Research/Practice
I'importancede I'utilisationde la gomme abase de nicotine pannis les membresd'un HMO, de caracteriser les prescripteurs et les utilisateurs, et de decrire I'utilisation de la gomme sur une periodede deux ans. Environ0.4 pourcentdes membresdu KaiserPermanente, Northwest Regionont ete exposes a la gomme. Lors de la periodede deux ans, 1970membresont recu au moins une boitede gomme(soit96 morceaux). Presque70 pourcentdes usagersn'ont recu qu'une seule boite.Environ 1.5pourcentdes usagerssemblaient utiliserla gommesur une base reguliere aune dose quotidienne correspondant ala dose de remplacement pour les fumeursdependanta la nicotine, et ce, pour une
periodesuperieure ala recommendation de troismois.Un autregroupe (2.5 pourcent) utilisaitaussi la gommeregulierement mais aune dose inferieure ala dose de remplacement pour fumeursdependant a la nicotinepour une periodedepassant Ie maximumrecomrnande de six mois. La presenced'une assurance couvrantce produitinfluence directement Ie fait qu'une personneutilise ou non la gommeet la duree de I'utilisation. Les variations importantes noteesdans cetteetude souleventla questiondes raisonsjustifiantun tel usageet de I'efficacite du produitconsommede cette facon. MARC PARENT
PHARMACOTHERAPY CASE REPORT INTRAVENOUS ESMOLOL IN ACUTE AORTIC DISSECTION Subodh K. Mohindra and George O. Udeani
ABSTRACf, Acuteaorticdissection is a devastating condition requiring promptintensive pharmacologic management gearedtowardcontrolof bloodpressureand reduction in myocardial contractility (changein velocity/change in time).The treatmentof choicecurrentlyis sodium nitroprusside and intravenous propranolol hydrochloride. Duringacute aorticdissection, hemorrhage may spreadinto the interatrial septum, extending to the atrioventricular junctionaltissues, thus causing conduction abnormalities. Adverseeffectsof long-acting beta-blockers, including bradycardia, heart failure, and bronchospasm, may limittheir usefulness becausetheseeffectspersistfor a long time after discontinuation. This may be detrimental, especially in patientswith compromised cardiacfunction, bronchospastic disease,or both. We reporta case of a 64-year-old woman withcompromised cardiac function and aorticdissection who was successfully treatedwith esmolol hydrochloride (an ultrashort-acting beta-blocker) and sodium nitroprusside.
D1CPAnn Pharmacother 1991;25:735-8. ACUTE AORTIC DISSECTION is one of the most devastating disease processes involving the human aorta. Approximately 2000 new cases are reported in the US annually.P Major advances in the diagnosis and management of this
SUBODH K. MOHINDRA, M.D., is the Director. Critical Care Unit, South Chicago Community Hospital, 2320 E. 93rd St., Chicago. IL; and GEORGE O. UDEANI, Pharm.D., is an Assistant Clinical Professor, Department of Pharmacy Practice (MiC 886), College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612. Reprints: George O. Udeani, Pharm.D.
