Effects of Post-operative Sedation on Clinical Outcomes in Patients Receiving Endovascular Thrombectomy for Acute Ischemic Stroke

Theoretically, general anesthesia (GA) has profound brain protection potential, because it can induce a sedative status in patients, reduce brain tissue metabolism and oxygen consumption, inhibit neuro-excitotoxicity, and decrease the core body temperature to a certain degree. All these features indicate GA may possess neuro-protective properties and should be beneficial to ischemic brain, i.e., patients with acute ischemic stroke (AIS).

However, in the clinics, application of GA is limited in intra-operative period, which corresponds to only part of the ischemic period, in AIS patients undergoing endovascular thrombectomy (ET) surgery. Several recent well-designed RCT studies demonstrated that patients who underwent the surgery under GA achieved a more favorable functional outcomes at 3 months compared with those having the surgery without GA and the better outcome was mainly a direct effect of GA per se. Meanwhile, it is worth noting that, although recent studies tend to favor certain potential benefits of GA for patients undergoing ET surgery, the protective effects of GA uncovered by these trials seem consistently weak. Why? We speculate that this is mainly due to the short exposure time to GA. Around 2 hour-implementation of GA during the surgery is not long enough to exert obvious protection in such big brain damage. Ideally, GA would provide maximum protection effect if the AIS patients could receive sedation once they are diagnosed, i.e., before, during and after the ET surgery, which seems practically impossible. More feasibly, we propose that a prolonged exposure to GA in AIS patients undergoing ET, which includes both ischemic and reperfusion periods, would result in considerable improvements in these patients.

Therefore, considering the safety and feasibility of modern anesthetic technique, we intend to conduct a multi-center, prospective, randomized, controlled clinical trial to investigate whether prolonged Post-Operative Sedation would benefit AIS patients undergoing Endovascular Thrombectomy on their clinical outcomes (POSET). Patients who achieve successful reperfusion after ET surgery under GA will be randomly assigned to control group or post-operative sedation group, in which, the control group will recover from GA immediately after the surgery, whereas those assigned to the post-operative sedation group will receive mechanical ventilation under sedation for another 6 hrs before extubation. The primary outcome is the score on the mRS at around 90 days after randomization. The current study may provide new therapeutic strategy, which is both practical and safe for neuroprotection in AIS patients.

Sample size is calculated according to the results of previous studies and our previous experience. We assume distribution of mRS scores at 90 days after surgery in the control group is: 0: 4.6%; 1: 12%; 2: 10.7%; 3: 20%; 4: 19.3%; 5: 8.7%; 6: 24.7%. For the intervention group, based on our previous experience, we assume that the common odds ratio (cOR) value is 1.4, which corresponds to a difference of 7 percent points between the patients in the intervention group who have a mRS score in the range of 0~2 and those in the control group. After 5000 times of simulation using Monte Carlo, a sample size of 1152 subjects can provide a power of 90%.

Interim analysis will be carried out when 25%, 50% and 75% of patients have been enrolled, respectively. The termination rule for efficiency is defined by using the Pocock analog boundaries. Three interim analysis will increase the sample size by 1.027, therefore making the sample size 1152×1.027=1184. Taking into account a 8% dropout rate, a final sample size of 1286 is needed, 643 per arm.