How to use meropenem in pediatric patients undergoing CKRT? Integrated meropenem pharmacokinetic model for critically ill children.

Standard dosing could fail to achieve adequate systemic concentrations in ICU children or may lead to toxicity in children with acute kidney injury. The population pharmacokinetic analysis was used to simultaneously analyze all available data (plasma, prefilter, postfilter, effluent, and urine concentrations) and provide the pharmacokinetic characteristics of meropenem. The probability of target fT > MIC attainment, avoiding toxic levels, during the entire dosing interval was estimated by simulation of different intermittent and continuous infusions in the studied population. A total of 16 critically ill children treated with meropenem were included, with 7 of them undergoing continuous kidney replacement therapy (CKRT). Only 33% of children without CKRT achieved 90% of the time when the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) for an MIC of 2 mg/L. In dose simulations, only continuous infusions (60-120 mg/kg in a 24-h infusion) reached the objective in patients <30 kg. In patients undergoing CKRT, the currently used schedule (40 mg/kg/12 h from day 2 in a short infusion of 30 min) was clearly insufficient in patients <30 kg. Keeping the dose to 40 mg/kg q8h without applying renal adjustment and extended infusions (40 mg/kg in 3- or 4-h infusion every 12 h) was sufficient to reach 90% fT > MIC (>2 mg/L) in patients >10 kg. In patients <10 kg, only continuous infusions reached the objective. In patients >30 kg, 60 mg/kg in a 24-h infusion is sufficient and avoids toxicity. This population model could help with an individualized dosing approach that needs to be adopted in critically ill pediatric patients. Critically ill patients subjected to or not to CKRT may benefit from the administration of meropenem in an extended or continuous infusion.

Volumetric capnography and return of spontaneous circulation in an experimental model of pediatric asphyxial cardiac arrest.

A secondary analysis of a randomized study was performed to study the relationship between volumetric capnography (VCAP) and arterial CO2 partial pressure (PCO2) during cardiopulmonary resuscitation (CPR) and to analyze the ability of these parameters to predict the return of spontaneous circulation (ROSC) in a pediatric animal model of asphyxial cardiac arrest (CA). Asphyxial CA was induced by sedation, muscle relaxation and extubation. CPR was started 2 min after CA occurred. Airway management was performed with early endotracheal intubation or bag-mask ventilation, according to randomization group. CPR was continued until ROSC or 24 min of resuscitation. End-tidal carbon dioxide (EtCO2), CO2 production (VCO2), and EtCO2/VCO2/kg ratio were continuously recorded. Seventy-nine piglets were included, 26 (32.9%) of whom achieved ROSC. EtCO2 was the best predictor of ROSC (AUC 0.72, p < 0.01 and optimal cutoff point of 21.6 mmHg). No statistical differences were obtained regarding VCO2, VCO2/kg and EtCO2/VCO2/kg ratios. VCO2 and VCO2/kg showed an inverse correlation with PCO2, with a higher correlation coefficient as resuscitation progressed. EtCO2 also had an inverse correlation with PCO2 from minute 18 to 24 of resuscitation. Our findings suggest that EtCO2 is the best VCAP-derived parameter for predicting ROSC. EtCO2 and VCO2 showed an inverse correlation with PCO2. Therefore, these parameters are not adequate to measure ventilation during CPR.

A conditional RNA Pol II mono-promoter drives HIV-inducible, CRISPR-mediated cyclin T1 suppression and HIV inhibition.

Gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) targeted to HIV proviral DNA has shown excision of HIV from infected cells. However, CRISPR-based HIV excision is vulnerable to viral escape. Targeting cellular co-factors provides an attractive yet risky alternative to render viral escape irrelevant. Cyclin T1 is a critical modulator of HIV transcription and mediates recruitment of positive transcription elongation factor-b (P-TEFb) kinase for transcriptional elongation. Hence, a CRISPR-mediated cyclin T1 inactivation will silence HIV transcription, locking it in an inactive form in the cell and thereby serving as an effective antiviral and possibly effecting a functional cure. However, cellular genes play important roles, and their uncontrolled inhibition can promote undesirable effects. Here, we demonstrate a conditional inducible RNA polymerase II (RNA Pol II) mono-promoter-based co-expression of a CRISPR system targeting cyclin T1 from a single transcription unit. Co-expression of guide RNA (gRNA) and CRISPR-associated protein (Cas9) is observed only in HIV-infected cells and leads to sustained HIV suppression in stringent chronically infected cell lines as well as in T cell lines. We further show that incorporation of cis-acting ribozymes immediately upstream of the gRNA further enhances HIV silencing.

