CASE REPORT epinephrine, overdose; labetalol
Labetalol in the Treatment of Epinephrine Overdose A 31-year-old man being treated for asthma accidently received 3 mg SQ epinephrine. He began retching and vomiting and developed agitation and profuse diaphoresis. He was treated with 5 mg IV labetalol. His symptoms improved significantly, and he required no further treatment. Although he felt a transient increase in his respiratory effort shortly after administration of the drug, he did not develop wheezing or require additional therapy for bronchospasm. The B-blocking effect of labetalol is greater than the antagonism. The patient exhibited evidence of mild a stimulation due to incomplete blockade. This is consistent with previous studies in that labetalol tends to less completely antagonize the ~ effects of a mixed ~/~ agonist, resulting in a net clinical picture of mild ~ agonism. [Larsen LS, Larsen A: Labetalol in the treatment of epinephrine overdose. Ann Emerg Med June 1990:19:680-682.] INTRODUCTION Epinephrine overdose is u n c o m m o n and almost exclusively related to medication errors. Epinephrine has both ~- and ~-agonist actions, and t r e a t m e n t should be directed at b o t h effects. Labetalol, an IV a- and f3-blocker, theoretically is an appropriate agent for treatment. We report a case of accidental epinephrine overdose treated in the prehospital setting with, labetalol.
L Scott Larsen, MD, FACEP Somerville and Morristown, New Jersey Anna Larsen Raritan, New Jersey From Somerset Medical Center, Somerville, New Jersey; the Residency in Emergency Medicine, Morristown, New Jersey; and Robert Wood Johnson Pharmaceutical Research Institute, Raritan, New Jersey. Received for publication November 15, 1989. Accepted for publication December 18, 1989. Address for reprints: L Scott Larsen, MD, FACER 13 Pleasant Way, Flemington, New Jersey 08822.
CASE REPORT A 31-year-old man with a history of mild asthma presented to a walk-in urgent medical care facility complaining of difficulty in breathing. He had been seen several days earlier by his private physician and started on theophylline and erythromycin. He had asthma since childhood but currently did not require any daily medication. The patient denied other medical problems but stated later that he had a history of "strong reactions" to epinephrine. He had no prior history of cardiovascular disease. He was treated at the urgent care center with nebulized metaproterenol and epinephrine. His vital signs were blood pressure of 132/78 m m Hg; pulse, 87; and respirations, 22. A medication error occurred, and the patient received 3 mg rather than 0.3 mg SQ epinephrine. The patient rapidly became pale and diaphoretic and began retching and vomiting. Vital signs taken within five minutes of the epinephrine administration were blood pressure, 130/50 m m Hg; and respirations, 36. No pulse was noted in the records. We were alerted to the incident by the treating physician before our mobile intensive care unit (MICU) was dispatched; therefore, the nurses staffing the MICU were given labetalol to take with them. When the MICU arrived on scene, the patient was alert but moaning and agitated. He was pale and profusely diaphoretic. He had a sinus tachycardia with a cardiac monitor rate of 142 without ectopy. His blood pressure was 110/42 m m Hg, and respirations were 28. His lungs were clear, and the remainder of the examination was normal except as noted. An IV line of lactated Ringer's~had been started before MICU arrival. The patient was given 5 mg IV labetalol. Although this was one fourth of the recommended initial 20-mg dose for hypertension, we were concerned about elieiting rebound bronchospasm. Because there is no known optimal dose for this indication, we thought that it would be prudent to start with
19:6 June 1990
Annals of Emergency Medicine
680/109
LABETAL©L Larsen & Larsen
a low dose and administer additional medication as necessary to achieve the desired degree of a n t a g o n i s m w i t h o u t complicating the patient's p u l m o n a r y status. The patient responded during the next five minutes with a significant decrease in nausea, vomiting, and diaphoresis. His color improved. He was alert and felt better but developed weak peripheral pulses that were difficult to obtain in the moving ambulance. Shortly after the medication was given, he developed chest tightness that felt to him like asthma. He had no pain. The tightness increased with inspiration and did not appear to be of cardiac origin. This feeling, however, was transient, and he showed no respiratory distress. On arrival at the emergency department 16 minutes after labetalol administration, he was alert, oriented, and in no distress. His radial pulses were still thready and this was thought tO be due to vasoconstriction. His blood pressure was 154/98 m m Hg; pulse, from 80 to 90 and regular; and respirations, 24. His lungs were clear. His hands were still pale, but this gradually resolved. The remainder of the patient's examination was unremarkable. He was observed for two hours, during which he remained asymptomatic, and subsequently discharged.
