Background and Purpose Despite efforts to reduce the delay between stroke onset and new interventional treatments, no studies have analyzed the repercussions of early neurological attention on the clinical outcome of stroke patients.
Methods Data were obtained from 721 patients admitted consecutively for a transient ischemic attack or stroke to the neurology departments of 18 Spanish hospitals that followed the same diagnostic and therapeutic guidelines in the acute phase. Factors assessed were age, sex, Canadian Stroke Scale score on admission, previous Barthel Index, and delay before attention by the first physician, by emergency services, by a neurologist, and before hospitalization. Patients’ outcomes were classified as good (Barthel Index >60) or poor (Barthel Index ≤60 or in-hospital death) depending on patients’ functional capacity on discharge. The individual contribution of each of these variables on clinical outcome was estimated with logistic regression analysis.
Results Patients in worse neurological condition on admission presented earlier to the first physician, emergency department, and neurologist. The mortality rate was not significantly modified by early or late presentation at the different medical stages. Logistic regression analysis revealed that the relative risk of poor outcome in patients seen by the neurologist after the first 6 hours from symptom onset was 5.6 (95% confidence interval, 3.4 to 9.2) (P<.0001). Multiple linear regression analysis showed that the delay before the patient received neurological attention correlated positively with the duration of hospitalization (P<.0001). The delays before the patient was seen by the first physician or the emergency department and before hospitalization were not independently related to clinical outcome or length of hospitalization.
Conclusions Early neurological attention in acute stroke is related to better functional outcome and shorter hospitalization.
Clinical and experimental studies suggest that cerebral ischemia persisting more than 6 hours produces permanent neurological damage,1 2 and reperfusion occurring after this time window may lead to the development of intracerebral hemorrhage.3 4 Most thrombolytic and neuroprotective ongoing drug trials include patients who presented at the hospital within this short period of time. Promotional programs to the public are important to facilitate early treatment to reduce the time between stroke onset and hospital admission.5 Recently, several reports have studied the delay before hospital arrival and the factors associated with early presentation of acute stroke in EDs.6 7 8 9 10 11 12 13 14 15 16 17 These reports focused on the number of patients seen within the first 6 hours after symptom onset but did not analyze the influence of a short delay in neurological care on the clinical outcome. Early diagnostic and therapeutic procedures by a neurologist experienced in stroke management may lead to a better prognosis in cases of acute stroke.
Our hypothesis was that early hospital arrival and neurological care could significantly improve the clinical outcome in nonselected patients with acute stroke.
Subjects and Methods
Eighteen hospitals distributed in 12 different cities of Spain participated in a cohort observational study. Eleven hospitals were university hospitals, 7 were community hospitals, and all supported postgraduate training programs. Before and during the study period no promotional programs to the public were conducted, but in many hospitals educational lectures were given to the medical staff concerning the urgent evaluation and treatment of stroke patients. Participating hospitals had a neurological ward and at least one neurologist particularly interested in cerebrovascular diseases; 8 hospitals had a neurologist or a neurological resident on duty, and therefore stroke patients were seen shortly after admission; 2 hospitals had a stroke unit. Stroke patients were managed in the acute phase in accordance with the recommendations of the Spanish Cerebrovascular Study Group.18 Main strategies included the following: (1) CT on admission; (2) CSS evaluation; (3) maintenance of blood pressure without the use of hypotensive drugs unless systolic blood pressure was >220 mm Hg or diastolic blood pressure >120 mm Hg; (4) early treatment of hyperglycemia, avoiding glucose perfusions; (5) prevention of pulmonary thromboembolism with low-dose heparin; (6) early antiplatelet therapy except when anticoagulants were recommended (arterial dissections, progressing stroke especially if vertebrobasilar, cardioembolic stroke without clinical or radiological signs of a large cerebral infarct); and (7) conservative treatment of intracerebral hemorrhage. No therapeutic trials were in progress in the participating hospitals during the study period with the exception of the IST in 3 hospitals and the ECASS in 3 hospitals. Each hospital had its own policy for diagnostic investigations, rehabilitation, and discharge criteria.
