Pouya Tahsili-Fahadan, MD
This article tackles a very important and popular question since the introduction of Mechanical Thrombectomy (MT) for treatment of acute ischemic stroke: Sedation. Endotracheal intubation and anesthesia may be indicated regardless of MT for airway protection and in those with acute respiratory failure after stroke. In other patients, however, risks versus benefits of general anesthesia (GA) versus conscious sedation are less clear. Multiple earlier reports had pointed towards the choice of sedation as a potential factor in patients’ outcomes after MT with a majority of them favoring GA. Accordingly, the American Heart Association recommended “it might be reasonable to favor conscious sedation over general anesthesia during endovascular therapy for acute ischemic stroke” (Powers et al., Stroke 2015).
Twenty-two previous reports, including 3 randomized control trials, with a total of 4716 patients, were included in this meta-analysis. 1819 patients (38.5%) underwent GA. The primary end-point of the study was good functional outcome defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days after MT. GA group was associated with lower odds of good functional outcome (OR, 0.58; 95% CI, 0.48–0.64) along with higher odds of mortality (OR 2.02; 95% CI, 1.66–2.45), vascular complications (OR, 1.43; 95% CI, 1.01–2.03), and respiratory complications (OR, 1.70; 95% CI, 1.22–2.37) in comparison to patients in the non-GA group. Although symptomatic hemorrhagic conversion was more common among patients in the GA group, it did not reach statistical significance (OR, 1.43; 95% CI, 0.85–2.39).
Several theories have been proposed for the deleterious effects of GA. Higher National Institutes of Health Stroke Scale (NIHSS) at baseline is a known factor for worse functional outcomes. Therefore, higher baseline NIHSS in patients undergoing GA can justify these findings. However, after adjustment for baseline NIHSS, GA was still associated with lower odds of mRS 0-2 (OR 0.59; 95% CI, 0.29–0.94) and higher odds of death (OR, 1.80; 95% CI, 1.23–2.68), although this approach cannot completely rule out the possibility of selection bias towards GA for patients with more severe strokes. Another proposed mechanism is the increased risk of intra-procedural hypotension and, hence, cerebral hypoperfusion associated with GA (Lowhagen Henden et al., Stroke 2015 and Whalin et al., AJNR 2017). Consistent with this hypothesis, GA and non-GA patients had similar functional outcomes in studies that had reported hemodynamic stability during GA (John et al., Cerebrovasc Dis 2014 and Schonenberger et al, JAMA 2016). Delayed treatment associated with GA can also result in worse outcomes (Berkhemer et al., Neurology 2016). On the other hand, one may argue that GA may result in faster and more successful recanalization. In this report, time to groin puncture was longer in the GA group (weighted mean difference, 14.18 minutes), but procedure time was faster (weighted mean difference, −4.63 minutes). Besides, successful recanalization was not different between GA and non-GA patients. GA may also be associated with fewer vascular complications (secondary to patient movement) or respiratory complications associated with emergent intubation. Nevertheless, neither of these complications was more common in the non-GA group based on the current results, and the overall rate of conversion from non-GA to GA group was only about 3%.
A few important things need to be considered in interpretation of these results. First, introduction of stentriever and aspiration devices have revolutionized acute treatment of stroke and resulted in higher rates of recanalization with better functional outcomes. Therefore, it is more important and relevant to determine GA-related outcomes in the modern MT era. Accordingly, authors of the current meta-analysis performed a sensitivity analysis to compare effects of GA on outcomes between the pre- and post- stentriever/aspiration thrombectomy eras. Sensitivity analysis confirmed the association of GA with worse functional outcomes and mortality for the pre-stentriever/aspiration thrombectomy era (OR, 0.44; 95% CI, 0.37–0.52 and (OR, 2.69; 95% CI, 2.11–3.45, respectively). But importantly, no statistically significant association was found for GA with poor functional outcomes and mortality in the modern stentriever/aspiration thrombectomy era (OR, 0.84; 95% CI, 0.67–1.06 and OR, 1.27; 95% CI, 0.93–1.75, respectively).
Another important consideration is that a majority of the data in regard to GA-related outcomes is provided by observation and retrospective studies. Interestingly, when only randomized controlled trials were included in the sensitivity analysis, GA group had even higher odds of favorable neurological outcomes (OR, 1.83; 95% CI, 1.18–2.84). However, generalization of these results also needs to be approached very cautiously. These randomized trials enrolled a relatively small number of cases at single institutions. Most importantly, highly specialized anesthesiologists and neurointensivists conducted GA in these randomized controlled trials with short procedural delays and very low rate of intra-procedural hypotension. Such levels of expertise may not be readily available in many centers performing MT. In addition, higher rates of conversion from the non-GA to GA group were seen in these trials (Lowhagen Henden et al, Stroke 2015 and Schonenberger et al, JAMA 2016) that can increase onset-to-reperfusion times and procedural complications and thereby exaggerate the outcomes in the non-GA patients on intention to treat analysis.
Effect of GA on outcomes of posterior circulation strokes is even less clear. In fact, the benefits of modern MT in the posterior circulation strokes are not well established in contrast to the anterior circulation. All 3 randomized controlled trials included in this meta-analysis had only enrolled patients with anterior circulation strokes, while the observational studies had more patients with posterior circulation strokes. However, a recent study (Bouslama et al., Stroke 2017) did not find a significant effect for GA on outcome of patients undergoing MT for posterior circulation strokes on multivariate analysis. At the end, we still need larger multi-central randomized trials to determine the best sedation strategy during mechanical thrombectomy.