Intensive Care Med (1992) 18:247-249
IntensiveCare Medicine 9 Springer-Verlag 1992
Severe acute myocardial infarction during a staphylococcal septicemia with meningoencephalitis A possible contraindication to thrombolytic treatment C.A. Reynard ~, P. Calain 2, G.P.
Pizzolato 4 and J.C. Chevrolet 3
1Cardiology Center, 2Division of Infectious Diseases, 3Medical Intensive Care Unit, Geneva University Hospital, and 4Department of Pathology (Neuropathology), Centre M6dical Universitaire, Geneva, Switzerland Received: 18 May 1991; accepted: February 4, 1992
Abstract. We r e p o r t t h e first c a s e o f l e t h a l i n t r a c r a n i a l h a e m o r r h a g e c o m p l i c a t i n g a t r e a t m e n t b y r t - P A in a p a t i e n t p r e s e n t i n g w i t h a s i m u l t a n e o u s s t a p h y l o c o c c a l septicemia with meningoencephalitis and an acute myocardial i n f a r c t i o n w i t h c a r d i o g e n i c s h o c k . T h e p r e s e n c e o f microvascular lesions in the central nervous system seems to be important risk factor for intracranial haemorrhage a n d we r e c o m m e n d e x t r e m e c a u t i o n in t h e u s e o f t h r o m b o l y t i c t r e a t m e n t in s e p t i c e m i c p a t i e n t s w i t h a c u t e m y o cardial infarction, particularly when neurological sympt o m s are p r e s e n t .
Key words: M y o c a r d i a l i n f a r c t i o n Meningitis -
Thrombolysis
-
Staphylococcus
Case report A 45-year old male patient with a 34-year history of insulin-dependent diabetes was admitted to the University Hospital of Geneva for headache, confusion and fever of 24 h duration. On admission he was ill, disorientated and febrile (40.4~ Erythematous, crusty, ulcerated but non-suppurative warm lesions were seen on the anterior side of both legs and nonpalpable purpuric lesions were noted on the fingers and on the toe tips. Pulse was 132/min and blood pressure 140/80 mmHg. Cardiac, pulmonary and abdominal examinations were normal. The patient was confused but the neurological examination was otherwise normal. Signs of non-proliferative retinopathy were noted on the fundus but there was no haemorrhage or exudate. Laboratory values were: haematocrit 45.1070, white-cell count 9100/mm 3 with 8~ band form and platelet count 107,000/ram 3. Prothrombin time was 85~ partial thromboplastin time 34.4 s (control: 2 5 - 31 s) and fibrinogen 0.44 g/1. Plasma glucose was 23 mmol/1, urea nitrogen, creatinine, electrolytes and hepatic function were normal. Creatine kinase was 220 U/I, with a MB fraction of 11 (5%). The CSF was clear with a glucose of 10.7 retool/l, protein of 0.79 g/1 and a white cell count of 206/rnm 3 with 98~ polymorphonuclear cells. Gram stain was negative. Our initial diagnosis was sepsis with meningo-encephalitis and septic emboli. Flucloxacillin and ceftriaxone were started. Two hours after admission, the patient developed ventricular tachycardia which promptly responded to an external DC shock. ECG (normal on admission) showed Pardee waves in the inferior and lateral leads. The diagnosis of
acute myocardial infarction was further confirmed by an elevation of the CK values (650 U/1 with a MB fraction of 65) and by echocardiography (akinesy of the inferior and lateral wails of the/eft ventricle). The clinical situation rapidly deteriorated with malignant arrhythmias and refractory shock, poorly responsive to vasoactive agents (dobutamine, dopamine, and finally noradrenaline). The patient was intubated and anticoagulation (heparin: 1000 U/h) and fibrinolysis (rtPA: 10 mg loading dose, then 50 mg during the first hour and 20 mg/h during the second and the third hour) were started (30 min after VT). The arrhythmia rapidly corrected and the hemodynamic course was favourable. Unfortunately, bilateral mydriasis developed while spontaneous respiration, response to pain and brain-stem reflexes disappeared. The patient died 4 days following admission. Blood cultures were positive for Staph. aureus. Autopsy (Fig. 1) revealed a fresh postero-septal lateral and right ventricular wall myocardial infarction, a fresh thrombus within the circumflex artery as well as a scar compatible with an old lateral and posterolateral subendocardial infarction. No valvular vegetation was recovered from gross examination of the heart. On histological examination the cardiac valves were unremarkable, and there was no septic coronary embolism. The brain showed bilateral edema, bilateral temporal-lobe and cerebellar tonsfllar herniations, and multiple haematomas in both hemispheres and in the brain stem. One haematoma (in the left frontal lobe) perforated in the left ventricle and the subarachnoid space causing a diffuse subarachnoid and intraventricular haemorrhage. Microscopically, there were diffuse neuronal necrosis, and multiple microabscesses in both hemispheres and in the brain stem. Infiltration by polymorphonuclear cells were found in the wall of numerous cerebral vessels consistent with vasculitis. No bacteria were seen on direct examination and on the Gram stain.
