Associate Professor Supranee Niruthisard Department of Anesthesiology Faculty of Medicine Chulalongkorn University January 21, 2008
PAIN MECHANISMS Somatic Nociceptive Visceral Inflammatory response sensitizes nociceptors Central Neuropathic Peripheral Repetitive nociceptive stimuli Hyperalgesia Neuro- plasticity Hyperexcitability (wind-up) Psychological financial & social factors
PAIN ASSESSMENT Pain Pain is a subjective experience Self Self assessment is more reliable than observer assessment Pain Pain should be assessed and recorded as the 5 th vital sign by Visual analogue scales Numeric rating scale Categorial rating scale VAS NRS S. Niruthisard
LOCATION OF PAIN Generalized pain Regionalized pain Baseline pain Procedural pain Specific Rx Symptomatic Rx Pharmacologic Non-pharmacologic Analgesic drugs Physical therapy - non-opioid opioid Topical - opioid Psychological Adjuvants + Neural blockade S. Niruthisard
Three steps analgesic ladder Severe pain score = 7-10 Moderate pain score = 4-6 Mild pain score = 1-1 3 S. Niruthisard
GUIDELINES FOR ANALGESIC DRUG ORDERS Pain symptom Intensity Route? drug selection? Mild Moderate Severe Neuropathic Nociceptive Psychogenic Mixed Oral Buccal,, SL Rectal Transdermal IV, IM, Sc,TT Constant moderate to severe pain Intermittent pain Long-acting analgesics PRN short acting analgesics + PRN short-acting analgesics S. Niruthisard
ANALGESICS FOR SYMPTOM CONTROL Non- opioids Acetaminophen (500 mg) NSAID, ASPIRIN Opioid Weak opioid - codeine tramadol Strong opioid - morphine, pethidine fentanyl,, methadone, temgesic, pentazocine, nalbuphine S. Niruthisard
ANALGESICS FOR SYMPTOM CONTROL Adjuvants Antidepressants : TCA, Anticonvulsants : carbamazepine, phenytoin, clonazepam N- type calcium channel blockers : gabapentin NMDA antagonistis : ketamine, dextromethophan S. Niruthisard
ANALGESICS FOR MILD TO MODERATE PAIN (PAIN SCORE 2-5) 2 ACETAMINOPHEN Mechanism : inhibit the release of PG in SC inhibit COX-3 isoenzyme spinal pain inhibition via serotonin mech. no anti-inflammatory inflammatory effects Oral, Oral, rectal, (IM, IV) S. Niruthisard
ANALGESICS FOR MILD TO MODERATE PAIN (PAIN SCORE 2-2 5) ACETAMINOPHEN Usual dose : 10 mg/kg/dose effective dose for pain control in adult = 1 gm po qid children = 10-15 15 mg/kg po initial PR dose 40 mg/kg then 20 mg/kg Toxic doses = 10-15 15 gm/d Additive effects by coadministration with NSAIDS/opioids S. S. Niruthisard
NSAIDs Mechanism : inhibit COX in the peripheral and central nervous system Mild to moderate pain - conventional NSAIDS Moderate to severe pain - specific COX-2 inhibitor or + opioid Improve analgesia (opioid( sparing) Ceiling effects Use one type of NSAIDs at a time S. Niruthisard
NSAIDs selectivity classification Class Classical Selective COX-2 Inhibitors Specific COX-2 Inhibitors Criteria Drugs COX-2 2 IC 50 >COX-1 1 IC 50 Aspirin, indomethacin, ibuprofen, diclofenac, oxicam COX-2 2 IC 50 <COX-1 1 IC 50 Meloxicam, menisulide, Inhibit COX-1 1 at higher etodolac therapeutic dose COX-2 2 IC 50 <<COX-1 1 IC 50 Celecoxib, rofecoxib Uninhibit COX-1 1 at parecoxib, valdecoxib, therapeutic dose etoricoxib, lumilarcoxib S. Niruthisard
SIDE EFFECTS OF NSAIDs Gastropathy - bleeding/ulceration Homeostatic function - platelet function Nephrotoxicity Hepatic Hepatic dysfunction Hypersensitivity reaction S. Niruthisard
Algorithm for the use of COX-2 2 inhibitors and NSAIDs in an aging patient 1. Taking oral antihypertensives? renal disease? Impaired LV function? No 2. On low dose aspirin? No 3. Advanced aging History of peptic ulcer Taking steroid? Taking anticoagulant/ steroid Regular use? Yes High risk Yes Avoid NSAIDs and COX-2 inhibitor Take NSAIDs + PPI Take COX-2 2 inhibitor or nothing Intermittent use? High risk Take NSAIDs
CODEINE Opium Opium alkaloid, pro drug of morphine Mechanism: Weak mu agonist Oral Oral dose = 30-60 mg every 4-4 6 h S/E S/E - nausea, constipation, addiction
TRAMADOL Mechanism : weak mu agonist non- opioid spinal and CNS effects via norepinephrine and serotoninergic mechanism Racemic mixture Advantages : minimal sedation, respiratory depression, GI stasis, abuse potential S/E : dizziness, nausea, dry mouth Dose : 1-1 2 mg/kg every 6-6 8 h
AFFINITY OF DRUGS AT OPIATE RECEPTORS Drugs Mu Delta Kappa Sigma Morphine +++ + ++ N Codeine + + + N Methadone ++ + ++ N Meperidine ++ + + N Fentanyl ++++ + N N Buprenorphine P N +++ N Nalbuphine -- N ++ N Pentazocine -- + ++ + Naloxone --- -- -- N
MEPERIDINE Potency 1/10 of morphine,, duration : 3-4 h Atropine- like side effects Active metabolite - normeperidine (t1/2 15-20 hrs) causes CNS excitation, excreted by kidney Good for shivering in low dose
PARENTERAL MEPERIDINE IS NOT APPROPRIATE FOR Long- term use (beyond several days) Chronic Chronic pain syndrome Elderly Elderly patients Patients Patients with renal dysfunction
APS recommends : Meperidine should not be used more than 48 hrs. for acute pain in patients without renal or CNS diseases, or at doses greater than 600 mg/24 hrs., and should not be prescribed for chronic pain.
