Wilbert H. Mason

The Treatment of Kawasaki Syndrome with Intravenous Gamma Globulin

We compared the efficacy of intravenous gamma globulin plus aspirin with that of aspirin alone in reducing the frequency of coronary-artery abnormalities in children with acute Kawasaki syndrome in a multicenter, randomized trial. Children randomly assigned to the gamma globulin group received intravenous gamma globulin, 400 mg per kilogram of body weight per day, for four consecutive days; both treatment groups received aspirin, 100 mg per kilogram per day, through the 14th day of illness, then 3 to 5 mg per kilogram per day. Two-dimensional echocardiograms were interpreted blindly and independently by two or more readers. Two weeks after enrollment, coronary-artery abnormalities were present in 18 of 78 children (23 percent) in the aspirin group, as compared with 6 of 75 (8 percent) in the gamma globulin group (P = 0.01). Seven weeks after enrollment, abnormalities were present in 14 of 79 children (18 percent) in the aspirin group and in 3 of 79 (4 percent) in the gamma globulin group (P = 0.005). No child had serious adverse effects from receiving gamma globulin. We conclude that high-dose intravenous gamma globulin is safe and effective in reducing the prevalence of coronary-artery abnormalities when administered early in the course of Kawasaki syndrome.

A Single Intravenous Infusion of Gamma Globulin as Compared with Four Infusions in the Treatment of Acute Kawasaki Syndrome

BACKGROUND Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen. METHODS We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day). RESULTS The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient. CONCLUSIONS In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.

Diagnosis and Management of Bronchiolitis

Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection. It is the most common lower respiratory infection in this age group. It is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, increased mucus production, and bronchospasm. The American Academy of Pediatrics convened a committee composed of primary care physicians and specialists in the fields of pulmonology, infectious disease, emergency medicine, epidemiology, and medical informatics. The committee partnered with the Agency for Healthcare Research and Quality and the RTI International-University of North Carolina Evidence-Based Practice Center to develop a comprehensive review of the evidence-based literature related to the diagnosis, management, and prevention of bronchiolitis. The resulting evidence report and other sources of data were used to formulate clinical practice guideline recommendations. This guideline addresses the diagnosis of bronchiolitis as well as various therapeutic interventions including bronchodilators, corticosteroids, antiviral and antibacterial agents, hydration, chest physiotherapy, and oxygen. Recommendations are made for prevention of respiratory syncytial virus infection with palivizumab and the control of nosocomial spread of infection. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent comprehensive peer review before it was approved by the American Academy of Pediatrics. This clinical practice guideline is not intended as a sole source of guidance in the management of children with bronchiolitis. Rather, it is intended to assist clinicians in decision-making. It is not intended to replace clinical judgment or establish a protocol for the care of all children with this condition. These recommendations may not provide the only appropriate approach to the management of children with bronchiolitis.

Development, Testing, and Findings of a Pediatric- Focused Trigger Tool to Identify Medication-Related Harm in US Children's Hospitals

OBJECTIVES. The purposes of this study were to develop a pediatric-focused tool for adverse drug event detection and describe the incidence and characteristics of adverse drug events in childrens hospitals identified by this tool. METHODS. A pediatric-specific trigger tool for adverse drug event detection was developed and tested. Eighty patients from each site were randomly selected for retrospective chart review. All adverse drug events identified using the trigger tool were evaluated for severity, preventability, ability to mitigate, ability to identify the event earlier, and presence of associated occurrence report. Each trigger and the entire tool were evaluated for positive predictive value. RESULTS. Review of 960 randomly selected charts from 12 childrens hospitals revealed 2388 triggers (2.49 per patient) and 107 unique adverse drug events. Mean adverse drug event rates were 11.1 per 100 patients, 15.7 per 1000 patient-days, and 1.23 per 1000 medication doses. The positive predictive value of the trigger tool was 3.7%. Twenty-two percent of all adverse drug events were deemed preventable, 17.8% could have been identified earlier, and 16.8% could have been mitigated more effectively. Ninety-seven percent of the identified adverse drug events resulted in mild, temporary harm. Only 3.7% of adverse drug events were identified in existing hospital-based occurrence reports. The most common adverse drug events identified were pruritis and nausea, the most common medication classes causing adverse drug events were opioid analgesics and antibiotics, and the most common stages of the medication management process associated with preventable adverse drug events were monitoring and prescribing/ordering. CONCLUSIONS. Adverse drug event rates in hospitalized children are substantially higher than previously described. Most adverse drug events resulted in temporary harm, and 22% were classified as preventable. Only 3.7% were identified by using traditional voluntary reporting methods. Our pediatric-focused trigger tool is effective at identifying adverse drug events in inpatient pediatric populations.

