Postgrad Med J 1999;75:213–218 © The Fellowship of Postgraduate Medicine, 1999 Postgrad Med J: first published as 10.1136/pgmj.75.882.213 on 1 April 1999. Downloaded from

Orthostatic haemodynamic responses in acute

B Panayiotou, J Reid, M Fotherby, P Crome

Summary tension in this age group reduces cerebral blood Little is known about orthostatic blood flow and carries considerable morbidity from pressure regulation in acute stroke. We dizziness, falls and injury.4 In acute stroke, cer- determined postural haemodynamic re- ebral perfusion is dependent on systemic blood sponses in 40 patients with acute stroke pressure because cerebrovascular autoregula- (mild or moderate severity) and 40 non- tion is impaired.5 Thus, postural in stroke control in-patients, at two days acute stroke patients may further impair (‘Day 1’) and one week (‘Week 1’) post- cerebral blood flow, increase stroke size, or admission. Following a 10-minute supine hinder recovery. Data on postural hypotension rest and baseline readings, subjects sat up in acute stroke may have implications for early and blood pressure and heart rate were rehabilitation and the use of vasoactive drugs. taken for 5 minutes. The procedure was The objective of this study was to determine repeated with subjects moving from su- postural haemodynamic responses in the acute pine to the standing posture. Haemody- and recovery phases of stroke. namic changes from supine data were analysed. On standing up, the control Materials and methods group had a transient significant fall in mean arterial blood pressure on Day 1 but SUBJECTS not Week 1. No significant changes were Patients aged >65 years with a mild or moder- 6 seen on either day when sitting up. In con- ate (Canadian Neurological scale score >70) trast to controls, the stroke group showed acute ischaemic stroke (WHO definition) were increases in mean arterial blood pressure considered for the study. Those with haemor- on moving from supine to the sitting and rhagic stroke confirmed on computed tomog- standing positions on both days. Persist- raphy (CT) scanning or suspected clinically by ent postural hypotension defined as >20 the presence of headache, neck stiVness and vomiting, and patients with a Guy’s score7 pre- mmHg systolic fall occurred in <10% of http://pmj.bmj.com/ either of the study groups on both days. dicting a <90% chance of an ischaemic stroke Sitting and standing heart rates in both were not included. An age- and sex-matched groups were significantly faster than su- control group was selected from admissions pine heart rate on both days. The orthos- without history of cerebrovascular disease. tatic blood pressure elevation is consistent Both groups had to be conscious and coopera- tive, previously mobile and living at home with sympathetic nervous system overac- 8 tivity which has been reported in acute (Modified Rankin scale score <3), and have stroke. Upright positioning as part of early no history of dizziness or falls. As about 50% of on September 27, 2021 by guest. Protected copyright. rehabilitation and mobilisation following patients with acute stroke have a known history of hypertension and are receiving antihyperten- mild-to-moderate stroke would, there- 910 fore, not predispose to detrimental pos- sive therapy, patients were included whether tural reductions in blood pressure. they were on antihypertensive drugs or not. Subjects were excluded if they had coexisting Keywords: stroke; orthostatic hypotension; hypoten- illnesses which can aVect blood pressure regu- sion lation (eg, diabetes, Parkinson’s disease), se- vere ischaemic heart disease or heart failure, myocardial infarction in the previous 6 Lesions of the central nervous system frequently months, atrial fibrillation, evidence of dehydra- cause disturbances of the cardiovascular and tion, anaemia, bleeding, , septicae- autonomic nervous systems. In acute stroke, mia, renal failure, respiratory failure, or pulmo- raised levels of circulating ,1 nary embolism. The study was approved by the parasympathetic system hypofunction,2 tran- local ethics committee, and informed consent sient hypertension, and attenuated or reversed was obtained from all participating subjects. Elderly Care Department, Manor circadian variation in blood pressure and heart 3 Hospital, Walsall rate are common. However, little is known MEASUREMENTS WS2 9PS, UK about orthostatic haemodynamic responses in Both groups were studied within 3 days of B Panayiotou the first few days post-stroke. admission (‘Day 1’), and again 4–7 days after J Reid Stroke occurs predominantly in the elderly, the first study (‘Week 1’). In stroke patients, M Fotherby P Crome who are prone to orthostatic hypotension Day 1 had to be within 3 days of stroke onset. because of the eVects of ageing and comorbid- Blood pressure and heart rate readings were Accepted 19 November 1998 ity on blood pressure regulation. Postural hypo- taken using an automatic SpaceLabs 90207 214 Panayiotou, Reid, Fotherby, et al

