脑卒中的紧急救治与长期管理
TITLE: Acute treatment and long-term management of stroke in developing countriesAUTHOR: Prof Michael Brainin MD , Yvonne Teuschl PhD and Lalit Kalra MD
第一部分
Summary
Developing countries have some of the highest stroke mortality rates in the world that account for over two-thirds of stroke deaths worldwide. Hospital-based studies suggest that the patterns of stroke types and causes of stroke differ between developing and developed countries, resulting in differing needs for acute and long-term care. Data on stroke care provision in developing countries are sparse and most of the available studies are biased towards urban settings in reasonably resourced health-care systems. A general overview shows that the quality and quantity of stroke care is largely patchy in low-income and middle-income countries, with areas of excellence intermixed with areas of severe need, depending upon patients' location, socioeconomic status, education, and cultural beliefs. Here we review the available literature on acute and long-term stroke management in developing countries. On the basis of available studies, largely from developed countries, we discuss the need to develop basic organised stroke-unit care in developing countries.
Introduction
Stroke is the second commonest cause of mortality worldwide1 and remains a leading cause of adult physical disability. Developments in stroke care over the past two decades, particularly in acute management as well as in rehabilitation and long-term care, have greatly reduced mortality and dependence in many developed countries. Indeed, 10 year stroke mortality rates collected by the WHO MONICA project in Europe and China showed that changes in mortality rates in nine countries were mainly due to changes in case fatality rather than to changes in stroke incidence, suggesting that changes in the quality of stroke care may be responsible for changes in stroke mortality.2,3 By contrast, there has been limited progress in the management of patients with stroke in developing countries, despite increasing incidence of stroke and high stroke mortality rates that account for over two-thirds of stroke deaths worldwide.4 The slow uptake of evidence into clinical practice can be attributed to several reasons mainly relating to geography, limited health-care provision for the population as a whole, socioeconomic considerations, and health behaviour of different populations. In addition, hospital-based studies suggest differences in the type and causes of stroke between developed and developing countries, with higher incidence of haemorrhagic stroke and higher prevalence of stroke due to infective or inflammatory causes. Although many of the advances associated with reduced stroke mortality and morbidity will be equally applicable to developing countries, differences in types and causes of stroke, limitations posed by geography, accessibility of health care, availability of resources, social beliefs, and cultural expectations need to be taken into account when extrapolating stroke-management strategies from the developed to developing countries.5
第二部分
Specific issues in the treatment of stroke in developing countries
Research on stroke-care provision in developing countries is sparse and most of the available studies are biased towards urban settings in affluent economies with reasonably resourced health-care systems. A general overview shows that the quality and quantity of stroke care is largely patchy in low-income and middle-income countries (or low-developed and medium-developed as defined by the United Nations Development Program6), with areas of excellence intermixed with areas of severe need depending upon location, socioeconomic status, education, and cultural beliefs.
Stroke awareness and use of hospitals
The importance of stroke awareness has been highlighted in many studies, which show poor recognition of stroke symptoms in developing countries. Only one in 25 patients attending a stroke clinic and 27% of patients presenting to the stroke services in a tertiary hospital in India were aware that they had suffered a stroke.7,8 Equally importantly, 80% of the patients in the first study thought that the organ affected was the heart and only 33% of patients in the tertiary hospital setting knew that the brain was involved in stroke. Moreover, 29% of patients with stroke in the second study did not know a single warning sign. However, in another study in the same hospital in India, 55% of the relatives of patients without history of stroke identified the brain as the affected organ, and only 23% could not cite a single stroke symptom.9 A study in a university hospital in Oman found that 35% of patients with high risk of stroke stated that the organ affected by a stroke is the brain and 68% identified at least one stroke symptom.10 However, stroke awareness and knowledge is poor even in developed countries and varies as in developing countries9,10 with income, education, age, and sex.11–15 The proportion of people correctly identifying the brain as the organ involved in stroke in developed countries was between 45% and 73%,11,12,15,16 and between 30% and 90% knew at least one stroke warning sign.11–18
The multiplicity of health-care options, many of which may not be rooted in biological sciences, may be a significant impediment to early intervention in patients with acute stroke. In an Indian study in an urban setting, 59% of patients with stroke consulted a private doctor before seeking hospital care and only 38% of patients presented directly to hospital.8 Studies in rural South Africa show that 40–80% of patients complement medical care with help from traditional healers or churches and as many as 10–33% of patients may go to traditional healers first rather than seek medical help.19,20 The rural–urban split in access to stroke treatment is also reflected in studies from Taiwan and Bolivia, which show that 10% and 50%, respectively, of patients with stroke in rural settings do not go to hospital or see a doctor.21,22 Hospital is the first point of investigation and treatment for many patients. Overall, the proportion of patients with incident stroke who present to hospitals in poorly developed or moderately developed countries is difficult to estimate. A hospital-based study from the Philippines suggests 81% of patients present at hospitals;23 whereas a prospective population study from the Ukraine showed that 66% were hospitalised.24 These estimates are derived from regions with reasonably well-developed health services and may not be representative of other developing countries.
