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Blood Pressure Management in Intracerebral Haemorrhage: when, how much, and for how long? Chloe A. Mutimer1 · Nawaf Yassi1,2 · Teddy Y Wu3,4€7,49
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Abstract
Purpose of Review When compared to ischaemic stroke, there have been limited advances in acute management of intracer-
ebral haemorrhage. Blood pressure control in the acute period is an intervention commonly implemented and recommended
in guidelines, as elevated systolic blood pressure is common and associated with haematoma expansion, poor functional
outcomes, and mortality. This review addresses the uncertainty around the optimal blood pressure intervention, specifically
timing and length of intervention, intensity of blood pressure reduction and agent used.
Recent Findings Recent pivotal trials have shown that acute blood pressure intervention, to a systolic target of 140mmHg,
does appear to be beneficial in ICH, particularly when bundled with other therapies such as neurosurgery in selected cases,
access to critical care units, blood glucose control, temperature management and reversal of coagulopathy.
Summary Systolic blood pressure should be lowered acutely in intracerebral haemorrhage to a target of approximately
140mmHg, and that this intervention is generally safe in the ICH population.
Introduction deterioration, poor functional outcome and mortality [1,
2]. Haemostatic therapy (recombinant factor VIIa [3,
Intracerebral haemorrhage (ICH) accounts for 15–30% 4] or tranexamic acid [5, 6]) are not utilised in clinical
of stroke and has high 30-day mortality of approximately practice with randomised trials showing variable effects
40%, with only 12 to 39% of patients achieving independ- on haematoma expansion, safety, functional outcome
ent functional recovery [1]. While there have been many and mortality. The current mainstay of management in
recent advances in management of acute ischaemic stroke, ICH remains supportive care in a stroke unit, reversal of
there are currently very few treatments for ICH. Acute anticoagulation if appropriate and acute blood pressure
interventions in ICH have targeted haematoma expansion (BP) lowering. Surgical evacuation is typically reserved
(HE), which occurs in up to one third of patients within for selected patients with more severe ICH, particularly
the first 24 h and is strongly associated with neurological lobar, and can result in reduction of ICH volume and
mass effect, and potential mitigation of secondary injury
from iron toxicity and peri-haematomal oedema. The
* Chloe A. Mutimer recently published Early Minimally Invasive Removal
chloe.mutimer@mh.org.au
of Intracerebral Hemorrhage (ENRICH) trial is the only
1
Department of Medicine and Neurology, Melbourne Brain surgical evacuation trial to have shown benefit of hae-
Centre at The Royal Melbourne Hospital, University matoma evacuation on functional outcome (in the group
of Melbourne, Parkville 3050, Australia with lobar haemorrhage) [7]. However, the optimal sur-
2
Population Health and Immunity Division, The Walter gical technique is not known, with ongoing trials inves-
and Eliza Hall Institute of Medical Research, Parkville 3052, tigating minimally invasive techniques currently being
Australia
undertaken. Other surgical procedures such as external
3
Department of Neurology, Christchurch Hospital, ventricular drains and decompression, for significant
Christchurch, New Zealand
hydrocephalus and posterior fossa bleeds, respectively,
4
Department of Medicine, University of Otago, Christchurch, may be performed as life-saving procedures.
New Zealand
Vol.:(0123456789)
, Current Neurology and Neuroscience Reports
Hypertension on ICH presentation is common, and the however, no time specific quality metrics, similar to door-
main rationale for hypertensive therapy is to reduce hae- to-needle time in acute ischaemic stroke, that are specified
matoma expansion and therefore prevent further clinical for care of ICH patients.
deterioration and long-term poor functional outcomes [8••]. More recently, bundled care for ICH, incorporating
However, inconsistent results amongst clinical trials [9 ••, control of BP, blood glucose, temperature and correction
10••, 11] have led to weak recommendations in guidelines of coagulopathy has been supported by the INTERACT3
regarding acute blood pressure therapy [1, 12–14]. Contro- trial [11•], with the primary outcome of ordinal mRS at
versies persist over the target, timing, intensity and agents 6 months improved in the intervention arm (OR = 0.86,
used. This review aims to summarise the recent literature 95% CI 0.76–0.97; p = 0.015). Patients were eligible if
and current guidelines regarding acute blood pressure low- randomised within 6 h of symptom onset and the target
ering in ICH. systolic blood pressure was less than 140mmHg within 1 h
of treatment commencement, although the actual median
time to reach target was 2.3 h (IQR 0.8–8.0 h). In contrast
When? to INTERACT2 and ATACH-2, severe ICH patients were
included. Given the trial design, it is difficult to know how
The principle of “time is brain” from ischaemic stroke has much benefit stemmed from blood pressure control alone.
driven interest in early blood pressure lowering in ICH, The implementation of bundled care and quality metrics,
particularly given that the rate of haematoma expansion has been further supported by an expert consensus state-
is highest in the first 3 h and the amount of haematoma ment in the European Stroke Journal [17] and a “Code
expansion increases the odds of dependence or death [8••]. ICH” article in Stroke [18] with a proposed door-to-first
In the last decade, there have been two randomised clini- antihypertensive time of ≤ 30 min in the former, and a
cal trials and one other international cluster-randomised door-to-target time of ≤ 60 min in both articles.
trial that have investigated early, intensive blood pressure The role of pre-hospital blood pressure management
control on long-term clinical outcomes in ICH (Table 1). has also been explored. RIGHT-2 (Prehospital transdermal
Both the INTERACT2 (Intensive blood pressure Reduc- glyceryl trinitrate in patients with ultra-acute presumed
tion in Acute Cerebral Haemorrhage Trial) and ATACH-2 stroke) and MR ASAP (Prehospital transdermal glyceryl
(Antihypertensive Treatment of Acute Cerebral Haemor- trinitrate in patients with presumed acute stroke) were both
rhage) trials aimed for a reduction in systolic blood pres- ambulance-based trials of topical nitrates for presumed
sure (SBP) for patients presenting within 6 h and 4.5 h acute stroke (ischaemic and haemorrhagic) with neutral
of symptom onset respectively, but included on average overall outcomes (ordinal mRS at 90 days). Additionally,
patients with mild-moderate severity ICH with relatively there was suggestion of harm in ICH in both trials, which
small baseline haematoma volume [9••]. INTERACT2 lead to early termination of MR ASAP [19, 20]. Given
aimed for blood pressure to be at target after 1 h. Both these findings, management of hypertension in suspected
trials did not meet their primary outcome of improving stroke in the pre-hospital setting is not recommended.
functional outcome at 90-days, although INTERACT2 The advent of mobile stroke units allows for ultra-early
showed a positive effect on ordinal mRS analysis (pooled diagnosis and intervention for all stroke types, including
OR = 0.87, 95% CI 0.77-1.00, p = 0.04). There was no blood pressure control in ICH [21]. This has been formally
clear benefit found for those randomised in the early time investigated in a sub-study of the B_PROUD (Berlin_Pre-
window (< 4 h) compared to a late time window (≥ 4 h). hospital Or Usual Care Delivery in acute Stroke) study
Additionally, neither trial showed a statistically signifi- [22], where ICH patients were prospectively evaluated
cant effect on reducing haematoma expansion. A post- and compared to patients seen by conventional ambu-
hoc analysis of ATACH-2 did show benefit in achieving lance. This study had small patient numbers and was a
functional independence (modified Rankin Scale [mRS] neutral study, although the primary endpoint was mor-
0–2) and reducing haematoma expansion in the ultra-early tality at 7 days (aOR = 1.43, 95% CI 0.68–3.31), rather
(2 h) and “fast-bleeding” (haematoma growth > 5 ml/hr) than functional outcome. It was shown that systolic blood
treatment groups [15, 16]. Current best practice guideline pressure was lower for the MSU cohort on hospital arrival
recommendations are based on these trials, with Ameri- (161mmHg vs. 177mmHg), but there was no improve-
can Heart Association/American Stroke Association and ment in the secondary endpoint of mRS ≥ 3 outcome
European Stroke Organisation guidelines providing weak (aOR = 1.21, 95% CI 0.56–2.61). Further data is needed to
recommendations with the aim to institute blood pressure determine the efficacy of ultra-early blood pressure man-
lowering within 2 h of symptom onset (Table 2). There are, agement for ICH in the mobile stroke unit setting.
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