oscillometric device (SpaceLabs Inc, Red- parametric data between treated and untreated Postgrad Med J: first published as 10.1136/pgmj.75.882.213 on 1 April 1999. Downloaded from mond, WA, USA) which meets the validation patients were made with the Mann-Whitney U criteria of the British Hypertension Society.11 test. In stroke patients, the cuV was applied to the non-paretic arm. In all subjects the same arm Postural hypotension was used for the two studies. Patients were The incidence of postural hypotension as studied before or >2 hours after meals on both defined by >20 mmHg systolic drop was days. determined, and the chi-square for trend test Following 10 minutes of supine rest, the was used to assess changes with time in each mean of two successive blood pressure and group. Between-group comparison of the heart rate readings were recorded. Single frequency of postural hypotension was made measurements of blood pressure and heart rate by the chi-square test. were then taken at 1, 3, and 5 minutes after moving to the sitting position. Following a fur- Study power calculation ther 10-minute supine rest and baseline meas- It was calculated that, given that the SD of the urements, the procedure was repeated with supine to standing SBP diVerence in elderly subjects in the standing position. Stroke hospitalised patients is ±10 mmHg,12 28 patients who were unable to stand independ- subjects would be needed to detect a within- ently or with minimal help (eg, because of their group orthostatic SBP change of >6 mmHg neurological deficits), were not investigated in with a power of 80% at the 5% significance the standing posture. Hypotensive symptoms level. To show a diVerence of >6 mmHg during the sitting or standing phases (dizziness, between stroke and control subjects with the light-headedness, disturbance of conscious same power and significance level, 40 subjects level) were noted. would be needed in each group.

ANALYSIS Results

Haemodynamic data SUBJECTS Mean arterial blood pressure (MABP) was cal- Forty stroke patients (21 male), mean age 76 culated using the formula: years (SD 7.3, range 65–92), were studied, of whom 35 had hemiplegia or monoplegia, and MABP = DBP + [SBP− DBP] / 3, five had only facial paralysis, language and/or where DBP and SBP stand for diastolic and swallowing impairment. Their median Cana- systolic blood pressure, respectively. All dian Neurological scale score was 90 (range haemodynamic data were entered into a 70–105) and Modified Rankin score was 2 computerised database. Within- and between- (range 0–3). A CT scan was performed in 18 group comparisons for baseline parametric patients (45%) in whom cerebral infarction data were made with the Student’s paired and was diagnosed. unpaired t-tests, respectively, the significance The 40 control patients (20 male) had a http://pmj.bmj.com/ level being 5%. Paired t-tests were used in each mean age of 75 years (SD 6, range 65–90) group to compare 1-minute sitting and stand- (versus stroke group, p>0.05), and premorbid ing with supine haemodynamic parameters. median Modified Rankin score of 2 (range Haemodynamic changes from supine to 1 0–3). Their presenting diagnoses were: exacer- minute (after transformation to percentage bation of chronic bronchitis (14), angina (five), changes to allow for baseline inequalities arthritis (four), musculoskeletal chest pain between the stroke and control groups) were (three), two each with thrombophlebitis, calf

