Critical Illness Is a (Mal)-Adaptive, Metabolic Response to Systemic Inflammation

Sunday, February 14, 2016: 1:30 PM-4:30 PM
Marshall Ballroom West (Marriott Wardman Park)
Mervyn Singer, University College London, London, United Kingdom
The human body is a wondrous, integrative, highly sophisticated apparatus that has evolved to deal impressively with a myriad of insults – infection, trauma, starvation, climate changes, etc. However, advanced age, comorbidities that would not have allowed survival in days past, and the brute force of modern medicine are alien – and often detrimental – to the body’s innate responses. This is particularly borne out in critical care where improvements in patient outcome over the last few decades have revolved around doing less to the patient, rather than through the introduction of any breakthrough technology. Where we strove to normalize deranged physiology and biochemistry, we are now much more accommodating of acceptable degrees of abnormality, analogous to altitude acclimatization. Recognizing how the body (and mind) modifies its processes and activities to deal with acute illness is key. It is thus incumbent upon the clinician to work with, rather than against, the patient’s stressed body and its coping mechanisms. Critical care focuses upon artificially supporting failed body organs to enhance chances of recovery. Yet, paradoxically, these failed organs usually show minimal histological evidence of destruction, and recover well should the patient survive. The failure is functional rather than structural, implicating a metabolic ‘shutdown’ akin to hibernation or estivation. Yet organ failure carries a negative connotation though the body may be far smarter than the doctors treating it. ‘Failure’ may actually represent an extreme coping mechanism. Under attack, the stressed body emits a characteristic signature that is largely independent of the initiating stressor. This signature stretches across circulatory, inflammatory, immune, hormonal, bioenergetic and metabolic pathways, but is more exaggerated in those who proceed to die. Scarily, this survival differentiation can even be made at or soon after emergency admission to hospital, calling into question our effectiveness at reversing, rather than simply prolonging, the dying process. Rationally, we need to promptly identify the excessively stressed patient and then ‘de–stress their distress’ to a greater degree than those who stress response is appropriate, adaptive and protective. I will provide examples in lab models, which relate well to the human patient, where ‘one–size–fits–all’ strategies, the mantra of current medical practice, benefitted predicted non-survivors but harmed survivors. A personalized approach to stress modification could thus significantly improve outcomes.