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The Role of Short-acting Opioids in Current Anesthesia Practice

The Role of Short-acting Opioids in Current Anesthesia Practice. Sponsored by Integrity Continuing Education, Inc. Supported by an educational grant from Mylan.

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The Role of Short-acting Opioids in Current Anesthesia Practice

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  1. The Role of Short-acting Opioids in Current Anesthesia Practice Sponsored by Integrity Continuing Education, Inc. Supported by an educational grant from Mylan.

  2. Bernadette Henrichs, PhD, CRNAProfessor & DirectorNurse Anesthesia ProgramGoldfarb School of Nursing Barnes-Jewish CollegeSt. Louis, Missouri

  3. Overview of General Anesthesia • Goals of general anesthesia • Rapid induction and maintenance of optimal operating conditions • Reduction of side effects • Rapid emergence and recovery • A combination of agents is used to induce and maintain general anesthesia in current practice • IV hypnotics and sedatives • Volatile inhalational agents • Opioids • Muscle relaxants • Mandel, J. E. J Clin Anesth. 2014;26(1 Suppl):S1-7.

  4. Volatile Inhalation Agents for the Maintenance of General Anesthesia • Common agents include sevoflurane (SEVO), desflurane (DES), and nitrous oxide (N2O) • N2O with SEVO or DES provides fast, reliable recovery and lowers risk of myocardial depression • Associated adverse events: • *May have deleterious effects in critically ill and pediatric patients; Mandel, J. E. J Clin Anesth. 2014;26(1 Suppl):S1-7.

  5. Total Intravenous Anesthesia (TIVA) • An alternative to the use of volatile agents for maintenance of anesthesia • Anesthesia is produced entirely using IV anesthetics administered by target-controlled infusion or manual injection • Short-acting opioids play a central role (though not always required for minimally stimulating procedures) • Short-acting agents enable rapid recovery even after long infusions Cole CD, et al. Neurosurgery. 2007;61(5 Suppl 2):369-377. DeConde AS, et al. Int Forum Allergy Rhinol. 2013;3(10):848-854. Lerman J, et al. PaediatrAnaesth. 2009;19(5):521-534. Mandel JE. J Clin Anesth. 2014;26(1):S1-S7. Mani V, et al. PaediatrAnaesth. 2010;20(3):211-222.

  6. IV Agents for the Induction and Maintenance of General Anesthesia • Mandel, J. E. J Clin Anesth. 2014;26(1 Suppl):S1-7.

  7. Clinical Comparisons of Anesthesia Techniques • TIVA compared to inhalation anesthesia (IA) in vertebral disk surgery: • Shorter recovery times (spontaneous ventilation, extubation, eye opening, and ability to give name and date of birth)* • Less PONV • Greater analgesic demand • TIVA compared to IA in pediatric ENT surgery: • Lower perioperative heart rate • Less postoperative agitation • TIVA and balanced volatile anesthesia in intracranial surgery were found to be comparable *P<.05 GozdemirM, et al. Adv Ther. 2007;24(3):622-631. Grundmann U, et al. ActaAnaesthesiol Scand. 1998;42(7):845-850. MagniG, et al. J NeurosurgAnesthesiol. 2005;17(3):134-138.

  8. Monitoring of Vital Signs to Assess Depth of Anesthesia • Potential signs of intraoperative awareness/stress: • Tachycardia (rapid heart rate) • Hypertension • Sweating • Lacrimation (tear production) • Movement/grimacing • Tachypnea (rapid breathing) • New technologies for monitoring (EEG, BIS) • Helps to indicate the level of unconsciousness • Does not guarantee against intraoperative awareness Shepherd J. Health Technology Assessment 2013;17:34.

  9. Maintaining Appropriate Depth of Anesthesia • Excessive level of anesthesia • Increases risk of postoperative nausea, vomiting, and cognitive dysfunction • Insufficient level of anesthesia • Places patient at risk for intraoperative awareness • Although relatively rare, intraoperative awareness can cause depression, anxiety, and post-traumatic stress disorder Shepherd J. Health Technology Assessment. 2013;17:34.

