For those who clicked on the previous post and expected to read more on the shrinking Surviving Sepsis guideline, this follow up post is for you. the Surviving Sepsis Campaign is predicated on the idea that sepsis is a medical emergency and demands an immediate muscular response. From the current version: “sepsis and septic shock are medical emergencies and treatment and resuscitation should begin immediately.” I absolutely agree that these entities are medical emergencies, but there is a disconnect between SSC guidance and evidence for emergent initial resuscitation. Resuscitation is the process of correcting physiological abnormalities in a patient. These include restoration of circulation in cardiac arrest by performing vigorous chest compressions with CPR. In sepsis, resuscitation includes correcting low blood pressure and restoring perfusion in sepsis. The SSC implies that sepsis resuscitation should be approached in the same manner as an impending cardiac arrest – every moment counts and efforts to normalize physiologic parameters will forestall even worse outcomes. This might be true, but this assertion is based on the lowest quality observational data. Prospective randomized controlled trials have almost uniformly favored less aggressive treatment. As described in yesterday’s post, evidence supports more conservative transfusion targets, lower blood pressure targets, higher blood sugar targets, and also less aggressive ventilation (lower tidal volumes) in critically ill sepsis patients. Restoration of oxygen delivery has been sidelined with trials showing no benefit to EGDT. With the addition of the LOVIT trial results, we learned we should not try to restore Vitamin C levels. With PROWESS-Shock, we discovered we should not try to “improve” activated Protein C levels. The LeoPARDS trial showed that we should not attempt to normalize cardiac contractility. The RIFLE trial indicated no benefit to early renal replacement therapy in patients with sepsis. Even though hypotension and multi-organ failure in sepsis is provoked by the TLR4-LPS axis, the ACCESS, EUPHRATES, CHESS trials show that we shouldn’t bother intervening there (and those are just the just ones with cool names; don’t get me started with J5, E5 anti-sera studies, etc).

In other words, thousands and thousands of real live patients have been enrolled in sepsis trials that yielded results that we didn’t like – favoring either no intervention or a less aggressive intervention. Those study subjects took on substantial risk in enrolling in those trials. I argue that it is unethical to pretend those trials never happened and continue making the same assumptions about sepsis treatment. Given the track record of null and negative sepsis trials, we should not assume anything about sepsis management. Equipoise exists about the timing and intensity of resuscitation in sepsis. Maybe going slow could give the same or better outcomes. I am not advocating this, necessarily, but cautioning that we’d be wise to tread carefully when dealing with sepsis.

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Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine