Time for a New Main Squeeze in Distributive Shock?

Volume 19, Issue 2

Distributive shock, which is most commonly septic in origin, continues to impart significant morbidity and mortality in the United States. Nearly two-thirds of all shock states are distributive in etiology, and distributive shock carries a roughly 40% to 50% mortality rate despite contemporary interventions.

Patients with distributive shock are initially given fluid resuscitation for hemodynamic support. However, many will also require vasopressor support in order to maintain perfusion of vital organs.

The historical gold standard for hemodynamic support in distributive shock is catecholamine vasopressors, with norepinephrine being the first-line agent. Unfortunately, catecholamines are cardiotoxic molecules, and higher doses are associated with an increased mortality in patients with distributive shock.

Vasopressin is a common second line agent for patients with catecholamine-refractory vasodilatory shock, based largely on the premise that a significant number of these patients have a relative vasopressin deficiency. Unfortunately, the cost of vasopressin has increased steadily in recent years, and more than 50% of patients with distributive shock do not respond to vasopressin.

The roll of the renin-angiotensin aldosterone system (RAAS) in distributive shock is under-discussed and underappreciated. Most students are taught the importance of the catecholamine and arginine vasopressin systems in maintaining perfusion during distributive shock states, but the RAAS is an important third pathway.

In distributive shock, angiotensin II levels fall due to depletion of the angiotensin-converting enzyme (ACE). This results in an accumulation of angiotensin I, which can then be converted into various vasodilatory compounds which worsen the shock state. Exogenous administration of angiotensin II can reverse this maladaptive process and the shock state.

In the pivotal ATHOS-3 trial, administration of angiotensin II was shown to improve mean arterial blood pressure in over 70% of patients who received treatment. While the trial did not demonstrate a significant reduction in mortality, there were signals that sicker patients, like those with severe renal failure, may derive a mortality benefit.

Angiotensin II is an exciting new agent that can be used to manage patients with catecholamine-refractory cardiogenic shock. Based on the underlying physiology of distributive shock, which includes ACE deficiency in a significant number of patients, those with catecholamine-refractory shock should be considered as candidates for angiotensin II therapy.