catastrophic condition have occurred in the last 20 years. About 90 percent of patients with aortic dissection have hypertension. Other predisposing factors includepregnancy,Marfansyndrome, congenital bicuspid aorticvalve,and coarctation of the aorta.' The major symptom of acute aortic dissection is sudden onset of excruciating pain that is commonly locatedin the chest but may be more prominent in the neck and jaw. In some patients it may not presentin the chest and may be localizedin the abdomen, especially if the gastric or mesenteric arteriesare involved. Debakey et al. classified aortic dissections into types I, II, and III. Based on Debakey's nomenclature, types I and II dissections both begin in the ascending arch and aorta, whereas type II is confmed to the ascending aorta. Type III dissection starts in the descending aorta and propagatesdistally for a variable distance.' Daily et al. use a simplerclassification scheme, which disregards the site of origin of the dissection. In their classification, all dissections involving the ascending aorta are termed type A and those that do not, type B.5 Throughout this report, we will use Daily's classification schemefor acute aorticdissection. This condition may be diagnosed from patient history and physical examination; however, this diagnosis must be approachedcautiously because acute aortic dissection has been frequently mistaken for conditions such as myocardial infarction (MI), pulmonary embolism, pneumothorax, colic, pericarditis, and acute arterialembolism.' Diagnosis
DICP,TheAnnalsofPharmacotherapy • 1991 July/August, Volume 25 • Downloaded from aop.sagepub.com at UNIV NEBRASKA LIBRARIES on January 5, 2016
735
100
is further ascertained with chest X-ray, which frequently shows abnormally widened contour. Computed tomography (Cf) scan of the thorax may be helpful in the diagnostic process, but [mal confirmation may depend upon aortic angiography, which may show site of intimal tear, false lumen, and extent of dissection.' Once a positive diagnosis has been established, it is essential to institute medical therapy promptly because of the high rate of mortality associated with the condition. Acute aortic aneurysm occurs as a result of two processes acting on the aorta. The initial process involves disruption of the media and intimal lining of the blood vessel by trauma or disease. Once the tear occurs, propagation of the dissection depends on continuing cardiac impulse with pulsatile flow and elevated blood pressure," Intensive medical therapy should be geared toward decreasing the steepness of the pulse wave, thus lowering the velocity of left ventricular ejection (change in velocity/change in time [dv/dtD and blood pressure. This helps arrest progression of the dissecting hematoma. Pharmacologic agents such as intravenous propranolol hydrochloride or trimethaphan camsylate combined with sodium nitroprusside are often used to manage these patients. Because of nitroprusside's arterial vasodilating property, it may stimulate catecholamine release, thereby increasing myocardial contractility (dv/dt). Concomitant beta-blockage is necessary to offset this undesirable effect of nitroprusside. Intravenous propranolol is a suitable beta-blocker for managing aortic dissection. In some patients with acute aortic dissection, hemorrhage may spread into the interatrial septum and extend into the area of specialized atrioventricular junctional tissues, causing conduction abnormalities.' Esmolol hydrochloride, because of its ultrashort-acting potential (half-life of nine minutes) offers the clinician more advantages over propranolol, especially in patients with compromised cardiac function, increased airway resistance, or both. Such individuals easily could be rescued from further decline in cardiac status simply by terminating the esmolol infusion rather than by attempting to counter the effects of a longer-acting agent (such as propranolol or labetalol hydrochloride) with various antidotes. We report a case of a 64-year-old woman with acute aortic dissection who was successfully treated with esmo101 and nitroprusside.
80
ie
60
w
~
a:
Ii:c
w
40
x
20
O+--~--~--~-~--..------r---I
1000
1200
1400
1600
1800
2000
2200
2400
TIME (h)
Figure I. Blood pressure control achieved with esmolol and sodium nitroprusside. DBP =diastolic blood pressure; MAP =mean arterial pressure; SBP =systolic blood pressure.
on the inferior leads. BP recorded in both arms was 200/110 rom Hg. Heart rate was 65 beats/min and respiratory rate was 16 breaths/rnin. Physical examination showed normal first and second heart sounds. No gallops, murmurs, or rubs were heard. Abdomen was noted to be benign. No pulsatile mass was felt. Laboratory data were within normal limits. The patient was given three doses of sublingual nitroglycerin 0.4 mg, with no apparent relief in chest pain. She also was given sublingual nifedipine 10 mg with slight reduction in systolic BP (from 200/110 to 180/110 rom Hg). Chest X-ray revealed normal cardiac size. Mediastinal widening (commonly associated with aortic dissection) was observed. No previous chest X-rays were available for comparison. She had a past medical history of hypertension and was on a long-acting beta-blocker (long-acting propranolol 120 mg/d). She had had an Ml six years ago, but she denied any angina in recent years. She was subsequently transferred to the intensive care unit where a diagnosis of acute aortic dissection was made. This diagnosis was established and clearly distinguished from Ml by: (I) the lack of electrocardiographic evidence of Ml; (2) widened mediastinum on chest X-ray; (3) posterior chest pain, radiating anteriorly, unresponsive to sublingual nitroglycerin; and (4) IT scan of the thorax confirming dissection of the aorta. While the diagnosis was being established, she was started on nitroglycerin 50 mg iv in 250 mL of D5W at 10 l1g/min, titrated to 2411g/rnin,and esmolol5 g in 500 mL of D5W at 50 l1g/kg/min titrated to 150 l1g/kg/min, with appropriate hemodynamic monitoring. Infusion rate adjustments were made approximately every 15 minutes, based on mean arterial pressure (MAP). Our goals were to achieve an MAP of 100-120 rom Hg and a heart rate of approximately 50-60 beats/rnin, thus minimizing tachycardia. Relief of chest pain and control of BP was not satisfactory with these medications. Intravenous nitroglycerin was replaced (when the diagnosis was apparent) by intravenous nitroprusside 50 mg in 250 mL of D5W at 3 l1g/kg/rnin, titrated to 8 l1g/kg/min.This titration occurred at a rate of 0.5 l1g/kg/min, approximately every 10-15 minutes over the first one and a half hours, based on MAP. The combination of esmolol and nitroprusside provided prompt BP control with relief of chest discomfort (Figure l/Table I).
