Lisa Manning

Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial

BACKGROUND High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood pressure variability in participants of INTERACT2, an open-label randomised controlled trial (ClinicalTrials.gov number NCT00716079). METHODS INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150-220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mm Hg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2-7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles. FINDINGS We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05-1·90; ptrend=0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14-2·17; ptrend=0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14-1·80; ptrend=0·0014; for the acute phase OR 1·46, 95% CI 1·13-1·88; ptrend=0·0044). INTERPRETATION Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure. FUNDING National Health and Medical Research Council of Australia.

Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke Systematic Review

Background and Purpose— Blood pressure variability (BPV) may be an important prognostic factor acutely after stroke. This review investigated the existing evidence for the effect of BPV on outcome after stroke, also considering BPV measurement techniques and definitions. Methods— A literature search was performed according to a prespecified study protocol. Two reviewers independently assessed study eligibility and quality. Where appropriate, meta-analyses were performed to assess the effect of BPV on poor functional outcome. Results— Eighteen studies from 1359 identified citations were included. Seven studies were included in a meta-analysis for the effect of BPV on functional outcome (death or disability). Systolic BPV was significantly associated with poor functional outcome: pooled odds ratio per 10-mm Hg increment, 1.2; confidence interval (1.1–1.3). A descriptive review of included studies also supports these findings, and in addition, it suggests that systolic BPV may be associated with increased risk of intracranial hemorrhage in those treated with thrombolytic therapy. Conclusions— This systematic review and meta-analysis suggest that greater systolic BPV, measured early from ischemic stroke or intracerebral hemorrhage onset, is associated with poor longer-term functional outcome. Future prospective studies should investigate how best to measure and define BPV in acute stroke, as well as to determine its prognostic significance.

Short-Term Blood Pressure Variability in Acute Stroke: Post Hoc Analysis of the Controlling Hypertension and Hypotension Immediately Post Stroke and Continue or Stop Post-Stroke Antihypertensives Collaborative Study Trials

Background and Purpose— Short-term blood pressure variability (BPV) may predict outcome in acute stroke. We undertook a post hoc analysis of data from 2 randomized controlled trials to determine the effect of short-term BPV on 2-week outcome. Methods— Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS) was a trial of BP-lowering, enrolling 179 acute stroke patients (onset <36 hours). Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) compared a strategy of continuation versus temporarily stopping prestroke antihypertensive therapy in 763 acute stroke patients (onset <48 hours). BPV at baseline (defined as SD, coefficient of variation, variation independent of the mean, and average real variability) was derived from standardized casual cuff BP measures (6 readings <30 minutes). Adjusted logistic regression models were used to assess the relation between BPV and death and disability (modified Rankin scale>3) at 2 weeks. Results— Seven hundred six (92.5%) and 171 (95.5%) participants were included in the analysis for the COSSACS and CHHIPS data sets, respectively. Adjusted logistic regression analyses revealed no statistically significant associations between any of the included BPV parameters with 2-week death or disability in either study data set: COSSACS, odds ratio SD systolic BP 0.98 (0.78–1.23); CHHIPS, odds ratio SD systolic BP 0.97 (0.90–1.11). Conclusions— When derived from casual cuff BP measures, short-term BPV is not a useful predictor of early (2 weeks) outcome after acute stroke. Differing methodology may account for the discordance with previous studies indicating long-term (casual BPV) and short-term (beat-to-beat BPV) prognostic value. Clinical Trial Registration— COSSACS was registered on the International Standard Randomised Controlled Trial Register; URL: http://www.isrctn.com. Unique identifier: ISRCTN89712435. CHHIPS was registered on the National Research Register; URL: http://public.ukcrn.org.uk. Unique identifier: N0484128008.

Control of Blood Pressure in Hypertensive Neurological Emergencies

Neurological hypertensive emergencies cause significant morbidity and mortality. Most occur in the setting of ischaemic stroke, spontaneous intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH), but other causes relate to hypertensive encephalopathy and reversible cerebral vasoconstriction syndrome (RCVS). Prompt and controlled reduction of blood pressure (BP) is necessary, although there remains uncertainty as to the optimal rate of decline and ideal antihypertensive agent. There is probably no single treatment strategy that covers all neurological hypertensive emergencies. Prompt diagnosis of the underlying disorder, recognition of its severity, and appropriate targeted treatment are required. Lack of comparative-effectiveness data leaves clinicians with limited evidence-based guidance in management, although significant developments have occurred recently in the field. In this article, we review the management of specific neurological hypertensive emergencies, with particular emphasis on recent evidence.

