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Early Management of Intracerebral Hemorrhage

5th Edition
2015 UPDATE
June 2015

The Canadian Stroke Best Practice Recommendations for Hyperacute Stroke Care, 5th Edition (2015) is published in the International Journal of Stroke (IJS) and available freely online. To access the specific recommendations for Early Management of Intracerebral Hemorrhage and all other sections of the Hyperacute Stroke Care recommendations, please click on this URL which will take you to the recommendations online in the IJS: http://onlinelibrary.wiley.com/doi/10.1111/ijs.12551/full

For the French version of these recommendations, open the appendix at this link :  http://onlinelibrary.wiley.com/store/10.1111/ijs.12551/asset/supinfo/ijs12551-sup-0001-si.zip?v=1&s=cdf3d494242426450aaa522f104ace17857f037a

All other supporting information, including performance measures, implementation resources, evidence summaries and references, remain available through www.strokebestpractices.ca, and not through the IJS.  Please click on the appropriate sections on our website below for this additional content.

Box Seven: Symptoms of Intracerebral Hemorrhage: (updated 2014)

Clinical assessment cannot reliably distinguish intracerebral hemorrhage from ischemic stroke; brain imaging is required.

  • Alteration in level of consciousness (approximately 50%)
  • Nausea and vomiting (approximately 40-50%)
  • Sudden, severe headache (approximately 40%)
  • Seizures (approximately 6-7%)
  • Sudden weakness or paralysis of the face, arm or leg, or numbness, particularly on one side of the body
  • Sudden vision changes
  • Loss of balance or coordination
  • Difficulty understanding, speaking (slurring, confusion), reading, or writing

The classic presentation of ICH is sudden onset of a focal neurological deficit that progresses over minutes to hours with accompanying headache, nausea, vomiting, decreased consciousness, and elevated blood pressure. Rarely patients present with symptoms upon awakening from sleep. Neurologic deficits are related to the site of parenchymal hemorrhage. Thus, ataxia is the initial deficit noted in cerebellar hemorrhage, whereas weakness may be the initial symptom with a basal ganglia hemorrhage. Early progression of neurologic deficits and decreased level of consciousness can be expected in 50% of patients with ICH. (Ramandeep Sahni and Jesse Weinberger; Vasc Health Risk Manag. 2007 October; 3(5): 701–709.)

 

 

 

Rationale

Intracerebral hemorrhage is a life-threatening emergency and requires prompt recognition and action. Intracerebral hemorrhage commonly occurs in about 12 to 15 percent of all stroke patients admitted to Canadian hospitals, and is associated with high rates of early mortality – 25 to 50 percent in the first 30 days. Patients who survive an intracerebral hemorrhage are often left with moderate to severe persistent functional deficits which place a significant burden on families and the healthcare system.

 

 

 

System Implications

  • Timely access to diagnostic services such as neuro-imaging, with protocols for prioritizing potential stroke patients.
  • Timely access to specialized stroke care (i.e. a neuro-intensive care unit) and neurosurgical specialists for hemorrhagic patient management, including rapid referral process if neurosurgical services not available within the initial treating hospital.
  • Access to organized stroke care, ideally stroke units with a critical mass of trained staff and an interprofessional team.
  • Education for pre-hospital, emergency department, and hospital staff on the characteristics and urgency for management of intracerebral hemorrhage

 

 

 

 

Performance Measures

  1. Risk-adjusted mortality rates for intracerebral hemorrhage in-hospital, 30-day and one year (core).
  2. Percentage of intracerebral hemorrhage patients who receive a CT or MRI within 25 minutes and one hour of hospital arrival.
  3. Percentage of intracerebral hemorrhage patients who require surgical intervention.
  4. Percentage of intracerebral hemorrhage patients who experience intraoperative complications and mortality during surgery for intracerebral hemorrhage.
  5. Distribution of functional ability measured by standardized functional outcome tools at time of discharge from hospital.

