Optimizing Discharge Planning

Clinical Predictors of Longer Stay After Recombinant Tissue Plasminogen

Activator for Acute Stroke
Gustavo Saposnik, MD, MSc; Fiona Webster, MA;
Chris O’Callaghan, BAppSc; Vladimir Hachinski, MD, DSc, FRCPC

Background and Purpose—The length of stay (LOS) is the main cost-determining factor for inpatients with acute stroke.
Although studies have identified variables associated with LOS, few have analyzed predictors of longer stay after
receiving thrombolytic therapy for acute stroke.
Methods—We studied all consecutive acute stroke patients receiving intravenous recombinant tissue plasminogen activator
(rtPA) admitted to the London Health Sciences Center, in London, Ontario, Canada, from 1999 to 2003. Longer stay
was defined as LOS ⱖ7 days after admission. Demographic as well as baseline clinical, laboratory, and imaging
variables were analyzed to identify predictors of LOS. Significant variables were entered into a multivariate logistic
regression analysis.
Results—Among 216 acute stroke patients receiving rtPA, the median LOS was 6 days. LOS was ⬎7 days in 102 (49%)
patients. Age ⱖ70 (odds ratio [OR], 2.2; 95% CI, 1.2 to 4.0), lack of improvement at 24 hours (OR, 2.5; 95% CI, 1.4
to 4.4), prestroke modified Rankin Scale ⱖ2 (OR, 2.4; 95% CI, 1.2 to 4.9), baseline National Institutes of Health Stroke
Scale score ⱖ15 (OR, 9.4; 95% CI, 3.2 to 27.6), cortical involvement (OR, 2.2; 95% CI, 1.2 to 3.9), and new infarction
on the control computed tomography (CT; OR, 2.8; 95% CI, 1.4 to 5.9) were independent predictors of longer stay.
Conclusions—Lack of improvement at 24 hours after rtPA, cortical involvement, and new infarction on the 24-hour CT
scan are relevant variables that can independently affect the LOS. These new variables may be useful for establishing
policy in relation to the organization and planning of the health care system. (Stroke. 2005;36:147-150.)
Key Words: complications 䡲 hospitalization 䡲 outcome 䡲 prognosis 䡲 stroke 䡲 thrombolytic therapy
Downloaded from http://ahajournals.org by on May 19, 2023

䡲 tissue plasminogen activator

T he length of stay (LOS) is the main cost-determining

factor during hospitalization.1 The average LOS for
stroke varies among different countries, which may reflect the
impact of the differences in health care system organization.
For example, the LOS in the United States2 for patients with
acute ischemic stroke ranges from 6 to 11 days compared
with much longer hospitalizations (17 to 26 days) in Canada,3
Europe,4 and Asia.5 Information that can predict longer LOS
in stroke patients will be useful for clinical and systems
management, for example, as a marker for discharge plan-
ning, resource utilization, and cost implications.6 Few articles
identify clinical factors associated with longer hospitalization
in stroke patients who receive thrombolytic therapy.7,8 Most
articles concerning LOS take into account the perspective of
the administrators, are focused on costs, and do not neces-
sarily consider the clinical relevance of findings.5
The aim of the present study was to determine clinical
predictors for longer hospitalization in stroke patients after
receiving recombinant tissue plasminogen activator (rtPA).
We hypothesized that (1) baseline clinical, imaging, or
laboratory factors are associated with LOS; and (2) these
factors are different from those described previously in the
prethrombolytic period or in patients not receiving rtPA.
Patients and Methods
We analyzed all consecutive acute stroke patients who received
rtPA. All patients were admitted to the London Health Sciences
Center, University Campus (LHSC-UC) in London between January
1999 and March 2003. London is the largest city in Southwestern
Ontario, with a population of 336 540 inhabitants (432 450 in the
metropolitan area). It has 2 academic medical centers with 24-hour
access to computed tomography (CT) and MRI. These academic
hospitals are a referral center for a large part of Ontario. In addition
to serving the local population, LHSC-UC receives acute stroke
referrals from 33 rural hospitals from 7 counties. Hospital charac-
teristics, population served, and catchment area were outlined in
previous articles.9,10 Demographic variables, stroke severity at ad-
mission and at 24 hours, functional status at admission, comorbidity,
and outcomes were prospectively collected. Time of symptom onset

