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1.  Resource use and outcome in critically ill patients with hematological malignancy: a retrospective cohort study 
Critical Care  2008;12(3):R75.
Introduction
The paucity of data on resource use in critically ill patients with hematological malignancy and on these patients' perceived poor outcome can lead to uncertainty over the extent to which intensive care treatment is appropriate. The aim of the present study was to assess the amount of intensive care resources needed for, and the effect of treatment of, hemato-oncological patients in the intensive care unit (ICU) in comparison with a nononcological patient population with a similar degree of organ dysfunction.
Methods
A retrospective cohort study of 101 ICU admissions of 84 consecutive hemato-oncological patients and 3,808 ICU admissions of 3,478 nononcological patients over a period of 4 years was performed.
Results
As assessed by Therapeutic Intervention Scoring System points, resource use was higher in hemato-oncological patients than in nononcological patients (median (interquartile range), 214 (102 to 642) versus 95 (54 to 224), P < 0.0001). Severity of disease at ICU admission was a less important predictor of ICU resource use than necessity for specific treatment modalities. Hemato-oncological patients and nononcological patients with similar admission Simplified Acute Physiology Score scores had the same ICU mortality. In hemato-oncological patients, improvement of organ function within the first 48 hours of the ICU stay was the best predictor of 28-day survival.
Conclusion
The presence of a hemato-oncological disease per se is associated with higher ICU resource use, but not with increased mortality. If withdrawal of treatment is considered, this decision should not be based on admission parameters but rather on the evolutional changes in organ dysfunctions.
doi:10.1186/cc6921
PMCID: PMC2481472  PMID: 18538003
2.  The opinion of clinical staff regarding painfulness of procedures in pediatric hematology-oncology: an Italian survey 
Background
Beliefs of caregivers about patient's pain have been shown to influence assessment and treatment of children's pain, now considered an essential part of cancer treatment. Painful procedures in hematology-oncology are frequently referred by children as the most painful experiences during illness. Aim of this study was to evaluate professionals' beliefs about painfulness of invasive procedures repeatedly performed in Pediatric Hemato-Oncology Units.
Methods
Physicians, nurses, psychologists and directors working in Hemato-Oncology Units of the Italian Association of Pediatric Hematology-Oncology (AIEOP) were involved in a wide-nation survey. The survey was based on an anonymous questionnaire investigating beliefs of operators about painfulness of invasive procedures (lumbar puncture, bone marrow aspirate and bone marrow biopsy) and level of pain management.
Results
Twenty-four directors, 120 physicians, 248 nurses and 22 psychologists responded to the questionnaire. The score assigned to the procedural pain on a 0-10 scale was higher than 5 in 77% of the operators for lumbar puncture, 97.5% for bone marrow aspiration, and 99.5% for bone marrow biopsy. The scores assigned by nurses differed statistically from those of the physicians and directors for the pain caused by lumbar puncture and bone marrow aspiration. Measures adopted for procedural pain control were generally considered good.
Conclusions
Invasive diagnostic-therapeutic procedures performed in Italian Pediatric Hemato-Oncology Units are considered painful by all the caregivers involved. Pain management is generally considered good. Aprioristically opinions about pain depend on invasiveness of the procedure and on the professional role.
doi:10.1186/1824-7288-37-27
PMCID: PMC3127832  PMID: 21663631
3.  Impact of Continuous Renal Replacement Therapy on Oxygenation in Children with Acute Lung Injury after Allogeneic Hematopoietic Stem Cell Transplantation 
Pediatric blood & cancer  2010;55(3):540-545.
Background
Acute lung injury (ALI) continues to carry a high mortality rate in children after allogeneic hematopoietic stem cell transplant (HSCT). Continuous renal replacement therapy (CRRT) is often used for these patients for various indications including renal failure and fluid overload, and may have a beneficial effect on oxygenation and survival. Therefore, we sought to determine the effect of CRRT on oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI, and to document survival to intensive care unit discharge in this at-risk population receiving both mechanical ventilation and CRRT.
Procedure
Retrospective analysis of a pediatric allogeneic HSCT cohort admitted to intensive care unit of a single pediatric oncology center from 1994 to 2006 who received CRRT during a course of mechanical ventilation for ALI.
Results
Thirty post-HSCT mechanically ventilated children with ALI who underwent CRRT were included. There was a significant improvement in PaO2/FiO2 with median increase of 31 and 43 in the 24 and 48 hour intervals after initiation of CRRT compared with the 24 hour interval before CRRT (p = 0.0008 and 0.0062, respectively). This improvement in PaO2/FiO2 correlated significantly with reduction of fluid balance achieved after initiation of CRRT (p=0.0001). There was a trend not reaching statistical significance in improvement in mean airway pressure 48 hours after CRRT in survivors compared to non-survivors.
Conclusions
CRRT improved oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI.
doi:10.1002/pbc.22561
PMCID: PMC3214656  PMID: 20658627
Hematopoietic stem cell transplantation; Critically ill; Acute lung injury; Pediatrics; Renal replacement therapy; Oxygenation
4.  Early recognition and management of septic shock in children 
Pediatric Reports  2012;4(1):e13.
Septic shock remains a major cause of morbidity and mortality among children, mainly due to acute hemodynamic compromise and multiple organ failures. In the last decade, international guidelines for the management of septic shock, as well as clinical practice parameters for hemodynamic support of pediatric patients, have been published. Early recognition and aggressive therapy of septic shock, by means of abundant fluid resuscitation, use of catecholamines and other adjuvant drugs, are widely considered of pivotal importance to improve the short and long-term outcome of these patients. The aim of this paper is to summarize the modern approach to septic shock in children, particularly in its very initial phase, when pediatric healthcare providers may be required to intervene in the pre-intensive care unit setting or just on admission in the pediatric intensive care unit.
doi:10.4081/pr.2012.e13
PMCID: PMC3357612  PMID: 22690305
septic shock; children.
5.  Fertility Preservation in Girls 
Children that undergo treatment for cancer are at risk of suffering from subfertility or hormonal dysfunction due to the detrimental effects of radiotherapy and chemotherapeutic agents on the gonads. Cryopreservation of ovarian tissue prior to treatment offers the possibility of restoring gonadal function after resumption of therapy. Effective counseling and management of pediatric patients is crucial for preserving their future reproductive potential. The purpose of this article is to review recent literature and to revise recommendations we made in a 2007 article. Pediatric hemato-oncology, reproductive endocrinology, surgery, anesthesia and bioethics perspectives are discussed and integrated to propose guidelines for offering ovarian cryopreservation to premenarcheal girls with cancer.
doi:10.1155/2012/139193
PMCID: PMC3307018  PMID: 22496695
6.  Pediatric Intensive Care Unit admission criteria for haemato-oncological patients: a basis for clinical guidelines implementation 
Pediatric Reports  2011;3(2):e13.
Recent advances in supportive care and progress in the development and use of chemotherapy have considerably improved the prognosis of many children with malignancy, thus the need for intensive care admission and management is increasing, reaching about 40% of patients throughout the disease course. Cancer remains a major death cause in children, though outcomes have considerably improved over the past decades. Prediction of outcome for children with cancer in Pediatric Intensive Care Unit (PICU) obviously requires clinical guidelines, and these are not well defined, as well as admission criteria. Major determinants of negative outcomes remain severe sepsis/septic shock association and respiratory failure, deserving specific approach in children with cancer, particularly those receiving a bone marrow transplantation. A nationwide consensus should be achieved among pediatric intensivists and oncologists regarding the threshold clinical conditions requiring Intensive Care Unit (ICU) admission as well as specific critical care protocols. As demonstrated for the critically ill non-oncologic child, it appears unreasonable that pediatric patients with malignancy can be admitted to an adult Intensive Care Unit ICU. On a national basis a pool of refecence institutions should be identified and early referral to an oncologic PICU is warranted.
doi:10.4081/pr.2011.e13
PMCID: PMC3133495  PMID: 21772950
intensive care; malignancy; Pediatric Intensive Care Unit admission criteria; children; critically ill.
7.  Assessment of Serologic Immunity to Diphtheria-Tetanus-Pertussis After Treatment of Korean Pediatric Hematology and Oncology Patients 
The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination.
doi:10.3346/jkms.2012.27.1.78
PMCID: PMC3247779  PMID: 22219618
Serologic Immunity; Immunocompromised Children; Diphtheria; Tetanus; Pertussis; Vaccination
8.  Identifying futility in a paediatric critical care setting: a prospective observational study 
Archives of Disease in Childhood  2001;84(3):265-268.
AIMS—To determine the extent of futile care provided to critically ill children admitted to a paediatric intensive care setting.
METHODS—Prospective evaluation of consecutive admissions to a 20 bedded multidisciplinary paediatric intensive care unit of a North London teaching hospital over a nine month period. Three previously defined criteria for futility were used: (1) imminent demise futility (those with a mortality risk greater than 90% using the Paediatric Risk of Mortality (PRISM II) score); (2) lethal condition futility (those with conditions incompatible with long term survival); and (3) qualitative futility (those with unacceptable quality of life and high morbidity).
