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What's Going on in Anesthesia

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What's Going on in Anesthesia 9/1/2017 Conflict of Interest What’s Going on in • Member, Pharmacy Curriculum Development Group, Pacira Anesthesia: Practice Updates Pharmaceuticals Julie Golembiewski PharmD University of Illinois Hospital & Health Sciences System Conflicts of interest were resolved through peer review Pharmacist Learning Objectives Pharmacy Technician Learning Objectives 1. Explain the current state of neuromuscular reversal and the role of 1. Identify medications utilized for reversal of neuromuscular blockade. sugammadex. 2. Identify advantages and disadvantages of IV Acetaminophen. 2. Discuss multimodal analgesia in the perioperative setting and the role of IV Acetaminophen. 3. Recognize practices that prevent drug diversion in the OR setting. 3. Recognize why a comprehensive and interdisciplinary approach to diversion surveillance is necessary in the OR setting. Pre‐Test 1 Pre‐Test 2 Select the FALSE statement about neuromuscular blockade and reversal. Which statement is FALSE? A. Celecoxib does not increase the risk of surgical bleeding. A. The effects of cisatracurium and atracurium are reversed by neostigmine. B. Local infiltration around the wound is most effective for procedures with a smaller component of visceral pain. B. The effects of rocuronium and vecuronium are reversed by sugammadex. C. The IV route is preferred to the oral route when providing analgesia for surgical patients. C. Sugammadex eliminates the need for monitoring the depth of block from rocuronium. D. The addition of gabapentin to a multimodal analgesia regimen may increase the respiratory depressant effect of the opioid. D. The onset of action of neostigmine is about 15 minutes. 1 9/1/2017 Pre‐Test 3 Diversion of anesthesia CS can be prevented by Roadmap ensuring 100% accountability of all controlled • Section 1: Reversal of neuromuscular blockade • Current state substances and tracking the number of • Role of sugammadex discrepancies by provider. • Section 2: Multimodal analgesia in the perioperative setting A. True • Early recovery after surgery • Role of nonopioids B. False • Role of IV acetaminophen • Section 3: Preventing drug diversion in the Operating Room (OR) • Draft ASHP Guidelines on Perioperative Pharmacy Services, Anesthesia Controlled Substances Nondepolarizing NMBAs Section 1: • Normal neuromuscular transmission • Release of ACh opens ion channel motor Primary Route of Neuromuscular Basics end plate potential muscle contraction Drug Onset Duration CV Effects • AChE rapidly hydrolyzes ACh motor end Elimination plate repolarizes muscle relaxes Rocuronium 60 ‐ 90 sec 30 ‐ 40 min Biliary, 30% renal None ACh = acetylcholine Nerve axon • Nondepolarizing neuromuscular (aminosteroid) blocking agents (NMBAs, a.k.a. muscle relaxants or paralytics) Atracurium 2 – 3 min 30 – 40 min Hofmann elimination, ↓ BP Vesicles • Competitive ACh receptor antagonist (benzylisoquinolinium) ester hydrolysis with ACh blocks muscle contraction paralysis • Types Cisatracurium 2 – 3 min 30 – 40 min Hofmann elimination. None ACh • Aminosteroid (rocuronium, vecuronium, NMBA pancuronium) (benzylisoquinolinium) ester hydrolysis (nicotinic) ACh • Benzylisoquinolinium (cisatracurium, receptors atracurium) • Indications Vecuronium 2 – 3 min 30 – 40 min Hepatic, 15% renal None • Facilitate endotracheal intubation (aminosteroid) Acetylcholinesterase enzyme (AChE)V V VVV • Improve surgical conditions Motor end plate • Facilitate mechanical ventilation Pancuronium > 3 min > 60 min Renal HR (muscle) (aminosteroid) Neuromuscular Basics – Reversal Agents Neostigmine • AChE inhibitor at nicotinic and muscarinic receptors • Peak effect ACh = acetylcholine Nerve axon AChE inhibitor Neostigmine (increased ACh to • About 15 minutes Edrophonium compete with • Adverse effects Vesicles Pyridostigmine NMBA muscle • Muscarinic (cholinergic) effects N/V, bradycardia, increased secretions, contraction) miosis ACh NMBA • Limitations (nicotinic) ACh Gamma‐cyclodextrin • Ceiling effect cannot reverse a deep/profound/intense block receptors Sugammadex (encapsulates • Concurrent administration of anticholinergic (glycopyrrolate, atropine) to rocuronium & Acetylcholinesterase enzyme (AChE)V V VVV minimize muscarinic (cholinergic) side effects Motor end plate vecuronium (muscle) inactive complex) Expert Opinion on Pharmacotherapy 2016;17(6):819 2 9/1/2017 Dose‐Dependent Effects of Neostigmine Sugammadex • Depending on the dose, reverses moderate, deep and intense block from No/Minimal Block Moderate Block Deep Block rocuronium and vecuronium Too much neostigmine is Neostigmine 40 – 60 mcg/kg NOT EFFECTIVE until after • Peak effect administered to patients who (with anticholinergic) spontaneous recovery has • About 2 minutes when