Do Racial/Ethnic and Economic Factors Affect the Rate of Complicated Appendicitis in Children?

INTRODUCTION: Appendicitis continues to be one of the most common surgical conditions in the pediatric population. We set out to determine demographic and practice variations among children admitted with appendicitis and highlight the racial/ethnic and healthcare access role in relation to the rate of complicated appendicitis using the 2012 Kids' Inpatient Database (KID). Methodology. A retrospective cross-sectional database study was performed using the 2012 KID. All children (age 1 months to 20 years) with appendicitis were identified using the ICD-9 diagnosis codes. Children with a diagnosis of appendicitis were compared with all other discharges. Among children with appendicitis, demographic and practice variations and the rate of complicated appendicitis were evaluated. Univariate and multivariate analyses were done to analyze the data. Sample weighing was done to present national estimates. RESULTS: In 2012, a total of 89, 935 out of 2.7 million pediatric hospital discharges (3.3%) had a diagnosis of appendicitis. The incidence of appendicitis was higher in males (4.7%), 6-15-year age group (7.43%), Hispanics (5.2%), and in the Western region (5.2%) and was lower in infants (0.02%) and African American children (1.2%) (p < 0.0001). The proportion of children with peritonitis or abscess was higher in children's hospitals (48.2% vs. 29.0%; OR 2.3, 95% CI: 2.2-2.4). The risk of complicated appendicitis was inversely related to age, while racial and ethnic minority status, bottom quartile of the income group, and government insurance increased the risk. Laparoscopic appendectomy was performed more frequently at children's hospitals (84.8% vs. 74.3%; p < 0.0001). CONCLUSIONS: Appendicitis is more common in Hispanics, males, older children, and in the Western region. Complicated appendicitis is more common in younger children, minority groups, low-income group, and children with government insurance. Children's hospitals manage more children with complicated appendicitis and are more likely to perform laparoscopic appendectomy.

The impact of body mass index on resource utilization and outcomes of children admitted to a pediatric intensive care unit.

INTRODUCTION: Obesity is associated with poor health outcomes but may be protective in intensive care unit patients. The objective of this study is to describe the characteristics of underweight, normal weight, and obese children, and to compare their length of stay, resource utilization, and mortality. METHODS: The charts of 1447 patients who were admitted to a tertiary-level pediatric intensive care unit during 1 calendar year were reviewed. Patients were divided into three groups: underweight (<5th percentile), normal (5th-95th percentiles), and obese (>95th percentile). Body mass index for age percentile was used for children older than age 2 years, and weight-for-height percentile was used for children younger than age 2 years. Demographic data, Pediatric Index of Mortality 2 score, Pediatric Index of Mortality 2 risk of mortality, hospital mortality, hospital length of stay, the use and duration of ventilator support, hemodynamic support, and dialysis were determined. RESULTS: Fifteen percent of children were underweight, while 61.5% were normal weight and 23.5% were obese; 54.9% of the patients were male. The overall mortality was 1.87%, with no significant difference between the three weight groups. The racial distribution, prevalence, and duration of invasive and noninvasive ventilation, and the use of vasopressors, central venous lines, and dialysis were similar between three groups. Tube feeding and parenteral nutrition were used more often in the underweight group. Pediatric intensive care unit and hospital lengths of stays were higher in underweight children. Underweight children were younger when compared to normal or obese children. Pediatric Index of Mortality 2 scores and Pediatric Index of Mortality 2 risk of mortality scores were higher in underweight children. CONCLUSION: There were no significant differences between the three weight groups in mortality. Underweight children were younger and sicker, and received tube feeding and parenteral nutrition more frequently.

Extremity Arterial Thromboses in Hospitalized Children: A National Database Analysis of Prevalence and Therapeutic Interventions.

