From the Departments of Neurology (K.C.J., E.C.H.) and Neurosurgery
(J.Y.L., E.C.H.), University of Virginia (Charlottesville); the Department of
Neurology, University of California at San Diego (P.D.L.); Park Nicollet
Medical Foundation, St Louis Park, Minn (S.K.H.); Foothills Hospital, Calgary,
Alberta, Canada (T.E.F.); the Department of Neurology, Medical College of
Georgia (Augusta) (R.J.A.); and the Department of Neurology, University of
Alabama (Birmingham) (R.E.F.).
Correspondence to Karen C. Johnston, MD, Department of Neurology, Box 394, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail kj4v{at}virginia.edu
Methods—Rates of serious (life-threatening) and nonserious
medical and neurological complications and mortality were derived from
the placebo limb of the Randomized Trial of Tirilazad Mesylate in Acute
Stroke (RANTTAS) database (n=279). Complications were correlated with
clinical outcome using logistic regression techniques.
Results—Of all patients, 95% had at least one
complication. The most common serious medical complication was
pneumonia (5%), and the most common serious neurological complication
was new cerebral infarction or extension of the admission infarction
(5%). The 3-month mortality was 14%; 51% of these deaths were
attributed primarily to medical complications. Outcome was
significantly worse in patients with serious medical complications,
after adjustment for baseline imbalances, as measured by the Barthel
Index (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.5 to
15.1) and by the Glasgow Outcome Scale (OR, 11.6; 95% CI, 4.3 to
30.9). After death was discounted, serious medical complications were
associated with severe disability at 3 months as determined by the
Glasgow Outcome Scale (OR, 4.4; 95% CI, 1.3 to 14.8).
Conclusions—Medical complications that follow
ischemic stroke not only influence mortality but may influence
functional outcome.
The relationship between serious medical complications and functional
outcome has not been systematically examined. The purpose of this study
was to describe the rates of medical and neurological complications in
an acute ischemic stroke cohort and then to investigate the
impact of these complications on functional outcome and mortality.
Eligible patients included those who had a serious neurological deficit
due to focal ischemia, could be treated within 6 hours of
stroke onset, were 18 years of age or older, were not pregnant if
female, and from whom informed consent could be obtained (patient
and/or representative). Subjects were excluded if they
had sensory loss, ataxia, or dysarthria alone; coma due to mass effect
by CT scan; severe hypertension (mean arterial pressure of
>160 mm Hg); seizure at onset; stroke as a complication of a
medical or surgical procedure (not including cardiac
catheterization or cerebral angiography);
hemorrhage on initial CT scan; or severe concomitant medical,
neurological, or psychiatric illness. The most frequent reasons for
exclusion included stroke onset >6 hours (36%) and transient deficit
(12%). Further details of the study population have been described
previously.9 Each patient who met eligibility
criteria was randomly assigned to receive either tirilazad mesylate or
vehicle (sodium citrate) diluted with sodium chloride (recommended
concentration, 0.9% or 0.45%) for a total volume of 250 mL
administered as a rapid intravenous infusion over 10 to 30
minutes. A head CT scan without contrast was required before
administration of subsequent doses. If each component of the complete
evaluation (including laboratory work, CT scan, and clinical
examination) obtained before the second dose met the eligibility
criteria, then the patient was allowed to continue participation in the
study as a fully eligible patient. Only the fully eligible patients
received subsequent doses (250 mL per dose or an alternatively lower
volume [based on weight] for patients with central lines or who could
not tolerate the total volume) of study drug or vehicle every 6 hours
for 11 additional doses (12 doses total).
Patients in the RANTTAS study were managed in an acute-care area
with current 1990s medical therapy according to standard practice in
each center. Treatment with corticosteroids and the
calcium channel blockers nicardipine and nimodipine, or
any experimental stroke therapy (including thrombolytic
therapy at that time), was prohibited. Allowed medical therapies
included heparin, antiplatelet agents, volume expansion,
vasopressors, mannitol, anticonvulsants, and all antihypertensive
agents except for nicardipine and nimodipine. Emergency
surgery was also allowed if judged to be clinically indicated.
The frequency of complications and death was monitored
continuously and prospectively by the investigators and coordinators at
each site during the trial. A standardized medical event coding guide
based on the COSTART medical dictionary was used to code complication
events.10 This dictionary includes both symptoms
and diagnoses. Specific diagnoses are used when known; however, the
system allows a default to a symptom when the diagnosis is unknown.
Adverse events were only reported if clinically significant. Data on
serious complications (ie, those that were immediately
life-threatening, prolonged or resulted in hospitalization, or resulted
in death) were collected by investigators and coordinators at each site
for 3 months. Data on nonserious complications were collected for the
first 7 to 10 days only. Neurological complications included those that
occurred in the nervous system, whereas medical complications were all
other events reported. Clinical outcome was measured at 7 to 10 days,
discharge, and at 3 months according to the BI,11
the GOS,12 and the NIHSS.13
Primary and contributing causes of death and disability were designated
by the treating investigator based on clinical judgment. New infarction
and extension of infarction were combined for the analysis due
to the somewhat arbitrary assignment of the event in some cases of
limited information.
