CORRESPONDENCE I ntracardiac Route for Epinephrine CHANGE IN HEART RATE FOLLOWING
To the Editor: The study presented in "Comparison of the Pharmacological Effects of E p i n e p h r i n e A d m i n i s t e r e d by the I n t r a v e n o u s and E n d o t r a c h e a l Routes," by Roberts et al (7:260-264, 1978) is long overdue. The type of inf o r m a t i o n t h e y present has been lacking in the medical l i t e r a t u r e . One f u r t h e r step would be to compare not only the intravenous (IV) and e n d o t r a c h e a l (ET) routes, b u t also the i n t r a c a r d i a c (IC) route. The i n t r a c a r d i a c route was s o m e w h a t a l l u d e d to in the article, " P a r a m e d i c Use of I n t r a c a r d i a c Medications in P r e h o s p i t a l Sudden Cardiac Death, " by A m e y et al (7:130-134, 1978). P e r s o n a l c o m m u n i c a t i o n w i t h Dr. A m e y indicates t h a t f u r t h e r information r e g a r d ing this method will be forthcoming. One guestion, however, t h a t arises in the Roberts a r t i c l e is in r e g a r d to v e n t r i c u l a r f i b r i l l a t i o n . The function of epinephrine in v e n t r i c u l a r fibrillation is to convert fine fibrillation into coarse fibrillation so t h a t d e f i b r i l l a t i o n c a n be a c c o m p l i s h e d . The h e a r t r a t e change is g r e a t e s t with IV e p i n e p h r i n e but requires a l m o s t t h r e e m i n u t e s to be" accomplished and the initial c h a n g e is b r a d y c a r d i a ( F i g u r e la). A l t h o u g h the change w i t h ET route is much more rapid, it is not as significant as w i t h the IV route. The question arises, then, as to w h e t h e r a d e l a y of two to t h r e e m i n u t e s in the onset of the t a c h y c a r d i a indicates t h a t k i n d of a d e l a y in the responsiveness of the m y o c a r d i u m to the effect of epinephrine, t h a t is, converting from a vent r i c u l a r f i b r i l l a t i o n to a coarse fibrillation. P e r h a p s the a u t h o r s will comment on w h a t t h e y suspect the effect m i g h t be in this conversion, which route t h e y suspect would be t h e most effective and if they i n t e n d to f u r t h e r e v a l u a t e the use of e p i n e p h r i n e by performing t h i s study on dogs.
70 60
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2
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6
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8
9 I0 II
i2 13 14 r5
Trrne (Minutes)
Fig. l a . The change in heart rate over time compares the ET and IV routes following a dose of 0.09 mg/kg. cal conversion of a fine v e n t r i e u l a r fibrillation to a coarse one by e p i n e p h r i n e reflects direct action on the m y o c a r d i u m by the epinephrine. Consequently, no conclusion ought to be d r a w n from this specific d a t a (ie, h e a r t rate) r e g a r d i n g the efficacy with which endot r a c h e a l l y a d m i n i s t e r e d epinephrine may or m a y not convert a fine v e n t r i c u l a r fibrillation to a coarse one. Indeed, the question raised by Dr. McSwain (ie, d i r e c t m y o c a r d i a l r e s p o n s i v e n e s s to e n d o t r a c h e a l l y a d m i n i s t e r e d epinephrine) is a crucial one. In our laboratory, this a r e a is p r e s e n t l y being actively investigated. P r e l i m i n a r y studies reveal t h a t in dogs epinephrine is efficacious in the conversion of pharmacologic a l l y i n d u c e d c a r d i o v a s c u l a r c o l l a p s e i n t o sinus rhythm with n o r m a l blood pressure. Some results of these e a r l y studies a p p e a r in this issue (p. 53). E a r l y results lead us to believe t h a t the endotracheal route m a y provide an excellent route for a d m i n i s t r a t i o n of e p i n e p h r i n e w h e n a d i r e c t m y o c a r d i a l r e s p o n s e is d e s i r a b l e . H o w e v e r , a l l r e c o m m e n d a t i o n s concerning the clinical use of epinephrine in h u m a n s must a w a i t more c o n t r o l l e d s t u d y of this r o u t e of d r u g administration.
