ORIGINAL CONTRIBUTION atropine; cardiac arrest, pupils
Systemic Atropine Administration During Cardiac Arrest Does Not Cause Fixed and Dilated Pupils Obiectives: Systemic administration of atropine during CPR m a y postpone brain death determination because of its reputed ability to produce fixed and dilated pupils. We studied the effect of atropine administered in the usual doses as an adTunct to endotracheal intubation and for cardiac arrest to determine if it would interfere with neurological assessment. Design: Two groups of children were studied. Group i consisted of 28 patients who received atropine (0.03 ~ 0.003 mg/kg) prior to endotracheal intubation. Group 2 consisted of 21 patients previously w i t h o u t evidence of brainstem disease who suffered a w~tnessed arrest and had prompt return of spontaneous circulation and received an atropine dose of 0.03 z 0.01 mg/kg. Results: In group 1, pupillary size averaged 4.02 z 0.78 m m before and 4.75 m m z .84 m m after atropine (P < .001). In group 2. the pupillary examination was conducted 30 m i n u t e s after return of spontaneous circulation. The pupillary diameter was 4.80 +- 0.91 ram. All pupils were reactive to light in both groups. Conclusion: A t r o p i n e a d m i n i s t r a t i o n in c o n v e n t i o n a l doses causes slight pupillary dilation but does not abolish pupillary light reactivity. [Goetting MG, Contreras E: Systemic atropine administration during cardiac arrest does not cause fixed and dilated pupils. A n n Emerg Med January 1991;20:55-57.]
Mark G Goetting MD*t Elizabeth Contreras MD* Detroit. Michigan From the Deoartments of Pediatrics* and Emergency Medicine.¢ Henry Ford Hosoital Detroit. Mich gan. Received for 9ublication March 21, 1990. Revision receive(] ,June 27. 1990. Acceote(] for oublication July 12, 1990. Presented ar the Society for Academic Emergency Medicine Annual Meeting in Minneapolis. Minnesota, May 1990. Address for reprints: Mark G Goetting, MD, Department of Pediatrics, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202.
INTRODUCTION Assessment of the pupillary light reflex is important after cardiac arrest. This reflex is reported to be a useful discriminator between cognitive survival and vegetative or fatal outcome. 1-3 Its absence is essential for the diagnosis of brain death. Atropine, a potent parasympatholytic, is used to treat cardiac arrest, especially asystole and bradyasystoleA Topical ocular application and severe systen~ic poisoning are known to cause mydriasis and internal ophthalmoplegia.5, 6 It is widely believed that the usual therapeutic doses for cardiac arrest may interfere with the postarrest neurologic assessment by producing reversibly fixed and dilated pupils. 7-9 We prospectively evaluated pupillary diameter and reactivity after atropine administration for endotracheal intubation and cardiac resuscitation. MATERIALS A N D M E T H O D S We studied the impact of IV atropine on the pupil in two groups of critically ill children during a 36-month period. Group 1 comprised consecutive, hemodynamically stable patients undergoing endotracheal intubation for which atropine was used. Immediately before and 30 minutes after ad-. ministration, the right pupil was assessed for diameter and response to light. Dosage, patient weight, and coadministered medications also were noted. Ambient lighting was held constant. A paired t test determined the statistical significance of the change in pupillary diameter, with significance prospectively defined as P < .05. Group 2 comprised consecutive patients with no previous history of brainstem dysfunction who suffered a witnessed cardiac arrest for which atropine was administered and who, 30 minutes after return of spontaneous circulation, had the brainstem reflexes of gag, cough, corneal, and
78/55
Annals of Emergency Medicine
20:1 January 1991
ATROPINE Goetting & Contreras