RESULTS—A total of 662 children accounting for 3409 patient bed days were studied. Thirty four patients fulfilled at least one of the criteria for futility, and used a total of 104 bed days (3%). Only 33 (0.9%) bed days were used by patients with mortality risk greater than 90%, 60 (1.8%) by patients with poor long term prognosis, and 16 (0.5%) by those with poor quality of life. Nineteen of 34 patients died; withdrawal of treatment was the mode of death in 15 (79%).
CONCLUSIONS—Cost containment initiatives focusing on futility in the paediatric intensive care unit setting are unlikely to be successful as only relatively small amounts of resources were used in providing futile care. Paediatricians are recognising futility early and may have taken ethically appropriate measures to limit care that is futile.


doi:10.1136/adc.84.3.265
PMCID: PMC1718671  PMID: 11207181
9.  At the coalface--medical ethics in practice. Futility and death in paediatric medical intensive care. 
Journal of Medical Ethics  1996;22(5):279-281.
We have conducted a retrospective study of deaths on a paediatric medical intensive care unit over a two-year period and reviewed similar series from outside the UK. There were 89 deaths out of 651 admission (13.7% mortality). In almost two-thirds of the cases death occurred with a decision to limit medical treatment or withdraw mechanical ventilation, implying that additional or further therapy was considered futile. We highlight this as a crucially important issue in the practice of intensive care. More comprehensive studies are needed to help clinicians derive consensus on what constitutes a futile intervention, and therefore when such an intervention should be withheld. This will help families and society better understand the limitations of intensive care.
PMCID: PMC1377059  PMID: 8910779
10.  Extremes of weight centile are associated with increased risk of mortality in pediatric intensive care 
Critical Care  2011;15(2):R106.
Introduction
Although numerous studies have linked extremes of weight with poor outcome in adult intensive care patients, the effect of weight on intensive care outcome has not previously been reported in the pediatric population. The aim of this study was to investigate the relationship between admission weight centile and risk-adjusted mortality in pediatric intensive care patients.
Methods
Data were collected on 6337 consecutively admitted patients over an 8.5 year period in a 15 bed pediatric intensive care unit (ICU) located in a university-affiliated tertiary referral children's hospital. A weight centile variable was entered into a multivariate logistic regression model that included all other pediatric index of mortality (PIM-2) variables, in order to determine whether weight centile was an independent risk factor for mortality.
Results
Weight centile was associated with mortality in both univariate and multivariate analysis, with the lowest mortality being associated with weights on the 75th centile and increasing symmetrically around this nadir. A transformed weight centile variable (absolute value of weight centile-75) was independently associated with mortality (odds ratio 1.02, P = 0.000) when entered into a multivariate logistic regression model that included the PIM-2 variables.
Conclusions
In this single-center cohort, weight centile was an independent risk factor for mortality in the ICU, with mortality increasing for patients at either end of the weight spectrum. These observations suggest that the accuracy of mortality prediction algorithms may be improved by inclusion of weight centile in the models. A prospective multicenter study should be undertaken to confirm our findings.
doi:10.1186/cc10127
PMCID: PMC3219384  PMID: 21453507
11.  Application of the Pediatric Risk of Mortality Score (PRISM) score and determination of mortality risk factors in a tertiary pediatric intensive care unit 
Clinics  2010;65(11):1087-1092.
INTRODUCTION:
To establish disease severity at admission can be performed by way of the mortality prognostic. Nowadays the prognostic scores make part of quality control and research. The Pediatric Risk of Mortality (PRISM) is one of the scores used in the pediatric intensive care units.
OBJECTIVES:
The purpose of this study is the utilization of the PRISM and determination of mortality risk factors in a tertiary pediatric intensive care unit.
METHODS
: Retrospective cohort study, in a period of one year, at a general tertiary pediatric intensive care unit. The pediatric risk of mortality scores corresponding to the first 24 hours of hospitalization were recorded; additional data were collected to characterize the study population.
RESULTS:
359 patients were included; the variables that were found to be risk factors for death were multiple organ dysfunction syndrome on admission, mechanical ventilation, use of vasoactive drugs, hospital‐acquired infection, parenteral nutrition and duration of hospitalization (p < 0,0001). Fifty‐four patients (15%) died; median pediatric risk of mortality score was significantly lower in patients who survived (p = 0,0001). The ROC curve yielded a value of 0.76 (CI 95% 0,69–0,83) and the calibration was shown to be adequate.
