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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.
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.
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.
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.
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.
PMCID: PMC2481472  PMID: 18538003
2.  The opinion of clinical staff regarding painfulness of procedures in pediatric hematology-oncology: an Italian survey 
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.
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.
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.
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.
PMCID: PMC3127832  PMID: 21663631
3.  Evaluation of Prescribing Medications for Terminal Cancer Patients near Death: Essential or Futile 
The purpose of this study is to evaluate the prescription of essential or futile medications for terminal cancer patients during their final admission.
Materials and Methods
We conducted a retrospective review of the medical charts of terminally ill cancer patients admitted to the Hemato-oncology Department of two teaching hospitals from March 1, 2007 to December 31, 2009. Essential medications were based on the drugs listed by the International Association for Hospice and Palliative Care, while futile medications were defined when short-term benefit to patients with respect to survival, quality of life, or symptom control was not anticipated.
A total of 196 patients were included. Among essential medications, strong opioids were the most frequently prescribed drugs during the last admission (62.2% fentanyl, 44.3% morphine), followed by megestrol (46.0%), and metoclopramide (37.2%); 51% of gastric protectors were prescribed with potential futility. Anti-hypertensive and antiglycemic agents were administered to those who experienced arterial blood pressure below 90 mm Hg (47.3%) or presented with a single measurement of fasting glucose below 50 mg/dL (10.7%), respectively. Statins were prescribed to 6.1% (12/196) of patients, and 75% of those prescriptions were regarded as futile.
Our data suggest that effective prescription of essential medications and withdrawal from futile medications should be actively reconciled for improvement of a patient's end-of-life care.
PMCID: PMC3804734  PMID: 24155681
Drug therapy; Medical futility; Neoplasms; Symptom
4.  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.
PMCID: PMC3133495  PMID: 21772950
intensive care; malignancy; Pediatric Intensive Care Unit admission criteria; children; critically ill.
5.  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.
PMCID: PMC3357612  PMID: 22690305
septic shock; children.
6.  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.
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.
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.
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.
CRRT improved oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI.
PMCID: PMC3214656  PMID: 20658627
Hematopoietic stem cell transplantation; Critically ill; Acute lung injury; Pediatrics; Renal replacement therapy; Oxygenation
7.  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.
PMCID: PMC3307018  PMID: 22496695
8.  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.
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.
The purpose of this study is the utilization of the PRISM and determination of mortality risk factors in a tertiary pediatric intensive care unit.
: 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.
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.
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.
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.
PMCID: PMC2999700  PMID: 21243277
Quality of care; Prognostic scores; Multiple organ dysfunction syndrome; Critical care; Mortality rate
9.  Respiratory syncytial virus - associated intensive care unit admission in children in Southern China 
BMC Research Notes  2013;6:447.
There are incomplete data on the global burden of viral lower respiratory tract infection, in particular the role of Respiratory Syncytial Virus, in children requiring health services.
In this study set in a large urban area of southern China from 1 January 2007 to 31 December 2010, children 1 month to 14 years of age with RSV-associated “severe” or “very severe pneumonia” according to World Health Organization definitions, and meeting local criteria for admission to the pediatric intensive care unit, were followed for the course of their admission. The median age was 3 months and 79% (135/171) of children with RSV were under six months of age. All children needed supplemental oxygen, and 22% required mechanical ventilatory support. The mortality rate was 3.5%. In multivariate analysis, congenital heart disease and Trisomy 21 were associated with death.
Children admitted to an intensive care unit with RSV-associated severe/very pneumonia in a large urban setting in southern China were most commonly ≤ six months old and almost one quarter of these had respiratory failure. The overall mortality rate was 3.5%. RSV vaccine strategies that would protect children from early infancy are urgently needed.
PMCID: PMC3830112  PMID: 24206961
Respiratory syncytial virus; Intensive care; Child; Hospitalization
10.  Performance of the pediatric index of mortality 2 (PIM-2) in cardiac and mixed intensive care units in a tertiary children’s referral hospital in Italy 
BMC Pediatrics  2013;13:100.
Mortality rate of patients admitted to Intensive Care Units is a widely adopted outcome indicator. Because of large case-mix variability, comparisons of mortality rates must be adjusted for the severity of patient illness at admission. The Pediatric Index of Mortality 2 (PIM-2) has been widely adopted as a tool for adjusting mortality rate by patients’ case mix. The objective of this study was to assess the performance of PIM-2 in children admitted to intensive care units after cardiac surgery, other surgery, or for other reasons.