0culocephalic. We selected these criteria because it would be very unlikely for hypoxic-ischemic injury to abolish pupillary reactivity and spare other brainstem reflexes, allowing a better evaluation of drug effect on pupillary function. 1-3 Bilateral pupillary diameter and light reactivity were noted, again at 30 minutes. Atropine dosage, patient weight, and coadministered medications were recorded. RESULTS Group 1 comprised 28 patients with a median age of 3 years (range, 1 m o n t h to 20 years) and m e d i a n weight of 16.5 kg (range, 4 to 64 kg). The atropine dosage was 0.03 +_ 0.003 mg/kg (mean _+ SD). Concomitant m e d i c a t i o n s included neuromuscular blockers (71%), barbiturates (61%), catecholamines (25%), ketamine (18%), opiates (11%), and diazepam {7%). The average pupillary diameter increased from 4.02 --_ 0.78 to 4.75 ± 0.84 m m (P < :001) (Figure). The diameter did not change i n two patients and decreased in another two. All pupils reacted to light for at least 24 hours after dosing. Group 2 comprised 21 c h i l d r e n . Median age was 2 years (range, 3 m o n t h s to 18 years), and median weight was 14 kg (range, 5 to 81 kg). Patient ECG r h y t h m s were bradyasystole (76%) and asystole (34%). All received epinephrine, and 71% received sodium bicarbonate IV. Atropine dose averaged 0.03 +_ 0.01 mg/ kg. Average time to return of spontaneous circulation was 6.1 _+ 2.2 minutes. At the time of pupil measurement, 62% of patients were on catecholamine drips, usually dopamine at a rate of 10 to 15 Fg/kg.min. Average postarrest pupillary diameter was 4.80 + 0.91 ram. Two patients had anisocoria with a 0.5-ram difference. All pupils were reactive to light. N0ne developed iridoplegia during the first postarrest day. DISCUSSION Despite controlled animal and human studies demonstrating lack of efficacy, to,11 atropine remains a standard drug i n the treatment of some forms of cardiac arrest. 4 Atropine is a selective competitive antagonist of acetylcholine that blocks "(agal tone and decreases saliva p r o d u c t i o n , making it a useful adjunct to tracheal intubation. 12 The standard dose for 20:! January 1991
FIGURE. Effect of atropine on pupil]ary diameter in group 1.
t
¢¢
asystole and bradycardia is 0.01 rag/ kg or as much as 2 mg in an adult. 4 The dose for other uses is as much as 0.05 mg/kg. 13 These doses produce a maximum vagolytic effect. 14 Topical atropine and very high systemic doses cause pupillary dilation and loss of light reactivity.S, 6 In conventional doses, mild mydriasis can occur. Miles described an average pupillary diameter increase of 0.85 m m after 2.0 mg IM in adults, is Herxheimer reported that 0.5, 1.0, and 2.0 mg increased the pupil by approximately 0.3, 0.7, and 1 ram, respectively. ~a Rozsival and Ciganek noted a m a x i m a l pupillary diameter increase of 50% after 4.0 mg. 16 Mirakur found a more robust response, with a pupillary increase of approximately 2 m m after 2 rag. 17 None of these studies commented on light reactivity. The 0.73-mm increase in our patients receiving 0.0287 mg/kg (2 mg in a 70-kg person) is slightly less than that reported in these other studies. However, the peak effect may not have yet occurred. The time to peak effect on the pupil after IV injection is unknown. However, IM administration results in maximum dil a t i o n o c c u r r i n g .at six h o u r s or later.12,17 The delay in peak effect on the pupil may be because of delayed e q u i l i b r a t i o n w i t h the a q u e o u s humor, which functions as a reservoir, accumulating atropine when extracellular concentrations were high, followed by slow redistribution to the iris and ciliary muscle, la If IV dosing has a similar delayed peak effect, we would not have missed druginduced iridoplegia because we followed the patients for 24 hours. Pupillary light reactivity after cardiac arrest may have important clinical significance. In an animal model, brief circulatory arrest causes pupillary c o n s t r i c t i o n in the first minute and is followed by profound dilation that persists until return of Spontaneous circulation. 18 The pupils immediately constrict markedly, returning to their baseline diameter in 20 minutes. Most human beings have midsized pupils during CPR.1 Pupillary reactivity may prognosticate outcome after resuscitation. Jorgensen and Malchow-Moller found Annals of Emergency Medicine
"'
5-1
g
4-t
-
3
o.
