SGEM#413: But Even You Cannot Avoid…Pressure – Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage

Date: August 14, 2023 Reference: Ma et. al. The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial. Lancet 2023 Guest Skeptic: Dr. Mike Pallaci is a Professor of Emergency Medicine (EM) for the Northeast Ohio Medical University, and an Adjunct Clinical Professor of EM for the Ohio University Heritage College of Osteopathic Medicine. He has been program director for two EM residency programs, and is currently a core faculty member for the EM residency at Summa Health System in Akron, OH, where he also serves as the Medical Director of the Virtual Care Simulation Lab. This episode originated because of a thread Mike posted on the social media site formerly known as Twitter.  The tweet said: “I am sick and tired of some non-EM docs/specialists slamming EM when we don’t aggressively lower BP in ICH.” It certainly got a lot of attention. It got a lot of attention both on the positive side (mostly from EM docs who share the frustration) and on the negative side from some neurologists who didn’t seem to particularly care for the premise of the tweet or for the generally positive response. It started out with venting on Twitter about an unpleasant interaction with one of Mike's partners and turned into a week-long discussion that culminated in an invitation to be the guest skeptic on the SGEM to critically appraise INTERACT-3. Mike backed up his position on blood pressure (BP) lowering using evidence. Specifically, he pointed out that the evidence behind the guidelines re BP management in intracranial hemorrhage (ICH) is relatively weak. This received a mixed response on Twitter. Most EM physicians shared the frustration and made positive comments. Some neurologists disagreed with the premise of the tweet and challenged it. I responded by posting the 2013 SGEM episode on INTERACT-2 (SGEM#73) which showed no statistical difference between intensive (<140 mmHg) and guideline directed (<180 mmHg).  In 2017, the SGEM reviewed the ATACH-2 trial (SGEM#172) which showed similar results. A meme was also posted of Charlton Heston from the classic movie the Ten Commandments. It emphasized that GUIDElines are not GODlines. The literature should inform and guide our care, but it should not dictate our care. This is a core principle of evidence-based medicine (EBM). Often the available evidence on a specific medical question is weak. We still need to apply our clinical judgement and ask the patient about their values and preferences. Case: A 67-year-old male presents to the emergency department obtunded with left hemiplegia.  Symptoms began just prior to presentation.  His blood pressure (BP) is 194/110 mmHg.  CT reveals a hemorrhage in the right internal capsule, suggestive of acute hypertensive hemorrhagic stroke.  Should the blood pressure be treated?  If yes, what should the target blood pressure be? How quickly do we want to get there? And are there any other physiologic variables we want to be aggressive about controlling in the early treatment window? Background: We have covered the common issue of elevated BP after ICH on SGEM#73 and SGEM#172. The 2022 AHA/ASA guidelines give several recommendations on this topic. The class (strength) of their recommendation is 2a/2b based upon Level B and Level C quality of evidence.   It is really important to pay attention to the specific language used in the guidelines. First of all, as we’ve already covered, a guideline is something developed by humans giving their best interpretation of the evidence to serve as a guide, not something given to Moses on Mount Sinai. But that point aside, the basis of this discussion was that the strength of the evidence behind these guidelines and the strength of the recommendations in the guidelines themselves are frequently misunderstood and/or misrepresented by our consultants. The specific language used in the guidelines is as follows: “In patients with spontaneous ICH in whom acute BP lowering is considered, initiating treatment within 2 hours and reaching target within 1 hour can be beneficial to reduce the risk of HE and improve functional outcome” They give this a Class 2a recommendation, “Moderate”: is reasonable, can be beneficial; Level of Evidence C-LD (Limited Data). We would say than it would also be reasonable not to acutely lower the BP “In patients with spontaneous ICH of mild to moderate severity presenting with SBP between 150 and 220 mmHg, acute lowering of SBP to a target of 140 mmHg with the goal of maintaining in the range of 130 to 150 mmHg is safe and may be reasonable for improving functional outcomes.” This was a Class 2b recommendation, “Weak”: may be reasonable, may be beneficial, effectiveness not well established; Level of Evidence B-R (Randomized; moderate quality evidence from 1 or more RCTs or meta-analyses of moderate-quality RCTs). Listeners to the SGEM know when the word “may” is used it can be substituted with the phrase “may not” “In patients with spontaneous ICH presenting with large or severe ICH or those requiring surgical decompression, the safety and efficacy of intensive BP lowering are not well established.” Another Class 2b recommendation, “Weak”: may be reasonable, may be beneficial, effectiveness not well established; Level of Evidence C-LD (Limited Data). This does not sound like language describing an intervention that is a “central component of management”. Yet that is what is what many physicians believe the guideline tells us. All you have to do is read the guideline itself to recognize that even the people writing these guidelines, who I would argue are biased toward aggressively treating BP in this scenario, recognize that the answer here is not clear. But when our consultants come to the ED they frequently act as though it is a clear and accepted truth and that this is what we should be doing. Clinical Question: Can the implementation of a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, improve outcomes for patients with acute spontaneous intracerebral hemorrhage? Reference: Ma et. al. The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial. Lancet 2023 Population: Adults patients 18 years of age and older presenting within 6 hours after the onset of ICH Exclusions: Definite evidence that the ICH is secondary to a structural abnormality in the brain or previous thrombolysis. Also, if the attending clinician felt there was a high likelihood that the patient will not adhere to the study treatment and follow-up regimen. Intervention: A goal-directed intensive care bundle protocol correcting hypertension, hyperglycemia, pyrexia and hypercoagulability, with the goal of achieving treatment targets within one hour of initiating treatment and maintaining them for 7 days (or until discharge or death, whichever came first) Comparison: Usual care at the discretion of the treating physician Outcome: Primary Outcome: Functional recovery measured at 6 months according to the modified Rankin Scale (mRS) score and analyzed as an ordinal outcome (shift across all categories) The authors state that one of the “efforts to improve the success of randomized controlled trials in identifying an effective treatment for ICH have included…to extend the assessment of functional outcome beyond the conventional 90 days, because recovery from ICH takes longer than from acute ischemic stroke.” Secondary Outcomes: Functional recovery according to a shift analysis of scores on the National Institutes of Health Stroke Scale (NIHSS) at seven days. Dichotomous mRS outcomes at 6 months 0-2 vs. 3-6 and 0-2 vs. 3-5 (i.e. – major disability in survivors) Death at 6 months Death or neurological deterioration at seven days Health-related quality of life (HRQoL) using the EuroQoL Group 5-Dimension self-report questionnaire (EQ-5D) Residence at six months (own home vs. other) Time to hospital discharge Safety Outcomes: All-cause and cause-specific serious adverse events were recorded for the duration of follow-up. Type of Study: A pragmatic, international (10 countries), multicenter (121 hospitals), blinded endpoint, stepped wedge cluster randomized controlled trial. Authors’ Conclusions: “Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure