Martin C. J. Kneyber

Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria

ObjectiveThe present study was undertaken to evaluate the practicability of the proposed pediatric RIFLE (pRIFLE) criteria in a patient population at risk for acute kidney injury (AKI) and to analyze the prevalence and association of AKI as defined by pRIFLE with mortality.DesignRetrospective, descriptive cohort study.SettingSingle-center, 9-bed PICU facility.PatientsChildren with respiratory failure requiring mechanical ventilation for more than 4 days admitted between January 2002 and December 2006.InterventionsNone.Measurements and resultsData of 103 patients were studied. Median age was 4.5 years (range 1 month–17 years). Six patients received renal replacement therapy. Seventeen patients (17%) died. Sixty patients (58%) developed AKI by pRIFLE. Mean time to attainment of the first RIFLE stratum was 1.9 ± 1.6 days. By pRIFLE, 34 of the 60 patients fulfilled the maximum AKI criteria on the first day after admission based on the estimated creatinine clearance criterion. Patients with AKI according to the pRIFLE scoring system had five times higher mortality than patients without AKI (25 vs. 5%, P < 0.05).ConclusionsWe observed a high incidence of significant AKI in a PICU population at risk, which was associated with high mortality. Pediatric RIFLE criteria may guide in the early identification of patients at risk for AKI and in the initiation of therapy.

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review.

One of the major questions regarding long‐term side effects of bronchiolitis by respiratory syncytial virus (RSV) is whether or not it induces asthma in later life. In this quantitative review, the data of 10 controlled studies are analysed. Methods: Follow‐up studies of RSV bronchiolitis published between January 1978 and December 1998 were identified through a MEDLINE search. Studies were selected if (i) postnatal age at the time of the inital illness was below 12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the diagnosis RSV was virologically confirmed in all cases, and (iv) a control group was used. Results: Six studies met all selection criteria. Up to 5 y of follow‐up after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared to only 11% in the control group (p < 0.001). Between 5 and 10 y of follow‐up 22% of the bronchiolitis group reported wheezing against 10% of the control group (p= 0.19). The incidence of recurrent wheezing as defined by three or more wheezing episodes also decreased with increasing years of follow‐up: at 5 or more years of follow‐up the difference between the RSV group and the control group was no longer significant. Furthermore, the presence of either a personal and/or a family history of either atopy and/or asthma did not differ between the two groups.

Risk factors for respiratory syncytial virus associated apnoea

Abstract Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Childrens Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO2, pCO2 and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO2 and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8 – 6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3 – 12.9) in children with recurrent episodes of apnoea. Conclusions Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea.

Relationship between clinical severity of respiratory syncytial virus infection and subtype.

The relationship between clinical severity of respiratory syncytial virus (RSV) infection and distribution of subtype A or B was investigated. The data of 232 children, who were admitted with RSV infection or diagnosed in the outpatient department of the Sophia Childrens Hospital, Rotterdam between 1992 and 1995, were studied. The diagnosis of RSV was confirmed by a direct immunofluorescence assay. Subtyping was performed by an indirect immunofluorescence assay using specific monoclonal antibodies. Gender, age at diagnosis, gestational age and birth weight, the presence of underlying diseases, feeding difficulties, the presence of wheezing and retractions, respiratory rate, temperature, clinical diagnosis at presentation, oxygen saturation (SaO2), carbon dioxide tension (PCO2), and pH, characteristics of hospitalisation, and the need for mechanical ventilation were observed. Analysis was performed on data from all patients diagnosed with RSV infection in the period between 1992 and 1995 spanning three RSV seasons, and separately on the RSV season 1993-4. The outcome of the three year analysis (150 (64.7%) subtype A v 82 (35.3%) subtype B) was compared with the outcome of the season 1993-4, a mixed epidemic with 37 (60.7%) subtype A and 24 (39.3%) subtype B isolates. None of the variables observed in the season 1993-4 differed significantly between RSV subtype A and B. Similar results were obtained from the analysis in the period 1992 until 1995, with the exception of PCO2 (a higher PCO2 was found in subtype A, p < 0.001) and retractions (more retractions were noted in patients with subtype A, p = 0.03). After correcting for possible confounders using regression analysis, these differences were not significant anymore. The data indicate that there is no relationship between clinical severity of RSV infection and subtype.

Treatment and prevention of respiratory syncytial virus infection

Abstract This review discusses the current knowledge on treatment and prevention of respiratory synctial virus (RSV) infections in children. Unfortunately, an effective therapy is not yet available. The efficacy of corticosteroids and bronchodilators has not yet been adequately documented and the use of ribavirin is only indicated in a highly selected group of high risk patients with T-cell immunodeficiency. The results of studies on the efficacy of vitamin A, interferon and antibiotics showed disappointing results. Vaccination research has produced candidate vaccines such as the recombinant vaccine BBG2Na, a subunit vaccine PFP-2 and cold-passaged-temperature sensitive vaccines. However, phase III efficacy trials in infants, young children and the elderly are still lacking. Passive protection against infections by RSV can be conferred by the use of RSV hyperimmune globulin or by the administration of palivizumab, a monoclonal antibody. However, large costs are involved. In addition, major differences have been reported in the prevalence of RSV lower respiratory tract infections in different countries, regions and even within well-known high-risk populations. Conclusion We suggest the development of local and regional guidelines based on hospitalisation rates in high-risk infants and cost-benefit analysis studies.