given at appearance of second twitch have fully (or near fully) started recovered from block ≤ 60 mcg/kg after TOF count ≥ 2 • Adverse effects residual block and increased less risk of postop pulmonary • Hypersensitivity reactions, most often occurring within 5 min of administration risk of respiratory complications complications • Transient (< 60 min) effect on coagulation (aPTT, PT/INR) (due to upper airway collapsibility, impaired • Drug Interaction progesterone may bind to sugammadex pharyngeal muscles) separate • From the PI: “If an oral contraceptive is taken on the same day that sugammadex is from NMBA effects administered, patient must use an additional, non‐hormonal contraceptive method or Empiric full‐dose reversal not back‐up method of contraception (such as condoms and spermicides) for the next 7 recommended days” Anesthesiology 2015;122(6):1183 & 1201 Drugs 2016;76:1041‐1052 NMBA = neuromuscular blocking agent Anesthesiology 2017;126(1):173 Expert Opinion on Pharmacotherapy 2016;17(6):819 Sugammadex package insert (PI) Factors Influencing Incidence of Adverse Effects of Monitoring Postop Residual Neuromuscular Blockade Residual Neuromuscular • Why monitor? Blockade • Rocuronium 0.6 mg/kg, opioid‐nitrous oxide general anesthesia 1 • Type and dose of NMBA • Hypoxemia, upper airway Onset Duration • Degree of block obstruction and other Median 1.8 min 31 min • Type (inhalational vs. TIVA) and duration of anesthesia critical respiratory events in Range 0.6 – 13 min 15 – 85 min • Use of monitoring (TOF) PACU • Clinical signs of recovery from neuromuscular blockade have poor sensitivity and • Dose of anticholinesterase reversal drug • Postoperative pulmonary are unreliable 2 • Time of reversal administration complications (atelectasis, • Types 2,3 • Situational awareness of surgical timing pneumonia) • Qualitative conventional peripheral nerve stimulator [train‐of‐four (TOF) stimulation] • Patient factors (metabolic derangements, • Symptoms and signs of • Allows rationale drug administration • Redosing of NMBA, timing and dose of reversal agent hypothermia) muscle weakness • Widely available • Less reliable detection of TOF ratio between 0.4 and 0.9 NMBA = neuromuscular blocking agent • Quantitative e.g. acceleromyography TIVA = total intravenous anesthesia 1 Rocuronium package insert Anesth Analg 2010;111(1):120 • Reliable detection of TOF ratios between 0.4 and 0.9 2 Anesth Analg 2010;111:129 TOF = train of four Anesth Analg 2015;121(2):366 • Limited availability, expensive, none are ideal 3 Curr Opin Anesthesiol 2014;27:616‐622 PACU = postanesthesia care unit From the Literature . Our Approach at UI Health • Monitoring is important regardless of the reversal agent • Drug cost • “The introduction of sugammadex has produced a hope that residual neuromuscular • Rocuronium 50 mg = vecuronium 10 mg; cisatracurium ~ 10 x cost blockade after rocuronium would be virtually eliminated. Unfortunately, the data • Sugammadex 200 mg = 1.4 x (neostigmine + glycopyrrolate) indicate otherwise! The use of sugammadex is not an excuse to avoid monitoring the depth of blockade for every case when rocuronium or vecuronium is used.” 1 • “A quantitative monitor is no substitute for education and skill.” 1 • Anesthesia record audit, rocuronium shortage and addition of • When is paralysis really necessary? sugammadex led to revisiting NMBA selection, dosing, monitoring • Decision to administer muscle relaxant should not be taken lightly and reversal practices • What depth of block for what procedure? • Emphasis on appropriate depth of block, dosing and monitoring • Is deep blockade really necessary in certain laparoscopic procedures? • Vecuronium, not rocuronium, as NMBA of choice • POPULAR trial: POst‐operative PULmonary complications After use of muscle • Rocuronium for rapid sequence intubation not routine use Relaxants across Europe • Cisatracurium in patients with impaired renal/hepatic function • Designed to evaluate the effects of management of neuromuscular blockade on post‐ • Does mivacurium have a role? operative pulmonary complications • Restrict sugammadex 1 Anesthesiology 2017;126(1):13 Expert Opinion on Drug Metabolism & Toxicology 2016;12(9):1097 • Criteria for use and attending anesthesiologist approval Acta Anaesth Scand 2015;59:1 and 2016;60:710 Anesthesiology 2015;122(6):1183 http://www.esahq.org/POPULAR 3 9/1/2017 Select the FALSE statement about Section 2: Enhanced Recovery After Surgery (ERAS) neuromuscular blockade and reversal. Multimodal Care A. The effects of cisatracurium and atracurium are reversed by neostigmine. “No single element by itself will improve outcomes of surgery.” B. The effects of rocuronium and vecuronium are reversed by • “The approach to perioperative care must be multimodal, using all sugammadex. available elements of care that improve
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