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Multimodal Regiments for Acute Pain Management - Prof. A. Husni Tanra
This document provides information on multimodal regiments for acute pain management. It discusses the goals of multimodal analgesia including reducing opioid use through additive or synergistic effects. Key points: - Multimodal analgesia involves using two or more analgesics with different mechanisms to better treat multiple pain sources and reduce side effects. - Postoperative pain involves peripheral and central sensitization, so multimodal regiments target both levels. - Common regiments discussed include paracetamol, NSAIDs, COXIBs, ketamine, gabapentinoids, clonidine and opioids. Low dose ketamine and gabapentinoids are highlighted for their anti-hyperalgesic effects. - Combining
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Multimodal Regiments for Acute Pain Management - Prof. A. Husni Tanra
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- 2. Multimodal Regiments forAcute Pain Management A. Husni Tanra Department of Anesthesiology IC and Pain Management Faculty of Medicine Hasanuddin University Makassar Indonesia
- 3. What is multimodalanalgesia? Is a combination of two or more analgesics that act at different mechanisms, produce additive or synergistic analgesia Main goals of Multimodal Analgsia is to reduce the amount of Opioid
- 4. 1. Synergetic .............2+2>4 2. Additive ................ 2+2=4 3. Subadditive ........... 2+2=3
- 5. Why we needmultimodal analgesia for posoperative pain? No single analgesic is perfect and no single analgesic can treat all types of pain. Multimodal Analgesia potentiating in efficacy, reduced doses, minimal adverse effect. Improve the outcome. Most of the pain is a multifaceted and multiple-sources.
- 6. Characteristic of PostoperativePain Postop pain Nociceptor sensitisation Somatic Pain muscle, fascia, ligament Cortical Responses Cutaneous Somatic pain Visceral Pain Reflex response Muscle spasm Referred pain
- 7. Different types of pain Differentpain intensity Different location of pain Different risks and benefits of analgesic techniques Different surgical procedures have characteristic pain profiles Different procedures
- 8. •Tissue damage •Inflamed tissue Surgery Nociceptive input PAIN Surgeryhas a biphasic insults to the body 1. Trauma to tissue 2. Inflammatory response
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- 10. PERIPHERAL ACTIVITY CENTRAL SENSITIZATION Decreased threshold to peripheral stimuli Increased spontaneous activityExpansion of receptive field Hyperalgesia Allodynia Tissuedamage Primary Hyperalgesia Nerve damage Spontaneous pain Secondary Hyperalgesia 2 .Central Sensitization
- 11. So, after thesurgery there is a change in NS what we called: “Neuro-Plasticity of the Nervous System”
- 12. Neuro-Plasticity of theNS Primary hyperalgesiaPeripheral sensitization Secondary hyperalgesia Spinal “wind-up” Central sensitization Histamine, Leukotrienes, Norepinephrine, Cytokines, Bradykinin, Prostaglandins, Neuropeptides, 5-HT, Purines, H+/K+ions Modify by AHTAfter the injury the NS will changed neuro-plasticity
- 13. After surgery Pain Sensitization: Hyperalgesia and Allodynia Normal pain response Sensitised pain response Injury X HYPERALGESIA Stimulus intensity Pain intensity for stimulus X normal pain response Pain intensity for stimulus X sensitised pain response ALLODYNIA Painintensity 10 8 6 4 2 0
- 14. • ALLODYNIA • HYPERALGESIA •PROLONGED PAIN • REFERRED PAIN CLINICAL PAIN (PATHOPHYSIOLOGICAL PAIN ) Vanished after healing Chronic Pain (1 %)X
- 15. Basic Principle ofPostop Pain Management is preemptive analgesia Peripheral and Central sanitization prevent the occurrence of reduced the process of Neuroplasticity By Giving Anti-hyperalgesic & Anti-allodynia
- 16. Antihyperalgesic Drugs • NSAIDs(Nonsteroidal anti-inflammatory drugs) • COXIBs (Selective COX-2 inhibitors) • lidocaine (iv and topical) • Ketamine (low-dose) and other NMDA antagonist • Clonidine (iv and Intrathecal) • Gabapentinoid (Gabapentin and Pregabalin) • Amitriptyline • TENS • Midazolam (Intratheca
- 17. Antiallodynic Drugs • Lidocaineiv • Ketamine (low-dose) & other NMDA antagonist • Gabapentin (Oral and intrathecal) • Clonidine (iv and intrathecal) • Propofol (low dose) • Midazolam (intrathecal)
- 18. Anti-hyperalgesic Therapy: Opioid-Sparing ~30% reduction Opioid Opioid Painintensity X Stimulus intensity Anti- hyper algesic Normal pain response Sensitised painresponse Partially desensitised pain response
- 19. Philosophy of MultimodalAnalgesia Not only just giving 2 or more drugs which different mechanism, but; • One drug should be effective at peripheral sensitization and other at central sensitization. • Combine drugs must be synergetic or addictive. • Must be proven by laboratory or clinical data. • Some drugs may act at several point at nociceptive pathway.