Received September 1, 2004; final revision received October 13, 2004; accepted October 19, 2004.
From the Stroke Program, Department of Clinical Neurological Sciences and Southwestern Ontario Coordinated Stroke Strategy, London Health
Science Center, The University of Western Ontario, London, Ontario.
Correspondence to Dr Gustavo Saposnik, 339 Windermere Rd, Stroke Service, Office 7-GE5, London Health Sciences Center, London, ON –N6A 5A5,
Canada. E-mail gsaposni@uwo.ca
© 2004 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org DOI: 10.1161/01.STR.0000150492.12838.66

147
 148 Stroke January 2005

was defined by the time when patients were “last seen to be well.” TABLE 1. Population Characteristics
Time of rtPA was obtained from the nurse records as onset to needle
time for the rtPA infusion. Baseline National Institutes of Health Mean (median) 25th to 75th
Stroke Scale (NIHSS) score was performed by a certified neurologist or No. (%) Percentile
just before treatment with rtPA. Current medications were also Clinical variables
recorded if they were regularly consumed in the previous month.
Age (SD) 71.5 (74) 65.0–80.0
All patients had a baseline and 24-hour CT scan. A single
neuroradiologist blinded to clinical data reviewed scans to determine Age ⱖ70 years (%) 144 (66)
the presence of new infarction, cortical involvement, and extension Sex, male (%) 111 (51)
of the ischemic lesion.
City of onset, London (%) 129 (59)
The decision to treat with rtPA was made according to the
National Institute of Neurological Disorders and Stroke (NINDS) NIHSS on admission 13 (13) 8–18
protocol. Inclusion and exclusion criteria were applied with a major LOS 12.1 (6) 4–12
difference from NINDS: stroke patients with involvement of more
Frequency of risk factors, (%)
than one third of the middle cerebral artery territory on the baseline
CT scan were excluded. Hypertension 135 (62)
An evaluation to determine the stroke mechanism and subtype in Diabetes mellitus 50 (23)
all patients included: routine laboratory tests, ECG, transthoracic
Hypercholesterolemia 81 (38)
echocardiogram, and carotid ultrasound. Outcomes at 3 months were
assessed according to the modified Rankin score. Coronary artery disease 68 (31)
Smoking 41 (19)
Definition of Variables Excessive alcohol intake 17 (8)
We analyzed the distribution of all variables by graphic and analytic
methods (frequency distribution by quartiles or quintiles). When Prior transient ischemic attack 24 (11)
there was no clear relationship, we used clinical criteria to analyze History of atrial fibrillation 50 (23)
the variables. In our analysis, dose of rtPA, time to treatment, Previous medications
glucose, and white cell count were considered continuous variables.
Age, baseline NIHSS, and modified Rankin Scale (mRS), were Use of aspirin 89 (42)
categorized a priori according to common cutoff described in the Use of angiotensin-converting enzyme 44 (26)
literature. inhibitors
Because the distribution of LOS was skewed to the right, the Use of statins 47 (23)
results were summarized be median and 25th and 75th percentile
values. Stroke subtype, (%)
Stroke subtype (lacunar versus nonlacunar) was based on pres- Lacunar 24 (11)
Downloaded from http://ahajournals.org by on May 19, 2023

