Septic shock (sometimes called blood poisoning) is a life-threatening condition caused by severe infection. For reasons still poorly understood, in some patients, the inflammation in their system doesn’t reduce after an infection. Instead of fighting the infection, an ongoing inflammatory state results in widespread injury to the body and failure of normal functioning of the body’s vital organs, such as the lungs, heart, brain and kidneys. A common indicator of septic shock is a very low blood pressure that does not improve, even when treated with an intravenous fluid drip, which is the usual treatment for very low blood pressure.

For many years, we have routinely used in clinical practice a group of drugs known as ‘catecholamines’ to increase the patient’s blood pressure back to normal. The objective is that this will help their vital organs to function properly and to recover. The most commonly used catecholamine is noradrenaline, a synthetic form of a hormone produced by the body to deal with stressful situations. However, noradrenaline does carry side-effects when given at high doses and for extended periods of time, including adverse effects on the heart, the immune system and the patient’s metabolism. Thus, the drug treatment itself, which is given to help the body’s own production of these hormones, may achieve the short-term goal of increasing blood pressure, but at the possible expense of more damage to the body. The use of catecholamines is therefore being questioned.

In 2013, a doctor called Morelli showed that when patients were being treated with a very high dose of noradrenaline, and were also given a beta blocker (a type of drug that reduces the heart rate), patients on average got better more often, more quickly. We propose to repeat their study in multiple (approx. 30-35) intensive care units throughout the UK to see if we can confirm the safety and benefits of using beta blockers. We are also going to take blood samples to measure effects of the beta blocker on the patient’s immune system, metabolism and heart function so that we may better understand how it works. We also propose to store blood samples for analysis of the genes and proteins that may predispose patients to become so severely septic and to identify those who respond better to beta blocker therapy.

340 participants

The primary outcome will be the mean SOFA score between treatment groups over the first 14 days from entry to the trial and whilst in ICU.

51 months