DISCUSSION E p i n e p h r i n e is u s e d to t r e a t a s t h m a because of its B2 effect, which causes bronchodilatation. It is not [3-selective and also causes stimulation of [31 receptors with inotropic and chronotropic effects on the heart. The a effects consist mainly of vasoconstriction. The net effect is a reduction of blood flow to the skin and gut with an increase in flow to voluntary muscle.L2 The response to therapeutic epinephrine doses is variable, and blood pressure and pulse may decrease in asthmatics being treated, especially older patients. Peak levels are reached 20 to 40 minutes after a SQ injection, and the bronchodilatory effect lasts a maxim u m of four hours. 2 Labetalol is both an a- and [3-comp e t i t i v e a n t a g o n i s t . Its [3 a c t i o n predominates with a ratio of 6.9:1 B:a in the IV form. The oral form differs with a [3:a ratio of 3:1. 3 Labetalol nonselectively blocks [31- and [32-receptor sites. There is no significant 110/681
[31-agonist activity, but there may be some intrinsic [32-agonist activity. Labetalol's a-blocking activity is limited to postsynaptic al antagonism with no c¢2 activity. There is also evidence of direct v a s o d i l a t o r y and membrane-stabilizing effects. After IV infusion for hypertension, a significant decrease occurs w i t h i n five minutes, with maximal effect occurring in 20 to 40 minutes. 4 Labetalol has been studied for its effect in blocking epinephrine-induced physiological changes, but this is the first report of which we are aware of the clinical use of labetalol to a n t a g o n i z e e p i n e p h r i n e . T h e studies, which are summarized below, must be interpreted with caution because both labetalol and epinephrine have dose-dependent response profiles and their interaction is complex. Epinephrine, in low doses, will cause a decrease in blood pressure due to stimulation of the [3~receptors causing vasodilatation. In moderate doses generally used for therapy there is usually an increase in the systolic pressure with a decrease in the diastolic. In high doses the a-mediated vasoconstrictive effects predominate and both systolic and diastolic pressures rise. 5 Labetalol has a stronger ~ than a effect at all doses, but as the dose rises the [3 effects dominate. 3 In one study, patients pretreated orally with either propranolol or labetalol were given epinephrine infusions for five minutes at 30-minute intervals. 6 Patients treated with the [3 antagonist propranolol had an increase in diastolic blood pressure. Those treated with labetalol had a mild decrease in diastolic blood pressure, and the untreated group had an even greater decrease. The pressor effect of the propranolol group was attributed to incomplete a antagonism in the setting of more completely opposed [3-mediated v a s o d i l a t a t i o n . Systolic blood pressures were not reported. The dose of epinephrine (2.5 txg/min for five minutes for a total of 0.0125 mg) was small. This, however, may not be clinically relevant bec a u s e the net a:[3 effect of epinephrine changes with the dose as noted above. In a more relevant study 7 using doses of epinephrine closer to the therapeutic range, healthy volunteers were subjected to a progressive infusion of 8, 16, and 32 ixg/min epiAnnals of Emergency Medicine