- 20. Local anesthetics Corticosteroids NSAIDs COXIBs Local Anesthetic DRG Opioids Gabapentinoids Clonidine Modifyby AHT Ketamin Paracetamol COXIBs Transduction TransductionModulation Perception Transmission Modulation Target Point of Analgesic Drugs
- 21. WHAT IS THEMOST REGIMENTS There are many regiments for multimodal analgesia, but the most popular are: Opioid Local Anesthetic Paracetamol NSAIDs and Coxibs NMDA Antagonist (Ketamin) -2 antagonist (Clonidine) 2 (subunit of Ca Channel) agonist (Gabapentinoid)
- 22. 1. Paracetamol Acetaminophen/APPA Para-aminophenol Analgesic EffectsAntipyretic Effect Route of Administration - Orally - Rectally - Intravenously Oscier CD & Milner QJ (2009) Peri-operative use of paracetamol. Anaesthesia 64(1): 65–72. No Anti-Histamine Effects
- 23. Central Antinociceptive Effect Bertoliniet al, 2006; Botting, 2006; Pickering et al, 2006; Mallet et al, 2008; Pickering et al, 2008; Mancini et al, 2003 Mechanism Of Action Central COX (Cyclooxygenase) Inhibition Activation of the endocannabinoid system and serotonergic pathways) prevent prostaglandin production at the cellular level.
- 24. Paracetamol is verysafe drug as long as it is given within recommended doses (Adult < 4 gr/day, Infant and children 20-40 mg/kgBW) 1. All Age – from Infant to Elderly 2. From pregnant to Lactating Woman 3. Can be used for patients with renal and hepatic impairment. Paracetamol
- 25. Guidelines line forpostoperative pain management state that: “Unless contraindication, all patients should receive an around-the clock(ATC) regiment on NSAIDs, COXIBs, or Paracetamol”. American Society of Anesthesiologists Task Force on Acute Pain Management 2004;100:1573-1581
- 26. Hyllested M, JonesS, Pedersen JL et al (2002) Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth 88(2): 199–214. Paracetamol can be the best alternative to NSAID especially for high risk patients It is appropriate to administer acetaminophen with NSAID, or COXIBs additive or synergistic effects Intravenous form of paracetamol has more predictable onset and duration of actions Qualitative Review of Paracetamol and NSAIDs
- 27. 1.Sindet-Pedersen S.1997. Dataon file. * I.V. paracetamol was administered as a bio-equivalent dose of propacetamol. Fast onset of action * 1 Sindet-Pedersen S, 1997 Rapid onset: 5min Peak at ideal time: 30min IV paracetamol for dental Good residual effect at >6hrs
- 28. Paracetamol has OpioidSparing Effects I.V. paracetamol in these studies was administered as a bio- equivalent dose of propacetamol.
