Paediatric sepsis survivors are resistant to sepsis-induced long-term immune dysfunction.

BACKGROUND AND PURPOSE: Sepsis-surviving adult individuals commonly develop immunosuppression and increased susceptibility to secondary infections, an outcome mediated by the axis IL-33/ILC2s/M2 macrophages/Tregs. Nonetheless, the long-term immune consequences of paediatric sepsis are indeterminate. We sought to investigate the role of age in the genesis of immunosuppression following sepsis. EXPERIMENTAL APPROACH: Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. Likewise, sepsis-surviving mice were inoculated intranasally with Pseudomonas aeruginosa or by subcutaneous inoculation of the B16 melanoma cell line. Finally, blood samples from sepsis-surviving patients were collected and the concentration of IL-33 and Tregs frequency were assessed. KEY RESULTS: In contrast to 6-week-old mice, 2-week-old mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in 6-week-old but not 2-week-old post-septic mice. Moreover, impaired IL-33 production in 2-week-old post-septic mice was associated with increased DNA methylation in lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in 2-week-old mice. Clinically, adults but not paediatric post-septic patients exhibited higher counts of Tregs and seral IL-33 levels. CONCLUSION AND IMPLICATIONS: These findings demonstrate a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression. Thus, a better understanding of this process may lead to differential treatments for adult and paediatric sepsis.

Risk factors for mortality from sepsis in an intensive care unit in Ecuador: A prospective study.

ABSTRACT: To investigate risk factors for mortality from sepsis in an intensive care unit (ICU) in Quito-Ecuador and their association to adherence to Surviving Sepsis Campaign recommendations.Prospective cohort study of patients with severe sepsis/septic shock admitted to the ICU of a public Ecuadorian hospital from March, 2018 to March, 2019. Demographic, clinical, treatment, and outcome data were collected from patients' health records. Patients were divided into 2 groups according to ICU survival or death. Log-binomial regression models were used to identify risk factors for mortality.In total, 154 patients were included. Patients who died in the ICU (n = 42; 27.3%) had higher sequential organ failure assessment score (median 11.5 vs 9; P<.01), more organ dysfunction (median 4 vs 3; P<.0001), and received greater volumes of fluid resuscitation in the first 6 hours (median 800 vs 600 mL; P = .01). Dysfunction of > 2 organs was a risk factor for mortality (relative risks [RR] 3.80, 95% CI 1.33-10.86), while successful early resuscitation (RR 0.32, 95% CI 0.15-0.70), successful empirical antibiotic treatment (RR 0.38, 95%CI 0.18-0.82), and antibiotic de-escalation (RR 0.28, 95%CI 0.13-0.61) were protective factors.Dysfunction of >2 organs was a risk factor for mortality from sepsis while successful early resuscitation and appropriate antibiotic treatment were protective.

Epidemiology and factors associated with the severity of viral acute lower respiratory infection in children hospitalized in Manaus, Amazonas, in 2017-2018: An observational study.

ABSTRACT: To investigate the epidemiology and factors associated with the severity of viral acute lower respiratory infection (ALRI) in children hospitalized in Manaus, Amazonas, in 2017 to 2018.Retrospective cohort study of children hospitalized at the Hospital and Emergency Room Delphina Rinaldi Abdel Aziz, in Manaus, from April 01, 2017 to August 31, 2018, with a clinical diagnosis of ALRI and nasopharyngeal aspirates positive for at least 1 respiratory virus.One hundred forty-six children aged 0.2 to 66 months (median 7 months) were included. Patients were divided into 2 groups according to the disease severity classified by an adapted Walsh et al score: moderate disease, score 0-4, n = 66 (45.2%) and severe disease, score 5-7, n = 80 (54.8%). A greater number of viral ALRI cases were observed in the rainiest months. Respiratory syncytial virus was the most prevalent (n = 103, 70.3%), followed by metapneumovirus (n = 24, 16.4%), influenza virus (n = 17, 11.6%), parainfluenza virus (n = 11, 7.5%), and adenovirus (n = 4, 2.7%). Co-detections of 2 to 3 viruses were found in 12 (8.2%) patients. The presence of viral coinfection was an independent risk factor for disease severity (adjusted relative risk [RR] 1.53; 95% CI 1.10-2.14). Twelve patients (8.2%) died, all with severe disease. Risk factors for death were shock (adjusted RR 10.09; 95% CI 2.31-43.90) and need for vasoactive drugs (adjusted RR 10.63; 95% CI 2.44-46.31).There was a higher incidence of viral ALRI in Manaus in the rainy season. Respiratory syncytial virus was the most prevalent virus. The presence of viral coinfection was an independent risk factor for disease severity.

