Nathan Kuppermann

Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study

BACKGROUND CT imaging of head-injured children has risks of radiation-induced malignancy. Our aim was to identify children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary. METHODS We enrolled patients younger than 18 years presenting within 24 h of head trauma with Glasgow Coma Scale scores of 14-15 in 25 North American emergency departments. We derived and validated age-specific prediction rules for ciTBI (death from traumatic brain injury, neurosurgery, intubation >24 h, or hospital admission >or=2 nights). FINDINGS We enrolled and analysed 42 412 children (derivation and validation populations: 8502 and 2216 younger than 2 years, and 25 283 and 6411 aged 2 years and older). We obtained CT scans on 14 969 (35.3%); ciTBIs occurred in 376 (0.9%), and 60 (0.1%) underwent neurosurgery. In the validation population, the prediction rule for children younger than 2 years (normal mental status, no scalp haematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 s, non-severe injury mechanism, no palpable skull fracture, and acting normally according to the parents) had a negative predictive value for ciTBI of 1176/1176 (100.0%, 95% CI 99.7-100 0) and sensitivity of 25/25 (100%, 86.3-100.0). 167 (24.1%) of 694 CT-imaged patients younger than 2 years were in this low-risk group. The prediction rule for children aged 2 years and older (normal mental status, no loss of consciousness, no vomiting, non-severe injury mechanism, no signs of basilar skull fracture, and no severe headache) had a negative predictive value of 3798/3800 (99.95%, 99.81-99.99) and sensitivity of 61/63 (96.8%, 89.0-99.6). 446 (20.1%) of 2223 CT-imaged patients aged 2 years and older were in this low-risk group. Neither rule missed neurosurgery in validation populations. INTERPRETATION These validated prediction rules identified children at very low risk of ciTBIs for whom CT can routinely be obviated. FUNDING The Emergency Medical Services for Children Programme of the Maternal and Child Health Bureau, and the Maternal and Child Health Bureau Research Programme, Health Resources and Services Administration, US Department of Health and Human Services.

Risk factors for cerebral edema in children with diabetic ketoacidosis

BACKGROUND Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. METHODS In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. RESULTS A comparison of the children in the cerebral-edema group with those in the random control group showed that cerebral edema was significantly associated with lower initial partial pressures of arterial carbon dioxide (relative risk of cerebral edema for each decrease of 7.8 mm Hg [representing 1 SD], 3.4; 95 percent confidence interval, 1.9 to 6.3; P<0.001) and higher initial serum urea nitrogen concentrations (relative risk of cerebral edema for each increase of 9 mg per deciliter [3.2 mmol per liter] [representing 1 SD], 1.7; 95 percent confidence interval, 1.2 to 2.5; P=0.003). A comparison of the children with cerebral edema with those in the matched control group also showed that cerebral edema was associated with lower partial pressures of arterial carbon dioxide and higher serum urea nitrogen concentrations. Of the therapeutic variables, only treatment with bicarbonate was associated with cerebral edema, after adjustment for other covariates (relative risk, 4.2; 95 percent confidence interval, 1.5 to 12.1; P=0.008). CONCLUSIONS Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.

A decision rule for identifying children at low risk for brain injuries after blunt head trauma

STUDY OBJECTIVE Computed tomography (CT) is frequently used in evaluating children with blunt head trauma. Routine use of CT, however, has disadvantages. Therefore, we sought to derive a decision rule for identifying children at low risk for traumatic brain injuries. METHODS We enrolled children with blunt head trauma at a pediatric trauma center in an observational cohort study between July 1998 and September 2001. We evaluated clinical predictors of traumatic brain injury on CT scan and traumatic brain injury requiring acute intervention, defined by a neurosurgical procedure, antiepileptic medications for more than 1 week, persistent neurologic deficits, or hospitalization for at least 2 nights. We performed recursive partitioning to create clinical decision rules. RESULTS Two thousand forty-three children were enrolled, 1,271 (62%) underwent CT, 98 (7.7%; 95% confidence interval [CI] 6.3% to 9.3%) had traumatic brain injuries on CT scan, and 105 (5.1%; 95% CI 4.2% to 6.2%) had traumatic brain injuries requiring acute intervention. Abnormal mental status, clinical signs of skull fracture, history of vomiting, scalp hematoma (in children < or =2 years of age), or headache identified 97/98 (99%; 95% CI 94% to 100%) of those with traumatic brain injuries on CT scan and 105/105 (100%; 95% CI 97% to 100%) of those with traumatic brain injuries requiring acute intervention. Of the 304 (24%) children undergoing CT who had none of these predictors, only 1 (0.3%; 95% CI 0% to 1.8%) had traumatic brain injury on CT, and that patient was discharged from the ED without complications. CONCLUSION Important factors for identifying children at low risk for traumatic brain injuries after blunt head trauma included the absence of: abnormal mental status, clinical signs of skull fracture, a history of vomiting, scalp hematoma (in children < or =2 years of age), and headache.

