(Stroke. 2001;32:891.)
© 2001 American Heart Association, Inc.
Original Contributions |
From the Departments of Neurology (J.C.H., D.C.B., L.B., S.C.J.) and Neurosurgery (G.T.M.), University of California, San Francisco.
Correspondence to J. Claude Hemphill III, MD, Department of Neurology, San Francisco General Hospital, Room 4 M62, 1001 Potrero Ave, San Francisco, CA 94110. E-mail jchiii{at}itsa.ucsf.edu
| Abstract |
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MethodsRecords of all patients with acute ICH presenting to the University of California, San Francisco during 19971998 were reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the ICH Score) was developed with weighting of independent predictors based on strength of association.
ResultsFactors
independently associated with 30-day mortality were Glasgow Coma Scale
score (P<0.001), age
80
years (P=0.001), infratentorial
origin of ICH (P=0.03), ICH
volume (P=0.047), and presence
of intraventricular hemorrhage
(P=0.052). The ICH Score was
the sum of individual points assigned as follows: GCS score 3 to 4 (=2
points), 5 to 12 (=1), 13 to 15 (=0); age
80 years yes (=1), no (=0);
infratentorial origin yes (=1), no (=0); ICH volume
30
cm3 (=1), <30
cm3 (=0); and
intraventricular hemorrhage yes (=1), no
(=0). All 26 patients with an ICH Score of 0 survived, and all 6
patients with an ICH Score of 5 died. Thirty-day mortality increased
steadily with ICH Score
(P<0.005).
ConclusionsThe ICH Score is a simple clinical grading scale that allows risk stratification on presentation with ICH. The use of a scale such as the ICH Score could improve standardization of clinical treatment protocols and clinical research studies in ICH.
Key Words: intracerebral hemorrhage medical management outcome prognosis surgery
| Introduction |
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In contrast to the lack of efficacious treatments for ICH, there exist a number of prognostic models for mortality and functional outcome after ICH.13 14 15 16 17 These models usually include criteria related to neurological condition, various other clinical and laboratory parameters, and neuroimaging findings. Current models vary in complexity, with some including terms for degree of hydrocephalus or intraventricular hemorrhage (IVH) and some using algebraic equations to calculate predicted outcome.13 15 16 Thus, while these models may accurately predict outcome, they vary in their ease of use, especially by personnel not specifically trained in neuroimaging and statistical analysis. Despite the accuracy of several of these outcome models, no grading scale for ICH is consistently used for triage and acute intervention, whether as part of clinical care or clinical research. The purpose of this study was to define a clinical grading scale for ICH which uses criteria that are predictive of outcome and that can be rapidly and accurately assessed at the time of presentation, especially by personnel not specifically trained in stroke neurology.
| Subjects and Methods |
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All variables used for outcome model development were abstracted from data available at the time of initial ICH evaluation. Pulse pressure (defined as systolic blood pressure minus diastolic blood pressure), Glasgow Coma Scale (GCS) score, presence of IVH, and ICH volume were recorded because these are components of previously validated ICH outcome models13 14 and can be accurately assessed by personnel without extensive training in stroke neurology.18 19 The first blood pressure recorded after hospital arrival was used to determine pulse pressure. The GCS score at the time of transfer from the emergency department (to intensive care unit, operating room, or hospital ward) was used because this is the point at which initial acute intervention would be considered. GCS scores recorded in the medical record were verified against the concurrent documented neurological examination to ensure accuracy of GCS assessment; when the GCS score was not specifically recorded in the medical record, it was calculated from the neurological examination.14 ICH hematoma volume was measured on the initial head CT scan with the use of the ABC/2 method, in which A is the greatest diameter on the largest hemorrhage slice, B is the diameter perpendicular to A, and C is the approximate number of axial slices with hemorrhage multiplied by the slice thickness.19 The presence or absence of IVH was also noted on initial head CT. Other recorded parameters included sex, age, site of ICH, presumed cause (assessed as impression of the attending physician of record at the time of death or hospital discharge), and first serum glucose level obtained after emergency department arrival. Two parameters related to in-hospital treatment (whether external ventricular drain [EVD] placement or surgical hematoma evacuation was undertaken) were also recorded. Outcome was assessed as mortality at 30 days after ICH. For patients in whom 30-day outcome was not available from medical records (n=31), Internet-based mortality records (California Death Records; Social Security Death Index) were searched. Patients who were alive at hospital discharge and did not have a recorded date of death in any of these records were assumed to have been alive at 30 days after ICH.
