Source of pain relievers for nonmedical use among users 12 years or older:

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1 ACUTE PAIN MANAGEMENT OF THE OPIOID TOLERANT TRAUMA PATIENT James D. Colson, MS, MD Department of Anesthesiology WVU Hospitals

2 Learning Objectives Identify criteria pertaining to the opioid-tolerant patient; Determine opioid equianalgesic equivalence; Review the resultant effects of chronic opioid use; Gain an understanding of the multimodal strategies available for managing pain in the opioid-tolerant patient; Identify assessment and intervention parameters involved in treating the opioid-tolerant patient.

3 Overview Opioids are the mainstay of analgesic therapy. Opioid consumption in the USA has increased tremendously over the past decade. Chance of encountering a trauma patient with a current history of opioid use is high. Therapeutic challenges confronting the provider in managing the opioid-tolerant patient s pain are considerable.

4 Increase in therapeutic opioid use from 1997 to 2007 (mg/person) Methadone: 1214% Oxycodone: 899% Fentanyl: 496% Hydrocodone: 265% Morphine: 209% Overall Change: 402% Source:

5 DIVERSION OF PRESCRIPTION-TYPE TYPE PAIN RELIEVERS Source of pain relievers for nonmedical use among users 12 years or older: Manchikanti L, et al.. Pain Physician 2010; 13:

6 Illicit drug use from 1998 to 2008 Heroin: -19% Marijuana: -12% Cocaine: -17% Source: SAMHSA, Office of Applied Studies, National Survey on Drug Use and Health,

7 DRUG OVERDOSE DEATHS Unintentional drug overdose deaths by major type of drug, United States, Source: National Vital Statistics System Manchikanti L, et al. Pain Physician 2010; 13:

8 Adverse Outcomes Associated With Inadequate Analgesia Increased metabolic, stress response- increased catecholamines, cortisol, ADH, protein catabolism, sodium/water retention, hyperglycemia; Cardiac, sympathetic hyperactivity- tachycardia, hypertension, dysrrhythmias, increased O2 consumption/demand; Pulmonary complications- decreased lung volumes, atelectasis, V/Q mismatch, hypoxemia, hypercarbia, pneumonia, impaired mechanical ventilatory support;

9 Adverse Outcomes Associated With Inadequate Analgesia Hypercoagulability- thromboembolic events; Immunosuppression Decreased mobility- delayed recovery/rehabilitation; Increased length of ICU/hospital stay; Chronic,,p persistent pain; Psychological disorders-ptsd

10 Long-Term Sequelae of Opioid Consumption Tolerance Physical Dependence Addiction Opioid-Induced Hyperalgesia (OIH)

11 Tolerance State of physiologic adaptation in which continued exposure to a drug induces changes resulting in diminishing one or more effects of the drug over time; Creates the need for progressive increases in dose to achieve a particular level of effect; Mediated by NMDA receptors; Development of tolerance is not necessarily a sign of addiction; Tolerance is necessary for OIH, not visa versa.

12 Physical Dependence A bio-physiologic adaptive condition manifested by a drug class specific withdrawal syndrome that can result from the abrupt cessation, rapid dose reduction, or administration i ti of an antagonist; t Mediated by mesolimbic dopaminergic system; Continuous opioid intake of an IV morphine equivalent of at least 30 mg for more than 2 to 4 weeks is considered a risk for withdrawal; Onset of withdrawal can occur 6-18 hrs after the last dose of morphine or hrs after methadone.

13 Addiction A biopsychosocial state involving genetic, psychologic, and environmental factors influencing its development and manifestations; Characterized by the 4 Cs : impaired control over drug use; compulsive use; continued use despite harmful results; and drug craving; Pseudoaddiction refers to drug seeking behavior in response to under-treatment

14 Opioid-Induced Hyperalgesia Paradoxical lowering of the pain threshold in response to long-term exposure to opioids; Escalating opioid doses result in the development of hypersensitivity to pain, hyperalgesia and allodynia; A form of pain sensitization induced by opioids, which occurs within the CNS;

15 Opioid-Induced Hyperalgesia Mechanism appears to involve enhanced NMDA activity, increased levels of pronociceptive spinal dynorphin and increased excitatory descending pathways from rostral ventromedial medulla to the dorsal horn; Drugs having NMDA, kappa receptor antagonist activity may mitigate OIH.