nephrine for four minutes at each level, resulting in a total dose of 0.26 mg over 12 minutes. There was a dose-related rise in the systolic blood pressure. The diastolic blood pressure decreased initially, returning to baseline range during the 32 ~g/min rate. The subjects were later pretreated with 1 mg/kg IV labetalol and the identical infusion was administered. The effect on diastolic blood pressure became a consistent pressor response after labetalol pretreatment. This effect can be explained by the blockade of the [32-vasodilatory receptors with less complete antagonism of the a-mediated vasoconstriction. There was also a concomitant decrease in heart rate as expected with [3 blockade. The effect on diastolic pressure is similar to the increase seen when propranolol is used to antagonize epinephrine infusions except that the labetalol did not produce the degree of diastolic pressor response seen with propranolol. Labetalol has been used in the treatment of other conditions arising from sympathomimetic administration; the most notable of these is cocaine overdose. Propranolol has been reported to be useful in the treatment of cocaine overdose.S, 9 However, hypertension attributed to unopposed a stimulation was reported with this modality, lo Although the cause of the hypertension was questioned,~ this theory appears to be strongly supported by the studies with epinephrine infusions. Subsequently, treatment with labetalol has proved efficacious w i t h o u t a hypertensive response in two cases. 12,13 Labetalol has been used to treat pseudoephedrine-induced hypertension, 14 hyperadrenergic states secondary to tetanus ls-17 and pheochromocytoma, TM and postoperative hypertension.19 Hypertensive emergencies remain the primary indication of labetalol therapy. 2o
SUMMARY It will be argued that the half-life of epinephrine is short and therefore symptoms will be self-limiting. If we elect to treat only life-threatening emergencies, then a majority of our patients will go unaided. To a patient, symptomatic treatment is of foremost importance; to this end, we were successful. Severely symptomatic individuals require treatment. In those with significant arrhythmias or 19:6 June 1990
ischemic cardiac symptoms, this consideration is even m o r e imperative. L a b e t a l o l w a s e f f i c a c i o u s in treating the symptoms of e p i nephrine overdose in our patient. Extreme c a u t i o n and titration are req u i r e d to p r e v e n t r e b o u n d bronc h o s p a s m . In p a t i e n t s w i t h m i l d s y m p t o m s , t h e risks o u t w e i g h the benefits, and its use is not recommended. T h e u s e of t h i s m e d i c a t i o n in treating hypertensive crisis has been demonstrated. Its role in managing cocaine intoxication as w e l l as other hyperadrenergic states is b e c o m i n g delineated. Incomplete a blockade in the face of m o r e complete J3 blockade remains a potential problem. The clin i c i a n m u s t be aware of this and monitor the patient for signs of excess ~ stimulation. REFERENCES 1. Myers FH, Jawetz E, Goldfien A: Review of Medical Pharmacology, ed 6. Los Altos, California, Lange Medical Publications, 1978, p 79-89. 2. Cydulka R, Davison R, Grammer L, et ah The use of epinephrine in the treatment of older
19:6 June 1990
adult asthmatics. Ann Emerg Med 1988;17: 322-326. 3. Richards DA, Prichard BNC, Boakes AJ, et al: Pharmacological basis for antihypertensive effects of intravenous labetalol. Br Heart J 1977;39:99-106. 4. MacCarthy EP, Bloomfield SS: Labetaloh A review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy 1983;3:193-219. 5. Goodman AG, Gillman LS, Rail TW, et ah The Pharmacological Basis of Therapeutics, ed 7. New York, Macmillan Publishing Co, 1985, p 151-158. 6. Doshi BS, Kulkarni RD, Dattani KK, et ah Effects of labetalol and propranolol on responses to adrenaline infusion in healthy volunteers. Inv l Clin Pharmacol Res 1984;4:29-33.