compared between the two groups with deep vein , mild left ventricular fail- on September 27, 2021 by guest. Protected copyright. unpaired t-tests. Two-way analysis of variance ure, irritable bowel syndrome, constipation, (ANOVA) was used in each group to assess and depression, and one each with polymyalgia whether haemodynamic changes from baseline rheumatica and tension headache. diVered significantly at 1, 3, and 5 minutes of sitting and standing. Pearson’s correlation ANTIHYPERTENSIVE THERAPY coeYcient was used in both study groups to Twenty-three of the stroke and 15 of the assess the correlation between postural haemo- control patients were admitted on antihyper- dynamic changes and (a) pre-stroke Modified tensive agents, including drugs given for other Rankin score, and (b) Canadian Neurological indications but with known antihypertensive scale score in stroke patients. Non-parametric properties (eg, -converting enzyme data were compared between the stroke and inhibitors and calcium antagonists). Antihy- control groups with the Mann-Whitney U test. pertensive agents were withdrawn in some patients on admission, and during the period of Antihypertensive therapy study 19 (48%) stroke and 13 (33%) control Postural haemodynamic changes were also patients received antihypertensive drugs analysed within the stroke and control groups (p>0.05). The median number of antihyper- for patients on or oV antihypertensive drugs. tensive drugs taken per patient was 0 (range Paired t-tests were used for changes from base- 0–2) in the stroke group and 0 (0–2) in the line to 1 minute in treated and untreated control group (p>0.05). patients. The haemodynamic changes at 1 There was no significant diVerence within minute were compared between treated and the stroke or control group between treated untreated patients within each group using and untreated patients as regards age (stroke unpaired t-tests. Comparisons of non- group: 75±7 vs 78±7 years; control group: 76±5 Orthostatic blood pressure regulation in stroke 215

Ta bl e 1 Postural blood pressure (mmHg) and heart rate changes (±SD) in stroke patients and controls Postgrad Med J: first published as 10.1136/pgmj.75.882.213 on 1 April 1999. Downloaded from

Stroke patients Control patients

SBP DBP MABP HR n SBP DBP MABP HR n

Day 1 Supine 157±26 83±14 108±16 75±14 40 142±26 76±12 98±16 78±14 40 Change on sitting 1min −1±11 5±7*** 2±10 4±7†** 40 0±61±71±65±5*** 40 3 min 3±10 5±10 4±82±7† 40 0±82±71±73±840 5 min 1±13 4±10 2±92±5† 40 −1±10 2±82±93±640 Supine 156±26 83±11 108±13 75±16 40 140±26 76±11 97±14 77±14 40 Change on standing 1min −4±16 3±80±10† 9±6** 26 −8±14††*** −2±7†† −4±8†††** 11±10*** 40 3 min 0±16 5±93±10† 6±826−4±12†† 0±7†† 0±8††† 11±940 5 min 1±15 5±83±9† 6±11 23 −3±16†† 2±8†† 1±9††† 12±10 39 Week 1 Supine 149±21 79±13 102±13 73±15 40 140±25 73±995±13 79±13 40 Change on sitting 1min −1±10 4±7** 3±6** 3±6††*** 40 0±72±72±65±5†††*** 40 3 min 0±93±92±72±6†† 40 1±63±73±63±5††† 40 5min −1±11 2±81±71±6†† 40 −2±13 3±71±72±5††† 40 Supine 148±21 79±14 102±14 72±14 40 137±26 73±11 94±15 77±13 40 Change on standing 1min −5±15†††* 3±10† 0±11†† 8±14** 36 −7±13††** 2±8−1±813±9†*** 39 3 min 2±13††† 5±8† 4±9†† 5±10 35 −2±15†† 2±91±10 10±9† 38 5 min 2±12 ††† 7±9† 5±8†† 7±12 33 −2±14†† 3±82±810±8† 38

SBP: systolic blood pressure, DBP: diastolic blood pressure, MABP: mean arterial blood pressure; *p<0.05, **p<0.01, ***p<0.001 (paired t-test, 1 minute vs supine); †p<0.05, ††p<0.01, †††p<0.001 (2-way ANOVA: 1,3,5 minutes).