16 19 th Century Observation: OIH At such times I have certainly felt it a great responsibility to say that pain, which I know is an evil, is less injurious than morphia, which may be evil. Does morphia tend to encourage theverypainitpretendstorelieve? it pretends to relieve? C. Albutt. On the abuse of hyperdermic injections of morphia. Practitioner, 1870; 5:

17 Mechanism of OIH Neuroanatomical sites and mechanisms implicated in the development of opioid- induced hyperalgesia: (1) Sensitization of peripheral p nerve endings. (2) Enhanced descending facilitation of nociceptive signal transmission. (3) Enhanced production and release as well as diminished reuptake of nociceptive neurotransmitters. (4) Sensitization of second-order order neurons to nociceptive neurotransmitters.

18 Tolerance vs. OIH Carroll IR, et al. Reg Anesth Pain Med 2004; 29:

19 Pain Sensitization Pain Sensitization

20 Opioid-Tolerant Patient The minimum i daily opioid id dose and duration of use that would signify an opioid-tolerant condition predisposing to increased post-trauma trauma opioid requirements and pain are not known. Criteria: Use of at least 30 mg of oral morphine equivalents daily for 2 weeks or longer. Patients ate tse exhibit btopoddepe opioid dependence, ce,addcto addiction issues, es,co consume high opioid doses, report greater pain intensity. Postoperatively, often a 30-50% increase in opioid requirements compared with preop equivalents Whether legitimate therapeutic use or illicit misuse/abuse.

21 Impact of Chronic Opioid Therapy on Postoperative Pain Retrospective case analysis of 360 patients; Average daily opioid dose of 30 mg po morphine equivalence; Found a 3-fold greater increase in postoperative opioid requirements. Rapp SE, et al: Pain 1995; 61:

22 Opioid Equivalency Allows dosage conversion from one opioid type to another or from one route of opioid administration to another. Determines the equianalgesia dose between 2 opioids, which will provide comparable pain relief. Accounts for the relative potency or dose ratio between opioids necessary to produce an equivalent analgesic effect.

23 Opioid Equivalence Dose conversions are usually initiated at 40-50% of the calculated dose to allow for incomplete cross-tolerance between opioids and variable pharmacokinetics. Subsequent doses are titrated to effect.

24 Opioid Conversions Drug Morphine Parenteral Oral 10 mg 30 mg Codeine 100 mg 200 mg Oxycodone Hydromorphone Methadone Fentanyl Meperidine NA 15 mg 2 mg 6 mg 1 mg 2 mg 25ug/hr x24 hr = morphine 50mg/24 hr 75 mg 300 mg

25 Opioid Conversion Acute Trauma/Perioperative Period: NPO status Chronic use MS Contin 200 mg po TID; Convert daily po morphine dose to IV = 8mg/hr; Initiate IVPCA morphine, basal rate 50% of calculate rate/hr, set bolus dose at least 50% higher than for opioid naïve patient, 1.5mg q 6 minutes, maximum hourly dose of 15 mg; Add adjunctive medications, as appropriate.

26 Opioid Conversion Post-Trauma Transition Period: Convert IV opioid regimen to an oral equivalence; Calculate total IV opioid consumption into morphine equivalents over the past 24 hours; Administer 50-60% of this dose as a long-acting opioid; Add a short-acting opioid at a dose 5-15% of the daily dose, on a prn basis, to cover breakthrough pain.

27 Opioid Conversion Post-Trauma Transition Period: Incrementally increase the baseline long-acting opioid by 30% of the prn dose used, approx every 5 half-lifes lifes until reaching desired effect or dose-limiting side effects. Rapid onset opioids, i.e oral transmucosal fentanyl or fentanyl film strips are designed for rescue therapy in sudden, severe flare-ups. Continue adjunctive medications.

28 Question Equianalgesic equivalence refers to which of the following: 1. A physiologic adaptation in which continued drug exposure induces changes resulting in diminishing a drug s effect. 2. The impaired control, craving, compulsive, and continued use of a drug despite harmful effects. 3. The abrupt discontinuation of the long-term use of a drug resulting in a characteristic withdrawal syndrome. 4. The relative dose of 2 drugs that provides approximately equal pain relief.

29 Answer Equianalgesic equivalence refers to which of the following: 4. The relative dose of 2 drugs that provides approximately equal pain relief.

30 Multimodal Therapy Rationale is to optimize analgesic benefits of medications and interventions and minimize adverse effects; Take advantage of the characteristic synergistic/additive pharmacologic actions between drugs and interventional techniques; Serve to reduce or avoid complications inherent to an opioid-centered analgesic regimen.