CASE REPORT A 64-year-old woman was seen in the emergency room at about 0900 with a history of severe chest pain, shortness of breath, and nausea, which started approximately five hours earlier. This pain was described as a sharp pain originating in the posterior interscapular region and radiating anteriorly. Electrocardiogram (ECG) performed in the emergency room showed evidence of left ventricular hypertrophy with ST-segment and unifocal Twave changes. Occasional ventricular premature contractions were recorded on the ECG. Prominent Q waves also were noted
Table 1. Time/Drug Infusion Rates TIME (h)
IV DRUG (j.lg/kg/min )
Nitroglycerin Sodium nitroprusside Esmolol
736 •
1000
1030
1100
1130
1200
1230
1300
1330
1400
1430-2400
10
12
15
18
21
24
50
75
100
125
125
125
12 3 150
5 150
6 150
8 150
DICP,TheAnnalsof Pharmacotherapy • 1991 July/August, Volume 25 Downloaded from aop.sagepub.com at UNIV NEBRASKA LIBRARIES on January 5, 2016
Case Reports
cr scanning and arteriographydemonstrateddissection of the aorta in the arch. The dissection extended downward to just above the renal arteries. This was a type B dissection. Surgical intervention was considered risky and unnecessaryas the patient appearedto be respondingto drug therapy.No significant change in heart rate was noted during therapy with esmolol (Figure 2/ Table I). Esmolol and nitroprussidewere graduallytaperedover the next three days and replaced with oral agents, namely longacting propranolol 160 mg/d, verapamil 80 rng tid, and furosemide 40 mg qam, with effective BP control. Systolic BPs of 130-140 mm Hg and diastolic BPs of 80-90 mm Hg were recorded during subsequent follow-up visits. She did well subsequently and did not reveal any evidence of progression six months after the aortic dissection. Serial chest X-raysdone every month for four months showed no changes in mediastinal size.
SBP
280 .
-+--
240
MAP
220
--e--
200
DBP
180
~
160
~
140 120
100 80 80
.......~:=:!'Ic=s-.'f!,
-f...................................................................
