Assessment of the Effects of a High Amikacin Dose on Plasma Peak Concentration in Critically Ill Children.

OBJECTIVES: This study aimed to assess the incidence of amikacin plasma peak concentration (Cmax) below 60 mg·L-1 in critically ill children receiving an amikacin dosing regimen of 30 mg kg-1·day-1. Secondary objectives were to identify factors associated with low Cmax and to assess the incidence of acute kidney injury (AKI). METHODS: A retrospective observational study was performed in two French pediatric intensive care units. All admitted children who received 30 mg·kg-1 amikacin and had a Cmax measurement were eligible. Clinical and biological data, amikacin dose, and concentrations were collected. RESULTS: In total, 30 patients were included, aged from 3 weeks to 7 years. They received a median amikacin dosage of 30 mg kg-1·day-1 (range 29-33) based on admission body weight (BW), corresponding to 27 mg kg-1·day-1 (range 24-30) based on actual BW. Cmax was < 60 mg·L-1 in 21 (70%) children and none had a Cmax ≥ 80 mg·L-1. Among the 15 patients with a measured minimum inhibitory concentration (MIC), 13 (87%) had a Cmax/MIC ratio > 8. Univariate analysis showed that factors associated with Cmax < 60 mg·L-1 were high estimated glomerular filtration rate (p = 0.015) and low blood urea concentration (p = 0.001). AKI progression or occurrence was observed after amikacin administration in two (7%) and six (21%) patients, respectively. CONCLUSIONS: Despite the administration of the maximal recommended amikacin dose, Cmax was below the pharmacokinetic target in 70% of our pediatric population. Further studies are needed to develop a pharmacokinetic model in a population of critically ill children to optimize target attainment.

Postoperative B-type natriuretic peptide monitoring for the assessment of the magnitude of shunting through Blalock-Taussig anastomoses.

BACKGROUND: The Modified Blalock-Taussig shunt (MBTS) is the most common palliative operation performed in patients with complex cardiac defects. Postoperative morbidity and mortality rates are high, mainly due to shunt thrombosis and over-shunting. Over-shunting may be difficult to identify postoperatively based on conventional criteria. Since plasma B-type natriuretic peptide (BNP) concentrations correlate with the magnitude of shunting in various left-to-right shunt cardiac defects, we investigated its ability to identify postoperative MBTS over-shunting. METHODS AND RESULTS: This retrospective, observational study included 42 consecutive patients (median age 9.50days, IQR: 6.00-58.25) undergoing MBTS for obstruction of the pulmonary blood flow at a tertiary referral pediatric cardiac center. The BNP threshold concentrations which accurately predicted outcome and MBTS over-shunting were derived using the ROC methodology. 443 BNP concentrations were analysed. The presence of atrio-ventricular valve regurgitation was the most important component of overall variance (72.75%). In 34 patients without regurgitation, BNP concentrations were predictive of a duration of mechanical ventilation >8days and of intensive care stay >11days, with ROC areas of 0.655 [0.597-0.719], 0.650 [0.589-0.711], a negative predictive value for the >1035pgmL-1 threshold of 0.93 and 0.96 respectively. SaO2 was less accurate for the prediction of both outcomes. In patients in whom the pulmonary flow was entirely MBTS-supplied, a BNP concentrations >1052pgmL-1 was predictive of a pulmonary-to-systemic ratio>2. CONCLUSION: In MBTS patients without atrio-ventricular valve regurgitation, maintaining BNP below 1000pgmL-1 may represent a therapeutic target to avoid over-shunting.