DISCUSSION:
It is imperative for pediatric intensive care units to implement strict quality controls to identify groups at risk of death and to ensure the adequacy of treatment. Although some authors have shown that the PRISM score overestimates mortality and that it is not appropriate in specific pediatric populations, in this study pediatric risk of mortality showed satisfactory discriminatory performance in differentiating between survivors and non‐survivors.
CONCLUSIONS:
The pediatric risk of mortality score showed adequate discriminatory capacity and thus constitutes a useful tool for the assessment of prognosis for pediatric patients admitted to a tertiary pediatric intensive care units.
doi:10.1590/S1807-59322010001100005
PMCID: PMC2999700  PMID: 21243277
Quality of care; Prognostic scores; Multiple organ dysfunction syndrome; Critical care; Mortality rate
12.  Admission source and mortality in a pediatric intensive care unit 
Background and Aims:
Studies carried out in different countries have shown that source of patient admission in Intensive Care Units (ICUs) is associated to death. Patients admitted from wards show a greater ICU mortality. The aim of the present study was to investigate the association between admission source and outcome in a Pediatric Intensive Care Unit (PICU).
Materials and Methods:
We studied all PICU admissions that took place between January 2002 and December 2005 in a tertiary hospital in Brazil. The major outcome studied was death while in the PICU. The independent variable analyzed was admission source, defined either as pediatric emergency room (PER), wards, operating room (OR) of the same hospital or other sources.
Results:
A total of 1823 admissions were studied. The overall expected mortality based on the Pediatric Index of Mortality 2 was 6.5% and the observed mortality was 10.3%. In adjusted analysis, the mortality was doubled in patients admitted from wards when compared with the PER patients.
Conclusions:
Observed mortality rates were higher in patients admitted from wards within the same hospital, even after adjustment.
doi:10.4103/0972-5229.99114
PMCID: PMC3439783  PMID: 22988362
Child; intensive care units; mortality; patient admission; pediatric
13.  Pediatric Neurocritical Care 
Neurotherapeutics  2011;9(1):3-16.
Pediatric neurocritical care is an emerging multidisciplinary field of medicine and a new frontier in pediatric critical care and pediatric neurology. Central to pediatric neurocritical care is the goal of improving outcomes in critically ill pediatric patients with neurological illness or injury and limiting secondary brain injury through optimal critical care delivery and the support of brain function. There is a pressing need for evidence based guidelines in pediatric neurocritical care, notably in pediatric traumatic brain injury and pediatric stroke. These diseases have distinct clinical and pathophysiological features that distinguish them from their adult counterparts and prevent the direct translation of the adult experience to pediatric patients. Increased attention is also being paid to the broader application of neuromonitoring and neuroprotective strategies in the pediatric intensive care unit, in both primary neurological and primary non-neurological disease states. Although much can be learned from the adult experience, there are important differences in the critically ill pediatric population and in the circumstances that surround the emergence of neurocritical care in pediatrics.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-011-0093-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s13311-011-0093-6
PMCID: PMC3271153  PMID: 22183817
Pediatric neurocritical care; Children; Pediatric TBI; Childhood stroke; Neuroprotection; Nonconvulsive seizures
14.  Assessing the Guidelines for Potassium Replacement in Pediatric Oncology Patients Receiving Amphotericin B 
OBJECTIVE
To examine the practice of potassium chloride (KCl) replacement in pediatric oncology patients receiving amphotericin B (amp-B).
METHODS
A retrospective observational chart review was conducted of patients who received amp-B on the oncology unit between August 2000 and May 2001. A survey was distributed to pediatric oncology pharmacists at other pediatric institutions to assess KCl infusion guidelines across North America.
RESULTS
Twenty hypokalemic episodes were identified within 22 patient admissions. Fifty-five percent used KCl replacement (by all combined routes) at rates exceeding the institution's guidelines. Other pediatric institutions varied with respect to the maximum rates and concentration of KCl permitted on non-intensive care units.
CONCLUSIONS
Based on the data from this review, the KCl administration guidelines for our hospital were changed. We now allow a maximum peripheral line concentration of 60 mEq/L, a maximum central line concentration of 120 mEq/L and a maximum KCl infusion rate of 0.4 mEq/kg/hr without the requirement of a heart monitor. Parenteral Nutrition is now restricted to maximum potassium concentration of 80 mEq/L and fluid-restricted patients are restricted to a maximum concentration of 150 mEq/L.
doi:10.5863/1551-6776-11.4.223
PMCID: PMC3468105  PMID: 23115538
15.  Extracorporeal life support for status asthmaticus: the breath of life that's often forgotten 
Critical Care  2009;13(2):136.