2.J
PREDOSE
POSTDOSE
that adults with absent response to light after 12 minutes did not regain consciousness. 1 Others noted that iridoplegia was the best single early predictor of severe disability or death after cardiac arrest.2;3 However, they did not examine most of the patients for at least three hours after resuscitation. More recent studies have refuted the predictive value of the pupillary light response immediately after return of spontaneous Circulation.19,2o The diagnosis of brain death requires that iridoplegia not be drug induced. In the patient with brain injury either due to or associated with cardiac arrest who otherwise appears clinically brain dead, the use of c0nventional doses of systemic atropine should not preclude the, diagnosis. If there is concern that topical or massive s y s t e m i c a d m i n i s t r a t i o n occurred, topical application o f 1% pilocarpine w i l l not cause constriction of the pharmacologically dilated pupil but will reverse mydriasis due to neurologic injury, al Other medications m a y comprom i s e p u p i l l a r y f u n c t i o n . Trimethaphan, a potent ganglionic blocker, can cause mydriasis and iridoplegia, 9,22 but its effect reverses rapidly after discontinuation. Valey expressed c o n c e r n that mydriasis may be caused by sympathomimetics in the postarrest patient, as Most of our patients were on eateeholamine drips after return of spontaneous circulation, yet only four had pupils that were from 6.0 to 6.5 m m and two of them were not on pressors. We studied the effect of atropine on pupillary function in children; the conclusions probably apply to adults as well. The previous studies we cited reported similar findings in a d u l t s ; h o w e v e r , n o n e of t h e s e studies specifically considered adults after cardiac arrest. The dose per weight is lower in adults than in 56/79
ATROPINE Goetting & Contreras
children. Nonetheless, caution must
be exercised when extrapolating our f i n d i n g s to a d u l t s in the postresuscitation state. CONCLUSION Our study demonstrated that conventional doses of IV atropine cause minimal pupillary dilation but not iridoplegia in children. A child with fixed and dilated pupils after arrest probably has suffered hypoxic-~schemic injury. Topical ocular application and systemic overdosing with atropine can be ruled out by pilocarpine drops. REFERENCES
citation (CPR) and emergency cardiac care (ECC). lAMA 1986;255:2939.
and the resting heart rate in man. A m Heart J 1970 i 80:469-474.
5. Shader RI, Greenblatt DJ: Belladonna alkaloids and synthetic anticholinergics: Uses and toxicity, in Shader RI (ed}: Psychiatric Cmnplications of Medical Drugs. New York, Raven Press Publishing, 1972 r p 103-147.
15. Miles S: Some Effects of Injection of Atropine &tiph a t e in Healthy Young Men. Salisbury, Wiltshire, United Kingdom, 1955, Chemical Defense Experimental Establishment, Porton Technical Paper No. 514.
6. Weiner N: Atropine, scopolamine, and related anti muscarinic drugs, in Gilman AG, Goodman LS, Gilman A (eds): Goodman and Gilman's Pharmacological Basis of Therapeutics, ed 6. New York, Macmillan Publishing, 1980, p 130-144.
16. Rozsival P, Ciganek L: Subjective visual functions and objective ocular symptomatology after large doses of atropine. Cesk OftalmoI 1978;34:409 412.
7. Brust JCM: Coma, in Rowland LP (ed): Merrit's Text booli of Neurology, ed 7. Philadelphia, Lea & Febiger, 1984, p 18. 8. Bartlett RL: Resuscitative thoracotomy, in Roberts JR, Hedges JR (eds): Clinical Procedures in Emergency Medicine. Philadelphia, WB Saunders, 1985, p 251. 9. Diringer MN: Perspectives in brain death criteria: Clinician's perspective. Crit Care Rep 1989;1:125-129. 10 Coon GA, Clinton JE, Ruiz E: Use of atyopine for brady-asystolic prehospita] cardiac arrest. Ann Emerg Med 1981;10:462-466.
1. Jorgensen RO, Malchow-Moiler A: Cerebral prognostic signs during cardiopnlmonary resuscitation. Resuscitation 1978;6:217-225.
11. Redding J8, Haynes RR, Thomas JD: Drug therapy in resuscitation from eleetromechanical dissociation. Crit Care Med 1983;11:681-684.
