J. M. Dean

Effect of epinephrine on cerebral and myocardial perfusion in an infant animal preparation of cardiopulmonary resuscitation.

We assessed the efficacy of conventional cardiopulmonary resuscitation (CPR) in 2-week-old piglets. We determined intrathoracic vascular pressures, cerebral (CBF) and myocardial blood flows (MBF), and cerebral oxygen uptake during conventional CPR in this infant animal preparation and contrasted these results with those of previous work on adult animals. We further examined the effects of the infusion of epinephrine on these pressures and flows and on cerebral oxygen uptake, which has not been previously evaluated in adult preparations. Conventional CPR was performed on pentobarbital-anesthetized piglets with a 20% sternal displacement with the use of a pneumatic piston compressor. Chest recoil was incomplete, leading to an 18% to 27% reduction in anteroposterior diameter during the relaxation phase. Aortic and right atrial pressures in excess of 80 mm Hg were generated. These pressures are greater than those generally obtained in adult animals with similar percent pulsatile displacements. CBF and MBF were also initially greater than those reported in adult animals undergoing conventional CPR. However, when CPR was prolonged beyond 20 min, aortic pressure fell and CBF and MBF declined to the near-zero levels seen in adult preparations. At 5 min of CPR, CBF and MBF were 24 +/- 7 and 27 +/- 7 ml . min-1 x 100 g-1 (50% and 17% of the values during cardiac arrest), respectively. With the continuous infusion of epinephrine (4 micrograms/kg/min) in another group of animals, MBF was significantly greater at 20 min of CPR and CBF and cerebral O2 uptake were greater at 35 min of CPR as a result of higher perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine Dosage Effects on Cerebral and Myocardial Blood Flow in an Infant Swine Model of Cardiopulmonary Resuscitation

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.

Improved blood flow during prolonged cardiopulmonary resuscitation with 30% duty cycle in infant pigs.

BackgroundSustained compression is recommended to maximize myocardial and cerebral blood flow during cardiopulmonary resuscitation (CPR) in adults and children. We compared myocardial and cerebral perfusion during CPR in three groups of 2-week-old anesthetized swine using compression rates and duty cycles (duration of compression/total cycle time) of 100 per minute, 60%; 100 per minute, 30%; and 150 per minute, 30%1. Methods and ResultsVentricular fibrillation was induced and CPR was begun immediately with a sternal pneumatic compressor. Epinephrine was continuously infused during CPR. Microsphere-determined blood flow and arterial and sagittal sinus blood gas measurements were made before cardiac arrest was induced and after 5, 10, 20, 35, and 50 minutes of CPR. At 5 minutes of CPR, ventricular and cerebral blood flows were greater than 25 ml · min-1 · 100 g-1 and were not significantly different between groups. When CPR was prolonged, however, myocardial and cerebral blood flows were significantly higher with the 30% duty cycle than with the 60% duty cycle. By 35 minutes, all myocardial regions had less than 5 ml · min-1 · 100 g-1 flow with the 60%1 duty cycle. In contrast, CPR with the 30% duty cycle at either compression rate provided more than 25 ml min 1 · 100 g-1 to all ventricular regions for 50 minutes. By 20 minutes, most brain regions received 50% less flow with the 60% duty cycle compared with animals undergoing CPR with the 30% duty cycle (p < 0.05). Cerebral oxygen uptake was better preserved with the 30% duty cycle. Chest deformation from loss of recoil was greater with the 60%o duty cycle compared with the 30% duty cycle. ConclusionsWe conclude that the shorter duty cycle provides markedly superior myocardial and cerebral perfusion during 50 minutes of CPR in this infant swine model. These data do not support recommendations for prolonged compression at rates of 100 per minute during CPR in infants and children.

Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine.

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.