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Management of Pain. C. Brian Warriner, MD, FRCPC Professor and Chair UBC Department of Anesthesiology, Pharmacology and Therapeutics brian.warriner@vch.ca. Management of Pain. Agenda: Definitions Pathophysiology Analgesics Gases (N 2 O) Opiates NSAID’s Acetaminophen

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Management of Pain


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    1. Management of Pain C. Brian Warriner, MD, FRCPC Professor and Chair UBC Department of Anesthesiology, Pharmacology and Therapeutics brian.warriner@vch.ca

    2. Management of Pain • Agenda: • Definitions • Pathophysiology • Analgesics • Gases (N2O) • Opiates • NSAID’s • Acetaminophen • Phencyclidine – derivatives (NMDA antagonists) • Alpha2-adrenergic agonists

    3. Management of Pain • Agenda (continued) • Analgesics • Local anesthetics – combination therapy • Modes of delivery • Oral • Rectal • Systemic • Neuraxial • Modes of Delivery – Case reports • Obstetrics

    4. Management of Pain • Definition: • Oxford Pocket Dictionary • Strongly unpleasant bodily sensation such as is caused by illness or injury • Mental suffering or distress • Vulgar as in “pain in the neck” or other anatomical areas • Great cares or troubles • Verb (idiomatic) – to pain

    5. Management of Pain • Descriptors: • Sharp, crushing, burning, cramping, gassy, throbbing, cutting, aching, dull, deep, pinching, slashing, pin-point, continuous, spasm, tearing, lancing, knifing, etc…

    6. Management of Pain • The Pain Team: • The patient • Nurses (nurse-clinician) • Anesthesiologist • Clinical pharmacologist • Psychiatrist • Pharmacist • Psychologist • Physiotherapist • Occupational therapist • Radiologist • Neurosurgeon • Social worker • The family • Pastoral care • Obstetrical pain: patient, partner, coach, midwife, obstetrician

    7. Management of Pain • Incidence: • Appears to be independent of race, culture, economic status • 30% of adults have “chronic pain” at any given time • 12% have severe pain • 2% have disabling pain • 80,000 British Columbians have disabling pain – more common that cancer or heart disease

    8. Management of Pain Pathophysiology of Pain

    9. Management of Pain • Pain neurotransmission – simplified • Nociceptive receptors in periphery respond to pH, ATP, and ligands to create afferent nerve conduction to dorsal root ganglia, dorsal horn of the spinal cord, brainstem, thalamus, hypothalamus, and cortex • Modulation occurs at all levels and is mediated by opioid peptides, norepinephrine, glycine, and GABA

    10. Management of Pain • Opioid peptides inhibit synaptic transmission at several sites: beta-endorphin, enkephalins, dynorphins. • Opiate receptors are mu, delta and kappa

    11. Management of Pain • Opioids produce analgesia because of their actions in the brain, brainstem, spinal cord, and peripheral terminals of primary afferent nerves. • Brain: Alter mood in response to pain • Brainstem: stimulate release of inhibitory signals • Spinal cord: inhibit primary afferent activity • Peripheral sites: inhibit afferent response

    12. Management of Pain • Types of Pain: • Acute – severe but usually managed with opioids, NSAID’s, acetaminophen, local anesthetics • Transitional: not easily diagnosed, needs aggressive treatment to prevent transition to chronic • Chronic: long-lasting, difficult to treat, personality changes, drug seeking

    13. Management of Pain • Complex regional pain syndromes: • Previously called reflex sympathetic dystrophy • Transitional to chronic in nature • Can be initiated by relatively minor insults • Peripheral sensitization resulting in allodynia and hyperalgesia • Requires very aggressive team approach to therapy • Can result in completely non-functional limb requiring amputation

    14. Management of Pain • Neuropathic pain: • Injury to peripheral nerves and CNS can lead to functional and structural changes in the pathways • Nerve regeneration after injury can produce a nidus of intense pain • Flitting, shock-like pain • Often very difficult to treat