Status asthmaticus continues to be significant cause of intensive care admission, morbidity, and mortality in pediatric populations. Furthermore, despite improved outpatient management and broader use of controller medications, patients with severe status asthmaticus account for a notable proportion of these admissions. There is variability in management and outcomes between institutions; however, early and aggressive management to avoid respiratory failure is paramount. In those patients who progress to develop severe respiratory failure, extracorporeal life support (ECLS) can be a life-saving therapy. Here, we briefly overview the use of ECLS for status asthmaticus, as reported through the Extracorporeal Life Support Organization, including the specific institutional experience at Children's Healthcare of Atlanta at Egleston, and consider how earlier initiation of ECLS may benefit patients with severe status asthmaticus refractory to conventional medical therapy.
doi:10.1186/cc7757
PMCID: PMC2689481  PMID: 19439044
16.  Endotoxemia in pediatric critical illness - a pilot study 
Critical Care  2011;15(3):R141.
Introduction
The aim was to investigate the prevalence of endotoxemia in children admitted to pediatric intensive care unit (PICU), and its association with disease severity and outcome.
Methods
We conducted a prospective, observational cohort study of children admitted to PICU at St. Mary's Hospital, London over a 6-month period. One hundred consecutive patients were recruited. Demographic and clinical data were collected. Severity of illness was assessed by the pediatric index of mortality 2 (PIM2) score. The pediatric logistic organ dysfunction (PELOD) score was performed daily for the first 4 days. Patients were categorized according to primary reason for PICU admission. Blood samples were taken within 24 hours of admission and endotoxemia was measured using the endotoxin activity assay (EAA). Patients were stratified according to EAA level (high, EAA > 0.4, low, EAA < 0.4) and categorized as septic, post-surgical, respiratory or other. Data were analyzed using appropriate non-parametric tests.
Results
EAA level was significantly lower in PICU controls versus other PICU admissions (P = 0.01). Fifty-five children had endotoxemia on admission. Forty-one (75%) of these were eventually diagnosed with an infectious cause of admission. Nine children without infection had elevated EAA on admission. An infectious cause of admission was significantly associated with endotoxemia (P < 0.005). Of 15 children with gram-negative infection, only 9 (60%) had endotoxemia on admission. Endotoxemia on admission was not associated with shock or death. However, there was a tendency for increased PELOD score and length of stay in endotoxemic children.
Conclusions
Endotoxemia is common in children admitted to intensive care. Understanding the implications of endotoxemia and potential anti-endotoxin strategies may have the potential to reduce severity of illness and length of PICU stay in critically ill children.
doi:10.1186/cc10264
PMCID: PMC3219013  PMID: 21651808
17.  Ethical issues at the interface of clinical care and research practice in pediatric oncology: a narrative review of parents' and physicians' experiences 
BMC Medical Ethics  2011;12:18.
Background
Pediatric oncology has a strong research culture. Most pediatric oncologists are investigators, involved in clinical care as well as research. As a result, a remarkable proportion of children with cancer enrolls in a trial during treatment. This paper discusses the ethical consequences of the unprecedented integration of research and care in pediatric oncology from the perspective of parents and physicians.
Methodology
An empirical ethical approach, combining (1) a narrative review of (primarily) qualitative studies on parents' and physicians' experiences of the pediatric oncology research practice, and (2) comparison of these experiences with existing theoretical ethical concepts about (pediatric) research. The use of empirical evidence enriches these concepts by taking into account the peculiarities that ethical challenges pose in practice.
Results
Analysis of the 22 studies reviewed revealed that the integration of research and care has consequences for the informed consent process, the promotion of the child's best interests, and the role of the physician (doctor vs. scientist). True consent to research is difficult to achieve due to the complexity of research protocols, emotional stress and parents' dependency on their child's physician. Parents' role is to promote their child's best interests, also when they are asked to consider enrolling their child in a trial. Parents are almost never in equipoise on trial participation, which leaves them with the agonizing situation of wanting to do what is best for their child, while being fearful of making the wrong decision. Furthermore, a therapeutic misconception endangers correct assessment of participation, making parents inaccurately attribute therapeutic intent to research procedures. Physicians prefer the perspective of a therapist over a researcher. Consequently they may truly believe that in the research setting they promote the child's best interests, which maintains the existence of a therapeutic misconception between them and parents.
