Vaso VS Levo

I’ve been trying to look for studies and trials comparing norepinephrine to vaso but there aren’t many out there. Also vaso vs levo in cardiogenic shock. But let’s go over the basics first.

Vasopressin is a natural hormone that is secreted by the pituitary gland. It has a few names: AVP and ADH. We also made man-made synthetic forms of it too: vasostrict and DDAVP (analogue). Understanding the hormone will allow you to understand what our synthetic pressor does.

They attach to a few receptors for the effect we want. V1a receptors are on your vascular smooth muscle — activating this causes direct vasoconstriction that increases the peripheral vascular resistance. V2 receptors are on your renal tubular cells in the collecting duct — activating this causes more h2o re-absorption. You’ll see V1b activation too, which is in the pituitary gland and does other stuff we can leave out for now. All this is how we try to up the BP.

After my lit review this morning, I answered parts of my question. So let’s say I have a patient with low flow shock (with BiV dysfunction) who is acutely hypotensive on DBA of 10 mcg/kg/min. And the pt is up to 0.5 mcg/kg/min on levo (weight-based) and more hypotensive…with high PA filling pressures. I’m going to start vaso. The effects of going up on high-dose levo will cause more alpha activation (vascular, GI, cardiac vascular smooth muscles). If I’m worried about the RV and I’m increasing pulmonary vascular resistance (alpha) then the RV will struggle against that afterload and then my LV pre-load goes down and then I’m in that RV spiral of death. But vaso doesn’t target the pulmonary beds as much. So if I allow the vaso to go up and come down on the levo, hopefully the BP might improve a bit. This is a common clinical scenario we see in the CCU and CVICU a lot (I know — you might just say, well then just place a crash IABP or Impella or the patient needs VA ECMO — fair but besides the point). Point is, if I’m worried about the right side then maybe I need vaso more than high dose levo (yea, too much alpha). Vaso spares the pulmonary vascular beds and ideally helps those with pulmonary hypertension. The PVR/SVR ratio decreases with vaso while the ratio increases with levo.

Second question: are mortality outcomes or other outcomes any different if I change my dosages or titrations of vaso? Well….using a primary outcome of achieving MAP≥65 mmHg in the first 6-hours inseptic shock patients, one retrospective study shows that using vaso 0.03 U/min vs vaso 0.04 U/min with levo did not make a difference in achieving a MAP of 65 first.

I’m going to talk about two more trials. The VANISH trial in 2016 and VASST trial in 2008. Both RCTs so all good. (Dr. Fauci said these are the best ones, remember?)

The question the VANISH (The Vasopressin vs Norepinephrine As Initial Therapy in Septic Shock) wanted to answer was if initially starting vaso (up to 0.06 U/min) vs initially starting levo would change the incidence of kidney failure-free days in septic shock pts in 28-days. They only used 409 patients (so not a lot). Kidney failure was defined by the AKIN group stage 3 (sCr>3, anuric for 12-hours, starting RRT, or UOP<0.3/ml/kg/h X 24h). Starting vaso vs starting levo didn’t make a difference in the number of kidney-failure free days. Mortality rates did not differ either. However, less pt ended up on RRT in the vaso group compared to the levo group. Hm.

The VASST trial (Vasopressin Vs Norepinephrine Infusion in Patients with Septic Shock) questioned a primary outcome 28-day mortality rate (death from any cause) in low dose vaso with low dose levo vs just levo. 778 randomized patients. Secondary outcomes were 90-day mortality and rates of organ dysfunction. There were no statistical difference between the two groups. Although the levo group vs vaso group showed a slightly higher trend for cardiac arrest (2.1% vs 0.8%) and vaso group showed more digital ischemia. But bottom line, mortality didn’t change. Also, death from any cause is a limitation.

Will this change my management of patients?

Depends on the patient. I do deal with mixed shock patients with sepsis, cardiogenic, and obstructive. These studies were only conducted in septic shock patients. But after reading these studies, I might use more vasopressin and go to 0.06 if needed in hypotensive cardiogenic shock patients in addition to my inotropes. Tachycardia might lead to badness too since I don’t want to cause a supply vs demand mismatch in the coronaries/heart. I’ll probably always still start with levo first in my undifferentiated shock patients first because I want my beta effects (and because my favorite Surviving Sepsis Campaign and SCCM said so).

Dk

(These are my personal opinions and should inform care but not dictate care for your patients)

Things I read:

Bauer SR, Sacha GL, Lam SW, Wang L, Reddy AJ, Duggal A, Vachharajani V. Hemodynamic Response to Vasopressin Dosage of 0.03 Units/Min vs. 0.04 Units/Min in Patients With Septic Shock. J Intensive Care Med. 2020 Nov 28:885066620977181. doi: 10.1177/0885066620977181. Epub ahead of print. PMID: 33251906.

Demiselle, J., Fage, N., Radermacher, P. et al. Vasopressin and its analogues in shock states: a review. Ann. Intensive Care 10, 9 (2020). https://doi.org/10.1186/s13613-020-0628-2

José António Lopes, Sofia Jorge, The RIFLE and AKIN classifications for acute kidney injury: a critical and comprehensive review, Clinical Kidney Journal, Volume 6, Issue 1, February 2013, Pages 8–14, https://doi.org/10.1093/ckj/sfs160

Roy A, Dellinger RP. Attempting to define and refine vasopressin use in septic shock: the VANISH trial. Ann Transl Med. 2016;4(24):501. doi:10.21037/atm.2016.12.11

Russell, J, et al. Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock. N Engl J Med 2008; 358:877–887
DOI: 10.1056/NEJMoa067373

Sarkar J, Golden PJ, Kajiura LN, Murata LA, Uyehara CF. Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a porcine model of severe hemorrhagic shock. Shock. 2015 May;43(5):475–82. doi: 10.1097/SHK.0000000000000325. PMID: 25565637.

Zhou FH, Song Q. Clinical trials comparing norepinephrine with vasopressin in patients with septic shock: a meta-analysis. Mil Med Res. 2014;1:6. Published 2014 May 1. doi:10.1186/2054–9369–1–6