Statistical Analysis
Table 3
Fig 1
Tables 4
All reported serious neurological complications are shown in
Table 7
The primary and contributing causes of death of the 37 patients who
were dead at 3 months are shown in Fig 2
At 3 months, 41% of patients were alive and newly disabled since their
admission stroke. Fig 4
Logistic regression analysis, adjusted for admission NIHSS
score, age, and history of diabetes mellitus, demonstrated that serious
medical and serious neurological events were each associated with poor
outcome at 3 months. For patients with a serious medical event, the OR
for a poor outcome as measured by the BI was 6.1 (95% CI, 2.5 to
15.1); by the GOS it was 11.6 (95% CI, 4.3 to 30.9). The OR in
patients with serious neurological complications was 11.3 (95% CI, 3.8
to 33.4) for the BI and 9.4 (95% CI, 3.2 to 27.4) for the GOS.
Because this analysis included mortality as poor outcome,
and to clarify whether death was driving the association, the
association between serious events and severe disability alone was
examined, excluding the patients who were dead at 3 months. Serious
medical events were associated with severe disability as determined by
the GOS (OR, 4.4; 95% CI, 1.3 to 14.8) but not the BI (OR, 1.2; 95%
CI, 0.3 to 4.4). For comparison, serious neurological complications
were associated with severe disability as measured by the BI (OR, 6.1;
95% CI, 1.4 to 26.1) and the GOS (OR, 4.6; 95% CI, 1.2 to 17.8).
An unintentional bias may have slightly affected our study population.
Despite the fact that coma was not exclusionary unless due to mass
effect seen on the initial CT, there were no patients in this cohort of
279 with an NIHSS level of consciousness score of 3 (unresponsive) on
baseline examination. Twelve patients (4.3%) had level of
consciousness scores of 2 (obtunded). Of the 3193 patients excluded
from the 3853 screened in this trial, however, only 19 (0.6%) were
excluded for coma due to mass effect. Therefore, while this may have
biased the population in this cohort, we would argue that the effect of
this bias is minimal.
The influence of medical complications on outcome in stroke patients
has been studied. Davenport et al6 found that
complications in ischemic and hemorrhagic stroke patients were
associated with an increased risk of death during admission. Chambers
et al5 looked at potential prognostic factors in
predicting outcome in stroke patients and concluded that deaths after 2
weeks were primarily due to cardiac and pulmonary
complications. They developed a short-term and long-term model that
could predict poststroke outcome and reported that a history of heart
disease and hypertension were in the long-term
model.5 They did not address the relevance of
peristroke complications in their model. Sacco et
al,2 using the Framingham study data, concluded
that if patients survived their initial stroke, being free of
hypertension and cardiac comorbidity increased their chances of
survival.
Medical complications are clearly a leading cause of death in acute
ischemic stroke patients. The attribution of 50% of deaths in
this study to medical complications is consistent with that
previously reported.3 7 8 Medical complications,
however, were not frequently reported as a cause of 3-month disability
in this cohort. Despite the investigators' impressions that their
patients' disability was not secondary to medical complications,
logistic regression analysis, corrected for severity of stroke,
showed an association between serious medical events and severe
disability. This suggests that there is a relationship between serious
medical complications and severe disability that was not due to
severity of stroke and was not attributed to medical complications by
the investigators. The etiology of this association is unclear. Several
of the following mechanisms may be at play: (1) Serious medical
complications may delay or prevent aggressive rehabilitation, resulting
in worse disability. (2) Serious medical complications and/or their
treatments may result in neurological worsening that may not be
appreciated by caretakers as other than the natural evolution of the
stroke. (3) Tenuous prestroke medical conditions (ie, borderline
disabling conditions) may result in disability after stroke and serious
medical complication. (4) Depression accompanying life-threatening
events may reduce motivation, producing worse scores on functional and
neurological scales, and magnify existing disability. (5) Medical
complications may be a marker for, not a cause of, severe disability.
Because of the relatively small number of patients who had a
serious medical event and severe disability in this cohort (n=13),
definitive conclusions cannot be drawn. These hypotheses should be
tested in larger studies.
The clinical significance of these findings rests in the fact that some
of these complications may be preventable. Some pneumonias, for
example, may be preventable with the development of protocols for
airway protection before oral feeding.21
These data provide valuable information regarding rates of
complications in an ischemic stroke cohort treated within 6
hours excluding the very mild strokes (ie, pure sensory). This
information not only provides a benchmark of event rates that may help
physicians measure the success of their individual care, but it also
sheds some light on necessary preventative therapy. In addition, these
rates may be helpful as reference for stroke clinical trials that are
introducing new compounds that may have previously undetected side
effects. Baseline rates such as those provided may alert investigators
to potential safety concerns early in drug development, when only small
numbers of patients are being exposed, with equally small or
smaller numbers included in the placebo group. As we have seen a marked
decrease in urinary and skin complications with improved medical
therapies, these rates will also likely improve.