- 29. Quantitative Systemic Review2010 Paracetamol and NSAIDs (cox1 and cox2) Combination of paracetamol and an NSAIDs may offer superior analgesia compared with either drug alone (Anesth Analg 2010)
- 30. Combination of paracetamoland parecoxib may useful in patients who are susceptible to haemorrhagic complications of NSAIDs Parecoxib and Acetominophen
- 31. A combination of1000 mg paracetamol and 30mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal, with no significant difference of side effects during the 12 hour period studied Paracetamol vs Paracetamol + Codeine In post-operative dental pain
- 32. Tramadol/paracetamol combination tabletsprovided analgesic efficacy with a better safety profile to tramadol capsules in patients postoperative pain following ambulatory hand surgery. Paracetamol + Tramadol
- 33. Advantages of MultimodalAnalgesia Elia N, Lysakowski C & Tramer MR (2005) Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology 103(6): 1296–304. Acetaminophen, NSAIDs, or COXIBs Added To PCA Morphine All of analgesic agent provided an opioid- sparing effect However, the decrease in morphine use did not consistently result in a decrease in opioid-releted adverse effects NSAIDs + Morphine was associated with a decrease in the incidence of PONV and sedation
- 34. NSAIDs vs COXIBsFor Postoperative Pain Romsing J & Moiniche S (2004) A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain. Acta Anaesthesiol Scand 48(5): 525–46. Demonstrate Equipotent Analgesic Efficacy After Minor and Major Surgical Procedure NSAIDs COXIBs COXIBs Better Alternative TO NSAIDs in the perioperative setting COXIBs associated with: Reduce gastrointestinal side effects Absence of anti-platelet activity
- 35. Limitation of TraditionalNSAIDS: (Aspirin/NSAID) sensitive asthma • The COX-2 selective inhibitors celecoxib1,2 and rofecoxib3,4 given orally do not cause bronchospasm in patients with aspirin/conventional NSAID- sensitive asthma 1. Gyllfors et al. Allergy Clin Immunol 2003;111:1116; 2. Martin-Garcia et al. J Investig Allergol Clin Immunol 2003;13:20; 3. Stevenson et al. J Allergy Clin Immunol 2001;108:47; 4. Martin-Garcia et al. Chest 2002;121:1812
- 36. Anesthesia Dose morethan 2 mg/kg (iv) anesthesia + produce side effects such us Psychomimetic effect • Excessive sedation • Cognitive Dysfunction • Hallucination • Nightmares Subanesthesia Dose (Low Dose) < 1 mg/kg demonstrated significant analgesic efficacy without these side effects Very Low dose (0,15 mg/kg) single intraoperative injection of ketamine 0,15 mg/kg improve analgesia and passive knee mobilization 24 hour after arthroscopy
- 37. Ketamin More Frequently Usein Postorthopedic Surgical Pain Management Arthroscopic Anterior Cruciate Ligament Surgery Outpatient Knee Arthroplasty Total Knee Arthroplasty A Single intraoperative injection of ketamin (0,15 mg/kg) improved analgesia and passive knee mobilization 24 hour after surgery Improved Postoperative Outcome When combine with epidural or femoral nerve block, increase postoperative pain relief for total knee arthroplasty. •Menigaux C, Guignard B, Fletcher D, Dupont X, Guirimand F, Chauvin M. Anesth Analg. 2000;90:129–135. •Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Anesth Analg. 2001;93:606–612. •Himmelseher S, Ziegler-Pithamitsis D, Agiriadou H, Martin Jjelen-Esselborn S, Koch E. Anesth Analg. 2001;92: 1290–1295. •Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D. Anesth Analg. 2005;100:475–480.
- 38. Why I gaveketamin low dose to this patient?
- 39. progressive increase in responseof second order neurons to repetitive C-fiber input “Wind-Up” Mendel and Wall, 1965 Now is appreciated that “wind-up” is a crucial factor for chronic pain after surgery NMDA unblocked NMDA blocked (AP5) Stimulus frequency applied to C-fiber nerve endings Actionpotentialdischargein Secondorderspinalneurons 60 50 40 30 20 10 0 2 4 6 8 10 12 14
- 40. Ongoing activation afterinjury, the receptive fields of these neurons expand, leading to spread of pain. Recruitment
- 48. • Low-dose ketamineis not really an ‘analgesic’, but better described as: ‘anti-hyperalgesic’ ‘anti-allodynic’ ‘tolerance-protective’ of opioid Opioid-induced Hyperalgesia
- 49. Gabapentin and Pregabalin EckhardtK, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G. Anesth Analg. 2000;91:185–191. Hurley RW, Chatterjea D, Rose Feng M, Taylor CP, Hammond DL.. Anesthesiology. 2002; 97:1263–1273. Gilron I, Orr E, Tu D, O’Neill JP, Zamora JE, Bell AC. Pain. 2005;113:191–200. Reuben SS,Buvanendran A,Kroin JS, Raghunathan. Anesth Analg. 2006;103:1271–1277. Enhanced Analgesic effects of:Gabapentin Gabapentin and pregabalin Provide anti-hyperalgesiacan synergically with NSAID Pregabalin Superior to either single drugs for postoperative pain following spinal fusion surgery and Celecoxib
