Multi-organ-system-failure is a constellation of several horrible problems, each of which would be life-threatening all on its own. This entity is a luxury of our enlightened age. In the olden days people never survived long enough to develop this syndrome.
As per Oh's Manual, The Definition is: "in an acutely ill patient, the function in two or more organ systems altered such that homeostasis cannot be maintained without intervention"
Mechanism of pathogenesis
- increased endothelial permeability,
- slowed microcirculation,
- formation of microthrombi,
- de-recruitment of capillaries
- and thus decreased tissue perfusion
Tissue injury through hypoxia
The hypoxia is a result of multiple factors, among which is poor lung function, poor cardiac output, microvascular insufficiency, and poor oxygen utilization at the level of the mitochondria.
The decrease in oxygen consumption may be out of proportion to the decrease in oxygen delivery; this is “tissue dysoxia”.
It is due to Nitric Oxide and general reactive oxygen species inhibiting the mitochondrial respiratory chain, as well as decreasing pyruvate delivery into the Krebs cycle. The result is anaerobic metabolism, and lactic acidosis. Plus, the mitochondria may lyse, releasing calcium and other proapoptotic factors.
Not just mitochondrial lysis, but also the various cytokines released as a part of a systemic inflammatory response will be received as apoptotic signals by cells- particularly in the gut, liver, kidney and heart.
The consequences, the clinical features:
- Encephalopathy: delirium, drowsiness, coma.
- Cardiomyopathy: depressed contractility, decreased lusitropy, decreased afterload and thus decreased coronary perfusion
- ARDS as a feature of the generalized microvascular injury, with resulting hypoxia
- Renal failure, with subsequent acidosis
- Increased intestinal permeability with bacterial and endotoxin translocation
- Ileus, pancreatitis, gastric ulceration, acalculous cholecystitis, gut ischaemia
- Hepatic dysfunction and thus decreased glyconeogenesis and decreased lactate clearance
- Coagulopathy due to both consumption of products in DIC and bone marrow failure
The Outcomes: mortality due to multiorgan system failure
Mortality 60-98% if 3 or more organs are down for over 1 week, stratified by age.
In determining mortality, cardiovascular dysfunction is the single most important organ failure
SOFA score at day 6 is more predictive of Day 7 mortality than SOFA score on admission.
Whatever the cause, 47% of people could not return to work or normal function at 1 year follow-up.
Supportive management of multi-organ system failure
Strategies described below are independent of specific organ failure Rather, they are strategies to manage the complex quagmire of multiple organ failure problems into which your patient is rapidly sinking.
Obviously, you are going to be supporting the various individual organs which are failing, and you are going to be trying to resolve the initiating cause of the MODS.
While this is going on, a few other strategies have been shown to help. Not all of them are free of controversy. Another confounding feature is that most studies of MODS have been performed in septic patients. Thus, many of the strategies seem aimed at decreasing end-organ damage from the cytokine storm associated with sepsis.
Glycaemic control (meaning, with insulin and dextrose infusion)
- Hyperglycaemia causes endothelial cell apoptosis and mitochondrial dysfunction
- Insulin seems to promote endothelial cell survival
- Tight blood sugar control has caused an absolute mortality risk reduction of 3.4% in MODS (single centre study)
- ARDS and sepsis patients may benefit from Omega-3 acids.
- The mechanism is something to do with decrease in cytokine production.
Stress dose steroids
- Some vague evidence that these are helpful in sepsis.
- Enough evidence, it seems, to get into the Surviving Sepsis Guidelines
- The mechanisms seems to be the inhibition of the induceable Nitric Oxide Synthase (iNOS)
Hemofiltration with highly permeable membranes may clear out enough of the circulating "middle molecule" size cytokines to be useful in severe MODS, but its unclear whether it is the cytokine depletion or the control of hyperthermia and acidosis. In any case, survival is improved.
Nitric Oxide Synthase Inhibitors
L-NMMA and Methylene blue have been trialed, as they both inhibit nitric oxide synthase.
So far, L-NMMA kills more people than it saves. Methylene blue has some cause for cautious optimism.