The association between medical complications and severe disability
shown by our data is provocative, although it clearly
requires further exploration.
RANTTAS Participants
Medical College of Georgia (Augusta)—Principal
Investigator: Robert Adams, MD. Clinical Coordinator: Elizabeth Carl,
CRA. Coinvestigators: Fenwick Nichols, MD; David Hess, MD; Brad Boop,
MD.
Johns Hopkins Bayview Medical Center (Baltimore,
Md)—Principal Investigator: Christopher Earley, MD. Clinical
Coordinator: Donna Rae Smith, RN. Coinvestigators: Peter Kaplan, MD;
Constance Johnson, MD; Christopher Morrow, MD; Elliott Frohman, MD;
Neil Porter, MD; Kevin Flanigan, MD; Lewis Morganstern, MD; Neil
Holland, MD; Alan Stein, MD; Eric Aldrich, MD; George Oyler,
MD.
University of Alabama (Birmingham)—Principal Investigator:
Edward Faught, MD. Clinical Coordinator: Vicki Mitchell, RN.
Coinvestigators: Howard Liu, MD, PhD; Frank Thomas, MD; David
Wenzel, MD; Badr Mustafa Dajani, MD; Julie Pan, MD; Robert Yapundich,
MD; Yoshio Futatsugi, MD; Susan Geerlings, MD; Tal Moskowitz, MD;
Anthony Nicholas, MD; John Brockington, MD; Anthony Collins, MD; J.
Mark Bailey, DO, PhD; Anna Tseng, MD.
Massachusetts General Hospital (Boston)—Principal
Investigator: Walter J. Koroshetz, MD. Clinical Coordinators: Ufuk Can,
MD; Anna Felix, MD. Coinvestigators: M. Cudkowtiez, MD; F.
Buonanno, MD; L. Schwamm, MD; M. Elkind, MD; J.P. Kistler, MD; S.
Finkelstein, MD; J. Cha, MD; S. Murphy, MD; H. Blumenfeld, MD; M.
Lopez-Bresnahan, MD; U. Can, MD; K. Goslin, MD; S. Cramer, MD; N.
Suwanwela, MD.
Northwestern University Medical School (Evanston, Ill), Glenbrook
Hospital—Principal Investigator: Daniel Homer, MD. Clinical
Coordinator: Jackie Carpenter, RN. Coinvestigators: Tom Mattio, MD;
Michael Rezak, MD.
Wayne State University (Detroit, Mich), Detroit Receiving
Hospital—Principal Investigators: Anne Guyot, MD; Patti Peterson,
MD. Clinical Coordinators: Linda Tvardek, RN; Julie Schmidt, RN.
Coinvestigators: Aashish Despande, MD; Walid Freij, MD; Balbir Gandhi,
MD; Farah Minhas, MD; Jagdish Shah, MD; Cesar Zahke, MD.
University of Alberta (Edmonton, Alberta, Canada), MacKenzie
Health Science Center—Principal Investigator: Andrew Penn, MD.
Clinical Coordinators: Judy Sherman, RN; Yu-Ling Li, RN.
Coinvestigators: M.G. Elleker, MD; P. Stenerson, MD.
Indiana University (Indianapolis), Wishard
Memorial—Principal Investigators: Robert Pascuzzi, MD; Martin
Farlow, MD. Clinical Coordinators: Marsha Bales, RN; Judy Caress.
University of Kentucky (Lexington), VA Medical
Center—Principal Investigator: Creed Pettigrew, MD. Clinical
Coordinators: Charlotte Waugh, RN; Anna Rockich, RPH. Coinvestigators:
Robert Fallis, MD; Alex Tikhtman, MD.
University of California at Los Angeles—Principal
Investigator: Sidney Starkman, MD. Clinical Coordinator: Glenn
Schubert. Coinvestigators: D. Dobkin, MD; N. Martin, MD; J. Saver,
MD.
Park Nicollet Medical Foundation (St Louis Park, Minn),
Fairview Southdale, Methodist Hospital—Principal Investigator:
Sandra Hanson, MD. Clinical Coordinator: Ann Weaver, RN.
Coinvestigators: Karen Porth, MD; Rafael Magana, MD; John Davenport,
MD; Bruce Idelkope, MD; Carols Espanosa, MD; Manuel Ramerez-Lassepas,
MD.
Medical College of Pennsylvania
(Philadelphia)—Principal Investigator: Milton Alter, MD. Clinical
Coordinators: Rodrigo Ribeiro, MD; Mary Lloyd, RN. Coinvestigators:
Steven Scheiner, MD; Arthur Puff, MD; Sherry Boyle, MD; Neena Gupta,
MD; Kellie White, MD; Sharon Carney, MD; Michael Moulton, MD; Samual
LaCapra, MD; David Hassard, MD; S. Rizwan A. Shah, MD; Arthur Newmark,
MD; Asha Gupta, MD; David Cone, MD; Iqbal Khan, MD; Beth ; Cohen, MD;
Rosie Bopari, MD; John O'Connell, MD; Aatif Hussian, MD; Kishor Patil,
MD; Jalil Shojari, MD; Rodrigo Ribeiro, MD.
