Endovascular Abdominal Aortic Aneurysm Repair: Does Anesthesia Type Matter?

BACKGROUND: Given the various types of anesthesia used for endovascular abdominal aortic aneurysm repair (EVAR), we sought to determine the effect of anesthesia type in the outcomes of elective EVAR in a large multiinstitutional healthcare maintenance organization. METHODS: A retrospective chart review was conducted on all elective EVAR conducted from August 2010 to August 2017 in 14 regional hospitals of Kaiser Permanente Southern California. Patients undergoing emergent, nonelective abdominal aortic aneurysm repairs, thoracoabdominal aneurysm repair, requiring conversion to open surgery or general anesthesia were excluded from the study. Basic demographic information, medical risk factors, anesthesia type, operative data, and postoperative morbidity and mortality data were obtained for univariate and multivariate statistical analysis. RESULTS: A total of 1,536 patients underwent EVAR, of which 1,206 met inclusion criteria. A total of 788 patients underwent general anesthesia, 164 patients underwent spinal anesthesia, 82 patients underwent epidural anesthesia, and 172 patients underwent local and monitored anesthesia care (AC). There was a significant difference in length of stay and operative time when comparing local/monitored AC to general anesthesia. No significant difference was noted in 30-day morbidity or mortality among the anesthesia groups. CONCLUSIONS: Local and regional anesthesia is a safe and effective approach for elective EVAR.

Identification of Selective Dual ROCK1 and ROCK2 Inhibitors Using Structure-Based Drug Design.

A HTS campaign identified compound 1, an excellent hit-like molecule to initiate medicinal chemistry efforts to optimize a dual ROCK1 and ROCK2 inhibitor. Substitution (2-Cl, 2-NH2, 2-F, 3-F) of the pyridine hinge binding motif or replacement with pyrimidine afforded compounds with a clean CYP inhibition profile. Cocrystal structures of an early lead compound were obtained in PKA, ROCK1, and ROCK2. This provided critical structural information for medicinal chemistry to drive compound design. The structural data indicated the preferred configuration at the central benzylic carbon would be ( R), and application of this information to compound design resulted in compound 16. This compound was shown to be a potent and selective dual ROCK inhibitor in both enzyme and cell assays and efficacious in the retinal nerve fiber layer model after oral dosing. This tool compound has been made available through the AbbVie Compound Toolbox. Finally, the cocrystal structures also identified that aspartic acid residues 176 and 218 in ROCK2, which are glutamic acids in PKA, could be targeted as residues to drive both potency and kinome selectivity. Introduction of a piperidin-3-ylmethanamine group to the compound series resulted in compound 58, a potent and selective dual ROCK inhibitor with excellent predicted drug-like properties.

Zoledronic acid-induced severe hypocalcaemia in a prostate cancer patient with extensive osteoblastic bone metastases.

A 74-year old white man was undergoing treatment with palliative chemotherapy for Stage IV Prostate Adenocarcinoma with multiple osteoblastic metastases. He was started on intravenous Zoledronic acid for reduction of bone pain and prevention of skeletal complication from multiple bone metastases. Four days after intravenous Zoledronic acid, the patient presented to emergency room with complaints of carpopedal spasm and bronchospasm. On admission, serum calcium and albumin was 3.5 mg/dl and 3.7 g/dl respectively. QT interval was more than 500 m sec. The patient was started on intravenous calcium gluconate. He received 174 gm of intravenous calcium for total of 12 days. His serum calcium returned to a normal range in three months with Vitamin D and calcium supplement. Before starting Zoledronic acid therapy, the patient's serum calcium level was 6.9 mg/dl.