Big Five Personality Traits and Compulsive Buying: The Mediating Role of Self-Esteem.

The inter-relationships between the Big Five personality traits, self-esteem, and compulsive buying are supported by strong empirical evidence. What is yet unknown is to what extent self-esteem can channel the influence of personality traits on compulsive buying. The main objective of this study is to explore the possible mediating role of self-esteem in the link between the Big Five personality traits and compulsive buying. Path analysis results, using a sample of 487 university students, generally confirm the suitability of the proposed model in which self-esteem mediated the effects of the Big Five personality traits (neuroticism, extraversion, agreeableness, openness to experience, and conscientiousness) on compulsive buying. Moreover, a direct effect of neuroticism and conscientiousness on compulsive buying was found. Finally, based on the finding that self-esteem acts as a necessary filter in the analysis of the five factors-compulsive buying relationship, several action-oriented guidelines for the prevention or intervention of this behavioral problem are suggested.

Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy.

OBJECTIVES: Despite that piperacillin-tazobactam combination is commonly used in critically ill children, increasing evidence suggests that the current dosing schedules are not optimal for these patients. The aim of this work is to develop a population pharmacokinetic model for piperacillin to evaluate the efficacy of standard dosing in children with and without continuous kidney replacement therapy (CKRT) and to propose alternative dosing schemes maximizing target attainment. METHODS: Four hundred twenty-nine piperacillin concentrations measured in different matrices, obtained from 32 critically ill children (19 without CKRT, 13 with CKRT) receiving 100 mg/kg of piperacillin/tazobactam every 8 hours (increased to 12 hours after the fourth dose) were modelled simultaneously using the population approach with NONMEM 7.4. The percentage of patients with 90% fT > MIC and target attainment (percentage of dosing interval above MIC) were estimated for different intermittent and continuous infusions in the studied population. RESULTS: Piperacillin pharmacokinetic was best described with a two-compartment model. Renal, nonrenal, and hemofilter clearances were found to be influenced by the glomerular filtration rate, height (renal clearance), weight (nonrenal clearance), and filter surface (hemofilter clearance). Only seven (37%) children without CKRT and seven (54%) with CKRT achieved 90% fT > MIC with the current dosing schedule. Of the alternative regimens evaluated, a 24-hour continuous infusion of 200 mg/kg (CKRT) and 300 mg/kg (no CKRT) provided 100% fT > MIC (percent of time free drug remains above the minimum inhibitory concentration) (≤16 mg/L) and target attainments ≥90% across all evaluated MICs. DISCUSSION: In children with and without CKRT, standard dosing failed to provide an adequate systemic exposure, while prolonged and continuous infusions showed an improved efficacy.

Early Enteral Nutrition and Gastrointestinal Complications in Pediatric Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population. METHODS: A retrospective single-center analysis (2006-2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded. RESULTS: One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9-63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children.Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality.Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN). CONCLUSIONS: Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.

Life Aspirations, Generativity and Compulsive Buying in University Students.

The study of goal-oriented behaviour, because of its undeniable repercussions on physical and mental health, is one of the target topics of contemporary research. However, the content of life aspirations, emphasised from the self-determination theory, has received little attention from the field of compulsive buying although it plays an important role in the regulation of behaviour and well-being. Generativity, the personal construct that captures the intentions and/or the need to contribute (leave a legacy) to others, has never been analysed with respect to compulsive buying although it has been the source of interest of related fields (responsible consumption). Accordingly, this study seeks to shed light on the role of both constructs (life aspirations and generativity) in compulsive buying among university students. The sample consisted of 1093 Spanish university students classified either as non-compulsive buyers or compulsive buyers. Estimated prevalence of compulsive buying was 7.9%. The results of Student's test confirm that, besides gender (women report greater propensity to the phenomenon), compulsive buyers score higher and show statistically significant differences with respect to non-compulsive buyers in all extrinsic goals (financial success, image, popularity and conformity) and hedonism. Non-compulsive buyers show significantly higher scores for the intrinsic goals of self-acceptance, affiliation and community feeling and also report a higher generative concern. The logistic regression analysis confirms that being female and the life aspirations of image, popularity and hedonism act as risk factors in compulsive buying in university students while generativity and the importance granted to the intrinsic goals of self-acceptance and affiliation are protective factors. Potential lines of action for this worrying phenomenon are discussed in the light of the findings.

Big Five Personality Traits, Coping Strategies and Compulsive Buying in Spanish University Students.

Personality traits and coping strategies have historically been two key elements in the field of health psychology. It is, therefore, striking that there is no study in the field of compulsive buying that integrates the most generic, decontextualized and stable aspects (traits) with those having a more marked processual and dynamic nature, which are closer to goal-based views of human nature (coping strategies). Another weakness of the compulsive buying field is that, despite the confirmed growing increase in compulsive buying in the younger age groups, most studies have been conducted with adult samples. Hence, this study seeks to clarify the role of the Big Five domains and different coping strategies in university students' compulsive buying. The sample consisted of 1093 participants who were classified as either compulsive buyers or non-compulsive buyers. Both groups were compared regarding sociodemographic variables (gender, age), the Big Five personality traits, and coping strategies through chi-square tests or Student's t-tests. Besides, a multivariate logistic regression analysis was conducted to determine which of these determinants might play a part in the construction of a risk profile for compulsive buying. The results showed that other than gender (specifically being female), Neuroticism and the use of such coping strategies as problem avoidance and wishful thinking are risk factors that increase the propensity for compulsive buying. The use of active coping strategies such as problem solving, cognitive restructuring and social support, as well as the Conscientiousness dimension are protection factors that decrease the likelihood of becoming a compulsive buyer. Finally, and on the basis of the findings obtained, possible guidelines are given, which, hopefully, may effectively contribute to the prevention of and/or intervention in compulsive buying among young adults.

Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury.

Background: Ceftolozane-tazobactam is a new antibiotic against multidrug-resistant pathogens such as Pseudomonas aeruginosas. Ceftolozane-tazobactam dosage is still uncertain in children, especially in those with renal impairment or undergoing continuous renal replacement therapy (CRRT). Methods: Evaluation of different ceftolozane-tazobactam dosing regimens in three critically ill children. Ceftolozane pharmacokinetics (PK) were characterized by obtaining the patient's specific parameters by Bayesian estimation based on a population PK model. The clearance (CL) in patient C undergoing CRRT was estimated using the prefilter, postfilter, and ultrafiltrate concentrations simultaneously. Variables such as blood, dialysate, replacement, and ultrafiltrate flow rates, and hematocrit were integrated in the model. All PK analyses were performed using NONMEM v.7.4. Results: Patient A (8 months of age, 8.7 kg) with normal renal function received 40 mg/kg every 6 h: renal clearance (CLR) was 0.88 L/h; volume of distribution (Vd) Vd1 = 3.45 L, Vd2 = 0.942 L; terminal halflife (t1/2,ß) = 3.51 h, dosing interval area under the drug concentration vs. time curve at steady-state (AUCτ,SS) 397.73 mg × h × L-1. Patient B (19 months of age, 11 kg) with eGFR of 22 mL/min/1.73 m2 received 36 mg/kg every 8 h: CLR = 0.27 L/h; Vd1 = 1.13 L; Vd2 = 1.36; t1/2,ß = 6.62 h; AUCSS 1481.48 mg × h × L-1. Patient C (9 months of age, 5.8 kg), with severe renal impairment undergoing CRRT received 30 mg/kg every 8 h: renal replacement therapy clearance (CLRRT) 0.39 L/h; Vd1 = 0.74 L; Vd2= 1.17; t 1/2,ß = 3.51 h; AUCτ,SS 448.72 mg × h × L-1. No adverse effects attributable to antibiotic treatment were observed. Conclusions: Our results suggest that a dose of 35 mg/kg every 8 h can be appropriate in critically ill septic children with multi-drug resistance Pseudomonas aeruginosa infections. A lower dose of 10 mg/kg every 8 h could be considered for children with severe AKI. For patients with CRRT and a high effluent rate, a dose of 30 mg/kg every 8 h can be considered.

Renal function in children assisted with extracorporeal membrane oxygenation.

Acute kidney injury is a frequent complication in patients requiring extracorporeal membrane oxygenation. A single-center retrospective analysis from a prospective observational database assessing the incidence of acute kidney injury in children undergoing extracorporeal membrane oxygenation, the use of continuous renal replacement therapy and its association with outcomes was performed. One hundred children were studied. Creatinine was normal in 33.3% of children at the beginning of extracorporeal membrane oxygenation, between 1.5 and 2 times its baseline levels in 18.4% of children (stage I acute kidney injury), between 2 and 3 times baseline levels (stage II) in 20.7%, and over 3 times baseline levels or requiring continuous renal replacement therapy (stage III) in 27.6% of the patients. Eighteen patients were on continuous renal replacement therapy before the beginning of extracorporeal membrane oxygenation, 81 required continuous renal replacement therapy during extracorporeal membrane oxygenation, and 38 after weaning from extracorporeal membrane oxygenation, but none of them did at discharge from the pediatric intensive care unit. Fifty-one children survived to pediatric intensive care unit discharge. Mortality was lower in children with normal kidney function or with stage I acute kidney injury at the beginning of extracorporeal membrane oxygenation than in those with stage II or III acute kidney injury (33.3% vs 58.3%, p = 0.021). Mortality in children requiring continuous renal replacement therapy during extracorporeal membrane oxygenation was 54.3% and 21.1% in the rest of patients (p < 0.01). We conclude that kidney function is significantly impaired in a high percentage of children undergoing extracorporeal membrane oxygenation and many of them are treated with continuous renal replacement therapy. Patients treated with continuous renal replacement therapy have a higher mortality than those with normal kidney function or stage I acute kidney injury at the beginning of extracorporeal membrane oxygenation. Most patients surviving to pediatric intensive care unit discharge recover normal renal function after weaning from extracorporeal membrane oxygenation.

Hemodynamic impact of the connection to continuous renal replacement therapy in critically ill children.

BACKGROUND: Continuous renal replacement therapy (CRRT) is the treatment of choice for critically ill children with acute kidney injury. Hypotension after starting CRRT is frequent but very few studies have analyzed its incidence and clinical relevance. METHODS: A prospective, observational study was performed including critically ill children treated with CRRT between 2010 and 2014. Hemodynamic data and connection characteristics were collected before, during, and 60 min after CRRT circuit connection. Hypotension with the connection was defined as a decrease in > 20% of the mean arterial pressure from baseline or when intravenous fluid resuscitation or an increase in vasopressors was required. RESULTS: One hundred sixty-one connections in 36 children (median age 18.8 months) were analyzed. Twenty-eight patients (77.8%) were in the postoperative period of cardiac surgery, 94% had mechanical ventilation, and 86.1% had vasopressors. The heparinized circuit priming solution was discarded in 8.7% and infused to the patient in 18% of the connections. The circuit was re-primed in the remaining 73.3% using albumin (79.3%), red blood cells (4.5%), or another crystalloid solution without heparin (16.2%). Hypotension occurred in 49.7% of the connections a median of 5 min after the beginning of the therapy. Fluid resuscitation was required in 38.5% and the dose of vasopressors was increased in 12.4% of the connections. There was no relationship between hypotension and age or weight. Re-priming the circuit with albumin reduced the incidence of hypotension from 71.4 to 44.6% (p = 0.004). CONCLUSIONS: Hypotension after the connection to CRRT is very frequent in critically ill children. Re-priming the circuit with albumin could improve hemodynamics during connection.

Correction: Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

[This corrects the article DOI: 10.1371/journal.pone.0149013.].

Hemodynamic Effects of Connection to Continuous Renal Replacement Therapy in a Pediatric Animal Model.

To assess the hemodynamic effects of connection to continuous renal replacement therapy (CRRT) in a pediatric experimental animal model. Prospective experimental study was performed using piglets between 2 and 3 months of age and 9-11 kg. CRRT with a PrismaflexR monitor and HF20 filter (surface of 0.2 m2 ) was started after monitoring and anesthetic induction with an initial blood flow at 20 mL/min with 10 mL/min increases every minute until the goal flow of 5 mL/kg/min was achieved. Heart rate, blood pressure, central venous pressure, cardiac index, and renal blood flow were registered at baseline, 5, 15, 30, 60, 120, 180, 240, and 360 min. IBM SPSS Statistics 20.0 package was used for analysis. A P value of <0.05 was considered statistically significant. Thirty-four piglets were studied. Blood pressure, cardiac output, and systemic vascular resistance significantly decreased 5-min after CRRT connection (mean arterial pressure from 85.5 to 70.8 mm Hg, P < 0.001, cardiac index from 3.6 to 3.3 L/min/m2 P = 0.024, and systemic vascular resistance index from 1759 to 1607 dyn.s/cm5 P = 0.012). No significant changes were found in renal blood flow or central venous pressure. All parameters gradually increased at 15 and 30 min after connection but complete recovery was never achieved. Connection to CRRT produces a significant decrease in arterial pressure, cardiac index, and peripheral vascular resistances in hemodynamically stable piglets.

Hematologic Disorders in Children with Continuous Renal Replacement Therapies.

The objective of this study was to analyze hematologic disorders, coagulation disorders, and transfusion requirements in children with continuous renal replacement therapies (CRRT). This is a retrospective analysis of a prospectively collected database of children receiving CRRT between 2010 and 2015. Patient characteristics, CRRT parameters, hematologic and coagulation parameters, and need for transfusions were recorded and analyzed. We compared patients after heart surgery and noncardiac patients, those requiring extracorporeal membrane oxygenation (ECMO) and those without ECMO, and patients with different anticoagulation therapies: heparin and citrate. Eighty-seven patients were included (69% after heart surgery). Thirty-four percentage of patients required ECMO. Hematologic alterations throughout the therapy included a descent in hematocrit from 33.6% to 30.3% (p = 0.002) and in platelet count from 159.291 to 101.163 (p < 0.001). Coagulation parameters improved as international normalized ratio decreased from 1.5 to 1.2 (p < 0.001), fibrinogen increased from 328 to 437 mg/dl (p = 0.04), and activated partial thromboplastin time (APTT) was normalized. There were no significant differences in hematologic parameters or need for blood products between patients after heart surgery and the rest of patients, or between patients receiving heparin or citrate for anticoagulation. Ninety percentage of patients received blood products, but patients on ECMO and those who deceased required more transfusions than the rest of the patients (p < 0.01). We conclude that children undergoing CRRT show a descent in hematocrit and platelet count and require large amounts of blood products, especially those ECMO and patients who died.

Impulsivity and eating behavior in males / Impulsividad y conducta alimentaria en varones

Introduction: Impulsivity is a personality trait related with the control of behaviour and emotions and it is found in different psychopathological alterations, including those referred to eating behaviour. Objective: The aim of this study was to analyse the relationship among the infl uence of the aesthetic body shape model, eating behaviour (and risk for specific disorders), body mass index and impulsivity. Method: A total of 178 males were included in the study, with a mean age of 20.18 ± 2.48. Height and weight were assessed in order to obtain the body mass index. All participants fulfilled the following questionnaires: Barratt Impulsivity Scale (BIS-11), Questionnaire of Infl uences on the Body Shape Model for males (CIMEC-V) and the Eating Attitudes Test (EAT-40). Results: With respect to possible cases of eating disorders, 5.06% were found. Scores of some items of BIS-11 correlated significantly with the EAT-40 and CIMEC-V scores. Overweight participants (39.89%) showed higher level of impulsivity as well as those with EAT-40 scores above the cut-off point for that test. Conclusions: The assessment of impulsivity from a psychological point of view might be a preventive tool with regards to disordered eating behaviours. Respecting the patients with eating disorders/overweight/obesity, that assessment might be a relevant aspect in order to improve the therapeutical approach.