This was a prospective cohort study, conducted in a 607 inpatient-bed tertiary-care pediatric hospital in Italy, with three pediatric intensive care Units (PICUs) and one cardiac Unit (CICU). In 2009–11, all consecutive admissions to PICUs/CICU of children aged 0–16 years were included in the study. Discrimination and calibration measures were computed to assess PIM-2 performance. Multivariable logistic regression analysis was used to assess the association of patients’ main reason for intensive care admission (cardiac-surgical, other-surgical, medical), age, Unit and year with observed mortality, adjusting for PIM-2 score.
PIM-2 data collection was completed for 91.2% of total PICUs/CICU patient admissions (2912), and for 94.8% of patients who died in PICUs/CICU (129). Overall observed mortality was 4.4% (95% CI, 3.7-5.2), compared to 6.4% (95% CI, 5.5-7.3) expected mortality. Standardised mortality ratio was 0.7 (95% CI: 0.6-0.8). PIM-2 discrimination was fair (area under the curve, 0.79; 95% CI: 0.75-0.83). Calibration was less satisfactory, mainly because of the over two-fold overprediction of deaths in the highest risk group (114.7 vs 53; p < 0.001), and particularly in cardiac-surgical patients. Multivariable logistic analysis showed that risk of death was significantly reduced in cardiac-surgical patients and in those aged 1 month to 12 years, independently from PIM-2.
The children age distribution and the proportion of cardiac-surgical patients should be taken into account when interpreting SMRs estimated using the PIM-2 prediction model in different Units. A new calibration study of PIM-2 score might be needed, and more appropriate cardiac-focused risk-adjustment models should be developed. The role of age on risk of death needs to be further explored.
PMCID: PMC3695834  PMID: 23799966
Critical care; Risk adjustment; Mortality pediatric index of mortality; Cardiac surgery, Pediatrics; Quality indicators
11.  Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission 
BMC Pediatrics  2014;14:83.
Hyperlactatemia upon admission is a documented risk factor for mortality in critically ill adult patients. However, the predictive significance of a single lactate measurement at admission for mortality in the general population of critically ill children remains uncertain. This study evaluated the predictive value of blood lactate levels at admission and determined the cut-off values for predicting in-hospital mortality in the critically ill pediatric population.
We enrolled 1109 critically ill children who were admitted to a pediatric intensive care unit between July 2008 and December 2010. Arterial blood samples were collected in the first 2 hours after admission, and the lactate levels were determined. The Pediatric Risk of Mortality III (PRISM III) scores were calculated during the first 24 hours after admission.
Of the 1109 children admitted, 115 (10.4%) died in the hospital. The median (interquartile range) blood lactate level in critically ill children was 3.2 mmol/l (2.2-4.8). Among the children, 859 (77.5%) had a lactate concentration >2.0 mmol/l. The blood lactate level upon admission was significantly associated with mortality (odds ratio [OR] = 1.38; 95% confidence interval [CI], 1.30-1.46; p <0.001), even after adjustment for age, gender, and illness severity assessed by PRISM III (OR = 1.27; p <0.001). Multivariate regression analysis showed that a high blood lactate level (OR = 1.17; 95% CI, 1.07-1.29; p = 0.001), a high PRISM III score (OR = 1.15; 95% CI, 1.11-1.20; p <0.001), and a low serum albumin (OR =0.92; 95% CI, 0.88-0.96; p <0.001) were independent risk factors for mortality in critically ill children. Blood lactate achieved an area under-the-receiver-operating-characteristic curve (AUC) of 0.79 (p <0.001) for predicting mortality that was similar to that of PRISM III (AUC = 0.82; p <0.001). The p-value for a comparison of both AUCs was 0.318. Blood lactate displayed a sensitivity of 61% and a specificity of 86% in predicting mortality at the optimal cut-off value of 5.55 mmol/l, and the positive and negative likelihood ratios were 4.5 and 0.45, respectively.
A high blood lactate level at admission is independently associated with and predictive of in-hospital mortality in the general population of critically ill children.
PMCID: PMC3976355  PMID: 24673817
Blood lactate; Critically ill children; Cut-off value; In-hospital mortality; Pediatric risk of mortality III (PRISM III); Predictive test
12.  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.
PMCID: PMC3247779  PMID: 22219618
Serologic Immunity; Immunocompromised Children; Diphtheria; Tetanus; Pertussis; Vaccination
13.  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.

PMCID: PMC1718671  PMID: 11207181
14.  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.
PMCID: PMC2689481  PMID: 19439044
15.  Extremes of weight centile are associated with increased risk of mortality in pediatric intensive care 
Critical Care  2011;15(2):R106.
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.
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.
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.
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.
PMCID: PMC3219384  PMID: 21453507
16.  Macrophage Activation Syndrome in Children with Systemic Lupus Erythematosus and Juvenile Idiopathic Arthritis 
Arthritis and rheumatism  2012;64(12):4135-4142.
