SIR ROBERT MUIR, SEPSIS AND SCOTTISH HEALTHCARE

In Muir’s time it was believed that septicaemia was due to an ‘overflow’ of bacteria from the organs into the blood, which usually resulted in fatality. Muir observed bacterial colonisation in the blood of septic hamsters, and also made the accurate observation that colonisation of the blood is not observable through a microscope in human cases of septicaemia. From this observation came the theory that septicaemia is the result of the host response to disease, rather than the invading organisms themselves. There was no clinical evidence for invasion of bacteria into the blood, and therefore the host must be causing the illness. 

In the 1960s, clinical trials were modulated to test the impact of administration of immunosuppressive glucocorticoids to septic patients. However, these trials proved ineffective.  Investigations into the use of anti-inflammatory treatments for septicaemia continued for almost 40 years, and targets included blockade of inflammatory cytokine TNFa and prevention of complement cascade through inhibition of C1. All of the clinical trials conducted failed, due in part to an inability to define the immune status of the individuals taking part in the studies. The immune system undergoes many changes during the course of septicaemia, and changes from one patient to the next can vastly alter the outcomes of clinical trials. At the end of the twentieth century, after the failure of so many clinical trials, it was considered that there may be more systems at work than simply excessive inflammation in septic patients. 

Since the turn of this century, it has been established that septicaemia involves not only extreme inflammation, but immunosuppression as well. During septicaemia, the innate immune system can lose the ability to kill invading organisms and Hotchkiss et.al have shown that there is huge apoptosis-induced loss of immune effector cells during septicaemia by harvesting tissues from patients dying of sepsis, no matter the patient age.  Anti-apoptotic therapies have been shown to prevent death in animal models of sepsis meaning that anti-apoptotic drugs may become septicaemia therapies in future. 

Views on septicaemia have altered considerably in the 91 years since Muir wrote about it in his textbook, but there is still much to be discovered about this enigmatic disease.