Spontaneous Breathing Trial for Prediction of Extubation Success in Pediatric Patients Following Congenital Heart Surgery: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the usefulness of a spontaneous breathing trial for predicting extubation success in pediatric patients in the postoperative period after cardiac surgery compared with a physician-led weaning. STUDY DESIGN: Randomized, controlled trial. SETTING: PICU of a tertiary-care university hospital. PATIENTS: A population of pediatric patients following cardiac surgery for congenital heart disease. INTERVENTIONS: Patients on mechanical ventilation for more than 12 hours after surgery who were considered ready for weaning were randomized to the spontaneous breathing trial group or the control group. The spontaneous breathing trial was performed on continuous positive airway pressure with the pressure support of 10 cmH2O, the positive end-expiratory pressure of 5 cmH2O, and the fraction of inspired oxygen less than or equal to 0.5 for 2 hours. Patients in the control group underwent ventilator weaning according to clinical judgment. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was extubation success defined as no need for reintubation within 48 hours after extubation. Secondary outcomes were PICU length of stay, hospital length of stay, occurrence rate of ventilator-associated pneumonia, and mortality. One hundred and ten patients with the median age of 8 months were included in the study: 56 were assigned to the spontaneous breathing trial group and 54 were assigned to the control group. Demographic and clinical data and Risk Adjustment for Congenital Heart Surgery-1 classification were similar in both groups. Patients undergoing the spontaneous breathing trial had greater extubation success (83% vs 68%, p = 0.02) and shorter PICU length of stay (median 85 vs 367 hr, p < 0.0001) compared with the control group, respectively. There was no significant difference between groups in hospital length of stay, occurrence rate of ventilator-associated pneumonia, and mortality. CONCLUSIONS: Pediatric patients with congenital heart disease undergoing the spontaneous breathing trial postoperatively had greater extubation success and shorter PICU length of stay compared with those weaned according to clinical judgment.

Human coronavirus alone or in co-infection with rhinovirus C is a risk factor for severe respiratory disease and admission to the pediatric intensive care unit: A one-year study in Southeast Brazil.

OBJECTIVE: We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. DESIGN: Prospective observational cohort study. SETTING: A tertiary-care university hospital in Brazil. PATIENTS: Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal aspirates were collected from patients from June 1st, 2008 to May 31st, 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15-4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23-4.58) was independently associated with PICU admission. CONCLUSIONS: The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.

Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis.

BACKGROUND: Neutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown. METHODS: Infant (2 weeks old) and adult (6 weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured. RESULTS: Infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs. CONCLUSION: This study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis.

Neuropsychological outcome of children with traumatic brain injury and its association with late magnetic resonance imaging findings: A cohort study.

