Upsala J Med Sci 92: 75-78, 1987 Reatment of Severe Hypertension with Peroral Labetalol Goran Frithz Department of Medicine, Central Hospital, Eskilstuna, Sweden ABSTRACT 22 p a t i e n t s w i t h u n t r e a t e d , e s s e n t i a l h y p e r t e n s i o n ( d i a s t o l i c blood-pressure 2140 mmHg) and i n most cases a l s o showing n e u r o l o g i c a l symptoms were g i v e n a s i n g l e o r a l dose o f 400 mg l a b e t a l o l . All p a t i e n t s d i s p l a y e d a g r a d u a l decrease o f t h e blood-pressure down t o a d i a s t o l i c p r e s s u r e about 110 mmHg w i t h r e l i e f o f t h e symptoms. There were no s i g n s o f n e u r o l o g i c a l d e f i c i t due t o t h e reduc- t i o n o f blood-pressure. INTRODUCTION There i s s t i l l disagreement as t o when an e l e v a t e d blood-pressure s h o u l d be regarded as a m e d i c a l emergency and a c u t e t r e a t m e n t i n i t i a t e d . However, most c l i n i c i a n s would agree t h a t a p e r s i s t e n t d i a s t o l i c blood-pressure o f 1 140 mm Hg and/or s i g n s o f encephalopathy r e q u i r e a c u t e m e d i c a l i n t e r - v e n t i o n . On t h e o t h e r hand, i t is w e l l known t h a t t o o v i g o r o u s t r e a t m e n t and r a p i d r e d u c t i o n o f t h e blood-pressure may r e s u l t i n unwanted e f f e c t s and even permanent s i g n s o f c e r e b r a l damage. L a b e t a l o l , a combined a- and p-adrenoceptor-blocking agent, has been used i n t r a v e n o u s l y i n m i n i b o l u s doses or by c o n t r o l l e d i n t r a v e n o u s i n f u s i o n t o t r e a t v e r y severe h y p e r t e n s i o n . It has been shown t h a t l a b e t a l o l i s r a p i d l y absorbed and e x e r t s i t s maximum p h a r m a c o l o g i c a l a c t i o n two h o u r s a f t e r o r a l a d m i n i s t r a t i o n ( 3 ) . S i n g l e o r a l doses have been r e p o r t e d t o cause a marked r e d u c t i o n o f blood- p r e s s u r e ( 2 ) . The a c u t e blood-pressure r e d u c t i o n is m a i n l y achieved by an a-receptor-mediated r e d u c t i o n o f t h e t o t a l p e r i p h e r a l r e s i s t a n c e as l a b e t a l o l has b o t h a - r e c e p t o r and P - r e c e p t o r b l o c k i n g p r o p e r t i e s . The l a t t e r p r o p e r t y c o u n t e r a c t s t h e r e f l e x i n c r e a s e o f h e a r t - r a t e caused by t h e blood-pressure decrease (1 ) . T h i s communication r e p o r t s our experience o f 5 y e a r s ' use o f l a b e t a l o l i n severe h y p e r t e n s i o n i n an emergency ward. 75 PATIENTS AND METHODS 22 patients, 14 men and 8 women (mean age 53.4 years), were consecutively treated in the emergency ward and Intensive Care Unit. They were all admitted to the hospital with a diastolic blood-pressure of 2 140 mmHg (range 140-160) and neurological symptoms, such as headache, vertigo and dizziness, were present in most cases. Six patients had choked optic discs (fundus hypertonicus I V ) . None had a history of cerebrovascular lesion, myocardial infarction o r renal failure and no antihypertensive treatment had been given. A complete physical exami- nation was performed and recorded immediately upon the patient’s arrival. The pressure and heart-rate in the supine position were registered every half hour during the first few hours without any treatment. When the blood-pressure was persistently elevated, treatment was initiated with a single oral dose of 400 mg labetalol. In 6 patients, an intravenous injection of 40-80 mg furosemide was also given owing to signs of left ventricular strain. No other medication was given at the same time. The patients were continuously observed for 6-8 hours with repeated registrations of blood-pressure and heart-rate. The blood-pressure was measured with a mercury sphygomanometer and the diastolic pressure was registered as Korotkoff phase V . After the initial period, the patients were transferred to an ordinary medical ward for further treatment and examinations. In five patients there were signs of an impaired renal function with elevated serum creatinine levels (range 138-236 pmol/l. Normal upper limit < I 2 5 pmol/l). No one was found to have any endocrine disorder. Student’s t-test for paired differences was used for statistical evaluation. RESULTS AND DISCUSSION The effect of the treatment upon systolic and diastolic blood-pressure and heart-rate is shown in Table I. There was a highly significant reduction of the blood-pressure after one hour (systolic blood-pressure p <0.001, diastolic blood-pressure p < 0 . 