Septic shock is the most severe form of sepsis. This is a life-threatening condition that arises when the body’s response to severe infection causes injury to its own tissues and organs. The mortality from septic shock remains very high (>40% in 3 randomised trials reported in the New England Journal of Medicine in 2014 and >60% with high noradrenaline doses and tachycardia). Despite huge research efforts over the last 20-30 years, the survival rate has remained stubbornly unchanged. Outcomes have improved for sepsis in general through earlier recognition and intervention with antibiotics, however once septic shock takes hold, the risk of dying remains very high. There is growing interest in the use of beta-adrenergic blockade following supportive results in animal and preliminary human studies. Recently, an Italian group used the short-acting beta blocker esmolol to reduce, and then maintain, heart rates of patients with septic shock at between 80-95 beats per minute. The study was not powered for mortality but marked improvements were seen in survival as well as time on vasopressors, and biochemical and functional markers of renal, pulmonary and cardiac function. Their study was relatively small recruiting 154 patients from a single centre. If replicable in larger studies, this represents an unexplored mechanism in sepsis and has important implications for the treatment and outcomes of this high-risk population. A recent review concluded that there was currently insufficient evidence to justify the routine use of beta-blockade in septic shock and further adequately powered multi-centred randomised controlled clinical trials were required. We aim to repeat the Rome study in 340 patients from approximately 35 UK ICUs to see if we can confirm the safety and benefits that were seen.
To assess the efficacy, tolerability, safety and mechanisms of beta-blockade in patients with septic shock requiring prolonged (>24 hours) support with high-dose vasopressor agents.