Norman E. McSwain, Jr, MD, F A C S Associate Professor of Surgery Tulane University, New Orleans, Louisiana
Author's Reply Dr. McSwain is indeed correct when he points out t h a t e p i n e p h r i n e is useful in c o n v e r t i n g a fine t y p e v e n t r i c u l a r f i b r i l l a t i o n into a coarse type, which is more a m e n a b l e to electrical defibrillation. Epinephrine h a s o t h e r p h a r m a c o l o g i c a l effects as well. As noted in our paper, epinephrine will increase h e a r t r a t e as well as myocardial c o n t r a c t i l i t y via its positive inotropic and chronotropic actions. The c h a n g e s w h i c h Dr. M c S w a i n refers to a r e c h a n g e s in h e a r t r a t e in e x p e r i m e n t a l a n i m a l s . In fact, e n d o t r a c h e a l l y a d m i n i s t e r e d e p i n e p h r i n e provides a significant increase in h e a r t r a t e w h e n comp a r e d w i t h i n t r a v e n o u s l y a d m i n i s t e r e d epinephrine. This increase in h e a r t rate p r o b a b l y reflects, to some degree at least, peripheral alpha-type actions of e p i n e p h r i n e as the drug is absorbed into the systemic circulation. It is impossible to guess at w h a t proportion of this effect is p e r i p h e r a l a n d w h a t p a r t is due to action directly on t h e myocardium. The pharmacologi-
8:2 (February) 1979
ENOOTRACHEAL AND
INTRAVENOUS EPINEPHRINE {0 09mg/kg)
Michael I. Greenberg, MD Chief Resident, Emergency Medicine The Medical College of Pennsylvania and Hospital Philadelphia, Pennsylvania
Steroids in Near Drowning Questioned To the Editor: In " N e a r Drowning," by Knopp (7:249-254, 1978), on page 253 the a u t h o r states, "There is no evidence to r e c o m m e n d the r o u t i n e use of steroids. Yet, in reduci n g c e r e b r a l e d e m a s e c o n d a r y to a n o x i a in n e a r drowning, steroids are often used and m a y be helpful."
JACEP
91/73
To the Editor: The study presented in "Comparison of the Pharmacological Effects of E p i n e p h r i n e A d m i n i s t e r e d by the I n t r a v e n o u s and E n d o t r a c h e a l Routes," by Roberts et al (7:260-264, 1978) is long overdue. The type of inf o r m a t i o n t h e y present has been lacking in the medical l i t e r a t u r e . One f u r t h e r step would be to compare not only the intravenous (IV) and e n d o t r a c h e a l (ET) routes, b u t also the i n t r a c a r d i a c (IC) route. The i n t r a c a r d i a c route was s o m e w h a t a l l u d e d to in the article, " P a r a m e d i c Use of I n t r a c a r d i a c Medications in P r e h o s p i t a l Sudden Cardiac Death, " by A m e y et al (7:130-134, 1978). P e r s o n a l c o m m u n i c a t i o n w i t h Dr. A m e y indicates t h a t f u r t h e r information r e g a r d ing this method will be forthcoming. One guestion, however, t h a t arises in the Roberts a r t i c l e is in r e g a r d to v e n t r i c u l a r f i b r i l l a t i o n . The function of epinephrine in v e n t r i c u l a r fibrillation is to convert fine fibrillation into coarse fibrillation so t h a t d e f i b r i l l a t i o n c a n be a c c o m p l i s h e d . The h e a r t r a t e change is g r e a t e s t with IV e p i n e p h r i n e but requires a l m o s t t h r e e m i n u t e s to be" accomplished and the initial c h a n g e is b r a d y c a r d i a ( F i g u r e la). A l t h o u g h the change w i t h ET route is much more rapid, it is not as significant as w i t h the IV route. The question arises, then, as to w h e t h e r a d e l a y of two to t h r e e m i n u t e s in the onset of the t a c h y c a r d i a indicates t h a t k i n d of a d e l a y in the responsiveness of the m y o c a r d i u m to the effect of epinephrine, t h a t is, converting from a vent r i c u l a r f i b r i l l a t i o n to a coarse fibrillation. P e r h a p s the a u t h o r s will comment on w h a t t h e y suspect the effect m i g h t be in this conversion, which route t h e y suspect would be t h e most effective and if they i n t e n d to f u r t h e r e v a l u a t e the use of e p i n e p h r i n e by performing t h i s study on dogs.