Conclusion
Due to the integration of research and care, their different ethical perspectives become intertwined in the daily practice of pediatric oncology. Increasing awareness of what this means for the communication between parents and physicians is essential. Future research should focus on efforts that overcome the problems that the synchronicity of research and care evokes.
doi:10.1186/1472-6939-12-18
PMCID: PMC3229434  PMID: 21943406
18.  Diarrhea in neutropenic children with cancer: An Egyptian center experience, with emphasis on neutropenic enterocolitis 
Background:
Diarrhea is a frequent complication in children with cancer who received intensive chemotheraputic regimens. It may be caused by several factors, neutropenic enterocolitis (NE) being the most serious.
Aim:
To study diarrhea in neutropenic cancer patients in the pediatric age group, with its underlying etiologies and risk factors, especially the bacterial causes, with special concern on NE.
Materials and Methods:
This study was carried out at the Pediatric Hematology and Oncology Units, Zagazig University Hospitals, Egypt, from January 2009 to September 2010. All children with malignant diseases who are ≤12 years of age were included. Patients who were neutropenic (<500/ mm3) on admission or who became neutropenic during their stay in the hospital were monitored regularly (daily) for diarrhea. Neutropenic cancer patients with diarrhea were grouped into two groups: Group 1, with NE, and group 2, with neutropenic diarrhea rather than NE. On the first day of diarrhea, patients were subjected to complete blood count, blood cultures, stool microscopy and culture. Abdominal ultrasonography was carried out within 3 days of diarrhea.
Results:
A total of 200 children ≤12 years old, suffering from different malignancies, with a total of 180 neutropenic episodes were followed. Diarrhea was observed in 100 episodes (55.5%). NE constituted 16% of these diarrheal episodes. All patients with NE had significantly more severe neutropenia, and this was of longer duration than the other group. All patients with NE were febrile, with 100% positive blood culture. Stool analysis diagnosed giardiasis in 4.8% of the non-NE patients and in none of the NE patients, while stool culture was positive in 75% of the NE patients compared with 40.5% of the other group.
Conclusions:
Diarrhea is a common complication in neutropenic cancer children. Gram negative bacteria and Candida are the most incriminated pathogens. Duration and severity of neutropenia carry a great risk for the development of NE.
doi:10.4103/0971-5851.99742
PMCID: PMC3439797  PMID: 22988351
Cancer; children; diarrhea; neutropenia; neutropenic enterocolitis
19.  Nutritional status and clinical outcome of children on continuous renal replacement therapy: a prospective observational study 
BMC Nephrology  2012;13:125.
Background
No studies on continuous renal replacement therapy (CRRT) have analyzed nutritional status in children. The objective of this study was to assess the association between mortality and nutritional status of children receiving CRRT.
Methods
Prospective observational study to analyze the nutritional status of children receiving CRRT and its association with mortality. The variables recorded were age, weight, sex, diagnosis, albumin, creatinine, urea, uric acid, severity of illness scores, CRRT-related complications, duration of admission to the pediatric intensive care unit, and mortality.
Results
The sample comprised 174 critically ill children on CRRT. The median weight of the patients was 10 kg, 35% were under percentile (P) 3, and 56% had a weight/P50 ratio of less than 0.85. Only two patients were above P95. The mean age for patients under P3 was significantly lower than that of the other patients (p = 0.03). The incidence of weight under P3 was greater in younger children (p = 0.007) and in cardiac patients and in those who had previous chronic renal insufficiency (p = 0.047). The mortality analysis did not include patients with pre-existing renal disease. Mortality was 38.9%. Mortality for patients with weight < P3 was greater than that of children with weight > P3 (51% vs 33%; p = 0.037). In the univariate and multivariate logistic regression analyses, the only factor associated with mortality was protein-energy wasting (malnutrition) (OR, 2.11; 95% CI, 1.067-4.173; p = 0.032).
Conclusions
The frequency of protein-energy wasting in children who require CRRT is high, and the frequency of obesity is low. Protein-energy wasting is more frequent in children with previous end-stage renal disease and heart disease. Underweight children present a higher mortality rate than patients with normal body weight.
doi:10.1186/1471-2369-13-125
PMCID: PMC3519513  PMID: 23016957
20.  Admission Chemokine (C-C motif) Ligand 4 Levels Predict Survival in Pediatric Septic Shock 
Objective
Stratification with an effective outcome biomarker could improve the design of interventional trials in pediatric septic shock. The objective of this study was to test the utility of chemokine (C-C motif) ligand 4 as an outcome biomarker for mortality in pediatric septic shock.
