- Explore the data for safety and efficacy of urgent blood pressure lowering in hemorrhagic stroke.
- Is there any benefit from management of elevated blood pressure in acute ischemic stroke that is not a candidate for tPA?
- What is the data for blood pressure target in subarachnoid hemorrhage awaiting definitive management?
PART 1: Hemorrhagic stroke
- Elevated BP is very common in acute hemorrhagic stroke
- There is an association with elevated BP and:
- Increase in hematoma size
|Qureshi A, Palesch Y, Barsan W, Hanley D, Hsu C, Martin R et al. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. New England Journal of Medicine. 2016;375(11):1033-1043.|
- Large randomized, multi-centere, open label, international study
- Like INTERACT, the outcome assessors were blinded
- N was 1000 – stopped early for futility of primary outcome
- Compared intensive 110-139 systolic vs 140-179 systolic
- Initially included from 3 hours of onset, increased to 4.5 hours
- Primary outcome was death or major disability
- sBP >240 x 2 measurements
- known neoplasm/AVM/aneurysm
- candidate for immediate neurosurgical intervention
- not a ICU candidate.
This study was more standardized in terms of drug usage with IV nicardipine being used as first line and labetalol added if BP target not reached within 30mins.
They screened 8500 patients and recruited 1000 patients. The initial goal was 1280. The mean SBP on presentation was just over 200 systolic. The baseline characteristics were very similar to both groups.
Comparing this population to the INTERACT study they were less sick with 56% having a GCS of 15.
The INTERACT study also included patients with lower BP whereas to be included in this study your arrival BP had to be >180.
The other very important point here is the mean hematoma volume. Dr Dowlatshahi has looked at a few studies in terms of the natural progression of these small volume hematomas and it seems that under 10 cc these hematomas don’t tend to expand, so they may not be the ones to benefit from rapidly decreasing the BP.
The mean interval between symptom onset and randomization was 182.2 minutes in the intensive-treatment group and 184.7 minutes in the standard-treatment group. So this was good because they got patients early in the window under 6 hours where hematoma expansion occurs.
The mean values of hourly minimum systolic blood pressure for the first 24 hours after randomization according to treatment group are shown above in Figure. 1. The mean systolic blood pressure during the first 2 hours was 128.9 in the intensive treatment group 141.1 in the standard-treatment group.
This is really important, Essentially what this trial was looking at was guideline treatment <140 versus very aggressive therapy. Once people saw it was safe to drop to <140 from the INTERACT study they did so.
This was a negative study which was stopped early for futility for the primary outcome which was death or disability which was seen 38.7% of the intensive group vs 37.7% of the standard group for an Relative Risk of 1.02.
If you look at the remainder of the secondary outcome there was no statistical difference in Death, Neurological deterioration in the first 24 hours or serious adverse events (SAE) within the first 72 hours.
There was a statistical difference in SAE at 3 months which was worse in the intensive group which was driven mainly by worse renal function in that group.
Having a look at the modified Rankin scores between the 2 groups they are roughly comparable.
So overall this study was negative but with a caveat in that the ‘less intensive group’ was actually treated quite aggressively to reduce their BP.
From speaking with Dr. Dowlatshahi, one of our Stroke Neurologists at The Ottawa Hospital, his opinion is that, unfortunately, we have 2 negative trials looking at aggressive BP reduction so likely the next practice guidelines will say to aim for BP < 180.
There is a population of patients who likely would benefit from rapid acute BP management. What number to aim for will depend on the patient. If there is a small volume hematoma < 10cc in a stable patient then < 180 is reasonable, If there is a large volume hematoma, if it is near ventricles or the patient is worsening then a more aggressive target would be reasonable: He would choose <160 and states some of his more aggressive colleagues may choose <140.
From an ICU perspective, I spoke with ED physician and intensivist at TOH/The Monfort Hospital, Dr Andy Pan. Obviously sBP has limitations and there has been a fair bit of talk in the ICU world about the use of ICP monitors and cerebral oxygenation monitors. That being said we aren’t going to have the benefit of those in the ED and his target would be to target 140-160.
- Standard therapy should target systolic BP <180
- Consider <160 in large hematomas/worsening clinically/sick enough for ICU
- I would say the current guidelines have this one incorrect. There is insufficient evidence to rapidly reduce to < 140 systolic
PART 2: Ischemic Stroke
What to do about BP control in ischemic stroke that is not TPA eligible?
- is commonly elevated
- Usually transiently
- Likely secondary to both the stroke and non-stroke factors
- 2011 Lancet Study
- 9 Northern European Countries
- Double blind RCT
- Looked at candesartan vs placebo in acute ischemic and hemorrhagic stroke
- Single Blind RCT
- Used multiple antihypertensives
- 2014 study in JAMA
- Primary outcome was death or major disability at discharge or 14 days
- Target reduce BP by 10-25% in first 24 hours
PART 3: Aneurysmal subarachnoid hemorrhage
What do the guidelines say?
Edited, Formatted and References by Dr. Rob Suttie, PGY2, Emergency Medicine