31 Multimodal Analgesia Morphine Potentiation NSAIDs, acetaminophen, nerve blocks Kehlet H, Dahl JB. Anesth Analg. 1993;77: Reduced doses of each analgesic Improved antinociception due to synergistic/additive effects May reduce severity of side

32 Pre-Emptive Analgesia Analgesia is initiated before the injurious event; Attempt to eliminate or reduce inciting nociceptive impulses, thus attenuate peripheral and central sensitization; Uses complimentary analgesic modalities targeting different sites of action; Not often possible in acute trauma.

33 Preventive Analgesia A broader application of the pre-emptive emptive analgesic concept; Incorporates multimodal analgesic therapies; Serves to reduce nociceptive inputs throughout the peri-traumatic/operative course; Provides a follow-through for continued analgesic therapy beyond the initial inciting trauma; Attenuates peripheral and central sensitization.

34 Multimodal Approach Pain Ascending Input Opioids, Descending Modulation Dorsal Horn alpha-2 agonists, NMDA antagonists, gabapentinoids Local anesthetics, opioids, id alpha-2 agonists, NMDA antagonists, gabapentinoids Spinothalamic tract Local anesthetics Trauma Peripheral nociceptors Peripheral Nerve Local anesthetics, NSAIDs Gottschalk A, Smith DS: Am Fam Physician 2001; 63:

35 Patient Controlled Analgesia A drug delivery system, which allows the patient to titrate their analgesic requirements by pushing a button that releases a dosage of opioid and/or local anesthetic into the blood stream, neuroaxial il space, or neural sheath. h

36 Patient Controlled Analgesia Applicable to intravenous, epidural, or nerve plexus drug delivery systems. Bolus dosage is pre-calculated. Limits are placed on the number of bolus activations per unit time. Time interval between activations (lockout interval). A maximum dosage over a given time period is set. Administration of a continuous basal infusion can be superimposed on the patient controlled boluses.

37 Intravenous Patient Controlled Analgesia Advantages over other intermittent, parenteral routes of analgesic drug delivery: High patient acceptance Better quality of analgesia Less total drug usage Fewer side effects Faster return to physical activity i

38 Neuroaxial Analgesia Involves placement of opioid and/or local anesthetic drugs into the intrathecal or epidural space. Neuroaxial opioids are not associated with sympathetic, sensory, or motor blockade Epidurally placed opioids diffuse across the dura to bind to opioid receptors in the substantia gelatinosa of the spinal cord. Intrathecal analgesia is limited by a single injection of opioid/local anesthetic.

39 Neuroaxial Analgesia Epidural analgesia can be provided by an intermittent injection or by a continuous catheter infusion. A 10-fold increase in epidural opioid dosage compared to an intrathecal dosage is required to produce a similar analgesic effect. Synergy between the combined analgesic effects of opioids and local anesthetics exists. Combination of opioids and local anesthetics allows for a decrease in dosage of each drug along with a decrease in the incidence id of side effects.

40 Peripheral Nerve Blocks Provide analgesia within a more limited anatomical distribution than neuroaxial blocks; Coverage is confined to a particular nerve or nerve plexus; Less disruptive of physiologic functions; Analgesia can be provided by a single injection or by a continuous nerve sheath catheter infusion of local anesthetic; Additive effects of combining clonidine with local anesthestic serve to prolong the duration and enhance the quality of the block.

41 Somatic Blockade of the Neck and Trunk Cervical Plexus Block Intercostal Nerve Block Thoracic Paravertebral Block Lumbar LmbrPr Paravertebral rtbrlbl Block Transversus Abdominis Plane Inguinal Nerve Block

42 Somatic Blockade of the Upper Extremity Brachial Plexus Block: Axillary Interscalene Supraclavicular Infraclavicular Blocks at the Elbow and Wrist: Radial Nerve Ulnar Nerve Median Nerve

43 Somatic Blockade of the Lower Sciatic Nerve Block Femoral Nerve Block Extremity Winnie s Three- in- One Block: Femoral Nerve Lateral Femoral Cutaneous Nerve Obturator Nerve Lumbar Plexus Block

44 Somatic Blockade of the Lower Popliteal Block: Tibial Nerve Common Peroneal Nerve Ankle Block: Saphenous Nerve Extremity Deep Peroneal Nerve Superficial Peroneal Nerve Posterior Tibial Nerve Sural Nerve

45 Pharmacologic Agents Multimodal adjuncts to an opioid-centered analgesic regimen; Act at different target sites; Provide additive/synergistic effects; Maximize therapeutic effects and minimize side effects; Goal is opioid-sparing.