OBJECTIVES: The purpose of this study was to evaluate the prevalence, demographics, predisposing conditions, therapeutic interventions, and outcomes of extremity arterial thrombosis in hospitalized children. DESIGN: Retrospective cohort study. PATIENTS: National discharge database analysis. MEASUREMENTS AND MAIN RESULTS: Cases of extremity arterial thrombosis in children and neonates were extracted from the Kids' Inpatient Database 2012. These were analyzed and compared with other discharges for prevalence, demographics, treatments, outcomes, and further analyzed by age group and select predisposing conditions. A total of 961 children with extremity arterial thrombosis (prevalence of 2.35/10,000 discharges) were included in our analysis. The median age of extremity arterial thrombosis patients was significantly lower when compared with other pediatric discharges (1 yr [interquartile range, 0-15 yr) vs 3 yr [interquartile range, 0-16 yr]; p < 0.0001). The proportion of females with extremity arterial thrombosis was lower (41.4% vs 53.3%; odds ratio, 0.62; 95% CI, 0.55-0.70) with no racial/ethnic variation in the prevalence of extremity arterial thrombosis. An upper extremity was involved in 18.1% and a lower extremity in 83.3%. Arterial cannulation and cardiac catheterization were much more common in the younger age groups. External trauma was documented in 13.2% of all patients with extremity arterial thrombosis and was more frequent in older age groups. A systemic thrombolytic medication was administered to 5.7% of the patients, thromboembolectomy was performed in 11.8% of the cases, and 3.1% of the patients required amputation. There was a significant variation in the use of thrombolysis, thrombectomy/embolectomy, or requirement for amputation limb based on age groups and underlying predisposing condition. CONCLUSIONS: The study describes the national prevalence of extremity arterial thrombosis in hospitalized children. The management strategies of extremity arterial thrombosis vary with age and underlying predisposing factors.

Heart Rate Variability in Children Following Drowning Injury.

Heart rate variability (HRV) has been used as prognostic tool in various disorders in pediatric and adult patients. In our study we aimed to evaluate heart rate variability indices and their association with neurological outcome in three children with anoxic brain injury following drowning. Three children included in the study were admitted following drowning and required mechanical ventilation and targeted temperature management. All physiologic data, including electrocardiography (ECG) and EEG were collected for a period of 3-5 days after enrollment. ECG signals were analyzed in both time and frequency domains. The spectral power of the low-frequency (LF) band (0.04-0.15 Hz) and that of the high-frequency (HF) band (0.15-0.4 Hz), the standard deviation of the average R to R ECG intervals (SDANN) were calculated. Mean low-frequency/high-frequency power ratios (LF/HF) were compared using a two-tailed t-test and ANOVA with Tukey-Kramer multiple comparisons. The power in the LF band, the LF/HF power ratio, and the SDANN, were lower in children who had a poor outcome, and during periods of isoelectric or burst suppression EEG patterns.

Effects of Closed Endotracheal Suctioning on Systemic and Cerebral Oxygenation and Hemodynamics in Children.

OBJECTIVES: To evaluate the effects of closed endotracheal tube suctioning on systemic oxygen saturation, cerebral regional oxygen saturation, and somatic regional (renal) oxygen saturation and hemodynamic variables in children. DESIGN: Prospective observational. SETTING: A tertiary care PICU. SUBJECTS: Children aged 0-18 years, requiring invasive mechanical ventilation and with an arterial line. INTERVENTIONS: Closed endotracheal suction. MEASUREMENTS AND MAIN RESULTS: The study included 19 sedated and intubated children, 0-18 years old. They were enrolled in an ongoing prospective observational study. We used near-infrared spectroscopy for cerebral regional oxygen saturation and somatic regional (renal) oxygen saturation. The timing of each closed endotracheal tube suctioning event was accurately identified from video recordings. We extracted systemic oxygen saturation, cerebral regional oxygen saturation, somatic regional (renal) oxygen saturation, heart rate, and systolic blood pressure and diastolic blood pressure for 5 minutes before and 5 minutes after each event and used these data for analysis. One-minute average values of these variables were used for repeated-measures analysis. We analyzed 287 endotracheal tube suctioning episodes in 19 children. Saline was instilled into the endotracheal tube during 61 episodes. The mean heart rate (107.0 ± 18.7 vs 110.2 ± 10.4; p < 0.05), mean arterial blood pressure (81.5 ± 16.1 vs 83.0 ± 15.6 mm Hg; p < 0.05), and the mean cerebral regional oxygen saturation (64.8 ± 8.3 vs 65.8 ± 8.3; p < 0.05) were increased after suctioning. The mean systemic oxygen saturation (96.9 ± 2.7 vs 96.7 ± 2.7; p = 0.013) was decreased, whereas the mean somatic regional (renal) oxygen saturation was not significantly different after endotracheal tube suctioning. Repeated-measures analysis revealed transient increases in heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure; a sustained increase in cerebral regional oxygen saturation; and transient decreases in systemic oxygen saturation and somatic regional (renal) oxygen saturation. Saline instillation did not affect oxygenation or hemodynamic variables. CONCLUSIONS: Closed endotracheal tube suctioning in sedated children is associated with transient but clinically insignificant changes in heart rate, blood pressure, cerebral regional oxygen saturation, systemic oxygen saturation, and somatic regional (renal) oxygen saturation. Saline instillation during endotracheal tube suctioning had no adverse effects on systemic or cerebral oxygenation.

Epidemiology and outcomes of children with accidental hypothermia: A propensity-matched study.

BACKGROUND: The purpose of this study was to explore the epidemiology and outcomes of hospitalized children with a diagnosis of accidental hypothermia. METHODS: The 2012 Kids' Inpatient Database, detailing discharge diagnoses in children admitted to US hospitals, was analyzed using International Classification of Diseases, Ninth Revision, Clinical Modification codes to filter out relevant patients. Children ages 1 month to 17 years were included in the analysis. Demographic and outcome variables in the hypothermia group were compared with the rest of the patients. In a separate analysis, children with hypothermia were matched 1:1 using a correlative propensity score using sex, age, hospital region, income quartiles, race, ventilation status, coagulopathy, drowning, and All Patient Refined Diagnosis Related Groups severity score and their outcomes were compared with controls. The sample data were weighted to get a national estimate. RESULTS: Accidental hypothermia was present in 1,028 cases out of 1,915,435 discharges. Children with hypothermia were more likely to be males (54.7% vs. 50.9%; p < 0.05) and infants (32.6% vs. 17.5%); they were less likely to be teens (30% vs. 37.8%). Children with hypothermia were more likely to be admitted in the Southern region (48.3% vs. 38.4%; p < 0.05) and have a higher mortality rate compared to all other discharges (8.5% vs. 0.3%; p < 0.05) or when compared with the matched controls (8.9% vs. 4.4%). CONCLUSIONS: The diagnosis of accidental hypothermia significantly increased mortality in hospitalized children. Interestingly, accidental hypothermia was more common in Southern states compared to the other areas of the United States. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level III.

Hemoglobin Threshold for Blood Transfusion in a Pediatric Intensive Care Unit.

