Increase in Incidence Rates and Risk Factors for Multidrug Resistant Bacteria in Septic Children: A Nationwide Spanish Cohort Study (2013-2019).

The emergence of multidrug-resistant (MDR) bacteria in children is a growing concern, particularly among septic patients, given the need for first-right dosing. Our aim was to determine the incidence rates and factors associated with MDR-sepsis in the pediatric intensive care unit (PICU), using data from the Spanish ENVIN-HELICS PICU registry between 2013 and 2019. The rate of MDR bacteria among septic children ranged between 5.8 and 16.2% throughout this study period, with a significant increase since 2015 (p = 0.013). MDR-gram-negative bacteria (92%), particularly EBL-Enterobacterales (63.7%), were the most frequent causative microorganisms of MDR-sepsis. During this study period, sixteen MDR-sepsis (32.6%) corresponded to intrahospital infections, and 33 (67.4%) had community-onset sepsis, accounting for 10.5% of the overall community-onset sepsis. Independent risk factors associated with MDR-sepsis were antibiotics 48 h prior to PICU admission (OR 2.38) and PICU onset of sepsis (OR 2.58) in >1 year-old children, and previous malnourishment (OR 4.99) in <1 year-old children. Conclusions: There was an alarming increase in MDR among septic children in Spain, mainly by gram-negative (ESBL-Enterobacterales), mostly coming from the community setting. Malnourished infants and children on antibiotics 48 h prior to PICU are at increased risk and therefore require closer surveillance.

Description of a Swine Infant Model of Volume-Controlled Hemorrhagic Shock.

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to guide resuscitation and comparison between different therapies is difficult in children due to the inherent heterogeneity of this population. As a result, compared to adults, appropriate management of pediatric hemorrhagic shock is still not well established. In addition, the scarcity of pediatric patients with hemorrhagic shock precludes the development of clinically relevant studies. For this reason, an experimental pediatric animal model is necessary to study the effects of hemorrhage in children as well as their response to different therapies. We present an infant animal model of volume-controlled hemorrhagic shock in anesthetized young pigs. Hemorrhage is induced by withdrawing a previously calculated blood volume, and the pig is subsequently monitored and resuscitated with different therapies. Here, we describe a precise and highly reproducible model of hemorrhagic shock in immature swine. The model yields hemodynamic data that characterizes compensatory mechanisms that are activated in response to severe hemorrhage.

Effect of three enteral diets with different protein contents on protein metabolism in critically ill infants: a randomized controlled trial.

INTRODUCTION: The optimal intake to improve protein metabolism without producing adverse effects in seriously ill infants has yet to be established. The aim of our study was to analyse whether an increased protein intake delivered through enteral nutrition would be associated with an improvement in nitrogen balance and serum protein levels in critically ill infants. METHODS: We conducted a multicentre, prospective randomized controlled trial (December 2016-June 2019). The sample consisted of critically ill infants receiving enteral nutrition assigned randomly to 3 protein content groups: standard diet (1.7 g/dL), protein-enriched diet (2.7 g/dL) and high protein-enriched diet (5.1 g/dL). Blood and urine tests were performed, and we assessed nitrogen balance at baseline and at 3-5 days of the diet. We analysed variations in nitrogen balance and serum protein levels (total protein, albumin, transferrin, prealbumin, and retinol-binding protein) throughout the study period. RESULTS: Ninety-nine infants (33 per group) completed the study. We did not find any differences were between groups in demographic characteristics, severity scores or prescribed medications, except for corticosteroids, administered in a higher proportion of patients in the third group. We observed significant increases in prealbumin and retinol-binding protein levels in patients receiving the protein-enriched and high protein-enriched diets at 3-5 days compared to baseline. The nitrogen balance increased in all groups, but the differences were not significant in the high protein-enriched group. There were no differences in gastrointestinal tolerance. Patients fed high protein-enriched formula had higher levels of serum urea, with a higher incidence of hyperuraemia in this group. CONCLUSION: Enteral administration of higher amounts of protein improves serum protein levels in critically ill children. A protein intake of 2.2 g/kg/day is generally safe and well tolerated, whereas an intake of 3.4 g/kg/day may produce hyperuraemia in some patients.

