- Department of Neurosurgery, Informatics and Documentation, Friedrich Schiller University, Jena, Germany
- Department of Neurology, Informatics and Documentation, Friedrich Schiller University, Jena, Germany
- Department of Medical Statistics, Informatics and Documentation, Friedrich Schiller University, Jena, Germany
Diaa A. Safatli
Department of Neurosurgery, Informatics and Documentation, Friedrich Schiller University, Jena, Germany
DOI:10.4103/2152-7806.187493Copyright: © 2016 Surgical Neurology International This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Safatli DA, Albrecht Günther, Schlattmann P, Schwarz F, Kalff R, Ewald C. Predictors of 30-day mortality in patients with spontaneous primary intracerebral hemorrhage. Surg Neurol Int 01-Aug-2016;7:
How to cite this URL: Safatli DA, Albrecht Günther, Schlattmann P, Schwarz F, Kalff R, Ewald C. Predictors of 30-day mortality in patients with spontaneous primary intracerebral hemorrhage. Surg Neurol Int 01-Aug-2016;7:. Available from: http://surgicalneurologyint.com/surgicalint_articles/predictors-30%e2%80%91day-mortality-patients-spontaneous-primary-intracerebral-hemorrhage/
Background:Intracerebral hemorrhage (ICH) is a life threatening entity, and an early outcome assessment is mandatory for optimizing therapeutic efforts.
Methods:We retrospectively analyzed data from 342 patients with spontaneous primary ICH to evaluate possible predictors of 30-day mortality considering clinical, radiological, and therapeutical parameters. We also applied three widely accepted outcome grading scoring systems [(ICH score, FUNC score and intracerebral hemorrhage grading scale (ICH-GS)] on our population to evaluate the correlation of these scores with the 30-day mortality in our study. We also applied three widely accepted outcome grading scoring systems [(ICH score, FUNC score and intracerebral hemorrhage grading scale (ICH-GS)] on our population to evaluate the correlation of these scores with the 30-day mortality in our study.
Results:From 342 patients (mean age: 67 years, mean Glasgow Coma Scale [GCS] on admission: 9, mean ICH volume: 62.19 ml, most common hematoma location: basal ganglia [43.9%]), 102 received surgical and 240 conservative treatment. The 30-day mortality was 25.15%. In a multivariate analysis, GCS (Odds ratio [OR] =0.726, 95% confidence interval [CI] =0.661–0.796, P P P = 0.009) were significant predictors for the 30-day mortality. After receiver operating characteristics analysis, we defined a “high-risk group” for an unfavorable short-term outcome with GCS 32 ml supratentorially or 21 ml infratentorially. Using Pearson correlation, we found a correlation of 0.986 between ICH score and 30-day mortality (P P = 0.001), and 0.924 between ICH-GS and 30-day mortality (P = 0.001).
Conclusions:GCS score on admission together with the baseline volume and localization of the hemorrhage are strong predictors for 30-day mortality in patients with spontaneous primary intracerebral hemorrhage, and by relying on them it is possible to identify high-risk patients with poor short-term outcome. The ICH score and the ICH-GS accurately predict the 30-day mortality.
Keywords: Cerebral hemorrhage, multivariate analysis, prognosis, risk factors, treatment outcome
Spontaneous intracerebral hemorrhage (ICH) still poses challenges in neurological and neurosurgical routines in terms of therapeutic decision making. Approximately 10-15% of strokes are caused by intra-axial bleeding, and despite substantial advances in diagnostics and therapy, only approximately 20% of the patients with spontaneous ICH regain functional independency within 3 months after the ictus.[
The clinical manifestation of spontaneous ICH varies depending on the location and volume of the hemorrhage, as well as on patient age and presence of other comorbidities.[
Considering this background, we performed a study to analyze the short-term course of a large patient group suffering from a primary spontaneous ICH and determine possible predictors of 30-day mortality.
We retrospectively analyzed data from 342 consecutive patients with the diagnosis of a primary spontaneous intracerebral hemorrhage treated in our institution between January 2005 and December 2013.
The exclusion criteria were secondary ICH caused by trauma, tumors, arteriovenous malformations (AVM) or aneurysms, insufficient medical records and patients with initial absence of brainstem reflexes on admission.
To define possible risk factors for death within 30 days, we created a data file that included the following parameters: Age, sex, initial neurologic status, medical history for the presence of comorbidities and consumption of antiplatelet and anticoagulant drugs, radiographic features, as well as type of treatment (surgical or conservative therapy).
The cornerstone of our work was assessing the short-term outcome, with short-term mortality as the primary outcome of interest. Therefore, we defined the primary endpoint of this study as death or follow-up of maximum 30 days.
