Multi modal analgesia

Multi modal analgesia

1. MULTIMODAL ANALGESIA Presenter- Dr. Suresh Pradhan Moderator- Prof. UC Sharma

2. Pain Latin – Poena – Pain International Association for the Study of Pain IASP – ‘An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’

3. more than 80% of patients who undergo surgical procedures experience acute postoperative pain and approximately 75% of those with postoperative pain report the severity as moderate, severe, or extreme

4. Classification of Pain

5. Physiological Effects of Pain cardiovascular system increases heart rate, blood pressure and peripheral vascular resistance MI, dysrhythmias gastrointestinal system impaired gastrointestinal function-delayed gastric emptying & reduced bowel motility, anastomotic failure respiratory system respiratory dysfunction atelectasis and pneumonia

6. genitourinary system increase the release of hormones and enzymes musculoskeletal system reflex muscle spasm venous stasis increased blood coagulability immune system depression of the immune system

7. hypercoagulable state: DVT, PE psychological and cognitive effects anxiety and depression, fatigue nausea and vomiting chronic pain

8. Methods to Treat Pain Pharmacologic Medications ( po , iv, im , sc , pr , transdermal) Acetaminophen NSAIDs Opioids Gabapentinoids NMDA antagonists Alpha-2 agonists Procedures Regional Anesthesia LA infiltration at incision site Surgical Intervention Non-Pharmacologic / Non-Surgical

9. WHO analgesic ladder for treating pain

10. New Adaptation of the analgesic ladder

11. the cornerstone of the WHO document rests on 5 simple recommendations for the correct use of analgesics to make the prescribed treatments effective this advice is applicable today, not only for cancer patients with pain, but also for all patients with either acute or chronic pain who require analgesics

12. The 5 points for the correct use of analgesics are as follows: Oral administration of analgesics oral form of medication should be privileged whenever possible Analgesics should be given at regular intervals to relieve pain adequately, it is necessary to respect the duration of the medication’s efficacy and to prescribe the dosage to be taken at definite intervals in accordance with the patient’s level of pain the dosage of medication should be adjusted until the patient is comfortable

13. Analgesics should be prescribed according to pain intensity as evaluated by a scale of intensity of pain pain-relief medications should be prescribed after clinical examination and adequate assessment prescription must be given according to the level of the patient’s pain and not according to the medical staff’s perception of the pain if the patient says that s/he has pain, it is important to believe her/him

14. Dosing of pain medication should be adapted to the individual there is no standardized dosage in the treatment of pain every patient will respond differently the correct dosage is one that will allow adequate relief of pain the posology should be adapted to achieve the best balance between the analgesic effect and the side effects

15. Analgesics should be prescribed with a constant concern for detail the regularity of analgesic administration is crucial for the adequate treatment of pain once the distribution of medication over a day is established, it is ideal to provide a written personal program to the patient in this way the patient, his family, and medical staff will all have the necessary information about when and how to administer the medications

16. Combi ning drugs may have 3 types of effects Synergetic ............. 2+2>4 Additive ................ 2+2=4 Subadditive ........... 2+2=3

17. Multimodal Analgesia is a pharmacologic method of pain management which combines various groups of medications for pain relief is achieved by combining different analgesics that act by different mechanisms and at different sites in the nervous system , resulting in additive or synergistic analgesia with lowered adverse effects of sole administration of individual analgesics

18. the most commonly combined medication groups include NSAIDs acetaminophen opioids gabapentinoids alpha-2 agonists NMDA antagonist local anesthetics

19. these regimens must be tailored to individual patients, keeping in mind the procedure being performed side effects of individual medications patients’ pre-existing medical conditions

20. multimodal analgesia is beneficial as: different drugs with different mechanisms/sites of action along pain pathway are used each can be used in a lower dose than if used alone provides additive or synergistic effects provides better analgesia with less side effects (mainly opiate related)

21. Why we need multimodal analgesia for post-operative pain? n o single analgesic is perfect and no single analgesic can treat all types of pain Multimodal Analgesia - potentiating in efficacy, reduced doses, minimal adverse effect . Overall- improve the outcome m ost of the pain is a multifaceted and multiple-source s

22. Local anesthetics NSAIDs COXIBs Local Anesthetic CNS DRG Opioids Gabapentinoids Clonidine Ketamin Paracetamol COXIBs Transduction Transduction Modulation Perception Transmission Modulation Target Points of Analgesic Drugs

23. REGIMENS There are many regiments for multimodal analgesia, but the most popular are:

24. Paracetamol Acetaminophen Route of Administration Orally Intravenously Rectally No Anti-Histamine Effects

25. Central Antinociceptive Effect Mechanism Of Action Central COX ( Cyclo o xygenase ) Inhibition 1 Activation of the endocannabinoid system and serotonergic pathways 2 prevent prostaglandin production at the cellular level 3

26. P aracetamol is very safe drug as long as it is given within recommended doses (Adult < 4 g m /day, Infant and children 20-40 mg/kgBW) All Age – from Infant to Elderly From p regnant to Lactating Woman Can be used for patients with r enal and h epatic impairment Paracetamol

27. PARACETAMOL , NSAIDS & COXIBS G uidelines line for postoperative pain management state that: “Unless contraindicated, all patients should receive an around-the clock (ATC) regimen on NSAIDs, COXIBs, or Paracetamol” American Society of Anesthesiologists Task Force on Acute Pain Management 2004;100:1573-1581

28. Hyllested M, Jones S, 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. Qualitative Review of Paracetamol and NSAIDs

29. 1. Sindet-Pedersen S.1997. Data on 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

30. Paracetamol has Opioid Sparing Effects I.V. paracetamol in these studies was administered as a bio-equivalent dose of propacetamol.

