Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.

Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Results: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Conclusion: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.

Tracheostomy for infants requiring prolonged mechanical ventilation: 10 years' experience.

BACKGROUND: Despite advances in care of critically ill neonates, extended mechanical ventilation and tracheostomy are sometimes required. Few studies focus on complications and clinical outcomes. Our aim was to provide long-term outcomes for a cohort of infants who required tracheostomy. METHODS: This study is a retrospective review of 165 infants born between January 1, 2000 and December 31, 2010 who required tracheostomy and ventilator support. Children with complex congenital heart disease were excluded. RESULTS: Median gestational age was 27 weeks (range 22-43), and birth weight was 820 g (range 360-4860). The number of male (53.9%) and female (46.1%) infants was similar (P = .312). Infants were divided into 2 groups based on birth weight ≤1000 g (A) and >1000 g (B). Group A: 87 (57.6%) infants; group B 64 (42.4%). Overall tracheostomy rate was 6.9% (87/1345) for group A versus 0.9% (64/6818) for B (P <.001). Group A had a longer time from intubation to positive pressure ventilation independence, 505 days (range 62-1287) vs 372 days (range 15-1270; P = .011). Infants who had >1 reason for tracheostomy comprised 78.8% of the sample; 69.1% of infants were discharged on ventilators. Birth weight did not affect time from tracheostomy to decannulation (P = .323). More group A infants were decannulated (P = .023). laryngotracheal reconstruction rate was 35.8%. Five-year survival was 89%. Group B had higher mortality (P = .033). 64.2% of infants had developmental delays; 74.2% had ≥2 comorbidities. CONCLUSIONS: Tracheostomy rates were higher for extremely low birth weight infants than previously reported rates for all infants. Decannulation rates and laryngotracheal reconstruction rates were consistent with previous studies. Survival rates were high, but developmental delay and comorbidities were frequent.

Incidental sinusitis in a pediatric intensive care unit.

OBJECTIVE: Intubation is a risk factor for nosocomial sinusitis in adult intensive care patients. Sinusitis in intubated adults can be an occult cause of fever. In children, nasal intubation may increase the risk of sinusitis. No pediatric study has determined the frequency of nosocomial sinusitis in the pediatric intensive care unit setting. We hypothesized that within a subset of patients who had head computed tomography imaging 1) the incidental frequency of sinusitis in pediatric intensive care unit patients exceeds the frequency in non-pediatric intensive care unit patients, 2) the frequency of sinusitis is greater in pediatric intensive care unit patients with a tube (nasotracheal, nasogastric, orotracheal, or orogastric) compared to those without a tube, and 3) nasal tubes confer an increased risk for sinusitis over oral tubes. DESIGN: Retrospective chart review. SETTING: Independent not-for-profit pediatric healthcare system. PATIENTS: Pediatric intensive care unit and non-pediatric intensive care unit (inpatients hospitalized on medical-surgical wards) patients referred for head computed tomography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Computed tomography images were scored using the Lund-MacKay staging system. Sinusitis was defined as a Lund-MacKay score ≥5. A total of 596 patients were studied, 395 (66.3%) in the pediatric intensive care unit. A total of 154 (44.3%) pediatric intensive care unit vs. 54 (26.9%) non-pediatric intensive care unit patients had sinusitis (p < .001). A total of 102 of 147 (69.4%) pediatric intensive care unit patients with a tube present had sinusitis vs. 73 of 248 (29.4%) patients without a tube present (p < .001). There was no difference in sinusitis based on tube location (p = .472). Of patients with sinusitis, 51.3% (81 of 158) compared to 39.4% (89 of 226) were febrile within 48 hrs of imaging (p = .021). A younger age or the presence of a tube increased the probability of sinusitis (p < .001). CONCLUSIONS: A total of 44.3% of our pediatric intensive care unit patients imaged for reasons other than evaluation for sinus disease had evidence of sinusitis, and 51.3% of these had fever. These findings raise the concern that sinusitis in pediatric intensive care unit patients is common and should be considered in the differential diagnosis of fever in pediatric intensive care unit patients.

Sedation with nitrous oxide compared with no sedation during catheterization for urologic imaging in children.

