Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets

PLoS One. 2013 May 20;8(5):e63069. doi: 10.1371/journal.pone.0063069. Print 2013.

Abstract

Background: Despite widespread use in sick infants, it is still debated whether vasopressor-inotropes have direct cerebral effects that might affect neurological outcome. We aimed to test direct cerebrovascular effects of three commonly used vasopressor-inotropes (adrenaline, dopamine and noradrenaline) by comparing the responses to those of nonpharmacologically induced increases in blood pressure. We also searched for reasons for a mismatch between the response in perfusion and oxygenation.

Methods: Twenty-four piglets had long and short infusions of the three vasopressor-inotropes titrated to raise mean arterial blood pressure (MAP) 10 mmHg in random order. Nonpharmacological increases in MAP were induced by inflation of a balloon in the descending aorta. We measured cerebral oxygenation (near-infrared spectroscopy), perfusion (laser-Doppler), oxygen consumption (co-oximetry of arterial and superior sagittal sinus blood), and microvascular heterogeneity (side stream dark field video microscopy).

Results: Vasopressor-inotropes increased cerebral oxygenation significantly less (p≤0.01) compared to non-pharmacological MAP increases, whereas perfusion was similar. Furthermore, cerebral total hemoglobin concentration increased significantly less during vasopressor-inotrope infusions (p = 0.001). These physiologic responses were identical between the three vasopressor-inotropes (p>0.05). Furthermore, they induced a mild, although insignificant increase in cerebral metabolism and microvascular heterogeneity (p>0.05). Removal of the scalp tissue did not influence the mismatch (p>0.05).

Conclusion: We demonstrated a moderate vasopressor-inotrope induced mismatch between cerebral perfusion and oxygenation. Scalp removal did not affect this mismatch, why vasopressor-inotropes appear to have direct cerebral actions. The statistically nonsignificant increases in cerebral metabolism and/or microvascular heterogeneity may explain the mismatch. Alternatively, it may simply reflect a vasopressor-inotrope-induced decrease in the arterial-to-venous volume ratio as detected by near-infrared spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Pressure / drug effects
  • Cell Hypoxia
  • Cerebral Cortex / blood supply*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dopamine / pharmacology*
  • Epinephrine / pharmacology*
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Norepinephrine / pharmacology*
  • Oxygen Consumption / drug effects
  • Regional Blood Flow / drug effects
  • Sus scrofa
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Vasoconstrictor Agents
  • Dopamine
  • Norepinephrine
  • Epinephrine

Grant support

This work was supported by grants from the Lundbeck Foundation, Aase and Einar Danielsens Foundation and The Augustinus Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.