40· 20 O+------.------,~--r--__r--.-----.----I
1000
Acute aortic dissection is a catastrophic ailment requiring immediate medical attention. Untreated patients often have a poor prognosis, frequentlyresulting in fatality. Mortality associated with this condition is very rapid, necessitating early diagnosis and institution of appropriate therapy. Anagnostopoulos et al. reported a mortality rate in untreated aortic dissectionranging from 20 percent within the first six hours to 90 percent within three months of onset of symptoms," Aggressive medical treatment was chosen for our patient because medical therapy is the initial treatment of choice in virtually all patients with suspected acute aortic dissection. Intensive medical therapy to control BP and reduce !J.v/!J.t as proposed by Wheat et al. is the key to acutely managing most individuals with this condition." Surgical intervention appeared unnecessary in this patient because she demonstrated freedom from pain and adequate BP control with the esmolol/nitroprusside combination. Also, surgery was considered risky because of her age and vascular disease. Continued freedom from pain is an important clinical sign in the management of this disease state, because continued pain indicates continuation of the dissection. Surgical intervention would have been considered if there were any evidence of continued dissection or inadequate blood pressure control within four hours of aggressive pharmacologicmanagement. The treatment approach in patients with acute dissecting aneurysms remains highly controversial and varies from center to center. In general, drug therapy appears to be the definitive approach for patients with acute type B dissections, whereas surgical interventionis reserved for individuals with type A dissectionscomplicated by aortic valve or coronary-cerebral artery Involvement.t-" Miller et aI., however,advocate surgical interventionfor both acute type A and acute type B dissections.P These investigators claim that operative mortality rates (associated with acute aortic dissection aneurysm) have substantially declined today as a result of various advancements in surgery, anesthesia, and medicine. They contend that earlier surgical intervention could result in reduction of risk factors such as irreversiblemajor endorgan ischemia, infarction,or both. Over the years, various pharmacologic agents capable of lowering blood pressure and !J.v/!J.t have been employed in the management of acute aortic dissection. These have included drugs such as guanethidine, reserpine, trimethaphan, and, more recently, nitroprusside in combination with beta-blockers, particularly propranolol. In dogs made hypertensive after creation of an acute dissection in the descending thoracic aorta, Moran et al. showed a better re-
--
300,-----------------,,-----, 280
1200
1400
1800
1800
2000
2200
2400
TIme (h)
Figure 2. Heart rate observed during esmolol and nitroprusside therapy.
duction in blood pressure and !J.v/!J.t with nitroprusside and propranolol than with nitroprusside alone." This drug combination has been used extensively in humans to manage this condition.IS Nitroprusside, through reduction in afterload and possible indirect stimulation of catecholamine release, could indirectly increase the force of ventricular contraction (!J.v/!J.t). Beta-blockers used in conjunction with nitroprusside can offset this undesirableeffect. Adverse effects of beta-blockers, especially bradycardia, heart failure, and respiratory insufficiency, can limit their usefulness.In patients with acute aortic dissection, particularly those with compromised cardiac function or increased airway resistance caused by asthma, short-acting beta-blockers can be used to achieve desirable effects, while minimizing the risks of unfavorable adverse effects. We chose the nitroprusside/esmolol combination because of the potency,rapid action, and short elimination half-life of these products. Also, esmolol offers a safe reduction in BP that can be titrated for adequate and effective pressure control. Intravenous labetalolhas been proposed as a longacting, simple, and inexpensive form of therapy for acute aortic dissection!' Its onset of antihypertensive action is 5 minutes; however, its long duration of action of up to 24 hours, seen in some individuals, made it less attractive than esmolol for use in this elderly patient