Br Heart J: first published as 10.1136/hrt.37.10.1059 on 1 October 1975. Downloaded from British HeartJournal, I975, 37, I059-I063. Factors predisposing to postural hypotensive symptoms in the treatment of high blood pressure S. Talbot and A. J. Smith From Sheffield Hypertension Clinic and Section of Therapeutics, Academic Division of Medicine, Royal Infirmary, Sheffield Symptoms due to orthostatic and exertional hypotension occurred in 23.4 per cent of 448 hypertensive patients treated with guanethidine, debrisoquine, or bethanidine. Symptoms were significantly more frequent in patients treated with guanethidine than in those treated with bethanidine or debrisoquine. Women rather than men and patients with radiological evidence of cardiomegaly, electrocardiographic evidence of left ventricular hypertrophy, or STIT wave changes, developed these symptoms signifcantly more often than other patients. A raised blood urea wasfound morefrequently in patients with postural hypotensive symptoms. Characteristically guanethidine produced early morning postural hypotensive symptoms, whereas hypo- tensive symptoms caused by bethanidine and debrisoquine occurred at other times of the day and particularly one to two hours after tablet ingestion. Debrisoquine andguanethidine had a significantly greater negative chronotropic effect than bethanidine. It is suggested that negative chronotropic effects of these drugs may potentiate hypotensive symptoms in patients with cardiovascular, renal, or cerebrovascular disease. It should be possible to minimize symptoms of postural hypotension by attention to predisposingfactors and selection of treatment accordingly. http://heart.bmj.com/ Treatment of hypertension with post-ganglionic yearly intervals. The patients in this study were seen sympathetic blocking drugs produces hypotension between February I972 and October I972 (inclusive) by related to posture: this is both an inevitable conse- one observer. If at this visit they had been on hypo- at quence of their mode of action and a possible cause tensive treatment for least i8 months and complained of dizziness, whether this was orthostatic dizziness or not of troublesome side effects. In mild cases other was identified by further questioning. Patients were con- drugs without orthostatic effects may be used, but sidered to have symptoms of postural hypotension if at treatment with post-ganglionic sympathetic blocking any visit there was a drop of systolic pressure of >30 on October 1, 2021 by guest. Protected copyright. drugs may be essential for more severe hypertension, mmHg (4.o kPa) on standing from the supine position and debrisoquine, bethanidine, and guanethidine or on walking up and down 75 stairs (exertional hypo- are the drugs most frequently employed. Debriso- tension), and ifthis drop ofpressure was related to symp- quine and bethanidine are said to produce fewer toms. Patients were not included if they complained of orthostatic symptoms than guanethidine (Bath, vertigo or dizziness, which was not clearly related to post- Pickering, and Turner, I967; Kitchin and Turner, ure and/or exertion. Patients were also excluded if they were on more than one drug (with or without a diuretic). I966). Bythese criteria all the patients eventually included in this It was the aim of this study to determine the study could be described as either symptomatic or proportion of hypertensive patients on treatment asymptomatic in respect of dizziness related to ortho- with these drugs who suffered from postural symp- static hypotension. toms and to identify any predisposing factors. Only symptoms and blood pressure levels found at least 6 months after the initiation of therapy were re- Method corded. Any patients in whom symptoms were thought Patients are reviewed at least every three months in the to be caused by inappropriate timing of doses or exces- Sheffield Hypertension Clinic. The electrocardiogram, sive therapy were not included in the survey unless blood urea, and chest radiograph are repeated at symptoms persisted after appropriate dose readjust- Received 27 January 1975. ments. Br Heart J: first published as 10.1136/hrt.37.10.1059 on 1 October 1975. Downloaded from Io6o Talbot and Smith The age, height, weight, and blood pressure levels The mean heart rates of all groups were similar of each patient before and after treatment with debriso- before treatment but afterwards there were signi- quine, guanethidine, or bethanidine were recorded as ficant differences. Debrisoquine and guanethidine well as the initial blood urea, the heart rate from the slowed the resting heart rate by i6 per cent but electrocardiogram, and electrocardiographic criteria of left ventricular hypertrophy (Sokolow and Lyon, bethanidine only slowed the heart rate by 5.6 per cent < were effects on the I949). ST/T wave changes were coded according to the (P o.oi). There parallel revised Minnesota Code (Rose and Blackburn, I968). standing heart rates, which for all groups were Radiological evidence of cardiomegaly was defined as a slightly higher than the supine