  10. Hemodynamic Stability During Surgery • Hemodynamic instability can result in complications • Hemodynamic measures are important indicators of the following: • Sufficient cardiac output • Adequate SV; Volume status • Organ perfusion • Adequacy of pain control • Depth of anesthesia LendvayV, et al. J Anesthe Clinic Res. 2010;1:103. Cove ME, Pinsky MR. Best Pract Res Clin Anaesthesiol. 2012;26(4):453-462.

  11. Rationale for the Use of Short-acting Opioids in General Anesthesia

  12. Opioid Receptors and Responseto Stimulation

  13. Advantages of the Use of Opioids for General Anesthesia • Analgesia • Blunts neuroendocrine activation • Hemodynamic stability • No direct myocardial depression • Blunts catecholamine response to noxious stimuli • Decreased stress response • Attenuates stress response during surgery • Decreased need for hypnotic anesthetics • Less propofol needed Brown EN., et al. Annu Rev Neurosci. 2011;34:601-628.Fukuda K (2010). Opioids. In RD Miller et al., eds., Miller's Anesthesia, 7th ed., pp. 2519-2700. Wilmore DW. Ann Surg. 2002;236(5):643-648.

  14. Specific Benefits Associated with the Use of Short-acting Opioids • Minimal effects of drug accumulation • Predictable and rapid onset and offset • Rapid patient response to titration allows close management of intraoperative status • Potential for faster recovery time and reduced PONV • Benefits are not generally affected by gender, age, weight, or renal/hepatic function • Wilhelm W, et al. Crit Care. 2008;12 (Suppl 3):S5. Egan TD. Curr OpinAnaesthesiol. 2000;13(4):449-455. Egan TD, et al. Anesthesiology. 1996;84(4):821-833. Minto CF, et al. Anesthesiology. 1997;86(1):10-23.

  15. Desirable Characteristics of the µ-Opioids

  16. Nonspecific Esterases Remifentanil Hydrolysis by Non-specific Esterases in the Blood and Tissues Remifentanil O C-O-CH3 O CH3-O-C-CH2-CH2-N O N-C-CH2-CH3 >95% Major Metabolite (Inactive) O O C-O-CH3 C-O-CH3 H-N O O H-O-C-CH2-CH2-N N-C-CH2-CH3 O N-C-CH2-CH3 GR94219 GR90291 Egan TD. Clin Pharmacokinet. 1995;29(2):80-94.

  17. Pharmacokinetic Properties of µ-Opioids *The time required for drug concentrations in blood or at effect site to decrease by 50%. Based on a 3-hour infusion. † Increases with increasing infusion duration due to accumulation. Data derived from manufacturers’ labeling and Egan TD, et al. Anesthesiology.1993;79:881-892. Egan TD, et al. Anesthesiology.1996;84:821-833. Scott JC, et al. Anesthesiology. 1991;74:34-42.

  18. Practical Considerations:Rapid Onset

  19. Opioid Infusion Front-end Kinetics: Quick to Steady State 100 80 60 40 20 0 Remifentanil Morphine Alfentanil Sufentanil Fentanyl Proportion of Steady-State Ce (%) Infusion begins at time zero 0 100 200 300 400 500 600 Infusion Duration (min) Egan TD (in Miller & Pardo). Elsevier;2011.

  20. Opioid Infusion Back-end Kinetics: Rapid Offset After Infusion 400 350 300 250 200 150 100 50 0 Fentanyl Morphine Time to 50% Decrement in Ce (%) Alfentanil Sufentanil Remifentanil 0 100 200 30 400 500 600 Infusion Duration (min) Egan TD (in Miller & Pardo). Elsevier;2011.