11. Silverstein W, Lewin N, Goldfrank L: Management of the cocaine intoxicated patient (letter). Ann Emerg Med 1987;16:234. 12. Dusenberry SJ, Hicks MJ, Mariani PJ: Labetalol treatment of cocaine toxicity (letter}. Ann Emerg Med 1987;16:235. 13. Gay G, Loper KA: The use of labetalol in the management of cocaine crisis. Ann Emerg Med 1988;17:282-283. 14. Mariani PJ: Pseudoephedrine-induced hypertensive emergency: Treatment with labetalol. Am J Emerg Med 1986;4:141-142. 15. Domenighetti GM, 8avary G, Stricker H: Hyperadrenergic syndrome in severe tetanus: Extreme rise in catecholamines responsive to labetalol. Br Med J 1986;288:1483-1484. 16. Dundee JW, Morrow WI:K: Labetalol in severe tetanus. Br Med f 1979;1:1121-1122.
7. Richards DA, Prichard BNC, Hernandez R: Circulatory effects of noradrenaline and adrenaline before and after labetalol. Br J Clin Pharmacol 1979;7:371-378.
17. Wesley AG, Hariparasad D, Pataher M, et ah Labetalol in tetanus: The treatment of sympathetic nervous system overactivity. Anesthesia 1983;38:243-249.
8. Gay GR: Clinical management of acute and chronic cocaine poisoning. Ann Emerg Med 1982;11:562-572.
18. Navaratnarajah M, White DC: Labetalol and pheochromocytoma. Br J Anaesth 1984;56:1179.
9. Rappoh RT, Gay G, Inaba DS, et ah Propranolol in the treatment of cardiopressor effects of cocaine (letter}. N Engl J Med 1976;295: 488. 10. Ramoska E, Sacchetti AD: Propranolol-induced hypertension in treatment of cocaine intoxication. Ann Emerg Med 1985;14:1112-1113.
Annals of Emergency Medicine
19. Leslie JB, Kalayjian RW, Sirgo MA, et ah Intravenous labetalol for treatment of postoperative hypertension. Anesthesiology 1987;67:3: 413-416. 20. Wilson DJ, Wallin JD, Vlachakis ND, et ah Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies. Am 1 Med 1983;75:95-102.
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Labetalol in the Treatment of Epinephrine Overdose A 31-year-old man being treated for asthma accidently received 3 mg SQ epinephrine. He began retching and vomiting and developed agitation and profuse diaphoresis. He was treated with 5 mg IV labetalol. His symptoms improved significantly, and he required no further treatment. Although he felt a transient increase in his respiratory effort shortly after administration of the drug, he did not develop wheezing or require additional therapy for bronchospasm. The B-blocking effect of labetalol is greater than the antagonism. The patient exhibited evidence of mild a stimulation due to incomplete blockade. This is consistent with previous studies in that labetalol tends to less completely antagonize the ~ effects of a mixed ~/~ agonist, resulting in a net clinical picture of mild ~ agonism. [Larsen LS, Larsen A: Labetalol in the treatment of epinephrine overdose. Ann Emerg Med June 1990:19:680-682.] INTRODUCTION Epinephrine overdose is u n c o m m o n and almost exclusively related to medication errors. Epinephrine has both ~- and ~-agonist actions, and t r e a t m e n t should be directed at b o t h effects. Labetalol, an IV a- and f3-blocker, theoretically is an appropriate agent for treatment. We report a case of accidental epinephrine overdose treated in the prehospital setting with, labetalol.
L Scott Larsen, MD, FACEP Somerville and Morristown, New Jersey Anna Larsen Raritan, New Jersey From Somerset Medical Center, Somerville, New Jersey; the Residency in Emergency Medicine, Morristown, New Jersey; and Robert Wood Johnson Pharmaceutical Research Institute, Raritan, New Jersey. Received for publication November 15, 1989. Accepted for publication December 18, 1989. Address for reprints: L Scott Larsen, MD, FACER 13 Pleasant Way, Flemington, New Jersey 08822.
