MR CLEAN Subanalyses Show Better Acute Stroke Outcomes With Local Anesthesia, Shorter Reperfusion Times

In an effort to better understand what can be done to improve the effectiveness of endovascular therapy for severe stroke, 2 presentations at the International Stroke Conference in Nashville, TN, delved deeper into data from the randomized MR CLEAN trial. One, on February 13, 2015, showed that general anesthesia is associated with worse outcomes than local anesthesia, while the other, on February 12, showed that patients who are not reperfused within 6 hours of symptom onset are unlikely to benefit from the procedure.Take Home: MR CLEAN Subanalyses Show Better Acute Stroke Outcomes With Local Anesthesia, Shorter Reperfusion Times

Published in the New England Journal of Medicine in December 2014, MR CLEAN enrolled 500 patients with proximal arterial occlusion in the anterior cerebral circulation confirmed on imaging who could be treated intra-arterially within 6 hours of symptom onset. Patients were randomized to intra-arterial intervention—catheter-based thrombolysis, mechanical treatment, or both—or usual care. Overall, intervention was favored, at an absolute difference of 13.5% in the rate of functional independence (modified Rankin score [mRS] 0-2), with no differences in mortality or symptomatic intracerebral hemorrhage rates.

General Anesthesia Negates Procedural Advantage

In the first analysis, Olvert A. Berkhemer, MD, of the Academic Medical Center (Amsterdam, the Netherlands), and colleagues assessed the impact of anesthesia type. Of 217 patients in the intra-arterial group who had angiography, 38% were given general anesthesia (defined as intubation combined with IV and/or inhaled anesthetic agents), while the rest received local anesthetics with or without conscious sedation.

Baseline characteristics were similar between the anesthesia groups. Slightly fewer than 5% of patients who initially received local anesthesia were switched to general anesthesia during the procedure. Additionally, general anesthesia was associated with delayed initiation of treatment.

After 90 days, 54% of patients given general anesthesia had at least 1 significant adverse event compared with 42% in the local anesthesia arm. There were no differences between the groups in symptomatic intracranial hemorrhage or mortality during follow-up.

Compared with controls in the overall MR CLEAN trial, patients who received general anesthesia during intra-arterial intervention had similar levels of function at 90 days (adjusted OR 1.09; 95% CI 0.69-1.71). But those who received local anesthesia had better functional outcomes than did controls (adjusted OR 2.13; 95% CI 1.46-3.11; P = .013 for interaction).

Moreover, endovascular therapy resulted in a good functional outcome (mRS ≤ 2) in 38% of the local anesthesia arm vs 23% of the general anesthesia arm (P = .026). Compared with controls in the main trial, intra-arterial intervention with local anesthesia was almost 3 times more likely to result in a good outcome (adjusted OR 2.79; 95% CI 1.70-4.59), while general anesthesia again showed no advantage over usual care.

Dr. Berkhemer concluded: “The effect on outcome that we found in the MR CLEAN trial was not observed in the subgroup of patients treated with general anesthesia.”

The Sooner, the Better

In the other analysis, Puck S. Fransen, MD, of Erasmus Medical Center (Rotterdam, the Netherlands), and colleagues divided all 500 MR CLEAN patients into tertiles based on the time from onset to reperfusion.

There was an interaction between timing and treatment effect in terms of functional outcome (P = .009). The effect of intervention was greatest in those treated within 2 hours (1 in 4 patients benefitted) and leveled out beyond 6 hours (1 in 10 benefitted).

“Patients with reperfusion after 6 hours likely do not benefit from intra-arterial treatment,” the researchers write in an abstract. “The effect of treatment is stronger and chances of reaching independence are better when patients reach reperfusion earlier.”

 


Sources:
1. Berkhemer OA. Impact of general anesthesia on treatment effect in the MR CLEAN trial: a post-hoc analysis. Presented at: International Stroke Conference; February 13, 2015; Nashville, TN.

2. Fransen PS. Time to reperfusion and effect of intra-arterial treatment in the MR CLEAN trial. Presented at: International Stroke Conference; February 12, 2015; Nashville, TN.

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Disclosures
  • Dr. Berkhemer reports receiving grants from AngioCare BV, Covidien/EV3, Medac Gmbh/Lamepro, Penumbra, and Top Medical/Concentric.
  • Dr. Fransen reports no relevant conflicts of interest.

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