55 vs 5,356, p < 0,001). Al final de l’estudi no s’observaren diferències significatives entre els grups referent a l’estància en UCIP o a l’estància hospitalària, tot i que va haver una menor estada a intensius en els pacients suplementats amb Gln. No es van detectar efectes adversos en cap grup. CONCLUSIONS: La suplementació amb Gln en pacients crítics contribueix al manteniment de majors nivells d’HSP-70, durant més temps. Aquesta suplementació no influeix en els nivells d’IL-10 i no mostra disminució significativa dels nivells d’IL-6. La Gln podria disminuir la estada en la UCIP.[eng] In a stress situation, there is a Glutamine (Gln) deficit owing to an increase in its consumption as much as a decrease of its availability. This amino acid acts as a source of energy and also intervenes in the cellular and tissue protection activating the Heat Shock Proteins (HSP) expression. The Gln average concentration value is associated with a fall in immune response. It has been also proved that, if a supplement of Gln is added, it stimulates the mechanisms of bacteria death and diminishes the cytotoxic response. OBJECTIVES: To determine if there exist differences in the inflammatory response in seriously ill patients who received Gln supplemented nutrition with regard to those who received standard nutrition. To evaluate the patient clinical response and mortality. METHODOLOGY: It was a prospective, interventional, double blind, randomized and stratified clinical trial. Collection of samples and data for patients admitted at the Pediatric Intensive Care Unit (PICU) of the “Sant Joan de Déu” Hospital in Barcelona. Inclusion criteria: Patients (1 month to 14 years) who require parenteral nutrition, with one of the following diagnosis: Systemic or local infection and Major abdominal surgery. Exclusion criteria: patient with prior illnesses and patients coming from other centers with more than 48 hours clinical evolution. Sample selection: Group 1: Standard total parenteral nutrition (NPS) (Aminopaed® o Vamin®) and Gln perfusion (Dipeptiven®), denominated NPS + Gln. Group 2: Standard total parenteral nutrition (Aminopaed® o Vamin®) without Gln, denominated NPS. It will be necessary to include 73 experimental units in the reference group and 73 units in the experimental group. Variables: Age; sex; Pediatric Risk Score of Mortality (PRISM-II) score at admission; illness cause for the admission; CD4, CD8 i CD4/CD8 lymphocyte levels; determination at 0 hours (h), 48 h and 5th day of Interleukins(IL), IL-6, IL-10 and HSP-70; and infection complication, multiorganic failure and death. RESULTS: Gln levels failed to show statistical differences between groups. At day 5, patients in the experimental group had significantly higher levels of HSP-70 as compared with the control group (68.6 vs 5.4, p = 0.014). In both groups, IL-6 levels showed a remarkable descent from baseline and day 2 (SPN: 42.24 vs 9.39, p < 0.001; SPN + Gln: 35.20 vs 13.80, p<0.001) but only the treatment group showed a statistically significant decrease between day 2 and day 5 (13.80 vs 10.55, p = 0.013). Levels of IL-10 did not vary among visits except in the SPN between baseline and day 2 (9.55 vs 5.356, p < 0.001). At the end of the study, no significant differences between groups for PICU and hospital stay were observed. Although there was a shorter stay in the supplemented patients. No adverse events were detected in any group. CONCLUSIONS: Gln supplementation in critically-ill children contributed to maintain high HSP-70 levels for longer. Glutamine supplementation had no influence on IL-10 and failed to show a significant reduction of IL-6 levels. The Gln could reduce PICU stay

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

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

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

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

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

Infection¿what else? The usefulness of procalcitonin in children after cardiac surgery

Objectives: Procalcitonin is a useful biomarker for predicting bacterial infection after cardiac surgery. However, sometimes procalcitonin rises following cardiac surgery without a confirmation of bacterial infection. The aim was to analyse procalcitonin levels in children without a bacterial infection after cardiac surgery. Study design: This is a prospective, observational study of children <18 years old admitted to the pediatric intensive care unit after cardiac surgery. Results: 1,042 children were included, 996 (95.6%) without a bacterial infection. From them, severe complications occurred in 132 patients (13.3%). Procalcitonin increased differentially depending on the type of complication. Patients who presented a poor outcome (n = 26, 2.6%) had higher procalcitonin values in the postoperative period than the rest of patients (<24 hours: 5.8 ng/mL vs. 0.6 ng/mL; 24-48 hours, 5.1 ng/mL vs. 0.8 ng/mL, and 48-72 hours, 5.3 ng/mL vs. 1.2 ng/mL), but these values remained stable over time (p = 0.732; p = 0.110). The AUC for procalcitonin for predicting poor outcome was 0.876 in the first 24 hours. The cut-off point to predict poor outcome was 2 ng/mL in the first 24 hours (sensitivity 86.9%, specificity 77.3%). Patients with bacterial infection (n = 46) presented higher values of procalcitonin initially, but they decreased in the 48-72 hours period (<24 hours: 4.9 ng/mL; 24-48 hours, 5.8 ng/mL, and 48-72 hours, 4.5 ng/mL). Conclusions: A procalcitonin value<2 ng/mL may indicate the absence of infection and poor outcome after cardiac surgery. The evolution of the values of this biomarker might help to discern between infection (where procalcitonin will decrease) and poor outcome (where procalcitonin will not decrease)

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

Lung Recruitment Maneuvers Assessment by Bedside Lung Ultrasound in Pediatric Acute Respiratory Distress Syndrome

The use of recruitment maneuvers (RMs) is suggested to improve severe oxygenation failure in patients with acute respiratory distress syndrome (ARDS). Lung ultrasound (LUS) is a non-invasive, safe, and easily repeatable tool. It could be used to monitor the lung recruitment process in real-time. This paper aims to evaluate bedside LUS for assessing PEEP-induced pulmonary reaeration during RMs in pediatric patients. A case of a child with severe ARDS due to Haemophilus influenzae infection is presented. Due to his poor clinical, laboratory, and radiological evolution, he was placed on venovenous extracorporeal membrane oxygenation (ECMO). Despite all measures, severe pulmonary collapse prevented proper improvement. Thus, RMs were indicated, and bedside LUS was successfully used for monitoring and assessing lung recruitment. The initial lung evaluation before the maneuver showed a tissue pattern characterized by a severe loss of lung aeration with dynamic air bronchograms and multiple coalescent B-lines. While raising a PEEP of 30 mmH2O, LUS showed the presence of A-lines, which was considered a predictor of reaeration in response to the recruitment maneuver. The LUS pattern could be used to assess modifications in the lung aeration, evaluate the effectiveness of RMs, and prevent lung overdistension