title: Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation.
abstract: Although epinephrine increases cerebral blood flow (CBF) and left ventricular blood flow (LVBF) during cardiopulmonary resuscitation (CPR), the effects of high dosages on LVBF and CBF and cerebral O2 uptake have not been examined during prolonged CPR. We determined whether log increment dosages of epinephrine would enhance LVBF and CBF and cerebral O2 uptake in an infant swine CPR model. We compared these responses with epinephrine to those with the alpha-adrenergic agonist, phenylephrine. CPR was performed in five groups (n = 6) of pentobarbital-anesthetized piglets (3.5-5.6 kg) receiving a continuous epinephrine infusion (0, 1, 10, and 100 micrograms.kg-1.min-1) or phenylephrine infusion (40 micrograms.kg-1.min-1). Plasma epinephrine concentrations increased 10-100-fold in the control group during CPR and in a stepwise manner such that concentrations were increased by more than 10(4) in the 100 micrograms.kg-1.min-1 epinephrine group. In the control group with no epinephrine infusion, LVBF decreased to less than 10 ml.min-1.100 g-1 by 5 min of CPR. With epinephrine in dosages of 10 and 100 micrograms.kg-1.min-1, LVBF at 5 min was 75 +/- 19 and 44 +/- 15 ml.min-1.100 g-1, respectively, which was significantly greater than values in the control group. With more prolonged CPR, LVBF remained significantly greater than that in the control group but only at 10 micrograms.kg-1.min-1 of epinephrine. Phenylephrine also increased LVBF for 10 min of CPR when compared with the control group. All dosages of epinephrine and phenylephrine maintained CBF close to prearrest values for 20 min of CPR. With prolonged CPR, 10 and 100 micrograms.kg-1.min-1 epinephrine resulted in significantly greater CBF than that in the control group. Incremental dosages of epinephrine did not statistically increase cerebral O2 uptake or lower the cerebral fractional O2 extraction when compared with the control group, despite the higher CBF that was generated. In this immature animal CPR model, 10 micrograms.kg-1.min-1 epinephrine is an optimal dosage for maximizing both CBF and LVBF, a dosage that substantially exceeds the current recommended epinephrine dosage for human infant CPR. In addition, for short periods of CPR, 40 micrograms.kg-1.min-1 phenylephrine increases CBF and LVBF to levels similar to those generated by high dosages of epinephrine.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland 21205.
authors.forename: I D
authors.initials: ID
authors.lastname: Berkowitz
authors.forename: H
authors.initials: H
authors.lastname: Gervais
authors.forename: C L
authors.initials: CL
authors.lastname: Schleien
authors.forename: R C
authors.initials: RC
authors.lastname: Koehler
authors.forename: J M
authors.initials: JM
authors.lastname: Dean
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006352:Heart Ventricles; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
chemical_list: D004837:Epinephrine