70 60
~
°°
~
4o
~
30
~
zo I0 Basalme ~,~ 0
g ~)
=0 -2O 3O -4O -5O -6O I
2
3
4 5
6
•
8
9 I0 II
i2 13 14 r5
Trrne (Minutes)
Fig. l a . The change in heart rate over time compares the ET and IV routes following a dose of 0.09 mg/kg. cal conversion of a fine v e n t r i e u l a r fibrillation to a coarse one by e p i n e p h r i n e reflects direct action on the m y o c a r d i u m by the epinephrine. Consequently, no conclusion ought to be d r a w n from this specific d a t a (ie, h e a r t rate) r e g a r d i n g the efficacy with which endot r a c h e a l l y a d m i n i s t e r e d epinephrine may or m a y not convert a fine v e n t r i c u l a r fibrillation to a coarse one. Indeed, the question raised by Dr. McSwain (ie, d i r e c t m y o c a r d i a l r e s p o n s i v e n e s s to e n d o t r a c h e a l l y a d m i n i s t e r e d epinephrine) is a crucial one. In our laboratory, this a r e a is p r e s e n t l y being actively investigated. P r e l i m i n a r y studies reveal t h a t in dogs epinephrine is efficacious in the conversion of pharmacologic a l l y i n d u c e d c a r d i o v a s c u l a r c o l l a p s e i n t o sinus rhythm with n o r m a l blood pressure. Some results of these e a r l y studies a p p e a r in this issue (p. 53). E a r l y results lead us to believe t h a t the endotracheal route m a y provide an excellent route for a d m i n i s t r a t i o n of e p i n e p h r i n e w h e n a d i r e c t m y o c a r d i a l r e s p o n s e is d e s i r a b l e . H o w e v e r , a l l r e c o m m e n d a t i o n s concerning the clinical use of epinephrine in h u m a n s must a w a i t more c o n t r o l l e d s t u d y of this r o u t e of d r u g administration.
Norman E. McSwain, Jr, MD, F A C S Associate Professor of Surgery Tulane University, New Orleans, Louisiana
Author's Reply Dr. McSwain is indeed correct when he points out t h a t e p i n e p h r i n e is useful in c o n v e r t i n g a fine t y p e v e n t r i c u l a r f i b r i l l a t i o n into a coarse type, which is more a m e n a b l e to electrical defibrillation. Epinephrine h a s o t h e r p h a r m a c o l o g i c a l effects as well. As noted in our paper, epinephrine will increase h e a r t r a t e as well as myocardial c o n t r a c t i l i t y via its positive inotropic and chronotropic actions. The c h a n g e s w h i c h Dr. M c S w a i n refers to a r e c h a n g e s in h e a r t r a t e in e x p e r i m e n t a l a n i m a l s . In fact, e n d o t r a c h e a l l y a d m i n i s t e r e d e p i n e p h r i n e provides a significant increase in h e a r t r a t e w h e n comp a r e d w i t h i n t r a v e n o u s l y a d m i n i s t e r e d epinephrine. This increase in h e a r t rate p r o b a b l y reflects, to some degree at least, peripheral alpha-type actions of e p i n e p h r i n e as the drug is absorbed into the systemic circulation. It is impossible to guess at w h a t proportion of this effect is p e r i p h e r a l a n d w h a t p a r t is due to action directly on t h e myocardium. The pharmacologi-
8:2 (February) 1979
ENOOTRACHEAL AND
INTRAVENOUS EPINEPHRINE {0 09mg/kg)
Michael I. Greenberg, MD Chief Resident, Emergency Medicine The Medical College of Pennsylvania and Hospital Philadelphia, Pennsylvania
Steroids in Near Drowning Questioned To the Editor: In " N e a r Drowning," by Knopp (7:249-254, 1978), on page 253 the a u t h o r states, "There is no evidence to r e c o m m e n d the r o u t i n e use of steroids. Yet, in reduci n g c e r e b r a l e d e m a s e c o n d a r y to a n o x i a in n e a r drowning, steroids are often used and m a y be helpful."
JACEP
91/73
