Hospital presentation after stroke in a community sample: the mobile stroke project.

ABSTRACT

Background. Existing data regarding time between stroke and presentation for treatment are largely derived from hospital-based or multicenter databases and may not accurately reflect presentation patterns for most hospitalized stroke patients.

Methods. We evaluated a consecutive series of all hospitalized patients in Mobile County, Alabama.

Results. We identified 1,010 hospitalized stroke patients. Of all patients with out-of-hospital stroke, 42% came to a hospital within 3 hours of symptom onset. There were no statistically significant interhospital differences. Being asleep at the time of stroke or being transported by family or friends significantly increased the likelihood of late arrival.

Conclusions. A minority of stroke patients arrive at a hospital early enough to qualify for acute intervention. Until development of acute therapies with longer therapeutic windows or more robust therapeutic benefit than tissue plasminogen activator (t-PA), effective stroke prevention strategies will exert a greater influence on stroke incidence and morbidity.

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INTRAVENOUS ADMINISTRATION of t-PA for the treatment of acute ischemic stroke must be accomplished within 3 hours of onset of symptoms. Unfortunately, most patients having ischemic stroke arrive at a hospital too late to be considered for thrombolysis. (1,2) Most emerging therapies for stroke also will have narrow therapeutic windows, highlighting the importance of rapid patient presentation. Existing data regarding presentation times after stroke are largely derived from hospital-based (3-7) or multicenter databases, (8-10) many of which involve hospitals with stroke teams. (4-8) Because of selection bias, these studies may not accurately reflect presentation patterns for the majority of hospitalized stroke patients. We therefore sought to determine the presentation times of all hospitalized stroke patients in our community and to evaluate factors influencing hospital presentation after acute stroke.

MATERIALS AND METHODS

Over a 13-month period beginning November 1, 1995, and ending November 30, 1996, we evaluated a consecutive series of patients admitted to all hospitals in Mobile County, Alabama, for treatment of acute stroke. The five study hospitals were a university medical center (UMC) (University of South Alabama), a university-affiliated community hospital (UCH), and three private medical centers (A, B, and C). Only the UMC and UCH had a stroke team in place. The five hospitals serve residents of Mobile County, which has a population of approximately 400,000. Patients were identified prospectively at the UMC and UCH via the University of South Alabama (USA) Stroke Center Stroke Code Log, described elsewhere, (7) and daily review of admission lists. Patients at A, B, and C were identified retrospectively via review of hospital discharge diagnoses. Specifically, medical records of all patients discharged with International Classification of Diseases, Ninth Revision (ICD-9) codes 431, 432, 433, 434, 436, and 437 were revi ewed on a monthly basis; only patients with acute ischemic or hemorrhagic stroke were included. Patients with iatrogenic stroke were excluded.

For patients at the UMC and the UCH, basic demographics and data regarding medical history, acute stroke presentation, initial physical examination, diagnostic evaluation, therapy, stroke distribution and mechanism, initial neurologic status, disposition 1 week after hospitalization, and therapy for secondary stroke prevention were collected and subsequently entered into a computerized database (Visual FoxPro 3.0). For patients at A, B, and C, more limited data regarding basic demographics, acute presentation, diagnostic evaluation, stroke mechanism, and disposition at 1 week after hospital presentation were recorded. For patients with out-of-hospital strokes, time to presentation was determined as the time from symptom onset to arrival in an emergency department. Patients unable to communicate the time of symptom onset or who had symptom onset during sleep were assumed to have onset when last known to be normal. One of the three of us who are stroke neurologists (R.M.Z., J.E.M., or J.F.R.) reviewed each dat a form before entry into the computerized database and determined stroke mechanism. Stroke severity was determined using a "collapsed" Rankin scale, which has been previously reported (11) (Appendix 1), and stroke cause was determined using modified Trial of ORG 10172 in Acute Stroke Treatment criteria (12) (Appendix 2).

Statistical analysis was done using Pearson's chi-square test to compare proportions and one-way analysis of variance to compare means of continuous variables (ie, age). Multivariate logistic regression analysis was done by forward selection procedure, using hospital presentation within 3 hours as the dependent variable and the following as independent variables: patient insurance status, facility, age, sex, race, stroke subtype, intracerebral hemorrhage (yes/no), mode of transportation to the hospital, stroke severity, history of chronic atrial fibrillation, history of diabetes mellitus, and asleep at time of onset (yes/no). A level of P < .05 was considered statistically significant.

