Dose equivalence for metaraminol and noradrenaline - A retrospective analysis.

BACKGROUND: Noradrenaline and metaraminol are commonly used vasopressors in critically ill patients. However, little is known of their dose equivalence. METHODS: We conducted a single centre retrospective cohort study of all ICU patients who transitioned from metaraminol to noradrenaline infusions between August 26, 2016 and December 31, 2020. Patients receiving additional vasoactive drug infusion were excluded. Dose equivalence was calculated based on the last hour metaraminol dose (in µg/min) and the first hour noradrenaline dose (in µg/min) with the closest matched mean arterial pressure (MAP). Sensitivity analyses were performed on patients with acute kidney injury (AKI), sepsis and mechanical ventilation. RESULTS: We studied 195 patients. The median conversion ratio of metaraminol to noradrenaline was 12.5:1 (IQR 7.5-20.0) for the overall cohort. However, the coefficient of variation was 77% and standard deviation was 11.8. Conversion ratios were unaffected by sepsis or mechanical ventilation but increased (14:1) with AKI. One in five patients had a MAP decrease of >10 mmHg during the transition period from metaraminol to noradrenaline. Post-transition noradrenaline dose (p < 0.001) and AKI (p = 0.045) were independently associated with metaraminol dose. The proportion of variation in noradrenaline dose predicted from metaraminol dose was low (R2 = 0.545). CONCLUSIONS: The median dose equivalence for metaraminol and noradrenaline in this study was 12.5:1. However, there was significant variance in dose equivalence, only half the proportion of variation in noradrenaline infusion dose was predicted by metaraminol dose, and conversion-associated hypotension was common.

Early solar system. Stellar origin of the ¹8²Hf cosmochronometer and the presolar history of solar system matter.

Among the short-lived radioactive nuclei inferred to be present in the early solar system via meteoritic analyses, there are several heavier than iron whose stellar origin has been poorly understood. In particular, the abundances inferred for (182)Hf (half-life = 8.9 million years) and (129)I (half-life = 15.7 million years) are in disagreement with each other if both nuclei are produced by the rapid neutron-capture process. Here, we demonstrate that contrary to previous assumption, the slow neutron-capture process in asymptotic giant branch stars produces (182)Hf. This has allowed us to date the last rapid and slow neutron-capture events that contaminated the solar system material at ~100 million years and ~30 million years, respectively, before the formation of the Sun.