To describe patient demographics, interventions, and outcomes in hospitalized children with macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA).
Retrospective cohort study of the Pediatric Health Information System (PHIS) database, Oct 1, 2006 to September 30, 2010. Participants had ICD-9-CM diagnosis codes for MAS and either SLE or JIA. The primary outcome was hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, critical care interventions, and medication use.
121 children at 28 children’s hospitals met inclusion criteria, including 19 with SLE and 102 with JIA. Index admission mortality was 7% (8/121). ICU admission (33%), mechanical ventilation (26%), and inotrope/vasopressor therapy (26%) were common. Compared to children with JIA, those with SLE had similar mortality (6% versus 11%, exact p = 0.6), more ICU care (63% versus 27%, p = 0.002), more mechanical ventilation (53% versus 21%, p = 0.003), and more cardiovascular dysfunction (inotrope/vasopressor 47% versus 23%, p = 0.02). Children with SLE and JIA received cyclosporine at similar rates, but more children with SLE received cyclophosphamide and mycophenolate mofetil and more children with JIA received interleukin-1 antagonists.
Organ system dysfunction is common in children with rheumatic diseases complicated by MAS, and children with underlying SLE require more organ system support than children with JIA. Current treatment of pediatric MAS varies based on the underlying rheumatic disease.
PMCID: PMC3505557  PMID: 22886474
17.  Chronic conditions among children admitted to U.S. PICUs: their prevalence and impact on risk for mortality and prolonged length of stay 
Critical Care Medicine  2012;40(7):2196-2203.
To estimate the prevalence of chronic conditions among children admitted to U.S. pediatric intensive care units (PICU) and to assess whether patients with complex chronic conditions (CCC) experience PICU mortality and prolonged LOS risk beyond that predicted by commonly-used severity-of-illness risk-adjustment models.
Retrospective cohort analysis of 52,791 pediatric admissions to 54 U.S. PICUs that participated in the Virtual Pediatric Intensive Care Unit Performance System (VPS) database in 2008.
Hierarchical logistic regression models, clustered by PICU site, for PICU mortality and length of stay (LOS) > 15 days. Standardized mortality ratios (SMR) adjusted for severity-of-illness score alone and with CCC.
Fifty-three percent of PICU admissions had a CCC, 18.5% had a non-complex chronic conditions (NCCC). The prevalence of these conditions and their organ system subcategories varied considerably across sites. The majority of CCC subcategories were associated with significantly greater odds of PICU mortality (odds ratios [OR] 1.25–2.9, all P values <0.02) compared to having a non-complex chronic condition (NCCC) or no chronic condition, after controlling for age, gender, trauma, and severity-of-illness. Only respiratory, gastrointestinal, and rheumatologic/orthopedic/psychiatric CCC were not associated with increased odds of PICU mortality. All subcategories were significantly associated with prolonged LOS. All NCCC subcategories were either not associated or negatively associated with PICU mortality, and most were not associated with prolonged LOS, compared to having no chronic conditions. Among this group of PICUs, adding CCCs to risk-adjustment models led to greater model accuracy but did not substantially change unit-level SMRs.
Children with CCC were at greater risk for PICU mortality and prolonged LOS than those with no chronic conditions, but the magnitude of risk varied across subcategories. Inclusion of CCCs into models of PICU mortality improved model accuracy but had little impact on SMRs.
PMCID: PMC3378726  PMID: 22564961
Child; Intensive Care Units, Pediatric; Mortality; Length of Stay; Chronic Disease; Risk Adjustment
18.  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.
PMCID: PMC3271153  PMID: 22183817
Pediatric neurocritical care; Children; Pediatric TBI; Childhood stroke; Neuroprotection; Nonconvulsive seizures
19.  Current management issues of immediate postoperative care in pediatric kidney transplantation 
Clinics  2014;69(Suppl 1):39-41.
The number of pediatric kidney transplants has been increasing in many centers worldwide, as the procedure provides long-lasting and favorable outcomes; however, few papers have addressed the immediate postoperative care of this unique population. Herein, we describe the management of these patients in the early postoperative phase. After the surgical procedure, children should ideally be managed in a pediatric intensive care unit, and special attention should be given to fluid balance, electrolyte disturbances and blood pressure control. Antibiotic and antiviral prophylaxes are usually performed and are based on the recipient and donor characteristics. Thrombotic prophylaxis is recommended for children at high risk for thrombosis, although consensus on the optimum therapy is lacking. Image exams are essential for good graft control, and Doppler ultrasound must be routinely performed on the first operative day and promptly repeated if there is any suspicion of kidney dysfunction. Abdominal drains can be helpful for surveillance in patients with increased risk of surgical complications, such as urinary fistula or bleeding, but are not routinely required. The immunosuppressive regimen starts before or at the time of kidney transplantation and is usually based on induction with monoclonal or polyclonal antibodies, depending on the immunological risk, and maintenance with a calcineurin inhibitor (tacrolimus or ciclosporin), an anti-proliferative agent (mycophenolate or azathioprine) and steroids.
PMCID: PMC3884160
Child; Intensive Care; Kidney; Postoperative Care; Transplantation
20.  The Value of Serum Uric Acid as a Mortality Prediction in Critically Ill Children 
Iranian Journal of Pediatrics  2010;20(3):323-329.
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.
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.
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).
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
21.  Electrographic Status Epilepticus is Associated with Mortality and Worse Short-Term Outcome in Critically Ill Children 
Critical care medicine  2013;41(1):210-218.
Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in critically ill children. We aimed to determine whether ES and ESE are associated with higher mortality or worse short-term neurologic outcome.
Prospective observational study.
Pediatric intensive care unit of a tertiary children’s hospital.
Non-neonatal children admitted to a pediatric intensive care unit (PICU) with acute encephalopathy underwent continuous electroencephalographic (cEEG) monitoring. EEGs were scored as (1) no seizures, (2) ES, or (3) ESE. Covariates included age, acute neurologic disorder category, prior neurodevelopmental status, sex, and EEG background category. Outcomes were mortality and worsening of Pediatric Cerebral Performance Category (PCPC) from pre-admission to PICU discharge. Chi-squared analysis, Fisher’s exact test, and multivariable logistic regression were used to evaluate the associations between ES or ESE and mortality or short-term neurologic outcome, using odds ratios (OR) and 95% confidence intervals (95%CI).
Main Results
Two hundred children underwent cEEG. Eighty-four (42%) had seizures which were categorized as ES in 41 (20.5%) and ESE in 43 (21.5%). Thirty-six subjects (18%) died and 88 subjects (44%) had PCPC worsening. In multivariable analysis ESE was associated with an increased risk of mortality (OR 5.1; 95%CI 1.4, 18, p=0.01) and PCPC worsening (OR 17.3; 95%CI 3.7, 80, p<0.001) while ES was not associated with an increased risk of mortality (OR 1.3; 95%CI 0.3, 5.1; p=0.74) or PCPC worsening (OR 1.2; 95%CI 0.4, 3.9; p=0.77).
ESE, but not ES, is associated with mortality and worse short-term neurologic outcome in critically ill children with acute encephalopathy.
PMCID: PMC3531581  PMID: 23164815
EEG Monitoring; Seizure; Status Epilepticus; Pediatric; Outcome; Non-Convulsive Seizure
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.  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.
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.
Observed mortality rates were higher in patients admitted from wards within the same hospital, even after adjustment.
PMCID: PMC3439783  PMID: 22988362
Child; intensive care units; mortality; patient admission; pediatric
24.  Progress in pediatrics in 2011. Choices in endocrinology, gastroenterology, hemato-oncology, infectious diseases, otolaryngology, pharmacotherapy and respiratory tract illnesses 
Main progresses in endocrinology, gastroenterology, hemato-oncology, infectious diseases, otolaryngology, pharmacotherapy, and respiratory tract illnesses selected from articles published in The Italian Journal of Pediatrics in 2011 were reviewed. Risk factors for gastroenteritis and appendicitis in developing countries may be useful in improving our understanding of these diseases. Childhood hearing impairment is a world-wide problem which continues to have an high prevalence in newborns. Among the mechanisms of diseases, obese children often have asthma and high hepcidin levels that may reduce serum iron concentrations. In cystic fibrosis, 18q distal deletion has been described as a novel mutation. Hypothyroidism in children with central nervous system infections may increase mortality rates. Infrared tympanic thermometer (IRTT) in oral mode for the measurement of body temperature may be useful in fever screening in a busy setup. In newborns, the transmission of CMV infection through breast milk may be prevented through freezing or pasteurization. Recent advances in treatment of constipation, urinary tract infections, leukemia, pain in children with cancer, neonates with sepsis or difficult weaning from mechanical ventilation will likely contribute towards optimizing management of these common disorders. The work of the Family Pediatricians Medicines for Children Research Network aims to develop competence, infrastructure, networking and education for pediatric clinical trials.
PMCID: PMC3431994  PMID: 22682313
Endocrinology; Gastroenterology; Hemato-oncology; Infectious diseases; Otolaryngology; Pharmacotherapy; Respiratory tract illnesses
25.  Endotoxemia in pediatric critical illness - a pilot study 
Critical Care  2011;15(3):R141.
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.
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.
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.
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.
PMCID: PMC3219013  PMID: 21651808

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