46 Buprenorphine Opioid mu receptor partial agonist, kappa antagonist Analgesic, opioid dependency therapy Long, variable half-life life of 37 hours (range hours) Prevents/reverses OIH Available in IV/IM, sublingual, transdermal, and SQ implant dosage forms

47 Methadone Opioid mu receptor agonist, NMDA antagonist, serotonin re-uptake inhibition Long, variable half-life life hrs, risk of accumulation, delayed adverse effects Prolongation of the QTc interval, prevalence of 16-33%, weak dose-dependence. dependence. Can prevent/reduce OIH.

48 Acetaminophen Analgesic, antipyretic Mechanism: inhibition at central COX-3 receptors Synergistic effects with opioids; at least 20% opioid- sparing Not studied in opioid-tolerant population Less sedation, N/V IV preparation, Ofirmev, 1000mg IV Q 6 h Max daily dose 4000 mg in divided doses

49 NSAIDS Analgesic, anti-inflammatory inflammatory Inhibit both COX-1 and COX-2 receptors, decreasing production of prostaglandins and thromboxane Consistently show opioid-sparing effects Not studied in the opioid-tolerant population Parenteral ketorolac 15mg IV ~30 mg IM Ceiling dose for analgesic effects Cardiac, renal, hematologic, and orthopedic considerations

50 Gabapentinoids Gabapentin, pregabalin Modulate neuropathic pain via DRG voltage dependent calcium ion channels Associated with increase sedation Not studied in opioid-tolerant patients Meta-analysis analysis studies on pre-op gabapentinoid use suggest decreased pain scores and opioid use post-opop May be useful analgesic adjuncts

51 Alpha-2 Adrenergic Agonists Dexmedetomidine, clonidine Analgesic, sedative, anxiolytic Modulate catecholamine responses at supraspinal, dorsal horn and peripheral sites Opioid-sparing, decrease OIH, blunt opioid withdrawal Not studied in opioid-tolerant population Hypotension, bradycardia

52 NMDA Receptor Antagonists Ketamine, dextromethorphan Activity at the thalamic and spinal cord dorsal horn Dissociative anesthesia, amnesia, analgesia Psychomimetic effects Studied in opioid-tolerant patients Reverses/reduces opioid tolerance and OIH, potent perioperative analgesic

53 Ketamine Perioperative Opioid- Sparing Effects Randomized,,p prospective, p double-blinded, blinded,,p placebo- controlled; 52 opioid-tolerant, chronic back pain patients undergoing back surgery; Intra-operatively, ketamine administered 0.5 mg/kg IV on induction, with continuous infusion at 10ug/kg/min until wound closure; Results: 37% reduction in opioid consumption over the 48 hr postop period, extending out to 6 weeks postop. Loftus RW, et al: Anesthesiology 2010; 113:

54 Question Multimodal pain therapy involves all of the following, except: 1. Uses drugs whose mechanism of action targets differing pain pathways. 2. Allows the use of smaller doses of individual drugs to minimize adverse effects. 3. Employs the exclusive use of opioids to manage pain. 4. Takes advantage of the additive or synergistic actions between drugs and interventional techniques.

55 Answer Multimodal pain therapy involves all of the following, except: 3. Employs the exclusive use of opioids to manage pain.

56 Nursing Assessment Identify the opioid-tolerant patient on intake; Obtain a complete medication history, pain- relievers and other meds; Determine the dose and frequency of opioid medications, last dose, any patches? Ascertain the baseline pain, character, and intensity; Use a validated pain assessment tool, VAS, NAS;

57 Nursing Plan Risk considerations- mental status, hemodynamic stability, respiratory functioning; Monitoring for oversedation, sleep apnea, withdrawal symptoms; Anticipate increased pain and opioid requirements; Determine baseline opioid conversions and equianalgesic equivalents; Consider multimodal therapies

58 Nursing Interventions Facilitate timely initiation of opioids, adjunctive medications, and regional techniques into the analgesic regimen; Monitor the analgesic progress and level of effectiveness and development of side effects. Ensure appropriate ordering and timing of administration for the analgesic regimen; Avoid analgesic gaps.

59 Question Which of the following is false in reference to the opioid-tolerant patient experiencing acute trauma pain? 1. Opioid pain requirements will increase. 2. Patient will experience withdrawal symptoms at higher h opioid id doses. 3. Multimodal therapies can be opioid-sparing. 4. Analgesic gaps can be avoided db by using scheduled d dosing administration and patient-controlled analgesia.

60 Answer Which of the following is false in reference to the opioid-tolerant patient experiencing acute trauma pain? 1. Patient will experience withdrawal symptoms at higher opioid doses.

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