Jefferson Medical College (Philadelphia, Pa), Thomas
Jefferson University Hospital—Principal Investigators: Rodney
Bell, MD; Daniel Gzech, MD. Clinical Coordinators: Toby Mazer, MPH;
Jill Grothusen, RN. Coinvestigators: P. Reyes, MD; J. Arastu, MD; T.
Strassburger, MD; C. Thomas, MD; R. Wolfe, MD; J. Fang, MD; M.
Scavina, MD; W. Wolfe, MD; D. Zeidwerg, MD; J. Chavin, MD; O.
Shachar, MD; L. Sandler, MD; D. McGarren, MD.
Pennsylvania Hospital (Philadelphia)—Principal
Investigator: Dara G. Jamieson, MD. Clinical Coordinator: Concetta
Gonnella. Coinvestigators: Thomas M. Bosley, MD; Debra Ann Pollack,
MD; John C. Andrefsky, MD; S. Hariharan, MD; Andrew Chang, MD; Marian
P. Lamonte, MD; Joseph Champellone, MD; Henry C. Hooker, MD; Jonathan
Fellus, MD; Veronica Sosa, MD; Adnan Zawawi, MD; Stephanie Raaf, MD;
Mark Friedman, MD; Zahir Ali, MD.
Roanoke Neurological Associates (Roanoke, Va), Community Hospital
of Roanoke Valley, Roanoke Memorial Hospital—Principal
Investigator: Gordon Burch, MD. Clinical Coordinators: Donna Atkins,
RN; Candy Foley, RN. Coinvestigators: D. Bivins, MD; W. Elias, MD; D.
Nolan, MD; M. Sisk, MD; J. Wilson, MD; A. Lloyd, MD; G. Stephens, MD;
R. Surrusco, MD; C. Lothes, MD; W. Humphries, MD; S. Pastemak, MD; M.
Donato, DO; E. Manetta, MD; J. Mitchell, MD; A. Briggs, MD; W. Grover,
MD; B. Bolton, MD.
University of California at San Diego, VA Medical
Center—Principal Investigator: Patrick Lyden, MD. Clinical
Coordinators: Stacey Lewis, RN; Karen Rapp. Coinvestigators: M. Brody,
MD; J. Rothrock, MD; C. Jackson, MD; P. Huott, MD; C. Kushida, MD; J.
Liss, MD; R. Zweifer, MD; L. Caylor, MD; D. Phan, MD; Z. Mahdavi, MD;
T. Tom, MD; H. Noack, MD; G. Forde, MD.
Lions Gate Hospital (North Vancouver, BC,
Canada)—Principal Investigator: Donald Cameron, MD. Clinical
Coordinator: Barbara Griesdale, RN. Coinvestigators: Vance Makin, MD;
C.B. Bozek, MD.
Winchester Medical Center (Winchester, Va)—Principal
Investigator: George Sheppard, MD. Clinical Coordinator: Sandra Massey,
RN. Coinvestigators: David Zontine, MD; Neil Crowe, MD; Katherine
Gustin, MD; Patrick Capone, MD.
Foothills Hospital (Calgary, Alberta,
Canada)—Principal Investigator: Thomas E. Feasby, MD.
Clinical Coordinator: Carolyn Robertson, RN.
Case Western Reserve University (Cleveland, Ohio), MetroHealth
Medical Center—Principal Investigators: Mark Rorick, MD; Marc
Winkelman, MD. Clinical Coordinator: Alice Liskay, RN. Coinvestigators:
James Schmidley, MD; Monroe Cole, MD; Mohammed Al-Jaberi, MD; Angela
Anagnos, MD; Mary Anderson, MD; Cynthia Bamford, MD; Eric Frederickson,
MD; Jacob Gordon, MD; Steven Grosser, MD; Adriana Kori, MD; Andrew
Kuntz, MD; Mohamed Murad, MD; Wassim Nasreddine, MD; Allen Pettee, MD;
Naji Riachi, MD; Howard Schecht, MD; John Stahl, MD; Jason Soriano, MD;
Joshua Sunshine, MD; Jose Suarez, MD; Joel Vandersluis, MD; Yahya
Al-Lanham, MD; Amani Ramahi, MD.
Royal University Hospital (Saskatchewan, Canada)—Principal
Investigator: Ashfaq Shuaib, MD. Clinical Coordinator: Edina
Kadribasic, RN. Coinvestigator: Bradley Stewart, MD.
Hôpital de Chicoutimi (Chicoutimi, Quebec)—Principal
Investigator: Michel Beaudry, MD. Clinical Coordinator: Mme Doris
Boivin, RN.