第三部分
Thrombolysis and hospital care
In developing countries, there is great variation in the time taken by patients with stroke to present to hospitals and the imaging or treatment facilities available for their management (table 1).23,25–35 Most studies suggest that patients with stroke who present to hospital, do so fairly soon after symptom onset. Studies from The Gambia show that most patients were admitted within 48 h of symptom onset,26 the median time to admission being 8 h.25 A study from Ethiopia reported a median time of 13·5 h before presenting to hospital.36 Studies from urban hospitals in India and the Philippines report that up to 35% of patients with stroke present within 3 h of symptom onset,8,23,30 which is no different to the times to presentation reported from developed countries.37
Table 1. Acute management of stroke in developing countries
The use of imaging also differs considerably between settings (table 1). In 1998, 18 African countries had no CT scanners and 13 countries had one each. Only northern African countries and South Africa had an appropriate number of CT and some MRI scanners.38 CT scanning facilities were not available in 27% of hospitals in the Philippines,23 but 83% patients with stroke in a general hospital in China had either CT (65%) or MRI (43%) scans.29 In 1998, Shanghai (China) and Malaysia had about one or two MRI scanners per million population whereas in Thailand, the Indian state Tamil Nadu, Indonesia, and the Philippines fewer than 0·5 scanners per million population were available.39
The reported rates for thrombolysis also vary substantially, ranging from 2·1% in a large study in 1624 patients in Thailand32 to 7% in a smaller study of 489 patients from India.31 Intravenous alteplase (recombinant tissue plasminogen activator; rtPA) is registered and introduced in many countries with medium development and some with low levels of development. Affordability was an important determinant of both investigations and treatment in some settings: only 101 of 1102 (9%) patients with stroke in Nigeria could afford to have CT scans;40 in Ethiopia, CT scan was only done in 38·3% of patients due to its high price;41 and 10% of 489 patients with incident stroke who meet all criteria for thrombolysis were not given the treatment in an Indian study because they could not afford alteplase.31
The length of hospital stay varied substantially according to region and affordability. The median hospital stay in Pakistan was only 3 days,35 compared with 32 days for insured patients in China.29 There is very little information on specialised stroke-unit care in developing countries. A study from Brazil showed no differences in outcome measured at 10 days after stroke onset or length of hospital stay between those managed on a stroke unit and those on general wards.34 However, there was a trend towards lower mortality at 1 month, 3 months, and 6 months in patients managed on the stroke unit, which did not achieve statistical significance, possibly because of the small sample size. Another study from Thailand that compared hospital care with hospitalisation and early supported discharge showed no differences in mortality but better patient perceptions of the care received in those managed at home.33
第四部分
Access to and availability of adequate rehabilitation facilities is also limited in countries with low or medium development. Only 47% of hospitalised patients with stroke were seen by a therapist in The Gambia;26 and in large teaching hospitals in southern China, routine care included no regular professional physiotherapy during the whole hospitalisation period.42 The mean duration between stroke onset and admission to a rehabilitation facility is 53 days in Thailand and 63 days and 76 days in two Turkish studies.43–45 In South Africa, only 39% of old and 56% of young patients with stroke attended outpatients' physiotherapy clinics once a week or once a month after hospital discharge.46
Secondary prevention
Most studies show poor outcomes in patients with stroke in terms of mortality and implementation of secondary prevention measures (table 2).19,25,26,33,34,42–51 Many of the problems of poor concordance with secondary prevention measures have been attributed to lack of equipment for the monitoring of blood pressure or other risk factors, non-availability of drugs, and affordability of treatment.19,50 A Chinese study showed that lower socioeconomic status was associated with higher 3 year mortality in patients with ischaemic stroke.49 Cost-effective secondary prevention has been proposed by WHO guidelines for low-income and middle-income populations, suggesting lifestyle changes and affordable, accessible, and effective pharmacological antihypertensive treatments, antiplatelet treatments, and blood-cholesterol reduction.52 Aspirin has been recommended as the most cost-effective antiplatelet medical therapy worldwide because it is cheap and easily available everywhere in the world but compliance with treatment is commonly poor.52–54 Studies from The Gambia26 and South Africa19 reported that although 65% and 83% respectively of stroke patients were treated with antihypertensive drugs at the time of discharge, only 13% of stroke survivors in The Gambia and 8% of survivors in South Africa were taking antihypertensive treatment after 1 year. Similarly, of the 71% of patients discharged on aspirin in The Gambia, only 7% were still taking aspirin 1 year later.26 In another study from The Gambia, 33% of stroke survivors were treated with antihypertensive medication at 6 months after stroke; 3–4 years later only 15% were satisfactorily controlled for hypertension and 15% received aspirin regularly.25 The WHO PREMISE study of ten medium developed countries (Brazil, Egypt, India, Indonesia, Islamic Republic of Iran, Pakistan, Russian Federation, Sri Lanka, Tunisia, and Turkey) reported high percentages of patients with cerebrovascular diseases using drugs for secondary prevention. Aspirin use ranged from 31% to 90%, the use of beta-blockers from 6·8% to 46%, angiotensin-converting-enzyme inhibitor use from 5% to 59%, and statin use from 2% to 37%.50 94% of these patients reported that their blood pressure had been measured within the past 12 months. Patients in this study were recruited from outpatient clinics, which may reflect better access to health services and greater acceptance of drug treatment than among the general population in these settings.
Table 2. Long-term management of stroke in developing countries
第五部分
Little information is available on lifestyle modification after stroke in developing countries. The PREMISE study suggests that 77–89% of patients have knowledge of the benefits of smoking cessation, diet modification, and regular physical activity. However, 52·5% did not engage in regular moderate physical activity, and 35% had difficulties in complying with dietary advice due to the expense and lack of availability of healthy food items.50 On the Kinmen islands, China, 36% of stroke survivors eat meat less than once per week and 36% exercise more than once per week compared with 19% and 18% respectively for people who had not had stroke.21 The figure shows the location of the studies covered in this Review.
Figure. Locations of the studies covered by this review
Purple circles indicate studies reporting data on stroke care in the strict sense; yellow circles indicate studies reporting data on additional care-relevant subjects according to high (green), medium (blue) and low (red) human development based on the Human development report 2005.1
Differences in stroke type and cause
Recent systematic reviews of population-based studies show only moderate geographical variations in stroke incidence in the world.55 Most of the stroke incidence in developing countries is likely accounted for by the increasing prevalence of conventional risk factors such as hypertension, diabetes, hypercholesterolaemia, and smoking as populations adopt a more urbanised lifestyle. However, there are some important differences in stroke type and cause between developed and developing countries, which become important from a management perspective. Many hospital-based studies suggest a significantly high proportion of stroke patients have intracranial haemorrhage, the proportion varying between 19–60% in various studies.23,26,40,41,47,48,56–61 However, hospital-based studies are likely to be biased towards the more severe end of the stroke spectrum in developing countries because of factors such as distance from hospital, access to transport, ability to afford hospital fees, and local beliefs about hospital attendance, which reduce rates of hospitalisation for patients with mild stroke. There are very few community-based studies in these settings and, therefore, a paucity of reliable data on stroke subtype prevalence in developing countries.