Measurement Notes:

  • Mortality rates should be risk-adjusted for age, gender, stroke severity and comorbidities
  • Time interval measurements should start from symptom onset of known or from triage time in the emergency department as appropriate.

 

 

 

 

Implementation Resources and Knowledge Transfer Tools

Health Care Provider Information

Patient Information

 

Summary of the Evidence, Evidence Tables and References

Evidence Table 7 Acute Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is the most fatal form of stroke and carries the poorest prognosis for survival and functional recovery. While baseline hematoma volume is a strong predictor of outcome, it is not a modifiable risk factor. In addition, 30-40% of patients will continue to bleed and experience hematoma expansion, which is also a predictor of poor outcome. Risk factors for hematoma expansion may include the presence of “spot sign” (contrast extravasation), early presentation, anticoagulation use and initial hematoma volume. The presence of the spot sign appears to be a strong predictor of hematoma expansion. In the PREDICT study, (Demchuck et al. 2012) CT scans were conducted on 268 patients to estimate the volume of ICH at baseline and follow-up and then to determine if hematoma expansion had occurred (defined as an absolute growth greater than 6 mL or relative growth of ≥33%). CT angiography (CTA) was used to determine presence/absence of the spot sign using standardized, accepted criteria. Hematoma expansion occurred more frequently in the spot-sign positive patients (60.7% vs. 21.6%, p<0.001). After adjusting for baseline factors, positive spot sign on CTA remained an independent predictor of hematoma expansion (RR=2.3, 95% CI 1.6 to 3.1). Delgado Almandoz et al. (2009) also reported that the spot sign (+/-) was an independent predictor of hematoma expansion in a cohort of 367 patients. Cucchiara et al. (2008) examined 303 patients enrolled in the placebo arm of the CHANT study to determine the effect of previous and current use of oral anticoagulant (OAT) use. Hemorrhage expansion (>33% increase in ICH volume from baseline to 72 hours) occurred more frequently in ICH determined to be of OAT etiology (56% vs. 26%, p=0.006) and mortality was significantly increased in OAT ICH (62% vs. 17%, p<0.001); however, only 21 OAT ICH patients were included. Baseline ICH volume and time to neuroimaging were also independent predictors of absolute change in ICH volume. Baseline serum C-reactive protein levels in excess of 10 mg/L was found to be an independent predictor of hematoma expansion and early neurological worsening among 399 patients admitted to hospital with ICH within 6 hours of symptom onset (Di Napoli et al. 2014). Elevated blood glucose levels, lower body mass index, increased serum creatinine and decreasing cholesterol levels have also been identified as additional independent predictors of changes in hemorrhage volume (Broderick et al. 2007).

One of the few pharmacological treatments available that may help to minimize hematoma expansion is recombinant activated factor VII. Unfortunately, while the results from the two largest trials suggested that treatment decreases hematoma expansion, it remains uncertain whether treatment is associated with improved odds of a favourable outcome at 3 months, or a greater likelihood of being alive.   In the phase II trial (Mayer et al. 2005) including 399 patients, those who had received the drug, particularly at higher doses, had smaller percentage increases in ICH volume from baseline to 24 hours on CT scans. The percentage increase for patients who received placebo, 40, 80, and 160 μg/kg were 29%, 16%, 14% and 11%, respectively. When results from all treatment groups were combined, the percentage of patients who were dead was lower compared with patients in the placebo group (18% vs. 29%, p=0.02), and there were fewer patients with a poor outcome in the treatment group (mRS 3-6) (53% vs. 69%, p=0.004). There were a total of 21 serious thromboembolic events in the combined treatment groups and 2 in the placebo group (p=0.12). There were more serious arterial thromboembolic events among patient in the treatment groups (16 vs. 0, p=0.01). In the phase III, FAST trial (Mayer et al. 2008), patients were randomized to receive placebo, or rFVIIa at a dose of 20 or 80 μg/kg. Compared with placebo there was a smaller mean increase in volume of ICH at 24 hours in patients in the 80μg group (11% vs. 26%, p<0.001), but no significant difference in the mean increase in volume of ICH at 24 hours in patients in the 20 μg group (18% vs. 26%, p=0.08). At 90 days there were no significant differences between groups (20μg vs. 80μg vs. placebo) on any of the clinical outcomes (death, dependency or the combined outcome of death or dependency). Once again, arterial events occurred more frequently in patients in the treatment group (80μg group (8% vs. placebo 4%, p=0.04). A meta-analysis including the results from 5 RCTs, which recruited patients with both spontaneous ICH (sICH) and traumatic ICH reported no benefit of treatment (Yuan et al. 2010). There was no significant overall reduction in mortality associated with treatment (OR=0.86, 95% CI 0.65 to 1.15, p=0.31). In the subset of patients restricted to sICH, the results were also not significant (OR=0.85, 95% CI 0.64 to 1.15, p=0.29). There was a significant increase in the odds of arterial thromboembolic events in the treatment group (OR=2.18, 95% CI 1.13 to 4.19, p=0.02) but not venous events (OR=0.73, 95% CI 0.36 to 1.47, p=0.38). It has been suggested that one of the reasons that treatment did not appear to be beneficial is because of the inclusion of patients who were less likely to suffer hematoma expansion. If so, then better selection criteria are required to identify more appropriate treatment candidates. Since the spot sign has been found to be an independent predictor of hematoma expansion, it is being used as a selection tool in two RCTs, currently recruiting subjects in trials of rFVIIa, STOP-IT and SPOT-LIGHT.