St Alphonsus Medical Center (Boise, Idaho)—Principal
Investigator: George Lyons, MD. Clinical Coordinator: Renae L. Dougal,
RN.
Fairfax Hospital (Fairfax, Va)—Principal Investigator:
James P. Simsarian, MD. Clinical Coordinator: Mary McGarvey, RN.
Coinvestigators: D. Grass, MD; L. Sigmond, MD; R. Kurtzke, MD; L.
Eberly, MD; D. Lipps, MD.
Hoosier Neurology Group, Methodist Hospital (Indianapolis,
Ind)—Principal Investigator: James T. Fesenmeier, MD. Clinical
Coordinator: Kathy Viater, RN. Coinvestigators: R. Alonzo, MD; W.
Cooper, MD; J. Scott, MD; P. Bustion, MD; J. Pappas, MD; M. Frazer, MD.
Other Participants
Project Manager: Don L. Shreve, BBA. Project Clinical
Coordinator: Sandra S. Wilkinson, RN, BSN. Director of Clinical
Services: Lori J. Elder, RN, BSN. Clinical Coordinators: Stella
Clements, RN; Elizabeth Cuccia, RN, MHM; Margaret Keller, RN, BSN; Rita
Lackey, RN; Karen Mimms, RN; Pat Protzman, RN; Lynda Sparrow, RN,
BSN. Data Manager: Angela Lightfoot, BS. Programming: A. Eugene
Lightfoot, BS; Benedict E. Bocchicchio, MA; Patricia Halley, BS. Image
Analysts: Angela Polin, BS; Richard Polin, MD. Biostatistician: Lie-Ju
Hwang, PhD, Sr. Statisticians: Mark C. Wolf, PhD; Laura L. Truskowski,
MS. Data Technology: Carolyn Galbrieth, RN, BSN; Reginald Johnson;
Sheila Johnson; Charlene Hill; Belinda Wilson; Annie Bartley; Gabriele
Ford; Mike Rumfelt; Valerie Wingate; Mike Smith; Tracy Childress.
NINDS Data and Safety Monitoring Board
Medical Officer, NINDS
RANTTAS Advisory Committee Members
The Upjohn Company, Kalamazoo, Mich
Canada—Clinical Research Director: Monica L. Bologa, MD.
Clinical Trials Specialist: Denise Legace, RN.
Medical and Technical Research Associates Inc (MTRA), Boston,
Mass
Received September 22, 1997;
revision received November 18, 1997;
accepted December 1, 1997.
2.
Sacco RL, Wolf PA, Kannel WB, McNamara PM. Survival
and recurrence following stroke: the Framingham study.
Stroke. 1982;13:290–295.
3.
Silver FL, Norris JW, Lewis AJ, Hachinski VC. Early
mortality following stroke: a prospective review. Stroke. 1984;15:492–496.
4.
Allen CM. Predicting the outcome of acute stroke: a
prognostic score. J Neurol Neurosurg Psychiatry. 1984;47:475–480.
5.
Chambers BR, Norris JW, Shurvell BL, Hachinski VC.
Prognosis of acute stroke. Neurology. 1987;37:221–225.
6.
Davenport RJ, Dennis MS, Wellwood I, Warlow CP.
Complications after acute stroke. Stroke. 1996;27:415–420.
7.
Bounds JV, Wiebers DO, Whisnant JP, Okazaki H.
Mechanisms and timing of deaths from cerebral infarction.
Stroke. 1981;12:474–477.
8.
Kalra L, Yu G, Wilson K, Roots P. Medical
complications during stroke rehabilitation. Stroke. 1995;26:990–994.
9.
RANTTAS Investigators. A randomized trial of tirilazad
mesylate in patients with acute stroke (RANTTAS). Stroke. 1996;27:1453–1458.
10.
Spilker B. Guide to Clinical Trials. New
York, NY: Raven Press; 1991:480.
11.
Mahoney FT, Barthel DW. Functional evaluation: Barthel
Index. Md Med J. 1965;14:61–65.
12.
Jennett B, Bond M. Assessment of outcome after severe
brain damage: a practical scale. Lancet. 1975;1:480–484.[Medline]
[Order article via Infotrieve]
13.
Lyden P, Brott T, Tilley B, Welch KM, Mascha EJ, Levine
S, Haley EC, Grotta J, Marler J. Improved reliability of the NIH Stroke
Scale using video training. NINDS TPA Stroke Study Group.
Stroke. 1994;25:2220–2226.[Abstract]
14.
Eguchi K, Endou M, Okamura CT, Suzuki M, Tsuchiya S,
Kano K, Onuki M, Fukuya Y. A comprehensive fact finding study of home
care elderly for planning of the community based rehabilitation system
in Koga City, Ibaraki Prefecture. Jpn J Public Health. 1992;39:743–757.
15.
Stokes ME, Davis CS, Koch GG. Categorical Data
Analysis Using the SAS System. Cary, NC: SAS Institute
Inc; 1995:163–246.
