New paradigm of microvascular physiology in renal acute kidney injury
General therapeutic implications of renal microvascular dysfunction
Avoid nonsteroidal anti-inflammatory drugs (NSAIDs), ACE-inhibitors, and Angiotensin-receptor blockers (ARBs)
Avoid hyperchloremic acidosis, typically by using balanced crystalloids
Norepinephrine improves renal perfusion and function
Low-dose vasopressin may improve renal function
Morelli 2009 randomized 45 patients with septic shock to fixed-dose infusion of terlipressin (1.3 ug/kg/hr), vasopressin (0.03 U/min) or norepinephrine (15 mcg/min) plus open-label norepinephrine. Patients in the vasopressin group had a stable creatinine whereas patients in the norepinephrine group elevated their creatinine over 48 hours (p < 0.001; table below).
The VASST trial randomized 778 patients with septic shock to receive open-label norepinephrine plus either 0.01-0.03 U/min vasopressin or 5-15 mcg/min norepinephrine. There was a 5.7% absolute mortality reduction in the vasopressin group which didn't reach statistical significance (p = 0.1). This improvement was restricted to the prospectively defined group of patients with less severe septic shock (defined as initial norepinephrine requirement <15 mcg/min), among whom p = 0.04 (figure below). This post-hoc subgroup analysis is open to multiple interpretations.
Aside from renal perfusion, another possible advantage of vasopressin is avoiding excessive beta-adrenergic stimulation of the heart. Norepinephrine has been established as superior to dopamine for most applications, due primarily to less intense beta-agonist activity than dopamine (e.g., norepinephrine causes fewer arrhythmias). However, recent research regarding esmolol in septic shock by Morelli 2013 raises the question of whether norepinephrine may also provide excessive beta-agonist activity in some cases. Vasopressin allows reduction of norepinephrine doses, thereby reducing beta-adrenergic stimulation.
- Avoidance of NSAIDs, ACE-inhibitors, and angiotensin-receptor blockers.
- Avoidance of hyperchloremic acidosis, typically by using balanced crystalloids for volume resuscitation.
- Support of mean arterial pressure with norepinephrine.
- Adjunctive low-dose vasopressin to maintain glomerular filtration.