Clinical and demographic factors associated with urinary tract infection in young febrile infants

Objective. Previous research has identified clinical predictors for urinary tract infection (UTI) to guide urine screening in febrile children <24 months of age. These studies have been limited to single centers, and few have focused on young infants who may be most at risk for complications if a UTI is missed. The objective of this study was to identify clinical and demographic factors associated with UTI in febrile infants who are ≤60 days of age using a prospective multicenter cohort. Methods. We conducted a multicenter, prospective, cross-sectional study during consecutive bronchiolitis seasons. All febrile (≥38°C) infants who were ≤60 days of age and seen at any of 8 pediatric emergency departments from October through March 1999–2001 were eligible. Clinical appearance was evaluated using the Yale Observation Scale. UTI was defined as growth of a known bacterial pathogen from a catheterized specimen at a level of (1) ≥50000 cfu/mL or (2) ≥10000 cfu/mL in association with a positive dipstick test or urinalysis. We used bivariate tests and multiple logistic regression to identify demographic and clinical factors that were associated with the likelihood of UTI. Results. A total of 1025 (67%) of 1513 eligible patients were enrolled; 9.0% of enrolled infants received a diagnosis of UTI. Uncircumcised male infants had a higher rate of UTI (21.3%) compared with female (5.0%) and circumcised male (2.3%) infants. Infants with maximum recorded temperature of ≥39°C had a higher rate of UTI (16.3%) than other infants (7.2%). After multivariable adjustment, UTI was associated with being uncircumcised (odds ratio: 10.4; bias-corrected 95% confidence interval: 4.7–31.4) and maximum temperature (odds ratio: 2.4 per °C; 95% confidence interval: 1.5–3.6). Factors that were reported previously to be associated with risk for UTI in infants and toddlers, such as white race and ill appearance, were not significantly associated with risk for UTI in this cohort of young infants. Conclusions. Being uncircumcised and height of fever were associated with UTI in febrile infants who were ≤60 days of age. Uncircumcised male infants were at particularly high risk and may warrant a different approach to screening and management.

Predictors of Occult Pneumococcal Bacteremia in Young Febrile Children

STUDY OBJECTIVE Occult pneumococcal bacteremia (OPB) occurs in 2.5% to 3% of highly febrile children 3 to 36 months of age, and 10% to 25% of untreated patients with OPB experience complications, including 3% to 6% in whom meningitis develops. The purpose of this study was to identify predictors of OPB among a large cohort of young, febrile children treated as outpatients using multivariable statistical methods. METHODS We derived and validated a logistic regression model for the prediction of OPB. We evaluated 6,579 outpatients 3 to 36 months of age with temperatures of 39 degrees C or higher who previously had been enrolled in a study of young febrile patients at risk of OPB in the emergency departments of 10 hospitals in the United States between 1987 and 1991; 164 patients (2.5%) had OPB. We randomly selected two thirds of this population for the derivation of the model and one third for validation. In the derivation set, we analyzed the univariate relationships of six variables with OPB: age, temperature, clinical score, WBC count, absolute neutrophil count (ANC), and absolute band count (ABC). All six variables were then entered into a logistic regression equation and those retaining statistical significance were considered to have an independent association with OPB. RESULTS Patients with OPB were younger, more frequently ill-appearing, and had higher temperatures, WBC, ANC, and ABC than patients without bacteremia. Only three variables, however, retained statistically significant associations with OPB in the multivariate analysis: ANC (Adjusted odds ratio [OR] 1.15 for each 1,000 cells/mm3 increase, 95% confidence interval [CI] 1.06, 1.25), temperature (adjusted OR 1.77 for each 1 degree C increase, 95% CI 1.21, 2.58), and age younger than 2 years (adjusted OR 2.43 versus patients 2 to 3 years old, 95% CI interval 1.11, 5.34). In the derivation set, 8.1% of patients with ANCs greater than or equal to 10,000 cell/mm3 had OPB (95% CI 6.3, 10.1%) versus .8% of patients with ANCs less than 10,000 cells/mm3 (95% CI .5, 1.2%). When tested on the validation set, the model performed similarly. CONCLUSION Independent predictors of OPB in children 3 to 36 months of age with temperatures of 39 degrees C or higher treated as outpatients include ANC, temperature, and age younger than 2 years. These predictors may be used to develop clinical strategies to limit laboratory testing and antibiotic administration to those children at greatest risk of OPB.