OBJECTIVE: To evaluate the hemoglobin threshold for red cell transfusion in children admitted to a pediatric intensive care unit (PICU). METHODS: Retrospective chart review study. Tertiary care PICU. Critically ill pediatric patients requiring blood transfusion. No intervention. RESULTS: We analyzed the charts of all children between 1 month and 21 years of age who received packed red blood cell (PRBC) transfusions during a 2-year period. The target patients were identified from our blood bank database. For analysis, the patients were subdivided into four groups: acute blood loss (postsurgically, trauma, or acute gastrointestinal bleeding from other causes), hematologic (hematologic malignancies, bone marrow suppression, hemolytic anemia, or sickle cell disease), unstable (FiO2 > 0.6 and/or on inotropic support), and stable groups. We also compared the pre-transfusion hemoglobin threshold in all unstable patients with that of all stable patients. A total of 571 transfusion episodes in 284 patients were analyzed. 28% (n = 160) of transfusions were administered to patients in the acute blood loss group, 36% (n = 206) to hematologic patients, 17% (n = 99) to unstable patients, and 18% (n = 106) to stable patients. The mean pre-transfusion hemoglobin (± SD) in all children as well as in the acute blood loss, hematologic, unstable and stable groups was 7.3 ± 1.20, 7.83 ± 1.32, 6.97 ± 1.31, 7.96 ± 1.37, 7.31 ± 1.09 g/dl, respectively. The transfusion threshold for acute blood loss and unstable groups was higher compared to hematologic and stable groups (p < 0.001; ANOVA with multiple comparisons). The mean pre-transfusion hemoglobin threshold for stable and unstable patients among all groups was 7.3 ± 1.3 and 7.9 ± 1.3 (p < 0.0001), respectively. The observed mortality rate was higher among children who received transfusion compared to other children admitted to PICU. CONCLUSION: The hemoglobin threshold for transfusion varied according to clinical conditions. Overall, the hemoglobin threshold for transfusion was 7.3 ± 1.20 g/dl.

Complications during the management of pediatric refractory status epilepticus with benzodiazepine and pentobarbital infusions.

The objective of this retrospective study was to evaluate complications in the management of refractory status epilepticus (RSE) treated with benzodiazepine and pentobarbital infusions. Of 28 children with RSE, eleven (39%) were treated with a pentobarbital infusion after failure to control RSE with a benzodiazepine infusion; while17 children (61%) required only a benzodiazepine infusion. The mean maximum pentobarbital infusion dosage was 5.2 ± 1.8 mg/kg/h. Twenty-five patients received a continuous midazolam infusion with an average dosage of 0.41 ± 0.43 mg/kg/h. The median length of stay was longer for the pentobarbital group. Children requiring pentobarbital therapy were more likely to develop hypotension, require inotropic support, need intubation, mechanical ventilation, peripheral nutrition, and blood products; furthermore, they were more likely to develop hypertension and movement disorder after or during weaning. In conclusion, children with RSE who required pentobarbital therapy had a longer hospital stay with more complications.

Coral snake bites and envenomation in children: a case series.

OBJECTIVE: North America is home to 2 families of venomous snakes, Crotalinae (pit viper family) and Elapidae (coral snake family). Although there are several published reports describing and reviewing the management of pit viper snakebites in children, there are no recent similar publications detailing the clinical course and management of coral snake envenomation. METHODS: Our case series describes the hospital course of children with coral snake bites admitted to our regional pediatric intensive care. We also reviewed prior published case reports of coral snake bites in the United States. RESULTS: We identified 4 patients with either confirmed or suspected coral snake envenomation from our hospital's records. In 2 cases, the snakebite occurred after apparent provocation. Antivenom was administered to 3 patients. The regional venom response team was consulted for management advice and supplied the antivenom. One patient had a prolonged hospital course, which was complicated by respiratory failure, bulbar palsy, and ataxia. All survived to discharge. CONCLUSIONS: Admission to pediatric intensive care is warranted after all Eastern coral snake bites. A specialized regional or national venom response team can be a useful resource for management advice and as a source of antivenom.

Outcome of children with acute encephalitis and refractory status epilepticus.

Acute encephalitis in children is a life-threatening neurological emergency. However, little is reported about the outcome of this devastating illness in the United States. The authors retrospectively reviewed the charts of patients admitted to a regional pediatric intensive care unit with the diagnosis of acute encephalitis between 2006 and 2011. In 41 cases that met the inclusion criteria, the most common presenting symptoms were fever (65.9%), altered mental status (61%), and seizures (58.5%). Eight patients (19.5%) who presented with refractory status epilepticus had a longer median length of stay in the pediatric intensive care unit (46 vs. 4 days; P < .0001) and a significant worsening of Pediatric Cerebral Performance Category score on discharge by 2 or more points (odds ratio 20.38; 95% confidence interval, 2.89-143.52). All children survived to hospital discharge. In conclusion, children with acute encephalitis who present with refractory status epilepticus have a worse neurological outcome and a longer stay in the pediatric intensive care unit.