The neurological outcome was estimated using the modified Rankin Scale (mRS).[
Comorbidities, such as hypertension, diabetes, history of tobacco abuse (consumption of more than 5 cigarettes per day at least 2 days every week for at least 12 months) and alcohol abuse (consumption or more than 24 doses per week for men and 16 for women), and the use of antiplatelet or anticoagulant drugs were also collected.
The initial imaging data (mainly computed tomography [CT] of the head) were reviewed to obtain possible radiographic risk factors, including location, volume and depth of bleeding. Furthermore, we also looked for the presence of interventricular hemorrhage (IVH) or accompanying subarachnoid hemorrhage (SAH). The hematoma volume was estimated on the initial head CT scan using 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 number of axial slices with bleeding multiplied by the slice thickness.[
To analyze the influence of treatment (conservative versus surgical) on the short-term outcome, we defined two groups. Group I comprised patients who underwent initial conservative therapy with medical treatment. Group II included the patients who underwent an early surgical evacuation of the bleeding within the first 72 h after the diagnosis of the ICH along with medical treatment. The placement of an external ventricular drainage was considered a tool for neurological monitoring within the bounds of the medical treatment and not as a primary active surgical treatment. Decision for surgery was made in each case by a responsible neurosurgeon individually, which was mainly based on the radiological features of the hemorrhage and the neurological status of the patient.
Finally, we determined three validated outcome grading scores[
First, an univariate logistic regression was used to assess the strength of association between the collected variables and the 30-day mortality. The assessed variables included age, gender, GCS, ICH volume, ICH location, IVH, SAH, arterial hypertension, diabetes, tobacco abuse, alcohol abuse, use of anticoagulation and/or antiplatelet therapy, and the kind of therapy (conservative therapy versus surgery). Multivariate analysis, with the 30-day mortality as dependent variable, on variables found to be significant by univariate analysis, was performed in a second step. We also derived cutoff values after performing receiver operating characteristics (ROC) analysis using the Youden Index. A Hosmer and Lemeshow test was used to assess the goodness of fit for the multivariate model. Results are reported as odds ratios (OR) together with a 95% confidence interval (CI). Pearson correlation analysis was performed to determine the correlation between applied outcome grading scores and 30-day mortality. The significance level was set to be 0.05. The analysis was performed using the Statistical Package for the Social Sciences, Version 22 (SPSS Inc., Chicago, IL, USA).
A total of 342 patients (mean age 67 ± 11.2 years; 172 males, 50.3%) with the diagnosis spontaneous primary ICH for whom sufficient medical records existed fulfilled the inclusion criteria. Mean GCS score on admission was 9 ± 3.66 (range: 3–15). The main characteristics of our patient cohort are summarized in
Arterial hypertension was present in 86.5% (n = 296), a history of diabetes in 28% (n = 96), a history of tobacco abuse in 5.8% (n = 20), and alcohol abuse in 8.8% (n = 30) of the patients.
A preoperative therapy that affected hemostasis comprising either antiplatelet (n = 76) or anticoagulant therapy (n = 88) was identified in 164 patients (48%). The most common location of the bleeding was the basal ganglia (43.9%, n = 158) followed by lobular (38%, n = 134), cerebellar (10.4%, n = 36), and brainstem (4.1%, n = 14) hemorrhage.
The mean ICH volume was 62.19 ± 59.46 ml (range: 5–382 ml). IVH was found on the initial CT of 198 patients (58%) and accompanying SAH in 32 patients (9.4%). Mean midline shift was 6.5 ± 4.8 mm and the minimum depth of the hematoma from the cortical surface was ≤10 mm in 100 patients (29.2%) and >10 mm in 242 patients (70.8%).
One hundred and two patients (29.8%) underwent an early surgical treatment for the bleeding. Of these, 10 patients had a stereotactic evacuation and 16 patients received an additional craniectomy. Two hundred and forty patients (70.2%) were treated conservatively without surgical evacuation of the hemorrhage.
Eighty six patients died within 30 days following the bleeding and hence the 30-day mortality was 25.15%. Half of these patients died within the first 48 h following bleeding. An unfavorable outcome (mRS > 2) was documented in 262 patients (76.7%) at the end of the short-term follow-up [
The univariate analysis showed the following variables as significant predictors of death within 30 days after ictus of spontaneous ICH: Initial neurological state, baseline volume of ICH, midline shift on initial head CT, localization of ICH (supra- vs. infratentorial), use of oral anticoagulants, presence of IVH and type of treatment (conservative vs. operative). In the second step, we performed a multivariate logistic regression analysis on variables found to be significant after univariate analysis with the 30-day mortality as the dependent variable.