OBJECTIVES: To evaluate neuropsychological outcome after traumatic brain injury (TBI) and its association with trauma severity and late magnetic resonance imaging (MRI) findings. METHODS: Prospective cohort study of patients with TBI admitted to the paediatric intensive care unit over 5 years. Trauma severity was determined by Glasgow Coma Scale (GCS), neurological outcome by King's Outcome Scale for Childhood Head Injury (KOSCHI) and neuropsychological outcome by Wechsler Intelligence Scale for Children - Fourth Edition. RESULTS: Twenty-five children (median age 6 years at trauma) were included. Patients were divided into Disability (DIS)(n = 10) and Good Recovery (GR)(n = 15) groups. Initial GCS score was not significantly different in both groups (median 6 vs. 10; p = 0.34). DIS group had lower values ​​of working memory index (WMI)(median 74 vs. 94; p = 0.004), perceptual reasoning index (PRI)(75 vs. 96; p = 0.03), verbal comprehension index (VCI)(65 vs. 84; p = 0.02), processing speed index (PSI)(74 vs. 97; p = 0.01) and full-scale intelligence quotient (FSIQ)(65 vs. 87; p = 0.008). In the GR group, 60% of patients had normal or minimally altered MRI versus 10% of patients in the DIS group (p = 0.018). Fractional anisotropy positively correlated with WMI(r = 0.65; p = 0.005), PRI(r = 0.52; p = 0.03) and FSIQ(r = 0.50; p = 0.04). CONCLUSIONS: Neuropsychological impairment was observed in 40% of children who suffered a TBI and was associated with late MRI abnormalities.

Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study.

OBJECTIVE: We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. DESIGN: Prospective observational cohort study. SETTING: Two eight-bed PICUs of a tertiary-care university hospital. PATIENTS: A heterogeneous population of critically ill children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. CONCLUSIONS: Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was associated with increased morbidity and mortality, and may lead to long-term renal dysfunction.

Diagnostic and prognostic value of serum cystatin C in critically ill children with acute kidney injury.

OBJECTIVES: We aimed to evaluate the value of serum cystatin C for detection of acute kidney injury and pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease categories in critically ill children and to investigate whether serum cystatin C was associated with outcome. DESIGN: Prospective cohort study. SETTING: PICU of a tertiary-care university hospital. PATIENTS: A heterogeneous population of critically ill children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood and 24-hour urine samples were collected daily over the first 2 days after PICU admission for measurement of serum cystatin C, serum creatinine, and creatinine clearance. Acute kidney injury was classified by pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria. One hundred twenty-two children were prospectively enrolled; 40 (32.8%) developed acute kidney injury. Serum cystatin C was higher in patients with acute kidney injury compared with those who did not develop acute kidney injury at PICU admission (median, 0.90 mg/L vs 0.51 mg/L) and on the first (1.12 mg/L vs 0.57 mg/L) and second PICU days (1.15 mg/L vs 0.58 mg/L). Serum creatinine was higher in acute kidney injury group only on the first (0.50 mg/dL vs 0.40 mg/dL) and second PICU days (0.60 mg/dL vs 0.40 mg/dL). Serum cystatin C was increasingly higher according to acute kidney injury severity (Failure > Injury > Risk). Area under the receiver operating characteristic curve of cystatin C for acute kidney injury detection was 0.89. Serum cystatin C greater than 0.70 mg/L was associated with longer length of PICU stay (adjusted hazard ratio, 1.64) and prolonged duration of mechanical ventilation (adjusted hazard ratio, 1.82). CONCLUSIONS: Cystatin C is an early and accurate biomarker for acute kidney injury and pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease categories, and it is associated with adverse clinical outcomes in a heterogeneous population of critically ill children.

Evaluation of adrenal function in critically ill children.