Blood pressure management is another potential method of reducing hematoma expansion. There is some evidence from the INTERACT I study (Anderson et al. 2008) and ATACH I (Quershi et al. 2010) pilot studies that aggressive BP management can attenuate hematoma expansion. The results from INTERACT 2 have recently been reported (Anderson et al. 2013). In this trial, 2,839 patients who had experienced a spontaneous ICH within the previous 6 hours, with elevated BP (150-220 mm Hg) were randomized to receive intensive or standard treatment for 7 days, or until discharge from hospital. Patients in the intensive group were treated with oral agents to achieve and maintain a target BP of <140 mm Hg, within 1 hour after randomization, while patients in the standard treatment group were treated according to best-practice guidelines to maintain a BP<180 mm). At 90 days, 52.0% of patients in the intensive group had experienced a poor outcome (mRS score 3-5) compared with 55.6% of patients in the standard treatment group (OR=0.87, 95% CI 0.75-1.01, p=0.06). There was no significant difference between groups in 90-day mortality (11.9% vs. 12.0%, OR=0.99, 95% CI 0.79-1.25, p=0.96). There was, however, a significant shift towards the distribution of mRS scores favouring less disability among patients in the intensive group (OR=0.87, 95% CI 0.77-1.00, p=0.04).

There are few reports of the outcomes of patients undergoing neurosurgical procedures following supratentorial intracerebral hemorrhage and uncertainty as to whether invasive treatment is beneficial. In the Surgical Trial in Intracerebral Hemorrhage (STICH) conducted in 2005, 1,033 patients with CT evidence of a spontaneous ICH that had occurred within 72 hours were randomized to early (within 24 hours) surgery for evacuation of the hematoma combined with appropriate and best medical treatment or to initial conservative treatment (Mendelow et al. 2005). Later evacuation was allowed if necessary due to neurological deterioration. The primary outcome was a favourable outcome at 6 months. There was no difference in the percentage of patients with a favourable outcome. 26% of patient in the early surgical group vs. 24% of patients in the medical management group, (OR=0.89, 95% CI 0.66-1.19, p=0.414, absolute benefit=2.3, 95% CI -3.2 to 7.7). There was speculation that the null findings may have been attributed, in part, to the inclusion of patients with Intraventricular hemorrhages with poorer prognosis and the late timing of intervention. Therefore, in the Surgical Trial in Lobar Intracerebral Haemorrhage (STICH II) trial (Mendelow et al. 2013), 601 patients were randomized to early craniotomy (within 12 hours) to evacuate haematoma or treated conservatively, following spontaneous superficial intracerebral haemorrhage affecting the lobar region, within 1 cm of the cortex and without ventricular extension, the subgroup of patients thought to be most likely to benefit. While there were no differences between groups in the proportion of patients who experienced a good outcome at 6 months (41% surgical group vs. 38% medical management group; OR=0.86, 95% CI 0.62-1.20, p=0.367) or who had died (18%. surgical vs. 24% medical management, OR=0.71, 95% CI 0.48-1.06, p=0.095), patients with poor prognosis were more likely to have a favourable outcome (OR=0.49, 95% CI 0.26-0.92, p=0.04). In contrast, patients with a good prognosis were no more likely to benefit from early surgery (OR=1.12, 95% 0.75-1.68, p=0.57).