CASE REPORT A 31-year-old man with a history of mild asthma presented to a walk-in urgent medical care facility complaining of difficulty in breathing. He had been seen several days earlier by his private physician and started on theophylline and erythromycin. He had asthma since childhood but currently did not require any daily medication. The patient denied other medical problems but stated later that he had a history of "strong reactions" to epinephrine. He had no prior history of cardiovascular disease. He was treated at the urgent care center with nebulized metaproterenol and epinephrine. His vital signs were blood pressure of 132/78 m m Hg; pulse, 87; and respirations, 22. A medication error occurred, and the patient received 3 mg rather than 0.3 mg SQ epinephrine. The patient rapidly became pale and diaphoretic and began retching and vomiting. Vital signs taken within five minutes of the epinephrine administration were blood pressure, 130/50 m m Hg; and respirations, 36. No pulse was noted in the records. We were alerted to the incident by the treating physician before our mobile intensive care unit (MICU) was dispatched; therefore, the nurses staffing the MICU were given labetalol to take with them. When the MICU arrived on scene, the patient was alert but moaning and agitated. He was pale and profusely diaphoretic. He had a sinus tachycardia with a cardiac monitor rate of 142 without ectopy. His blood pressure was 110/42 m m Hg, and respirations were 28. His lungs were clear, and the remainder of the examination was normal except as noted. An IV line of lactated Ringer's~had been started before MICU arrival. The patient was given 5 mg IV labetalol. Although this was one fourth of the recommended initial 20-mg dose for hypertension, we were concerned about elieiting rebound bronchospasm. Because there is no known optimal dose for this indication, we thought that it would be prudent to start with
19:6 June 1990
Annals of Emergency Medicine
680/109
LABETAL©L Larsen & Larsen
a low dose and administer additional medication as necessary to achieve the desired degree of a n t a g o n i s m w i t h o u t complicating the patient's p u l m o n a r y status. The patient responded during the next five minutes with a significant decrease in nausea, vomiting, and diaphoresis. His color improved. He was alert and felt better but developed weak peripheral pulses that were difficult to obtain in the moving ambulance. Shortly after the medication was given, he developed chest tightness that felt to him like asthma. He had no pain. The tightness increased with inspiration and did not appear to be of cardiac origin. This feeling, however, was transient, and he showed no respiratory distress. On arrival at the emergency department 16 minutes after labetalol administration, he was alert, oriented, and in no distress. His radial pulses were still thready and this was thought tO be due to vasoconstriction. His blood pressure was 154/98 m m Hg; pulse, from 80 to 90 and regular; and respirations, 24. His lungs were clear. His hands were still pale, but this gradually resolved. The remainder of the patient's examination was unremarkable. He was observed for two hours, during which he remained asymptomatic, and subsequently discharged.
DISCUSSION E p i n e p h r i n e is u s e d to t r e a t a s t h m a because of its B2 effect, which causes bronchodilatation. It is not [3-selective and also causes stimulation of [31 receptors with inotropic and chronotropic effects on the heart. The a effects consist mainly of vasoconstriction. The net effect is a reduction of blood flow to the skin and gut with an increase in flow to voluntary muscle.L2 The response to therapeutic epinephrine doses is variable, and blood pressure and pulse may decrease in asthmatics being treated, especially older patients. Peak levels are reached 20 to 40 minutes after a SQ injection, and the bronchodilatory effect lasts a maxim u m of four hours. 2 Labetalol is both an a- and [3-comp e t i t i v e a n t a g o n i s t . Its [3 a c t i o n predominates with a ratio of 6.9:1 B:a in the IV form. The oral form differs with a [3:a ratio of 3:1. 3 Labetalol nonselectively blocks [31- and [32-receptor sites. There is no significant 110/681
