David Bihari:
Thus, "delivery dependent oxygen consumption" obviously exists but no-one sensible ever suggested that "living human beings routinely suffer from flow dependent oxygen consumption during critical illness". Patients may have episodes of flow dependency, short or long - depending upon the vigilance of their medical attendents - usually related to episodes of hypovolaemia, and this may contribute to tissue hypoxia and the development of multiple organ failure.
I believe the debate about flow dependency is a bit sterile. The important thing is to appreciate that of all the mechanisms involved in the development of MOF, this is one that we might be able to prevent.
Aviel Roy-Shapira:
All the definitions of shock, best and otherwise, remind me of Persig's law "The number of rational hypotheses that can explain any given phenomenon is infinite" (Zen and the Art of Motorcycle Maintenance)
The definition has become a function of our tecnology. 150 years ago the lady swooned, was shocked, and smelling salts worked. Then blood pressure crashed, the pulse ran fast and the facies sweated - shock. Then Swan rocked up and a whole new load of variables were factored in. Then the energy substrates blah blah blah. It seems that the definition of "shock" sits somewhere on a line between the abstract and the concrete and we are simply trying to get to the final elusive, absolute answer which will tell us that this patient is in shock but this one is not!
Definitions of the abstract are impossible - "quality is a characteristic of thought and statement that is recognised by a non thinking process. Because definitions are a product of rigid, formal thinking, quality cannot be defined" (same author)
"There's no use trying,"she said: "One can't believe impossible things." "I daresay you haven't had much practice," said the Queen. "When I was your age, I always did it for half an hour a day. Why, sometimes I've believed an as many as six impossible things before breakfast."
I'll stick with inadequate tissue perfusion for the moment thank you.
Dick Burrows:
Much as I liked the book, I have to say that Persing was hardly the originator of this law. The law is equivalent to saying that there is an infinite number of general statements (All x are y) that can generate any finite set of particular statemtents (some x are y) This is turn implies that no general statement can be DEDUCED from any finite set of particular statements, however large.
If the law is to be attributed to anyone, it is to David Hume. who proved the last conjecture some 200 years ago.
A simple way to think about this is to realize that any finite set of points in space can be connected by an infinite number of lines (curved or streight) We usually pick the line that conforms to some simple rule (for example, if one of the possible lines is streight, or perfectly circular, we would prefer to think that this is the REAL Line, and state it as the law of nature) but that is very subjective - simple to one could be complex to another.
Mark E Finnis:
With reference to Ernest & D.Bihari's recent discussion/dispute on the definition of shock. As a registrar in training I still read the odd textbook (novel concept, I know), so here is a selection:-
Dorland's Medical Dictionary
"..a condition of acute peripheral circulatory failure due to derrangement of circulatory control or loss of circulating fluid."
Harrison's Principles of Internal Medicine 12th Ed.
"Shock may be defined as the state in which profound and widespread reduction in tissue perfusion leads first to reversible, and then, if prolonged, to irreversible, cellular injury. Since reduction in tissue perfusion is central to this definition...."
Skowronski, Intensive Care Manual, T.Oh 3rd Ed.
"..a severe pathophysiological syndrome associated with inadequate or disordered tissue perfusion and abnormal cellular metabolism."
Worthley, Synopsis of Intensive Care Medicine
"..a pathophysiological state in which there is reduced oxygen consumption by the peripheral tissues in accordance with their metabolic needs, produced by a reduction in the delivery of oxygenated blood or a reduced oxygen extraction by the peripheral tissues." While Tub's defn includes reduced peripheral extraction, his subsequent classification implies "distributive failure", rather than cellular mitochondrial block per se.
Schuster, Critical Care, Civetta, 2nd Ed.
"some researchers define shock as a metabolic defect, we prefer a more traditional definition that incorporates a perfusion abnormality as central to the pathophysiology. Shock is an acute clinical syndrome initiated by hypoperfusion resulting in severe dysfunction of organs..."
Tierne, Current Medical Diagnosis & Treatment, 1994
"..the circulation of arterial blood is inadequate to meet tissue metabolic needs"
We could go on, but I think the consensus is in D.Bihari's court, ie. tissue perfusion is central to the diagnosis, in contrast to definitions which relate to cellular hypoxia.
Ernest Benjamin:
Rolando is offering a very thoughtful attempt at "mediating" between two different views on a definition of shock. The problem is that this is much more than a semantic controversy.
If we accept the HYPOPERFUSION-ONLY definition of shock, we should not call shock the condition of a Jehovah's Witness patient with a hematocrit of 4.1 %, hemoglobin of 1.3 gm, a lactatemia of 19 mmol, and a cardiac output of 10 liters. If we move one step further to define shock as a state of inadequate tissue oxygenation, we put ourselves in a quandary. Although this definition would the above patient, it will miss all other states in which tissue oxygenation is OK, but energy production is uncoupled or abnormal. Besides, what is an adequate tissue oxygenation? Is it a normal tissue PO2? Clearly, if oxidation-phosphorylation is unimpeded, you may have normal energy production occurring in the presence of low tissue PO2. Conversely, high tissue PO2 is not a guaranty of adequate energy production if the O-P apparatus is not working well.
We must remember that, for the most part, oxygen acts only as an electron acceptor substrate in a vastly complex operation aimed at producing energy. We may not feel comfortable speaking of such "immaterial" thing as energy, but this is probably where the action is. By the way, even though ATP is the main energy currency in our economy, there is a huge difference between decreased cellular energy crisis and decreased ATP concentration. It is comparable to the loose link between the state of the national economy and the circulating monetary mass.