In a Cochrane review (Prasad et al. 2008) included the results from 10 RCTs wherein 2,059 patients with primary supratentorial intracerebral hematoma, confirmed by CT scanning were studied. Patients were treated with surgery (craniotomy, stereotactic endoscopic evacuation or stereotactic aspiration) plus medical management vs. medical management only. Overall, surgery was associated with a reduction in the odds of death or dependency at the end of follow-up (OR=0.71, 95% CI 0.58-0.88, p<0.001) and death (OR=0.74, 95% CI 0.61-0.90, p=0.0026. Steiner et al. (2011) reported on the outcomes of a subset of patients who were recruited for the Factor Seven for Acute Hemorrhagic Stroke Trial (FAST). The main purpose of this trial was to evaluate the effectiveness of recombinant factor VIIa as a treatment for reducing or stopping bleeding following ICH. Despite the fact that patients who were anticipated to require surgery within 24 hours were excluded, 55/851 patients (6.7%) did require surgery for symptoms of neurological deterioration. The authors examined whether surgery improved the odds of a good outcome controlling for a variety of factors, including demographic, comorbid conditions and prognostic variables. Separate analyses were conducted for patients who had received surgery for hematoma evacuation or who had surgery to place an external ventricular drain (EVD). The odds of unfavourable outcome (NIHSS ≥16) at day 90 were significantly elevated for patients in the EVD group (OR=4.77, 95% CI 1.24 to18.30, p=0.02) with a non-significant increase for patients who had hematoma removal (OR=2.68, 95% CI 0.54 to 13.34, p=0.23).

While it is now well-accepted that patients with ischemic stroke admitted to a stroke unit featuring dedicated beds and staff have better outcomes compared with patients admitted to general or less-specialized units, there is also evidence that the subset of patients who have experienced ICH realize the same benefits. In a systematic review, Langhorne et al (2013) included the results from 8 trials in which patients with ischemic and hemorrhagic stroke were randomized to receive care on a stroke unit or an alternative setting. Stroke unit care was associated with significant reductions in the risk of death or dependency (mRS 3-5) (RR=0.81, 95% CI 0.71-0.92, p<0.0001) and death (RR=0.79, 95% CI 0.64-0.97, p=0.02), with no significant interactions based on stroke type. Diringer & Edwards (2001) reviewed the charts of 1,038 patients who had been admitted to either a neuro-ICU (n=2) or a medical and/or surgical ICU (n=40) following ICH and reported that after adjusting for demographics, severity of ICH, and ICU and institutional characteristics, admission to a general ICU was associated with an increase in hospital mortality (OR=3.4; 95% CI 1.65–7.6). Additional independent predictors of higher mortality were advancing age, lower GCS scores, fewer ICH patients treated and smaller ICU size. In contrast, having a full time intensivist was associated with lower mortality rate. Ronning et al. (2001) also reported improved survival during the first 30 days and one year associated with acute stroke unit care. At 30 days, fewer patients in the stroke unit group were dead (39% vs. 63%, adjusted OR=0.40, 95% CI 0.17-0.94). There was no difference in one-year mortality between groups (52% vs. 69%, adjusted OR=0.58, 95% CI 0.24-1.38), or the number of patients discharged home between groups (27% vs. 52%, adjusted OR=1.60, 95% 0.62-4.00).