Imipenem/cilastatin treatment of bacterial meningitis in children.

The safety and efficacy of imipenem/cilastatin were evaluated in 21 children, ages 3 to 48 months, with bacterial meningitis. Eradication of bacteria from the cerebrospinal fluid was demonstrated within 24 hours of antibiotic therapy in all but 2 patients who had Haemophilus influenzae type b meningitis and ultimately achieved bacteriologic cure after 2 to 3 days of imipenem/cilastatin therapy. Cerebrospinal fluid penetrations of imipenem and cilastatin were determined at various times after drug administration with mean cerebrospinal fluid: serum ratios of 14 and 10% for imipenem and cilastatin, respectively. The study was terminated when 7 (33%) patients developed seizure activity after antibiotic therapy was administered. The usefulness of imipenem/cilastatin for the treatment of bacterial meningitis in children may be limited by a possible increased incidence of drug-related seizure activity.

Evaluation of Kawasaki Disease Risk-Scoring Systems for Intravenous Immunoglobulin Resistance

OBJECTIVES To assess the performance of 3 risk scores from Japan that were developed to predict, in children with Kawasaki disease, resistance to intravenous immunoglobulin (IVIG) treatment. STUDY DESIGN We used data from a randomized trial of pulsed steroids for primary treatment of Kawasaki disease to assess operating characteristics of the 3 risk scores, and we examined whether steroid therapy lowers the risk of coronary artery abnormalities in patients prospectively classified as IVIG resistant. RESULTS For comparability with published cohorts, we analyzed the data of 99 patients who were not treated with steroids (16% IVIG-retreated) and identified male sex, lower albumin level, and higher aspartate aminotransferase level as independent risk factors for IVIG resistance. The Kobayashi score was similar in IVIG-resistant and -responsive patients, yielding a sensitivity of 33% and specificity of 87%. There was no interaction of high-risk versus low-risk status by treatment received (steroid versus placebo) with any of the 3 risk score algorithms. CONCLUSION Risk-scoring systems from Japan have good specificity but low sensitivity for predicting IVIG resistance in a North American cohort. Primary steroid therapy did not improve coronary outcomes in patients prospectively classified as being at high-risk for IVIG resistance.

Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease

Study objectives (1) To determine those diseases that most often mimic Kawasaki disease (KD) in the United States. (2) To examine the physical findings and laboratory studies that influenced experienced clinicians to exclude the diagnosis of KD. (3) To compare epidemiologic features of patients with KD and patients referred for evaluation of possible KD in whom alternative diagnoses were established. Design: Case comparison study. Setting: Seven pediatric tertiary care centers. Patients: Consecutive sample of 280 patients with KD and 42 comparison patients examined within the first 14 days after onset of fever. Measurements and main results: (1) Infectious diseases, particularly measles and group A β-hemolytic streptococcal infection, most closely mimicked KD and accounted for 35 (83%) of 42 patients in the comparison group. (2) The standard diagnostic clinical criteria for KD were fulfilled in 18 (46%) of 39 patients in whom other diagnoses were established. (3) Patients with KD were significantly less likely to have exudative conjunctivitis or pharyngitis, generalized adenopathy, and discrete intraoral lesions, and more likely to have a perineal distribution of their rash. The patients with KD were also more likely to have anemia and elevated erythrocyte sedimentation rate; leukocyte count 3 /mm 3 and platelet count 3 /mm 3 were significantly less prevalent in patients with KD. (4) Residence within 200 yards of a body of water was more common among KD patients. Conclusions: (1) Measles and streptococcal infection should be excluded in patients examined for possible KD. (2) Laboratory studies that may be useful in discriminating patients with KD from those with alternative diagnoses include hemoglobin concentration, erthyrocyte sedimentation rate, and serum alanine aminotransferase activity. (3) Residence near a body of water may be a risk factor for the development of KD.