0 1 ) . A further decrease was observed up to four hours after tablet intake (Tab I). Thereafter, the blood-pressure seemed to stabilize at about 110 mmHg diastolic. No significant changes in heart-rate were observed. Linear regression analysis showed a significant correlation between the initial diastolic blood-pressure level and the pressure after four hours (r = 0.52, p <0.02). 76 I n a l l b u t one p a t i e n t t h e n e u r o l o g i c a l symptoms had vanished a f t e r 3 hours. Three p a t i e n t s complained o f moderate nausea d u r i n g t h e o b s e r v a t i o n p e r i o d . No severe s i d e e f f e c t s were r e g i s t e r e d d u r i n g t h e a c u t e t r e a t m e n t o r subsequently d u r i n g h o s p i t a l i z a t i o n . I n p a r t i c u l a r , t h e r e were no s i g n s o f n e u r o l o g i c a l d e f i c i t due t o an i m p a i r e d c e r e b r a l c i r c u l a t i o n . Tab. I. S y s t o l i c (SBP) and d i a s t o l i c (DBP) blood-pressure and h e a r t - r a t e (HR) b e f o r e and 1 , 4 and 8 h o u r s a f t e r o r a l a d m i n i s t r a t i o n o f 400 mg l a b e t a l o l . The s i g n i f i c a n c e s a r e i n r e l a t i o n t o t h e i n i t i a l values. Hours 0 1 4 8 SBP mmHg 242 f 10 210.7 f 9 172.1 f 8 168 f 6 p <0.001 p <0.001 p <0.001 DBP mmHg 145 * 7 137.8 2 9 114.5 2 6 112 -f 9 p <0.01 p <0.001 p <0.001 HR beat/min 7 2 2 6 7 8 f 4 7 0 2 5 72 f 4 n.s. n.s. n.s. The f i n d i n g s a r e i n accordance w i t h e a r l i e r o b s e r v a t i o n s t h a t l a b e t a l o l is r a p i d l y absorbed and i t s maximum e f f e c t upon i s o p r e n a l i n e - i n d u c e d haemo- dynamic changes is a t t a i n e d a f t e r about two hours ( 3 ) . The p r a c t i c a l l y unchanged h e a r t - r a t e i n c o m b i n a t i o n w i t h t h e decrease o f blood-pressure i n d i c a t e s a f a v o u r a b l e balance between t h e a - r e c e p t o r and P - r e c e p t o r - b l o c k i n g p r o p e r t i e s o f l a b e t a l o l . E x p e r i m e n t a l s t u d i e s have shown a r a t i o o f 1 : 3 between t h e a- and P - b l o c k i n g e f f e c t a f t e r o r a l a d m i n i s t r a t i o n ( I ) , which is a p p a r e n t l y a l s o f a v o u r a b l e i n t h e a c u t e s i t u a t i o n . The dose o f 400 mg l a b e t a l o l seems t o be adequate f o r t r e a t m e n t o f hyper- t e n s i v e emergencies. The m a t e r i a l is t o o s m a l l t o p r i n t r e l i a b l e c o n c l u s i o n s about t h e a d d i t i v e e f f e c t o f i n t r a v e n o u s d i u r e t i c s and i n t h i s study they were n o t used f o r t h e t r e a t m e n t o f h y p e r t e n s i o n per se. S e v e r a l a u t h o r s have warned a g a i n s t r a p i d r e d u c t i o n o f t h e blood-pressure i n severe h y p e r t e n s i o n and t h e t r e a t m e n t s h o u l d c e r t a i n l y o n l y be g i v e n upon s t r i c t i n d i c a t i o n s and i n h o s p i t a l . However, oral a d m i n i s t r a t i o n of l a b e t a l o l produces a g r a d u a l r e d u c t i o n o f t h e b l o o d pressure. I n this s t u d y , t h e dose used d i d n o t g i v e an excessive f a l l o f blood-pressure, which c o u l d l e a d t o a d i s t u r b e d c e r e b r a l c i r c u l a t i o n , w i t h t h e c l i n i c a l hazards t h i s e n t a i l s . ACKNOWLEDGEMENT Mrs K e r s t i n Blomberg is thanked f o r s k i l l f u l a s s i s t a n c e and h e l p . 77 REFERENCES 1 . Koch, G.: C a r d i o v a s c u l a r dynamics a f t e r acute and l o n g t e r m adrenoreceptor blockade a t r e s t , supine and s t a n d i n g and d u r i n g e x c e r c i s e . B r . J. 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