Acute kidney injury during vancomycin therapy in critically ill children.

STUDY OBJECTIVE: To determine the rate, risk factors, and outcome of vancomycin-associated acute kidney injury (AKI) in critically ill children. DESIGN: Retrospective cohort study. SETTING: Tertiary care children's hospital. PATIENTS: We reviewed the charts of children admitted to the pediatric intensive care unit during a 2-year period who were treated with vancomycin. Courses of vancomycin interrupted by 3 days or more were counted separately. Patients were excluded if they received vancomycin treatment for fewer than 3 days, had preexisting renal failure, or had incomplete serum creatinine (Scr ) data. MEASUREMENTS AND MAIN RESULTS: Demographic and laboratory data; vancomycin dose, duration, and concentrations; and concurrent use of nephrotoxic drugs were recorded. Acute kidney injury was defined as a decrease in estimated glomerular filtration rate of 50% or more from the beginning of vancomycin therapy. Descriptive statistics, step-wise logistic regression, and repeated measures ANOVA were used to analyze the data. A total of 284 patients were included, for a total of 391 courses of vancomycin (272 children and 119 infants). The mean duration of vancomycin therapy was 6.9 ± 4.5 days. Forty nine (17.2%) patients developed AKI during 61 (15.6%) courses. Elevated Scr concentrations returned to baseline after stopping vancomycin in 53 (87%) courses. Mortality was higher in children who developed AKI (p<0.001; Fisher's exact test). Administration of nephrotoxic drugs (odds ratio 2.23, Confidence Interval 1.27-3.93) and presence of high blood urea nitrogen (BUN):Scr ratio before vancomycin therapy (p<0.05) were associated with AKI. The BUN and Scr concentrations significantly increased during vancomycin therapy and decreased after vancomycin was discontinued (p<0.05). CONCLUSIONS: In critically ill children, the development of reversible AKI during vancomycin therapy is associated with administration of nephrotoxic drugs and an elevated BUN: Scr ratio.

Admission and treatment factors associated with the duration of acidosis in children with diabetic ketoacidosis.

BACKGROUND: Our goal was to determine the factors associated with prolonged acidosis in children with diabetic ketoacidosis. METHOD: The records of all children (109 admissions, 86 patients) admitted to the pediatric intensive care unit (PICU) during a 3-year period with the diagnosis of diabetic ketoacidosis were analyzed. RESULTS: The charts were reviewed after institutional review board approval was obtained. Demographic and serial laboratory data, time to correction of acidosis, as well as the first 24-hour chloride load, total fluid administered, fluid balance, and PICU and hospital lengths of stay were recorded. The anion gap (AG = Na - Cl - HCO(3)) and the delta gap (DG = AG - 12 - [24 - HCO(3)]) were calculated. Prolonged acidosis (HCO(3) < 15 mEq/L at 24 hours) was analyzed against various independent factors on admission and during therapy. Low Na (128 vs 133 mEq/L), HCO3 (4.7 vs 9.5 mEq/L), DG (-6.3 vs -2.8 mEq/L), pH (6.97 vs 7.16), PaCO(2) (15 vs 23 mm Hg), and base excess (-26 vs -18) as well as high chloride load (17 vs 11 mEq/kg per 24 hours) were associated with prolonged acidosis (t test, P < 0.05). Stepwise logistic regression eliminated all except base excess and DG in the model. Children with prolonged acidosis had longer PICU (45 vs 34 hours) and hospital stays (5.5 vs 2.5 days) (P < 0.05). The AG was normal in all cases at 24 hours. There were no deaths. CONCLUSIONS: Nongap acidosis was present in many children with prolonged metabolic acidosis. We suggest that a continuous acetate or bicarbonate therapy via maintenance fluid might be beneficial in this subgroup of patients.

