RESUMEN
Background/Objectives: Digital subtraction angiography (DSA) is the gold standard in the diagnosis of cerebral vasospasm, frequently observed after subarachnoid hemorrhage (SAH). However, less-invasive methods, such as computed tomography angiography (CTA), may be equally accurate. To further clarify comparability, this study evaluated the reliability of CTA in detecting cerebral vasospasm. Methods: This retrospective study included 51 patients with SAH who underwent both CTA and DSA within 24 h. The smallest diameter of the proximal cerebral arterial segments was measured in both modalities at admission and during the vasospasm period. The mean difference in diameter, the intraclass correlation coefficient (ICC) of CTA and DSA, the difference in grade of vasospasm and sensitivity, the specificity and the positive predictive value (PPV) for CTA were calculated. Results: A total of 872 arterial segments were investigated. At time of admission, arterial diameters were significantly smaller on CTA compared to DSA in all segments (-0.26 ± 0.12 mm; p < 0.05). At time of suspected vasospasm (day 9 ± 5), these differences remained significant only for the M1 segment (-0.18 ± 0.37 mm, p = 0.02), the P1 segment (-0.13 ± 0.24 mm, p = 0.04) and the basilar artery (-0.20 ± 0.37 mm, p = 0.0.04). The ICC between CTA and DSA was good (0.5-0.8). The sensitivity of CTA for predicting angiographic vasospasm was 99%, the specificity was 50% and the PPV was 92%. Conclusions: Arterial diameters measured on CTA may underestimate the arterial caliber observed in DSA; however, these absolute differences were minor. Importantly, vessel diameter alone does not fully reflect malperfusion, requiring additional imaging techniques such as CT perfusion.
RESUMEN
Meropenem is a broad spectrum carbapenem used for the treatment of cerebral infections. There is a need for data describing meropenem pharmacokinetics (PK) in the brain tissue to optimize therapy in these infections. Here, we present a meropenem PK model in the central nervous system and simulate dosing regimens. This was a population PK analysis of a previously published prospective study of patients admitted to the neurointesive care unit between 2016 and 2019 who received 2 g of meropenem intravenously every 8 h. Meropenem concentration was determined in blood, cerebrospinal fluid (CSF), and brain microdialysate. Meropenem was described by a six-compartment model: two compartments in the blood, two in the CSF, and two in the brain tissue. Creatinine clearance and brain glucose were included as covariates. The median elimination rate constant was 1.26 h-1, the central plasma volume was 5.38 L, and the transfer rate constants from the blood to the CSF and from the blood to the brain were 0.001 h-1 and 0.02 h-1, respectively. In the first 24 h, meropenem 2 g, administered every 8 h via intermittent and extended infusions achieved good target attainment in the CSF and brain, but continuous infusion (CI) was better at steady-state. Administering a 3 g loading dose (LD) followed by 8 g CI was beneficial for early target attainment. In conclusion, a meropenem PK model was developed using blood, CSF, and brain microdialysate samples. An 8 g CI may be needed for good target attainment in the CSF and brain. Giving a LD prior to the CI improved the probability of early target attainment.