Discussion I n t h e p r e - t h r o m b o l y t i c era, s t r o k e was r e p o r t e d to c o m p l i c a t e t h e c o u r s e o f a c u t e m y o c a r d i a l i n f a r c t i o n in 0 . 8 % - 2 . 4 % o f p a t i e n t s [1, 2]. A d d i t i o n a l risk a s s o c i a t e d with the use of fibrinolytic agents appears to be minimal. I n r e c e n t r a n d o m i s e d trials o f t h r o m b o l y t i c t h e r a p y , t h e t o t a l s t r o k e r a t e has r a n g e d f r o m 0 . 5 % - 2 . 5 % and the risk o f i n t r a c r a n i a l h a e m o r r h a g e ( I C H ) has r a n g e d f r o m 0 . 3 % - 1.50/0 [ 2 - 8 ] . A h i g h e r r a t e ( 5 % ) was h o w e v e r rec e n t l y r e p o r t e d [9]. T h e risk f a c t o r s f o r I C H in p a t i e n t s t r e a t e d w i t h t h r o m b o l y t i c t h e r a p y are c u r r e n t l y p o o r l y d e f i n e d . F o u r p a t i e n t s w h o s u f f e r e d I C H in T A M I trial p r e s e n t e d w i t h
248
Fig. 1. a Brain slice (left hemisphere) showinga large frontal haemorrhage perforating in the subarachnoid space and the lateral ventricle
molded by a large clot. b (Haematoxylineeosinex i60) cortical microabscess, c (HE x 160) acute vasculitisin the white matter
at least one of prespecified risk factors of ICH (age > 65 years, history of hypertension, history of cerebrovascular disease, aspirin use and acute hypertension). However 80~ of patients without I C H also had at least one risk factor and 31 070 had two risk factors [7]. Only one of six patients with ICH reported by Kase was hypertensive during rt-PA infusion, but all received heparin and had a prolonged partial thromboplastin time (from 81 to more than 150 s) [9]. Althouse found no association between these classical risk factors and ICH in patients treated with rt-PA; however, this author suggests that a transient elevation of systolic (180 mmHg) or diastolic (120 mmHg) blood pressure immediately prior to rt-PA infusion is a risk factor for ICH [10, 11], Diabetic retinopathy, particularly the proliferative type, may be considered as a relative contraindication for thrombolytic treatment. Unfortunately, no data are presently available in humans that could be used as guidelines. The unique available information to date was recorded in diabetic patients submitted to a vitrect0my: intraocular rt-PA was used for fibrin deposition prevention but this drug Caused significant intracameral haemorrhage [12]. Vascular involvement in staphylococcal septicemia or endocarditis corresponds to multiple mechanisms: emboll can cause infarction, abscess and aneurysm formation; microvascular damage can result from seeding of bacteria or f r o m immune complex deposition. Although 10~ of the patients with staphylococcal endocarditis present with neurological abnormalities, the prevalence of microvascu!ar lesions in the CNS is unknown [13]. One can suspect that most of them are clinically silent, whereas the only available information on the frequency of CNS bleeding in Staph. aureus meningitis is an 18070 prevalence o f disseminated intravascular coagulation in such a situation [14]. Similarly, an extensive literature research was unfruitful for evaluating the precise frequency of
bleeding complications in any type of bacterial or viral meningoencephalitis, except for herpes simplex virus encephalitis, in which a severe temporal haemorrhagic cerebral necrosis may occur in a significant number of untreated, or lately treated cases [15]. In our patient, endocarditis with septic cerebral embolisation can be excluded: echocardiographic examination did not show any sign compatible with valvular vegetation, whereas the histologic examination of the valves was normal, and the myocardial infarction was not due to a coronary embolism. Incidently, there are presently no available data concerning the exact risk/benefit ratio of anticoagulant treatment in endocarditis with septic embolism [13, 16]. A recent case report presents a patient with a streptococcal bacterial endocarditis and a myocardial infarction, treated by an infusion of 120 mg of rt-PA in 2 h, a too rapid infusion rate caused by a technical problem. This patient experienced a small occipital hemorrhage following reperfusion [17]. Our case is the first description of severe and lethal ICH complicating a treatment by rt-PA in a patient presenting simultaneously with an acute myocardial infarction and staphylococcal septicemia with meningoencephalitis. In our opinion, the presence of microvascular lesions in the CNS is a risk factor for ICH to be considered in patients treated with any fibrinolytic agent. Therefore, although based on an isolated observation, we recommend extreme caution with thrombolytic tlaerapy in septicemic patients when vascular lesions can be suspected: emergency percutaneous transluminal coronary angioplasty, if possible, should be attempted preferentially in such a difficult situation. One should be aware, however, that a coronary artery mycotic aneurysm has been described as a complication at the dilatation site in a patient presenting with bacterial endocarditis and myocardial infarction [17].