enting symptoms, physical examination, and neuroimaging. The
presence of cortical involvement, new infarction, or hemorrhagic
transformation was established according to the neuroradiology
report of the 24-hour CT scan.
Clinical Outcome Measures
Longer stay was defined as LOS ⱖ7 days. In previous studies, a
longer LOS was defined as 6 to 8 days.11,12 This measure is based on
the understanding that the provision of acute stroke care, identifica-
tion of the stroke mechanism, and preventing complications is
generally achieved within the first week of admission.
Outcome at 24 hours was defined as a lack of improvement (LOI)
determined by a ⱕ3-point difference between the baseline and
24-hour NIHSS. Three-month outcomes were determined using the
mRS. Poor outcome was defined as an mRS ⱖ3 or death.
Statistical Analysis
The association between demographic characteristics, clinical and
hemodynamic variables, and LOS was examined using univariate
logistic regression. Stepwise multivariate logistic regression, allow-
ing for entry at the 0.15 level of significance based on the score
statistic, was used to determine a subset of these variables indepen-
dently associated with LOS. Covariates were checked for collinearity
and interaction effects. Discrimination of the model was assessed by
the area under the receiver operating characteristic (ROC) curve, and
calibration was assessed using goodness of fit test.
Statistical analysis was performed using STATA 7.0 (StataCorp
LP). P values ⬍0.05 were considered significant.
Results
A total of 216 patients received intravenous rtPA at
LHSC-UC between January 1999 and March 2003. The mean
age was 71.5⫾12 years, and 111 (51%) were male. Baseline
characteristics are described in Table 1.
Nonlacunar 195 (89)
Seven patients (3.2%) were excluded because of missing
data. Finally, 209 patients were considered for the analysis.
Median LOS in stroke patients after rtPA was 6 days (25th to
75th percentile: 4 to 12 days; Table 1).
The LOS was ⬎7 days in 102 (49%) patients. There were
no statistically significant differences in sex, city of onset
(London versus other), vascular risk factors, previous medi-
cation, stroke subtype (lacunar versus non lacunar), glucose
level at admission, time to treatment, and rtPA dose between
both groups (LOS ⱕ7 days). Table 2 summarizes predictors
of longer stay in the univariate analysis. The overall asymp-
tomatic and symptomatic hemorrhage rates at 36 hours were
10.4% and 4.1%, respectively. Five patients (2.3%) with
symptomatic intracranial hemorrhage died. The presence of
symptomatic or any kind of bleeding was not associated with
longer stay (P⫽0.79 and 0.20, respectively).
Forty patients (18%) were treated outside the time window
(180 minutes). There was no statistically significant differ-
ence in the LOS between those patients treated within or
outside 180 minutes of symptom onset (P⫽0.29).
A total of 118 patients (55%) had poor outcome (mRS 3 to
5 or death) at 90 days. The frequency of longer stay was
significantly higher among patients with poor outcome at 3
months (74% versus 39.5%; P⬍0.001).
Multivariate Analysis
In logistic regression analysis, we identified 2 models with
similar performance and predicting values. In model A, age
 Saposnik et al Predictors of Longer Stay After rtPA for Acute Stroke 149

TABLE 2. Univariate Analysis of Predictors for LOS

LOS ⬎7 days Median LOS, days
Characteristic No. (%) OR (95% CI) (25th to 75th Percentile) P Value
Age ⬍0.01
⬍69 72 (34) 5 (3–9)
ⱖ70 137 (66) 2.2 (1.2–4.0) 7 (4–13)
LOI 24 hours after rtPA ⬍0.001
No 101 (47) 6 (4–10)
Yes 115 (53) 2.5 (1.4–4.4) 8 (4–14)
Prestroke mRS 0.01
0–1 163 (80) 6 (4–10)
2–5 41 (20) 2.4 (1.2–4.9) 11 (4–17.5)
Baseline NIHSS ⬍0.001
0–6 29 (14) reference 4 (4–5)
7–14 106 (51) 4.0 (1.4–11.0) 6 (3–12)
ⱖ15 74 (35) 9.4 (3.2–27.6) 9 (5–18)
Cortical involvement ⬍0.01
No 76 (39) 5.5 (3–9)
Yes 121 (61) 2.2 (1.2–3.9) 7 (4–14)
New infarction ⬍0.001
No 42 (20) 4 (3–7)
Yes 170 (80) 2.8 (1.4–5.9) 7 (4–14)

ⱖ70 years (odds ratio [OR], 2.10; 95% CI, 1.12 to 3.86), planning has been productivity, cost containment, and quality
baseline NIHSS ⱖ15 (OR, 2.22; 95% CI, 1.19 to 4.15), and of care. In daily practice, hospitals and health administrators
the presence of a new infarction (OR, 2.52; 95% CI ,1.16 to have to find strategies to manage different and often compet-
Downloaded from http://ahajournals.org by on May 19, 2023