Prospective observational study on the use of continuous intravenous ketamine and propofol infusion for prolonged sedation in critical care.

INTRODUCTION: Analgesia and sedation are a priority in paediatric intensive care. The combination of ketamine and propofol is a possible option in patients requiring prolonged or difficult sedation and to reduce the use of benzodiazepines and opiates. The aim of this study was to assess the efficacy and safety of combination ketamine and propofol in continuous infusion for prolonged analgesia/sedation in the paediatric intensive care setting. PATIENTS AND METHODS: Prospective, observational single-group cohort study in patients aged 1 month to 16 years admitted to the paediatric intensive care unit in 2016-2018 that received ketamine and propofol in continuous infusion for analgesia and sedation. We collected data on demographic and clinical characteristics, analgesia and sedation scores (MAPS, COMFORT-B and SOPHIA), haemodynamic parameters and adverse events. RESULTS: The study included 32 patients. The maximum dose of ketamine was 1.5 mg/kg/h (interquartile range [IQR], 1-2 mg/kg/h) and the infusion duration was 5 days (IQR, 3-5 days). The maximum dose of propofol was 3.2 mg/kg/h (IQR, 2.5-3.6 mg/kg/h) and the infusion duration, 5 days (IQR, 3-5 days). Thirty (93.7%) patients had previously received midazolam and 29 (90.6%) fentanyl. Analgesia scores did not change after initiation of the ketamine and propofol infusion. There was a statistically significant increase in the COMFORT-B score, but the score remained in the adequate sedation range (12-17). There were small but statistically significant decreases in the mean arterial pressure (from 64 mmHg to 60 mmHg; P = .006) and the diastolic blood pressure (from 50.5 to 48 mmHg; P = .023) 1 h after the initiation of the ketamine and propofol infusion, but this difference was not observed 12 h later and did not require administration of vasoactive drugs. No other major adverse events were detected during the infusion. CONCLUSIONS: The combination of ketamine and propofol in continuous infusion is a safe treatment in critically ill children that makes it possible to achieve an appropriate level of analgesia and sedation without relevant haemodynamic repercussions.

Multicenter randomized clinical trial comparing dexamethasone versus placebo in preventing upper airway obstruction after extubation in critically ill children.

To analyze the effectiveness of dexamethasone in preventing upper airway obstruction (UAO) symptoms after extubation and the need of reintubation in critically ill children. Multicenter, prospective, double-blind, randomized, phase IV clinical trial involving five pediatric intensive care units. Children between 1 month and 16 years-of-age intubated for more than 48 h were included. Patients were randomized to receive placebo or dexamethasone 0.25 mg/kg every 6 h, 6-to-12 h prior to extubation (four doses). 48 h follow-up was carried out after extubation. Severity of UAO symptoms (Taussig score, stridor) and reintubation requirement were compared. 147 patients were randomized (10 were excluded), 70 patients received dexamethasone and 67 placebo. No global differences were found in the presence of stridor or moderate-to-severe UAO symptoms (Taussig ≥ 5), but Taussig ≥ 5 was less frequent in patients less than 2 years-of-age treated with steroids (p = 0.014). Median Taussig score was lower in the dexamethasone group 1 h after extubation, p < 0.001. 27 patients required reintubation, 9 due to UAO: 3 (4.3%) in the dexamethasone group and 6 (8.9%) in the placebo group, p = 0.319. In those intubated > 5 days, reintubation due to UAO was higher in the placebo group (2.4% vs. 14.3, p = 0.052). Nebulized epinephrine and budesonide were required more frequently in the placebo group in the first 2 h (p = 0.041) and 1 h (p = 0.02) after extubation, respectively. No relevant side effects were observed. Dexamethasone prior to extubation did not significantly reduce moderate-severe UAO symptoms, except for patients under 2-years of age. Dexamethasone could decrease Taussig score and the need of rescue therapies, as well as reintubation rates in those intubated for more than 5 days.

Microcirculatory Changes in Pediatric Patients During Congenital Heart Defect Corrective Surgery.