249
References 1. Komrad MS, Coffey CE, Coffey KS, McKinnis R, Massey EW, Califf RM (1984) Myocardial infarction and stroke. Neurology 34:1403 - 1409 2. Wilcox RG, Olsson CG, Skene AM, Von Der Lippe G, Jensen G, Hampton JR for the ASSET Study Group (1988) Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet II: 526-530 3. Chesebro MD; Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Lundbrook P, Markis JE, Mueller H, Passamani ER, Powers ER, Ran AK, Robertson T, Ross A, Ryan TJ, Sobel BE, Willerson J, Williams DO, Zaret BL, Braunwald E (1987) Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 76:142-154 4. Gore JM, Sloane M, Price TR, Young Randall AM (1991) Intracerebral hermorrhage, cerebral infarction and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Circulation 83:448-459 5. Simoons ML, for the investigators of the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator (rt-PA) (1988) Thrombolysis with Tissue Plasminogen Activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. Lancet 1:197-202 6. Van De Werf F, for the investigators of the European Cooperative Study Group for recombinant Tissue-Type Plasminogen Activator (1988) Lessons from the European recombinant tissue-type plasminogen activator versus placebo trial. J Am Coll Cardiol 12:14A-19A 7. O'Connor M, Califf RM, Massey EW, Mark DB, Kereiakes DJ, Candela R J, Abbotsmith C, George B, Stack RS, Aronson L, Mantell S, Topol EJ (1990) Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and long-term prognosis. J Am Coil Cardiol 16:533-540 8. The International Study Group (1990) In-hospital mortality and
9.
10.
11.
12.
13. 14.
15.
16.
17.
clinical course of 20891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet II:71-75 Kase CS, O'Neal AM, Fisher M, Girgis GN, Ordia JI (1990) Intracranial hemorrhage after use of tissue plasminogen activator for coronary thrombolysis. Ann Intern Med 112:17-21 Althouse R, Maynard C, Olsufka M, Kennedy JW (1989) Risk factors for haemorrhage and ischemic stroke in myocardial infarction patients treated with tissue plasminogen activator. J Am Coll Cardiol 13:153A Althouse R, Weaver WD, Kennedy JW (1987) Transient elevation of diastolic blood pressure in acute myocardial infarction. A contraindication to thrombolytic therapy. Circulation 76:306-309 Dabbs C, Aaberg T, Aguilar H, Sternberg P, Meredith T (1989) Complications of the treatment of severe fibrinous response following diabetic vitrectomy with tissue plasminogen activator. Invest Ophtalmol Vis Sci 30 [Suppl]:273 Nolan C, Beaty H (1976) Staphylococcus aureus bacteremia: current clinical patterns. Am J Med 60:495-499 Sehlesinger L, Ross S, Schaberg D (1987) Staphylococcus aureus meningitis: a broad-based epidemiologic study. Medicine 66: 148-155 Nahmias A, Whitley R, Vinsintine A (1982) Herpes simplex encephalitis: laboratory evaluation and their diagnostic significance. J Infect Dis 145:829-834 Mandell G, Gordon Douglas R, Bennett J (1990) Principles and practice of infectious diseases, 3rd edn. Churchill Livingstone, New York, pp 670 and 1489 Herzog C, Henry T, Zimmer S (1991) Bacterial endocarditis presenting as acute myocardial infarction: a cautionary note for the era of reperfusion. Am J Meal 90:392-397
Dr. J. C. Chevrolet Medical Intensive Care Unit Geneva University Hospital CH-1211 Geneva 4 Switzerland
IntensiveCare Medicine 9 Springer-Verlag 1992
Severe acute myocardial infarction during a staphylococcal septicemia with meningoencephalitis A possible contraindication to thrombolytic treatment C.A. Reynard ~, P. Calain 2, G.P.