All patients were admitted consecutively through the emergency units for an acute stroke or transient ischemic attack between January and June 1994. Except when there was a lack of free beds, patients were allocated to the neurological wards. Information on the time intervals was obtained prospectively from the patient and the patient’s family and from the medical records. The time of stroke onset was considered the time when the symptoms were noted by the patient or by an observer. When the patient awakened with neurological deficits, the time when the patient was last known to be asymptomatic was recorded as the time of onset. Patients in whom these data were not available were excluded.
The delay before being attended by the first physician was defined as the number of hours between stroke onset and the first contact between the patient and any physician at home or in the ED. The time of hospital arrival was the time noted on the ED record; in the participating hospitals there was a minimal delay of less than 30 minutes between the time a stroke patient presented to the ED and the time a patient was seen by a physician. If the patient was transferred from another hospital, the time of ED arrival at the participating hospital was used. The time to see the first neurologist was defined as the number of hours between stroke onset and contact with a neurologist or resident in neurology in the participating hospital. The time until hospitalization was defined as the number of hours between stroke onset and the time noted on the hospitalization record in the neurological ward or in the stroke unit. When the time to see the first physician was equal to the time to ED arrival, we assumed that the patients were initially attended in the ED, and when the time to see the first physician was equal to the time to ED arrival and to the time to see a neurologist, we assumed that the patients were examined initially by a neurologist in a participating hospital.
Age, sex, days of hospitalization, and in-hospital mortality were recorded. The type of stroke was established by the principal investigator in each hospital according to unified criteria.19 Type of stroke was classified in four categories: transient ischemic attack, cerebral infarct, cerebral hemorrhage, and subarachnoid hemorrhage. To determine the neurological deficit, the CSS20 was measured by the participating neurologists on admittance and after 1 week. Functional capacity before the presenting stroke was estimated by the BI21 and was evaluated again on discharge. The questionnaire was restricted to time intervals and outcome and did not document other stroke characteristics, cardiovascular risk factors, and medical complications.
Time intervals, CSS scores, and BI were not normally distributed. As a log-transformation of the data did not completely correct the problem of a skewed distribution of the presentation times, nonparametric statistical tests were used. The cutoff value of 6 hours was chosen to compare BI and mortality between the group of patients attended within a short delay time (≤6 hours) versus a long delay time (>6 hours) in each of the time intervals recorded. Considering the functional outcome at discharge, we classified patients into two groups: the good outcome group (BI >60) and the poor outcome group (BI ≤60 or in-hospital death). Separate analyses were calculated in all stroke patients and in those with cerebral infarct.
To identify the time intervals independently related to clinical outcome, we used a logistic regression analysis based on the maximum likelihood ratio. Time intervals were treated as two dichotomies (0, delay ≤6 hours; 1, delay >6 hours) and included as covariates. The model was adjusted controlling for age (0, ≤65 years; 1, >65 years), previous BI (0, 100; 1, <100), and CSS score on admission (0, >5; 1, ≤5) classified in two categories. BI at discharge was used as the primary independent variable. We assigned a value of 1 to poor prognosis (BI ≤60) and a value of 0 to good prognosis (BI >60) to estimate RRs and 95% CIs. We set a value of 0 for CSS and BI when the patients were comatose or dead.
The influence of the different time intervals on the duration of hospitalization was assessed with a stepwise multiple linear regression analysis. Patients who died in the hospital were excluded from this analysis to avoid artificial shortening of their duration of hospitalization because of an early death. A log-transformation was used to normalize the distribution of the days of hospitalization. Time intervals, age, CSS score on admission, and BI were used as continuous variables.
A total of 721 patients were evaluated. During the study period, 23 patients were included in the IST and 4 patients in the ECASS. The time of presentation after stroke has been discussed in a recent report.22 Time intervals were significantly different between patients with severe (CSS score ≤5) or moderate (CSS score >5) neurological deficit on admission. Patients in worse neurological condition arrived earlier at the different medical stages (Table 1⇓). Ninety-one patients (23%) of 398 with initial CSS >5 and 98 patients (30%) of 323 with initial CSS ≤5 were seen by neurologists within the first 6 hours (P=.023). When patients who died during hospitalization were excluded from this analysis, we obtained similar significant results.
