Transcript Learning Objectives - MOANA | Missouri Association of
The Role of Short-acting Opioids in Current Anesthesia Practice
Sponsored by Integrity Continuing Education, Inc. Supported by an educational grant from Mylan.
Bernadette Henrichs, PhD, CRNA Professor & Director Nurse Anesthesia Program Goldfarb School of Nursing Barnes-Jewish College St. Louis, Missouri
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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.
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Volatile Inhalation Agents for the Maintenance of General Anesthesia
• Common agents include sevoflurane (SEVO), desflurane (DES), and nitrous oxide (N 2 O) • N 2 O with SEVO or DES provides fast, reliable recovery and lowers risk of myocardial depression • Associated adverse events:
SEVO/DES N 2 O
• Isolated cases of hepatotoxicity • Nausea and vomiting • Diffusional hypoxemia • Pulmonary bleb rupture • Pneumothorax expansion • Inactivation of vitamin B 12 * * May have deleterious effects in critically ill and pediatric patients; Mandel, J. E.
J Clin Anesth
. 2014;26(1 Suppl):S1-7.
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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.
Paediatr Anaesth
. 2009;19(5):521-534. Mandel JE.
J Clin Anesth
. 2014;26(1):S1-S7. Mani V, et al.
Paediatr Anaesth
. 2010;20(3):211-222.
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IV Agents for the Induction and Maintenance of General Anesthesia IV AGENT POTENTIAL ADVANTAGES POTENTIAL DISADVANTAGES Propofol
– – – Good recovery profile Short half-life Low PONV incidence – – – Bradycardia Hypotension Burning sensation
Etomidate
– Preferred if vasodilation and cardiac depression are contraindicated – – – Adrenal insufficiency Higher PONV incidence Burning sensation
Ketamine
– Preferred for reactive airway patients (bronchodilatory) – – – Cardiovascular stimulation Hallucinations, vivid dreams, delirium Benzodiazepines can improve but may slow emergence and recovery Mandel, J. E.
J Clin Anesth
. 2014;26(1 Suppl):S1-7.
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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
Gozdemir M, et al.
Adv Ther
. 2007;24(3):622-631. Grundmann U, et al.
Acta Anaesthesiol Scand
. 1998;42(7):845-850. Magni G, et al.
J Neurosurg Anesthesiol
. 2005;17(3):134-138.
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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.
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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.
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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 Lendvay V, et al.
J Anesthe Clinic Res
. 2010;1:103.
Cove ME, Pinsky MR.
Best Pract Res Clin Anaesthesiol
. 2012;26(4):453-462.
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Rationale for the Use of Short-acting Opioids in General Anesthesia
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Opioid Receptors and Response to Stimulation Receptor Mu-1 Response
•
Supraspinal analgesia Mu-2 Delta Kappa Sigma
• • • •
Depression of ventilation Cardiovascular effects Physical dependence Euphoria
•
Modulate mu receptors
• • •
Spinal analgesia Sedation Miosis
• •
Dysphoria Hypertonia
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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.
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 Opin Anaesthesiol
. 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.
Desirable Characteristics of the µ-Opioids Characteristic µ-Opioid receptor selectivity No histamine release Rapid response to titration Alfentanil X X Fentanyl X X Remifentanil Sufentanil X X X X X Rapid, predictable offset of opioid effects (5-10 min) X Elimination independent of renal or hepatic function X
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Remifentanil Hydrolysis by Non-specific Esterases in the Blood and Tissues Remifentanil
O CH 3 -O-C-CH 2 -CH 2 N O C-O CH 3 O N-C-CH 2 CH 3
>95% Major Metabolite (Inactive)
O O H-O-C-CH 2 -CH 2 N C-O-CH 3 O N-C-CH 2 CH 3 GR90291 Egan TD.
Clin Pharmacokinet
. 1995;29(2):80-94.
H-N GR94219 O C-O CH 3 O N-C-CH 2 CH 3
Pharmacokinetic Properties of µ-Opioids Pharmacokinetics Onset: blood-effect site equilibration, mean Organ-independent elimination Nonspecific esterase metabolism Offset: context-sensitive half-time, mean* Alfentanil 0.96 min No No 50-55 min † Fentanyl 6.6 min Remifentanil Sufentanil 1.6 min 6.2 min No No >100 min † Yes Yes 3-6 min No No 30 min †
*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. 17
Practical Considerations: Rapid Onset ADVANTAGES
• Rapid response to titration and bolus • Control of anesthetic depth • Hemodynamic stability • Predictable plasma & receptor level
DISADVANTAGES
• Increased risk for: – Bradycardia – Hypotension – Chest wall rigidity – Apnea
Opioid Infusion Front-end Kinetics: Quick to Steady State 100 80 60 40 Remifentanil Alfentanil Sufentanil Morphine Fentanyl 20 0 0
Egan TD (in Miller & Pardo). Elsevier;2011.
Infusion begins at time zero 100 200 300 400
Infusion Duration (min)
500 600
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Opioid Infusion Back-end Kinetics: Rapid Offset After Infusion 400 350 300 250 200 150 100 50 0 0 Fentanyl Morphine 100 200 Alfentanil Sufentanil Remifentanil 30 400
Infusion Duration (min)
500 600
Egan TD (in Miller & Pardo). Elsevier;2011.