2. Snyder BD, Gumnit RJ, Leppik IE, et al: Neurologic prognosis after cardiopulmonary arrest: IV. Brainstem reflexes. Neurology 1981;31:109271097.
12. Herxheimer A: A comparison of some atropine-like drugs in man, with particular reference to their end-organ specificity. Br J PharmacoI 1958;t3:184-192.
3. Levy DE, Caronna JJ, singer BH, et ah Predicting outcome from hypoxic-ischemic coma. lAMA 1985;253: 1420-i426.
13. Levin RH, Zenk KE: Medication table, in Rudolph AM, Hoffman lIE (eds): Pediatrics, ed 17. Norwalk, Connecticut, Appleton-Century-Crofts, 1982, p 789.
4. Standards and guidelines for cardiopulmonary resus-
14. O'Rourke GW, Greene NM: Autonomic blockade
80/57
Annals of Emergency Medicine
17. Mirakur RK: Comparative study of the effects of orai and IM atropine and hyoscine in volunteers. Br ] Anaesth 1978;50:591-598. 18. Kapp J, Paulson G: Pupil!ary changes induced by circulatory arrest. Neurology 1966;i6:226-229. 19. Nichols DG, Kettrick RD, Swedlow DB, et al: Factors influencing outcome of cardiopulmonary resuscitation in children. Pediatr Emerg Care 1986;12:1-5. 20. Bertini G, Margheri M, Giglioli C, et ah Prognostic significance of early clinical manifestations in post-anoxic coma: A retrospective study of 58 patients resuscitated after prehospital cardiac arrest. Crit Care Med 1989;17:627-633. 2i. O'Connor PS, M u m m a JV: Atropine toxicity. A m J OphthalmoI 1985;99:613-614. 22. Taylor P: Ganglionic s t i m u l a t i n g and blocking agents, in Gihnan AG, Goodman L8, Gilman A {eds}: Goodman and Gilman's Pharmacological Basis of Therapeutics, ed 6. New York, Macmillan Publishing, 1980, p 215-217. 23. Valey SC: Acute and semiacnte management of cardiac arrest. Crit Care Clin 1989;5:643-657.
20:1 January 1991
Systemic Atropine Administration During Cardiac Arrest Does Not Cause Fixed and Dilated Pupils Obiectives: Systemic administration of atropine during CPR m a y postpone brain death determination because of its reputed ability to produce fixed and dilated pupils. We studied the effect of atropine administered in the usual doses as an adTunct to endotracheal intubation and for cardiac arrest to determine if it would interfere with neurological assessment. Design: Two groups of children were studied. Group i consisted of 28 patients who received atropine (0.03 ~ 0.003 mg/kg) prior to endotracheal intubation. Group 2 consisted of 21 patients previously w i t h o u t evidence of brainstem disease who suffered a w~tnessed arrest and had prompt return of spontaneous circulation and received an atropine dose of 0.03 z 0.01 mg/kg. Results: In group 1, pupillary size averaged 4.02 z 0.78 m m before and 4.75 m m z .84 m m after atropine (P < .001). In group 2. the pupillary examination was conducted 30 m i n u t e s after return of spontaneous circulation. The pupillary diameter was 4.80 +- 0.91 ram. All pupils were reactive to light in both groups. Conclusion: A t r o p i n e a d m i n i s t r a t i o n in c o n v e n t i o n a l doses causes slight pupillary dilation but does not abolish pupillary light reactivity. [Goetting MG, Contreras E: Systemic atropine administration during cardiac arrest does not cause fixed and dilated pupils. A n n Emerg Med January 1991;20:55-57.]
Mark G Goetting MD*t Elizabeth Contreras MD* Detroit. Michigan From the Deoartments of Pediatrics* and Emergency Medicine.¢ Henry Ford Hosoital Detroit. Mich gan. Received for 9ublication March 21, 1990. Revision receive(] ,June 27. 1990. Acceote(] for oublication July 12, 1990. Presented ar the Society for Academic Emergency Medicine Annual Meeting in Minneapolis. Minnesota, May 1990. Address for reprints: Mark G Goetting, MD, Department of Pediatrics, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202.
INTRODUCTION Assessment of the pupillary light reflex is important after cardiac arrest. This reflex is reported to be a useful discriminator between cognitive survival and vegetative or fatal outcome. 1-3 Its absence is essential for the diagnosis of brain death. Atropine, a potent parasympatholytic, is used to treat cardiac arrest, especially asystole and bradyasystoleA Topical ocular application and severe systen~ic poisoning are known to cause mydriasis and internal ophthalmoplegia.5, 6 It is widely believed that the usual therapeutic doses for cardiac arrest may interfere with the postarrest neurologic assessment by producing reversibly fixed and dilated pupils. 7-9 We prospectively evaluated pupillary diameter and reactivity after atropine administration for endotracheal intubation and cardiac resuscitation. MATERIALS A N D M E T H O D S We studied the impact of IV atropine on the pupil in two groups of critically ill children during a 36-month period. Group 1 comprised consecutive, hemodynamically stable patients undergoing endotracheal intubation for which atropine was used. Immediately before and 30 minutes after ad-. ministration, the right pupil was assessed for diameter and response to light. Dosage, patient weight, and coadministered medications also were noted. Ambient lighting was held constant. A paired t test determined the statistical significance of the change in pupillary diameter, with significance prospectively defined as P < .05. Group 2 comprised consecutive patients with no previous history of brainstem dysfunction who suffered a witnessed cardiac arrest for which atropine was administered and who, 30 minutes after return of spontaneous circulation, had the brainstem reflexes of gag, cough, corneal, and
78/55
Annals of Emergency Medicine
20:1 January 1991
ATROPINE Goetting & Contreras
0culocephalic. We selected these criteria because it would be very unlikely for hypoxic-ischemic injury to abolish pupillary reactivity and spare other brainstem reflexes, allowing a better evaluation of drug effect on pupillary function. 1-3 Bilateral pupillary diameter and light reactivity were noted, again at 30 minutes. Atropine dosage, patient weight, and coadministered medications were recorded. RESULTS Group 1 comprised 28 patients with a median age of 3 years (range, 1 m o n t h to 20 years) and m e d i a n weight of 16.5 kg (range, 4 to 64 kg). The atropine dosage was 0.03 +_ 0.003 mg/kg (mean _+ SD). Concomitant m e d i c a t i o n s included neuromuscular blockers (71%), barbiturates (61%), catecholamines (25%), ketamine (18%), opiates (11%), and diazepam {7%). The average pupillary diameter increased from 4.02 --_ 0.78 to 4.75 ± 0.84 m m (P < :001) (Figure). The diameter did not change i n two patients and decreased in another two. All pupils reacted to light for at least 24 hours after dosing. Group 2 comprised 21 c h i l d r e n . Median age was 2 years (range, 3 m o n t h s to 18 years), and median weight was 14 kg (range, 5 to 81 kg). Patient ECG r h y t h m s were bradyasystole (76%) and asystole (34%). All received epinephrine, and 71% received sodium bicarbonate IV. Atropine dose averaged 0.03 +_ 0.01 mg/ kg. Average time to return of spontaneous circulation was 6.1 _+ 2.2 minutes. At the time of pupil measurement, 62% of patients were on catecholamine drips, usually dopamine at a rate of 10 to 15 Fg/kg.min. Average postarrest pupillary diameter was 4.80 + 0.91 ram. Two patients had anisocoria with a 0.5-ram difference. All pupils were reactive to light. N0ne developed iridoplegia during the first postarrest day. DISCUSSION Despite controlled animal and human studies demonstrating lack of efficacy, to,11 atropine remains a standard drug i n the treatment of some forms of cardiac arrest. 4 Atropine is a selective competitive antagonist of acetylcholine that blocks "(agal tone and decreases saliva p r o d u c t i o n , making it a useful adjunct to tracheal intubation. 12 The standard dose for 20:! January 1991
FIGURE. Effect of atropine on pupil]ary diameter in group 1.
