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INTRODUCTION OF TWO NEW ANESTHETIC AGENTS Dr.G.k.kumar Ropivacaine Dexmeditomedine Ropivacaine Ropivacaine • New local anesthetic agent • Introduced in 1996. • In India 2009. Ropivacaine • Lower systemic toxicity • Safest long acting local anesthetic agent. * Groban et al. Anesth Analg, 2001. Ohmura et al. Anesth Analg, 2001. Santos et al. Anesthesiology, 2001. Ropivacaine -Pharmacology Ropivacaine-Pharmacology • Long acting LA agent. • Aminio amide. • Pure enantiomer -S isomer. Ropivacaine-Pharmacology • Greater selectivity for sensory blockade -binds selectively to Na⁺channels 1.7 • Shorter motor block *Liu BG et al, AnesAnalg.2000May. Simpsons D et al,2005 Ropivacaine-Pharmacology •Ropivacaine is less lipid soluble. •A smaller volume of distribution. •Greater clearance. •Shorter elimination half-life than bupivacaine. -Shorter duration of action esp motor blockade – early recovery. Ropivacaine-Pharmacology •Ropivacaine undergoes hepatic biotransformation and renal excretion •Excreted 86% as metobolites •Safe in CESLD & CESRD *Jokinen MJ et al, Anesthesiology,2007Jan. Jokinen MJ et al,Clinical Anesthesiology,2005 Ropivacaine-Pharmacology • The specific gravity of Ropivacaine Injection -from 1.002 to 1.005 at 25°C. -Isobaric Ropivacine-Safe Dose • 3-5mg /kg. • Pediatric-1-2mg/kg Ropivacaine-Epidural dose Drug Conc% Volume Dose mg 15-30 40-225 15-20 180-350 LEVO 0.25-0.75 15-30 40-250 15-20 180-350 ROPI 0.25-0.75 15-30 40-250 15-20 180-350 BUPI 0.25-0.5 Onset Duration *Miller’s anesthesia,7th edition Ropivacaine-Spinal dose Drug (%) Bupi 0.5 0.75 Levo Ropi 0.5 0.75 0.5 0.75 Total Volume Dose (mL) (mg) 15-20 3-4 2-3 15-20 3-4 15-20 2-3 15-20 3-4 15-20 2-3 15-20 Duration Baricity (min) Iso Hyper Iso Hyper Iso Hyper 90-200 90-200 90-200 90-200 90-200 90-200 *Miller’s anesthesia,7th edition Ropivacaine – clinical efficacy • When used for spinal anesthesia, 0.75% ropivacaine produces less intense sensory and motor block than 0.5% bupivacaine. • Equipotent to bupivacaine when used for lumbar epidural labor analgesia and C-section. Ropivacaine – clinical efficacy • In epidural and other blocks bupivacaine and ropivacaine demonstrate similar intensity of sensory anesthesia. Ropivacaine – clinical efficacy • Ropivacaine motor block -delayed in onset. -less intense. -shorter in duration. Toxicity • Ropivacaine < Levobupivacaine < Bupivacaine • Even at 50% higher dosage!!! *Dony et al. Anesth Analg, 2000 Toxicity • Tolerated blood conc. level [ROP] >> [BUP] = [LBUP] • Mortality: BUP (50%) > LBUP (30%) > ROP (10%) • • • * Groban et al. Anesth Analg, 2001. Ohmura et al. Anesth Analg, 2001. Santos et al. Anesthesiology, 2001. Ropivacine-Why Safer Than Bupivacaine? • Bupivacaine is a 50:50 racemic mixture of the S- and Renantiomers. • The R isomer has greater affinity and binding time for voltagegated sodium channels, and so cardiotoxicity. Ropivacine-Why Safer Than Bupivacaine? • R-bupivacaine is also more arrhythmogenic. • Slows ventricular conduction 4.6 times as much as Sbupivacaine. Ropivacine-Why Safer Than Bupivacaine? • The Ropivacaine is the pure S-enantiomer so decreased cardiotoxicity . Ropivacine-Why Safer Than Bupivacaine? • Cumulative doses up to 770 mg over 24 hours (intraoperative block plus postoperative infusion) • Continuous epidural infusion at rates up to 28 mg per hour for 72 hours have been well tolerated in adults, ie, 2016 mg plus surgical dose of approximately 100-150 mg as top-up. *www.fda druginformation.com Ropivacine-Why Safer Than Bupivacaine? • Ropivacaine has a larger therapeutic index • 70% less likely to cause severe cardiac dysarrhythmias • Greater CNS tolerance • The improved safety profile is due to a lower lipid solubility Ropivacaine HYPE? HOPE? LA toxicity more in • Heart block, HT, structural heart disease. • >65yr,<12yr. • Pregnancy. • Acidosis. • Liver dysfunction. • Acutely ill and debilitated. Role of Ropivacaine • • • • • • SAFE PRACTICE Pediatric patients. Geriatric patients. Continuous infusions. For labour analgesia. Rescue spinal anesthesia. Ropivacaine LA toxicity treatment • Supportive care: intubation, vasopressors, appropriate defibrillation, fluids, stop injection of LA. • Intralipid…Bolus 1cc/kg of 20% intralipid, 0.25cc/kg/min of 20% intralipid for 10 minutes • Bolus can be repeated every 5 minutes up to a maximum of 8cc/kg of 20% intralipid LA toxicity treatment • Cardiac support should be continued as ACLS dictates • Adrenaline and vasopressin are usefull. Ropivacaine