Pizzolato 4 and J.C. Chevrolet 3
1Cardiology Center, 2Division of Infectious Diseases, 3Medical Intensive Care Unit, Geneva University Hospital, and 4Department of Pathology (Neuropathology), Centre M6dical Universitaire, Geneva, Switzerland Received: 18 May 1991; accepted: February 4, 1992
Abstract. We r e p o r t t h e first c a s e o f l e t h a l i n t r a c r a n i a l h a e m o r r h a g e c o m p l i c a t i n g a t r e a t m e n t b y r t - P A in a p a t i e n t p r e s e n t i n g w i t h a s i m u l t a n e o u s s t a p h y l o c o c c a l septicemia with meningoencephalitis and an acute myocardial i n f a r c t i o n w i t h c a r d i o g e n i c s h o c k . T h e p r e s e n c e o f microvascular lesions in the central nervous system seems to be important risk factor for intracranial haemorrhage a n d we r e c o m m e n d e x t r e m e c a u t i o n in t h e u s e o f t h r o m b o l y t i c t r e a t m e n t in s e p t i c e m i c p a t i e n t s w i t h a c u t e m y o cardial infarction, particularly when neurological sympt o m s are p r e s e n t .
Key words: M y o c a r d i a l i n f a r c t i o n Meningitis -
Thrombolysis
-
Staphylococcus
Case report A 45-year old male patient with a 34-year history of insulin-dependent diabetes was admitted to the University Hospital of Geneva for headache, confusion and fever of 24 h duration. On admission he was ill, disorientated and febrile (40.4~ Erythematous, crusty, ulcerated but non-suppurative warm lesions were seen on the anterior side of both legs and nonpalpable purpuric lesions were noted on the fingers and on the toe tips. Pulse was 132/min and blood pressure 140/80 mmHg. Cardiac, pulmonary and abdominal examinations were normal. The patient was confused but the neurological examination was otherwise normal. Signs of non-proliferative retinopathy were noted on the fundus but there was no haemorrhage or exudate. Laboratory values were: haematocrit 45.1070, white-cell count 9100/mm 3 with 8~ band form and platelet count 107,000/ram 3. Prothrombin time was 85~ partial thromboplastin time 34.4 s (control: 2 5 - 31 s) and fibrinogen 0.44 g/1. Plasma glucose was 23 mmol/1, urea nitrogen, creatinine, electrolytes and hepatic function were normal. Creatine kinase was 220 U/I, with a MB fraction of 11 (5%). The CSF was clear with a glucose of 10.7 retool/l, protein of 0.79 g/1 and a white cell count of 206/rnm 3 with 98~ polymorphonuclear cells. Gram stain was negative. Our initial diagnosis was sepsis with meningo-encephalitis and septic emboli. Flucloxacillin and ceftriaxone were started. Two hours after admission, the patient developed ventricular tachycardia which promptly responded to an external DC shock. ECG (normal on admission) showed Pardee waves in the inferior and lateral leads. The diagnosis of
acute myocardial infarction was further confirmed by an elevation of the CK values (650 U/1 with a MB fraction of 65) and by echocardiography (akinesy of the inferior and lateral wails of the/eft ventricle). The clinical situation rapidly deteriorated with malignant arrhythmias and refractory shock, poorly responsive to vasoactive agents (dobutamine, dopamine, and finally noradrenaline). The patient was intubated and anticoagulation (heparin: 1000 U/h) and fibrinolysis (rtPA: 10 mg loading dose, then 50 mg during the first hour and 20 mg/h during the second and the third hour) were started (30 min after VT). The arrhythmia rapidly corrected and the hemodynamic course was favourable. Unfortunately, bilateral mydriasis developed while spontaneous respiration, response to pain and brain-stem reflexes disappeared. The patient died 4 days following admission. Blood cultures were positive for Staph. aureus. Autopsy (Fig. 1) revealed a fresh postero-septal lateral and right ventricular wall myocardial infarction, a fresh thrombus within the circumflex artery as well as a scar compatible with an old lateral and posterolateral subendocardial infarction. No valvular vegetation was recovered from gross examination of the heart. On histological examination the cardiac valves were unremarkable, and there was no septic coronary embolism. The brain showed bilateral edema, bilateral temporal-lobe and cerebellar tonsfllar herniations, and multiple haematomas in both hemispheres and in the brain stem. One haematoma (in the left frontal lobe) perforated in the left ventricle and the subarachnoid space causing a diffuse subarachnoid and intraventricular haemorrhage. Microscopically, there were diffuse neuronal necrosis, and multiple microabscesses in both hemispheres and in the brain stem. Infiltration by polymorphonuclear cells were found in the wall of numerous cerebral vessels consistent with vasculitis. No bacteria were seen on direct examination and on the Gram stain.
