Effects of noradrenaline, vasopressin, phenylephrine or metaraminol on kidney and brain microcirculation in ovine cardiopulmonary bypass: a randomised trial.

Abstract

Intra-operative hypotension is common during cardiopulmonary bypass and may contribute to tissue hypoxia. Tissue hypoxia has been linked to the development of postoperative kidney and brain injury. Vasopressors are used to treat hypotension during and after cardiopulmonary bypass. However, the effects of these drugs on renal and cerebral tissue oxygenation and perfusion are unknown. We tested the effects of four vasopressors on renal and cerebral tissue perfusion and oxygenation in a clinically-relevant ovine model of cardiopulmonary bypass. We studied 16 sheep before and after induction of anaesthesia and during 2.5 h of cardiopulmonary bypass. After commencing cardiopulmonary bypass at a target non-pulsatile flow of 2.4 l.min^-1.m^-2, we observed a baseline period with a target mean arterial pressure of 50-60 mmHg, after which we targeted a mean arterial pressure of 75-85 mmHg using a continuous infusion of metaraminol (n = 8); noradrenaline (n = 8); phenylephrine (n = 8); or vasopressin (n = 7). Sheep were allocated randomly to receive two of the four vasopressors. Compared with the pre-induction state, cardiopulmonary bypass significantly decreased renal medullary tissue perfusion (median (IQR [range]) decrease 55 (4-82 [1-99])%; p = 0.01) and medullary oxygen tension (mean (SD) difference 3.1 (2.5) kPa; p < 0.001). Cardiopulmonary bypass did not significantly alter cerebral tissue perfusion or oxygenation compared with the pre-induction state. Infusing noradrenaline significantly decreased medullary oxygen tension (mean (SD) difference 2.7 (1.6) kPa; p = 0.003). This decrease in medullary oxygen tension was significant compared with vasopressin (mean difference -3.4 kPa, 95%CI -5.7 to -1.0; p = 0.008). No vasopressor infusion significantly altered renal medullary perfusion, cerebral tissue perfusion or oxygenation. Intra-operative noradrenaline during ovine cardiopulmonary bypass worsens renal medullary tissue oxygenation relative to vasopressin. These findings suggest that the choice of vasopressors may affect renal oxygenation.