5.47) were independent predictors of longer stay (Table 3). ing demands. This includes maintaining access to care in the
In model B, age ⱖ70 years (OR, 2.18; 95% CI, 1.15 to scenario of disabling diseases that predispose patients to
4.12), baseline NIHSS ⬎15 (OR, 2.48; 95% CI, 1.33 to 4.62), longer LOS balanced against the pressure to admit new
and LOI 24 hours after rtPA (OR, 2.70; 95% CI, 1.48 to 4.70) patients. Clearly, shortening the LOS and using the bed and
were independent predictors of longer stay (Table 3). personnel resources more efficiently are ways to achieve high
Goodness of fit test was not significant (model A P patient turnover, and subsequently, provide more effective
value⫽0.76; model B P value⫽0.21), indicating adequate acute care for stroke patients.
fitness. The discrimination of models was moderate to ade- In the NINDS trial, use of rtPA caused a statistically
quate with an under the curve area (ROC curve) of 0.69 and significant reduction in the average LOS by 2 days. Other
0.70 for models A and B, respectively. studies have shown that certain medical, psychological,
cognitive, and physical aspects of stroke correlate with LOS.
For example, NIHSS and Barthel index at admission, male
Discussion
gender, smoking, and stroke subtype were associated with
The cost-effectiveness of rtPA in acute stroke has been
longer stay.5,15 Our findings in relation to age, functional
analyzed previously.8,13,14 The analysis of LOS can provide
status, prestroke and post–rtPA, and stroke severity are in
valuable data for planning and policy in the health care
agreement with previous studies.16,17
system. After the approval of rtPA, the main focus of
The novel finding was that the presence of either a new infarction
or cortical involvement on the 24-hour CT scan independently
TABLE 3. Logistic Regression Models for LOS >7 Days predicted longer stay. More interestingly, LOI at 24 hours after
LOS ⱖ7 days OR SE P Value 95% CI receiving rtPA, as measured by NIHSS, was also a predictor of
LOS. These new variables were relevant explanatory factors for
Model A
longer LOS according to the logistic regression analysis.
Age ⱖ70 years 2.10 0.66 0.02 1.12–3.86
Our small sample size may limit the generalizability of the
Baseline NIHSS ⱖ15 2.22 0.71 0.01 1.19–4.15 results. However, this is an exploratory analysis aimed to
New infarction 2.52 0.99 0.02 1.16–5.47 identify clinical predictors of longer hospitalization after
Model B thrombolytic therapy rather than a predictive model.
Age ⱖ70 years 2.18 0.70 0.02 1.16–4.12
Baseline NIHSS ⱖ15 2.48 0.79 ⬍0.01 1.33–4.62
Potential Implications and Future Directions
LOS is the major determinant of acute care costs. Most
LOI 24 hours after rtPA 2.70 0.82 0.001 1.48–4.90
institutions focus their resources according to stroke severity,
 150 Stroke January 2005
as measured by mRS, Barthel index, or NIHSS. However,
other variables can add relevant clinical information that may
impact discharge planning. Our results suggest that age,
functional status prestroke, LOI at 24 hours after rtPA, stroke
severity, and CT findings can be independent predictors of
longer stay.
This information can be used to optimize discharge plan-
ning by (1) beginning the discharge planning at the time of
admission or 24 hours after the patient received rtPA; (2)
optimizing the level of care; (3) matching care provided to
care required; and (4) earlier rehabilitation or discharge to
long-term care. Further, resources can be reorganized and
guidelines developed that would ultimately provide more
efficient management for acute stroke patients.
Acknowledgments
We thank previous stroke fellows for their contribution in collecting
data. We also appreciate the daily help provided by the urgent TIA
clinical nurse, assistants, and research nurses. This research was
