Thrombectomy with Conscious Sedation Compared with General Anesthesia: A DEFUSE 3 Analysis.

BACKGROUND AND PURPOSE: The optimal patient sedation during mechanical thrombectomy for ischemic stroke in the extended time window is unknown. The purpose of this study was to assess the impact of patient sedation on outcome in patients undergoing thrombectomy 6-16 hours from stroke onset. MATERIALS AND METHODS: Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) was a multicenter, randomized, open-label trial of thrombectomy for ICA and M1 occlusions in patients 6-16 hours from stroke onset. Subjects underwent thrombectomy with either general anesthesia or conscious sedation at the discretion of the treating institution. RESULTS: Of the 92 patients who were randomized to intervention, 26 (28%) underwent thrombectomy with general anesthesia and 66 (72%) underwent thrombectomy with conscious sedation. Baseline clinical and imaging characteristics were similar among all groups. Functional independence at 90 days was 23% for general anesthesia, 53% for conscious sedation, and 17% for medical management (P = .009 for general anesthesia versus conscious sedation). Conscious sedation was associated with a shorter time from arrival in the angiosuite to femoral puncture (median, 14 versus 18 minutes; P = 0.05) and a shorter time from femoral puncture to reperfusion (median, 36 versus 48 minutes; P = .004). Sixty-six patients were treated at sites that exclusively used general anesthesia (n = 14) or conscious sedation (n = 52). For these patients, functional independence at 90 days was significantly higher in the conscious sedation subgroup (58%) compared with the general anesthesia subgroup (21%) (P = .03). CONCLUSIONS: Patients who underwent thrombectomy with conscious sedation in the extended time window experienced a higher likelihood of functional independence at 90 days, a lower NIHSS score at 24 hours, and a shorter time from femoral puncture to reperfusion compared with those who had general anesthesia. This effect remained robust in institutions that only treated patients with a single anesthesia technique.

Antidote control of aptamer therapeutics: the road to a safer class of drug agents.

Aptamers, or nucleic acid ligands, have gained clinical interest over the past 20 years due to their unique characteristics, which are a combination of the best facets of small molecules and antibodies. The high binding affinity and specificity of aptamers allows for isolation of an artificial ligand for theoretically any therapeutic target of interest. Chemical manipulations of aptamers also allow for fine-tuning of their bioavailability, and antidote control greatly expands their clinical use. Here we review the various methods of antidote control of aptamer therapeutics--matched oligonucleotide antidotes and universal antidotes. We also describe the development, recent progress, and potential future therapeutic applications of these types of aptamer-antidote pairs.

Antidote-controlled platelet inhibition targeting von Willebrand factor with aptamers.

Thrombus formation is initiated by platelets and leads to cardiovascular, cerebrovascular, and peripheral vascular disease, the leading causes of morbidity and mortality in the Western world. A number of antiplatelet drugs have improved clinical outcomes for thrombosis patients. However, their expanded use, especially in surgery, is limited by hemorrhage. Here, we describe an antiplatelet agent that can have its activity controlled by a matched antidote. We demonstrate that an RNA aptamer targeting von Willebrand factor (VWF) can potently inhibit VWF-mediated platelet adhesion and aggregation. By targeting this important adhesion step, we show that the aptamer molecule can inhibit platelet aggregation in PFA-100 and ristocetin-induced platelet aggregation assays. Furthermore, we show that a rationally designed antidote molecule can reverse the effects of the aptamer molecule, restoring platelet function quickly and effectively over a clinically relevant period. This aptamer-antidote pair represents a reversible antiplatelet agent inhibiting a platelet specific pathway. Furthermore, it is an important step towards creating safer drugs in clinics through the utilization of an antidote molecule.

Indications for admission to the surgical intensive care unit after radical cystectomy and urinary diversion.

PURPOSE: We analyzed the practice of mandatory surgical intensive care unit admission after radical cystectomy, and defined objective criteria to predict active treatment requirements and surgical intensive care unit stay. MATERIALS AND METHODS: We retrospectively reviewed the records of 115 consecutive patients admitted to the surgical intensive care unit after radical cystectomy and urinary diversion during the 36-month study period of January 1996 to December 1998. An Acute Physiology and Chronic Health Evaluation II score was calculated from postoperative patient parameters at admission to the unit. Active treatment mandating admission was defined as postoperative invasive cardiopulmonary monitoring, administration of vasopressors or inotropic medications, monitoring or treatment for life threatening complications, or mechanical ventilation for longer than 12 hours. We analyzed the correlation of outcome variables with the requirements for active treatment and surgical intensive care unit stay, and developed a stratification model of low versus high risk. Low risk was defined as a calculated likelihood of less than 10% for requiring active treatment postoperatively. RESULTS: Mean stay in the surgical intensive care unit plus or minus standard error was 34.4 +/- 3.1 hours. No active treatment was required in 63.5% of patients during the stay. The evaluation score, intraoperative complications and number of intraoperative transfusions were the strongest predictors of required postoperative active treatment. By combining these variables we developed a clinically applicable algorithm to stratify patients into a low and a high risk category. In patients at low and high risk the active treatment rate was 5.9% and 42.8% (p = 0.001), and the mean stay was 24.6 +/- 2.2 and 38.7 +/- 4.5 hours (p = 0.039), respectively. CONCLUSIONS: Mandatory surgical intensive care unit admission of all patients after radical cystectomy and urinary diversion does not appear indicated. A subset of patients at low risk for requiring active treatment may be identified who may be safely treated in an intermediate care setting after initial postoperative observation in the recovery room. The results of our retrospective analysis and risk stratification model should be validated in a prospective trial.