Beta blockade: the right time, the right dose, the right receptor!

In this issue of Critical Care Medicine, Ackland and colleagues (1) report findings from a series of experiments, using β blockade in rodent models of endotoxic shock and sepsis. Experiments included daily intraperitoneal injections of metoprolol and atenolol, both selective β1-adrenoceptor antagonists, commencing 2 days before or 6 hrs after induction of endotoxemia, using lipopolysaccharide. The authors demonstrated a significant survival advantage when either agent was given before, but not after, lipopolysaccharide administration. Not only was the survival benefit remarkable but they also found that, when administered with adequate fluid resuscitation at a dose to reduce heart rate by 20%, the agents did not cause hypotension, maintaining both cardiac output and blood pressure. Metoprolol pretreatment was also associated with lower interleukin-6 as well as reduced production of various inflammatory cytokines in hepatic and cardiac tissue.