with coronary artery disease.I? Esmolol is a relatively new, ultrashort-acting,cardioselective, intravenous beta-blocker. The elimination half-life of esmolol is 9 minutes in individuals with normal renal and hepatic function, whereas that of propranolol is approximately 3.9 hours.I 8,19 Murthy et al. demonstrated that cardiac slowing started within 1 to 2 minutes and reached steady-statewithin 6 minutes, with continuous esmolol infusion without a loading dose. The heart rate recovery occurred within 20 minutes after the end of the infusion.P In addition to this agent's attractive pharmacokinetic profile, esmolol demonstrates a dose-dependentfall in systolic pressure. Reilly et al. noted a dose-dependent reduction in systolic pressure by approximately 20 mm Hg, with 750 Ilg/kg/min of esmoloI. Only a 6-mm Hg drop in systolic pressure was noted with a propranolol infusion of 55 Ilg/min, following a 9.9-mg loading dose of the drug. High-dose esmolol (750 Ilg/kg/min) was associated with increased heart rate. Reilly et aI. postulated that the in-
D/CP, The AnnalsofPharmacotherapy • /99/ July/August, Volume 25 • Downloaded from aop.sagepub.com at UNIV NEBRASKA LIBRARIES on January 5, 2016
737
Case Reports
creased heart rate (2-10 beats/min) at the higher esmolol doses may have been associated with reflex cardiac stimulation in response to the fall in blood pressure." Byrd et al. also noted a dose-dependent fall in systolic pressure to
I'importancede I'utilisationde la gomme abase de nicotine pannis les membresd'un HMO, de caracteriser les prescripteurs et les utilisateurs, et de decrire I'utilisation de la gomme sur une periodede deux ans. Environ0.4 pourcentdes membresdu KaiserPermanente, Northwest Regionont ete exposes a la gomme. Lors de la periodede deux ans, 1970membresont recu au moins une boitede gomme(soit96 morceaux). Presque70 pourcentdes usagersn'ont recu qu'une seule boite.Environ 1.5pourcentdes usagerssemblaient utiliserla gommesur une base reguliere aune dose quotidienne correspondant ala dose de remplacement pour les fumeursdependanta la nicotine, et ce, pour une
periodesuperieure ala recommendation de troismois.Un autregroupe (2.5 pourcent) utilisaitaussi la gommeregulierement mais aune dose inferieure ala dose de remplacement pour fumeursdependant a la nicotinepour une periodedepassant Ie maximumrecomrnande de six mois. La presenced'une assurance couvrantce produitinfluence directement Ie fait qu'une personneutilise ou non la gommeet la duree de I'utilisation. Les variations importantes noteesdans cetteetude souleventla questiondes raisonsjustifiantun tel usageet de I'efficacite du produitconsommede cette facon. MARC PARENT
PHARMACOTHERAPY CASE REPORT INTRAVENOUS ESMOLOL IN ACUTE AORTIC DISSECTION Subodh K. Mohindra and George O. Udeani
ABSTRACf, Acuteaorticdissection is a devastating condition requiring promptintensive pharmacologic management gearedtowardcontrolof bloodpressureand reduction in myocardial contractility (changein velocity/change in time).The treatmentof choicecurrentlyis sodium nitroprusside and intravenous propranolol hydrochloride. Duringacute aorticdissection, hemorrhage may spreadinto the interatrial septum, extending to the atrioventricular junctionaltissues, thus causing conduction abnormalities. Adverseeffectsof long-acting beta-blockers, including bradycardia, heart failure, and bronchospasm, may limittheir usefulness becausetheseeffectspersistfor a long time after discontinuation. This may be detrimental, especially in patientswith compromised cardiacfunction, bronchospastic disease,or both. We reporta case of a 64-year-old woman withcompromised cardiac function and aorticdissection who was successfully treatedwith esmolol hydrochloride (an ultrashort-acting beta-blocker) and sodium nitroprusside.
D1CPAnn Pharmacother 1991;25:735-8. ACUTE AORTIC DISSECTION is one of the most devastating disease processes involving the human aorta. Approximately 2000 new cases are reported in the US annually.P Major advances in the diagnosis and management of this
SUBODH K. MOHINDRA, M.D., is the Director. Critical Care Unit, South Chicago Community Hospital, 2320 E. 93rd St., Chicago. IL; and GEORGE O. UDEANI, Pharm.D., is an Assistant Clinical Professor, Department of Pharmacy Practice (MiC 886), College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612. Reprints: George O. Udeani, Pharm.D.