RESULTS

During the study period, 1,010 hospitalized stroke patients were identified. There were interfacility differences in racial distribution. Relative to all other hospitals, patients at UMC were younger and more often black men. Compared with UGH, UMC patients were more likely to be active smokers (Table 1). There were no other significant differences in the distribution of demographic and clinical variables between the facilities.

Four percent of all strokes occurred in hospitalized patients (Table 2). Of all patients with out-of-hospital stroke, 42% presented to a hospital within 3 hours of symptom onset. There were no statistically significant interhospital differences. The Figure shows the percentage of patients seen within 3 hours, by facility and major stroke subtype (ie, ischemic vs intracerebral hemorrhage). Two hundred eighty-eight 288 patients (38%) who had ischemic stroke and 67 (67%) with intracerebral hemorrhage arrived within 3 hours of stroke onset (P= .005). For 86 patients (8.5%), time to presentation could not be determined from the medical record.

Demographic and clinical variables and their influence on time to arrival are presented in Table 3. According to univariate analysis, transportation via emergency medical service (EMS) (vs transportation by family or a friend) and intracerebral hemorrhage were associated with early hospital arrival. Table 4 shows the frequency of early presentation by ischemic stroke subtype. Patients with out-of-hospital lacunar ischemic stroke were less likely to present early than those with nonlacunar ischemic stroke (31% vs 39%, respectively), but this did not reach statistical significance when corrected for multiple comparisons (P= .09).

The multivariate logistic regression model indicated that a patient's being asleep at the time of stroke or being transported to the hospital by family or friends significantly increased the likelihood of late arrival (Table 5). The model failed to confirm an association between stroke subtype and presentation time.

DISCUSSION

Our data indicate that in Mobile County 44% of stroke patients have either an in-hospital stroke (4%) or have out-of-hospital stroke and arrive at a hospital within 3 hours (40%). Within our community, there is an academic medical center and a university-affiliated community hospital, both with designated stroke teams, as well as 3 private medical centers, none of which had such stroke teams during the period of this study. The proportion of patients arriving within 3 hours of stroke was not influenced by facility type or the presence of a stroke team. Overall, the percentage of patients with early poststroke arrival was slightly lower than the 50% to 59% figures reported by other investigators. (8,13,14) The factors associated with late arrival were stroke onset during sleep and utilization of private transportation (vs EMS).

Ischemic stroke (vs hemorrhagic) predicted late arrival in the univariate analysis only. These predictors of late arrival are consistent with several earlier studies. (5,8,19,15)

Although univariate analysis did indicate an association between early arrival arid hemorrhagic stroke, we failed to find a statistically significant association between ischemic stroke subtype and arrival time. Our power may have been limited by the high number of strokes we were forced to designate "stroke of unknown etiology." The proportion of strokes of unknown cause in our study exceeds figures reported in earlier studies, (16-19) and this may be explained in part by our relatively strict criteria for assigning a known etiology. Specifically, we categorized a stroke as unknown etiology because of an incomplete workup if no intracranial vascular evaluation was done (ie, transcranial Doppler study, magnetic resonance angiography, or conventional angiography).

Even though our findings indicate there may be a need for intensive community education in an attempt to significantly increase the number of patients who present themselves early after stroke, certain of the data suggest that the consequent impact on patient outcome would be limited. Specifically, our experience has been that only 19% of patients seen at the UMC or UGH within 3 hours of ischemic stroke onset qualify for and receive intravenous t-PA, the majority of exclusions being for significant spontaneous improvement or warfarin use. (1) As the only local facilities with designated stroke teams and a 24-hour "stroke code" system, the UMC and UGH may represent a "best case scenario" regarding treatment yield. If, then, we assume that 19% of all ischemic stroke patients in Mobile were to qualify for and receive t-PA, even a 20% absolute increase in the percentage of patients presenting within 3 hours (from 38% to 58%) would translate to a positive treatment response in only 11 patients annually (assuming a 12% absolute treatment response, as per the NINDS trial (20)). This calculation starkly highlights the importance of stroke prevention strategies and the critical need for therapies that carry a more robust treatment effect than t-PA or have a wider applicability (ie, longer therapeutic window), or both.