    15. Management of Pain • Classes of Drugs: • Opioid receptor agonists • Non-steroidal anti-inflammatory drugs • Tri-cyclic antidepressants • Anti-convulsants • NMDA receptor antagonists • Alpha2- agonists • 5HT1-agonists for migraine • Gases (N2O)

    16. Management of Pain • Opioid receptor agonists: • Morphine • Heroin • Meperidine • Codeine • Oxycodone • Hydromorphone • Fentanyl • Sufentanil • Remifentanil, alfentanil • methadone

    17. Management of Pain • Opioid receptor agonists: • Act on mu-receptors to produce both effects and side-effects – brain, brainstem, spinal cord, and peripheral terminals • Side effects: respiratory depression, nausea and vomiting, constipation, sedation, dizziness, euphoria, confusion, muscle rigidity, pruritus • Physical and psychological dependence

    18. Management of Pain • Opioid receptor agonists: • Tolerance can develop quickly (in a matter of minutes with remifentanil) • Morphine is the reference opioid – used primarily for treatment of acute pain – injury, surgery, acute abdomen, etc • Primary metabolism is in liver and oral morphine is rapidly reduced by first-pass metabolism

    19. Management of Pain • Opioid receptor agonists: • Many dosage forms: • Oral, transmucosal • Inhalation • Subcutaneous • Intramuscular • Intravenous (continuous, intermittent, PCA) • Intra-thecal • epidural

    20. Management of Pain • Opioid receptor agonists: • Codeine – methyl-morphine – rapidly converted to morphine by the liver – effective orally and intramuscularly – commonly used as antitussive and mild analgesic • Heroin – converted to morphine by liver – no real therapeutic advantage over morphine – addicted claim it produces more euphoria than morphine but studies inconclusive

    21. Management of Pain • Opioid receptor agonists: • Meperidine (Demerol) – first synthetic opioid – 1/10th potency of morphine • Less Sphincter of Vater spasm • Fentanyl – 100 times potency of morphine – intermediate duration – intravenous – used primarily by anesthesiologists and ER physicians

    22. Management of Pain • Opioid receptor agonists: • Sufentanil – 1000 times potency of morphine – intermediate duration – used only by anesthesiologists • Remifentanil – 70 times potency of morphine – very short duration of action - metabolized by ester hydrolysis in plasma – given only by continuous intravenous infusion by anesthesiologists

    23. Management of Pain • Opioid antagonists: • naloxone – very rapid reversal of opioid effects – given IV by ER physicians and anesthesiologists • Naltrexone – longer acting antagonist used in treatment of both opioid addiction and alcoholism

    24. Management of Pain • Non-steroidal anti-inflammatories • ASA and others of same class • Ibuprofen is a relatively low potency, short acting example of the family • Inhibit the action of cyclooxygenase enzymes (COX-1 and COX-2) and reduce the production of prostaglandins

    25. Management of Pain • NSAID’s : • Analgesia by reducing prostaglandin synthesis • Reduce the recruitment of leukocytes which produce inflammatory mediators • Directly inhibit the release of prostaglandins in the dorsal horn

    26. Management of Pain • NSAID’s: • Side effects: gastric hemorrhage, platelet dysfunction, renal toxicity • Specific drugs: • ASA – relatively short acting, little negative effect upon kidney • Acetaminophen – reduces central prostaglandin synthesis – no real anti-inflammatory effect – no renal effects – overdose can cause acute liver failure

    27. Management of Pain • NSAID’s: • Specific drugs: • Ibuprofen – relatively short acting • Naproxen, ketorolac (systemic), diclofenac, and others – relatively long acting – all have negative renal and gastric effects – likely also have cardiac effects • COX-2 inhibitors were introduced with the expectation of fewer side effects (particularly gastric) but caused increased incidence of ischemic cardiac events and were withdrawn from the market

    28. Management of Pain • Antidepressants: • Tri-cyclics • Increase norepinephrine and serotonin activity in spinal cord • Activate depressed chronic pain patients • Diabetic neuropathy and post-herpetic neuralgia • Amitriptyline, nortriptyline and imipramine