BACKGROUND: Various strategies to mitigate children's distress during voiding cystourethrography (VCUG) have been described. Sedation with nitrous oxide is comparable to that with oral midazolam for VCUG, but a side-by-side comparison of nitrous oxide sedation and routine care is lacking. OBJECTIVE: The effects of sedation/analgesia using 70% nitrous oxide and routine care for VCUG and radionuclide cystography (RNC) were compared. MATERIALS AND METHODS: A sample of 204 children 4-18 years of age scheduled for VCUG or RNC with sedation or routine care were enrolled in this prospective study. Nitrous oxide/oxygen (70%/30%) was administered during urethral catheterization to children in the sedated group. The outcomes recorded included observed distress using the Brief Behavioral Distress Score, self-reported pain, and time in department. RESULTS: The study included 204 patients (99 nonsedated, 105 sedated) with a median age of 6.3 years (range 4.0-15.2 years). Distress and pain scores were greater in nonsedated than in sedated patients (P < 0.001). Time in department was longer in the sedated group (90 min vs. 30 min); however, time from entry to catheterization in a non-imaging area accounted for most of the difference. There was no difference in radiologic imaging time. CONCLUSION: Sedation with nitrous oxide is effective in reducing distress and pain during catheterization for VCUG or RNC in children.

Extubation failure in pediatric intensive care incidence and outcomes.

OBJECTIVES: To evaluate the hypotheses that children requiring reintubation are at an increased risk of prolonged hospitalizations, congenital heart disease, and death compared with age- and disease-severity-matched control patients. DESIGN: Prospective decision to evaluate all children undergoing extubation over a 5-yr time interval (1997-2001) with retrospective analysis of all failed extubation patients. SETTING: A large multidisciplinary, dual-site, single-system pediatric intensive care unit caring for critically ill and injured children. PATIENTS: All children intubated and ventilated during the study period (1997-2001). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Failed extubation was defined as the unanticipated requirement to replace an endotracheal tube within 48 hrs of extubation. One hundred thirty children of 3,193 pediatric intensive care unit patients failed extubation (4.1%). The median age of children who failed extubation was 6.5 months, compared with a median age of 21.3 months in the control population. The median age of failed extubation in children with cardiac disease was 9.3 months. Failed extubation patients had lengthier hospital and pediatric intensive care unit stays, longer duration of mechanical ventilation, and a higher rate of tracheostomy placement than nonfailed extubation patients (p < .001). Children with congenital heart disease who failed extubation had the longest duration of hospitalization (40.0 +/- 5.4 days). Conversely, cardiac patients who did not fail extubation had the shortest length of stay (11.2 +/- 0.4 days). CONCLUSIONS: In the present trial, 4.1% of mechanically ventilated children failed extubation. Pediatric intensive care unit patients with failed extubation have longer hospital, pediatric intensive care unit, and ventilator courses but are not at increased risk of death relative to nonfailed extubation patients.

Extubation failure in pediatric intensive care: a multiple-center study of risk factors and outcomes.

OBJECTIVE: To determine a contemporary failed extubation rate, risk factors, and consequences of extubation failure in pediatric intensive care units (PICUs). Three hypotheses were investigated: a) Extubation failure is in part disease specific; b) preexisting respiratory conditions predispose to extubation failure; and c) admission acuity scoring does not affect extubation failure. DESIGN: Twelve-month prospective, observational, clinical study. SETTING: Sixteen diverse PICUs in the United States. PATIENTS: Patients were 2,794 patients from the newborn period to 18 yrs of age experiencing a planned extubation trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A descriptive statistical analysis was performed, and outcome differences of the failed extubation population were determined. The extubation failure rate was 6.2% (174 of 2,794; 95% confidence interval, 5.3-7.1). Patient features associated with extubation failure (p <.05) included age < or =24 months; dysgenetic condition; syndromic condition; chronic respiratory disorder; chronic neurologic condition; medical or surgical airway condition; chronic noninvasive positive pressure ventilation; the need to replace the endotracheal tube on admission to the PICU; and the use of racemic epinephrine, steroids, helium-oxygen therapy (heliox), or noninvasive positive pressure ventilation within 24 hrs of extubation. Patients failing extubation had longer pre-extubation intubation time (failed, 148.7 hrs, SD +/- 207.8 vs. success, 107.9 hrs, SD +/- 171.3; p <.001), longer PICU length of stay (17.5 days, SD +/- 15.6 vs. 7.6 days, SD +/- 11.1; p <.001), and a higher mortality rate than patients not failing extubation (4.0% vs. 0.8%; p <.001). Failure was found to be in part disease specific, and preexisting respiratory conditions were found to predispose to failure whereas admission acuity did not. CONCLUSION: A variety of patient features are associated with an increase in extubation failure rate, and serious outcome consequences characterize the extubation failure population in PICUs.