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1.
Biochem Biophys Res Commun ; 431(4): 647-51, 2013 Feb 22.
Article in English | MEDLINE | ID: mdl-23337501

ABSTRACT

Tumor resistance to cytotoxic therapeutics coupled with dose-limiting toxicity is a serious hurdle in the field of medical oncology. In the face of this obstacle, nitric oxide has emerged as a powerful adjuvant for the hypersensitization of tumors to more traditional chemo- and radio-therapeutics. Furthermore, emerging evidence indicates that nitric oxide donors have the potential to function independently in the clinical management of cancer. Herein, we discuss the role of nitric oxide in cancer and the potential for nitric oxide donors to support conventional therapeutics.


Subject(s)
Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Neoplasms/drug therapy , Nitric Oxide Donors/therapeutic use , Nitric Oxide/metabolism , Apoptosis/drug effects , Humans , Neoplasms/metabolism , Nitric Oxide Donors/pharmacology
2.
Reg Anesth Pain Med ; 48(9): 454-461, 2023 09.
Article in English | MEDLINE | ID: mdl-37085287

ABSTRACT

INTRODUCTION: Erector spinae plane blocks have become popular for thoracic surgery. Despite a theoretically favorable safety profile, intercostal spread occurs and systemic toxicity is possible. Pharmacokinetic data are needed to guide safe dosing. METHODS: Fifteen patients undergoing thoracic surgery received continuous erector spinae plane blocks with ropivacaine 150 mg followed by subsequent boluses of 40 mg every 6 hours and infusion of 2 mg/hour. Arterial blood samples were obtained over 12 hours and analyzed using non-linear mixed effects modeling, which allowed for conducting simulations of clinically relevant dosing scenarios. The primary outcome was the Cmax of ropivacaine in erector spinae plane blocks. RESULTS: The mean age was 66 years, mean weight was 77.5 kg, and mean ideal body weight was 60 kg. The mean Cmax was 2.5 ±1.1 mg/L, which occurred at a median time of 10 (7-47) min after initial injection. Five patients developed potentially toxic ropivacaine levels but did not experience neurological symptoms. Another patient reported transient neurological toxicity symptoms. Our data suggested that using a maximum ropivacaine dose of 2.5 mg/kg based on ideal body weight would have prevented all toxicity events. Simulation predicted that reducing the initial dose to 75 mg with the same subsequent intermittent bolus dosing would decrease the risk of toxic levels to <1%. CONCLUSION: Local anesthetic systemic toxicity can occur with erector spinae plane blocks and administration of large, fixed doses of ropivacaine should be avoided, especially in patients with low ideal body weights. Weight-based ropivacaine dosing could reduce toxicity risk. TRIAL REGISTRATION NUMBER: NCT04807504; clinicaltrials.gov.


Subject(s)
Nerve Block , Humans , Aged , Ropivacaine , Nerve Block/adverse effects , Pain, Postoperative/diagnosis , Anesthetics, Local/adverse effects , Pain Management
3.
Ann Card Anaesth ; 25(3): 362-365, 2022.
Article in English | MEDLINE | ID: mdl-35799570

ABSTRACT

The Tempo® Temporary Pacing Lead is a temporary, transvenous, active fixation pacemaker lead used exclusively in structural heart and electrophysiology procedures since regulatory approval in 2016. We utilized the Tempo lead for four patients undergoing redo-robotic cardiac surgery in which surgical epicardial leads could not be placed. No failure-to-pace events were encountered and patients were able to participate in various levels of physical activity without limitation.


Subject(s)
Cardiac Pacing, Artificial , Cardiac Surgical Procedures , Pacemaker, Artificial , Humans , Reoperation , Robotic Surgical Procedures
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