Life after angiotensin II
Furthermore, ATHOS-3 did find an increase in venous and arterial thromboembolic events in patients who received AT II (13% AT II vs 5% placebo). Previously, a systematic review of over 30,000 patients did not report this increased thromboembolic risk (Busse, et al. Crit Care. 2017;21[1]:324). According to the package insert, all patients receiving AT II should receive appropriate thromboembolic prophylaxis if medically indicated.
Where does AT II fit in our algorithm for resuscitation and the vasopressor toolbox?
Data from Wunderink et al indicate a potential mortality benefit in populations who are AT II depleted. However, we can only infer who these patients may be, as no commonly available assay can measure AT I and AT II levels. ATHOS and ATHOS-3 used AT II late during resuscitation, as did the Expanded Access Program (EAP) of the FDA, which gave physicians preliminary access to AT II while it was undergoing FDA review. Using similar inclusion criteria as ATHOS-3, the EAP did not permit patients to receive AT II until doses greater than or equal to 0.2 ug/kg/min of NE-equivalents were reached. In a recently published case report, AT II was successfully used in a patient with septic shock secondary to a colonic perforation (Chow, et al. Accepted for e-publication: A&A Practice. April 2018.). This individual was in vasodilatory shock despite standard resuscitation, 0.48 ug/kg/min of NE, and 0.04 units/min of vasopressin. Methylene blue and hydroxocobalamin had failed to relieve the vasoplegia, and only after the initiation of AT II at 40 ng/kg/min, the patient could be relieved of vasopressors and survived to be discharged from the hospital. In our opinion, best clinical practices would allow for an early multimodal vasopressor regimen that should include AT II at the earliest sign of rapid clinical decline (Jentzer, et al. Chest. 2018. Jan 9. pii: S0012-3692(18)30072-2. doi: 10.1016/j.chest.2017.12.021. [Epub ahead of print]).
Angiotensin II was recently approved by the FDA in December 2017 and is now available on the market for management of vasodilatory shock. This will undoubtedly have a profound impact on the way clinicians treat vasodilatory shock. Previously, we were confined to agents such methylene blue and hydroxocobalamin to rescue patients from profound vasoplegia. However, none of these agents are supported by robust evidence from randomized control trials.
Now, we can openly welcome a new challenger to the campaign, a new hue to the palette of vasopressor colors. This new class of vasopressor makes complete physiological sense and will provide an invaluable tool in our daily battle against sepsis and vasodilatory shock.
Dr. Chow is Assistant Professor, Division of Critical Care Medicine, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD; Dr. Khana is Assistant Professor of Anesthesiology, Staff Intensivist, Vice-Chief for Research, Center for Critical Care, Department of Outcomes Research & General Anesthesiology, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH
Editor’s note
For decades, our options to treat patients with profound vasoplegia have been limited to high-dose catecholamines and vasopressin. Clinicians are often faced with the need to initiate multiple catecholamine agents knowing that these drugs stimulate similar receptors. The recent ATHOS-3 trial introduces AT II as a new option for the management of patients with refractory vasodilatory shock. This drug has a distinct mechanism of action that complements the effect of other vasopressors. Moreover, recent data suggest that this new agent is most beneficial in patients who are AT II deficient. Just like cancer therapies have evolved to precision medicine, will we perhaps face the need to better understand and promptly identify patients with AT II deficiency? For now, we have a new player on our vasopressor team.
Angel Coz, MD, FCCP
Section Editor