A prospective, observational single-center study was carried out. Pediatric patients undergoing congenital heart defect surgery were evaluated before, during, and after surgery. At each time point, sublingual microcirculation and clinical parameters were assessed, along with analytical variables. Twenty-four patients were included. All microcirculatory parameters worsened during cardiopulmonary bypass and returned to baseline values after surgery (p ≤ 0.001). In the intraoperative evaluation, body temperature correlated with perfused small vessel density (p = 0.014), proportion of perfused small vessels (p < 0.001), small vessel microvascular flow index (p = 0.003), and small vessel heterogeneity index (p < 0.002). Patients with cyanotic disease exhibited higher small vessel density (p < 0.008) and higher density of perfused small vessels (p < 0.022) at baseline, and a lower microvascular flow index (p = 0.022) and higher heterogeneity (p = 0.026) in the intraoperative phase. Children with congenital heart disease exhibited decreased vascular density and microvascular blood flow and increased heterogeneity during cardiopulmonary bypass. All these parameters returned to baseline values after surgery.

A comparative two-cohort study of pediatric patients with long term stay in ICUs.

During the last decades, the number of patients with long stay admissions (LSA) in PICU has increased. The purpose of this study was to identify factors associated with PICU LSA, assessing healthcare resources use and changes in the profile of these patients. A retrospective, observational, single-center study was carried out. Characteristics of LSA were compared between two periods (2006-2010 and 2011-2015). During the earlier period there were 2,118 admissions (3.9% of them LSA), whereas during the second period, there were 1,763 (5.4% of them LSA) (p = 0.025). LSA accounted for 33.7% PICU stay days during the first period and 46.7% during the second (p < 0.001). Higher use of non-invasive ventilation (80.2% vs. 37.8%, p = 0.001) and high-flow oxygen therapy (68.8% vs. 37.8%, p = 0.005) was observed in the 2011-2015 cohort, whereas the use of arterial catheter (77.1% vs. 92.6%, p = 0.005), continuous infusion of adrenaline (55.2% vs. 75.9%, p = 0.004), and hemoderivative transfusion (74% vs. 89.2%, p = 0.010) was less frequent. In the 2006-2010 cohort, hospital-acquired infections were more common (95.2% vs. 68.8%, p < 0.001) and mortality was higher (26.8% vs. 13.8%, p = 0.026). The number of long-stay PICU admissions have increased entailing an intensive use of healthcare resources. These patients have a high risk for complications and mortality.

Case Report: Severe ARDS in a Pediatric Hematopoietic Stem-Cell Transplantation Recipient Caused by Disseminated Toxoplasmosis.

Toxoplasma gondii infection is a severe complication of hematopoietic stem-cell transplantation (HSCT) recipients that can remain unnoticed without a high clinical suspicion. We present the case of a 6-year-old patient with acute lymphoblastic leukemia and HSCT recipient who was admitted to the Pediatric Intensive Care Unit (PICU) on post-transplantation day +39 with fever, hypotension, severe respiratory distress and appearance of a lumbar subcutaneous node. She developed severe Acute Respiratory Distress Syndrome (ARDS) and underwent endotracheal intubation and early mechanical ventilation. Subsequently, she required prone ventilation, inhaled nitric oxide therapy and high-frequency oscillatory ventilation (HFOV). An etiologic study was performed, being blood, urine, bronchoalveolar lavage and biopsy of the subcutaneous node positive for Toxoplasma gondii by Polymerase Chain Reaction (PCR). Diagnosis of disseminated toxoplasmosis was established and treatment with pyrimethamine, sulfadiazine and folinic acid started. The patient showed clinical improvement, allowing weaning of mechanical ventilation and transfer to the hospitalization ward after 40 days in the PICU. It is important to consider toxoplasmosis infection in immunocompromised patients with sepsis and, in cases of severe respiratory distress, early mechanical ventilation should be started using the open lung approach. In Toxoplasma IgG positive patients, close monitoring and appropriate anti-infectious prophylaxis is needed after HSCT.

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain.

BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. METHODS: A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. RESULTS: Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. CONCLUSIONS: MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.

[Nutrition in children with continuous renal replacement therapy]. / Nutrición en niños tratados con técnicas de depuración extrarrenal continua.

