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Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes. A Secondary Analysis of the ATACH-2 Randomized Clinical Trial. 

Presented by Dr Jonathon Slater


In patients with intracerebral haemorrhage (ICH) is there an interaction between underlying small vessel disease (number of microbleeds and location) and intensive systolic blood pressure (SBP) control which may lead to a worse functional outcome or significant haematoma expansion?


Systolic blood pressure control in spontaneous ICH is frequently managed on or about 140mmHg (range 120mmHg – 160mmHg) and differs depending on the aetiology, location, and other medical comorbidities. The 120mmHg – 160mmHg range is within current research guidelines and recommendations. 


Specifically, there is little known about cerebral microbleeds. It is known that these microbleeds are remnants of prior micro-haemorrhages at the level of arterioles and capillaries and that such events can be visualised on T2 weighted (blood-sensitive) GRE MRI scans. In addition, these microbleeds are markers of underlying cerebral small vessel disease usually representing hypertensive arteriopathy.

There are two competing theories as to the impact of these microbleeds in ICH: 

  1. The fragility of cerebral microbleeds may increase the risk of haematoma expansion (and therefore increase the burden of injury).
  2. The vessels become more resilient over time and are therefore somewhat protective against further expansion. 

Haematoma expansion occurs early – usually within the first few hours and as much as a 10% increase can have a devastating effect. The jury is still out on the level of blood pressure reduction that provides the greatest benefit for reducing hematoma expansion. There is however, greater research, evidence, and understanding of the ‘general principals and management of ICH’:

  1. ICH is graded (Lisk) into 4 categories:
    1. 0 = No Intraventricular haemorrhage (IVH).
    1. 1 = Blood in the 3rdventricle or <1/3 of 1 lateral ventricle
    1. 2 = Blood in <1/2 of both lateral ventricles or 2/3 of 1 ventricle
    1. 3 = 1 ventricle completely filled or 2 more than 50% filled
  • Poorer outcomes for ICH are frequently seen with
    • Haematoma expansion 
    • ICH volume >60mls
    • IVH extension
    • ICH in certain areas (eg: cerebellum – requiring a high neurosurgical intervention; pons – 100% mortality) 
    • Low GCS <5 (and less researched)
  • Studies tend to remove those at highest risk – ICH has an on or about 20% mortality at 24 hours. The major RCTs exclude on or about 9 in 10 patients and as such generalisation/applicability of the results may be difficult. 
  • Early treatment of ICH has a positive impact – for instance, patients <70 years of age, with small ICH (<5mls), without IVH, and treated within 2.5 hours were shown to have reduced haematoma expansion and a ‘favourable’ OR for poor outcome of 0.28 at 90 days (FAST trial). The journal club today will look at the interplay of rapid initial treatment, prevention of haematoma expansion, and the effect of cerebral microbleeds. 
  • There are often difficult and competing risks – intracerebral pressure (ICP) in traumatic ICH may limit blood pressure targets and where there is suspicion of elevated ICP, CPP of 60-80mmHg is recommended and relaxing the lowering of BP targets may be needed.
  • Blood pressure is frequently elevated in acute non-traumatic ICH. Most research suggests 140mmHg is a reasonable systolic target although the INTERACT2 trial provides a cautionary tail that lower blood pressure (SBP <140mmHg) may improve functional outcomes. Ordinal analysis of Rankin scores (rather than ‘favourable’ vs ‘unfavourable’ scores) and quality of life scores were improved in the more intensive therapy group. However, many patients received mannitol (ICP monitoring data was not provided) and the use of specific antihypertensives not available in all countries may reduce the external validity. Further, whilst the use of multiple different antihypertensive agents was pragmatic in the trial, there may be some benefit from specific antihypertensives via non blood pressure pleiotropic effects that may have affected the results. 
  • The ATACH-2 trial showed no difference between Intensive and ‘Standard’ blood pressure treatment strategies for the first 24 hours on functional outcome at 3 months or haematoma expansion. The study ended early due to futility. Greater renal adverse events at 7 days were noted in the intensive therapy group.
  • Commonly used medications include, but are not limited to labetalol, hydralazine, nicardipine, clevidipine, and phentolamine.


Understanding whether cerebral microbleeds require greater blood pressure control will improve our appreciation of both the pathology and management of ICH with concurrent small vessel disease. More broadly speaking it will also help smaller centres to align their practices with tertiary and quaternary referral centres. 