Effect of Antibiotic Pretreatment on Cerebrospinal Fluid Profiles of Children With Bacterial Meningitis

OBJECTIVE. The goal of this study was to evaluate the effect of antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis. METHODS. We reviewed the medical records of all children (1 month to 18 years of age) with bacterial meningitis who presented to 20 pediatric emergency departments between 2001 and 2004. Bacterial meningitis was defined by positive cerebrospinal fluid culture results for a bacterial pathogen or cerebrospinal fluid pleocytosis with positive blood culture and/or cerebrospinal fluid latex agglutination results. Probable bacterial meningitis was defined as positive cerebrospinal fluid Gram stain results with negative results of bacterial cultures of blood and cerebrospinal fluid. Antibiotic pretreatment was defined as any antibiotic administered within 72 hours before the lumbar puncture. RESULTS. We identified 231 patients with bacterial meningitis and another 14 with probable bacterial meningitis. Of those 245 patients, 85 (35%) had received antibiotic pretreatment. After adjustment for patient age, duration and severity of illness at presentation, and bacterial pathogen, longer duration of antibiotic pretreatment was not significantly associated with cerebrospinal fluid white blood cell count, cerebrospinal fluid absolute neutrophil count. However, antibiotic pretreatment was significantly associated with higher cerebrospinal fluid glucose and lower cerebrospinal fluid protein levels. Although these effects became apparent earlier, patients with ≥12 hours of pretreatment, compared with patients who either were not pretreated or were pretreated for <12 hours, had significantly higher median cerebrospinal fluid glucose levels (48 mg/dL vs 29 mg/dL) and lower median cerebrospinal fluid protein levels (121 vs 178 mg/dL). CONCLUSIONS. In patients with bacterial meningitis, antibiotic pretreatment is associated with higher cerebrospinal fluid glucose levels and lower cerebrospinal fluid protein levels, although pretreatment does not modify cerebrospinal fluid white blood cell count or absolute neutrophil count results.

Frequency of sub‐clinical cerebral edema in children with diabetic ketoacidosis

Abstract:  Symptomatic cerebral edema occurs in approximately 1% of children with diabetic ketoacidosis (DKA). However, asymptomatic or subclinical cerebral edema is thought to occur more frequently. Some small studies have found narrowing of the cerebral ventricles indicating cerebral edema in most or all children with DKA, but other studies have not detected narrowing in ventricle size. In this study, we measured the intercaudate width of the frontal horns of the lateral ventricles using magnetic resonance imaging (MRI) in children with DKA during treatment and after recovery from the DKA episode. We determined the frequency of ventricular narrowing and compared clinical and biochemical data for children with and without ventricular narrowing. Forty‐one children completed the study protocol. The lateral ventricles were significantly smaller during DKA treatment (mean width, 9.3 ± 0.3 vs. 10.2 ± 0.3 mm after recovery from DKA, p < 0.001). Children with ventricular narrowing during DKA treatment (22 children, 54%) were more likely to have mental status abnormalities than those without narrowing [12/22 vs. 4/19 with Glasgow Coma Scale (GCS) scores below 15 during therapy, p = 0.03]. Multiple logistic regression analysis revealed that a lower initial PCO2 level was significantly associated with ventricular narrowing [odds ratio (OR) = 0.88, 95% confidence interval (95% CI) = 0.78–0.99, p = 0.047). No other variables analyzed were associated with ventricular narrowing in the multivariate analysis. We conclude that narrowing of the lateral ventricles is evident in just over half of children being treated for DKA. Although children with ventricular narrowing did not exhibit neurological abnormalities sufficient for a diagnosis of ‘symptomatic cerebral edema’, mild mental status abnormalities occurred frequently, suggesting that clinical evidence of cerebral edema in children with DKA may be more common than previously reported.

Epidemiology of a pediatric emergency medicine research network: the PECARN Core Data Project.