    29. Management of Pain • Anticonvulsants: • Reduce neuronal excitability • Gabapentin, carbamazepine • Chronic pain management • Diabetic neuropathy • Trigeminal neuralgia • Dizziness, somnolence, confusion, ataxia • Pre-gabalin new member of this class – fewer side effects –heavily marketed

    30. Management of Pain • NMDA receptor antagonists: • Reduce central sensitization due to increased NMDA • Ketamine (phencyclidine relative) – general anesthetic agent which, in small doses, is an effective analgesic • Used occasionally for labour analgesia and analgesia prior to surgery.

    31. Management of Pain • Alpha2-agonists: • Clonidine • Can be given orally or neuraxially • Sedation, severe postural hypotension, very dry mouth

    32. Management of Pain • 5HT1-agonists: (sumatriptan) • For the treatment of migraine headaches • Vasoconstriction and prevention of central sensitization • Vasoconstriction can increase risks in other vascular beds such as the cardiac

    33. Management of Pain • Local anesthetics as an adjunct to opiates: • Neuraxial analgesia • Sub-arachnoid (spinal) • Epidural • loss of sensation, muscle weakness, hypotension

    34. Management of Pain • Modes of delivery: • Oral – most drugs • Rectal – acetaminophen, NSAID’s, ASA • IM or IV – opiates, ketorolac (NSAID) – patient controlled analgesia (PCA) • Neuraxial – opiates, clonidine, local anesthetics • Percutaneous – fentanyl patch

    35. Management of Pain • Case 1: • A 27 year old male is in a fight and appears in the ER with severe abdominal pain and evidence of internal damage. He asks for pain relief. What would you do?

    36. Management of PainPCA

    37. Management of Pain • Case 2: • A 60 year old woman is admitted to the hospital with cancer of the lung. She requires a lobectomy. This is associated with very severe post-operative pain. What can be done to help?

    38. Management of PainEpidural

    39. Management of Pain • Case 3: • A 62 year old woman complains of continuous nagging, aching pain over her back and legs. Neurological and musculo-skeletal exam are essentially normal except for reduced range of motion of the back and lower limbs. How should her pain be managed?

    40. Obstetrical Pain • Each patient has a unique labour pain experience • Labour pain is mediated from t10 – l1 • Intermittent, increasing in intensity, very severe • Delivery pain is mediated from S2,3,4 and tends to be continuous or nearly so

    41. Downloaded from: Miller's Anesthesia (on 27 November 2006 01:15 AM) © 2005 Elsevier

    42. Downloaded from: Miller's Anesthesia (on 27 November 2006 01:15 AM) © 2005 Elsevier

    43. Obstetrical Pain • Pain varies greatly from patient to patient and pregnancy to pregnancy • Modes: • Psycho-prophylaxis – breathing, relaxation exercises • Massage, baths, acupuncture • Nitrous oxide – demand valve respirator for period during contraction only – effective analgesic but of only intermediate potency – can cause sedation, confusion

    44. Obstetrical Pain • Modes: • Intravenous narcotics: different effects on Mom and babe – potential for respiratory depression in new born • Ketamine – effective in small doses but effect short-lived and larger doses can cause neuro-psychiatric effects • Intramuscular narcotics – same problems as IV but longer lasting

    45. Obstetrical Pain • Modes: • Epidural – continuous infusion of local anesthetic (dilute) and opioid (usually fentanyl) – can cause reduced muscle strength and loss of urge to push – slows down early stages of labour but probably quickens entire labour time (controversial) • Various potential complications associated with the procedure

    46. Recent Developments • May, 2008 - British Columbia 1st province to include “chronic pain” as separate disease entity under the common heading of “chronic diseases” – allows funding for research and treatment to be released by Ministry of Health • October 31, 2008 – BC Pain Society approved by BC Legislature

    47. Management of Pain • brian.warriner@vch.ca