Discussion I n t h e p r e - t h r o m b o l y t i c era, s t r o k e was r e p o r t e d to c o m p l i c a t e t h e c o u r s e o f a c u t e m y o c a r d i a l i n f a r c t i o n in 0 . 8 % - 2 . 4 % o f p a t i e n t s [1, 2]. A d d i t i o n a l risk a s s o c i a t e d with the use of fibrinolytic agents appears to be minimal. I n r e c e n t r a n d o m i s e d trials o f t h r o m b o l y t i c t h e r a p y , t h e t o t a l s t r o k e r a t e has r a n g e d f r o m 0 . 5 % - 2 . 5 % and the risk o f i n t r a c r a n i a l h a e m o r r h a g e ( I C H ) has r a n g e d f r o m 0 . 3 % - 1.50/0 [ 2 - 8 ] . A h i g h e r r a t e ( 5 % ) was h o w e v e r rec e n t l y r e p o r t e d [9]. T h e risk f a c t o r s f o r I C H in p a t i e n t s t r e a t e d w i t h t h r o m b o l y t i c t h e r a p y are c u r r e n t l y p o o r l y d e f i n e d . F o u r p a t i e n t s w h o s u f f e r e d I C H in T A M I trial p r e s e n t e d w i t h
248
Fig. 1. a Brain slice (left hemisphere) showinga large frontal haemorrhage perforating in the subarachnoid space and the lateral ventricle
molded by a large clot. b (Haematoxylineeosinex i60) cortical microabscess, c (HE x 160) acute vasculitisin the white matter
at least one of prespecified risk factors of ICH (age > 65 years, history of hypertension, history of cerebrovascular disease, aspirin use and acute hypertension). However 80~ of patients without I C H also had at least one risk factor and 31 070 had two risk factors [7]. Only one of six patients with ICH reported by Kase was hypertensive during rt-PA infusion, but all received heparin and had a prolonged partial thromboplastin time (from 81 to more than 150 s) [9]. Althouse found no association between these classical risk factors and ICH in patients treated with rt-PA; however, this author suggests that a transient elevation of systolic (180 mmHg) or diastolic (120 mmHg) blood pressure immediately prior to rt-PA infusion is a risk factor for ICH [10, 11], Diabetic retinopathy, particularly the proliferative type, may be considered as a relative contraindication for thrombolytic treatment. Unfortunately, no data are presently available in humans that could be used as guidelines. The unique available information to date was recorded in diabetic patients submitted to a vitrect0my: intraocular rt-PA was used for fibrin deposition prevention but this drug Caused significant intracameral haemorrhage [12]. Vascular involvement in staphylococcal septicemia or endocarditis corresponds to multiple mechanisms: emboll can cause infarction, abscess and aneurysm formation; microvascular damage can result from seeding of bacteria or f r o m immune complex deposition. Although 10~ of the patients with staphylococcal endocarditis present with neurological abnormalities, the prevalence of microvascu!ar lesions in the CNS is unknown [13]. One can suspect that most of them are clinically silent, whereas the only available information on the frequency of CNS bleeding in Staph. aureus meningitis is an 18070 prevalence o f disseminated intravascular coagulation in such a situation [14]. Similarly, an extensive literature research was unfruitful for evaluating the precise frequency of
bleeding complications in any type of bacterial or viral meningoencephalitis, except for herpes simplex virus encephalitis, in which a severe temporal haemorrhagic cerebral necrosis may occur in a significant number of untreated, or lately treated cases [15]. In our patient, endocarditis with septic cerebral embolisation can be excluded: echocardiographic examination did not show any sign compatible with valvular vegetation, whereas the histologic examination of the valves was normal, and the myocardial infarction was not due to a coronary embolism. Incidently, there are presently no available data concerning the exact risk/benefit ratio of anticoagulant treatment in endocarditis with septic embolism [13, 16]. A recent case report presents a patient with a streptococcal bacterial endocarditis and a myocardial infarction, treated by an infusion of 120 mg of rt-PA in 2 h, a too rapid infusion rate caused by a technical problem. This patient experienced a small occipital hemorrhage following reperfusion [17]. Our case is the first description of severe and lethal ICH complicating a treatment by rt-PA in a patient presenting simultaneously with an acute myocardial infarction and staphylococcal septicemia with meningoencephalitis. In our opinion, the presence of microvascular lesions in the CNS is a risk factor for ICH to be considered in patients treated with any fibrinolytic agent. Therefore, although based on an isolated observation, we recommend extreme caution with thrombolytic tlaerapy in septicemic patients when vascular lesions can be suspected: emergency percutaneous transluminal coronary angioplasty, if possible, should be attempted preferentially in such a difficult situation. One should be aware, however, that a coronary artery mycotic aneurysm has been described as a complication at the dilatation site in a patient presenting with bacterial endocarditis and myocardial infarction [17].