For univariate analyses, overall
frequencies or mean±SD values of specific parameters (as
appropriate) were compared by
2
statistics for dichotomous variables. GCS, ICH volume, serum
glucose level, and pulse pressure were considered continuous
variables, with sex, site of ICH, presumed cause, and IVH as
categorical variables. Because age was only associated with outcome
for patients aged
80 years (patients aged <80,
P=0.41), age was considered a
dichotomous categorical variable with a cut point at 80 years.
Students t test was used to
compare continuous variables, and the Wilcoxon rank sum
test was used for categorical variables.
Outcome models were developed for cohorts including all ICH
patients and subgroups of infratentorial and
supratentorial patients, with 30-day mortality as
the dependent variable. Multivariate logistic
regression analyses were performed, initially including all
potential predictor variables in the model, with stepwise
elimination of variables not contributing to the model
(P>0.10). Independent
variables assessed in univariate and
multivariate analysis included GCS, ICH volume,
IVH, pulse pressure, age
80 years at ICH,
supratentorial versus infratentorial origin, sex,
and serum glucose level. First-order interaction terms were tested in
the final model.
An outcome risk stratification scale (the ICH Score) was developed with the use of variables associated with 30-day mortality in the all-patients model, with weighting based on the strength of independent association of the specified parameter. Cut points of variables were chosen to produce a simple and intuitive model and to incorporate values similar to those used in prior reports.13 14 Cuzicks nonparametric test of trend was used to assess association of the ICH Score with 30-day mortality.20 Statistical analysis was performed with SPSS (version 10.0) and Stata (version 5.0), and P<0.05 was considered statistically significant.
| Results |
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80 years, and
presence of IVH were all associated with 30-day mortality. Pulse
pressure (P=0.25), ICH
location, sex, and presumed cause were not associated with
outcome.
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Outcome prediction models for the UCSF ICH cohort were
developed for the subsets of supratentorial and
infratentorial ICH patients as well as for the entire group of all ICH
patients. The purpose of this was to assess whether different
characteristics were predictive of outcome for these different sites of
ICH origin and whether all ICH patients could be considered in a single
risk stratification scale or whether infratentorial and
supratentorial ICH require separate outcome
prediction tools.
Table 2
summarizes these outcome prediction models, which
in turn form the basis for the ICH Score.
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For the group of supratentorial ICH
patients, GCS score, age
80 years, and ICH volume were independent
predictors of outcome, with GCS score being most strongly associated
with outcome. For the group of infratentorial ICH patients, only GCS
score was a statistically significant independent predictor of outcome,
although there was a strong trend for IVH. ICH volume was not a
statistically significant predictor of outcome
(P=0.21) in infratentorial ICH
patients. In both groups, sex, pulse pressure, and serum glucose level
were not statistically significant independent outcome predictors. For
the group of all ICH patients, GCS score, age
80 years, ICH volume,
IVH, and infratentorial ICH origin were all strong predictors of
outcome. Once again, sex, pulse pressure, and serum glucose level were
not predictive of 30-day mortality.
Neither of the 2 treatment parameters assessed (EVD placement and surgical hematoma evacuation) was associated with outcome in univariate analysis. Additionally, when EVD placement and surgical hematoma evacuation were tested in the final outcome prediction models, neither parameter was independently associated with 30-day mortality. This was true for the group of all ICH patients as well as for the supratentorial and infratentorial patient groups individually.
The ICH Score
An outcome risk stratification scale (the ICH Score)
was developed from the logistic regression model for all ICH patients.
The 5 characteristics determined to be independent predictors of 30-day
mortality (and therefore included in the logistic regression model)
were each assigned points on the basis of the strength of association
with outcome. The total ICH Score is the sum of the points of the
various characteristics.