  1. Is there an interaction between underlying small vessel disease and intensive systolic blood pressure (SBP) control for functional outcome and haematoma expansion?
  2. Blood pressure targets in ICH and exceptions to general rule
  3. The high level of practice variation
  4. Differences between the ATACH-2 and INTERACT2 trials


No! As we will discuss at the journal club, cerebral microbleeds did not appear to have an impact on functional outcomes or mortality. Additionally, their presence was not associated with haematoma expansion or response to blood pressure management. 

Journal Club: BREATHE (JAMA 2018)

Effect of Protocolised Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure

JAMA, 2018. doi:10.1001/jama.2018.13763


Presented by Dr Joel Davis, ACCS CMT


In adults in whom weaning from invasive mechanical ventilation is “difficult” (ie a spontaneous breathing trial has failed), does protocolised weaning with early extubation to non-invasive ventilation reduce time to liberation from ventilation, compared with protocolised invasive weaning?


Invasive mechanical ventilation is one of the most common lifesaving interventions performed on our unit, but prolonged ventilation is associated with increased morbidity and mortality.

The authors of this paper state that 33% – 86% of invasively ventilated patients are “difficult to wean”, and this concords with our experience on the JVF. To provide a snapshot example, on the unit today we have 13 ventilated patients, of whom 8 have undergone tracheostomy – most of them for actual or anticipated difficulty weaning.

These patients consume a disproportionate amount of our resources. Any intervention that can reduce the morbidity, mortality, length of stay and cost associated with this would be very welcome.


Several previous studies have tried to address this question, but the majority of patients enrolled had COPD. In that cohort, weaning with NIV has been shown to reduce mortality as well as the rates of tracheostomy and ventilator-associated pneumonia (see the meta-analysis by Burns et al However, it is not known whether these results are generalizable to a modern general ICU population, in which fewer COPD patients are now invasively ventilated.



The earlier trials referred to above suggested that weaning to NIV does produce clinically important and statistically significant benefits for patients with COPD, but this does not reflect the case mix of ventilated patients on our ICU, who may have different pathological processes and lung mechanics hampering their weaning.

Importantly, this new trial also sought to mitigate a key source of potential bias by ensuring that both the control and intervention groups underwent protocolised weaning. In most previous studies, a protocol had been adopted only for the intervention group, making it difficult to distinguish whether any beneficial effects arose from the actual intervention or simply from the protocolisation.


  • Considering they had all failed an initial SBT, the patients in both arms of this trial had a surprisingly low duration of mechanical ventilation (2.9 days on average). This may have been because of the strict protocols, that called for weaning assessments q2 hours. It might not be feasible to offer this to every patient on the JVF, but should we at least consider protocolising our weaning plans more consistently?
  • Does it matter that only a small proportion of eligible patients were included (and we don’t know why); or that almost half of the patients were recruited from only 3 centres?
  • Although no benefit was seen in the primary outcome of liberation from all ventilation, the secondary outcome of total invasive ventilation time was reduced. This is surely beneficial – should it alone prompt us to change practice?
  • On the other hand, extubation to NIV did bring with it an increased risk of reintubation – is this a major concern? And what about other risks? (No mortality difference was seen, but the study was inadequately powered to detect one. The authors accept that reintubation is risky – see
  • What are our patients’ preferences?? (MyICUVoice could be very helpful here!)


As explained in an accompanying JAMA editorial (see below), the importance of this paper is in challenging the “dogma” that patients who fail an SBT necessarily require ongoing invasive ventilation. As we all know, reducing the total time that patients spend intubated could have major benefits for both the patient and for our ICU resource allocation, so these results suggest that we should strongly consider extubating to NIV in such cases – provided we recognise and mitigate any potential risks, particularly the increased risk of reintubation.

In fact, on the JVF we are increasingly extubating patients onto high-flow nasal oxygen (HFNO) when we anticipate that they will require extra support. In a 2016 paper, Hernandez et al showed HFNO to be non-inferior to NIV for patients they defined as ‘high-risk’ (although they had not necessarily actually failed a SBT). So, could HFNO provide another alternative strategy for extubating patients who fail their SBT?

The questions we should consider going forward are:

  • In spite of the negative results of this trial, are there cohorts of patients who would be liberated from ventilation more quickly if extubated to NIV after failing an SBT?
  • Even if the answer is no, should we consider it anyway, to reduce the time (and associated risk, resources etc) of invasive ventilation? Or is the reintubation risk unacceptable?
  • Whenever we find ourselves considering extubation to NIV, could we achieve comparable outcomes with HFNO instead? (More resource-friendly and almost certainly a less traumatic experience for the patient!)



A nice editorial of this article and its importance –


2013 meta-analysis of previous trials –


Summary of the Hernandez trial (HFNO in high-risk patients) –

And a useful lit review on the same topic –