catastrophic condition have occurred in the last 20 years. About 90 percent of patients with aortic dissection have hypertension. Other predisposing factors includepregnancy,Marfansyndrome, congenital bicuspid aorticvalve,and coarctation of the aorta.' The major symptom of acute aortic dissection is sudden onset of excruciating pain that is commonly locatedin the chest but may be more prominent in the neck and jaw. In some patients it may not presentin the chest and may be localizedin the abdomen, especially if the gastric or mesenteric arteriesare involved. Debakey et al. classified aortic dissections into types I, II, and III. Based on Debakey's nomenclature, types I and II dissections both begin in the ascending arch and aorta, whereas type II is confmed to the ascending aorta. Type III dissection starts in the descending aorta and propagatesdistally for a variable distance.' Daily et al. use a simplerclassification scheme, which disregards the site of origin of the dissection. In their classification, all dissections involving the ascending aorta are termed type A and those that do not, type B.5 Throughout this report, we will use Daily's classification schemefor acute aorticdissection. This condition may be diagnosed from patient history and physical examination; however, this diagnosis must be approachedcautiously because acute aortic dissection has been frequently mistaken for conditions such as myocardial infarction (MI), pulmonary embolism, pneumothorax, colic, pericarditis, and acute arterialembolism.' Diagnosis
DICP,TheAnnalsofPharmacotherapy • 1991 July/August, Volume 25 • Downloaded from aop.sagepub.com at UNIV NEBRASKA LIBRARIES on January 5, 2016
735
100
is further ascertained with chest X-ray, which frequently shows abnormally widened contour. Computed tomography (Cf) scan of the thorax may be helpful in the diagnostic process, but [mal confirmation may depend upon aortic angiography, which may show site of intimal tear, false lumen, and extent of dissection.' Once a positive diagnosis has been established, it is essential to institute medical therapy promptly because of the high rate of mortality associated with the condition. Acute aortic aneurysm occurs as a result of two processes acting on the aorta. The initial process involves disruption of the media and intimal lining of the blood vessel by trauma or disease. Once the tear occurs, propagation of the dissection depends on continuing cardiac impulse with pulsatile flow and elevated blood pressure," Intensive medical therapy should be geared toward decreasing the steepness of the pulse wave, thus lowering the velocity of left ventricular ejection (change in velocity/change in time [dv/dtD and blood pressure. This helps arrest progression of the dissecting hematoma. Pharmacologic agents such as intravenous propranolol hydrochloride or trimethaphan camsylate combined with sodium nitroprusside are often used to manage these patients. Because of nitroprusside's arterial vasodilating property, it may stimulate catecholamine release, thereby increasing myocardial contractility (dv/dt). Concomitant beta-blockage is necessary to offset this undesirable effect of nitroprusside. Intravenous propranolol is a suitable beta-blocker for managing aortic dissection. In some patients with acute aortic dissection, hemorrhage may spread into the interatrial septum and extend into the area of specialized atrioventricular junctional tissues, causing conduction abnormalities.' Esmolol hydrochloride, because of its ultrashort-acting potential (half-life of nine minutes) offers the clinician more advantages over propranolol, especially in patients with compromised cardiac function, increased airway resistance, or both. Such individuals easily could be rescued from further decline in cardiac status simply by terminating the esmolol infusion rather than by attempting to counter the effects of a longer-acting agent (such as propranolol or labetalol hydrochloride) with various antidotes. We report a case of a 64-year-old woman with acute aortic dissection who was successfully treated with esmo101 and nitroprusside.
80
ie
60
w
~
a:
Ii:c
w
40
x
20
O+--~--~--~-~--..------r---I
1000
1200
1400
1600
1800
2000
2200
2400
TIME (h)
Figure I. Blood pressure control achieved with esmolol and sodium nitroprusside. DBP =diastolic blood pressure; MAP =mean arterial pressure; SBP =systolic blood pressure.