heart rates. cardiothoracic ratio of >I:2. Dizziness was described Evidence of vascular and renal disease was signi- as mild if it was recorded on at least three occasions after ficantly more frequent in all the symptomatic the first 6 months of treatment, but had disappeared by groups (P < o.oi). Cardiomegaly and electrocardio- the date of the study; moderate if it had persisted up to graphic evidence of left ventricular hypertrophy this time; severe if it had been recorded on at least 6 were more often present in the symptomatic groups occasions or blackouts had occurred; and disabling if (P < o.oi). ST/T wave changes were more frequent treatment had had to be changed on its account. From the last clinic review the lying and standing in the patients with postural hypotensive symptoms, blood pressure levels and the heart rates were recorded, and pretreatment blood urea was significantly higher and also the blood urea, electrocardiographic changes, inthis group (P < o.oi). After treatment symptomatic and the radiological heart size. patients showed significantly greater rises of the blood urea and more frequent electrocardiographic Results evidence of left ventricular hypertrophy and radio- There were 448 patients treated with post-ganglionic graphic evidence of cardiomegaly (P < o.oi). Women sympathetic blocking drugs; 205 were taking had postural symptoms relatively more frequently guanethidine, I58 bethanidine, and 85 debrisoquine. than men (P < 0.02) (Table 2). Results for patients with postural symptoms of No permanent complications of postural hypo- different severity have been amalgamated for ease of tension were detected. Angina frequently occurred presentation. For each drug patients have been in patients who also complained of postural symp- divided into those with symptoms of postural toms (36, 34%), but angina rarely occurred at the hypotension and those without such symptoms. same time as the hypotensive symptoms even if There were no significant differences in the mean these occurred on exertion. However, in some supine and standing blood pressure levels and the patients before admission to the study it was noted average age and weight between these groups of that severe hypotensive episodes caused by inap- http://heart.bmj.com/ patients before treatment (Table i). propriate dose of drug were sometimes associated TABLE i Blood pressure levels and heart rates of patients treated with post-ganglionic sympathetic blocking drugs Guanethidine Debrisoquine Bethanidine Asymptomatic Symptomatic Asymptomatic Symptomatic Asymptomatic Symptomatic No. of patients I45 6o 70 I5 128 30 on October 1, 2021 by guest. Protected copyright. Blood pressure (mmHg) before, supine 2I7/I26 2I8/127 2IO/122 211/I26 2I4/I2I 220/I3I after, supine I75/I00 I78/IOI I68/IOO I68/98 I72/102 I84/98 Blood pressure (mmHg) before, standing 217/128 2I6/129 2IO/124 201/127 213/126 207/129 after, standing I60/94 I59/96 I60/96 I47/98 I56/96 159/99 Heart rate, before treatment (beats/min) (supine)* 74 77 75 85 78 8o Heart rate, after treatnent (beats/min) (supine)* 63 63 64 68 73t 78t Treatment period (yr) 5.7 5.5 2.2 2.5 2.9 3.0 Mean age (yr) 53.8 57.2 53.3 59.2 53.3 54.6 Weight (kg) 71.4 74.1 71.1 68.2 74.2 74.9 Daily dose (mg) 72.4 61.4 74.3 71.5 105.3 II0.9 * Significant differences between average heart rates before and after treatment for the total groups of patients on guanethidine, debrisoquine, and bethanidine (grouped 't' test, P <o.ooI). t Significant differences between the average heart rates after treatment with bethanidine and the average heart rates after treatment with debrisoquine and guanethidine (grouped 't' test, P <O.OI). Conversion factor from Traditional units to SI units: I mmHg 0.I33 KPa. Br Heart J: first published as 10.1136/hrt.37.10.1059 on 1 October 1975. Downloaded from Predisposition to postural hypotensive symptoms Io6I TABLE 2 Factors associated with postural hypotensive symptoms Guanethidine Debrisoquine Bethamdine Asymptomatic Symptomatic Aysmptomatic Symptomatic Asymptomatic Symptomatic No. of patients I45 60 70 15 I28 30 Mean blood urea* (mmol/l) initially 6.I 6.5 5.7 6.4 5.8 6.4 Rise of blood urea* (mmol/l) after treatment I.5 2.7 I.I 2.6 I.I 2.3 Initial cardiomegalyt 54 (37v.2) 38 (63.3) 30 (42.9) 9 (60.0) 49 (38.3) 2I (70.0) Persistent cardiomegaly after treatmentt 52 (35.9) 45 (75-0) 29 (4I.4) I2 (8o.o) 47 (36.7) 26 (86.7) Initial voltage criteria of left ventricular hyper- trophyt 25 (I7.3) 34 (56.7) 12 (I7I) 6 (40-0) 14 (I0.9) I7 (56.7) Voltage criteria of left ventricular hypertrophy after treatmentt 22 (I5.2) 42 (70.0) I0 (14.3) I2 (80.0) I5 (II.7) I9 (63.3) Initial electrocardiograms with ST/T wave changest 44 (30.3) 26 (43.3) I7 (24.3) 8 (53.3) I7 (I3-3) I3 (43.3) Electrocardiograms with ST/T wave changes after treatmentt 4I (28.3) 3I (5i.6) I5 (21.4) 8 (53.3) I7 (I3-3) I4 (46.7) Men - total number 1i: 87 24 39 6 72 i6 Women - total numberf 58 36 3I 9 56 I4 * Significant differences between the total group with symptoms and the group without symptoms using grouped 't' test (P<o.oi).