  21. Mean Concentration Over Time With Short-acting Opioids • Discontinuation of infusion Alfentanil Remifentanil • (n=5) • 0.5 mcg/kg/min • Mean Concentration (ng/mL) • (n=6) • 0.05 mcg/kg/min • Time (min) ULTIVA [Mylan Inc.] Available at: http://www.ultiva.com/files/Ultiva-Prescribing-Info.pdf

  22. Practical Considerations:Rapid Offset

  23. Procedure-associated Variability in Opioid Pharmacodynamics Probability of No Response (%) (n=37) 100 Intubation 50 Skin Incision Skin Closure 0 0 200 400 600 800 1000 Plasma Alfentanil (ng/mL) Ausems ME, et al. Anesthesiology. 1986;65:362-373.

  24. Ausems ME, et al. Anesthesiology. 1988;68:851-861. Opioid Pharmacodynamic Variability Probability of No Response to Surgical Incision (%) 100 50 0 200 400 600 Plasma Alfentanil (ng/mL)

  25. Risks Associated with the Use of Opioids in General Anesthesia • Respiratory depression • Bradycardia • Chest wall/laryngeal muscle rigidity • PONV • Pruritus • Delayed emergence • Dependency • Potential hyperalgesia Bowdle TA. Drug Saf. 1998;19(3):173-189. Egan TD. Clin Pharmacokinet. 1995;29(2):80-94. Fletcher D, et al. Br J Anaesth. 2014;112(6):991-1004. Komatsu R, et al. Anaesthesia. 2007;62(12):1266-1280.

  26. Choosing an Anesthetic Technique

  27. DiscussionQuestions: Technique Considerations • How do you determine which technique is most appropriate for a given patient? • What are the primary concerns associated with each technique?

  28. Impact of Inhalation vs Intravenous (IV) Administration of Agents • Less PONV and greater patient satisfaction has been observed with the following: • IV induction compared to inhalation induction* • TIVA compared to an inhalation component • Emergence and discharge for outpatients is essentially identical • Inhalational anesthesia may be economically advantageous over TIVA *Both followed by inhalation maintenance. Kumar, G., et al. Anaesthesia. 2014. [Epub ahead of print] Joshi GP. AnesthesiolClin North Am. 2003;21(2):263-272.

  29. The Anesthesia Technique You Use Should Be Based on Your Goals • Balanced anesthesia with opioid and volatile agent • Safe • Practiced for decades • TIVA • Safe • Relative newcomer to the OR • Outpatient > inpatient • May impact patient satisfaction OR, Operating Room

  30. Goals of Neuroanesthesia • Hemodynamic stability without vasodilators • Improved ability to rapidly change anesthetic depth • Rapid recovery with early ability to assess neurologic function • Improved SSEP monitoring with TIVA SSEP, somatosensory evoked potential.

  31. Goals of ENT • Hemodynamic stability without vasodilators • Decreased bleeding, improved operative conditions during nasal/sinus surgery or tonsillectomy • Rapid awakening, rapid ability to protect airway, rapid recovery

  32. Case Study #1

  33. Case Study #1: 17-year-old Female • Procedure: Septoplasty and sinus endoscopy • History: • Significant history of nasal passage obstruction and difficulty breathing • History of chronic sinusitis beginning at age 3 • Surgical history: • Tonsillectomy at age 7 related to obstructive sleep apnea (OSA); complicated by prolonged paralysis to succinylcholine

  34. Case Study #1: 17-year-old Female (cont’d) • Comorbidities: • Asthma • Obesity • OSA with nasal obstruction • Current medications: • Saline nasal irrigation qd • Albuterol prn • Allergies: • Penicillin • No other known allergies

  35. Case Study #1: Consideration of Patient Characteristics • How do the patient’s characteristics influence your approach to formulating a plan for anesthesia? • OSA • Obesity • Asthma • Atypical pseudocholinesterase deficiency • Specific concerns with regard to this type of surgical procedure: May be stimulating at times but no incision to close at end of case

  36. Emergence & Recovery

  37. Short-acting Opioid Improves Time to Orientation Compared With N2O 1.0 Remifentanil Nitrous oxide 0.8 Infusion of remifentanil 0.085 µg/kg/min compared with66% N2O 0.6 • Proportion Not Oriented 0.4 0.2 0.0 0 5 10 15 20 25 • Time (min) Mathews DM, et al. Anesth Analg. 2008;106:101-108.