INTRODUCTION: The aim of this study was to analyse the nutritional state, diet and gastrointestinal complications of children that require continuous renal replacement therapy (CRRT). MATERIAL AND METHODS: A retrospective analysis of a database, which included the information about patients who required CRRT between the years 2013 and 2017. Data were collected on the replacement technique, type of nutrition, calorie and protein intake, gastrointestinal complications, and clinical course. RESULTS: A total of 65 children (61.5% male) were treated with CRRT, and 24 patients (37%) also needed ECMO support. Just over one-quarter (27.7%) of patients had a weight less than P3, and 48.4% of them a height less than P3. At the beginning of the technique, 31 children (47.7%) received enteral nutrition, at the end, there were 52 patients receiving enteral nutrition (80%). The transpyloric tube was used to provide nutrition in 76% of the cases. The median caloric intake was 63kcal/kg/day, and the protein intake was 1.6g/kg/day. There were gastrointestinal difficulties during the process in 48 patients (73.8%), with 29 (44.6%) patients being diagnosed with gastric distension or excessive gastric remains, 22 (33.8%) with constipation, 8 (12.3%) with vomiting, and 4 (6.1%) diarrhoea. One patient treated with ECMO presented with intestinal ischaemia. Enteral nutrition was cancelled in 3 patients (4.6%) due to the complications. There was no relationship between complications and type of diet or ECMO assistance. CONCLUSIONS: A high percentage of children treated with CRRT showed undernutrition but they had adequate tolerance to the enteral nutrition. Although the gastrointestinal complications percentage was high in few subjects, these complications are the reason why enteral nutrition was stopped.

The Latin American and Spanish Survey on Nutrition in Pediatric Intensive Care (ELAN-CIP2).

OBJECTIVE: To characterize the practices of nutritional support in Latin American and Spanish PICUs. DESIGN: Survey with a questionnaire sent to Latin American Society of Pediatric Intensive Care members. SETTING: PICUs of participant hospitals. PATIENTS: Critically ill children between 1 month and 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-seven surveys from 17 countries were analyzed. Sixty-seven percent of PICUs were from university-affiliated hospitals, with a median of 380 admissions/yr. Sixty-eight percent and 48.9% had a nutritional support team and nutritional support protocol, respectively. Seventy-five percent completed nutritional evaluations, with 34.2% at admission. PICUs with high-volume admissions were likely to have a nutritional support team (p < 0.005), and university-affiliated hospitals showed a trend of having a nutritional support team (p = 0.056). Measured, estimated, and ideal weights were used in 75%, 14.6%, and 10.4%, respectively. Energy requirements were calculated using Holliday & Segar and Schofield equations in 90% of the PICUs; 43% used correction factors. Only three PICUs had indirect calorimetry. At day 3 of initiation of nutritional support, 57.3% of PICUs provided at least 50% of the calculated energy requirement, and 91.5% at day 5. Protein needs were estimated according to American Society for Parenteral and Enteral Nutrition and European Society for Clinical Nutrition and Metabolism/European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines in 55.3% and 40.4%, respectively. Enteral nutrition was the preferred feeding method, initiated in 97.7% at 48 hours. The feeding route was gastric (82.9%), by bolus (42.5%) or continuous (57.4%). Monitoring methods included gastric residual measurement in 55.3%. Enteral nutrition was discontinued in 82.8% when gastric residual was 50% of the volume. Prokinetics were used in 68%. More than half of PICUs used parenteral nutrition, with 95.8% of them within 72 hours. Parenteral nutrition was administered by central vein in 93.6%. Undernourished children received parenteral nutrition sooner, whether or not enteral nutrition intolerance was present. When enteral nutrition was not tolerated beyond 72 hours, parenteral nutrition was started in 57.4%. Parenteral nutrition was initiated when enteral nutrition delivered less than 50% in 97%. CONCLUSIONS: Nutritional practices are heterogeneous in Latin American PICUs, but the majority use nutritional support strategies consistent with international guidelines.

Infectious complications in paediatric patients treated with extracorporeal membrane oxygenation. / Complicaciones infecciosas en niños tratados con oxigenación por membrana extracorpórea.