Our study has several limitations that must be noted. First, we have not accounted for patients who were transferred to a Mobile hospital from a community hospital in a surrounding county. Although the percentage of such patients is small, this variable may have elevated presentation times, as we recorded time to presentation as time between stroke onset and arrival in a Mobile emergency department. In the future, we hope that most of these patients can receive acute stroke treatment locally and that only those requiring more intensive care will require transfer to Mobile. We did not record several variables at non-USA hospitals (eg, stroke risk factors, mode of transportation, stroke severity), thereby limiting our analysis of factors associated with late arrival. Specifically, this may account for our failure to identify intracerebral hemorrhage as a predictor of late arrival in the multivariate model. In addition, we have no reliable data regarding the precise causes of presentation delay, information tha t would be integral to developing effective community education programs. Finally, the publication of the NINDS t-PA trial results occurred during our study, and it is conceivable that presentation times subsequentiy have improved. Even so, a comparison of presentation times during the period before and subsequent to this publication revealed no significant difference.

Consistent with earlier studies, our data indicate that the minority of stroke patients arrive at a hospital early enough to qualify for acute intervention. The use of EMS and stroke onset while awake are associated with earlier arrival. Until development of acute treatments with longer therapeutic windows or more robust therapeutic benefit than t-PA, effective stroke prevention strategies will exert a far greater influence on stroke incidence and morbidity.

APPENDIX 1.

Definitions: University of South Alabama Functional Scale for Evaluation of Stroke Severity

Asymptomatic at time of initial examination, with normal or chronic findings

Symptomatic at time of initial examination, but with no new demonstrable signs

Mild new deficit (could return to work or usual baseline level of functioning)

Moderate new deficit (would be unable to return to work or usual baseline level of functioning, but would not require chronic institutionalization or assistance for activities of daily living: cooking, eating, dressing, personal toilet, etc)

Severe new deficit (would require chronic institutionalization and/or chronic assistance for basic personal needs)

Unknown

APPENDIX 2. Mobile Stroke Project: Criteria for Stroke Classification

Lacunar stroke

Age [greater than or equal to]45 years or any age with history of diabetes mellitus and/or hypertension

Clinical presentation consistent with one of the recognized lacunar syndromes: pure sensory, motor or sensorimotor (involving face, arm, leg, or arm and leg); dysarthria/clumsy hand; ataxic hemiparesis 

No other obvious cause for small-vessel distribution stroke (eg, no primary vasculitis, amphetamine use, hyperviscosity, coexisting cardiac disease with high embolic potential)

Computed tomography (CT) or magnetic resonance imaging (MRI) evidence of infarction [less than or equal to]2 cm in diameter, subcortical in location, in the distribution of a small, deep penetrating artery, and in a location appropriate for acute symptoms/signs; or CT or MRI done [greater than or equal to] 72 hours after stroke onset shows no acute infarction despite persisting neurologic deficit

Angiographic or carotid duplex evidence of no anatomically significant ulceration (2 mm) or linear stenosis (50%) in the proximal large-vessel supply; if infarction appears to be in the brain stem by symptoms/signs or neuroimaging, angiographic correlation required

Cardioembolic stroke

Known cardiac disease with high potential for embolization (eg, rheumatic mitral valve disease with or without atrial Fibrillation, nonvalvular atrial fibrillation, prosthetic mitral or aortic valve, anterior wall myocardial infarction within previous 6 weeks, dilated cardiomyopathy (with or without associated mural thrombus), ventricular aneurysm with or without associated thrombus, objective evidence of left ventricular mural thrombus, bacterial endocarditis, atrial myxoma, or demonstrated mitral or aortic valvular thrombus)

Ischemic Stroke, Cause Unknown

Clinical presentation consistent with embolic stroke (maxi mal stroke deficit at onset)

Angiogram or duplex evidence of no significant stenosis (ie, 50%) or ulceration (2 mm) in the proximal large vessel supply; if infarction is found in the posterior circulation distribution, angiographic correlation is required

Large-Vessel Atherothrombotic/Embolic Stroke (Includes Presumed Atherosclerotic Arterial to Arterial Embolic Stroke)

Clinical presentation does not suggest a lacunar syndrome

No other obvious source for ischemic stroke (eg, no cardiac disease with high embolic potential; no evidence of arterial dissection; no active or recent use of sympathomimetic drugs)

Angiography or carotid noninvasive testing performed within 30 days of stroke onset demonstrates 50% linear stenosis and/or ulceration 2 mm in the ipsilateral (to infarct) large-vessel supply; if stroke is in posterior circulation distribution, angiography is required. Lesion shown should be characterisuc of atherothrombosis in appearance and location.

Miscellaneous Stroke Causes

Includes well-documented cases of infarction due to arterial dissection (angiography required), recreational drug use, prothrombotic state, primary or acquired vasculitis, migraine, and other less common causes for ischemic stroke

Ischemic stroke not meeting the diagnostic criteria previously outlined because of incomplete workup, complete workup but no clear etiology, multiple potential causes (eg, a trial fibrillation and proximal atherothrombotic stenosis)

[GRAPH OMITTED]

TABLE 1

Clinical Characteristics of Patients

                                         Facility

                                 UMC             UCH

No. (%)                      196 (19)        52 (5)
Age (yr) (mean [+ or -] SD)  61 [+ or -] 15  68 [+ or -] 13
Female (%)                   38              52
Race (%)
   White                     49              83 ++
   Black                     51              17
Risk factors (%)
   Previous stroke           31              31
   Hypertension              69              67
   MI                        11              10
   Atrial fibrillation        8              16
   Smoker                    39              21
   Diabetes                  28              27
Mode of entry (%)
   Self                       2               0
   Family/friends            39              52
   EMS                       54              39
   Hospitalized               3               4
   Other                      3               6
Stroke severity (%)
   Mild                      16              19
   Moderate                  28              39
   Severe                    55              42
Stroke subtype (%)
   Small vessel              17              18
   Large vessel              10              22
   Cardioembolic              5               7
   Other                      1               0
   Unknown                   54              42
   Hemorrhage                14              11

                                         Facility

                                  A               B

No. (%)                      393 (39)        241 (24)
Age (yr) (mean [+ or -] SD)  70 [+ or -] 14  71 [+ or -] 12
Female (%)                   59              49
Race (%)
   White                     56 **           84 **
   Black                     44              14
Risk factors (%)
   Previous stroke           -               -
   Hypertension              -               -
   MI                        -               -
   Atrial fibrillation       -               -
   Smoker                    -               -
   Diabetes                  -               -
Mode of entry (%)
   Self                      -               -
   Family/friends            -               -
   EMS                       -               -
   Hospitalized              -               -
   Other                     -               -
Stroke severity (%)
   Mild                      -               -
   Moderate                  -               -
   Severe                    -               -
Stroke subtype (%)
   Small vessel              17              15
   Large vessel              12               8
   Cardioembolic              7               7
   Other                      1               1
   Unknown                   51              52
   Hemorrhage                12              18

                                 Facility

                             C               Total           P Valve

No. (%)                      128 (13)        1,010
Age (yr) (mean [+ or -] SD)  72 [+ or -] 14  69 [+ or -] 14  <.001 *
Female (%)                   56              52              <.001 +
Race (%)
   White                     77 ++           65              <.05
   Black                     23              34
Risk factors (%)
   Previous stroke           -               31                NS
   Hypertension              -               69                NS
   MI                        -               11                NS
   Atrial fibrillation       -               10               .06
   Smoker                    -               35               .02
   Diabetes                  -               28                NS
Mode of entry (%)                                              NS
   Self                      -                2
   Family/friends            -               42
   EMS                       -               51
   Hospitalized              -                3
   Other                     -                4
Stroke severity (%)                                            NS
   Mild                      -               17
   Moderate                  -               30
   Severe                    -               52
Stroke subtype (%)                                             NS
   Small vessel              14              16
   Large vessel              14              11
   Cardioembolic              7               7
   Other                      3               1
   Unknown                   47              51
   Hemorrhage                16              14

UMC = University medical center; UCH = university-affiliated community
hospital; A, B and C = three private medical centers; SD = standard
deviation; NS = not significant; MI = myocardial infarction; EMS =
emergency medical service.