vs 74±6 years), Modified Rankin score (stroke occurred in DBP on sitting up and in MABP group: 2 (range 0–3) vs 1 (0–3); control group: on standing up. DBP and MABP elevations 2(1–3) vs 2(0–3)), or Canadian Neurological were also seen on Week 1 after sitting and score in stroke patients (Day 1: 85 (70–110) vs standing up. The only significant change in 90 (70–115); Week 1: 90 (50–115) vs 95 SBP was a short-lived fall just after standing on (60–115)). Week 1. Heart rate increased significantly on Baseline blood pressure and heart rate (HR) both days at 1 minute after sitting and standing were also similar in treated and untreated up. The rate then fell between 1 and 5 minutes patients (p>0.05) in both groups, during both post-sitting up, but remained unchanged phases of the study: (Stroke group: Day 1: throughout the standing-up phases. MABP 111±15 vs 105±17 mmHg, HR 70±13 In contrast to stroke patients, the control vs 78±15 beats/min; Week 1: MABP 104±13 vs group on Day 1 exhibited transient falls in SBP, 101±13 mmHg, HR 70±13 vs 76±15 beats/ DBP, and MABP. At Week 1, standing DBP min. Control group: Day 1: MABP 96±16 vs and MABP were unchanged despite a transient http://pmj.bmj.com/ 99±16 mmHg, HR 80±15 vs 78±13 beats/min; SBP fall. Blood pressures were unchanged on Week 1: MABP 97±15 vs 95±13 mmHg, HR sitting up on both days. The patterns of heart 79±12 vs 78±13 beats/min). rate responses were similar to the stroke group. Direct comparisons of the two groups for all HAEMODYNAMIC STUDIES 1-minute data revealed a significantly greater The stroke group was studied a median of 2 DBP rise in stroke patients on Day 1 after sit- (range 1–2) days and 6 (range 5–9) days post- ting up (6%±10 vs 1.5%±10, p<0.05) and on September 27, 2021 by guest. Protected copyright. admission (< 3 and 6–10 days, respectively, standing up (3%±10 vs −2%±9, p<0.05). post-stroke), and the control group 2 (range 1–3) and 7 (range 5–10) days post-admission. Relationship to other parameters In every patient in both groups the two studies There was no significant correlation between were performed at least 4 days apart. Baseline the postural haemodynamic changes and the measurements and postural responses in HR, pre-stroke Modified Rankin scores in stroke or SBP, DBP, and MABP are summarised in table control groups, or the Canadian Neurological 1. None of the patients were discharged or died scale scores in stroke patients. during the study.

Supine data Relationship to antihypertensive therapy Supine blood pressure was significantly higher Statistical comparison of postural blood press- in the stroke group on both days (p<0.05). ure responses at 1 minute between patients on, Between Day 1 and Week 1 there was a signifi- and those not on antihypertensive drugs cant fall in all supine blood pressure param- revealed no significant diVerences in the stroke eters in , and in diastolic pressure in or control group. The MABP data (treated vs controls (p<0.01). The supine haemodynamic not treated patients) are summarised below: data preceding the sitting and standing phases Stroke group: Day 1, sitting up: −5±7 vs 1±11 on each day did not diVer significantly in either mmHg; standing:−4±11 vs -2±6 mmHg; Week group. 1, sitting up: −1±11 vs 0±8 mmHg; standing: −1±10 vs 0±11 mmHg. Control group: Day 1, Postural responses sitting up: 1±5 vs −1±7 mmHg; standing: 6±9 In stroke patients on Day 1 (table 1), vs 3±8 mmHg; Week 1, sitting up:−2±5 vs statistically significant, sustained elevations −2±6 mmHg; standing: 0±7 vs 1±8 mmHg. 216 Panayiotou, Reid, Fotherby, et al