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Mean Concentration Over Time With Short-acting Opioids Discontinuation of infusion
100
Alfentanil (n=5) 0.5 mcg/kg/min Remifentanil
10 1 0.1
0
(n=6) 0.05 mcg/kg/min
60 120 180 240 300 360 420 480
Time (min)
ULTIVA [Mylan Inc.] Available at: http://www.ultiva.com/files/Ultiva-Prescribing-Info.pdf
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Practical Considerations: Rapid Offset ADVANTAGES
• Rapid response to titration • Predictable emergence • High-dose opioid technique without need for post-op ventilation • Ideal for TIVA
DISADVANTAGES
• No residual analgesia – Hemodynamic instability
Procedure-associated Variability in Opioid Pharmacodynamics Probability of No Response (%) (n=37) 100 50
Intubation Skin Incision Skin Closure
0 0 200 400 600 Plasma Alfentanil (ng/mL) 800
Ausems ME, et al.
Anesthesiology.
1986;65:362-373.
1000
Opioid Pharmacodynamic Variability Probability of No Response to Surgical Incision (%) 100 50 0 200 400 Plasma Alfentanil (ng/mL)
Ausems ME, et al.
Anesthesiology.
1988;68:851-861.
600
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.
Choosing an Anesthetic Technique
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Discussion Questions: Technique Considerations
• How do you determine which technique is most appropriate for a given patient?
• What are the primary concerns associated with each technique?
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.
Anesthesiol Clin North Am
. 2003;21(2):263-272.
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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
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.
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
Case Study #1
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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
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
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
Emergence & Recovery
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Short-acting Opioid Improves Time to Orientation Compared With N 2 O 1.0
0.8
Remifentanil Nitrous oxide 0.6
0.4
Infusion of remifentanil 0.085 µg/kg/min compared with 66% N 2 O 0.2
0.0
0 5 10 15 Time (min)
Mathews DM, et al.
Anesth Analg
. 2008;106:101-108.
20 25
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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.
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Case Study #2
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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
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/1.73m
2 • Vascular evaluation: – 90% occlusion of right carotid – 50% occlusion of left carotid • Allergies: – No known allergies
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
Case Study #3
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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)
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
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.
Semin Cardiothorac Vasc Anesth
. 2010;14(1):51-53.
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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
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
Propofol Emergence Data
1.00
0.75
0.50
0.25
Target plasma concentration Recovery after: 10-day infusion 10-hour infusion 1-hour infusion Awakening 0.00
0 20 40 Minutes After End of Infusion 60 DIPRIVAN (propofol) injection, emulsion [APP Pharmaceuticals, LLC]. Available at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ee0c3437-614d-4631-a061-257f5f60c70b.
80 49
Postoperative Management: Analgesia
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Postoperative Pain
• Postoperative pain is a significant cause of delayed discharge after ambulatory surgery • Good pain control is important for prevention of negative outcomes: – Tachycardia – Hypertension – Myocardial ischemia – Decreased alveolar ventilation – Poor wound healing • Pain control must be individualized Vadivelu N, et al.
Yale J Biol Med
. 2010;83(1):11-25.
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Options for Postoperative Pain Management
• Choice of analgesia should be a multimodal approach: – Nonsteroidal agent administered IV or IM – IV acetaminophen – Major nerve block – Local anesthetic wound infiltration – Long-acting opioids administered 20 to 30 minutes before discontinuation of certain short-acting opioids – Consider epidural administration of an opioid and/or local anesthetic IM, intramuscular
Opioids in Postoperative Analgesia
• Give opioids prior to emergence as needed – IV Acetaminophen if not given at induction – Ketorolac 30 mg IV ~30 min or Caldolor IV – Dilaudid 0.2-2.0 mg IV ~ 20-30 min – MSO 4 0.1 to 0.2 mg/kg IV ~20 to 30 min – Fentanyl 1 to 1.5 u/kg IV ~5 min • • • Dose epidural if epidural placed Surgeon: Infiltrate with long-acting local anesthetic
Consider continuing remifentanil 0.05 to 0.1 mcg/kg/min in PACU
Considerations for Special Populations
• Age; Elderly more sensitive to narcotics • Body mass effects; Obese more sensitive to narcotics • Comorbid conditions • Current medications Strom C, et al.
Anaesthesia
. 2014;69(S1):35-44. Lerman J.
Eur J Anaesthesiol
. 2013;30(11):645-650. Ingrande J, et al.
Br J Anaesth
. 2010;105 (S1):16-23. Hachenberg T, et al.
Curr Opin Anaesthesiol
. 2014;27(4):394-402.Licker M, et al.
Int J Chron Obstruct Pulmon Dis
. 2007;2(4):493-515.
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Summary
• • • • Opioids used in anesthesia play a critical role in minimizing surgical pain and the associated adverse effects on patient outcomes The pharmacokinetic profiles of newer short-acting opioids are characterized by lower drug accumulation and rapid, predictable onset and offset The resulting rapid response to titration of short-acting opioids enables close intraoperative management of hemodynamics, patient stress response, and depth of anesthesia With appropriate use, short-acting opioids have the potential to improve recovery and overall patient experience and satisfaction 55