t
¢¢
asystole and bradycardia is 0.01 rag/ kg or as much as 2 mg in an adult. 4 The dose for other uses is as much as 0.05 mg/kg. 13 These doses produce a maximum vagolytic effect. 14 Topical atropine and very high systemic doses cause pupillary dilation and loss of light reactivity.S, 6 In conventional doses, mild mydriasis can occur. Miles described an average pupillary diameter increase of 0.85 m m after 2.0 mg IM in adults, is Herxheimer reported that 0.5, 1.0, and 2.0 mg increased the pupil by approximately 0.3, 0.7, and 1 ram, respectively. ~a Rozsival and Ciganek noted a m a x i m a l pupillary diameter increase of 50% after 4.0 mg. 16 Mirakur found a more robust response, with a pupillary increase of approximately 2 m m after 2 rag. 17 None of these studies commented on light reactivity. The 0.73-mm increase in our patients receiving 0.0287 mg/kg (2 mg in a 70-kg person) is slightly less than that reported in these other studies. However, the peak effect may not have yet occurred. The time to peak effect on the pupil after IV injection is unknown. However, IM administration results in maximum dil a t i o n o c c u r r i n g .at six h o u r s or later.12,17 The delay in peak effect on the pupil may be because of delayed e q u i l i b r a t i o n w i t h the a q u e o u s humor, which functions as a reservoir, accumulating atropine when extracellular concentrations were high, followed by slow redistribution to the iris and ciliary muscle, la If IV dosing has a similar delayed peak effect, we would not have missed druginduced iridoplegia because we followed the patients for 24 hours. Pupillary light reactivity after cardiac arrest may have important clinical significance. In an animal model, brief circulatory arrest causes pupillary c o n s t r i c t i o n in the first minute and is followed by profound dilation that persists until return of Spontaneous circulation. 18 The pupils immediately constrict markedly, returning to their baseline diameter in 20 minutes. Most human beings have midsized pupils during CPR.1 Pupillary reactivity may prognosticate outcome after resuscitation. Jorgensen and Malchow-Moller found Annals of Emergency Medicine
"'
5-1
g
4-t
-
3
o.
2.J
PREDOSE
POSTDOSE
that adults with absent response to light after 12 minutes did not regain consciousness. 1 Others noted that iridoplegia was the best single early predictor of severe disability or death after cardiac arrest.2;3 However, they did not examine most of the patients for at least three hours after resuscitation. More recent studies have refuted the predictive value of the pupillary light response immediately after return of spontaneous Circulation.19,2o The diagnosis of brain death requires that iridoplegia not be drug induced. In the patient with brain injury either due to or associated with cardiac arrest who otherwise appears clinically brain dead, the use of c0nventional doses of systemic atropine should not preclude the, diagnosis. If there is concern that topical or massive s y s t e m i c a d m i n i s t r a t i o n occurred, topical application o f 1% pilocarpine w i l l not cause constriction of the pharmacologically dilated pupil but will reverse mydriasis due to neurologic injury, al Other medications m a y comprom i s e p u p i l l a r y f u n c t i o n . Trimethaphan, a potent ganglionic blocker, can cause mydriasis and iridoplegia, 9,22 but its effect reverses rapidly after discontinuation. Valey expressed c o n c e r n that mydriasis may be caused by sympathomimetics in the postarrest patient, as Most of our patients were on eateeholamine drips after return of spontaneous circulation, yet only four had pupils that were from 6.0 to 6.5 m m and two of them were not on pressors. We studied the effect of atropine on pupillary function in children; the conclusions probably apply to adults as well. The previous studies we cited reported similar findings in a d u l t s ; h o w e v e r , n o n e of t h e s e studies specifically considered adults after cardiac arrest. The dose per weight is lower in adults than in 56/79
ATROPINE Goetting & Contreras
children. Nonetheless, caution must
be exercised when extrapolating our f i n d i n g s to a d u l t s in the postresuscitation state. CONCLUSION Our study demonstrated that conventional doses of IV atropine cause minimal pupillary dilation but not iridoplegia in children. A child with fixed and dilated pupils after arrest probably has suffered hypoxic-~schemic injury. Topical ocular application and systemic overdosing with atropine can be ruled out by pilocarpine drops. REFERENCES
citation (CPR) and emergency cardiac care (ECC). lAMA 1986;255:2939.
and the resting heart rate in man. A m Heart J 1970 i 80:469-474.