Ta bl e 2 Number of patients with postural systolic ance. This restores cardiac output with a fall or Postgrad Med J: first published as 10.1136/pgmj.75.882.213 on 1 April 1999. Downloaded from blood pressure fall of >20 mmHg (numbers in no change in systolic pressure, a rise in diasto- parentheses are percentages) lic pressure, and consequently a mean arterial 14 Stroke group Control group pressure similar to the supine level. A haemo- dynamic steady-state is normally reached Day 1 Day 2 Day 1 Day 2 within one minute.15 The same pattern is seen Sitting in healthy adults and the elderly, although in 1min 2(5) 2(5) 0 0 the latter the tachycardia and diastolic rise can 3min 0 0 1(3) 0 be less pronounced.14 5min 3(8) 2(5) 2(5) 3(8) Standing The rise we observed in postural blood 1 min 5 (19) 7 (19)† 7 (18) 6 (15) pressure post-stroke is likely to be due to sym- 3 min 3 (12) 2 (6)† 4 (10) 4 (11) 5 min 2 (9) 1 (3)† 3 (8) 3 (8) pathetic nervous system activation. Indices of baseline sympathetic nervous system activity, †p=0.05, ÷2 for trend. eg, serum and urinary catecholamines, are raised in the first week post-stroke.116This has been attributed to stress from acute illness, eVects of cerebral tissue damage, and ischae- Orthostatic hypotension mia of autonomic nervous system centres. A The frequency of patients with orthostatic positive correlation between the degree of sym- hypotension is shown in table 2. Between 3% pathetic overactivity and the level of resting and 19% of strokes and 8–18% of controls blood pressure in acute stroke has also been exhibited a systolic fall of >20 mmHg reported.16 A significant association has also (sustained or transient) during the standing been found between the extent of sympathetic phase in the two sessions. There was no signifi- activity and attenuation of the physiological cant diVerence within each group between the blood pressure fall at night.17 two days, or between groups on each day. However, only a few studies have sought to Prevalence of postural hypotension fell signifi- determine postural haemodynamic responses cantly in the stroke group during the standing following stroke. Korpelainen et al2 performed phase on Day 7. passive orthostasis (90° tilting, up to 7 minutes) in 40 ischaemic stroke patients (mean Symptoms age 51 years) within 10 days of onset, but did One stroke patient developed dizziness on not find a significant change in blood pressure. standing and had a systolic fall of >20 mmHg. While physiological responses to active orthos- In all remaining patients who were unable to tasis (standing up) and passive orthostasis complete the standing phase (see table 1) no (>70° tilting) are usually similar,18 Kor- hypotensive symptoms were reported, and the pelainen et al2 studied much younger patients, reasons for the inability to stand for the full 5 in whom resting sympathetic activity19 and its minutes were the motor deficits and poor response to orthostasis20 are known to be

balance due to their stroke. significantly less than in the elderly. Robinson http://pmj.bmj.com/ Five control patients reported orthostatic et al21 studied nine elderly patients and eight dizziness; in two of them it was mild and they matched non-stroke control subjects (60° were able to complete the study, but in three head-up tilt) and found a statistically signifi- the dizziness was severe and prevented them cant blood pressure fall in stroke patients com- from completing the standing phase (see table pared with control subjects. However, that 1). In these three patients, one had a systolic study was performed between one and three fall of >20 mmHg and the others <10 mmHg. weeks post-stroke rather than within the first 22 No symptoms were recorded in the stroke or week. Farnworth et al measured blood press- on September 27, 2021 by guest. Protected copyright. control group in the sitting position. ure in the sitting position and after 1 minute of standing in 15 elderly stroke patients (post- Discussion acute phase) who were receiving rehabilitation at a Day Hospital, and found a non-significant In agreement with previous studies of non- blood pressure rise of 12/10 mmHg. Naver et stroke elderly admissions,13 the control group al23 performed head-up tilt (80°, for 5 minutes) exhibited an orthostatic blood pressure fall soon in 23 patients (mean age 50 years) between 8 after admission. A week later, stability of mean and 48 days post-stroke (mean 18 days) and a blood pressure on standing was restored in matched group of healthy subjects. They these patients. Unlike the control group, acute reported that after 30 seconds the stroke stroke patients had significant elevations, rather patients had a significantly greater fall in SBP than falls, in diastolic and mean blood pressures than controls (9 vs 1 mmHg, p<0.05), without when they moved from the supine to the sitting a significant change in DBP.No further change or standing postures. The incidence of sus- was seen in the control group, whereas in tained postural hypotension defined as >20 stroke patients blood pressure continued to fall mmHg systolic fall was <10% in both groups. and stabilised at 2.5 minutes (magnitude of the Sudden orthostasis causes an immediate blood pressure fall was not given). Johnson et blood pressure fall because of peripheral al13 tested 100 unselected elderly acute admis- venous pooling and reduced cardiac output. sions and found >20 mmHg systolic fall within Normally, feedback from baroreceptors 2 minutes of standing in 17 patients. All of the quickly leads to sympathetic system activation latter patients were reported to have ‘evidence and parasympathetic inhibition, with compen- of cerebrovascular disease’ but it was not stated satory rises in heart rate and peripheral resist- how many had an acute stroke. Palmer24 also Orthostatic blood pressure regulation in stroke 217

reported significant orthostatic blood pressure The findings of the present study suggest Postgrad Med J: first published as 10.1136/pgmj.75.882.213 on 1 April 1999. Downloaded from reduction in chronic stroke. The present study that upright positioning as part of early was within the first 3 days of stroke onset, and rehabilitation in most patients with mild or showed orthostatic blood pressure stability or moderate acute ischaemic stroke is unlikely to rise. This is in contrast to the above studies cause detrimental falls in orthostatic blood which were predominantly in sub-acute and pressure and cerebral blood flow. However, a 2 13 21–24 chronic stroke, and showed either ortho- minority of patients did exhibit a significant static blood pressure reduction or no significant postural fall, even on sitting up. Also, we change. Detailed investigation of chronic stroke excluded patients whose stroke was severe, who patients has previously revealed sympathetic 25 had other coexisting severe illness, or were pre- nervous system hypofunction, whereas in the viously very disabled. Such patients have a first few days post-stroke, sympathetic nervous greater risk of postural hypotension.33 Further- system hyperactivity has been found.116 more, significant reductions in cerebral per- In both study groups, we found no difference fusion can occur even with small reductions of in orthostatic blood pressure responses between systemic pressure, especially in susceptible those on antihypertensive drugs and the re- maining patients. Similar results were reported individuals, eg, those with carotid or recently in elderly non-stroke inpatients.26 intracranial arterial stenoses. Randomised However, prospective studies of patients already acute stroke trials of neuroprotective agents on antihypertensives have shown that drug with co-existing hypotensive properties, re- withdrawal leads to a significantly reduced ported that resting systolic reduction as small prevalence of orthostatic hypotension as de- as <10 mmHg was associated with signifi- fined by >20 mmHg systolic fall.27 cantly worse neurological recovery and sur- In the present study, we sought to investigate vival, especially in older patients.34 As postural ischaemic strokes, which account for 85% of all hypotension may exacerbate cerebral damage, strokes. While haemorrhagic strokes were it is important to identify the subgroup of acute excluded by CT scanning in 45% of patients, stroke patients who are at risk by routinely tak- the remainder were included only if the Guy ing supine, sitting, and/or standing blood pres- score predicted >90% chance of non- sures. In a recent investigation of blood haemorrhagic stroke. Such scoring systems pressure evaluation in acute stroke, it was have limitations, and 10% of those diagnosed disappointing to find that postural readings as having had ischaemic stroke could have had were rarely carried out in the first week haemorrhagic stroke.28 Thus, about two pa- post-stroke.35 tients in the present study might have been Once patients at risk are identified, measures misclassified. Even though acute haemorrhagic aimed at minimising postural hypotension can strokes have a greater impact on the autonomic be taken. They include maintenance of ad- nervous system and blood pressure level than equate hydration, withholding certain drugs 29 ischaemic types, this small number would not (eg, vasodilators, anticholinergics, sedatives),

have significantly influenced our findings. Also, and avoiding fast changes in posture. Physical http://pmj.bmj.com/ we did not diVerentiate ischaemic strokes into exercise programmes which can be used before their diVerent sub-types, ie, cortical, subcorti- full mobilisation, have been shown to amelio- cal, lacunar, or brainstem. Recent evidence rate postural hypotension,36 although this has suggests diVerences between ischaemic sub- not been specifically assessed in acute stroke types in their eVect on sympathetic nervous patients. In the present study, patients were not system function and 24-hour blood pressure investigated soon after meals in order to avoid profiles.17 30 Another methodological aspect of the confounding eVect of the normal postpran- our study was the use of intermittent rather on September 27, 2021 by guest. Protected copyright. dial blood pressure fall that occurs in the than continuous haemodynamic recording. elderly.37 Postprandial hypotension is detri- Although the latter method enables beat-to- 37 beat haemodynamic monitoring, it is more mental to cerebrovascular blood flow, espe- cially in people with existing cerebrovascular prolonged changes which are of clinical 38 importance.31 Intermittent sphygmomanom- disease. It is therefore prudent to also etry has been found to be adequate for this minimise physiotherapy and postural changes 39 purpose,31 and recent comparative studies of in the first couple of hours post-prandially. the two methods showed high accuracy of sphygmomanometry in detecting postural We thank Mr R Sheaf of Boehringer Ingelheim Ltd for the loan hypotension.32 of the SpaceLabs 90207 device.

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