[31-agonist activity, but there may be some intrinsic [32-agonist activity. Labetalol's a-blocking activity is limited to postsynaptic al antagonism with no c¢2 activity. There is also evidence of direct v a s o d i l a t o r y and membrane-stabilizing effects. After IV infusion for hypertension, a significant decrease occurs w i t h i n five minutes, with maximal effect occurring in 20 to 40 minutes. 4 Labetalol has been studied for its effect in blocking epinephrine-induced physiological changes, but this is the first report of which we are aware of the clinical use of labetalol to a n t a g o n i z e e p i n e p h r i n e . T h e studies, which are summarized below, must be interpreted with caution because both labetalol and epinephrine have dose-dependent response profiles and their interaction is complex. Epinephrine, in low doses, will cause a decrease in blood pressure due to stimulation of the [3~receptors causing vasodilatation. In moderate doses generally used for therapy there is usually an increase in the systolic pressure with a decrease in the diastolic. In high doses the a-mediated vasoconstrictive effects predominate and both systolic and diastolic pressures rise. 5 Labetalol has a stronger ~ than a effect at all doses, but as the dose rises the [3 effects dominate. 3 In one study, patients pretreated orally with either propranolol or labetalol were given epinephrine infusions for five minutes at 30-minute intervals. 6 Patients treated with the [3 antagonist propranolol had an increase in diastolic blood pressure. Those treated with labetalol had a mild decrease in diastolic blood pressure, and the untreated group had an even greater decrease. The pressor effect of the propranolol group was attributed to incomplete a antagonism in the setting of more completely opposed [3-mediated v a s o d i l a t a t i o n . Systolic blood pressures were not reported. The dose of epinephrine (2.5 txg/min for five minutes for a total of 0.0125 mg) was small. This, however, may not be clinically relevant bec a u s e the net a:[3 effect of epinephrine changes with the dose as noted above. In a more relevant study 7 using doses of epinephrine closer to the therapeutic range, healthy volunteers were subjected to a progressive infusion of 8, 16, and 32 ixg/min epiAnnals of Emergency Medicine
nephrine for four minutes at each level, resulting in a total dose of 0.26 mg over 12 minutes. There was a dose-related rise in the systolic blood pressure. The diastolic blood pressure decreased initially, returning to baseline range during the 32 ~g/min rate. The subjects were later pretreated with 1 mg/kg IV labetalol and the identical infusion was administered. The effect on diastolic blood pressure became a consistent pressor response after labetalol pretreatment. This effect can be explained by the blockade of the [32-vasodilatory receptors with less complete antagonism of the a-mediated vasoconstriction. There was also a concomitant decrease in heart rate as expected with [3 blockade. The effect on diastolic pressure is similar to the increase seen when propranolol is used to antagonize epinephrine infusions except that the labetalol did not produce the degree of diastolic pressor response seen with propranolol. Labetalol has been used in the treatment of other conditions arising from sympathomimetic administration; the most notable of these is cocaine overdose. Propranolol has been reported to be useful in the treatment of cocaine overdose.S, 9 However, hypertension attributed to unopposed a stimulation was reported with this modality, lo Although the cause of the hypertension was questioned,~ this theory appears to be strongly supported by the studies with epinephrine infusions. Subsequently, treatment with labetalol has proved efficacious w i t h o u t a hypertensive response in two cases. 12,13 Labetalol has been used to treat pseudoephedrine-induced hypertension, 14 hyperadrenergic states secondary to tetanus ls-17 and pheochromocytoma, TM and postoperative hypertension.19 Hypertensive emergencies remain the primary indication of labetalol therapy. 2o
