Cerebrovascular accident (CVA) or stroke is a common disorder. Specifically, spontaneous intracerebral hemorrhage (ICH) is the second leading cause of CVA, following ischemic stroke (10–15%).1 The annual incidence of ICH is estimated to be between 16 and 33 cases/100,000 inhabitants, and its prevalence has increased in recent years in relation to aging of the general population and the increasingly widespread use of antithrombotic therapy in younger patients.2–7

As a result of the increasing frequency of the disorder and the associated need for specialized treatment, affected patients often require admission to the Intensive Care Unit (ICU) for adequate management.1,6 This fact, and subsequent admission to the conventional hospital ward, imply an important use of social and economic resources.8 However, despite advances in specialized care in the ICU, the mortality rate associated to ICH is very high–one-half of all deaths occurring within the first 48h–and the functional outcomes remain very disappointing: only 12–39% of those patients who survive the episode are functionally independent. These considerations justify the different studies that have sought to establish predictive mortality and functional outcome models based on different demographic, clinical and biological variables, with the aim of optimizing the ulterior management of patients with ICH.8–13 However, many of these investigations only address short-term mortality in the ICU or in hospital. On the other hand, uncertainty remains regarding the influence of different invasive procedures such as immediate surgery or intracranial pressure (ICP) catheter monitoring and brain tissue oxygenation pressure (PtiO2) upon the final outcome.11,14

The main objective of this study is to determine mortality and functional outcome in patients with severe ICH. Likewise, an evaluation is made of the clinical, radiological and therapeutic variables with the strongest predictive capacity in relation to mortality in the ICU and during hospital admission, and to poor functional outcome after 6 months.

A total of 186 patients with ICH met the study inclusion criteria. The patient characteristics, clinical parameters, CT findings, procedures and evolutive data of the sample are shown in Table 1. The median age was 60 years (IQR 49; 66), and 122 patients were males (65.6%). The most common risk factor in our series was arterial hypertension (66.7%), followed by antiplatelet drug treatment (23.1%). The median GCS score upon admission was 9 points (IQR 7; 12), and the basal ganglia represented the most frequent location of ICH (53.2%). The median hematoma volume was 39cc (IQR 21.7; 65.0). A total of 25.8% of the patients included in the study underwent surgical evacuation of ICH. The overall mortality rate was 46.7% (89 patients); of these subjects, 65 (34.9%) died in the ICU, 11.8% (21 patients) during hospital stay, and three in the course of the 6 months following stroke.

Table 2 shows the differences of the different variables between the patients that died and the survivors. Of note is the observation that elevated blood glucose upon admission and after 24h, diabetes, and oral anticoagulant therapy were associated to a higher mortality rate both in the ICU and in hospital. Among other variables, the level of consciousness upon admission, pupil response, bleeding location at brainstem level, the presence of IVH assessed by the Graeb scale, and the APACHE II score all showed differences between the patients that died in the ICU or in hospital and the survivors. Neurosurgical intervention also resulted in differences between the two groups, since survival was found to be greater among the patients that underwent surgical treatment. These data are summarized in Table 3.

Table 4 shows the results of the multivariate Cox regression analysis of those variables found to be independently associated to mortality after ICH both in the ICU and during admission to hospital. Of note is the fact that the radiological findings associated to increased mortality in the ICU and in hospital were the presence of IVH, bleeding location at brainstem level, and the presence of radiological evidence of repeat bleeding. On the other hand, hematoma volume upon admission and the presence of a mass effect were associated to mortality in the ICU and in hospital, respectively.

Lastly, the functional evaluation of the patients after 6 months is shown in Table 5. The multivariate analysis corresponding to Table 6 shows the presence of diabetes or previous anticoagulant treatment and the type of hemorrhage on the CT scan to be predictors of mortality and of poor functional outcome, while surgery was associated to increased survival and better functional outcomes.

In our series, ICH was associated to high mortality and poor functional outcome. A history of diabetes, previous anticoagulation treatment, the location and volume of the hematoma, and patient severity upon admission were associated to poor patient prognosis, while monitoring of ICP or the application of surgical treatment was associated to improved outcome.

In recent decades the incidence of ICH has dropped by up to 31%.2 We consider that this can be explained by improved control of arterial hypertension, though the mortality rate remains high and the functional outcomes are still poor, as evidenced by our own findings. This situation in turn is probably attributable to the increased use of anticoagulants and antiplatelet drugs.1 Recent studies have found no changes in immediate or long-term mortality despite advances in primary prevention, adherence to the current clinical management guides and the increasingly widespread practice of treating these patients in specialized neurocritical units.6,19

In our series the mortality rates were consistent with those reported in the literature. The systematic review and metaanalysis published by Van Asch et al.4 documented a mortality rate of 35–52% after 30 days, and one-half of these deaths occurred in the first 48–72h after the bleeding event. In our series mortality was in the upper range (46.7%), probably due to a number of reasons. Firstly, our sample exclusively consisted of critical patients requiring admission to the ICU. Secondly, the median age of our patients was 60 years, and in this regard it is known that mortality in the 45–59 years age interval is even higher than among patients over 75 years of age.2 The growing use of anticoagulants in younger populations as treatment for their background diseases or for prophylactic purposes has been shown to be an independent risk factor for mortality in ICH, and is associated to expansion of the hematoma or the recurrence of ICH.7,20 In our series, 23.1% of the patients had received prior antiplatelet medication, and 13.4% were receiving oral anticoagulants. On the other hand, the duration of follow-up in our study was longer than in other series. Most publications analyze mortality after 30 days. In our study we extended this period, assessing also usually occult mortality occurring after discharge from the ICU and frequently beyond the mentioned 30-day interval. In our case this mortality rate was 11.8%, which would also explain our higher mortality versus other series. However, methodological reasons precluded a more exhaustive and isolated analysis of this subgroup.