* UMC compared with each of the other facilities.

+ UMC vs all other facilities.

** p < .001 vs all other facilities.

++ p < .05 vs all other facilities.

TABLE 2

Time From Stroke Onset to Hospital Presentation (by Facility)

                                          Facility

                          UMC       UCH       A         B

Time to presentation (%)  NS
  <3 hours                37        39        43        37
  3-24 hours              39        33        32        37
  >24hours                21        26        23        20
In-hospital stroke         4         2         2         6

                           Facility

                          C         Total     P Value

Time to presentation (%)                        NS
  <3 hours                43         40
  3-24 hours              33         34
  >24hours                21         22
In-hospital stroke         3          4

UMC = University medical center; UCH = university-affiliated community
hospital; A, B, and C = three private medical centers; NS = not
significant.

TABLE 3

Variables Influencing Early Arrival

                                   Time to Arrival
                       [less than or equal to]  > 3 Hours       P Value
                        3 Hours

No. (%) *              373 (42)                 519 (58)
Age, mean [+ or -] SD  69 [+ or -] 8            69 [+ or -] 6    NS
Race (%)                                                         NS
  White                68                       65
  Black                31                       34
Female (%)             50                       53               NS
Risk factors (%) +                                               NS
  Previous stroke      21                       34
  Hypertension         72                       68
  MI                    7                       12
  Atrial fibrillation  11                        5
  Smoker               30                       40
  Diabetes             25                       32
Stroke severity (%) +                                            NS
  Mild                 15                       22
  Moderate             29                       35
  Severe               55                       43
Mode of entry (%) +                                             .004 **
  Self                  3                        2
  Family/friends       32                       57
  EMS                  65                       36
  Hospitalized          0                        0
  Other                 1                        1
Stroke subtype (%)                                             <.0001 ++
  Small vessel         12                       20
  Large vessel         10                       13
  Cardioembolic         7                        7
  Other                 1                        1
  Unknown              50                       54
  Hemorrhage           19                        7

SD = Standard deviation, NS = not significant, MI = myocardial
infarction, EMS = emergency medical service, UMC = university medical
center, UCH = university-affiliated community hospital.

* Of 892 with known times to presentation.

+ Recorded at UMC and UCH only.

** Family/friends vs EMA.

++ Hemorrhagic vs ischemic stroke subtypes.

TABLE 4

Presentation Time by Ischemic Stroke Subtype

                         Time to Arrival
                 [less than or equal  > 3 Hours
                     to] 3 Hours                 P Value
                       No. (%)        No. (%)

Stroke subtype                                    .09 *
  Small vessel         44 (31)        100 (69)
  Large vessel         36 (36)         65 (64)
  Cardioembolic        24 (41)         34 (59)
  Other                 5 (56)          4 (44)
  Unknown             179 (40)        273 (60)

* Small vessel vs all other ischemic subtypes.

TABLE 5

Multivariate Logistic Regression Analysis of Factors Associated With
Arrival More Than 3 Hours After Onset of Stroke

Factor                          OR   95% CI

Asleep at time of stroke       10.5   4-31
Transported by family/friends   5.0   2-11

OR = Odds ratio, CI = confidence interval.

Acknowledgment. We thank Naomi Walters for assistance with database management.

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RELATED ARTICLE: KEY POINTS

* Forty-two percent of patients with out-of-hospital stroke (38% with ishemic stroke and 67% with intracerebral hemorrhage) presented to a hospital within 3 hours.

* Being asleep at the time of stroke or being transported by family and/or friends were both statistically associated with likelihood of late arrival.

* A minority of stroke patients arrive at a hospital early enough to qualify for acute treatment with t-PA.

* Until treatment of more robust benefit or with a less stringent time requirement than t-PA is identified, acute stroke therapy will make little impact on overall stroke morbidity and mortality.

From the Stroke Center and Department of Mathematics and Statistics (Dr. Shah), University of South Alabama, Mobile.

Supported by a grant from the American Heart Association, Alabama affiliate.

Reprint requests to Richard M. Zweifler, MD, University of South Alabama Stroke Center, 10th Floor, Suite 1, 2451 Fillingim St, Mobile, AL 36617.