SUMMARY It will be argued that the half-life of epinephrine is short and therefore symptoms will be self-limiting. If we elect to treat only life-threatening emergencies, then a majority of our patients will go unaided. To a patient, symptomatic treatment is of foremost importance; to this end, we were successful. Severely symptomatic individuals require treatment. In those with significant arrhythmias or 19:6 June 1990
ischemic cardiac symptoms, this consideration is even m o r e imperative. L a b e t a l o l w a s e f f i c a c i o u s in treating the symptoms of e p i nephrine overdose in our patient. Extreme c a u t i o n and titration are req u i r e d to p r e v e n t r e b o u n d bronc h o s p a s m . In p a t i e n t s w i t h m i l d s y m p t o m s , t h e risks o u t w e i g h the benefits, and its use is not recommended. T h e u s e of t h i s m e d i c a t i o n in treating hypertensive crisis has been demonstrated. Its role in managing cocaine intoxication as w e l l as other hyperadrenergic states is b e c o m i n g delineated. Incomplete a blockade in the face of m o r e complete J3 blockade remains a potential problem. The clin i c i a n m u s t be aware of this and monitor the patient for signs of excess ~ stimulation. REFERENCES 1. Myers FH, Jawetz E, Goldfien A: Review of Medical Pharmacology, ed 6. Los Altos, California, Lange Medical Publications, 1978, p 79-89. 2. Cydulka R, Davison R, Grammer L, et ah The use of epinephrine in the treatment of older
19:6 June 1990
adult asthmatics. Ann Emerg Med 1988;17: 322-326. 3. Richards DA, Prichard BNC, Boakes AJ, et al: Pharmacological basis for antihypertensive effects of intravenous labetalol. Br Heart J 1977;39:99-106. 4. MacCarthy EP, Bloomfield SS: Labetaloh A review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy 1983;3:193-219. 5. Goodman AG, Gillman LS, Rail TW, et ah The Pharmacological Basis of Therapeutics, ed 7. New York, Macmillan Publishing Co, 1985, p 151-158. 6. Doshi BS, Kulkarni RD, Dattani KK, et ah Effects of labetalol and propranolol on responses to adrenaline infusion in healthy volunteers. Inv l Clin Pharmacol Res 1984;4:29-33.
11. Silverstein W, Lewin N, Goldfrank L: Management of the cocaine intoxicated patient (letter). Ann Emerg Med 1987;16:234. 12. Dusenberry SJ, Hicks MJ, Mariani PJ: Labetalol treatment of cocaine toxicity (letter}. Ann Emerg Med 1987;16:235. 13. Gay G, Loper KA: The use of labetalol in the management of cocaine crisis. Ann Emerg Med 1988;17:282-283. 14. Mariani PJ: Pseudoephedrine-induced hypertensive emergency: Treatment with labetalol. Am J Emerg Med 1986;4:141-142. 15. Domenighetti GM, 8avary G, Stricker H: Hyperadrenergic syndrome in severe tetanus: Extreme rise in catecholamines responsive to labetalol. Br Med J 1986;288:1483-1484. 16. Dundee JW, Morrow WI:K: Labetalol in severe tetanus. Br Med f 1979;1:1121-1122.
7. Richards DA, Prichard BNC, Hernandez R: Circulatory effects of noradrenaline and adrenaline before and after labetalol. Br J Clin Pharmacol 1979;7:371-378.
17. Wesley AG, Hariparasad D, Pataher M, et ah Labetalol in tetanus: The treatment of sympathetic nervous system overactivity. Anesthesia 1983;38:243-249.
8. Gay GR: Clinical management of acute and chronic cocaine poisoning. Ann Emerg Med 1982;11:562-572.
18. Navaratnarajah M, White DC: Labetalol and pheochromocytoma. Br J Anaesth 1984;56:1179.
9. Rappoh RT, Gay G, Inaba DS, et ah Propranolol in the treatment of cardiopressor effects of cocaine (letter}. N Engl J Med 1976;295: 488. 10. Ramoska E, Sacchetti AD: Propranolol-induced hypertension in treatment of cocaine intoxication. Ann Emerg Med 1985;14:1112-1113.
Annals of Emergency Medicine
19. Leslie JB, Kalayjian RW, Sirgo MA, et ah Intravenous labetalol for treatment of postoperative hypertension. Anesthesiology 1987;67:3: 413-416. 20. Wilson DJ, Wallin JD, Vlachakis ND, et ah Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies. Am 1 Med 1983;75:95-102.
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