Validation of a modified pediatric early warning system score: a retrospective case-control study.

The Pediatric Early Warning System (PEWS) score may be useful for detection of deterioration in clinical condition. In this retrospective study, the cases were patients transferred to the pediatric intensive care unit (PICU), and controls were those not transferred to the PICU. The maximum PEWS score in both groups were analyzed using Mann-Whitney U test and receiver operating characteristic curve (ROC). The study population included 100 cases and 250 controls. There was no difference in the age of cases and controls (6.3 vs 6.3 years). The length of hospital stay (18.09 ± 32 vs 3.93 ± 2.9 days; P < .001) and the maximum PEWS score (2.95 ± 1.5 vs 1.4 ± 0.8) were significantly higher for the cases (P < .0001). The PEWS score area under the ROC was 0.81 (95% confidence interval = 0.75-0.86). The sensitivity and specificity for a score 2.5 were 62% and 89%, respectively. The use of the modified PEWS score can help identify patients on wards who are at risk for deterioration.

Therapeutic hypercapnia enhances the inflammatory response to endotoxin in the lung of spontaneously breathing rats.

OBJECTIVE: To test the hypothesis that therapeutic hypercapnia enhances the proinflammatory responses to endotoxemia in the lung and spleen of rats. DESIGN: Prospective randomized study. SETTINGS: Hospital research institute. SUBJECTS: Forty-eight adult male rats. INTERVENTIONS: Rats were randomly assigned for a 24-hr period to four breathing groups (n = 11/group), including air (controls), normoxic air with 5% CO2 (therapeutic hypercapnia), air and endotoxemia (5 mg/kg endotoxin), and therapeutic hypercapnia with endotoxemia. After euthanasia, the lung and spleen were removed for pro- and anti-inflammatory cytokine analyses and pulmonary histology evaluation. Four additional rats were used to examine changes in gas exchange and acid-base balance during exposure to therapeutic hypercapnia with and without endotoxemia before and at 4, 12, and 24 hrs into the study, using a permanently catheterized femoral artery. MEASUREMENTS AND MAIN RESULTS: The ratios of proinflammatory cytokines (interleukin-1ß [IL-1ß] and IL-6) and an anti-inflammatory cytokine (IL-10) in the lungs and spleen were used as indices of inflammatory status. The wet-weight to dry-weight ratios, histologic changes in lung interstitial inflammation, and alveolar structures were used as indices of endotoxin-induced acute lung injury. IL-1ß and IL-6 expression was significantly high in the lung of therapeutic hypercapnia-treated endotoxemic rats compared to the lung of rats subjected to only endotoxemia (p < .05 and p < .001, respectively). In the spleen, therapeutic hypercapnia-treated endotoxemic rats had low expression of IL-1ß and IL-6 compared to rats subjected to only endotoxemia (p > .05 and p < .001). Therapeutic hypercapnia following endotoxemic challenge was associated with a proinflammatory response in the lung and an anti-inflammatory response in spleen, as assessed by the ratios of IL-1ß and IL-6 to IL-10. The wet-weight to dry-weight ratio and the interstitial space were significantly increased only in therapeutic hypercapnia-treated endotoxemic rats (p < .05). The alveolar-septal thickness was significantly increased by 21% in endotoxemic rats (p < .001) and by 33% in therapeutic hypercapnia-treated endotoxemic rats (p < .001). CONCLUSIONS: A 24-hr exposure to therapeutic hypercapnia in endotoxin-stimulated, spontaneously breathing rats is associated with a proinflammatory immune response in the lung and anti-inflammatory response in the spleen as well as an increase in certain histologic indices of endotoxin-induced lung injury.

Does hypercapnia ameliorate hyperoxia-induced lung injury in neonatal rats?

Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children's Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) > 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P < 0.05) and 3.0 with TH (P < 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P < 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P < 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P < 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.

Drug use density in critically ill children and newborns: analysis of various methodologies.

OBJECTIVE: To compare in the pediatric, cardiac, and neonatal intensive care units, three methods of assessing vancomycin and linezolid drug use density by number of: defined daily doses (DDDs), prescribed daily doses, and days of drug use per 100 patient days. DESIGN: Retrospective study. SETTING: A tertiary care children's hospital. PATIENTS: We reviewed the charts of patients admitted to the cardiac intensive care unit and neonatal intensive care unit in 2005 who were treated with vancomycin, and those admitted to the pediatric intensive care unit who were treated with vancomycin or linezolid during 2004 and 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The number of patients, treatment days, total amount of vancomycin/linezolid, total intensive care unit admissions, and patient days were recorded. We used the World Health Organization definition of DDD for vancomycin and linezolid (2000 and 1200 mg, respectively). The prescribed daily dose for each intensive care unit was calculated for each year by dividing the total amount of the medication administered by the total number of treatment days. The drug use densities were then calculated as the total DDDs, prescribed daily doses, and days of drug use per 100 patient days. The vancomycin use densities were significantly different among the three intensive care units when compared by each method. They were significantly lower in all three units when expressed as DDDs per 100 patient days. The vancomycin drug use density in the pediatric intensive care unit was significantly decreased during 2005 compared with 2004 by all three methods. CONCLUSIONS: In critically ill children, drug use density of vancomycin is significantly less when evaluated by the DDD method compared with the prescribed daily dose method, a more appropriate method in children. However, the simplest and most accurate method of assessing drug use density is the number of days of drug use method, which allows comparison of drug use density between different pediatric facilities or clinical units.

The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood.

OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37 degrees C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interferon-gamma concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-alpha and interleukin-1beta were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-alpha and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.

Carbon dioxide clearance in rabbits during expiratory phase intratracheal pulmonary ventilation.

The purpose of this study was to compare the efficacy of CO2 removal during conventional mechanical ventilation (CMV) with and without expiratory phase intratracheal pulmonary ventilation (expiratory ITPV or Exp-ITPV); and to compare CO2 clearance during Exp-ITPV, in pressure-controlled ventilation (PCV) and in volume-controlled ventilation (VCV) modes. Seven anesthetized rabbits were tracheotomized and intubated using a 4 mm endotracheal tube. Venous and arterial lines were established. The rabbits were paralyzed, mechanically ventilated, and ventilation parameters were adjusted to achieve baseline arterial hypercapnia. Animals were then ventilated during 30-minute trials of CMV and Exp-ITPV, in both PCV and VCV modes. A custom-built, microprocessor-controlled solenoid valve was used to limit ITPV gas flow to the expiratory phase. Proximal and carinal airway pressures and hemodynamic variables were continuously recorded, and arterial blood gases were analyzed at the end of each trial. Exp-ITPV, as compared with CMV, reduced arterial PCO2 by 12% and 21% in PCV and VCV modes, respectively (p < 0.02 and p < 0.001; one-sided paired t test), without significant changes in other cardiorespiratory variables. In conclusion, Exp-ITPV is more effective than CMV in clearing CO2 through a small endotracheal tube. Exp-ITPV is also more effective in VCV mode than PCV mode.

Hypoxic respiratory failure in term newborns: clinical indicators for inhaled nitric oxide and extracorporeal membrane oxygenation therapy.

