Demonstrating Feasibility of an Opportunistic Sampling Approach for Pharmacokinetic Studies of ß-Lactam Antibiotics in Critically Ill Children.

There has been increasing interest in incorporating ß-lactam precision dosing into routine clinical care, but robust population pharmacokinetic models in critically ill children are needed for these purposes. The objective of this study was to demonstrate the feasibility of an opportunistic sampling approach that utilizes scavenged residual blood for future pharmacokinetic studies of cefepime, meropenem, and piperacillin. We aimed to show that opportunistic samples would cover the full concentration-versus-time profiles and to evaluate stability of the antibiotics in whole blood and plasma to optimize future use of the opportunistic sampling approach. A prospective observational study was conducted in a single-center pediatric intensive care unit, where pediatric patients administered at least 1 dose of cefepime, meropenem, or piperacillin/tazobactam and who had residual blood scavenged from samples obtained for routine clinical care were enrolled. A total of 138 samples from 22 pediatric patients were collected in a 2-week period. For all 3 antibiotics, the samples collected covered the entire dosing intervals and were not clustered around specific times. There was high variability in the free concentrations and in the percentage of drug bound to protein. There was less than 15% degradation for meropenem or piperacillin when stored in whole blood or plasma at 4°C after 6 days. Cefepime degraded by more than 15% after 3 days. The opportunistic sampling approach is a powerful and feasible method to obtain sufficient samples to study the variability of drug concentrations and protein binding for future pharmacokinetic studies in the pediatric critical care population.

Paediatric ganciclovir dosing in extracorporeal membrane oxygenation: Is standard dosing good enough?

WHAT IS KNOWN AND OBJECTIVE: Ganciclovir is a first-line antiviral agent to treat cytomegalovirus disease in immunocomprimised patients. Ganciclovir pharmacokinetics in ECMO is unknown. CASE DESCRIPTION: A 6-year-old with a stage IV extra-renal rhabdoid tumor with respiratory failure leading to extracorporeal membrane oxygenation had increasing serum CMV DNAemia while on ganciclovir. WHAT IS NEW AND CONCLUSION: This is the first case report of ganciclovir pharmacokinetics in either paediatric or adult ECMO populations. Recommended dosing provided a low, subtherapeutic AUC24 with an associated increase CMV viral load. Higher doses of ganciclovir may be required in ECMO patients, especially without concurrent CRRT.

Hypertension, age, and location predict rupture of small intracranial aneurysms.

BACKGROUND: Although current guidelines for the management of unruptured intracranial aneurysms (IAs) suggest aneurysms larger than 7 mm should be considered for treatment, a significant number of subarachnoid hemorrhages are caused by IAs 7 mm or smaller. Thus, we sought to identify risk factors associated with the rupture of IAs 7 mm or smaller. METHODS: We identified 100 patients with subarachnoid hemorrhage resulting from IAs 7 mm or smaller between January 2001 and 2004. Patients were compared with controls (n = 51) with unruptured IAs 7 mm or smaller, diagnosed by conventional angiography or three-dimensional computerized angiography, with respect to aneurysm characteristics (size, location, and age of presentation) and risk factors (hypertension, smoking, cocaine use, and family history). RESULTS: Hypertensive patients with IAs 7 mm or smaller were 2.6 times more likely to experience rupture (P = 0.01; 95% confidence interval, 1.21-5.53) than patients with normal blood pressure. Posterior circulation aneurysms were 3.5 times more likely to rupture than anterior circulation aneurysms (P = 0.048; 95% confidence interval, 0.95-19.4). After adjustment for location and hypertension, the age of patient on presentation was associated with a trend toward inverse correlation with aneurysmal rupture risk (P = 0.07). Hypertension and posterior location remained significant independent predictors in the logistic regression model. CONCLUSION: Among patients with small aneurysms (< or = 7 mm), hypertension, relatively young age, and posterior circulation were significant risk factors for rupture. Given the minimal long-term morbidity and mortality of treatment of unruptured aneurysms in large, tertiary medical centers, management of unruptured aneurysms 7 mm or smaller should be governed by factors other than size, specifically age, history of hypertension, and location.