16.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love
BB, Gordon DL, Marsh EE III. Classification of subtype of acute
ischemic stroke: definitions for use in a multicenter clinical
trial, TOAST, Trial of Org 10172 in Acute Stroke Treatment.
Stroke. 1993;24:35–41.
17.
STIPAS Investigators. Safety study of tirilazad
mesylate in patients with acute ischemic stroke (STIPAS).
Stroke. 1994;25;418–423.
18.
Grotta JC. Post-stroke management concerns and
outcomes. Geriatrics. 1988;43:40–48.
19.
Haley EC Jr, Kassell NF, Torner JC, and Participants. A
randomized controlled trial of high dose intravenous
nicardipine in aneurysmal subarachnoid
hemorrhage: a report of the Cooperative Aneurysm Study.
J Neurosurg. 1993;78:537–547.[Medline]
[Order article via Infotrieve]
20.
Howard G, Anderson R, Johnson NJ, Sorlie P, Russell G,
Howard VJ. Evaluation of social status as a contributing factor to the
stroke belt region of the United States. Stroke. 1997;28:936–940.
21.
Adams HP Jr, Brott TG, Crowell RM, Furlan AJ, Gomez CR,
Grotta J, Helgason CM, Marler JR, Woolson RF, Zivin JA, Feinberg W,
Mayberg M. Guidelines for the management of patients with acute
ischemic stroke. Stroke. 1994;25:1901–1914.[Medline]
[Order article via Infotrieve]
© 1998 American Heart Association, Inc.
Original Contributions
Medical and Neurological Complications of Ischemic Stroke
Experience From the RANTTAS Trial
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
Background and Purpose—Medical
and neurological complications after acute ischemic stroke may
adversely impact outcome and in some cases may be preventable. Limited
data exist regarding the frequency of such complications occurring in
the first days after the ictus and the relationship of these
complications to outcome. Our objective was to identify the types,
severity, and frequency of medical and neurological complications
following acute ischemic stroke and to determine their role in
mortality and functional outcome.
Key Words: complications • stroke • stroke, acute • stroke outcome
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
Ischemic stroke
remains the third leading cause of death after heart disease and cancer
in the United States.1 Mortality rates have
declined over the last several decades1 and are
now consistently reported to be approximately
20%,2 3 4 5 although this rate varies from 15% to
58% depending on stroke subtype.3 Medical
complications are also known to be common in stroke patients, although
the implications of these complications have less frequently been
studied. Davenport et al6 retrospectively
reported complication rates in 597 stroke patients (ischemic
and hemorrhagic). They found 59% had complications and 23% died in
the hospital. Silver et al3 reported that
approximately 40% of deaths were from medical complications in a
series of nearly 1000 ischemic stroke patients. They also noted
that while most deaths occurring in the first week were due to brain
edema associated with stroke, most deaths in the second and third weeks
after stroke could be attributed to medical
complications.3 In a retrospective autopsy review
from 1966 to 1975, Bounds et al7 found that
>50% of deaths occurred secondary to medical complications. Kalra et
al8 reported medical complications occurring in
60% of the 245 patients involved in a stroke rehabilitation
program.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
Our study population included the 279 fully eligible,
vehicle-treated stroke patients from the Randomized Trial of Tirilazad
Mesylate in Patients with Acute Stroke
(RANTTAS).9 This was a multicenter, randomized,
double-blinded, vehicle-controlled trial that evaluated the efficacy
and safety of intravenous tirilazad mesylate in patients
with acute ischemic stroke. Patients were selected based on
eligibility criteria (see below) from all patients with acute
ischemic stroke admitted to each of 27 participating North
American centers from May 1993 through December 1994. The protocol was
approved by each center's institutional review board.
Poor outcome was defined as severe disability (a BI score
of <6014 or a GOS rating of severe disability or
vegetative survival) or death at 3 months. For patients who were dead
at 3 months, the worst possible score (BI=0, GOS=5) was assigned.
Logistic regression analysis15 was used
to evaluate the association between (1) serious events and poor outcome
(severe disability and death) and (2) serious events and severe
disability. Each analysis was adjusted for admission NIHSS
score, patient age, and the presence of diabetes mellitus, since each
of these factors was independently associated with outcome in the
RANTTAS trial.9
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
From May 1993 through December 1994, trial subjects were
selected by eligibility criteria from a total of 3853 patients admitted
within 12 hours of stroke onset registered in the combined stroke logs
of the centers. A total of 660 patients (329 vehicle-treated and 331
tirilazad-treated) were randomized. Of those who received treatment,
556 (280 vehicle and 276 tirilazad) were fully eligible and 104 (49
vehicle and 55 tirilazad) were subsequently excluded. Of the 280 fully
eligible, vehicle-treated group, 1 patient was determined to not have a
stroke but to have a conversion disorder, and this patient was excluded
from this analysis. The fully eligible, vehicle-treated stroke
group used for this analysis included 279 patients. Patients in
the tirilazad-treated group were excluded because this is not
considered standard stroke care, and the possibility that some of the
events were drug related could not be excluded. Patient characteristics
are summarized in Table 1
. The median
time from onset of symptoms to admission to the emergency department
was slightly more than 1 hour. The mean age was 69 years, most patients
were white with a slight male preponderance, and the median NIHSS score
reflected a moderate deficit with a minimum NIHSS score of 1 and a
maximum of 30. Over 60% of patients had a history of hypertension,
over 50% had a history of cardiac disease, and less than one quarter
had a history of prior transient ischemic attack or stroke.
Over 90% of patients were able to lead a full and independent life
before the presenting stroke. The rates of antiplatelet and
anticoagulant treatment prescribed for these patients, both in the
first 10 days and at the 3-month follow-up are reflected in Table 2. Nearly half of patients were treated
with aspirin in the first 10 days, and a slightly lower proportion were
taking aspirin at 3 months. Intravenous heparin was used in
40% of patients in the first 10 days. Warfarin therapy was prescribed
in approximately one third of patients in the first 10 days and at 3
months.
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Table 1. Baseline Characteristics of Fully Eligible
Vehicle-Treated Patients (n=279)
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[in a new window]
Table 2. Recurrent Stroke Prevention Therapy (n=279) shows the ischemic
stroke subtypes as determined by the investigator at 7 to 10 days using
the Trial of Org 10172 in Acute Stroke Treatment (TOAST)
criteria.16 Cardioembolic stroke was the most
common subtype, accounting for nearly a third of strokes. Small-vessel
occlusive disease and large-vessel atherosclerosis each
accounted for approximately one quarter of the strokes.
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[in a new window]
Table 3. Ischemic Stroke Subtype: Day 7 to 10 (n=279) displays the rates of complications
and death in the full cohort of 279 patients. Ninety-five percent of
patients had at least one event, 32% had at least one serious event,
and 14% of patients were dead at 3 months.
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Figure 1. Rates of complications and death in the full
cohort of 279 patients. and 5 list all of the serious medical
complications reported, and Table 4 lists the rates of combined serious
and nonserious events. Nonserious injection site reactions were
excluded from this table because these were assumed to be a response to
the vehicle injection (known to cause a high rate of local
reaction17 ) not the stroke itself. Pneumonia
(both aspiration and other) was the most common serious medical event,
reported in 5% of patients. Aspiration pneumonia accounted for 60% of
the serious pneumonias. Congestive heart failure and gastrointestinal
bleeding were reported as a serious event in 3%. Cardiac
ischemia, sepsis, urinary tract infection, deep venous
thrombosis, and pulmonary embolism were less frequently
reported as serious events, although urinary tract infection was
frequently reported as a nonserious event (11%). Table 6 displays some common complications that
were reported as nonserious events. Nausea/vomiting, fever, and
constipation were the most frequently reported.
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Table 4. Most Common Serious Medical Events
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Table 5. Uncommon (<1%) Serious Medical Events
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[in a new window]
Table 6. Frequent Nonserious Medical Events , again with the combined (serious
and nonserious) rates also reported. New stroke/extension of stroke
(5%) and brain edema (4%) were the two most frequently reported
serious neurological events. Table 8
lists common nonserious neurological complications. Headache was
reported in 22% of patients and never as a serious event. Agitation
and insomnia were not uncommon.
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Table 7. All Serious Neurological Events
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Table 8. Frequent Nonserious Neurological Events .
Medical complications were reported to be the primary cause of death in
over 50% of patients and at least contributed to death in an even
larger proportion. Direct effect of stroke was the primary cause of
death in one third of patients and contributed to nearly another 20%
of deaths. New stroke was the primary cause in <10%. The timing of
these deaths, shown in Fig 3, reflects
the bimodal distribution previously
reported.3 5 7 The first peak, occurring in the
first week, predominantly reflects deaths from direct effect of stroke.
The second peak occurred several weeks after the stroke, and the
majority of these deaths were attributed to medical complications.
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Figure 2. Rates of primary and contributing causes of death
in the 37 patients (14%) who were dead at 3 months. ICH indicates
intracerebral hemorrhage.
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Figure 3. Distribution of the timing of death in the 37
patients who were dead at 3 months. shows the primary
and contributing causes of disability in these patients as determined
by the investigators at 3 months. This includes mild, moderate, and
severe disability. Direct effect of stroke was cited as the primary
cause of disability in 86% of patients and at least contributed to
disability in over 90%. Medical complications were rarely reported by
the investigators as the primary or contributing cause of their
patient's disability at 3 months. The "other" category primarily
included chronic diagnoses that were not previously disabling but
became the primary cause of disability after stroke. This category
included such diagnoses as arthritis, dementia, and alcohol use.
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Figure 4. Rates of primary and contributing causes of
disability in the 115 patients (41%) of patients disabled at 3 months.