31. Quantitative Systemic Review 2010 Paracetamol and NSAIDs (cox1 and cox2) Combination of paracetamol and an NSAID s may offer superior analgesia compared with either drug alone ( Anesth Analg 2010 )

32. C ombination of paracetamol and parecoxib may useful i n p atients who are susceptible to haemorrhagic complications of NSAIDs Parecoxib and Acetominophen

33. A combination of 1000 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

34. Tramadol/ paracetamol combination tablets provided analgesic efficacy with a better safety profile to tramadol capsules in patients postoperative pain following ambulatory hand surgery. Paracetamol + Tramadol

35. META-ANALYSIS

36. META-ANALYSIS Advantages of Multimodal Analgesia 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. 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

37. SYSTEMIC REVIEW NSAIDs vs COXIBs For 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

38. Limitation of T raditional NSAIDS: ( Aspirin/NSAID )  sensitive asthma The COX-2 selective inhibitors celecoxib 1,2 and rofecoxib 3,4 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

39. KETAMINE Anesthesia Dose more than 2 mg/kg (iv)  anesthesia + produce side effects such us Psychomimetic effect Excessive sedation Cognitive Dysfunction Hallucination Nightmares Subanesthesic 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 ketamin e 0.15 mg/kg improve analgesia and passive knee mobilization 24 hour after arthroscopy

40. Ketamin e More Frequently Use in 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.

41. KETAMINE Low-dose ketamine is not really an ‘analgesic’, but better described as: ‘anti- hyperalgesic ’ ‘anti- allodynic ’ ‘tolerance-protective’ of opioid  Opioid -induced Hyperalgesia

42. GABAPENTINOIDS

43. GABAPENTINOIDS Gabapentin and Pregabalin Eckhardt K, 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- hyperalgesia can synergically with NSAID Pregabalin Superior to either single drugs for postoperative pain following spinal fusion surgery and Celecoxib

44. S edation can be interpreted as a negative outcome of gabapentin , however its can be benefical in the perioperative setting as an anxiolysis

45. Paracetamol and Gabapentin BUT m ore episodes of nausea and vomiting and higher levels of sedation

46. MULTIMODAL ANALGESIA …. contd

47. World Federation of Societies of Anesthesiologists (WFSA) Analgesic Ladder has been developed to treat acute pain initially, the pain can be expected to be severe and may need controlling with strong analgesics in combination with local anesthetic blocks and peripherally acting drugs

48. the oral route for the administration of drugs may be denied because of the nature of the surgery and drugs may have to be given by injection normally, postoperative pain should decrease with time and the need for drugs to be given by injection should cease

49. the second rung on the postoperative pain ladder is the restoration of the use of the oral route to deliver analgesia strong opioids may no longer be required and adequate analgesia can be obtained by using combinations of peripherally acting agents and weak opioids the final step is when the pain can be controlled by peripherally acting agents alone

50. WFSA Analgesic Ladder

51. Clonidine Alpha-2 Agonist

52. 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 Potentiation Clonidine (intravenous) Opioid (iv or PCA) Clonidine

53. Intrathecal (SAB) 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 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

54. systemic perioperatve administraton (oral, IM, IV) of the alpha-2 agonists clonidine and dexmedetomidine decreases postoperatve pain intensity opioid consumption nausea without prolonging recovery times ( Blaudszun 2012 , 30 RCTs, n=1,792)

55. common adverse effects include arterial hypotension and bradycardia effects on development of chronic pain or hyperalgesia remain unclear due to lack of data

56. Peripheral Nerve Block (PNB)

57. 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 reduced opioid-related side effects Disadvantages require technical skill infrastructure to manage catheter, especially outpatient Peripheral Nerve Block (PNB)

58. Adams HA, Saatweber P, 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

59. Reuben SS, Buvanendran A, 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 e

60. EPIDURAL BLOCK Epidural Block Local Anesthetic Neuroendocrine Stress Response ACTH ADH GH TSH Central COX-2 inhibition Cytokines IL-1 β IL-2 IL-6 TNF Norepinephrine Epinephrine Cortisol Aldosterone Renin Sympathetic efferent Humoral stress response

61. 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

62. Multimodal Analgesia Using 5 Type of Analgesic Drugs (a preliminary study) G abapentin 1200 mg Dexamethasone 8 mg K etamine 0.15 mg/kgBW P aracetamol 1000 mg K etorolac 15 mg P aracetamol 1000 mg K etorolac 15 mg Placebo superior in pain control than Group I Group II

63. O PIOID NSAID COXIB Tramadol Ketamine Gabapentanoid ( Gabapentin , Pregabalin ) PARACETAMOL Local Anesthetic (Epidural Block, Nerve Block) Clonidine

64. Multimodal Analgesia Improved Analgesia Lowered Dose Reduced Side Effects Early Mobilization Early Enteral Feeding Rapid Recovery low cost Aggressive pain management with multimodal analgesia, including epidural or nerve block not only produce optimal analgesia but also may prevent the occurrence of chronic pain after surgery Conclusion

65. Crile 1913 “Patients Given Inhalation 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

66. THANK YOU!!!