第六部分
Uncontrolled and commonly undiagnosed hypertension remains the most important cause of intracerebral haemorrhage in developing countries, but a high proportion is attributable to aneurysms and arteriovenous malformations.28,62 Although the prevalence of atherosclerotic and cardioembolic stroke seems to be the same in developing and developed countries, cardioembolic strokes occur at a younger age and are more commonly caused by valvular involvement in rheumatic or congenital heart disease in developing countries;62,63 there is also a higher prevalence of strokes caused by sickle-cell disease, vasculitis due to infection, or inflammation and coagulopathies (table 3).64,65
Table 3. Causes of stroke specific to developing countries65
Implementing evidence-based management in developing countries
A major development over the past decade has been the setting up of specialised stroke centres in many developed countries to provide early thrombolysis and clot removal therapy for acute patients with ischaemic stroke, on the basis of the principle that “time is brain”.66,67 The approval and licensing of thrombolytic therapy for ischaemic stroke in North America and Europe has helped to spread the practice of specialised stroke care from tertiary academic centres to large networks of acute stroke units in local hospitals and the emergence of guidelines for the management of acute stroke.68,69 There are now precise North American and European definitions of the organisation of acute stroke centres that take into account the range of interventions and imaging facilities.67,70 While large tertiary academic centres may offer a range of highly specialised therapy options—such as interventional neuroradiological and neurosurgical therapies, including the technical set-up for intra-arterial thrombolysis, haematoma evacuation, hemispheric craniotomy, and carotid surgery—local stroke units in regional hospitals may offer a smaller, less costly, but nevertheless effective service including rapid diagnosis assisted by CT imaging; intravenous thrombolysis in eligible patients; acute stroke care to maintain physiological homoeostasis and prevent stroke-related complications; management of dysphagia, nutrition, and communication; early mobilisation; and therapy for sensorimotor and cognitive impairments. Despite limited access to highly specialised procedures, local centres have the potential to deal with most strokes and stroke-related complications and selected patients need to be transferred to large centres only rarely.
第七部分
The mainstay of management in any setting, whether a highly specialised tertiary stroke centre or a low-level local stroke unit, is a structured approach towards patients with acute stroke and their continuous management in the postacute phase by dedicated staff trained to recognise, monitor, and treat stroke-related problems.71 There is general consensus among stroke specialists that the most effective components of acute stroke that improve overall outcomes consist of rapid and precise diagnosis, proactive general measures for prevention, and early recognition of complications and early mobilisation.72 Hankey and Warlow have extrapolated data from randomised studies to efficiency measures with a population-based approach and shown that the benefits of treatment in stroke units are much greater than those of treatment with intravenous thrombolysis.73 This is because the proportion of patients likely to be treated in stroke units is much greater than that treated with thrombolysis at present.
Many developing countries have stroke centres that can provide imaging and interventional facilities comparable to major academic centres in developed countries. However, a high rate of thrombolysis does not reflect the overall quality of stroke care, but only represents a good prehospital setup and an effective rapid response to stroke presenting as an emergency. Although thrombolysis may result in significant improvements for individual patients, its effectiveness as an intervention to improve population outcomes is likely to be diluted because of its limited use in highly selected patients presenting early to specialist centres. The highest priority for providers of a stroke service in less well organised or less affluent settings must be to establish a stroke unit and multidisciplinary team to deliver organised stroke care.73 This approach has been widely adopted in developed countries, where the bulk of stroke care is provided by networks of local stroke units. Countries with low and medium levels of development might be best off aiming for a stepwise development of specialist stroke services, which favours the establishment of a basic stroke unit before setting up specialised teams for thrombolysis. This is particularly important because a higher proportion of patients in developing countries have haemorrhagic stroke and it may be difficult to implement sophisticated management paradigms for time-dependent interventions in patients with ischaemic stroke because of inadequate prehospital facilities and unreliable transportation.
第八部分
Specialised stroke units are an ideal opportunity for education and information on stroke prevention to patients and their families. Studies have shown that patients provided with structured information on measures to prevent further strokes in such settings have the highest adherence to long-term medication and lifestyle changes after stroke in developed countries.74 Non-compliance for long-term treatment—even for aspirin—is relatively high in developing countries. Education on behavioural modification and medical therapies during hospitalisation by specialists using simple messages adapted to patients' education and cultural background may be an opportunity to increase adherence to secondary prevention measures. The family has an important role in developing countries and should be included in health education to encourage and help patients with drug intake and lifestyle changes.
Conclusions
Developing countries have some of the highest stroke mortality rates in the world that comprise over two-thirds of stroke deaths worldwide. Patterns of stroke types and causes of stroke differ between developing and developed countries but there are few studies of acute stroke care or long-term management to guide clinical practice. The quality and quantity of stroke care is patchy in developing countries, with areas of excellence intermixed with areas of severe need depending upon patients' location, local hospital facilities, ability to pay, education, and cultural, social, or religious beliefs. A population-based approach to improving acute care and rehabilitation for stroke is needed, which is evidence based and maximises the effectiveness of such care. Existing literature, largely from developed countries, supports the development of basic organised stroke-unit care, which must be tailored by health needs, service patterns, and affordability of individual settings. Further research is also needed to develop customised acute care and rehabilitation strategies most appropriate to the needs and circumstances of developing countries to help them alleviate the growing burden of stroke.
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