Ventilator-induced Lung Injury. Similarity and Differences between Children and Adults

It is well established that mechanical ventilation can injure the lung, producing an entity known as ventilator-induced lung injury (VILI). There are various forms of VILI, including volutrauma (i.e., injury caused by overdistending the lung), atelectrauma (injury due to repeated opening/closing of lung units), and biotrauma (release of mediators that can induce lung injury or aggravate pre-existing injury, potentially leading to multiple organ failure). Experimental data in the pediatric context are in accord with the importance of VILI, and appear to show age-related susceptibility to VILI, although a conclusive link between use of large Vts and mortality has not been demonstrated in this population. The relevance of VILI in the pediatric intensive care unit population is thus unclear. Given the physiological and biological differences in the respiratory systems of infants, children, and adults, it is difficult to directly extrapolate clinical practice from adults to children. This Critical Care Perspective analyzes the relevance of VILI to the pediatric population, and addresses why pediatric patients might be less susceptible than adults to VILI.

Outcome after resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia: Dutch nationwide retrospective cohort study

Objectives To evaluate the outcome of drowned children with cardiac arrest and hypothermia, and to determine distinct criteria for termination of cardiopulmonary resuscitation in drowned children with hypothermia and absence of spontaneous circulation. Design Nationwide retrospective cohort study. Setting Emergency departments and paediatric intensive care units of the eight university medical centres in the Netherlands. Participants Children aged up to 16 with cardiac arrest and hypothermia after drowning, who presented at emergency departments and/or were admitted to intensive care. Main outcome measure Survival and neurological outcome one year after the drowning incident. Poor outcome was defined as death or survival in a vegetative state or with severe neurological disability (paediatric cerebral performance category (PCPC) ≥4). Results From 1993 to 2012, 160 children presented with cardiac arrest and hypothermia after drowning. In 98 (61%) of these children resuscitation was performed for more than 30 minutes (98/160, median duration 60 minutes), of whom 87 (89%) died (95% confidence interval 83% to 95%; 87/98). Eleven of the 98 children survived (11%, 5% to 17%), but all had a PCPC score ≥4. In the 62 (39%) children who did not require prolonged resuscitation, 17 (27%, 16% to 38%) survived with a PCPC score ≤3 after one year: 10 (6%) had a good neurological outcome (score 1), five (3%) had mild neurological disability (score 2), and two (1%) had moderate neurological disability (score 3). From the original 160 children, only 44 were alive at one year with any outcome. Conclusions Drowned children in whom return of spontaneous circulation is not achieved within 30 minutes of advanced life support have an extremely poor outcome. Good neurological outcome is more likely when spontaneous circulation returns within 30 minutes of advanced life support, especially when the drowning incident occurs in winter. These findings question the therapeutic value of resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia.

STRUCTURAL CHANGES OF THE HEART DURING SEVERE SEPSIS OR SEPTIC SHOCK

ABSTRACT Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors.

Tidal Volume and Mortality in Mechanically Ventilated Children: A Systematic Review and Meta-Analysis of Observational Studies

Objective:To determine whether tidal volume is associated with mortality in critically ill, mechanically ventilated children. Data Sources:MEDLINE, EMBASE, and CINAHL databases from inception until July 2013 and bibliographies of included studies without language restrictions. Study Selection:Randomized clinical trials and observational studies reporting mortality in mechanically ventilated PICU patients. Data Extraction:Two authors independently selected studies and extracted data on study methodology, quality, and patient outcomes. Meta-analyses were performed using the Mantel-Haenszel random-effects model. Heterogeneity was quantified using I2. Study quality was assessed using the Newcastle-Ottawa Score for cohort studies. Data Synthesis:Out of 142 citations, seven studies met the inclusion criteria, and additional two articles were identified from references of the found articles. One was excluded. These eight studies included 1,756 patients. Mortality rates ranged from 13% to 42%. There was no association between tidal volume and mortality when tidal volume was dichotomized at 7, 8, 10, or 12 mL/kg. Comparing patients ventilated with tidal volume less than 7 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg and tidal volume less than 8 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg also showed no association between tidal volume and mortality. Limiting the analysis to patients with acute lung injury/acute respiratory distress syndrome did not change these results. Heterogeneity was observed in all pooled analyses. Conclusions:A relationship between tidal volume and mortality in mechanically ventilated children could not be identified, irrespective of the severity of disease. The significant heterogeneity observed in the pooled analyses necessitates future studies in well-defined patient populations to understand the effects of tidal volume on patient outcome.