New Insights into Blood Pressure Control for Intracerebral Haemorrhage

Although blood pressure (BP) levels may rise in the weeks preceding intracerebral haemorrhage (ICH), in contrast to findings in the ischaemic stroke population, the initial post-ICH BP is often much higher than the last pre-morbid level. Elevated BP is therefore common in acute ICH, often with markedly elevated levels, and is associated with poor outcomes, though the exact pathophysiological mechanisms remain unclear. The Antihypertensive Treatment of Acute Cerebral Haemorrhage (ATACH) trial and the INTEnsive blood pressure Reduction in Acute Cerebral haemorrhage Trial (INTERACT) demonstrated that early and intensive lowering of elevated BP in the acute ICH period is feasible and safe. Importantly, recent CT perfusion studies have shown that early, intense BP reduction does not reduce cerebral blood flow or promote cerebral ischaemia. The recent, large INTERACT2 trial confirmed the safety of early BP lowering in ICH and suggested that intensive target-driven BP reduction may improve outcomes, with a non-significant trend towards reduced death and major disability and a significant favourable shift of scores on the modified Rankin scale compared with guideline-based treatment. BP lowering in acute ICH may reduce haematoma growth, particularly when target levels are achieved early and are sustained, though the evidence is partly conflicting. Other aspects of BP may also be important following acute ICH, with maximum systolic BP and systolic BP variability being independent predictors of poor outcomes in a recent study. This chapter gives an overview of the current evidence regarding BP in ICH and covers the following topics: the incidence of elevated BP in acute ICH and the patterns of BP observed before and after the event; the effect of elevated BP on outcomes in ICH and the potential underlying pathophysiological mechanisms; the safety and feasibility of BP lowering; the effects of BP lowering on clinical and radiological outcomes; other important aspects of BP in ICH; and the choice of antihypertensive agent.

Palliative care for frail older people.

It is now widely accepted that palliative care should be available to all those in need regardless of age, diagnosis or care setting.1 Despite this, the palliative care needs of older patients are often under assessed and undertreated.2 Given that 58% of patients still die in hospital,1 all physicians need to be able to identify and manage the palliative care needs of frail older patients, many of whom will have multiple comorbidities and a significant symptom burden.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke:An Individual Patient Data Meta-Analysis

Over 50% of patients are already taking blood pressure–lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ⩽48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ⩽48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80–1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ⩽12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke

Over 50% of patients are already taking blood pressure–lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ⩽48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ⩽48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80–1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ⩽12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions.

Balancing satisfaction and stress: carer burden among White and British Asian Indian carers of stroke survivors

ABSTRACT Objectives: This paper presents the findings of a qualitative study exploring White and British Indian informal stroke carers’ experiences of caring, factors contributing to their stress, and strategies used to overcome stress. Design: A qualitative approach involving in-depth interviews was used to explore informal carers’ experiences of caring for stroke survivors and the stress of caring at one and three to six months from the onset of stroke. Interviewers bilingual in English and Gujarati or Punjabi conducted interviews with carers. Socio-demographic data of carers and stroke survivors were collected at one, and three to six months by dedicated stroke research nurses. Results: A total of 37 interviews with carers caring for stroke survivors with a wide range of physical and mental impairments were completed. A majority of carers had assumed the task of caring within a few weeks of the stroke. Irrespective of ethnicity, carers’ emotional and physical well-being was undermined by the uncertainty and unpredictability of caring for stroke survivors, and meeting their expectations and needs. The strain of managing social obligations to care was common to all carers irrespective of gender and ethnicity, but the higher levels of anxiety and depression reported by Indian British female carers appeared to stem from the carers’ pre-existing physical ailments, their cultural and religious beliefs, and household arrangements. Carers’ strain in extended households was exacerbated by the additional responsibility of caring for other dependent relatives. Conclusion: Since the role of carers is clearly indispensable in the successful rehabilitation of survivors, it is vital to ensure that their well-being is not undermined by a lack of information and training, and that their need for professional support is prioritised.

The SOMNOtouch device as a novel method for measuring short-term blood pressure variability: a comparison with the Finometer.

BackgroundCurrent noninvasive techniques to capture short-term blood pressure variability (BPV) have methodological and practical limitations. This study assessed the ability of a novel device, the SOMNOtouch, which derives continuous blood pressure (BP) measures from pulse transit time, to estimate BPV, compared with the widely used Finometer. MethodsBP monitoring was performed simultaneously on the SOMNOtouch and Finometer devices in 16 healthy volunteers. Systolic and diastolic BPVs, defined as SD and coefficient of variation, were derived from measurements from each device for three predefined periods: 0–3, 7–10, and 0–10 min. ResultsAgreement in BPV indices from the two devices was assessed using the Bland–Altman technique. For all BPV parameters, over all measurement periods, broad scatter was observed on Bland–Altman plots. Bias (limits of agreement) for minutes 0–10: SD of systolic BP, −3.03 mmHg (−10.88 to +4.55), SD of diastolic BP −1.65 mmHg (−4.41 to +1.11). ConclusionsThe poor agreement observed in BPV estimates between the devices may reflect the inability of the current pulse transit time method to sensitively detect changes in BP. Further investigation is needed before such methods can be reliably used to measure short-term BPV.