Hereafter initial GCS (OR = 0.726 per one point on GCS, 95% CI = 0.661–0.796, P < 0.001), the volume of the bleeding (OR = 1.012 per ml, 95% CI = 1.007–1.017, P < 0.001), and the infratentorial location of the ICH (OR = 5.381, 95% CI = 2.166–13.356, P = 0.009) were significant predictors for the 30-day mortality. The use of oral anticoagulants was not a significant prognostic factor in our multivariate analysis, although there was a tendency towards significance in terms of higher 30-day mortality [
On performing an ROC analysis (using the Youden Index), a cutoff value of 11 was determined for the GCS. In addition, cutoff values for the volumes for supratentorial bleeding and infratentorial could be identified as 32 ml and 21 ml respectively. This “high-risk group” of spontaneous ICH patients with an initial GCS <11 and ICH volume >32 ml supratentorially or 21 ml infratentorially showed a 30-day mortality exceeding 50% and an unfavorable outcome (mRS > 2) in almost 100% [
Surgery versus nonsurgical treatment
Concerning the influence of the type of treatment (conservative vs. surgery) on the short-term outcome in our study, statistical analysis of the entire cohort showed a trend towards lower mortality in the early surgery group compared to the conservatively treated group (15.7% vs. 29.2%), although this result was not statistically significant (P = 0,097). The outcome at 30 days after bleeding in both groups, that is, surgery and conservative treatment, is illustrated in
Notably, the distribution of the characteristics with regard to the volume and depth of hemorrhage between the patients (surgery vs. nonsurgery), was significantly different in both therapy groups [
Predicting 30-day mortality using outcome grading scores
We applied three known and validated outcome grading scores to our cohort to determine their corrrelation with 30-day mortality.[
When using the ICH score and the ICH-GS, the 30-day mortality increased in accordance with increases in the scores’ values. The FUNC score correlated negatively to a lesser degree with the short-term mortality in our study. Pearson correlation showed correlations of 0.986 between ICH score and 30-day mortality (P < 0.001), 0.853 between FUNC score and 30-day mortality (P = 0.001), and 0.924 between ICH-GS and 30-day mortality (P = 0.001).
Spontaneous intracerebral hemorrhage remains an important and frequent medical emergency, often with severe and devastating consequences for the patient. Optimal management is still under discussion and subject of many studies in the medical literature dealing inter alia with various treatment options[
The 30-day mortality of patients with spontaneous ICH has been reported as ranging from 25 to 52%.[
Concerning the short-term outcome, 23.4% of the patients had a favorable outcome after 30 days. In a meta-analysis, Van Asch et al. presented a functional outcome with independency rates of between 12 and 39% corresponding to our data.[
Consistent with other previously published studies neither gender nor age was a significant outcome predictor.[
Concerning possible risk factors for a poor outcome, our study confirmed the initial neurological status and the volume of ICH as the strongest predictors of outcome as described in others.[
Our statistical model revealed that a bleeding volume of more than 32 ml supratentorially and 21 ml infratentorially correlated with a poor short-term outcome (death or dependence) of >80% and approaching 100% when combined with an initial GCS of 11 or less. Flemming et al. identified 40 ml as a critical volume predicting a poor outcome in his study with a population of patients with lobar hemorrhage who were primarily medically treated.[
The location of the hemorrhage was also a significant risk factor for 30-day mortality. An infratentorial location correlated with a high 30-day mortality in our study which is consistent with results from other studies.[
Patients who underwent surgical therapy had a higher survival rate compared to patients who received the conservative best medical treatment. However, this survival advantage was not statistically significant. In addition, the rate of functional disability was higher in surviving patients in the surgical therapy group, especially in the subgroup with a GCS of <11 on admission and baseline ICH volume of >32 ml supratentorially and >21 ml infratentorially. Hence, further prospective studies evaluating the long-term outcome of these patients are necessary.
Several limitations have to be considered when interpreting our data. First, the retrospective character disposes to an incomplete documentation of the various analyzed variables. Second, because the decision on the treatment modality (surgical or conservative) was made individually by different physicians, it probably contributed to the diverse distribution of the variables in both therapy groups. However, our study confirms some existing data, using a relatively big cohort of patients, and additionally defines a “high-risk” group for an unfavorable outcome.
Our study also compared three validated outcome grading scores and showed that the ICH score and the ICH-GS accurately predict short-term mortality. The FUNC score, originally designed to estimate the 90-day outcome, correlated to a lesser degree with the mortality at 30 days in our study cohort.