Table 3
indicates the specific point assignments used in
calculating the ICH Score. Because GCS score was most strongly
associated with outcome, it was given the most weight in the scale. The
GCS was divided into 3 subgroups (GCS scores of 3 to 4, 5 to 12, and 13
to 15) to more accurately reflect the very strong influence of GCS
score on outcome. Of note, in the UCSF ICH cohort, only 1 of 35
patients with a presenting GCS score of 3 or 4 survived to 30 days,
and only 5 of 60 patients with a presenting GCS score of 13 to 15
died, whereas 29 of 57 patients with a GCS score of 5 to 12 died within
30 days. Age
80 years was also very strongly associated with 30-day
mortality. Because age in the prediction models was dichotomized around
the cut point of 80 years and was not associated with outcome in the
infratentorial group of patients, only 1 point was assigned for
patients aged
80 years. IVH, infratentorial ICH origin, and ICH
volume all had relatively similar strengths of outcome association and
were therefore weighted the same in the ICH Score. IVH and
infratentorial ICH origin are dichotomous variables with points
assigned when present. ICH volume was dichotomized to <30 and
30
cm3. Thirty cubic centimeters was chosen
because it represented a cut point for increased mortality
in the UCSF ICH cohort, is easy to remember, and is similar to ICH
volume cut points used in prior
models.13 14
Furthermore, no patient with infratentorial ICH origin in the UCSF ICH
cohort had a hematoma volume
30 cm3.
Additional points were not assigned for larger hematomas (eg, >60
cm3) because, when tested, this did not
improve the accuracy of the ICH Score and would have
represented equal weighting with the GCS score, which was
not justified on the basis of strength of outcome association in the
logistic regression model.
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The ICH Score was an accurate predictor of outcome assessed
as 30-day mortality
(Figure
).
The range of ICH Scores was 0 to 5, and ICH Scores from the cohort were
distributed among the various categories. Each increase in the ICH
Score was associated with a progressive increase in 30-day mortality
(P<0.005 for trend). This was
evident in the entire cohort of ICH patients, as well as when patients
were divided into supratentorial and infratentorial
subgroups (P<0.005 for both
subgroups), suggesting that the ICH Score is an applicable risk
stratification tool to all ICH patients, not just a particular
subgroup. No patient with an ICH Score of 0 died, whereas all patients
with an ICH Score of 5 died. Thirty-day mortality rates for patients
with ICH Scores of 1, 2, 3, and 4 were 13%, 26%, 72%, and 97%,
respectively. No patient in the UCSF ICH cohort had an ICH Score of 6
because no patient with an infratentorial ICH had a hematoma volume
30 cm3. However, given that no patient
with an ICH Score of 5 survived, an ICH Score of 6 would be expected to
be associated with a very high risk of
mortality.
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| Discussion |
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Clinical grading scales serve several valuable purposes that follow from the standardization of assessment afforded by these tools. While many grading scales are used for prognostication and treatment selection in neurological disease, the foremost purpose of these scales is to improve communication and consistency among healthcare providers. This, in fact, was the initial purpose behind the GCS21 and has become a fundamental aspect of the clinical care of patients with traumatic brain injury (GCS), aneurysmal SAH (Hunt-Hess and WFNS), and ischemic stroke (NIHSS). From this standardized assessment has followed the ability to use these scales for risk stratification for treatment selection in clinical care and enrollment criteria for clinical research.
Several prognostic models for ICH have been previously developed and validated.13 14 15 16 26 27 28 These models have found several characteristics associated with outcome, as measured by mortality and functional outcome. Among these various characteristics, level of consciousness on hospital admission (often assessed as GCS score) and hematoma volume have usually been the most robust outcome predictors, with other factors, such as presence and amount of IVH, also associated with outcome in some models.13 14 15 16 28 A number of these models have been demonstrated as highly accurate in predicting long-term outcome, and this finding has led to the use of GCS score and ICH hematoma volume as enrollment criteria for various studies of intervention in ICH.7 8 29 However, several of these models use complex algebraic equations in outcome prediction, and none have been simplified into a standard clinical grading scale analogous to the GCS, NIHSS, Hunt-Hess, WFNS, or Spetzler-Martin scales. It is likely that this lack of a uniform ICH scale has contributed to variability in enrollment criteria for ICH studies as well as to heterogeneity in clinical ICH care.
To be generally applicable, a clinical grading scale must be simple enough to use without significant special training, statistical knowledge, or extensive time commitment. It also must be reliable in patient stratification and should be composed of elements that are associated with outcome and that would likely be assessed, in general, as part of routine clinical care. In essentially every clinical grading scale there exists a compromise between simplicity and accuracy of outcome prediction. To strike the appropriate balance between these 2 factors, the general purpose of the grading scale must be considered. The ICH Score is a clinical grading scale composed of factors related to a basic neurological examination (GCS), a baseline patient characteristic (age), and initial neuroimaging (ICH volume, IVH, infratentorial/supratentorial origin). The purpose of this grading scale is to provide a standard assessment tool that can be easily and rapidly determined at the time of ICH presentation by physicians without special training in stroke neurology and that will allow consistency in communication and treatment selection in clinical care and clinical research.
Specific elements of the ICH Score deserve discussion. The
GCS score is now a standard neurological assessment tool that is
reproducible and reliable.18
It has been associated with ICH outcome in other prediction models, as
it is in the UCSF ICH
cohort.13 14 15 28
The unique element of the GCS component of the ICH Score compared with
other ICH prediction models is the division of the scale into 3, not 2,
subgroups. Most other prediction models have grouped patients into
those with GCS score >8 versus those
8.13 14 This
assumes that the influence of level of consciousness on outcome is very
similar for a patient with a GCS score of 8 and a patient with a GCS
score of 3. This was not the case in the UCSF ICH cohort since patients
with GCS scores of
4 did much worse than those with higher GCS scores
regardless of other factors. In fact, this is being increasingly
recognized in other diseases, such as traumatic brain injury, in which
patients with GCS scores of 3 or 4 have been analyzed
separately regarding outcome or are being considered for exclusion from
certain clinical trials.30
Likewise, patients with GCS scores of
13 tend toward much better
long-term outcome, as in the UCSF ICH cohort. Because the GCS score is
overwhelmingly the strongest outcome predictor in acute ICH, weighting
this component of the ICH Score more than others is justified, and
dividing it into these 3 groups is more clinically meaningful than
dichotomizing toward the middle of the range of possible GCS scores
(range, 3 to 15).
Age has been found to be an independent predictor of ICH
outcome in some prior prediction models, while age has not been
associated with outcome in
others.13 14 15 28
In the UCSF ICH cohort, only very old age (
80 years) was associated
with 30-day mortality. The fact that age has been an
inconsistent ICH outcome predictor among various models and may
have its strongest influence among the group of very elderly patients
suggests 2 possibilities. Either the very elderly sustain worse
neurological injury from ICH irrespective of size or location, or
overall medical care decisions in elderly patients are less aggressive
even if ICH-related neurological injury is not as profound. In the UCSF
ICH cohort, 3 elderly patients who would have been expected to survive
their ICH on the basis of clinical neurological condition were provided
hospice care because of concurrent medical problems such as dementia or
newly diagnosed cancer. This care approach was not taken in any
patients aged <80 years. While age is not a component of other risk
stratification scales such as the GCS, the Hunt-Hess or WFNS scales,
the NIHSS, or the Spetzler-Martin scale, very old age is frequently
among exclusion criteria for enrollment in various clinical studies of
aggressive intervention in traumatic brain injury and stroke.
Validation of the ICH Score on other patient populations will help to
elucidate the impact of age on risk stratification after ICH and may
help to delineate whether this influence is due to age-related ICH
injury, differences in clinical care of the very elderly, or
both.
ICH volume is consistently associated with outcome in ICH prediction models.13 14 Often ICH volume has been divided into 3 groups representing small, medium, and large hematoma size.13 14 While the specific volume cut points vary depending on the specific model, small hematomas have often been considered as <30 cm3 and large hematomas as >60 cm3.14 While ICH volume is a component of the ICH Score, its association with outcome was not as strong as some other predictors. In fact, ICH volume was not an independent predictor for outcome in infratentorial hemorrhages. This may be because small hemorrhages in the brain stem or cerebellum may have catastrophic consequences, making location, not size, the more important predictor for infratentorial ICH. Additionally, while larger supratentorial ICH volumes were associated with increased mortality, the addition of a "large hematoma" group did not improve the model because patients with larger hematomas who died also had other predictors such as low GCS score, advanced age, or IVH that influenced outcome to a greater degree. This has practical implications for patient treatment in that we believe that the logistic regression model and ICH Score derived from the UCSF ICH cohort would not justify exclusion of a patient for treatment solely on the basis of a large hematoma in the absence of other poor outcome predictors such as low GCS score, advanced age, or IVH. Thus, the ICH volume component of the ICH Score is dichotomized to reflect the strength of association with outcome and weighted accordingly. Importantly, assessment of ICH volume by the ABC/2 method has been shown as accurate and with good interrater reliability.19
The presence of any IVH and infratentorial hemorrhage origin were the other factors independently associated with 30-day mortality in the UCSF ICH cohort and therefore included in the ICH Score. Both are easy to assess and are dichotomous variables. Undoubtedly, further characterization of the degree of IVH and IVH-associated hydrocephalus could provide additional prognostic information,16 but these are also more subjective measures that are more complicated to assess and therefore were not included in this model. We believed that it was important to create a single model that would include all ICH and not limit the assessment to supratentorial ICH, as in some other models.13 15 16 27 Including a term for infratentorial hemorrhage and selecting the cut point for ICH volume as previously described allowed this to be accomplished. Other factors may have prognostic value after ICH, such as medical comorbidities, changes on follow-up neuroimaging, and progression of neurological deficit. These were not included in the ICH Score because they are not readily assessable on initial ICH presentation or might require more complex medical judgments. Additionally, while serum glucose level was associated with 30-day mortality in univariate analysis, it was not independently associated with outcome in multivariate logistic regression analysis for any group (all patients, supratentorial only, or infratentorial only). Thus, any contribution to outcome prediction afforded by initial serum glucose level was taken into account by other factors that are independently associated with outcome and already components of the ICH Score. Whether hyperglycemia is injurious to the brain after ICH and deserves treatment is a separate issue not addressed by this study.