- 50. Sedation can beinterpreted as a negative outcome of gabapentin ,however its can be benefical in the perioperative setting as an anxiolysis
- 51. Paracetamol and Gabapentin Paracetamol + Gabapentin Analgesic + Antihyperalgesic postoperative pain scores & Rescue Analgesics but more episodes of nausea and vomiting and higher levels of sedation
- 54. De Kock MF,Pichon G & Scholtes JL (1992) Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia. Can J Anaesth 39(6): 537–44. Jeffs SA, Hall JE & Morris S (2002) Comparison of morphine alone with morphine plus clonidine for postoperative patient-controlled analgesia. Br J Anaesth 89(3): 424– 7. Marinangeli F, Ciccozzi A, Donatelli F et al (2002) Clonidine for treatment of postoperative pain: a dose-finding study. Eur J Pain 6(1): 35–42 Clonidine (intravenous) REDUCED DOSES • Opioid postoperative requirements IMPROVED EFFECACY • Improved Postoperative Analgesia REDUCE SIDE EFFECTS • Nausea and Vomiting Cautions !!! • Sedation and Hypotension dose- dependent Alpha-2 Agonist Clonidine
- 55. Alpha-2 Agonist Intrathecal (SAB) DeKock MF, Pichon G & Scholtes JL (1992) Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia. Can J Anaesth 39(6): 537–44. Jeffs SA, Hall JE & Morris S (2002) Comparison of morphine alone with morphine plus clonidine for postoperative patient-controlled analgesia. Br J Anaesth 89(3): 424– 7. Marinangeli F, Ciccozzi A, Donatelli F et al (2002) Clonidine for treatment of postoperative pain: a dose-finding study. Eur J Pain 6(1): 35–42 Advantages Clonidine 15-150 mcg + Local anesthetic Prolonged time of regression Prolonged time to analgesic request Increased speed of onset and duration. Improved early analgesia Prolonged analgesia
- 56. Continuous PNB Chelly JE,Ben-David B,Williams BA,KentorML.. Orthopedics. 2003;26:S865–S871. Capdevilla X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d’Athis F.. Anesthesiology. 1999;91:8–15. Richman JM, Liu SS, Courpas G, et al.. Anesth Analg. 2006;102:248–257. Advantages Superior Pain Relief with movement Reduce Surgical Stress Improved Rehabilitation Reduced opioid consumption and reduced opioid-related side effects Disadvantages Required technical skill Infrastructure to manage catheter, especially outpatient Peripheral Nerve Block (PNB)
- 57. Adams HA, SaatweberP, Schmitz CS, Hecker H. Postoperative pain management in orthopedic patients: no differences in pain score, but improved stress control by epidural anaesthesia. Eur J Anaesthesiol. 2002;19:658–665. De Leon-Casasola OA. When it comes to outcome, we need to define what a perioperative epidural technique is. Anesth Analg. 2003;96:315–318. Advantages Significant pain relief Reduced Neuroendocrine Response Superior to either PNB or PCA in blunting surgical response ↓ Incidence of pulmonary complications, myocardial infarction, DVT and Pulmonary Embolism Epidural Blockade
- 58. Reuben SS, BuvanendranA, Kroin JS, et al. Postoperative modulation of central nervous system prostaglandins E2 by cyclooxygenase inhibitors after vascular surgery. Anesthesiology. 2006;104:411–416. Samad TA, Sapirstein A,Woolf CJ. Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets. Trends Mol Med. 2002;8:390–396. Limitation Has no effects on humoral cytokine proinflammatory response (it may be blocked only by COXIBs). Epidural Blockade Epidural can only block pain tranmissions but not humoral respons
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- 60. From this theory •We can conclude that epidural with LA alone, may not able to prevent/block release cytokines due to tissue injury. • So combine Epidural with Coxibs may produce excellent analgesia. • It can be the future analgesia.
- 61. Multimodal Analgesia Using 5Type of Analgesic Drugs (a preliminary study) 1. Gabapentin 1200 mg 2. Dexamethasone 8 mg 3. Ketamine 0.15 mg/kgBW 4. Paracetamol 1000 mg 5. Ketorolac 15 mg 1. Paracetamol 1000 mg 2. Ketorolac 15 mg 3. Placebo superior in pain control than Group I Group II
- 62. PARACETAMOL • Paracetamol asa single analgesic is only for mild and moderate pain. • However it can be combined with many analgesics to provide strong effect. • So, it can be the basic regiment for Multimodal Analgesia.
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- 64. Multimodal Analgesia Lowered Dose ReducedSide Effects • Early Mobilization • Early Enteral Feeding • Rapid Recovery • low cost Aggressive preemtive multimodal including epidural or nerve block not only produce optimal analgesia but also may prevent the occurrence of chronic pain after surgical Conclusion
- 65. Crile 1913 “Patients GivenInhalation anesthesia still need to be protected by regional anesthesia, otherwise they might suffer persistent central nervous systems changes and enhanced postoperative pain ” Stated That: This is not new