249
References 1. Komrad MS, Coffey CE, Coffey KS, McKinnis R, Massey EW, Califf RM (1984) Myocardial infarction and stroke. Neurology 34:1403 - 1409 2. Wilcox RG, Olsson CG, Skene AM, Von Der Lippe G, Jensen G, Hampton JR for the ASSET Study Group (1988) Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet II: 526-530 3. Chesebro MD; Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Lundbrook P, Markis JE, Mueller H, Passamani ER, Powers ER, Ran AK, Robertson T, Ross A, Ryan TJ, Sobel BE, Willerson J, Williams DO, Zaret BL, Braunwald E (1987) Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 76:142-154 4. Gore JM, Sloane M, Price TR, Young Randall AM (1991) Intracerebral hermorrhage, cerebral infarction and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Circulation 83:448-459 5. Simoons ML, for the investigators of the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator (rt-PA) (1988) Thrombolysis with Tissue Plasminogen Activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. Lancet 1:197-202 6. Van De Werf F, for the investigators of the European Cooperative Study Group for recombinant Tissue-Type Plasminogen Activator (1988) Lessons from the European recombinant tissue-type plasminogen activator versus placebo trial. J Am Coll Cardiol 12:14A-19A 7. O'Connor M, Califf RM, Massey EW, Mark DB, Kereiakes DJ, Candela R J, Abbotsmith C, George B, Stack RS, Aronson L, Mantell S, Topol EJ (1990) Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and long-term prognosis. J Am Coil Cardiol 16:533-540 8. The International Study Group (1990) In-hospital mortality and
9.
10.
11.
12.
13. 14.
15.
16.
17.
clinical course of 20891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet II:71-75 Kase CS, O'Neal AM, Fisher M, Girgis GN, Ordia JI (1990) Intracranial hemorrhage after use of tissue plasminogen activator for coronary thrombolysis. Ann Intern Med 112:17-21 Althouse R, Maynard C, Olsufka M, Kennedy JW (1989) Risk factors for haemorrhage and ischemic stroke in myocardial infarction patients treated with tissue plasminogen activator. J Am Coll Cardiol 13:153A Althouse R, Weaver WD, Kennedy JW (1987) Transient elevation of diastolic blood pressure in acute myocardial infarction. A contraindication to thrombolytic therapy. Circulation 76:306-309 Dabbs C, Aaberg T, Aguilar H, Sternberg P, Meredith T (1989) Complications of the treatment of severe fibrinous response following diabetic vitrectomy with tissue plasminogen activator. Invest Ophtalmol Vis Sci 30 [Suppl]:273 Nolan C, Beaty H (1976) Staphylococcus aureus bacteremia: current clinical patterns. Am J Med 60:495-499 Sehlesinger L, Ross S, Schaberg D (1987) Staphylococcus aureus meningitis: a broad-based epidemiologic study. Medicine 66: 148-155 Nahmias A, Whitley R, Vinsintine A (1982) Herpes simplex encephalitis: laboratory evaluation and their diagnostic significance. J Infect Dis 145:829-834 Mandell G, Gordon Douglas R, Bennett J (1990) Principles and practice of infectious diseases, 3rd edn. Churchill Livingstone, New York, pp 670 and 1489 Herzog C, Henry T, Zimmer S (1991) Bacterial endocarditis presenting as acute myocardial infarction: a cautionary note for the era of reperfusion. Am J Meal 90:392-397
Dr. J. C. Chevrolet Medical Intensive Care Unit Geneva University Hospital CH-1211 Geneva 4 Switzerland