supported in part by a competitive grant of the Heart Stroke
Foundation of Canada (HSFC) and Canadian Institute for Health
Research (CIHR) given to G.S.
References
1. Caro JJ, Huybrechts KF, Duchesne I. Management patterns and costs of
acute ischemic stroke: an international study. For the Stroke Economic
Analysis Group. Stroke. 2000;31:582–590.
2. Samsa GP, Bian J, Lipscomb J, Matchar DB. Epidemiology of recurrent
cerebral infarction: a medicare claims-based comparison of first and
recurrent strokes on 2-year survival and cost. Stroke. 1999;30:338 –349.
3. Tu JV, Gong Y. Trends in treatment and outcomes for acute stroke
Downloaded from http://ahajournals.org by on May 19, 2023
patients in Ontario, 1992–1998. Arch Intern Med. 2003;163:293–297.
4. van Straten A, van der Meulen JH, van den Bos GA, Limburg M. Length
of hospital stay and discharge delays in stroke patients. Stroke. 1997;28:
137–140.
5. Chang KC, Tseng MC, Weng HH, Lin YH, Liou CW, Tan TY. Prediction
of length of stay of first-ever ischemic stroke. Stroke. 2002;33:
2670 –2674.
6. Caro JJ, Huybrechts KF, Kelley HE. Predicting treatment costs after acute
ischemic stroke on the basis of patient characteristics at presentation and
early dysfunction. Stroke. 2001;32:100 –106.
7. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R,
Boysen G, Bluhmki E, Hoxter G, Mahagne MH, et al. Intravenous
thrombolysis with recombinant tissue plasminogen activator for acute
hemispheric stroke. The European Cooperative Acute Stroke Study
(ECASS). J Am Med Assoc. 1995;274:1017–1025.
8. Fagan SC, Morgenstern LB, Petitta A, Ward RE, Tilley BC, Marler JR,
Levine SR, Broderick JP, Kwiatkowski TG, Frankel M, Brott TG, Walker
MD. Cost-effectiveness of tissue plasminogen activator for acute ische-
mic stroke. NINDS rt-PA Stroke Study Group. Neurology. 1998;50:
883– 890.
9. Merino JG, Silver B, Wong E, Foell B, Demaerschalk B, Tamayo A,
Poncha F, Hachinski V; Southwestern Ontario Stroke Program.
Extending tissue plasminogen activator use to community and rural stroke
patients. Stroke. 2002;33:141–146.
10. Saposnik G, Young B, Silver B, Di Legge S, Webster F, Beletsky V, Jain
V, Nilanont Y, Hachinski V. Lack of improvement in patients with acute
stroke after treatment with thrombolytic therapy. J Am Med Assoc. 2004;
292:1839 –1844.
11. Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, Fineberg
SE, Tierney WR. Effects of admission hyperglycemia on mortality and
costs in acute ischemic stroke. Neurology. 2002;59:67–71.
12. Wade DT, Langton Hewer R. Hospital admission for acute stroke: who,
for how long, and to what effect? J Epidemiol Community Health.
1985;39:347–352.
13. Sinclair SE, Frighetto L, Loewen PS, Sunderji R, Teal P, Fagan SC, et al.
Cost-Utility analysis of tissue plasminogen activator therapy for acute
ischaemic stroke: a Canadian healthcare perspective. Pharmacoeco-
nomics. 2001;19:927–936.
14. Patel A, Knapp M, Perez I, Evans A, Kalra L. Alternative strategies for
stroke care: cost-effectiveness and cost-utility analyses from a pro-
spective randomized controlled trial. Stroke. 2004;35:196 –203.
15. Galski T, Bruno RL, Zorowitz R, Walker J. Predicting length of stay,
functional outcome, and aftercare in the rehabilitation of stroke patients.
The dominant role of higher-order cognition. Stroke. 1993;24:
1794 –1800.
16. Effect of intravenous recombinant tissue plasminogen activator on ische-
mic stroke lesion size measured by computed tomography. NINDS; The
National Institute of Neurological Disorders and Stroke (NINDS) rt-PA
Stroke Study Group. Stroke. 2000;31:2912–2919.
17. Chapman KM, Woolfenden AR, Graeb D, Johnston DC, Beckman J,
Schulzer M, Teal PA. Intravenous tissue plasminogen activator for acute
ischemic stroke: a Canadian hospital’s experience. Stroke. 2000;31:
2920 –2924.