Date Published: January 31, 2017
Publisher: Public Library of Science
Author(s): Vibeke Ramsgaard Eriksen, Martin Bo Rasmussen, Gitte Holst Hahn, Gorm Greisen, Christopher Torrens.
Hypotensive neonates who have been treated with dopamine have poorer neurodevelopmental outcome than those who have not been treated with dopamine. We speculate that dopamine stimulates adrenoceptors on cerebral arteries causing cerebral vasoconstriction. This vasoconstriction might lead to a rightward shift of the cerebral autoregulatory curve; consequently, infants treated with dopamine would have a higher risk of low cerebral blood flow at a blood pressure that is otherwise considered “safe”.
In anaesthetized piglets, perfusion of the brain, monitored with laser-doppler flowmetry, and cerebral venous saturation was measured at different levels of hypotension. Each piglet was studied in two phases: a phase with stepwise decreases in MAP and a phase with stepwise increases in MAP. We randomized the order of the two phases, whether dopamine was given in the first or second phase, and the infusion rate of dopamine (10, 25, or 40 μg/kg/min). In/deflation of a balloon catheter, placed in vena cava, induced different levels of hypotension. At each level of hypotension, fluctuations in MAP were induced by in/deflations of a balloon catheter in descending aorta.
During measurements, PaCO2 and arterial saturation were stable. MAP levels ranged between 14 and 82 mmHg. Cerebral autoregulation (CA) capacity was calculated as the ratio between %-change in cerebrovascular resistance and %-change in MAP induced by the in/deflation of the arterial balloon. A breakpoint in CA capacity was identified at a MAP of 38±18 mmHg without dopamine and at 44±18, 31±14, and 24±14 mmHg with dopamine infusion rates of 10, 25, and 40 μg/kg/min (p = 0.057). Neither the index of steady-state cerebral perfusion nor cerebral venous saturation were affected by dopamine infusion.
Dopamine infusion tended to improve CA capacity at low blood pressures while an index of steady-state cerebral blood flow and cerebral venous saturation were unaffected by dopamine infusion. Thus, dopamine does not appear to impair CA in newborn piglets.
Hypotension in newborn infants is associated with higher incidence of mortality and cerebral injury[1–5]. Cerebral injuries caused by hypotension are heterogeneous with both peri- and intraventricular haemorrhage as well as ischemic cerebral lesions[1–3,5]; predominantly the white matter being the most vulnerable area to hypotensive periods. These cerebral injuries result in poorer long-term neurodevelopmental outcome[4,7]. Maintaining adequate perfusion of vital organs, especially the brain, is the rationale of treating hypotension in newborn infants. Dopamine raises mean arterial blood pressure (MAP) effectively[8,9] and is the most commonly used vasopressor in newborn infants. It stimulates both dopaminergic and adrenergic receptors on the arterial smooth muscle cells, and has a concentration-dependent biphasic response: vasodilation at low concentrations, caused by stimulation of dopaminergic receptor, and vasoconstriction at higher concentrations due to adrenergic stimulation.
The Danish Animal Experiments Inspectorate approved the experimental protocol: 2014-15-0201-00123.
Our hypothesis was that dopamine affected CA negatively by inducing cerebral vasoconstriction. We used three different measures to examine our hypothesis. Cerebral venous saturation is a global estimate of the venous saturation from both hemispheres, whereas the two other measures: CA capacity, as an estimate of cerebral vasoreactivity, and the index of steady-state cerebral blood flow are based on perfusion in a very small area of cortex as interrogated by the laser Doppler light probe. Surprisingly, CA capacity rather tended to improve with increasing infusion rates of dopamine while there was no suggestion of an effect of dopamine treatment on the index of steady-state cerebral blood flow or cerebral venous saturation at low levels of MAP.
Dopamine tended to improve cerebral autoregulation capacity at low arterial blood pressure; however, a beneficial effect of dopamine was not confirmed by improved cerebral blood flow or cerebrovenous oxygen saturation. We conclude that dopamine therapy does not appear to affect cerebral autoregulation negatively in hypotensive newborn piglets.