Considering their functional abilities at discharge, we classified 403 patients (55.9%) in the good outcome group and 318 (44.1%) in the poor outcome group. Table 2⇓ shows demographic and clinical characteristics as well as delays in both outcome groups. Older age, CSS score ≤5, and hemorrhagic strokes were significantly more frequent in the patients with poor outcome. Eight patients admitted with a transient ischemic attack had neurological or medical complications during hospitalization that caused some degree of functional incapacity at discharge. Early examination by a neurologist favorably influenced the BI at discharge. In the poor outcome group 18% of patients were seen by a neurologist within the first 6 hours from symptom onset, and in the good outcome group 32% of patients were attended in this time interval (P<.0001). Delays of less than 6 hours before the patient was seen by the first physician or the ED and before hospitalization were not significantly related to a better functional outcome. The median duration of hospitalization was 19 days in the poor outcome group and 13 days in the good outcome group (P<.0001, Mann-Whitney rank sum test).
The differences in mortality rate between the group of patients with early or late presentation to the first physician (12% versus 9.9%), ED (12.4% versus 9.6%), or neurologist (12.2% versus 11.1%) were not statistically significant.
Logistic regression analysis revealed that CSS score on admission and the time before the patient was seen by the neurologist independently predicted the clinical outcome (P<.0001) (Table 3⇓). The RR of poor outcome in patients seen by the neurologist after the first 6 hours from symptom onset was 5.6 (95% CI, 3.4 to 9.2). When only patients with cerebral infarcts were studied, the RR of poor outcome in those who presented to a neurologist after the first 6 hours was 5.7 (95% CI, 3.1 to 10.2). Age, previous functional abilities, and delays before the patient was seen by the first physician or the ED and before hospitalization were not significantly related to clinical outcome in this model. A supplementary analysis was performed with 6, 12, and 24 hours as cutoff points for the variable of time before a neurologist was seen. The RRs of poor outcome were 5.6 (95% CI, 3.1 to 10.0) when the time before a neurologist was seen was 6 to 12 hours, 5.2 (95% CI, 2.9 to 9.3) for 12 to 24 hours, and 6.2 (95% CI, 3.4 to 11.4) for more than 24 hours.
The duration of hospitalization was significantly shorter in the group of patients with a short delay before being seen by the first physician or the ED or before hospitalization than in those with a long delay (P<.001, Mann-Whitney rank sum test). The median duration of hospitalization was 11 days (range, 5 to 31) in patients examined by a neurologist within the first 6 hours and was 19 days (range, 1 to 81) when they were evaluated after this period (P<.001). Multiple linear regression analysis in all stroke patients (Table 4⇓) and in those with cerebral infarct revealed that the time before consultation with a neurologist correlated positively with the log-transformation of days of hospitalization, independent of age, previous functional abilities, and CSS score on admission. The delays before the patient was seen by the first physician or the ED and before hospitalization did not reach statistical significance. The adjusted R2 of the time before consultation with a neurologist was 8%, and thus this factor predicted more than one third of the explained log duration of hospitalization of the model.
There is presently a general agreement to strongly recommend emergency diagnostic and therapeutic interventions for acute stroke patients in a hospital unit with a specialized interest in the treatment of cerebrovascular diseases.23 The beneficial effects of thrombolytics and neuroprotective drugs in the first hours of cerebral ischemia are being widely investigated in clinical research protocols, and many have high expectations of them. Early hospital arrival of patients with acute ischemic stroke facilitates their allocation to these clinical trials and increases the chance that both types of therapy will be helpful. However, neurological and general early supportive care could improve outcome after stroke and prevent medical complications independent of the acute reperfusion and neuronal protection therapies. An overview analysis of 10 controlled trials demonstrated a better prognosis for patients admitted into stroke units, although it is not clear which interventions improve survival.24 Stroke units combine acute medical treatment, a multidisciplinary approach, early and intensive rehabilitation, and a nursing program. One of the most important contributors to better outcome could be the management of stroke by an experienced team applying standardized diagnostic evaluations and treatments.25
The potential benefit of early neurological attention after acute stroke has not been investigated previously. Our results suggest that patients seen by a neurologist within the first 6 hours after symptom onset have a better outcome and shorter duration of hospitalization. We cannot offer a firm explanation regarding why the outcome was better when the patients were examined earlier by neurologists because our study was observational, not interventional. Physicians trained in stroke management have a better knowledge of how and when to use potential therapies and diagnostic procedures. The participating neurologists were particularly sensitive to acute stroke care and used common diagnostic evaluation and treatment strategies in the acute phase that were established in a preceding consensus.18 Although there are no proven beneficial therapies for acute stroke, we can speculate that some standardized interventions within the first 6 hours, such as resolutions based on CT findings, and a better management of hypertension and hyperglycemia could be of benefit to our patients. Recently, a study of stroke management in EDs observed that blood pressure was excessively lowered in 31% of hypertensive patients and hypotonic dextrose intravenous fluids were inappropriately given to 69% of all patients.26
The conclusions of this observational study may be limited by several potential confounding factors. Some factors, such as a tendency for earlier neurological attention for patients in better condition on admission and an artificial shortening of the duration of hospitalization as a result of the lower neurological deficit of survivors, may be reasonably ruled out. However, other biases may confound our results. Patients seen earlier by neurologists were not younger than patients attended after 6 hours,22 but we cannot exclude relevant differences between the two groups in cardiovascular risk factors and other prognostic variables that were not recorded. In addition, a few patients were included in clinical trials within the first 6 hours after stroke onset, and this could have resulted in a better outcome. Finally, CSS scores could have been unstable during the time period of the study, so that patients might have had a lower score previously and a subsequent increase. Most of this potential confounding effect has been neutralized by the adjustment in the delay before a neurologist was seen, since this delay was equal to the interval from symptom onset to the measurement of the CSS score. Furthermore, in our experience, when acute stroke patients are evaluated within the first 8 hours after symptom onset, they frequently deteriorate, and a worsening of the CSS score is more common than an improvement in the following 48 hours.27
The present study was limited to the patients allocated to the neurological wards and to the patients in whom the time of symptom onset or the delay was known. Although we cannot extrapolate our conclusions to the general population, we believe that they may have important health and economic repercussions. In our study the delay before hospital arrival was quite different from the delay before contact with a neurologist. The mean delay from ED arrival to neurological intervention was 10.5 hours in this series,22 which is similar to that in the study of Feldmann et al10 and longer than that in the study of Malik et al.8 It is interesting that early neurological attention in the participating hospitals, but not early ED arrival, was a factor predictive of good outcome. Although the causes of this benefit are not clear, it is reasonable to recommend the early intervention of a neurologist or a physician experienced in stroke management, preferably in the first 6 hours. Further studies are needed to confirm these results and to identify the mechanisms that lead to a better outcome when patients are seen early by neurologists.
Selected Abbreviations and Acronyms
|CSS||=||Canadian Stroke Scale|
|ECASS||=||European Cooperative Acute Stroke Study|
|IST||=||International Stroke Trial|
The following members of the Cerebrovascular Diseases Study Group of the Spanish Society of Neurology participated in the study: M. Aguilar, Hospital Mutua de Tarrasa (Barcelona); J. Alvarez, Hospital Vall d’Hebrón (Barcelona); A. Arboix, Hospital L’Aliança (Barcelona); J. Castillo, Hospital Xeral de Galicia (Santiago de Compostela); A. Dávalos, Hospital Dr Josep Trueta (Girona); E. Diez-Tejedor, Hospital La Paz (Madrid); J.A. Egido, Hospital San Carlos (Madrid); C. García-Sancho, Hospital Virgen del Cristal (Ourense); J.M. Juan-Togores, Hospital Na Sa Candelaria (Tenerife); J.M. Lainez, Hospital General Universitario (Valencia); R. Martín, Hospital de Villajollosa (Alicante); F. Martinez, Hospital Xeral (Lugo); E. Martinez-Vila, Clinica Universitaria (Pamplona); J. Matías-Guiu, Hospital General (Alicante); E. Mostacero, Hospital Clínico (Zaragoza); J.R. Rodriguez, Hospital Montecelo (Pontevedra); F. Rubio, Hospital de Bellvitge (Barcelona); J. Vivancos, Hospital de la Princesa (Madrid).
The authors wish to extend their gratitude to Dr Jaume Marrugat (Institut Municipal Investigació Mèdica de Barcelona) for his helpful comments on design and statistical analysis.
Reprint requests to Dr Antoni Dávalos, Section of Neurology, Hospital de Girona Dr Josep Trueta, Ctra Francia s/n, 17007 Girona, Spain.
A complete list of the participants in this research study appears in the Appendix.
- Received June 6, 1995.
- Revision received August 8, 1995.
- Accepted September 12, 1995.
- Copyright © 1995 by American Heart Association
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