From ancient Greece, where physicians believed disease resulted from the gods wreaking havoc on humans in acts of vengeance, to the more body orientated approach of Hippocrates and Galen, to our modern day, one thing has remained true. Physicians have had a very long tradition of getting it so spectacularly wrong at times as to cause needless suffering and death while refusing to believe it. Frequently wrong, rarely in doubt, has been the mainstay of practicing physicians for centuries. Ignoring their mistakes, an art form.
Many medical historians and physicians imagine medical history as a long triumphant arc of steady progress resulting from the discoveries of genius while ignoring thousands of years of harm at the hands of average physician practitioners. So complete is the propaganda, that medical students today swear to uphold the teachings of Hippocrates while reciting the school's oath – where insuring proper payment to teachers is number one on the list of things to do, followed by homage to the gods (pleural), and a promise never to perform abortions.
From blood-letting, to blistering, to the inhalation of noxious gases in order to sweat out the Pox (and kill people by the thousands) – physicians have had, over thousands of years, a long unwavering tradition of sureness even while being spectacularly wrong. Relentlessly so. And whereas the rare geniuses are responsible for medicine’s advancements it wasn’t until modern times, when the scientific method finally found its way into medicine around 1900, that every day clinical medicine changed in meaningful ways, over thousands of years.
George Washington, while suffering from epiglottis, was bled - repeatedly - despite the suggestion by a less esteemed junior physician to perform a new experimental procedure at the time - a tracheostomy - that would have probably saved his life. But bleeding was what had been done for millenia, it was the proven remedy, and by gosh that's what his more esteemed senior physicians were going to do. As it was he died, with all his physicians, save perhaps one, leaving his death bed absolutely convinced everything possible had been done - they had given him his best chance - having learned nothing.
Even today physicians frequently do not learn from their mistakes, choosing instead to rewrite history and prop up prestige – grand and glorious. In my experience this continues today in critical care medicine.
I remember it as a cold and stormy November night, 2001, when two seminal papers appeared in the same issue of The New England Journal. Intensive Insulin Therapy in Critically Ill Patients [1] and Early Goal-Directed Therapy (EGT) in Treatment of Severe Sepsis and Septic Shock [2]. Both studies were small, single center studies, and as time would finally tell, both studies were eventually proven incorrect. But oh my, what a fuss they caused. Probably to the surprise of the investigators.
Entire careers were made on implementing tight glucose control only for us to learn a decade later that we were probably killing 1 in 37 patients unnecessarily[3]. An entire campaign was begun in response to EGT – the Surviving Sepsis Campaign – to ensure that the first six hours of treatment adhered to an EGT approach. Since 2001 three large clinical studies have revealed that EGT in sepsis, as per this single center study, was folly[4-6].
We did manage to learn that early antibiotics and infection source control were the only interventions in sepsis found to make a difference. Despite this we had to tolerate ridiculous, non-physiologic hemodynamic ‘guidelines’ that were more like commandments from the Mount than guidelines from our leaders, despite a lack of evidence as to efficacy. Central venous pressure – one size fits all. Aggressive fluid resuscitation in everyone based on the unproven assumption that sepsis patients always present hypovolemic and/or would benefit with IV fluid administration. And whereas it is true vascular permeability is increased in sepsis, experts for the most part have ignored the lymphatic’s ability to dramatically increase fluid return to the central veins in such circumstances. And so, sepsis representing, per se, a hypovolemic state has become gospel despite being unproven, as was blood-letting for thousands of years I suppose.
But after more than a decade of physicians and physiologists pointing out how un-physiologic the SSC resuscitation recommendations were, our leaders decided to take it out of realm of physiology and reduce the recommendations to commands. You will give 30ml/kg IVF to every septic shock patient, and you will follow lactate. Don’t do that in the State of New York since 2013 and face criminal charges. No attempt was made to explain the cardiovascular physiologic effects, or reasons, just do it. And no attempt to explain where the recommendations came from since there is no evidence, none, that this is the right amount of fluid to give to anyone for any reason, or that following lactate improves outcome. But we all know sepsis causes hypovolemia on presentation so this seems reasonable. Except we do not know that. Separate from insensible and GI losses we have no idea if early sepsis represents a hypovolemic state. We do know that 60% of patients with sepsis presenting to the ED are not fluid responsive[7]. We do know that most do not have peripheral or pulmonary edema prior to resuscitation - begging the question where does all that extravasated fluid go? We do know that early sepsis patients are not hemoconcentrated (2). And finally, and most importantly, we do know one size does not fit all in medicine – ever – underlying the absurdity of such recommendations.
I could go on. But here is the point. Did we learn anything from our tight glycemic control experience despite probably causing excess death? Well we went on to prove it was dangerous and thus increased knowledge, but at what cost? How many people died unnecessarily in our rush to certainty in a treatment strategy based on faulty, incomplete information? And did we learn not to rush to certainty and try to apply rigid guidelines from these experiences? I would argue no, we did not. Most centers just chose another glucose target, without evidence, completely ignoring the complex metabolic effects of insulin or the harm their new target may be doing. Did we learn anything from the EGT in sepsis experience? Again, we went on to prove it mostly nonsensical, but did we learn not to rush to certainty or try to apply rigid rules or algorithms? – again, no, we have not. Instead of learning the lessons from these experiences our leaders just made up a whole new set of baseless guidelines and on and on we go.
I am not trying to pick on well-intentioned investigators. I have used tight glycemic control and EGT therapy only as examples to expose a more pervasive and alarming trend to sureness in clinical medicine today. The studies were small and meant as a call to more investigation. It was the reaction to the studies I find fault with. These studies, much to the surprise of their investigators I'm sure, sparked international certainty and rigidness of care that far outweighed evidence. A rush to certainty – unfortunately not new to medicine for these thousands of years.
The art of medical care cannot be reduced to two-dimensional algorithm. Nor can we tolerate ever-encroaching sureness in the face of ignorance or lack of evidence by our government, that has now resorted to applying financial pressure and even arrest to force adherence to unproven guidelines. Hospital administrators follow their lead, as do medical leaders, who seem intent on reducing clinical care to formula.
Certainty in the face of ignorance is pervasive throughout the history of medicine and seems to be becoming more so in these modern times – despite the huge advantaged of having introduced the scientific method 120 years ago - its potential to harm, great.
1. van den Berghe, G., et al., Intensive insulin therapy in critically ill patients. N Engl J Med, 2001. 345(19): p. 1359-67.
2. Rivers, E., et al., Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med, 2001. 345(19): p. 1368-77.
3. Investigators, N.-S.S., et al., Intensive versus conventional glucose control in critically ill patients. N Engl J Med, 2009. 360(13): p. 1283-97.
4. Pro, C.I., et al., A randomized trial of protocol-based care for early septic shock. N Engl J Med, 2014. 370(18): p. 1683-93.
5. Investigators, A., et al., Goal-directed resuscitation for patients with early septic shock. N Engl J Med, 2014. 371(16): p. 1496-506.
6. Mouncey, P.R., et al., Trial of early, goal-directed resuscitation for septic shock. N Engl J Med, 2015. 372(14): p. 1301-11.
7. Douglas, I.S., et al., Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial. Chest, 2020. 158(4): p. 1431-1445.
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