on the inferior leads. BP recorded in both arms was 200/110 rom Hg. Heart rate was 65 beats/min and respiratory rate was 16 breaths/rnin. Physical examination showed normal first and second heart sounds. No gallops, murmurs, or rubs were heard. Abdomen was noted to be benign. No pulsatile mass was felt. Laboratory data were within normal limits. The patient was given three doses of sublingual nitroglycerin 0.4 mg, with no apparent relief in chest pain. She also was given sublingual nifedipine 10 mg with slight reduction in systolic BP (from 200/110 to 180/110 rom Hg). Chest X-ray revealed normal cardiac size. Mediastinal widening (commonly associated with aortic dissection) was observed. No previous chest X-rays were available for comparison. She had a past medical history of hypertension and was on a long-acting beta-blocker (long-acting propranolol 120 mg/d). She had had an Ml six years ago, but she denied any angina in recent years. She was subsequently transferred to the intensive care unit where a diagnosis of acute aortic dissection was made. This diagnosis was established and clearly distinguished from Ml by: (I) the lack of electrocardiographic evidence of Ml; (2) widened mediastinum on chest X-ray; (3) posterior chest pain, radiating anteriorly, unresponsive to sublingual nitroglycerin; and (4) IT scan of the thorax confirming dissection of the aorta. While the diagnosis was being established, she was started on nitroglycerin 50 mg iv in 250 mL of D5W at 10 l1g/min, titrated to 2411g/rnin,and esmolol5 g in 500 mL of D5W at 50 l1g/kg/min titrated to 150 l1g/kg/min, with appropriate hemodynamic monitoring. Infusion rate adjustments were made approximately every 15 minutes, based on mean arterial pressure (MAP). Our goals were to achieve an MAP of 100-120 rom Hg and a heart rate of approximately 50-60 beats/rnin, thus minimizing tachycardia. Relief of chest pain and control of BP was not satisfactory with these medications. Intravenous nitroglycerin was replaced (when the diagnosis was apparent) by intravenous nitroprusside 50 mg in 250 mL of D5W at 3 l1g/kg/rnin, titrated to 8 l1g/kg/min.This titration occurred at a rate of 0.5 l1g/kg/min, approximately every 10-15 minutes over the first one and a half hours, based on MAP. The combination of esmolol and nitroprusside provided prompt BP control with relief of chest discomfort (Figure l/Table I).
CASE REPORT A 64-year-old woman was seen in the emergency room at about 0900 with a history of severe chest pain, shortness of breath, and nausea, which started approximately five hours earlier. This pain was described as a sharp pain originating in the posterior interscapular region and radiating anteriorly. Electrocardiogram (ECG) performed in the emergency room showed evidence of left ventricular hypertrophy with ST-segment and unifocal Twave changes. Occasional ventricular premature contractions were recorded on the ECG. Prominent Q waves also were noted
Table 1. Time/Drug Infusion Rates TIME (h)
IV DRUG (j.lg/kg/min )
Nitroglycerin Sodium nitroprusside Esmolol
736 •
1000
1030
1100
1130
1200
1230
1300
1330
1400
1430-2400
10
12
15
18
21
24
50
75
100
125
125
125
12 3 150
5 150
6 150
8 150
DICP,TheAnnalsof Pharmacotherapy • 1991 July/August, Volume 25 Downloaded from aop.sagepub.com at UNIV NEBRASKA LIBRARIES on January 5, 2016
Case Reports
cr scanning and arteriographydemonstrateddissection of the aorta in the arch. The dissection extended downward to just above the renal arteries. This was a type B dissection. Surgical intervention was considered risky and unnecessaryas the patient appearedto be respondingto drug therapy.No significant change in heart rate was noted during therapy with esmolol (Figure 2/ Table I). Esmolol and nitroprussidewere graduallytaperedover the next three days and replaced with oral agents, namely longacting propranolol 160 mg/d, verapamil 80 rng tid, and furosemide 40 mg qam, with effective BP control. Systolic BPs of 130-140 mm Hg and diastolic BPs of 80-90 mm Hg were recorded during subsequent follow-up visits. She did well subsequently and did not reveal any evidence of progression six months after the aortic dissection. Serial chest X-raysdone every month for four months showed no changes in mediastinal size.
SBP
280 .
-+--
240
MAP
220
--e--
200
DBP
180
~
160
~
140 120
100 80 80
.......~:=:!'Ic=s-.'f!,
-f...................................................................
