A listener, Dave Glaser, points out that one portion of the EGDT protocol doesn't get spoken about very often: the use of vasodilators for MAP optimization.
In the original trial, patients in the EGDT arm of the study got a vasodilator if their MAPs were >90. The original trial publication makes no mention of which vasodilator and how many patients received it. If you want that information, you need to go to the Otero et. al publication (Chest 2006;130;1579-1595), which expanded on the original trial with additional information. Here is the relevant excerpt:
Vasodilator Therapy
After adequate volume and hemoglobin targets were met, we surprisingly found that 9% of EGDT patients met the protocol criteria for afterload reduction for a mean arterial pressure (MAP) of > 90 mm Hg by utilizing nitroglycerin therapy. Nitroglycerin was chosen because of its effects on preload, afterload, and coronary vasodilation. All of these patients had a history of hypertension and congestive heart failure. The median baseline Scvo2 was 46% in this subset of patients. Although the use of nitroglycerin was unexpected on study initiation, therapy with afterload reduction is not without precedent in treating sepsis patients.
Cerra et al (J Surg Res 1978;25:180–183) provided vasodilator therapy to sepsis patients with low cardiac output and observed physiologic improvement.
Spronk et al (Lancet. 2002 Nov 2;360(9343):1395-6) found that nitroglycerin may improve microcirculatory flow in normotensive or even hypotensive patients with septic shock.
It is becoming increasingly evident that disordered microcirculatory flow is associated with systemic inflammation, acute organ dysfunction, and increased mortality. Using new technologies to directly image microcirculatory blood flow may help to define the role of microcirculatory dysfunction in oxygen transport and circulatory support.
I can't remember the last time I saw a patient who would be eligible for this therapy b/c of high MAP. We have given nitroglycerin occasionally for a patient that is not clearing their lactate with a high ScvO2.
For anyone who really wants to dive deep on this issue, there is a free supplement in Critical Care.
Scott Weingart
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8 Comments on "Vasodilators for Severe Sepsis"
This opens up more questions than answers:
1) Doesn’t it depend where on the Starling curve the patient is following volume resuscitation or pressor support?
2) Does an elevated MAP represent pathology, over-treatment (iatrogenesis) or the normal physiological state of the patient?
3) Which part of the microcirculation are we actually targeting and to what end? (sepsis represents an overall vasoplegic, dilated state with a combination of inappropriate perfusion of some vascular beds and underperfusion of other vascular beds)
4) Is really possible to target with any precision, the venous or arterial side of the circulation with vasodilators (let alone specific vascular beds of interest).
5) Finally, is the inappropriate use of the combination of fluids, inotropes and vasoactive drugs according to an unvarying ‘recipe’ doing more harm to some patients than good. Shouldn’t we evaluate all haemodynamic parameters according to the underlying pathophysiology and the baseline co-morbidities and physiological state individual to that patient?
All good questions! All treatments must be evaluated in the individual patient. Guidelines and protocols give a starting recipe. The art is being a chef and altering based on the humidity, the quality of you ingredients, and the individual ineffable factors of the day.
A nice little review. We have blunt tools for the microcirculation.
http://anaesthetics.ukzn.ac.za/Libraries/Documents2011/Dr_Alphonsuss_FMM_Booklet.sflb.ashx
will read asap
[…] also took a deep dive into the peculiar world of Vasodilators for Severe Sepsis — not something you see every […]