Journal Club Podcast #31: October 2016
A short discussion of optimal blood pressure management in ICH, looking at intensive BP control vs. guideline-based control...
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Article 1: Tsivgoulis G, Katsanos AH, Butcher KS, Boviatsis E, Triantafyllou N, Rizos I, Alexandrov AV. Intensive blood pressure reduction in acute intracerebral hemorrhage: a meta-analysis. Neurology. 2014 Oct 21;83(17):1523-9. Answer Key.
Article 2: Qureshi AI, Palesch YY, Barsan WG, et al; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43. Answer Key.
Article 4: Anderson CS, Heeley E, Huang Y, et al; INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013 Jun 20;368(25):2355-65. Answer Key.
It's a slow Sunday morning in TCC when you get a page that a fifty-year-old patient with a sudden onset of confusion is en route. Per the page, the patient's BP is 210/110, with a heart rate of 85. The patient arrives to the ED awake, alert, but clearly confused. He answers all questions inappropriately and only follows commands with repeated questioning. His BP is still elevated (208/113).
After getting a finger-stick blood sugar, which is 105, a normal ECG, and sending off labs, you rush the patient for a head CT. The CT shows an intraparenchymal hemorrhage in the left basal ganglia without intraventricular extension. The volume of blood is about 30 mL.
You immediately place a consult to neurology while the patient is transported back to the room. The nurse rechecks the patient's BP, which is now 218/115, and asks what you would like to do to treat this hypertension. You remember learning that when managing BP in intracerebral hemorrhage (ICH) there is a balance between reducing further bleeding and perfusing the rest of the brain, but you aren't sure what the optimal goal BP is or how quickly you should try and achieve this goal. After discussing this with the neurologist, you decide to do a quick literature search and see what the evidence shows...
Population: Adult patients with spontaneous ICH and elevated BP
Intervention: Aggressive lowering of blood pressure
Comparison: Standard lowering of blood pressure (i.e. SBP below ~180 mmHg)
Outcome: Death, functional status, quality of life, cost, length of stay
A PubMed “Clinical Queries” search was performed using the terms “intracerebral hemorrhage” AND “blood pressure” with category set to Therapy and scope to Broad. The search was then limited to studies published in the last 5 years using human subjects (http://tinyurl.com/zhj7zgs). This strategy resulted in 143 articles, of which 3 randomized controlled trials and 1 meta-analysis were chosen. The Cochrane database of systematic reviews was also searched, but did not identify an additional meta-analysis.
Optimal blood pressure management in patients with spontaneous intracerebral hemorrhage (ICH) is complicated by the balance between hematoma size and cerebral perfusion. An association between maximum systolic blood pressure and hematoma enlargement has been shown (Ohwaki 2004), but must be tempered by the opposing risk of reduced cerebral blood flow with overly aggressive reductions in blood pressure (Butcher 2003). A small study published in 2013, however, found no difference in relative perihematoma blood flow in patients treated with more aggressive BP goals (SBP < 150 mmHg) compared to traditional goals (SBP < 180 mmHg). This finding opened the door to further clinical research on the effects of aggressive BP lowering in ICH.
In 2010, the AHA guidelines for management of ICH suggested that in patients with significantly elevated blood pressure (SBP > 180 or MAP > 130), a “modest reduction” in BP should be considered (SBP < 160, MAP < 110). This arbitrary BP goal was challenged in 2013 by the publication of the INTERACT2 trial. This seminal trial compared traditional BP management to more intensive BP lowering (goal SBP < 140 mm Hg within one hour), and found no statistically significant improvement in the primary outcome of functional status. The authors performed a post hoc analysis of the data, however, and did find an improvement in functional status using the newly popularized “ordinal analysis” of the data. This finding spurred further debate, resulting in additional studies on this subject.
A meta-analysis published in 2014 sought to shed further light on this subject, pooling the results of the INTERACT2 trial with its pilot study (INTERACT1), the ICH ADAPT study, and one additional study that lacked the funding to devise a kickass acronym. This meta-analysis confirmed the results of the INTERACT2 trial, which is far from surprising when you consider that the vast majority of patients (~85) came from that particular study.
Earlier this year, the ATACH-2 trial was published. Using similar methodology to the INTERACT2 trial investigators, the authors of this international, multi-center trial also found no statistically significant improvement in functional outcomes with more aggressive BP reduction, thereby confirming the prior results of INTERACT2 and the pursuant meta-analysis.