---11111111 CHEST editorials VOLUME 97 / NUMBER 6 / JUNE, 1990
Optimizing Drug Therapy During Cardiopulmonary Resuscitation The importance of adequate myocardial and cerebral perfusion pressures during cardiopulmonary resuscitation has been emphasized by numerous investigators.!" The use of vasopressor agents during resuscitation efforts has been standard since the work of Redding and Pearson' :" in the 1960s. Resuscitation outcome studies by these investigators and selective (X- and l3-adrenergic blockade studies by Yakaitis et all and Otto et al" clearly have shown the importance of o-adrenergic stimulation in increasing aortic diastolic pressure with resulting increases in myocardial perfusion pressure and successful resuscitation, Currently, the advantages of epinephrine, an (X1.z- 131,2agonist vs more selective o-agonists are widely debated . In this issue of Chest (see page 1458) Lindner and colleagues compared epinephrine and norepinephrine for their effects on myocardial perfusion, myocardial oxygen delivery and consumption, and successful resuscitation outcome. They found that both pressor agents had a similar effect on mean arterial blood pressure, resulting in a significant increase compared with placebo control. Likewise, epinephrine and norepinephrine increased myocardial blood flow by essentially equal amounts compared with placebo. These results, though not unexpected, are important in assuring equipotent dosing with both agents, allowing more confidence in other comparisons performed during the study. Myocardial oxygen delivery (defined as myocardial blood flow x arterial oxygen content) paralleled the rise in myocardial blood flow seen with both agents. No difference in MDO z was found between epinephrine and norepinephrine usage . However, myocardial oxygen consumption (defined as myocardial blood flow x arterial oxygen content minus coronary vein oxygen content) was significantly greater with epinephrine, though not so with norepinephrine administration. Since myocardial blood flows were not significantly different with the two agents, the major effect must be on the coronary vein oxygen content. Following epinephrine, further oxygen was extracted from the myocardium decreasing coronary venous
blood oxygen content and increasing the oxygen "extraction ratio ," Such an effect was not seen with norepinephrine; in fact , because of the increase in oxygen delivery accompanied by no further drop in coronary venous oxygen content, the extraction ratio decreased and returned toward levels seen during normal sinus rhythm . Livesay and coworkers!- measured oxygen uptake in fibrillating hearts under steadystate conditions (supported at a perfusion pressure of 65 mm Hg on cardiopulmonary bypass), They noted a similar finding that epinephrine increased myocardial oxygen demands while a more "selective" (Xagonist, methoxamine, did not. Since norepinephrine has l3-activity similar to epinephrine , the difference in myocardial oxygen consumption found by Lindner and coworkers needs further explanation, Though both agents have (Xactivity and in equipotent doses create similar peripheral vasoconstriction , they have been reported to difJer in their ability to increase myocardial contractility through (X ,-sti m ulation . I:. Unfortunately, accu rate physiologic measurement of this increased contractility is difficult , Likewise, ill t ~i(jo separation of whether 131- or (XI-stimulation is responsible for any such increase in contractility is difficult within the realm of a clinically realistic experimental model. The importance of 132-adrenergic stimulation by epinephrine in this study remains unknown, During normal sinus rhythm, pharmacologic stimulation of I3z-receptors by isoproterenol during 13.-blockade produces modest coronary dilatation, especially within the subepicardial region .11.15 During cardiac arrest and cardiopulmonary resuscitation where maximal vasodilatation already exists, this effect is probably negligible, Furthermore, a recent study by Bjornerheim et al'" suggests that porcine myocardium may lack 132adrenergic receptors. Hence, the differences seen with epinephrine and norepinephrine in the study of Lindner et al are probably not the result of any difJi.·n·ncl's in l3-agonism between these agents. Differences in myocardial oxygen consumption aside, the most important issue in comparing other adrenergic agonists with epinephrine is whether resuscitation outcome is improved. Lindner et '11 found no difference in resuscitation success between control and epinephrine-treated animals (3rt "S 3rt), but norepinephrine was significantly better than either (7/ CHEST I 97 I 6 I JUNE , 1990
1281
7 vs 3n; p
Optimizing Drug Therapy During Cardiopulmonary Resuscitation The importance of adequate myocardial and cerebral perfusion pressures during cardiopulmonary resuscitation has been emphasized by numerous investigators.!" The use of vasopressor agents during resuscitation efforts has been standard since the work of Redding and Pearson' :" in the 1960s. Resuscitation outcome studies by these investigators and selective (X- and l3-adrenergic blockade studies by Yakaitis et all and Otto et al" clearly have shown the importance of o-adrenergic stimulation in increasing aortic diastolic pressure with resulting increases in myocardial perfusion pressure and successful resuscitation, Currently, the advantages of epinephrine, an (X1.z- 131,2agonist vs more selective o-agonists are widely debated . In this issue of Chest (see page 1458) Lindner and colleagues compared epinephrine and norepinephrine for their effects on myocardial perfusion, myocardial oxygen delivery and consumption, and successful resuscitation outcome. They found that both pressor agents had a similar effect on mean arterial blood pressure, resulting in a significant increase compared with placebo control. Likewise, epinephrine and norepinephrine increased myocardial blood flow by essentially equal amounts compared with placebo. These results, though not unexpected, are important in assuring equipotent dosing with both agents, allowing more confidence in other comparisons performed during the study. Myocardial oxygen delivery (defined as myocardial blood flow x arterial oxygen content) paralleled the rise in myocardial blood flow seen with both agents. No difference in MDO z was found between epinephrine and norepinephrine usage . However, myocardial oxygen consumption (defined as myocardial blood flow x arterial oxygen content minus coronary vein oxygen content) was significantly greater with epinephrine, though not so with norepinephrine administration. Since myocardial blood flows were not significantly different with the two agents, the major effect must be on the coronary vein oxygen content. Following epinephrine, further oxygen was extracted from the myocardium decreasing coronary venous
blood oxygen content and increasing the oxygen "extraction ratio ," Such an effect was not seen with norepinephrine; in fact , because of the increase in oxygen delivery accompanied by no further drop in coronary venous oxygen content, the extraction ratio decreased and returned toward levels seen during normal sinus rhythm . Livesay and coworkers!- measured oxygen uptake in fibrillating hearts under steadystate conditions (supported at a perfusion pressure of 65 mm Hg on cardiopulmonary bypass), They noted a similar finding that epinephrine increased myocardial oxygen demands while a more "selective" (Xagonist, methoxamine, did not. Since norepinephrine has l3-activity similar to epinephrine , the difference in myocardial oxygen consumption found by Lindner and coworkers needs further explanation, Though both agents have (Xactivity and in equipotent doses create similar peripheral vasoconstriction , they have been reported to difJer in their ability to increase myocardial contractility through (X ,-sti m ulation . I:. Unfortunately, accu rate physiologic measurement of this increased contractility is difficult , Likewise, ill t ~i(jo separation of whether 131- or (XI-stimulation is responsible for any such increase in contractility is difficult within the realm of a clinically realistic experimental model. The importance of 132-adrenergic stimulation by epinephrine in this study remains unknown, During normal sinus rhythm, pharmacologic stimulation of I3z-receptors by isoproterenol during 13.-blockade produces modest coronary dilatation, especially within the subepicardial region .11.15 During cardiac arrest and cardiopulmonary resuscitation where maximal vasodilatation already exists, this effect is probably negligible, Furthermore, a recent study by Bjornerheim et al'" suggests that porcine myocardium may lack 132adrenergic receptors. Hence, the differences seen with epinephrine and norepinephrine in the study of Lindner et al are probably not the result of any difJi.·n·ncl's in l3-agonism between these agents. Differences in myocardial oxygen consumption aside, the most important issue in comparing other adrenergic agonists with epinephrine is whether resuscitation outcome is improved. Lindner et '11 found no difference in resuscitation success between control and epinephrine-treated animals (3rt "S 3rt), but norepinephrine was significantly better than either (7/ CHEST I 97 I 6 I JUNE , 1990
1281
7 vs 3n; p
