Metaraminol in Critical Care

Abstract

Shock is a life-threatening illness defined as circulatory failure leading to hypotension, inadequate cellular oxygen utilisation and organ dysfunction. International guidelines recommend the use of norepinephrine as a first-line vasopressor for the treatment of hypotension in critically ill patients with cardiogenic or septic shock. However, metaraminol; a sympathomimetic amine vasopressor, is increasingly being used in critically ill patients with shock in rates up to 42% although it is not mentioned in the international guidelines for the management of shock. The evidence regarding the role of metaraminol in critical care has not been systematically evaluated. The aim of this thesis is to assess the pharmacoepidemiology, efficacy, safety, and dose equivalence of metaraminol in critically ill patients with shock. This thesis comprises of six studies ordered sequentially to reflect the thesis aims. The thesis findings indicate that there is very low-quality evidence supporting metaraminol use in this population and it is often used as a preferred first-line peripheral vasopressor agent for patients who do not have a central venous cannula inserted, locally, and broadly across hospitals in the UK and Australia. Metaraminol use is associated with a longer time to resolution of shock compared to norepinephrine based on local data. There is no difference in the rate of adverse events in those who received metaraminol compared to those who received norepinephrine with or without metaraminol. A conversion ratio of 10:1 (metaraminol (µg.kg-1.min-1) : norepinephrine (µg.kg-1.min-1)) can be utilised for dose-equivalence calculations in critically ill patients with shock. In conclusion, the studies conducted in this thesis provide contemporary evidence describing the use of metaraminol in critically ill patients with shock. Overall, the findings from this doctoral thesis can inform the conduct of prospective trials to further delineate the role of metaraminol in critical care.