This includes patients who were alive, not previously disabled, and who
had a GOS score of moderate disability, severe disability, or
vegetative survival at 3 months. ICH indicates
intracerebral hemorrhage.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
This study provides prospectively collected multicenter data
on medical and neurological complications in an acute ischemic
stroke cohort admitted within 6 hours of onset of symptoms. It
furnishes the prospective data suggested by Davenport et
al6 for a fixed period of time after stroke. The
frequency of complications in this series is higher than previously
reported. We speculate that this is a result of the rigorous, acute,
and prospective method used for collection of complication data. The
detailed safety data collection used in this clinical trial was
necessary for potential registration of a new compound, and it likely
provides a more complete representation of complication events
than previously reported rates. The mortality rate in this cohort is
similar to those previously reported for ischemic
stroke.2 3 4 5 The frequency of severe disability
(nonambulatory and totally dependent) has been reported to be from 7%
to 19%,18 which is consistent with the
16% severe disability rate in this study. Primary as well as primary
and contributing cause of death or disability were reported because the
cause of death or disability in this population is often
multifactorial, and the primary cause may be chosen arbitrarily. We
therefore report primary alone and primary and contributing together in
an attempt to more closely approximate the true cause of death. This
approach has been used previously in the subarachnoid
hemorrhage literature for similar
reasons.19 These rates of complications and
disability may be helpful for reference for future clinical stroke
trials. The recent literature continues to suggest that rates of stroke
mortality vary widely across regions of the United
States,20 which may make reference rates from
this multicenter trial more generalizable to other multicenter stroke
trials.
Selected Abbreviations and Acronyms
BI
=
Barthel Index
CI
=
confidence interval
GOS
=
Glasgow Outcome Scale
NIHSS
=
National Institutes of Health Stroke Scale
OR
=
odds ratio
RANTTAS
=
Randomized Trial of Tirilazad Mesylate in Acute Stroke
Participating Centers
University of Michigan (Ann Arbor), St Joseph Mercy
Hospital, William Beaumont Hospital—Principal Investigators:
Phillip Scott, MD; William Barsan, MD. Clinical Coordinator:
Shirley Frederiksen, RN. Coinvestigators: Steven Kronick, MD; Brian J.
Zink, MD; Robert M. Domeier, MD; James C. Mitchiner, MD; Frank P.
Judge, MD; Robert J. Levy, MD; Anastasios Alexiou, MD; Hanna Reinche,
MD; John D. Segall, MD; Brad Walters, MD; Robert Swor, DO; John Gilroy,
MD; Raymond, Jackson, MD; Daniel Richardson, MD; Jim Cisek, MD;
Julia Randall, MD; Steven Schecter, MD; Keith Wilkinson, MD.
Virginia Neurological Institute, Neuroclinical Trials
Center (Charlottesville, Va)—Principal Investigator: E. Clarke
Haley, Jr, MD. Project Director: Wayne Alves, PhD. Coinvestigators:
Neal F. Kassell, MD; Karen C. Johnston, MD; Gwen Ford, MD; Nina
Solenski, MD.
William J. Powers, MD (Chair), Washington School of Medicine, St
Louis, Mo; Michael Walker, MD (ex officio), Division of Stroke and
Trauma NINDS, Bethesda, Md; Joseph L. Fleiss, PhD, Columbia University,
New York (NY); Michael Frankel, MD, Emory University, Atlanta, Ga;
Roger P. Simon, MD, University of Pittsburgh (Pa).
John Marler, MD, Bethesda, Md.
Harold P. Adams, Jr, MD (Chair), University of Iowa
Hospitals (Iowa City); Thomas G. Brott, MD, University of
Cincinnati Medical Center (Ohio); Sung Choi, PhD, Medical College of
Virginia (Richmond); John F. Kurtzke, MD, Veteran's Administration
Hospital, Washington, DC; James C. Torner, PhD, University of Iowa
(Iowa City).
United States—Medical Clinical Monitor: Gary R.
Peters, MD. Clinical Trials Specialists: Susan Eckert, RN; William J.
Bryan, MS.
Clinical Projects Manager: Karen M. Brennan, RN and
staff.
Acknowledgments
This study was supported in part by the National Institutes of
Health–National Institute of Neurological Disorders and Stroke
(RO1-NS31554), Pharmaceutical Research and Manufacturers of America
Foundation, University of Virginia, and Pharmacia and Upjohn Company
(Kalamazoo, Mich).
Footnotes
1 The investigators and participating centers are listed in the Appendix.
Appendix 1
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
This work was presented in part at the 49th Annual Meeting of the American Academy of Neurology, April 17, 1997.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
Appendix 1
References
1.
Wolf PA, Cobb JL, D'Agostino RB.
Epidemiology of stroke. In: Barnett HJ, Mohr
JP, Stein BM, Yatsu FM, eds. Stroke Pathophysiology, Diagnosis,
and Management. New York, NY: Churchill Livingstone Inc;
1992:3–27.
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|
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|
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|
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