Design
A cross-sectional, observational study.
Setting
18 Pediatric Intensive Care Units in the United States of America.
Patients
156 pediatric patients with septic shock.
Interventions
Serum samples were obtained within 24 hours of admission to the Pediatric Intensive Care Unit. Serum levels of chemokine (C-C motif) ligand 4 were measured via ELISA and compared to mortality in a training set of 34 patients. These data were used to generate a cut-off value whose utility was evaluated through prospective application—without post-hoc modification—to a larger validation set of 122 patients.
Measurements and Main Results
Upon inspection of the training set data, a cut-off value of 140 pg/mL was chosen. When applied to the validation set, serum chemokine (C-C motif) ligand 4 levels greater than 140 pg/mL yielded a sensitivity of 92% and a specificity of 40% for mortality. A serum level of 140 pg/mL or less had a negative predictive value for mortality of 98%.
Conclusions
A serum level of chemokine (C-C motif) ligand 4 of 140 pg/mL or less, when obtained within 24 hours of admission, predicts a very high likelihood of survival in pediatric septic shock. Exclusion of patients with a chemokine (C-C motif) ligand 4 level of 140 or less from interventional clinical trials in pediatric septic shock could create a study population in which survival benefit from the study agent could be more readily demonstrated.
doi:10.1097/PCC.0b013e3181b8076c
PMCID: PMC2837132  PMID: 19794326
Chemokine CCL4; Biological Markers; Sepsis; Shock; Septic; Pediatrics; Clinical Trials as Topic
21.  The Value of Serum Uric Acid as a Mortality Prediction in Critically Ill Children 
Iranian Journal of Pediatrics  2010;20(3):323-329.
Objective
The role of initial serum uric acid on admission in critically ill patients is controversial; we presumed that uric acid level can predict the mortality of the admitted patients to intensive care unit as a simple test.
Methods
Totally, 220 consecutively admitted children (96 girls, 124 boys) with mean age 3.5 years, who were at least 24 hours in pediatric intensive care unit (PICU), were enrolled in a prospective cohort study during January 2006 to December 2007. The subsequent PICU admission in the same hospitalization, those who were discharged from the hospital and then re-admitted to the PICU during the observation period, and the patients with chronic renal failure were excluded. Serum uric acid level was measured during the first day of PICU admission. Death or transfer from PICU was considered as final outcome. The statistical analysis was done by using linear regression analysis, ROC curve, Student t-test, and Chi- square. P value less than 0.05 was considered significant.
Findings
From 44 patients who had serum uric acid level more than 8 mg/dl, 17 cases died showing with a higher relative risk of 1.88, higher mortality (P<0.05). The relative risk of death in patients who had serum uric acid >8 mg/dl and needed vasopressor was 1.04, and in those under mechanical ventilation 1.33. In patients who scored pediatric risk of mortality of >38 it was 1.4, and in septic cases 4 (P<0.05). Stepwise linear regression analysis showed that mainly the need for mechanical ventilation (P=0.001) and vasopressor had statistically significant correlation with the poor outcome (P=0.001).
Conclusion
Uric acid level during the first day of intensive critical care admission is not an independent risk of mortality in PICU. Need for mechanical ventilation or inotropic agents was associated with poor outcome and only higher uric acid level in sepsis played an additive risk factor role.
PMCID: PMC3446040  PMID: 23056724
Uric Acid; Mortality; Intensive care; Death; Pediatrics; Sepsis; Hyperuricemia
22.  Quantitative quality assurance in a community hospital pediatric intensive care unit. 
Western Journal of Medicine  1992;157(2):149-151.
Unbiased, objective evaluations of quality of care are preferred over subjective evaluations. We observed 681 admissions to a pediatric intensive care unit of a community hospital from 1989 through 1990 for outcomes and physiologic profiles of the patients on the admission day using the Pediatric Risk of Mortality score to assess severity of illness. Mortality adjusted for severity of illness was compared with that predicted from a pediatric intensive care unit of a tertiary medical center: 32.6 deaths were predicted based on the physiologic profiles, and 23 occurred. The number of outcomes and their distribution according to mortality risk indicated close agreement between observed and predicted results. Thus, a quality-assurance technique developed in tertiary care centers can be used to indicate a comparable level of care in a community hospital.