Prevention of Central Venous Catheter–Associated Bloodstream Infections in Pediatric Intensive Care Units: A Performance Improvement Collaborative

OBJECTIVE The goal of this effort was to reduce central venous catheter (CVC)-associated bloodstream infections (BSIs) in pediatric intensive care unit (ICU) patients by means of a multicenter evidence-based intervention. METHODS An observational study was conducted in 26 freestanding childrens hospitals with pediatric or cardiac ICUs that joined a Child Health Corporation of America collaborative. CVC-associated BSI protocols were implemented using a collaborative process that included catheter insertion and maintenance bundles, daily review of CVC necessity, and daily goals. The primary goal was either a 50% reduction in the CVC-associated BSI rate or a rate of 1.5 CVC-associated BSIs per 1,000 CVC-days in each ICU at the end of a 9-month improvement period. A 12-month sustain period followed the initial improvement period, with the primary goal of maintaining the improvements achieved. RESULTS The collaborative median CVC-associated BSI rate decreased from 6.3 CVC-associated BSIs per 1,000 CVC-days at the start of the collaborative to 4.3 CVC-associated BSIs per 1,000 CVC-days at the end of the collaborative. Sixty-five percent of all participants documented a decrease in their CVC-associated BSI rate. Sixty-nine CVC-associated BSIs were prevented across all teams, with an estimated cost avoidance of

Risk factors for early infection of central venous catheters in pediatric patients

2.9 million. Hospitals were able to sustain their improvements during a 12-month sustain period and prevent another 198 infections. CONCLUSIONS We conclude that our collaborative quality improvement project demonstrated that significant reduction in CVC-associated BSI rates and related costs can be realized by means of evidence-based prevention interventions, enhanced communication among caregivers, standardization of CVC insertion and maintenance processes, enhanced measurement, and empowerment of team members to enforce adherence to best practices.

Nebulized Hypertonic Saline for Bronchiolitis: A Randomized Clinical Trial

BACKGROUND In an effort to avoid infections that can lead to the premature removal of indwelling central venous catheters (CVCs), the surgical technique and host factors present in pediatric recipients of permanent CVCs were reviewed. STUDY DESIGN All patients receiving CVCs over a 17-month period were identified. Those patients with fever and positive blood cultures drawn through the CVC within 45 days of line placement were labeled as having early infection. A case-control design was used to select two control patients for each infected patient. Charts from both the infection and control groups were reviewed for several factors present at the time of CVC placement, including fever, neutropenia (absolute neutrophil count [ANC] < 500 and ANC < 1,000), use of perioperative antibiotics, diagnosis, CVC site, and type of CVC. Chi-square test with Yates correction was used to compare the groups. Odds ratios (ORs) and 95% confidence intervals were derived. RESULTS Among the 473 CVCs placed, early infections developed in 53 patients (12%). The control group consisted of 106 patients. Neutropenia was present in 16 of 53 infected patients versus 8 of 106 controls (p = 0.004, OR = 5.30). Perioperative antibiotics were given to 25 of 53 infected patients versus 72 of 106 controls (p = 0.02, OR = 0.42). Fever was present in 12 of 53 infected patients versus 14 of 106 controls (p = 0.19, OR = 1.92). Factors that were equally prevalent between the groups and that did not appear to influence the CVC infection rate included a diagnosis of malignancy, CVC type, and site of placement. Of the 53 infected catheters, 16 (30%) could not be cleared of infection and were removed. CONCLUSIONS This study documents that neutropenia and failure to administer prophylactic antibiotics are risk factors for the development of early CVC infection in pediatric patients. To avoid early infection and possible premature CVC removal, we recommend that placement of permanent CVCs be postponed until the ANC is > 1,000. Perioperative antibiotics should be given. A trend toward higher infection rates was seen in patients with preoperative fever.