OBJECTIVE: There is no consensus on adequate adrenal response to critical illness. We aimed to evaluate adrenal function in critically ill children and its association with clinical outcome. We hypothesized that salivary cortisol would be a more appropriate tool to evaluate adrenal function in critically ill children. METHODS: This was a prospective cohort study. The concentrations of serum total and salivary cortisol were measured in 34 critically ill children before and after stimulation with 250 µg adrenocorticotropic hormone (ACTH), and values were compared to a control group of healthy children (n = 15). Association between outcome and adrenal insufficiency defined by an increment in serum cortisol ≤250 nm (9 µg/dl) post-ACTH was assessed. RESULTS: Serum total and salivary cortisol concentrations pre- and post-ACTH were significantly higher in patients, and they were correlated at baseline (r = 0·67; P < 0·0001) and after ACTH (r = 0·41; P = 0·02). The incidence of adrenal insufficiency was 32·3%. This group had higher Paediatric Risk of Mortality III score (P = 0·04) but Paediatric Logistic Organ Dysfunction and vasoactive inotropic scores, duration of mechanical ventilation and length of paediatric intensive care unit and hospital stay were not significantly different compared with those with an increment >250 nm (9 µg/dl) post-ACTH. An inverse correlation between salivary cortisol post-ACTH and vasoactive inotropic score (r = -0·56; P = 0·0008) was observed. A salivary cortisol concentration post-ACTH of ≤226 nm (8·2 µg/dl) had a sensitivity of 79% and a specificity of 62% to discriminate need for vasoactive or inotropic support (area under receiver operating characteristic (ROC) curve 0·74). CONCLUSION: Adrenal insufficiency defined by the 'delta criterion' was not associated with outcome. A post-ACTH salivary cortisol of ≤226 nm (8·2 µg/dl) may be suggestive of an insufficient adrenal response to critical illness.

Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing ventilator-associated pneumonia after cardiac surgery: an observational study.

BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery. METHODS: This was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1. RESULTS: Thirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29). CONCLUSION: Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.

Oxidative stress markers are not associated with outcomes after pediatric heart surgery.

OBJECTIVES: To investigate whether perioperative serum levels of oxidative stress markers, thiobarbituric acid reactive substances (TBARS), and carbonyl moieties are associated with outcomes in children after heart surgery. BACKGROUND: Oxidative stress markers are increased following heart surgery with cardiopulmonary bypass (CPB) and can play a role in ischemia-reperfusion injury, but its associations with myocardial dysfunction, low cardiac output syndrome (LCOS), and outcomes are not proven. METHODS: In a retrospective secondary analysis of a cohort study comprising 55 children (median age, 109 [2-611] days), we compared pre-, intra- and postoperative serum levels of TBARS and carbonyl moieties among patients with and without postoperative LCOS, cyanotic and acyanotic congenital heart disease (CHD), and survivors and nonsurvivors. We also assessed the independent effect of TBARS and carbonyl moieties peak levels on the mortality-adjusted hospital length of stay (aLOS). RESULTS: Patients who developed postoperative LCOS (n = 36) were significantly younger, more frequently cyanotic, more severely ill, and underwent more complex procedures with longer CPB. However, TBARS and carbonyl moieties serum levels did not change significantly over time. Moreover, they were not significantly different in patients with or without LCOS, cyanotic and acyanotic CHD, or survivors and nonsurvivors. There was a significant correlation between TBARS and tumor necrosis factor alpha (TNF-α) peak serum levels. Neither TBARS nor carbonyl moieties peak serum levels were independently associated with aLOS. CONCLUSIONS: In conclusion, oxidative stress markers TBARS and carbonyl moieties were not associated with the development of LCOS, the aLOS, or mortality in children after heart surgery with CPB.

Pain assessment in neonates and infants in the post-operative period following cardiac surgery.

PURPOSE: We aimed to test the convergent validity of the COMFORT scale and the Cardiac Analgesic Assessment Scale (CAAS) and to evaluate changes in physiological parameters over time in response to a painful procedure in neonates and infants following cardiac surgery. METHODS: From October 2006 to May 2008, 16 children were prospectively evaluated over 1-3 days after cardiac surgery while they remained on mechanical ventilation and received infusions of sedatives and analgesics. Pain was assessed by the COMFORT scale and CAAS before and during endotracheal tube suctioning. Heart rate, systemic systolic blood pressure, pulmonary artery pressure, oxygen saturation and pupil size were recorded at the same times. RESULTS: During endotracheal suctioning on the first day, there was a significant increase in COMFORT and CAAS scores, systemic systolic blood pressure tended to decrease, pulmonary artery pressure significantly increased and there was a significant reduction in oxygen saturation. Heart rate and pupil size did not change significantly during the painful procedure throughout the study. COMFORT scores significantly correlated with CAAS scores on all days. Nevertheless, agreement for the detection of pain between both scales was weak (κ<0.5). The COMFORT scale detected more patients with pain. CONCLUSIONS: There was poor agreement between the COMFORT scale and CAAS for detection of pain in neonates and infants who had undergone cardiac surgery. A reduction in systemic systolic blood pressure and a rise in pulmonary artery pressure were observed during painful stimulation on the first post-operative day. For this population, a pain scale scoring physiological parameters according to their variation to higher and lower values should be developed.