5. Shader RI, Greenblatt DJ: Belladonna alkaloids and synthetic anticholinergics: Uses and toxicity, in Shader RI (ed}: Psychiatric Cmnplications of Medical Drugs. New York, Raven Press Publishing, 1972 r p 103-147.
15. Miles S: Some Effects of Injection of Atropine &tiph a t e in Healthy Young Men. Salisbury, Wiltshire, United Kingdom, 1955, Chemical Defense Experimental Establishment, Porton Technical Paper No. 514.
6. Weiner N: Atropine, scopolamine, and related anti muscarinic drugs, in Gilman AG, Goodman LS, Gilman A (eds): Goodman and Gilman's Pharmacological Basis of Therapeutics, ed 6. New York, Macmillan Publishing, 1980, p 130-144.
16. Rozsival P, Ciganek L: Subjective visual functions and objective ocular symptomatology after large doses of atropine. Cesk OftalmoI 1978;34:409 412.
7. Brust JCM: Coma, in Rowland LP (ed): Merrit's Text booli of Neurology, ed 7. Philadelphia, Lea & Febiger, 1984, p 18. 8. Bartlett RL: Resuscitative thoracotomy, in Roberts JR, Hedges JR (eds): Clinical Procedures in Emergency Medicine. Philadelphia, WB Saunders, 1985, p 251. 9. Diringer MN: Perspectives in brain death criteria: Clinician's perspective. Crit Care Rep 1989;1:125-129. 10 Coon GA, Clinton JE, Ruiz E: Use of atyopine for brady-asystolic prehospita] cardiac arrest. Ann Emerg Med 1981;10:462-466.
1. Jorgensen RO, Malchow-Moiler A: Cerebral prognostic signs during cardiopnlmonary resuscitation. Resuscitation 1978;6:217-225.
11. Redding J8, Haynes RR, Thomas JD: Drug therapy in resuscitation from eleetromechanical dissociation. Crit Care Med 1983;11:681-684.
2. Snyder BD, Gumnit RJ, Leppik IE, et al: Neurologic prognosis after cardiopulmonary arrest: IV. Brainstem reflexes. Neurology 1981;31:109271097.
12. Herxheimer A: A comparison of some atropine-like drugs in man, with particular reference to their end-organ specificity. Br J PharmacoI 1958;t3:184-192.
3. Levy DE, Caronna JJ, singer BH, et ah Predicting outcome from hypoxic-ischemic coma. lAMA 1985;253: 1420-i426.
13. Levin RH, Zenk KE: Medication table, in Rudolph AM, Hoffman lIE (eds): Pediatrics, ed 17. Norwalk, Connecticut, Appleton-Century-Crofts, 1982, p 789.
4. Standards and guidelines for cardiopulmonary resus-
14. O'Rourke GW, Greene NM: Autonomic blockade
80/57
Annals of Emergency Medicine
17. Mirakur RK: Comparative study of the effects of orai and IM atropine and hyoscine in volunteers. Br ] Anaesth 1978;50:591-598. 18. Kapp J, Paulson G: Pupil!ary changes induced by circulatory arrest. Neurology 1966;i6:226-229. 19. Nichols DG, Kettrick RD, Swedlow DB, et al: Factors influencing outcome of cardiopulmonary resuscitation in children. Pediatr Emerg Care 1986;12:1-5. 20. Bertini G, Margheri M, Giglioli C, et ah Prognostic significance of early clinical manifestations in post-anoxic coma: A retrospective study of 58 patients resuscitated after prehospital cardiac arrest. Crit Care Med 1989;17:627-633. 2i. O'Connor PS, M u m m a JV: Atropine toxicity. A m J OphthalmoI 1985;99:613-614. 22. Taylor P: Ganglionic s t i m u l a t i n g and blocking agents, in Gihnan AG, Goodman L8, Gilman A {eds}: Goodman and Gilman's Pharmacological Basis of Therapeutics, ed 6. New York, Macmillan Publishing, 1980, p 215-217. 23. Valey SC: Acute and semiacnte management of cardiac arrest. Crit Care Clin 1989;5:643-657.
20:1 January 1991