In concordance with other studies, a total of 66.7% of the patients included in our series had high blood pressure–the latter being identified as the leading risk factor for ICH. Recent studies have underscored the importance of adequate blood pressure control in these patients, though such control has only been shown to offer benefits in terms of functional outcome, with no demonstrated impact upon mortality–in coincidence with our own observations.5

On relating the study variables to mortality in the ICU and in hospital, diabetic patients were seen to have a twofold higher risk of death, in coincidence with the observations in other neurocritical conditions.21 Other independent mortality factors in both cases were the APACHE II severity score upon admission, the presence of IVH, and hematomas located at brainstem level. In contrast, mortality was found to be lower in patients subjected to surgical treatment or with ICP monitoring–both of these factors being found to exert a protective effects against mortality. One of the main mechanisms implicated in mortality and in functional outcome after ICH refers to hematoma expansion in the first 24h. In this regard, prompt surgical intervention could have an important impact upon outcome. On the other hand, although invasive multimodal neuromonitoring was initially designed for use in patients with severe traumatic brain injury, we consider that it may offer useful information for the management of neurocritical patients in general.19,22,23 Close monitoring of the neurological situation would allow early therapeutic actions and interventions, and thus could improve the functional outcome, as suggested by our findings referred to invasive ICP monitoring.

Many studies have evaluated the risk/benefit ratio of early surgical treatment (in the first 12h) versus initial conservative management.13 In this regard, the STICH trial reported no benefit of surgery versus medical treatment.3 Probably in this case the time from ICH symptoms onset to surgery was too long to avoid expansion of the hematoma (median time 30h). On the other hand, 26% of the patients assigned to the conservative treatment arm subsequently experienced neurological worsening and were crossed over to the surgical treatment arm–increasing the median time to 60h.3 In coincidence with our own findings, a metaanalysis published in 2008, with the inclusion of 10 articles, documented a lesser mortality and dependency risk in those patients who underwent surgery.11 Recently, the STICH-2 trial, designed to compare the results of early surgery versus conservative management in patients with lobar hematomas,14 likewise recorded no benefit from surgery following ICH. Probably these results were due to the fact that the patients had a normal level of consciousness and specifically presented lobar bleeding; there consequently was no intracranial hypertension, in contrast to our own series, where the patients probably would benefit from surgery. In any case, it should be noted that the European guides on the management of ICH support the existence of improved functional outcomes in patients subjected to neurosurgical treatment.24

In coincidence with Ruijiun et al.,8 we identified a number of variables related to functional outcome after 6 months: diabetes, the APACHE II score upon admission, initial hematoma volume, and hematoma location at brainstem level. In turn, we identified anticoagulation as a risk factor, in coincidence with other Spanish series, and found early hematoma evacuation to improve the patient prognosis.20

Our study has a number of limitations, including its single-center observational design. Nevertheless, our hospital is a third-level reference center for neurocritical patients. On the other hand, despite adherence to the clinical practice guides, the criterion for surgery in some cases was decided by the neurosurgical team on duty. In turn, the number of deaths during hospital stay, after passing through the ICU, did not allow exhaustive analysis of the factors associated to occult mortality. Lastly, we did not collect precise information on the type of surgical technique employed, and did not include signs of active intracranial bleeding among the radiological criteria.25 Nevertheless, we wish to point out that these aspects will be addressed in future studies. At present, we are conducting a multicenter trial designed to include these variables and contrast the findings obtained.

As strong points of our study, we followed-up on patients at discharge from the ICU and from hospital. In this respect, some studies limit analysis to a 30-day time window, thus preventing the obtainment of data on the evolution of the patients after they leave the hospital center. In turn, although patient recruitment was conducted on a single-center basis and during the period of the study, we consider that the sample size was adequate for a descriptive and exploratory analysis of the characteristics of our population.

In our series, ICH remains a disease with high mortality and poor patient functional outcome. The presence of comorbidities such as diabetes, or previous treatment with anticoagulants, as well as the type of brain CT findings (bleeding at brainstem or intraventricular level, and the presence of repeat bleeding, among others) are predictors of mortality and poor functional outcome, while ICP monitoring and early surgical treatment are associated to improved survival and better functional outcome. In any case, we consider that further research is needed, with the conduction of a multicenter trial, in order to validate our findings and subsequently assess strategies designed to improve the management of patients with severe ICH.

The authors declare that they have no conflicts of interest.