Objective: To examine the epidemiology of pediatric patient visits to emergency departments (ED). Methods: We conducted a cross-sectional study of pediatric ED visits at the participating Pediatric Emergency Care Applied Research Network (PECARN) hospitals in 2002. We provide descriptive characteristics of pediatric ED visits and a comparison of the study database to the National Hospital Ambulatory Medical Care Survey (NHAMCS). Bivariate analyses were calculated to assess characteristics associated with hospital admission, death in the ED, and length of ED visit. We also performed multivariate regression to model the likelihood of admission to the hospital. Results: Mean patient age was 6.2 years; 53.5% were boys; 47.5% black; and 43.2% had Medicaid insurance. The most common ED diagnoses were fever, upper respiratory infection, asthma, otitis media, and viral syndromes. The inpatient admission rate was 11.6%. The most common diagnoses requiring hospitalization were asthma, dehydration, fever, bronchiolitis, and pneumonia. In multivariate analysis, patients who were black or Hispanic, had Medicaid insurance or were uninsured, or were older than 1 year were less likely to be hospitalized. Demographics of the PECARN population were similar to NHAMCS, with notable exceptions of a larger proportion of black patients and of admitted patients from the PECARN EDs. Conclusion: We describe previously unavailable epidemiological information about childhood illnesses and injuries that can inform development of future studies on the effectiveness, outcomes, and quality of emergency medical services for children. Most pediatric ED patients in our study sought care for infectious causes or asthma and were discharged from the ED. Hospital admission rate differed according to age, payer type, race/ethnicity, and diagnosis.

Occult bacteremia in young febrile children

The evaluation of nontoxic-appearing, young, febrile children has been a subject of considerable debate. Of young, nontoxic-appearing children aged 3 to 36 months with temperatures of 39 degrees C or more and no clear source, approximately 2% to 3% have occult bacteremia. Of these bacteremias, approximately 90% are caused by S. pneumoniae, 5% by nontyphoidal Salmonella sp., and 1% by N. meningitidis. Most children with occult pneumococcal bacteremia improve spontaneously, but approximately 25% of untreated patients have persistent bacteremia or develop new focal infections, including 3% to 6% who develop meningitis. Occult meningococcal bacteremia, although rare, has frequent complications, including meningitis in approximately 40% and death in approximately 4%. Less is known about the natural history of untreated occult nontyphoidal Salmonella bacteremia. Empiric antibiotic treatment of children with occult bacteremia decreases the rate of complications, including meningitis. Few disagree that febrile, young children at risk for occult bacteremia require a careful clinical evaluation and close follow-up. The benefits of laboratory screening and selective empiric antibiotic treatment of febrile children at risk for occult bacteremia have to be weighed against the costs of screening tests and blood cultures, inconvenience, temporary discomfort to patients, risk for side effects of antibiotics, and the role of antibiotics in the development of bacterial resistance. Although great debate exists concerning the role of empiric antibiotics, a strategy for obtaining blood cultures and empirically administering antibiotics on the basis of an increased ANC, in addition to close clinical follow-up, may be effective in reducing the frequency and severity of uncommon but adverse sequelae. A highly effective S. pneumoniae bacterial conjugate vaccine will soon be available, which will benefit all children, and will alter the ways that clinicians evaluate fully immunized young, febrile children.

Identifying Children at Very Low Risk of Clinically Important Blunt Abdominal Injuries

STUDY OBJECTIVE We derive a prediction rule to identify children at very low risk for intra-abdominal injuries undergoing acute intervention and for whom computed tomography (CT) could be obviated. METHODS We prospectively enrolled children with blunt torso trauma in 20 emergency departments. We used binary recursive partitioning to create a prediction rule to identify children at very low risk of intra-abdominal injuries undergoing acute intervention (therapeutic laparotomy, angiographic embolization, blood transfusion for abdominal hemorrhage, or intravenous fluid for ≥2 nights for pancreatic/gastrointestinal injuries). We considered only historical and physical examination variables with acceptable interrater reliability. RESULTS We enrolled 12,044 children with a median age of 11.1 years (interquartile range 5.8, 15.1 years). Of the 761 (6.3%) children with intra-abdominal injuries, 203 (26.7%) received acute interventions. The prediction rule consisted of (in descending order of importance) no evidence of abdominal wall trauma or seat belt sign, Glasgow Coma Scale score greater than 13, no abdominal tenderness, no evidence of thoracic wall trauma, no complaints of abdominal pain, no decreased breath sounds, and no vomiting. The rule had a negative predictive value of 5,028 of 5,034 (99.9%; 95% confidence interval [CI] 99.7% to 100%), sensitivity of 197 of 203 (97%; 95% CI 94% to 99%), specificity of 5,028 of 11,841 (42.5%; 95% CI 41.6% to 43.4%), and negative likelihood ratio of 0.07 (95% CI 0.03 to 0.15). CONCLUSION A prediction rule consisting of 7 patient history and physical examination findings, and without laboratory or ultrasonographic information, identifies children with blunt torso trauma who are at very low risk for intra-abdominal injury undergoing acute intervention. These findings require external validation before implementation.