Lastly, David, can we maintain the intellectual discourse free of any useless adjectives that do not contribute to the understanding of the topics being debated?
David Bihari:
No offence intended Ernest. In my view your Jehovah's witness has "anaemic hypoxia" but is not necessarily shocked. Shock remains essentially something you recognise (and perhaps feel) at the bedside - a clinical diagnosis in so far as the inadequate supply of oxygen to respiring tissues is associated with some abnormalities in end organ function which brings the problem to the attention of the physician. Disturbances of oxygen transport and states of cellular energy deficiencies are best left for the seminar room .
I come back to that extra-mitochondrial oxygen deficiency that probably becomes important in the tissue injury that occurs during states of prolonged hypoxia - hypoxia that is not enough to disturb the energy supply (the Km of cytochrome aa3 being so low - perhaps 1 mm Hg) but enough to switch the metabolism of arachidonate from the cyclo-oxygenase controlled pathway (Km 16 mm Hg) to the lipoxygenase controlled pathway (Km 9 mm Hg).
Given these different affinities for oxygen, these reactions are inhibited at different levels of hypoxia, way above that required for the cellular energy crisis that some regard as crucial to the discussion. This may go some way to explain the macrophage activation that occurs in mild hypoxic states.
Truely, I am not trying to "muddy the waters" - we started off trying to answer the question of whether or not "delivery dependent oxygen consumption" actually exists, transiently or as a distinct and abnormal metabolic state in the critically ill.
Ernest Benjamin:
I am always worried when somebody provides the "best" of anything. This certainly applies also to the "best" definition of shock, as perceived by David Bihari:
The best definition of SHOCK is "an inadequate delivery of oxygen (and other vital substrates) to respiring cells" (and of course, the inadequate removal of the waste products of metabolism - hence importance of CO2 monitoring)
I think this definition, although the most commonly accepted, does not account for certain models of shock in which "oxygen delivery" is not primarily compromised. These include cyanide intoxication, salicylate poisoning, malignant hyperthermia, or neuroleptic malignant syndrome. At times, shock may result from inability to convert oxygen into energy, or from the insufficiency of the energy produced to meet the energy requirements of the functioning tissues. The key word here is energy, although energy production accounts for only about 90% of oxygen use.
An alternative definition of shock (certainly not the "best") is a profound systemic energy crisis due to the inadequacy of cellular energy production to meet cellular metabolic demand. This energy crisis is usually caused by inadequate oxygen delivery, but it may also result from impaired or uncoupled oxidative phosphorylation, or excessive energy requirements.
Redirecting the focus towards energy imbalance rather the simplistic notion of insufficient oxygen delivery would help understand that increasing oxygen delivery will work in some cases and fail in others where decreased oxygen delivery was not the problem. By the way, who knows what the systemic cells perceive in terms of oxygen delivery and energy balance in sepsis? What about regional (or even local) variations on that theme? We know so little about such a complicated matter that we should remain humble when we think that what we propose is the "best".
David Bihari:
Someone has to try to produce something worthwhile - "in pursuit of excellence" and all that. I fear there is some confusion here - shock is an abnormality of the circulation - nothing to do with "hypoxia" which seems to be the other major concern.
Obviously shock - an inadequate delivery of oxygen (and other vital substrates) to respiring cells - may lead to tissue hypoxia but once the cell has become seriously depleted of ATP (as measured by NMR), you are on to a hiding for nothing ! The cells swell up, burst and die. Bad outcome. Can we not try to correct things a little earlier ! Or perhaps, dare I say it (with MaestroShoemaker and Dr. Boyd) even prevent the oxygen deficiency occurring in the first place!
Don't get so hung up on energy - think of the extramitochondrial oxygen requiring reactions (30% of oxygen consumption in the critically ill liver) which may be switched off before you see anything in L:P ratios, ketone body ratios, purine metabolites, infrared spectroscopy, NMR etc. - all designed to assess the redox potential of the cell.
On the issue of "hypoxia", another subject beloved and often misunderstood by "intensivists" (more intensive than caring!), I hang out with Barcroft - hypoxic, stagnant, anaemic and histiotoxic ! Stagnant hypoxia (low flow or maldistribution) is indeed a form of late shock but let's not say that every metabolic abnormality in the ICU (cyanide intoxication, salicylate poisoning, malignant hyperthermia, or neuroleptic malignant syndrome) is a form of shock. What about acute liver failure or uraemia ? Obviously they may all lead to some form of circulatory failure and shock over a period of time and then that stagnant component (low flow / maldistribution of flow) will require recognition and treatment.
If "words mean what I want them to mean", then we should all go and sit on the cyber wall with Humpty Dumpty. Loose talk is loose thought !
Ernest Benjamin:
At times, shock may result from inability to convert oxygen into energy, or from the insufficiency of the energy produced to meet the energy requirements of the functioning tissues. The key word here is energy, although energy production accounts for only about 90% of oxygen use.
An alternative definition of shock (certainly not the "best") is a profound systemic energy crisis due to the inadequacy of cellular energy production to meet cellular metabolic demand. This energy crisis is usually caused by inadequate oxygen delivery, but it may also result from impaired or uncoupled oxidative phosphorylation, or excessive energy requirements.
Redirecting the focus towards energy imbalance rather the simplistic notion of insufficient oxygen delivery would help understand that increasing oxygen delivery will work in some cases and fail in others where decreased oxygen delivery was not the problem. By the way, who knows what the systemic cells perceive in terms of oxygen delivery and energy balance in sepsis? What about regional (or even local) variations on that theme? We know so little about such a complicated matter that we should remain humble when we think that what we propose is the "best".