INTRODUCTION: The aim of this study was to analyse the incidence, treatment and evolution of infections in children treated with ECMO. METHODS: A retrospective study based on a prospective database was performed. Children under the age of 18 years treated with ECMO from September 2006 to November 2015 were included. The patients' clinical characteristics were collected, together with ECMO technique, cultures and treatment of infection. RESULTS: One hundred patients with a median age of 11 months were analysed. Heart disease was diagnosed in 94 patients. An infection was suspected and antibiotic treatment was initiated in 51 patients, although only 22 of them were microbiologically confirmed. The most common infection was sepsis (49%), followed by pneumonia (35.3%) and urinary tract infection (9.8%). There were no differences in haematological parameters and acute phase reactants between children with infection and those without. Children who died had a higher incidence of infection during ECMO (60.4%) than the survivors (40.3%), but the difference did not reach statistical significance (P=.07). The duration of admission in the PICU was 57 days in patients with infection vs 37 days in patients without infection but the difference was not statistically significant (P=.067). CONCLUSIONS: Infection in children with ECMO is common. There are no specific infection parameters and less than half of the clinical infections are confirmed microbiologically. There was no statistically significant correlation between infection and mortality or duration of PICU stay.

[Materials for the paediatric resuscitation trolley or backpack: Expert recommendations]. / Recomendaciones de expertos sobre el material del carro y mochila de reanimación cardiopulmonar pediátrica y neonatal.

Cardio-respiratory arrest (CPA) is infrequent in children, but it can occur in any place and at any time. This fact means that every health care facility must always have the staff and material ready to resuscitate a child. These recommendations are the consensus of experts of the Spanish Paediatric and Neonatal Resuscitation Group on the material and medication for paediatric and neonatal resuscitation and their distribution and use. CPR trolleys and backpacks must include the essential material to quickly and efficiently perform a paediatric CPR. At least one CPR trolley must be available in every Primary Care facility, Paediatric Intensive Care Unit, Emergency Department, and Pre-hospital Emergency Areas, as well as in paediatric wards, paediatric ambulatory areas, and radiology suites. This trolley must be easily accessible and exclusively include the essential items to perform a CPR and to assist children (from newborns to adolescents) who present with a life-threatening event. Such material must be familiar to all healthcare staff and also include the needed spare parts, as well as enough drug doses. It must also be re-checked periodically. The standardisation and unification of the material and medication of paediatric CPR carts, trolleys, and backpacks, as well as the training of the personnel in their use are an essential part of the paediatric CPR.

Exogenous surfactant and alveolar recruitment in the treatment of the acute respiratory distress syndrome.

OBJECTIVE: To investigate the effect of alveolar recruitment combined with surfactant administration on children with acute respiratory distress syndrome (ARDS). MATERIAL AND METHODS: A prospective, randomized, controlled and sequential study was carried out. Group A (16 children) was treated with both the alveolar recruitment manoeuvres (ARM) and the administration of the surfactant every 8 h for 3 days; group B (15) received the usual treatment only. The alveolar recruitment was carried out by increasing positive end-expiratory pressure 2 by 2 cm H2 O to improve the transcutaneous oxygen saturation values up to 88% and 90%. Demographic data, gasometric and ventilator parameters, chest radiography and 28-day mortality were evaluated. RESULTS: There were no significant differences in baseline characteristics between groups. An hour after treatment, significant differences (P < 0.001) were observed in transcutaneous oxygen saturation (SaO2 ; Group A: 94.1%, Group B: 89.9%), PaO2 /FiO2 (212.7 and 126.4) and oxygenation index (OI; 11.4 and 18.5). After 8 h, the differences in SaO2 (Group A: 94.6%, Group B: 90.3%), PaO2 /FiO2 (225.8 and 126.9) and OI (10.8 and 18.4) were also significant (P < 0.001). From the fifth dose of the surfactant, the static compliance (P = 0.0034) and radiological images (P = 0.002) were more greatly improved in group A than in group B. Survival was significantly higher in group A (81.3%) than in group B (26.7%) (P = 0.006). CONCLUSIONS: The combined treatment of surfactant administration and ARM resulted in a better oxygenation and survival in children with ARDS than when only recruitment was used.