40· 20 O+------.------,~--r--__r--.-----.----I
1000
Acute aortic dissection is a catastrophic ailment requiring immediate medical attention. Untreated patients often have a poor prognosis, frequentlyresulting in fatality. Mortality associated with this condition is very rapid, necessitating early diagnosis and institution of appropriate therapy. Anagnostopoulos et al. reported a mortality rate in untreated aortic dissectionranging from 20 percent within the first six hours to 90 percent within three months of onset of symptoms," Aggressive medical treatment was chosen for our patient because medical therapy is the initial treatment of choice in virtually all patients with suspected acute aortic dissection. Intensive medical therapy to control BP and reduce !J.v/!J.t as proposed by Wheat et al. is the key to acutely managing most individuals with this condition." Surgical intervention appeared unnecessary in this patient because she demonstrated freedom from pain and adequate BP control with the esmolol/nitroprusside combination. Also, surgery was considered risky because of her age and vascular disease. Continued freedom from pain is an important clinical sign in the management of this disease state, because continued pain indicates continuation of the dissection. Surgical intervention would have been considered if there were any evidence of continued dissection or inadequate blood pressure control within four hours of aggressive pharmacologicmanagement. The treatment approach in patients with acute dissecting aneurysms remains highly controversial and varies from center to center. In general, drug therapy appears to be the definitive approach for patients with acute type B dissections, whereas surgical interventionis reserved for individuals with type A dissectionscomplicated by aortic valve or coronary-cerebral artery Involvement.t-" Miller et aI., however,advocate surgical interventionfor both acute type A and acute type B dissections.P These investigators claim that operative mortality rates (associated with acute aortic dissection aneurysm) have substantially declined today as a result of various advancements in surgery, anesthesia, and medicine. They contend that earlier surgical intervention could result in reduction of risk factors such as irreversiblemajor endorgan ischemia, infarction,or both. Over the years, various pharmacologic agents capable of lowering blood pressure and !J.v/!J.t have been employed in the management of acute aortic dissection. These have included drugs such as guanethidine, reserpine, trimethaphan, and, more recently, nitroprusside in combination with beta-blockers, particularly propranolol. In dogs made hypertensive after creation of an acute dissection in the descending thoracic aorta, Moran et al. showed a better re-
--
300,-----------------,,-----, 280
1200
1400
1800
1800
2000
2200
2400
TIme (h)
Figure 2. Heart rate observed during esmolol and nitroprusside therapy.
duction in blood pressure and !J.v/!J.t with nitroprusside and propranolol than with nitroprusside alone." This drug combination has been used extensively in humans to manage this condition.IS Nitroprusside, through reduction in afterload and possible indirect stimulation of catecholamine release, could indirectly increase the force of ventricular contraction (!J.v/!J.t). Beta-blockers used in conjunction with nitroprusside can offset this undesirableeffect. Adverse effects of beta-blockers, especially bradycardia, heart failure, and respiratory insufficiency, can limit their usefulness.In patients with acute aortic dissection, particularly those with compromised cardiac function or increased airway resistance caused by asthma, short-acting beta-blockers can be used to achieve desirable effects, while minimizing the risks of unfavorable adverse effects. We chose the nitroprusside/esmolol combination because of the potency,rapid action, and short elimination half-life of these products. Also, esmolol offers a safe reduction in BP that can be titrated for adequate and effective pressure control. Intravenous labetalolhas been proposed as a longacting, simple, and inexpensive form of therapy for acute aortic dissection!' Its onset of antihypertensive action is 5 minutes; however, its long duration of action of up to 24 hours, seen in some individuals, made it less attractive than esmolol for use in this elderly patient with coronary artery disease.I? Esmolol is a relatively new, ultrashort-acting,cardioselective, intravenous beta-blocker. The elimination half-life of esmolol is 9 minutes in individuals with normal renal and hepatic function, whereas that of propranolol is approximately 3.9 hours.I 8,19 Murthy et al. demonstrated that cardiac slowing started within 1 to 2 minutes and reached steady-statewithin 6 minutes, with continuous esmolol infusion without a loading dose. The heart rate recovery occurred within 20 minutes after the end of the infusion.P In addition to this agent's attractive pharmacokinetic profile, esmolol demonstrates a dose-dependentfall in systolic pressure. Reilly et al. noted a dose-dependent reduction in systolic pressure by approximately 20 mm Hg, with 750 Ilg/kg/min of esmoloI. Only a 6-mm Hg drop in systolic pressure was noted with a propranolol infusion of 55 Ilg/min, following a 9.9-mg loading dose of the drug. High-dose esmolol (750 Ilg/kg/min) was associated with increased heart rate. Reilly et aI. postulated that the in-
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Case Reports
creased heart rate (2-10 beats/min) at the higher esmolol doses may have been associated with reflex cardiac stimulation in response to the fall in blood pressure." Byrd et al. also noted a dose-dependent fall in systolic pressure to
