Reversal of Vasodilatory Shock: Current Perspectives on Conventional, Rescue, and Emerging Vasoactive Agents for the Treatment of Shock

Jonathan H. Chow, MD; Ezeldeen Abuelkasem, MBBCh, MSc; Susan Sankova, MD; Reney A. Henderson, MD; Michael A. Mazzeffi, MD, MPH; Kenichi A. Tanaka, MD, MSc

Disclosures

Anesth Analg. 2019;130(1):15-30. 

In This Article

Dopamine as an Alternative in Highly Selected Populations

There is no role for the routine use of dopamine when NE, vasopressin, or Epi has failed to control shock. Dopamine should only be used as an agent for vasodilatory shock in highly selected populations with relative bradycardia and low risk of developing tachyarrhythmias. Through agonism of D1-type receptors, dopamine increases cardiac output through its inotropic and chronotropic effects on stroke volume and heart rate, respectively.[45]

Pharmacology

Dopamine is an endogenous catecholamine that is derived from the amino acid tyrosine (Figure 1) and synthesized in multiple sites throughout the body. Dopamine production is particularly important in the substantia nigra of midbrain, and its loss causes Parkinson disease.[46,47]

Dopamine has numerous physiologic effects on the heart, vasculature, and kidney, all of which can influence systemic blood pressure (Table 1). Five dopamine receptors (D1, D2, D3, D4, and D5) have been described, all of which are GPCRs. Dopamine receptors are classified into 2 groups: D1-type receptors (D1 and D5) and D2-type receptors (D2, D3, and D4).[45] Stimulation of D1-type receptors leads to direct arterial vasodilation by activation of adenylate cyclase (Figure 3). Conversely, stimulation of D2-type receptors inhibits adenylate cyclase and causes an increase in smooth vascular tone by decreasing cAMP.[48,49] At low doses (0.5–2 μg·kg−1·min−1), dopamine primarily acts on D1-type receptors, while at intermediate doses (2–10 μg·kg−1·min−1), it predominately acts on β1 receptors to cause enhanced chronotropy, inotropy, and lusitropy. At high doses (>10 μg·kg−1·min−1), dopamine's main effect is on α receptors, which causes vasoconstriction through an adenylate cyclase–mediated pathway (Figure 3).

Clinical Studies

Low-dose dopamine has been shown to increase renal blood flow by as much as 30%–40%, and there appears to be no additional increase in renal blood flow with doses above 3 μg·kg−1·min−1.[50,51] Dopamine leads to enhanced natriuresis with approximately a 2-fold increase in the 1–5 μg·kg−1·min−1 range.[50] Multiple mechanisms account for enhanced natriuresis, including increased renal blood flow and D1 receptor–mediated inhibition of the Na+H+ antiport in proximal tubular cells and the Na+K+-ATPase in both proximal tubular cells and the loop of Henle.[50] Despite this, there is strong evidence against the use of low-dose dopamine for renal protection in vasodilatory shock.[29]

Dopamine was compared as a first-line vasopressor against NE in over 1600 patients with septic shock.[2] There was no difference in 28-day mortality between patients in the 2 groups; however, patients receiving dopamine had a higher incidence of atrial fibrillation. Furthermore, in subgroup analysis, patients with cardiogenic shock who received dopamine had increased mortality. A contemporary meta-analysis that included 6 RCTs and 5 observational studies suggested that dopamine was associated with an increased risk of death compared to NE when used in patients with septic shock (RR of NE, 0.89; 95% CI, 0.81–0.98).[52] In septic shock, dopamine has been relegated as a tertiary drug and is not used for the routine management of vasodilatory shock. Because of its inotropic properties, dopamine may be useful in the subset of patients with impaired systolic heart function, but caution must be used due to its chronotropy and its tendency to increase mortality in cardiogenic shock.[2]

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