How might the ICH Score be used? Prognosis after ICH or other acute neurological disorders is often a fundamental question, and the various scales discussed above are often used to provide initial information regarding this. While prognostication is undoubtedly important to assess treatment benefits and risks and to provide patients and families with information regarding severity of illness, attempts to precisely prognosticate outcome may lead to inappropriate "self-fulfilling prophecies." The ICH Score and other clinical grading scales are most appropriately used to provide a framework for clinical decision making and to provide reliable criteria for assessing efficacy of new treatments.31 Thus, a scale such as the ICH Score could be used as part of risk stratification for ICH treatment studies, but not as a precise predictor of outcome. However, before this should be considered, validation of the ICH Score on an independent data set, especially using functional outcome (such as modified Rankin Scale score) at a meaningful time point, such as 6 or 12 months, should be undertaken. Additionally, factors not represented in the ICH Score, such as location of ICH (eg, basal ganglia, cerebellum), time of onset, medical comorbidities, and patient or family treatment preferences, will always play an important role in selection of patients for clinical treatment or clinical research studies. Despite these issues, improved standardization of clinical assessment with the use of a grading scale such as the ICH Score is likely to provide more consistency in clinical care and clinical research for ICH, just as similar assessment scales have provided consistency in traumatic brain injury, aneurysmal SAH, and ischemic stroke. This in turn could provide an important step in developing new treatments for ICH, a disease with no current treatment of proven benefit.
| Acknowledgments |
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Received September 21, 2000; revision received January 2, 2001; accepted January 23, 2001.
| References |
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Department of Neurology, Mount Sinai School of Medicine, New York, NY
| Introduction |
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The current study considered patients in the Emergency Department (ED). This is certainly a clinically important phase in the assessment and treatment of an ICH patient, but patients present to the ED at varying times from onset of their illness, and spend variable amounts of time in the ED. These times are not reported in the current study but may play an important part in determining which factors are most salient in determining treatment and predicting outcomes.R2 A patient with a large hematoma may present awake if evaluated with in an hour after onset but could be comatose at 6 hours. Conceivably, early intervention would be helpful in this situation but not if postponed until deterioration occurs. Certainly in cerebellar hematoma this seems to be the case. Consequently, we must be cautious in applying prognostic instruments which suggest that awake patients do well irrespective of ICH size.
In the current report, patients older than 80 years fared less well, and this factor was included in the scale. Age has been reported to be a significant independent outcome predictor in someR2 R4 but not the majority of previous studies. Age may appear important for several reasons. Younger patients tend to present to hospital sooner after ictusR2 ; conceivably, although no specific therapy has been demonstrated to have a significant effect on outcome in controlled trials, earlier treatment may reduce mortality. Second, the elderly, as the authors correctly point out, may not receive life-sustaining treatment as aggressive as that given to younger patients. Finally, age may serve as a proxy for many variables not included in the multivariate model, such as heart disease or other intercurrent illnesses that complicate the clinical situation. Too often the very elderly are excluded from clinical trials because of the assumption that their outcome may be different simply as a consequence of their age. Whether designing clinical trials or providing clinical care, we should never lose sight of the individual because of the date of birth.
ICH remains a condition with little proven effective therapy. Logistic regression modeling has helped to focus attention on potential targets for intervention (eg, intraventricular blood)R5 as well as to suggest which patients are most likely to have their outcome affected by a successful intervention. What is required now is the development and testing of those interventions.
Received September 21, 2000; revision received January 2, 2001; accepted January 23, 2001.
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