The GCS score on admission, together with baseline volume and localization of the hemorrhage are strong predictors for 30 day-mortality in patients with spontaneous primary ICH. An admission GCS of less than 11 and ICH volume of more than 32 ml supratentorially and 21 ml infratentorially define a high-risk group of patients for developing a poor short-term outcome. The ICH score and the ICH-GS accurately predict the 30-day mortality.
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1. Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): A randomised pilot trial. Lancet Neurol. 2008. 7: 391-9
2. Bhatia R, Singh H, Singh S, Padma MV, Prasad K, Tripathi M. A prospective study of in-hospital mortality and discharge outcome in spontaneous intracerebral hemorrhage. Neurol India. 2013. 61: 244-8
3. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: A guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation. 2007. 116: e391-413
4. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993. 24: 987-93
5. Counsell C, Dennis M. Systematic review of prognostic models in patients with acute stroke. Cerebrovasc Dis. 2001. 12: 159-70
6. Fieschi C, Carolei A, Fiorelli M, Argentino C, Bozzao L, Fazio C. Changing prognosis of primary intracerebral hemorrhage: Results of a clinical and computed tomographic follow-up study of 104 patients. Stroke. 1988. 19: 192-5
7. Flaherty ML, Haverbusch M, Sekar P, Kissela B, Kleindorfer D, Moomaw CJ. Long-term mortality after intracerebral hemorrhage. Neurology. 2006. 66: 1182-6
8. Flemming KD, Wijdicks EF, Li H. Can we predict poor outcome at presentation in patients with lobar hemorrhage?. Cerebrovasc Dis. 2001. 11: 183-9
9. Gebel JM, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002. 33: 2636-41
10. Godoy DA, Pinero G, Di Napoli M. Predicting mortality in spontaneous intracerebral hemorrhage: Can modification to original score improve the prediction?. Stroke. 2006. 37: 1038-44
11. Greenberg SM, Briggs ME, Hyman BT, Kokoris GJ, Takis C, Kanter DS. Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke. 1996. 27: 1333-7
12. Hemphill JC, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: A simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001. 32: 891-7
13. Hemphill JC, White DB. Clinical nihilism in neuroemergencies. Emerg Med Clin North Am. 2009. 27: 27-37
14. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Eng J Med. 2008. 358: 2127-37
15. Nilsson OG, Lindgren A, Brandt L, Saveland H. Prediction of death in patients with primary intracerebral hemorrhage: A prospective study of a defined population. J Neurosurgery. 2002. 97: 531-6
16. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Eng J Med. 2001. 344: 1450-60
17. Roquer J, Rodriguez Campello A, Gomis M, Ois A, Puente V, Munteis E. Previous antiplatelet therapy is an independent predictor of 30-day mortality after spontaneous supratentorial intracerebral hemorrhage. J Neurol. 2005. 252: 412-6
18. Rost NS, Smith EE, Chang Y, Snider RW, Chanderraj R, Schwab K. Prediction of functional outcome in patients with primary intracerebral hemorrhage: The FUNC score. Stroke. 2008. 39: 2304-9
19. Ruiz-Sandoval JL, Chiquete E, Romero-Vargas S, Padilla-Martinez JJ, Gonzalez-Cornejo S. Grading scale for prediction of outcome in primary intracerebral hemorrhages. Stroke. 2007. 38: 1641-4
20. Sacco S, Marini C, Toni D, Olivieri L, Carolei A. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke. 2009. 40: 394-9
21. Specogna AV, Patten SB, Turin TC, Hill MD. Cost of spontaneous intracerebral hemorrhage in Canada during 1 decade. Stroke. 2014. 45: 284-6
22. Sutherland GR, Auer RN. Primary intracerebral hemorrhage. J Clin Neurosci. 2006. 13: 511-7
23. Takahashi O, Cook EF, Nakamura T, Saito J, Ikawa F, Fukui T. Risk stratification for in-hospital mortality in spontaneous intracerebral haemorrhage: A classification and regression tree analysis. QJM. 2006. 99: 743-50
24. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974. 2: 81-4
25. Togha M, Bakhtavar K. Factors associated with in-hospital mortality following intracerebral hemorrhage: A three-year study in Tehran, Iran. BMC Neurol. 2004. 4: 9-
26. Tuhrim S, Dambrosia JM, Price TR, Mohr JP, Wolf PA, Heyman A. Prediction of intracerebral hemorrhage survival. Ann Neurol. 1988. 24: 258-63
27. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ.editors. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis. Lancet Neurol. 2010. 9: 167-76
28. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988. 19: 604-7
29. Zazulia AR, Diringer MN, Derdeyn CP, Powers WJ. Progression of mass effect after intracerebral hemorrhage. Stroke. 1999. 30: 1167-73