Authors: Matthew K. Whalin, M.D., Ph.D. et al
ASA Monitor 12 2018, Vol.82, 42-44.
Expanded Time Windows for Thrombectomy
During acute ischemic stroke (AIS), the expanding region of irreversibly damaged brain tissue is known as the infarct core. The core is surrounded by the ischemic penumbra, brain tissue that is at risk but salvageable. New imaging techniques identify core and penumbra during AIS and thereby guide patient selection for intervention.
Two recent trials, DAWN and DEFUSE 3, used advanced imaging technology for patients with limited infarct cores who presented much later than six hours after onset. The DAWN trial enrolled patients six to 24 hours since they were last known to be well.1 DEFUSE 3 had broader inclusion criteria for patients presenting six to 16 hours after they were last seen well.2 Both trials showed higher rates of functional independence at 90 days post-stroke for patients who received thrombectomy (>40 percent versus <20 percent). The updated 2018 guidelines recommend thrombectomy for patients presenting between six and 16 hours who meet criteria for either trial.3 Although many patients who present late will not have favorable imaging, these expanded treatment windows will probably lead to an increase in the volume of endovascular stroke procedures.
Sedation vs. General Anesthesia for Stroke Thrombectomy
In seven major trials that helped establish thrombectomy’s superiority over medical therapy, about 70 percent of the intervention patients received sedation as opposed to general anesthesia.4 Meta-analysis of these data suggested that patients receiving thrombectomy under general anesthesia had higher rates of functional independence at 90 days than those who received medical therapy (40 percent versus 31 percent) but lower rates than those who received thrombectomy under sedation (50 percent). The groups seem better matched than those in prior retrospective studies, but selection bias remains a concern.
Three small single-center randomized controlled trials (RCTs) of anesthesia for endovascular therapy have been published and larger trials are under way. First, the SIESTA trial randomized 150 patients in Germany to sedation or intubation.5 The groups received different doses of the same intravenous drugs for maintenance. Independence at 90 days was a secondary endpoint and was achieved in 37 percent of the intubated patients versus 18 percent of the sedated patients (p=0.01). Next, the AnStroke Trial randomized 90 patients in Sweden to sedation with a target-controlled infusion of remifentanil or general anesthesia maintained with sevoflurane and remifentanil.6 They found equivalent rates of functional independence at 90 days for the general anesthesia (42 percent) and sedation (40 percent) groups. Most recently, the GOLIATH Trial randomized 128 patients in Denmark to sedation with fentanyl boluses and low-dose propofol infusions or general anesthesia maintained with propofol and remifentanil.7 In the sedation group, 60 percent of patients were successfully reperfused and just over 50 percent were functionally independent at 90 days. In the general anesthesia group, 77 percent were successfully reperfused and nearly 70 percent were independent at 90 days.
The updated 2018 guidelines recommend thrombectomy for patients presenting between six and 16 hours who meet criteria for either trial. Although many patients who present late will not have favorable imaging, these expanded treatment windows will probably lead to an increase in the volume of endovascular stroke procedures.
It is difficult to reconcile the outcomes in the sedation groups of the anesthesia RCTs with those of the sedation patients in the major thrombectomy trials who had a 76 percent rate of reperfusion.4 Perhaps larger trials underway in China (CANVAS-NCT02677415) and France (GASS-NCT02822144) will provide additional insights.
For now, the 2018 stroke guidelines state that “It is reasonable to select an anesthetic technique during endovascular therapy for AIS on the basis of individualized assessment of patient risk factors, technical performance of the procedure, and other clinical characteristics.”3
Hemodynamic Management During Thrombectomy
Preserving the ischemic penumbra is critical whether thrombectomy is performed under sedation or general anesthesia. Decreases in blood pressure may compromise collateral flow to the penumbra and lead to expansion of the infarct core, but extreme hypertension (systolic >180 mmHg or diastolic >105 mmHg) may increase the risk of hemorrhage. The optimal blood pressure during thrombectomy probably varies from one patient to the next and remains an active research question. A landmark study by Davis and colleagues identified an association between lowest systolic blood pressure below 140 mm Hg and poor 90-day outcomes.8 Many centers, therefore, follow the Society for Neuroscience in Anesthesiology and Critical Care consensus statement by targeting a systolic blood pressure between 140 and 180 mmHg prior to reperfusion.9 It may make more sense to keep blood pressure near the patient’s pressure on presentation. One study in sedated patients found that maintaining MAP within 10 percent of the baseline value was strongly associated with good outcomes.10 In contrast, the GOLIATH investigators were unable to demonstrate a link between blood pressure and outcome.11 This may be because the duration of hypotension was quite short, especially in the general anesthesia group. Whatever goals are chosen, vigilance and aggressive treatment of decreases in blood pressure likely give patients the best chance of a good outcome.
References:
1. Nogueira RG, Jadhav AP, Haussen DC, et al; for DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11-21.
2. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-718.
3. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018; 49(3):e46-e110.
4. Campbell BCV, van Zwam WH, Goyal M, et al. Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurol. 2018;17(1):47-53.
5. Schönenberger S, Uhlmann L, Hacke W, et al. Effect of conscious sedation vs general anesthesia on early neurological improvement among patients with ischemic stroke undergoing endovascular thrombectomy: a randomized clinical trial. JAMA. 2016;316(19):1986-1996.
6. Löwhagen-Hendén P, Rentzos A, Karlsson JE, et al. General anesthesia versus conscious sedation for endovascular treatment of acute ischemic stroke: the AnStroke Trial (Anesthesia During Stroke). Stroke. 2017;48(6):1601-1607.
7. Simonsen CZ, Yoo AJ, Sørensen LH, et al. Effect of general anesthesia and conscious sedation during endovascular therapy on infarct growth and clinical outcomes in acute ischemic stroke: a randomized clinical trial. JAMA Neurol. 2018;75(4):470-477.
8. Davis MJ, Menon BK, Baghirzada LB, et al; for Calgary Stroke Program. Anesthetic management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology. 2012;116(2):396-405.
9. Talke PO, Sharma D, Heyer EJ, Bergese SD, Blackham KA, Stevens RD. Society for Neuroscience in Anesthesiology and Critical Care Expert consensus statement: anesthetic management of endovascular treatment for acute ischemic stroke*: endorsed by the Society of NeuroInterventional Surgery and the Neurocritical Care Society. J Neurosurg Anesthesiol. 2014;26(2):95-108.
10. Whalin MK, Halenda KM, Haussen DC, et al. Even small decreases in blood pressure during conscious sedation affect clinical outcome after stroke thrombectomy: an analysis of hemodynamic thresholds. AJNR Am J Neuroradiol. 2017;38(2):294-298.
11. Rasmussen M, Espelund US, Juul N, et al. The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke. Br J Anaesth. 2018;120(6):1287-1294.
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