Kate Madden

Vitamin D Deficiency in Critically Ill Children

OBJECTIVE: Vitamin D influences cardiovascular and immune function. We aimed to establish the prevalence of vitamin D deficiency in critically ill children and identify factors influencing admission 25-hydroxy vitamin D (25(OH)D) levels. We hypothesized that levels would be lower with increased illness severity and in children with serious infections. METHODS: Participants were 511 severely or critically ill children admitted to the PICU from November 2009 to November 2010. Blood was collected near PICU admission and analyzed for 25(OH)D concentration by using Diasorin radioimmunoassay. RESULTS: We enrolled 511 of 818 (62.5%) eligible children. The median 25(OH)D level was 22.5 ng/mL; 40.1% were 25(OH)D deficient (level <20 ng/mL). In multivariate analysis, age and race were associated with 25(OH)D deficiency; summer season, vitamin D supplementation, and formula intake were protective; 25(OH)D levels were not lower in the 238 children (46.6%) admitted with a life-threatening infection, unless they had septic shock (n = 51, 10.0%) (median 25(OH)D level 19.2 ng/mL; P = .0008). After adjusting for factors associated with deficiency, lower levels were associated with higher admission day illness severity (odds ratio 1.19 for a 1-quartile increase in Pediatric Risk of Mortality III score per 5 ng/mL decrease in 25(OH)D, 95% confidence interval 1.10–1.28; P < .0001). CONCLUSIONS: We found a high rate of vitamin D deficiency in critically ill children. Given the roles of vitamin D in bone development and immunity, we recommend screening of those critically ill children with risk factors for vitamin D deficiency and implementation of effective repletion strategies.

Delirium in Critically Ill Children: An International Point Prevalence Study*

Objectives: To determine prevalence of delirium in critically ill children and explore associated risk factors. Design: Multi-institutional point prevalence study. Setting: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. Patients: All children admitted to the pediatric critical care units on designated study days (n = 994). Intervention: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. Measurements and Main Results: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. Conclusions: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.

Critically Ill Children Have Low Vitamin D-Binding Protein, Influencing Bioavailability of Vitamin D.

RATIONALE Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) <20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acute-phase reactant affected by inflammation and injury. OBJECTIVES We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. METHODS We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. MEASUREMENTS AND MAIN RESULTS We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 μg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age <1 year, nonwhite race, being previously healthy, 25(OH)D <20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P < 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = -0.24, P < 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype. CONCLUSIONS Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results.

Survival of neonates with enteroviral myocarditis requiring extracorporeal membrane oxygenation.

Objectives: Neonates infected with enteroviruses may present with severe myocarditis and medically refractory cardiopulmonary collapse. Extracorporeal membrane oxygenation (ECMO) has been used to support patients in this setting, but its efficacy has not been systematically studied. We sought to review the Extracorporeal Life Support Organization registry to determine survival rates and identify predictors of inhospital mortality for these neonates. Design: Retrospective cohort study using data reported to the Extracorporeal Life Support Organization registry. Setting: Multi-institutional data. Patients: Patients ≤15 days old with enteroviral myocarditis who required ECMO support between 2000 and 2008. Interventions: None. Measurements and Main Results: Twenty-four neonates with enteroviral myocarditis were reported to the Extracorporeal Life Support Organization registry during the study period. The survival to hospital discharge rate was 33% (n = 8). Multisystem organ dysfunction was more common in nonsurvivors than in survivors (75% vs. 0%, p < .01). In particular, nonsurvivors had a higher prevalence of renal dysfunction (50% vs. 0%, p = .02). Nonsurvivors also had a greater number of ECMO-related complications (5 vs. 3.5, p = .03). Conclusions: Cardiopulmonary support with ECMO should be considered for neonates with severe enteroviral myocarditis that fails conventional medical therapies. Multisystem organ dysfunction, particularly with renal involvement, may portend a poor prognosis and is one of several factors that should be considered in the decision to initiate and/or continue mechanical support for these patients.

Mannose-binding Lectin Levels in Critically Ill Children With Severe Infections*

Objectives: Low mannose-binding lectin levels and haplotypes associated with low mannose-binding lectin production have been associated with infection and severe sepsis. We tested the hypothesis that mannose-binding lectin levels would be associated with severe infection in a large cohort of critically ill children. Design: Prospective cohort study. Setting: Medical and Surgical PICUs, Boston Children’s Hospital. Patients: Children less than 21 years old admitted to the ICUs from November 2009 to November 2010. Interventions: None. Measurements and Main Results: We measured mannose-binding lectin levels in 479 of 520 consecutively admitted children (92%) with severe or life-threatening illness. We genotyped 213 Caucasian children for mannose-binding lectin haplotype tagging variants and assigned haplotypes. In the univariate analyses of mannose-binding lectin levels with preadmission characteristics, levels were higher in patients with preexisting renal disease. Patients who received greater than 100 mL/kg of fluids in the first 24 hours after admission had markedly lower mannose-binding lectin, as did patients who underwent spinal fusion surgery. Mannose-binding lectin levels had no association with infection status at admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although mannose-binding lectin haplotypes strongly influenced mannose-binding lectin levels in the predicted relationship, low mannose-binding lectin–producing haplotypes were not associated with increased risk of infection. Conclusions: Mannose-binding lectin levels are largely genetically determined. This relationship was preserved in children during critical illness, despite the effect of large-volume fluid administration on mannose-binding lectin levels. Previous literature evaluating an association between mannose-binding lectin levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that mannose-binding lectin levels were lower after aggressive fluid resuscitation and suggest that studies of mannose-binding lectin in critically ill patients should assess mannose-binding lectin haplotypes to reflect preillness levels.

Case Report of a Child after Hematopoietic Cell Transplantation with Acute Aspergillus Tracheobronchitis as a Cause for Respiratory Failure

Rapid respiratory failure due to invasive mycosis of the airways is an uncommon presentation of Aspergillus infection, even in immunocompromised patients, and very few pediatric cases have been reported. Patients with Aspergillus tracheobronchitis present with nonspecific symptoms, and radiologic studies are often noninformative, leading to a delay in diagnosis. Prompt initiation of adequate antifungal therapies is of utmost importance to improve outcome. We report the case of a 9-year-old girl with chronic myelogenous leukemia who developed respiratory distress 41 days after hematopoietic cell transplantation and rapidly deteriorated despite multiple interventions and treatment modalities.

Septic shock and vasopressor requirement is associated with lower vitamin D levels in critically ill children

Vitamin D plays an important role in immune and cardiovascular function. There is evidence that low 25-hydroxyvitamin D (25(OH)D) levels are associated with an increased risk of life-threatening infections [1,2]. Our objective was to determine the prevalence of 25(OH)D deficiency (<20 ng/ml) in critically ill children and to identify any association with illness severity and infection.