PMCID: PMC1011233  PMID: 1441464
23.  Outcome of ventilatory support for acute respiratory failure in motor neurone disease 
Objectives: To review the outcome of acute ventilatory support in patients presenting acutely with respiratory failure, either with an established diagnosis of motor neurone disease (MND) or with a clinical event where the diagnosis of MND has not yet been established.
Methods: Outcome was reviewed in 24 patients with respiratory failure due to MND who received endotracheal intubation and intermittent positive pressure ventilation either at presentation or as a result of the unexpected development of respiratory failure. Patients presenting to local hospitals with acute respiratory insufficiency and requiring tracheal intubation, ventilatory support, and admission to an intensive therapy unit (ITU) before transfer to a regional respiratory care unit were selected. Clinical features of presentation, management, and outcome were studied.
Results: 24 patients with MND were identified, all being intubated and ventilated acutely within hours of presentation. 17 patients (71%) were admitted in respiratory failure before the diagnosis of MND had been made; the remaining seven patients (29%) were already known to have MND but deteriorated rapidly such that intubation and ventilation were initiated acutely. Seven patients (29%) died on ITU (between seven and 54 days after admission). 17 patients (71%) were discharged from ITU. 16 patients (67%) received long term respiratory support and one patient required no respiratory support following tracheal extubation. The daily duration of support that was required increased gradually with time.
Conclusion: When a patient with MND is ventilated acutely, with or without an established diagnosis, independence from the ventilator is rarely achieved. Almost all of these patients need long term ventilatory support and the degree of respiratory support increases with time as the disease progresses. The aim of management should be weaning the patient to the minimum support compatible with symptomatic relief and comfort. Respiratory failure should be anticipated in patients with MND when the diagnosis has been established.
doi:10.1136/jnnp.72.6.752
PMCID: PMC1737909  PMID: 12023419
24.  Frequency of intracranial pressure monitoring in infants and young toddlers with traumatic brain injury* 
Objective
To examine the use of intracranial pressure monitors and treatments for elevated intracranial pressure in brain-injured children of <2 yrs of age and compare them with the recently published management guidelines.
Design
Prospective, population-based study.
Setting
All pediatric intensive care units in the state of North Carolina.
Patients
All patients of <24 months of age admitted to a pediatric intensive care unit with a traumatic brain injury between January 2000 and December 2001.
Interventions
None.
Measurements and Main Results
Use of intracranial pressure monitoring devices and treatments for elevated intracranial pressure were measured. There were 136 children admitted to a pediatric intensive care unit with brain injury. A total of 54 (39.7%) had an admission Glasgow Coma Score of ≤8, and 80% were infants. Thirty-three percent of children with a Glasgow Coma Score of ≤8 received monitoring. Hyperosmolar therapy was the most frequently used treatment (57.1%). Treatment for elevated intracranial pressure was more common in, but not limited to, children with monitors. Logistic-regression modeling showed that children of ≤12 months of age had an odds ratio of 0.2 (95% confidence interval, 0.1–0.6) of receiving a monitor compared with children aged 12–24 months.
Conclusions
Brain injury in young children may lead to many years of lost quality of life. The utility of monitoring intracranial pressure in infants has not been well established, which may be a reason for its low use. As most infants with traumatic brain injury survive, high-quality studies with neurodevelopmental measures as the primary outcome are urgently needed to document best practice in this subpopulation.
doi:10.1097/01.PCC.0000164638.44600.67
PMCID: PMC2365507  PMID: 16148812
traumatic brain injury; intracranial pressure; hyperosmolar therapy; seizures; inflicted head injury
25.  Critical Illness Hyperglycemia in Pediatric Cardiac Surgery 
Critical illness hyperglycemia (CIH) is common in pediatric and adult intensive care units (ICUs). Children undergoing surgical repair or palliation of congenital cardiac defects are particularly at risk for CIH and its occurrence has been associated with increased morbidity and mortality in this population. Strict glycemic control through the use of intensive insulin therapy (IIT) has been shown to improve outcomes in some adult and pediatric studies, yet these findings have sparked controversy. The practice of strict glycemic control has been slow in extending to pediatric ICUs because of the documented increase in the incidence of hypoglycemia in patients treated with IIT. Protocol driven approaches with more liberal glycemic targets have been successfully validated in general and cardiac critical care pediatric patients with low rates of hypoglycemia. It is unknown whether a therapeutic benefit is obtained by keeping patients in this more liberal glycemic control target. Definitive randomized controlled trials of IIT utilizing these targets in critically ill children are ongoing.
PMCID: PMC3320819  PMID: 22401320
children; congenital heart defects; critical illness; glycemic control; hyperglycemia; insulin

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