Ginny Gildengorin

A Prospective Study of Ventilator-Associated Pneumonia in Children

OBJECTIVE. We conducted a prospective, observational study in a tertiary care pediatric center to determine risk factors for the development of and outcomes from ventilator-associated pneumonia. METHODS. From November 2004 to June 2005, all NICU and PICU patients mechanically ventilated for >24 hours were eligible for enrollment after parental consent. The primary outcome measure was the development of ventilator-associated pneumonia, which was defined by both Centers for Disease Control and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis. Secondary outcome measures were length of mechanical ventilation, hospital and ICU length of stay, hospital cost, and death. RESULTS. Fifty-eight patients were enrolled. The median age was 6 months, and 57% were boys. The most common ventilator-associated pneumonia organisms identified were Gram-negative bacteria (42%), Staphylococcus aureus (22%), and Haemophilus influenzae (11%). On multivariate analysis, female gender, postsurgical admission diagnosis, presence of enteral feeds, and use of narcotic medications were associated with ventilator-associated pneumonia. Patients with ventilator-associated pneumonia had greater need for mechanical ventilation (12 vs 22 median ventilator-free days), longer ICU length of stay (6 vs 13 median ICU-free days), higher total median hospital costs (

Positive Fluid Balance Is Associated with Higher Mortality and Prolonged Mechanical Ventilation in Pediatric Patients with Acute Lung Injury

308534 vs

A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes

252652), and increased absolute hospital mortality (10.5% vs 2.4%) than those without ventilator-associated pneumonia. CONCLUSIONS. In mechanically ventilated, critically ill children, those with ventilator-associated pneumonia had a prolonged need for mechanical ventilation, a longer ICU stay, and a higher mortality rate. Female gender, postsurgical diagnosis, the use of narcotics, and the use of enteral feeds were associated with an increased risk of developing ventilator-associated pneumonia in these patients.

Zinc homeostasis in pediatric critical illness.

Introduction. We analyzed a database of 320 pediatric patients with acute lung injury (ALI), to test the hypothesis that positive fluid balance is associated with worse clinical outcomes in children with ALI. Methods. This is a post-hoc analysis of previously collected data. Cumulative fluid balance was analyzed in ml per kilogram per day for the first 72 hours after ALI while in the PICU. The primary outcome was mortality; the secondary outcome was ventilator-free days. Results. Positive fluid balance (in increments of 10 mL/kg/24 h) was associated with a significant increase in both mortality and prolonged duration of mechanical ventilation, independent of the presence of multiple organ system failure and the extent of oxygenation defect. These relationships remained unchanged when the subgroup of patients with septic shock (n = 39) were excluded. Conclusions. Persistently positive fluid balance may be deleterious to pediatric patients with ALI. A confirmatory, prospective randomized controlled trial of fluid management in pediatric patients with ALI is warranted.

Lower alloimmunization rates in pediatric sickle cell patients on chronic erythrocytapheresis compared to chronic simple transfusions.

Painful episodes of vaso-occlusion are the leading cause of hospitalizations and emergency department visits in sickle cell disease, and are associated with increased mortality. Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease. Since arginine is the obligate substrate for nitric oxide production, and an acute deficiency is associated with pain, we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease. Thirty-eight children with sickle cell disease hospitalized for 56 episodes of pain were randomized into this double-blinded placebo-controlled trial. Patients received L-arginine (100 mg/kg tid) or placebo for 5 days or until discharge. A significant reduction in total parenteral opioid use by 54% (1.9±2.0 mg/kg versus 4.1±4.1 mg/kg, P=0.02) and lower pain scores at discharge (1.9±2.4 versus 3.9±2.9, P=0.01) were observed in the treatment arm compared to the placebo one. There was no significant difference in hospital length of stay (4.1±01.8 versus 4.8±2.5 days, P=0.34), although a trend favored the arginine arm, and total opioid use was strongly correlated with the duration of the admission (r=0.86, P<0.0001). No drug-related adverse events were observed. Arginine therapy represents a novel intervention for painful vaso-occlusive episodes. A reduction of narcotic use by >50% is remarkable. Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle cell-related pain in children. A large multi-center trial is warranted in order to confirm these observations.

Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study

Objective: We explored the hypothesis that marked decline in plasma zinc concentrations among critically ill children is related to shifts in metallothionein expression and inflammation. Design: Prospective pilot study. Setting: Intensive care unit of tertiary care children’s hospital. Patients: All children (<18 yrs) with unadjusted Pediatric Risk of Mortality III score >5 or at least one organ failure admitted to the pediatric intensive care unit from March through August 2006 were eligible for enrollment. Interventions: After consent, blood samples were collected on days 1 and 3 of illness and analyzed for serum chemistries, plasma zinc and copper levels, metallothionein isoform expression, and cytokine levels. Measurements and Main Results: Twenty patients were enrolled, with median age of 2.9 yrs (interquartile range, 0.7–10.1). Male to female ratio was 1.2:1. All patients had low zinc levels (mean, 0.43; range, 0.26–0.66 &mgr;g/dL) on day 1 of pediatric intensive care unit admission, and remained low (mean, 0.51; range, 0.26–0.81 &mgr;g/dL) on day 3, even when corrected for hypoalbuminemia. In comparison, serum copper levels were normal. On day 1, there was a positive correlation between zinc levels and expression of MT-1A (p < 0.01), MT-1G (p = 0.02), and MT-1H (p = 0.03). Plasma zinc levels correlated inversely with C-reactive protein levels (r = −.75, p = 0.01) and interleukin-6 levels (r = −.53, p = 0.04) on day 3. On day 3, patients with two or more organ failures had significantly lower plasma zinc concentrations compared with patients with ≤1 organ failure (p = 0.03). Conclusions: Plasma zinc concentrations are low in critically ill children. Plasma zinc correlated with measures of inflammation (C-reactive protein and interleukin-6) on day 3; low plasma zinc concentrations were associated with the degree of organ failure on day 3. These data serve as the basis for a larger study of shifts in plasma zinc concentrations in critically children to potentially identify patients who might benefit from zinc supplementation.

Reproductive capacity in iron overloaded women with thalassemia major.

BACKGROUND: Erythrocytapheresis (ECP), automated red blood cell exchange, is increasingly being used for chronic transfusion therapy in sickle cell disease (SCD) as it is an isovolumetric transfusion, is more effective in lowering hemoglobin (Hb)S, and can limit iron overload. Because ECP requires increased blood exposure compared to simple transfusions there is concern for increased transfusion complications, including alloimmunization. We compared alloimmunization rates between patients receiving simple or exchange chronic transfusions.

Efficacy and safety of lung recruitment in pediatric patients with acute lung injury.

Background In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006–2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. Methodology/Findings We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006–2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI95%:17%–29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI95%: 20%–39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT80)) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Conclusions Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at >1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

International survey of physician recommendation for tracheostomy for spinal muscular atrophy Type I

The pathophysiology of iron-induced compromised fertility in women with thalassemia major (TM) was evaluated in 26 adult TM females. Low gonadotropin secretion resulted in reduced ovarian antral follicle count and ovarian volume, but levels of anti-müllerian hormone (AMH), a sensitive marker for ovarian reserve independent of gonadotropin effect, were mostly normal. AMH correlated with non-transferrin-bound iron (NTBI), suggesting a role of labile iron in the pathogenesis of decreased reproductive capacity, possibly occurring in parallel to cardiac iron toxicity, as cardiac iron was associated with the presence of amenorrhea and with NTBI levels. AMH emerges as an important biomarker for assessment of reproductive capacity in TM, demonstrating that fertility is preserved in the majority of those younger than 30 to 35 years. AMH can be useful in future studies aiming at improved chelation for fertility preservation, whereas NTBI and labile plasma iron may be valuable for monitoring iron effect on the reproductive system.

High Rates of O’Nyong Nyong and Chikungunya Virus Transmission in Coastal Kenya

Objective: To assess the safety and efficacy of a recruitment maneuver, the Open Lung Tool, in pediatric patients with acute lung injury and acute respiratory distress syndrome. Design: Prospective cohort study using a repeated-measures design. Setting: Pediatric intensive care unit at an urban tertiary childrens hospital. Patients: Twenty-one ventilated pediatric patients with acute lung injury. Intervention: Recruitment maneuver using incremental positive end-expiratory pressure. Measurements and Main Results: The ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (Pao2/Fio2 ratio) increased 53% immediately after the recruitment maneuver. The median Pao2/Fio2 ratio increased from 111 (interquartile range, 73–266) prerecruitment maneuver to 170 (interquartile range, 102–341) immediately postrecruitment maneuver (p < .01). Improvement in Pao2/Fio2 ratio persisted with an increase of 80% over the baseline at 4 hrs and 40% at 12 hrs after the recruitment maneuver. The median Pao2/Fio2 ratio was 200 (interquartile range, 116–257) 4 hrs postrecruitment maneuver (p < .05) and 156 (interquartile range, 127–236) 12 hrs postrecruitment maneuver (p < .01). Compared with prerecruitment maneuver, the partial pressure of arterial carbon dioxide (Paco2) was significantly decreased at 4 hrs postrecruitment maneuver but not immediately after the recruitment maneuver. The median Paco2 was 49 torr (interquartile range, 44–60) prerecruitment maneuver compared with 48 torr (interquartile range, 43–50) immediately postrecruitment maneuver (p = .69), 45 torr (interquartile range, 41–50) at 4 hrs postrecruitment maneuver (p < .01), and 43 torr (interquartile range, 38–51) at 12 hrs postrecruitment maneuver. Recruitment maneuvers were well tolerated except for significant increase in Paco2 in three patients. There were no serious adverse events related to the recruitment maneuver. Conclusions: Using the modified open lung tool recruitment maneuver, pediatric patients with acute lung injury may safely achieve improved oxygenation and ventilation with these benefits potentially lasting up to 12 hrs postrecruitment maneuver.