Catch-up growth in children after repair of Tetralogy of Fallot.

PURPOSE: To evaluate the growth of children after repair of Tetralogy of Fallot, as well as the influence of residual lesions and socio-economic status. METHODS: A total of 17 children, including 10 boys with a median age of 16 months at surgery, were enrolled in a retrospective cohort, in a tertiary care university hospital. Anthropometric (as z-scores), clinical, nutritional, and social data were collected. RESULTS: Weight-for-age and weight-for-height z-scores decreased pre-operatively and recovered post-operatively in almost all patients, most markedly weight for age. Weight-for-height z-scores improved, but were still lower than birth values in the long term. Long-term height-for-age z-scores were higher than those at birth, surgery, and 3 months post-operatively. Most patients showed catch-up growth for height for age (70%), weight for age (82%), and weight for height (70%). Post-operative residual lesions (76%) influenced weight-for-age z-scores. Despite the fact that most patients (70%) were from low-income families, energy intake was above the estimated requirement for age and gender in all but one patient. There was no influence of socio-economic status on pre- and post-operative growth. Bone age was delayed and long-term-predicted height was within mid-parental height limits in 16 children (93%). CONCLUSION: Children submitted to Tetralogy of Fallot repair had pre-operative acute growth restriction and showed post-operative catch-up growth for weight and height. Acute growth restriction could still be present in the long term.

Late remote ischemic preconditioning in children undergoing cardiopulmonary bypass: a randomized controlled trial.

OBJECTIVE: Cardiopulmonary bypass is associated with ischemia-reperfusion injury to multiple organs. We aimed to evaluate whether remote ischemic preconditioning performed the day before surgery for congenital heart disease with cardiopulmonary bypass attenuates the postoperative inflammatory response and myocardial dysfunction. METHODS: This was a prospective, randomized, single-blind, controlled trial. Children allocated to remote ischemic preconditioning underwent 4 periods of 5 minutes of lower limb ischemia by a blood pressure cuff intercalated with 5 minutes of reperfusion. Blood samples were collected 4, 12, 24, and 48 hours after cardiopulmonary bypass to evaluate nuclear factor kappa B activation in leukocytes by quantification of mRNA of I kappa B alpha by real-time quantitative polymerase chain reaction and for interleukin-8 and 10 plasma concentration measurements by enzyme-linked immunosorbent assay. Myocardial dysfunction was assessed by N-terminal pro-B-type natriuretic peptide and cardiac troponin I plasma concentrations, measured by chemiluminescence, and clinical parameters of low cardiac output syndrome. RESULTS: Twelve children were allocated to remote ischemic preconditioning, and 10 children were allocated to the control group. Demographic data and Risk Adjustment for Congenital Heart Surgery 1 classification were comparable in both groups. Remote ischemic preconditioning group had lower postoperative values of N-terminal pro-B-type natriuretic peptide, but cardiac troponin I levels were not significantly different between groups. Interleukin-8 and 10 concentrations and I kappa B alpha gene expression were similar in both groups. Postoperative morbidity was similar in both groups; there were no postoperative deaths in either group. CONCLUSIONS: Late remote ischemic preconditioning did not provide clinically relevant cardioprotection to children undergoing cardiopulmonary bypass.

Evidence of Renal Infection in Fatal Cases of 2009 Pandemic Influenza A (H1N1).