Introducción: la impulsividad es un rasgo de personalidad relacionado con el control de la conducta y de las emociones y que se observa en diferentes alteraciones psicopatológicas, entre ellas las referidas a la conducta alimentaria. Objetivo: el objetivo del presente trabajo fue analizar la relación entre la influencia del modelo estético corporal, la conducta alimentaria (y riesgo de patología específi ca), el IMC y la impulsividad. Método: fueron incluidos en el estudio 178 varones con una edad media de 20,18 ± 2,48 años. De todos ellos se recogieron peso y talla para calcular el IMC, y los participantes cumplimentaron la escala de impulsividad de Barratt (BIS-11), el Cuestionario de Infl uencias del Modelo Estético Corporal, versión para varones (CIMEC-V) y el Eating Attitudes Test-40(EAT-40). Resultados: se encontró un 5,06% de posibles casos de trastornos alimentarios. Las puntuaciones en algunos ítems de la BIS-11 correlacionaron significativamente con las puntuaciones del EAT-40 y CIMEC-V. Los participantes en situación de sobrepeso (39,89%) presentaron mayor impulsividad, al igual que ocurrió con los participantes que obtuvieron una puntuación superior al punto de corte en el EAT-40. Conclusiones: la exploración de la impulsividad desde el punto de vista psicológico podría constituir un elemento preventivo con relación a las alteraciones alimentarias. En cuanto a pacientes con TCA/sobrepeso/obesidad, podría ser un aspecto a destacar de cara a mejorar su abordaje terapéutico.

Evaluation of sublingual microcirculation in a paediatric intensive care unit: prospective observational study about its feasibility and utility.

BACKGROUND: Evaluation of the microcirculation in critically ill patients is usually done by means of indirect parameters. The aim of our study was to evaluate the functional state of the microcirculation by direct visualization of sublingual microcirculation using Sidestream Dark Field Imaging, to determine the correlation between these findings and other parameters that are commonly used in the clinical practice and to assess the applicability of the systematic use of this technique in critically ill children. METHODS: A prospective observational study was carried out in a Pediatric Intensive Care Unit (PICU) of a tertiary referral hospital. All patients admitted to the PICU during a three-month period were included in the study after obtaining the informed consent from the patient. Systematic evaluation of sublingual microcirculation was done in these patients (Total Vessel Density, Proportion of Perfused Vessels, Perfused Vessel Density, De Backer Score, Microvascular Flow Index, Heterogeneity Index) within the first day of admission (T1) and between the second and third day of admission (T2). Other clinical, hemodynamic, and biochemical parameters were measured and registered simultaneously. When the evaluation of the microcirculation was not feasible, the reason was registered. Descriptive analysis of our findings are expressed as means, medians, standard deviations and interquartile ranges. Mann-Whitney-Wilcoxon and Fisher tests were used to compare variables between patients with and without evaluation of the microcirculation. Pearson Correlation Coefficient (ρ) was used to evaluate the correlation between microcirculatory parameters and other clinical parameters. RESULTS: One hundred fine patients were included during the study period. Evaluation of the microcirculation was feasible in 18 patients (17.1%). 95.2% of them were intubated. The main reason for not evaluating microcirculation was the presence of respiratory difficulty or the absence of collaboration (95.1% on T1 and 68.9% on T2). Evaluated patients had a higher prevalence of intubation and ECMO at admission (72.2% vs. 14.9% and 16.6% vs. 1.1%, respectively), and longer median duration of mechanical ventilation (0 vs. 6.5 days), vasoactive drugs (0 vs. 3.5 days) and length of stay (3 vs. 16.5 days) than non-evaluated patients. There was a moderate correlation between microcirculatory parameters and systolic arterial pressure, central venous pressure, serum lactate and other biochemical parameters used for motoring critically ill children. CONCLUSIONS: Systematic evaluation of microcirculation in critically ill children is not feasible in the unstable critically ill patient, but it is feasible in stable critically ill children. Microcirculatory parameters show a moderate correlation with other parameters that are usually monitored in critically ill children.

Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

OBJECTIVE: To design an experimental pediatric animal model of acute kidney injury induced by cisplatin. METHODS: Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study. RESULTS: 41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage. CONCLUSIONS: a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury.

Citrate anticoagulation for CRRT in children: comparison with heparin.

Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P = 0.028). 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I) of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.