  38. Comparison of the Short-acting Opioids: Impact on Patient Recovery Similar PONV is observed with fentanyl, remifentanil, alfentanil, and sufentanil Use of remifentanil vs other short-acting opioids is associated with the following: Faster postoperative recovery Less respiratory depression Higher postoperative analgesic requirements More shivering • Reviewed in: Komatsu R, et al. Anaesthesia. 2007;62(12):1266-1280.

  39. Case Study #2

  40. Case Study #2: 73-year-old Male • Procedure: Right carotid endarterectomy • Comorbid conditions: • Coronary artery disease • Type 1 diabetes • Hypertension • Peripheral vascular disease • Surgical history: • Left femoral popliteal bypass at age 71 • Stent inserted at age 68

  41. Case Study #2: 73-year-old Male (cont’d) • Current medications: • Lisonopril 20 mg qd • Insulin glargine 0.2 units/kg/day • Renal evaluation: • Renal insufficiency determined by glomerular filtration rate (GFR) of 61 mls/min/1.73m2 • Vascular evaluation: • 90% occlusion of right carotid • 50% occlusion of left carotid • Allergies: • No known allergies

  42. Case Study #2: Questions for Consideration • What considerations should be given for: • Regional vs general anesthesia? • Tracheal intubation vs laryngeal mask airway (LMA) device? • What monitoring would you employ intraoperatively? • Consider the patient’s medical history (HTN) and renal impairment in the anesthetic plan • Important to consider quick emergence to assess neurological function

  43. Case Study #3

  44. Case Study #3: 42-year-old Female • Procedure: • Multi-level laminectomy with lumbar fusion • Intraoperative neurophysiologic monitoring (sensory evoked potentials, motor evoked potentials) • Surgical history: • Previous back surgery to repair herniated disc 3 years ago • Medical history: • Current smoker • Current medications: • Naproxen sodium 500 mg bid (discontinued 10 days ago)

  45. Case Study #3: Questions for Consideration • What considerations are given for TIVA vs mixed anesthesia in this patient? • Consider intraoperative monitoring of this patient • Consider surgeon request for possible intraoperative wake up for neurologic examination • Consider patient’s history of chronic pain medication

  46. Intraoperative Neurophysiological Monitoring • Main modalities: • Somatosensory evoked potentials (SSEPs) • Motor evoked potentials (MEPs) • Electromyography (EMGs); transcranial monitoring • While both inhaled and intravenous agents blunt signal attainment, depression is greater with inhaled agents Deiner S. SeminCardiothoracVascAnesth. 2010;14(1):51-53.

  47. Case Study #3: Anesthetic Plan • TIVA with propofol and fast-acting opioid infusion • If intraoperative wake up is necessary, it will be possible • Consider patient’s history of chronic pain medication • Give pain medicine before emergence • IV Acetaminophen; IV NSAID; longer-acting narcotic

  48. Emergence and Recovery: Considerations • Goal is to prepare for and have a smooth transition to postoperative analgesia • Early planning is essential with an agent with a rapid offset of action (within 5-10 minutes) • Non-cumulative effects are beneficial during surgery, but a disadvantage postoperatively in terms of pain control • Need to be prepared and address pain • Risks for obstruction and for pulmonary aspiration are also important to consider

  49. Propofol Emergence Data Target plasma concentration 1.00 Recovery after: 10-day infusion 10-hour infusion 1-hour infusion 0.75 Awakening Plasma Propofol Concentration (mcg/mL) 0.50 0.25 0.00 0 20 40 60 80 Minutes After End of Infusion DIPRIVAN (propofol) injection, emulsion [APP Pharmaceuticals, LLC]. Available at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ee0c3437-614d-4631-a061-257f5f60c70b.

  50. Postoperative Management: Analgesia

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