Aspirin resistance in children with heart disease at risk for thromboembolism: prevalence and possible mechanisms.

Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB(2) levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

Left ventricular function and response to enalapril in patients with duchenne muscular dystrophy during the second decade of life.

The role of angiotensin-converting enzyme inhibitors in the management of cardiomyopathy related to Duchenne muscular dystrophy has not been completely defined. The purposes of this study were to describe the response to enalapril and its relation to dystrophin mutation type, ventricular size, or age at the onset of left ventricular (LV) systolic dysfunction. Serial clinical and echocardiographic data from 50 patients with Duchenne muscular dystrophy (aged 10 to 20 years) were retrospectively reviewed. Twenty-seven patients (46%) developed LV systolic dysfunction (mean age 13.2 +/- 2.4 years). Ten (43%) responded to enalapril with the normalization of function. Responders and nonresponders developed LV systolic dysfunction at similar ages (p = 0.91). At the onset of LV systolic dysfunction, only 2 patients (1 responder, 1 nonresponder) had dilated left ventricles. The positive response to enalapril was sustained in 7 patients (median follow-up 23 months, range 5 to 58). No specific mutation was associated with the response to enalapril (p = 0.66) or predictive of the development of LV systolic dysfunction (p = 0.8). In conclusion, 10 of 26 patients (43%) with Duchenne muscular dystrophy responded to the use of enalapril with normalization of the shortening fraction. Age at the onset of LV systolic dysfunction and the type of mutation were not predictors of response to enalapril.

Chloral hydrate sedation for pediatric echocardiography: physiologic responses, adverse events, and risk factors.

OBJECTIVE: The physiologic responses to chloral hydrate sedation in the setting of a pediatric echocardiography laboratory have not been well documented; neither has the population at risk been identified adequately. The purpose of this study was to describe the physiologic responses to chloral hydrate sedation, to report the occurrence of adverse events, and to identify any risk factors that predicted these adverse events in children who underwent sedation for echocardiography at our institution. METHODS: We analyzed retrospectively 1095 patients who were sedated for echocardiography. Vital signs and oxygen saturations were recorded every 5 minutes, and adverse events were noted. Potential risk factors for sedation-related adverse events were analyzed. RESULTS: Thirty-eight percent of patients were classified as American Society of Anesthesiologists class 3 or 4, reflecting the significant comorbidity in the study population. Hemodynamic responses to chloral hydrate sedation included > or = 20% decreases in heart rate (24% of the patients) and blood pressure (59% of the patients). There were no deaths or permanent morbidity. Adverse events occurred in 10.8% of patients and included apnea (n = 3 [0.3%]), airway obstruction (n = 15 [1.4%]), hypoxia (n = 65 [5.9%]), hypercarbia (n = 40 of 603 [6.6%]), hypotension with poor perfusion (n = 4 [0.4%]), vomiting (n = 4 [0.4%]), and prolonged sedation (n = 36 [3.3%]). No intervention was required in 92.5%, minor interventions were necessary in 7%, and major interventions were required in 0.5% of all patients. Multivariate analysis identified only age younger than 6 months as a predictor for adverse events, whereas cyanosis, hospitalization, American Society of Anesthesiologists class, fasting time, oxygen requirement, and use of additional sedation were not predictors. CONCLUSIONS: Moderate decreases in heart rate and blood pressure, in the absence of clinical deterioration, are expected responses to chloral hydrate sedation in this pediatric population. The majority of adverse events were minor, and major events were uncommon. Infants who were younger than 6 months were found to be at higher risk for serious adverse events.