PURPOSE: The criteria for starting extracorporeal membrane oxygenation (ECMO) therapy in term newborn patients with hypoxemic respiratory failure consist of an oxygenation index (OI) of 25 or higher and alveolar-arterial oxygen (Aao(2)) gradient of more than 600 at sea level. In such conditions, inhaled nitric oxide (iNO) may improve oxygenation and reduce the need for ECMO therapy. We studied early changes in OI and Aao(2) gradients in response to iNO treatment that may indicate a need to continue iNO treatment or the necessity to start an ECMO therapy. MATERIALS AND METHODS: In this prospective study, we used 34 outborn neonatal patients that were referred to our pediatric critical care unit in a children's hospital for ECMO therapy with diagnosis of hypoxemic respiratory failure. In all patients, iNO therapy, starting at 80 ppm, was instituted either during transport or on arrival to hospital. Response to iNO was assessed after 1 hour, at which time, iNO concentration was reduced to 40 ppm, provided there was more than 20% improvement in either or both oxygenation indices. Patients who did not respond positively to continuous iNO therapy and met ECMO criteria were given ECMO therapy. RESULTS: Inhaled nitric oxide therapy alone was successful in 10 (29%) of 34 patients. Eighteen patients (53%) required ECMO therapy within the first 10 hours of iNO treatment (early ECMO therapy), whereas 6 other neonates (18%) became eligible for ECMO therapy after prolonged (2-4 days) iNO treatment (late ECMO therapy). No mortality occurred with any treatment. Within 4 hours after iNO therapy, patients who required early ECMO therapy had significantly higher OI and Aao(2) gradients than patients who were treated with iNO therapy alone (P<.01, analysis of variance followed by Tukey-Kramer multiple comparison test). Six of 34 patients (18%), categorized as late ECMO therapy, on the average, had initially higher levels of OI and mean airway pressure than neonates in iNO treatment and early ECMO therapy. CONCLUSION: Persisting levels of OI of more than 20 or Aao(2) gradients of more than 600 after 4 hours of iNO therapy could be indicative of an immediate need for ECMO therapy.

Tracheobronchial injury during intratracheal pulmonary ventilation in rabbits.

OBJECTIVE: We compared tracheobronchial injury following short-term intratracheal pulmonary ventilation (ITPV) and conventional mechanical ventilation (CMV) in a healthy rabbit model. ITPV, a form of tracheal gas insufflation, has been shown to decrease deadspace ventilation and increase CO2 removal and therefore may reduce ventilator-induced lung injury. SETTING: Medical center laboratory. SUBJECTS: Twenty-five rabbits. INTERVENTIONS: Rabbits were randomly assigned to either ITPV or CMV (n = 15 and 10, respectively). Both groups were mechanically ventilated for 8 hrs at the same ventilator settings (FIO2, 0.4; rate, 30 breaths/min; flow, 4 L x min(-1); positive end-expiratory pressure, 4 cm H2O; tidal volume, 40 mL). Peak, mean, and end-expiratory carinal pressures, ITPV flow rate, and hemodynamic variables were continuously monitored. Tissue samples for histologic analysis were obtained postmortem from the trachea contiguous to the tip of the endotracheal tube, the distal trachea, the carina, and the main bronchus. The histologic sections were scored, in a single-blind fashion, for ciliary damage, ulceration, hemorrhage, overall inflammation, intraepithelial inflammatory infiltrate, and edema. MEASUREMENTS AND MAIN RESULTS: ITPV was associated with significantly lower Paco and deadspace ventilation ratio than CMV. The combined tracheobronchial injury scores for all samples were significantly higher in the ITPV group compared with the CMV group (p <.005; Mann-Whitney U test). The ITPV injury scores, compared with CMV injury scores, were significantly higher at the carina and main bronchus (p <.01; Kruskal-Wallis test followed by Dunn's multiple comparison test). The area adjacent to the endotracheal tube showed the same degree of damage in both groups. Analysis of the injury scores in individual damage categories demonstrated the greatest difference in the ulceration category (p <.001). CONCLUSIONS: In our study, ITPV, compared with CMV at the same minute ventilation, was associated with a significantly greater difference in tracheobronchial damage at the carina and main bronchus. We postulate that this difference may have been caused by the turbulence of the gas flow generated by the small-caliber ITPV catheter used in our neonatal-size animal model.