THE RATIONALE FOR PRESCRIBING PARENTERAL MEPERIDINE There There is intolerance to all other opioids and/or Brief Brief analgesia is needed
A case of CA stomach undergone total gastrectomy. Postoperative pain control?
PAINCIPLES OF ACUTE PAIN MANAGEMENT Determine source and magnitude of nociception Understand nociception v.s.. other components and treatment Achieve and maintain analgesic : drug levels Re- evaluate and refine therapy regularly
Acute perioperative pain is primarily nociceptive in nature.
ASA RECOMMENDATIONS : Clinical Practice Guideline for acute perioperative pain management Three safe and effective therapeutic options: PCA PCA with systemic opioids Epidural Epidural analgesia with opioid + LA Regional analgesia
DRUGS USED IN POSTOPERATIVE ANALGESIA NSAIDSNSAIDS Oral : alone (I), adjunct to opioid (I) Parenteral : ketorolac, parecoxib (I) Rectal (IV) Paracetamol Oral (II) Rectal(IV)
DRUGS USED IN POSTOPERATIVE ANALGESIA OpioidsOpioids Oral (II) IM Subcutaneous (I) : PCA (I) Intravenous (I) : PCA (I) Epidural/ Epidural/intrathecalintrathecal (I) Sublingual (IV) Local Local anesthetics Epidural/ Epidural/intrathecalintrathecal (I) Peripheral nerve block (I)
Average first 24 hr. morphine requirement (mg) Age >20 years = 100 - age in year Single dosage = average 24 hr. MO requirement 8 (frequency of drug used)
ANALGESIC RESPONSE Unconscious Apnea Respiratory depression Increased sedation Increased nausea & vomiting Opioid dose
CLINICAL MANIFESTATION OF OPIOIOD OVERDOSE Sedation Hypoventilation Apnea Coma Meiosis MANAGEMENT Support ventilation Naloxone : 1-1 2 microgram/kg IV q 10-15 min or continuous infusion 5 microgram/kg/hr
ADMINISTRATION OF OPIOIDS : BY TITRATION AIMS Patient comfort No severe respiratory depression Sedation score <2 RR >8/min REQUIREMENT An age- related range of dose Dose intervals appropriate to the route of administration Monitoring sedation score, pain score and RR, + side effects
A man with sudden onset of severe abdominal pain was transferred to the emergency room. Could an analgesic be given to him?
Somatovisceral convergence of visceral input onto dorsal horn neurons and role of referred pain
Intense visceral stimulation causes activation of corresponding spinal cord segments gives rise to painful sensations in the corresponding cutaneous distribution i.e. referred pain.
LATER CLINICAL FINDINGS Sensation referred to somatic structures of body wall Pain Pain becomes sharper, better defined and localized Qualitatively similar to somatic pain No No longer + marked neuro- vegetative/ emotional signs Referred pain may or may not + hyperalgesia
Inflammation of parietal peritoneum results in reflex muscle spasm of the area directly over the involved structure. - motor reflex, somatic reflex
A A 42- year old man with chronic arterial occlusion disease Dry Dry gangrene of left big toe with severe pain
ACUTE PAIN Acute pain Signal Signal of organic disease process Cause Cause usually obvious Disappearing with treatment of the cause OpioidsOpioids typically indicated and effective Chronic pain No No useful function served Cause Cause often unclear Often Often unresponsive to many forms of therapy OpioidsOpioids rarely indicated or effective Adjuvants provide the major rules
CA CA pancreas, inoperable Carcinomatosis peritonei
Therapeutic pain plan for patients with cancer
Who analgesic ladder
GUIDELINES FOR OPIOID ADMINISTRATION Around- the- clock dosing schedules are preferable to PRN dosing Titrate dose to effect using respiratory rate and excess sedation as endpoints Prophylactic treat side effects such as constipation Clinician familiarity with prescribed narcotic is essential Patient s s fears concerning addiction dependence, and tolerance need to be addressed
EFFECTIVE PAIN CONTROL (GOOD PAIN RELIEF, COST EFFECTIVENESS, LESS COMPLICATIONS) Knowledge in pain management Available of effective drugs Collaborated teamwork Supportive healthcare system Pain Pain practice guideline