The 2009 pandemic influenza A (H1N1) caused significant morbidity and mortality. Acute lung injury is the hallmark of the disease, but multiple organ system dysfunction can develop and lead to death. Therefore, we sought to investigate whether there was postmortem evidence of H1N1 presence and virus-induced organ injury in autopsy specimens. Five cases in which patients died of influenza A (H1N1) virus infection were studied. The lungs of all patients showed macroscopic and microscopic findings already described for H1N1 (consolidation, edema, hemorrhage, alveolar damage, hyaline membrane, and inflammation), and H1N1 viruses were present in alveolar cells in immunochemical studies. Acute tubular necrosis was present in all cases, but there was no evidence of direct virus-induced kidney injury. Nevertheless, H1N1 viruses were found in the cytoplasm of glomerular macrophages in the kidneys of 4 patients. Therefore, our data provide strong evidence that H1N1 presence is not restricted to the lungs.

Abdominal compartment syndrome caused by massive pyonephrosis in an infant with primary obstructive megaureter.

The authors report a case of abdominal compartment syndrome caused by massive pyonephrosis in an infant with primary obstructive megaureter successfully treated with emergency surgical decompression.

Effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia in children undergoing cardiac surgery.

OBJECTIVE: To evaluate the effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia and ventilator-associated pneumonia (VAP) in children undergoing cardiac surgery. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Pediatric intensive care unit (PICU) at a tertiary care hospital. PATIENTS: One hundred sixty children undergoing surgery for congenital heart disease, randomized into 2 groups: chlorhexidine (n = 87) and control (n = 73). INTERVENTIONS: Oral hygiene with 0.12% chlorhexidine gluconate or placebo preoperatively and twice a day postoperatively until PICU discharge or death. RESULTS: Patients in experimental and control groups had similar ages (median, 12.2 vs 10.8 months; P = .72) and risk adjustment for congenital heart surgery 1 score distribution (66% in category 1 or 2 in both groups; P = .17). The incidence of nosocomial pneumonia was 29.8% versus 24.6% (P = .46) and the incidence of VAP was 18.3% versus 15% (P = .57) in the chlorhexidine and the control group, respectively. There was no difference in intubation time (P = .34), need for reintubation (P = .37), time interval between hospitalization and nosocomial pneumonia diagnosis (P = .63), time interval between surgery and nosocomial pneumonia diagnosis (P = .10), and time on antibiotics (P = .77) and vasoactive drugs (P = .16) between groups. Median length of PICU stay (3 vs 4 days; P = .53), median length of hospital stay (12 vs 11 days; P = .67), and 28-day mortality (5.7% vs 6.8%; P = .77) were also similar in the chlorhexidine and the control group. CONCLUSIONS: Oral hygiene with 0.12% chlorhexidine gluconate did not reduce the incidence of nosocomial pneumonia and VAP in children undergoing cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00829842 .

Abdominal compartment syndrome: A review.

OBJECTIVES: The aims of this review were to summarize a) the consensus definitions of normal and pathologic intra-abdominal pressure (IAP); b) the techniques to measure IAP; c) the risk factors for intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS); d) the pathophysiology of ACS; and e) the current recommendations for management and prevention of ACS. DATA SOURCES: PubMed was searched using the following terms: ACS, IAH, IAP, and abdominal decompression. DATA SYNTHESIS: ACS represents the natural progression of end-organ dysfunction caused by increased IAP and develops if IAH is not recognized and treated appropriately. Although the reported incidence of ACS is relatively low in critically ill children (0.6%-4.7%) it may be under-recognized and under-reported. The diagnosis of IAH/ACS depends on a high index of suspicion and the accurate and frequent measurement of IAP in patients at risk. Mortality from ACS remains high (50%-60%) even when decompression of the abdomen is performed early, which highlights the importance of detection and treatment of elevated IAP before end-organ damage occurs. CONCLUSIONS: A widespread awareness of the recognition and current approach to management and prevention of IAH and ACS is needed among pediatric intensivists, so outcome of these life-threatening disease processes might be improved.

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I.

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4h PO as independent predictors of LCOS, while cTnI 4h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB.