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IMPROVING THE MANAGEMENT OF POSTOPERATIVE PAIN: MULTIMODAL APPROACHES IN CLINICAL PRACTICE ACUTE PAIN – EPIDEMIOLOGY Acute pain is very common 51.4 million surgical in-patient procedures were performed in 2010 in the United States Centers for Disease Control and Prevention. National Center for Health Statistics. www.cdc.gov/nchs/faststats/inpatient-surgery. Accessed July 8, 2015. ACUTE PAIN – SCOPE OF THE PROBLEM Almost all patients experience pain after surgery, procedure, or injury Survey of 300 US adults undergoing surgery: 86% experienced pain post surgery 75% had moderate to extreme pain in the immediate postsurgical period 74% still had pain post discharge Gan TJ et al. Curr Med Res Opin. 2014;30(1):149-160. ACUTE PAIN – SCOPE OF THE PROBLEM Studies suggest that after orthopedic, general, or cardiac surgery, 63% of patients experience pain resolution within 6 days That means that 37% of patients continued to have pain problems beyond discharge from the hospital However, in 25% of patients, the pain did not change, and in 12% the pain worsened in this period of time Chapman CR et al. J Pain. 2011;12(2):257-262. Chapman CR et al. Pain Res Treat. 2012;2012:608359. CURRENT PROBLEMS WITH THE ASSESSMENT OF ACUTE PAIN Current taxonomies for postoperative pain do not adequately describe an individual patient’s pain profile Harstall C, Ospina M. Pain: American Association for Marriage and Family Therapy Clinical Updates. 2003;11(2):1-4. World Health Organization. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. http://www.who.int/medicines/areas/quality_safety/children_persisting_pain/en/. Accessed July 8, 2015. CURRENT PROBLEMS WITH THE ASSESSMENT OF ACUTE PAIN When used alone, these taxonomies do not capture the multidimensionality of pain or the dynamics of pain over the course of a 24-hour day in an individual patient This approach may result in inadequate individualization of pharmacologic pain management Somatic vs neuropathic Pitfalls in the implementation of therapy to treat these patients: Multimodal therapy Opioid metabolism Drug-drug interactions Psychological issues: catastrophizing, anxiety, depression, etc History of opioid use preoperatively Preexisting pain Genetics: gene polymorphism MAKING THE DIFFERENTIAL DIAGNOSIS Is there an early neuropathic pain component present? Suspect in individuals who are still receiving high doses of opioids + adjuvants 4-5 days post surgery Must rule out opioid tolerance from preoperative opioid use or abuse CHALLENGES IN THE MANAGEMENT OF ACUTE PAIN Variable response to analgesics Older age = more sensitivity to opioids Ethnicity Psychological issues Type of surgical procedure The use of pre-emptive analgesic techniques Intraoperative anesthetic techniques: Regional anesthetic procedures vs general Ketamine use Genetics: gene polymorphism MAKING THE DIFFERENTIAL DIAGNOSIS Is there an early neuropathic pain component present? Suspect in individuals who are still receiving high doses of opioids + adjuvants 4-5 days post surgery Must rule out opioid tolerance from preoperative opioid use or abuse NEUROPATHIC PAIN (NP) DIAGNOSIS LANSS PAIN SCALE Leeds Assessment of Neuropathic Symptoms and Signs A. PAIN QUESTIONNAIRE • 5 Questions B. SENSORY TESTING • 2 Questions Maximum score = 24. If < 12, NP unlikely Bennett M. Pain. 2001;92(1-2):147-157. LEEDS ASSESSMENT OF NEUROPATHIC SYMPTOMS AND SIGNS Would you describe your pain as strange unpleasant sensations in your skin? (eg, pricking, tingling, pins and needles) Yes= 5/No= 0 Does the skin in the painful areas look different to normal? (eg, mottled, more red/pink than usual) Yes= 5 /No= 0 Is the skin in the affected area abnormally sensitive to touch? (eg, unpleasant sensations if lightly stroked, painful to wear tight clothes) Yes= 3/No= 0 Does your pain come on suddenly in bursts for no apparent reason when you are still? (eg, like electric shocks, 'bursting' or 'jumping' sensations) Yes= 2/No= 0 Do you feel that skin temperature in the painful area has changed (eg, hot, burning) Yes= 1/No= 0 Does stroking the affected area of skin with a piece of cotton wool produce an unpleasant painful sensation? Yes= 5/No= 0 Does touching the affected area of skin with a sharp needle feel sharper or duller when compared to an area of normal skin? Yes= 3/No= 0 Bennett M. Pain. 2001;92(1-2):147-157. CHALLENGES IN THE MANAGEMENT OF ACUTE PAIN Variable response to analgesics Older age = more sensitivity to opioids Ethnicity Psychological issues Type of surgical procedure The use of pre-emptive analgesic techniques Intraoperative anesthetic techniques: Regional anesthetic procedures vs general Ketamine use Genetics: gene polymorphism ACUTE PAIN IMPACTS PATIENTS’ LIVES Negative effects of inadequate acute pain management include: Increased hospital stay or more frequent readmissions Reduced quality of life (QOL) Impaired physical function Decreased functional recovery Increased complications Impaired sleep McCarberg BH et al. Am J Ther. 2008;15(4):312-320. Pavlin DJ et al. J Clin Anesth. 2004;16(3):200-206. Sinatra R. Pain Med. 2010;11(12):1859-1871. Morrison RS et al. J Am Geriatr Soc. 2009;57(1):1-10. INADEQUATE ACUTE PAIN MANAGEMENT CAN HAVE CONSEQUENCES Chronic pain may develop after surgery as a result of complex biochemical and pathophysiologic al mechanisms Clinically meaningful, severe acute postoperative pain may be a risk factor for the development of chronic pain Up to 50% of patients reportedly suffer from chronic pain following common surgery Sinatra R. Pain Med. 2010;11(12):1859-1871. Morrison RS et al. J Am Geriatr Soc. 2009;57(1):1-10. Voscopoulos C, Lema M. Br J Anaesth. 2010;105(suppl 1):i69-i85. Effectively managing acute pain can reduce the risk for pain progression IMPROVING POSTOPERATIVE PAIN MANAGEMENT Studies suggest that individualization of pain evaluations are important to determine: Preoperative risk factors The pattern of resolution for each patient The therapeutic approach to implement Chapman CR et al. J Pain. 2011;12(2):257-262. Chapman CR et al. Pain Res Treat. 2012;2012:608359. MULTIMODAL THERAPY Synchronous administration of ≥ 2 pharmacological agents or approaches, each with a distinct mechanism of action American Society of Anesthesiologists Task Force on Acute Pain Management. Practice Guidelines for Acute Pain Management in the Perioperative Setting. Anesthesiology. 2012;116:248-273. American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. MULTIMODAL THERAPY Key Practice Guidelines Recommendations Whenever possible, anesthesiologists should use multimodal pain management therapy. American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. MULTIMODAL THERAPY Rationale: Targeting of different pathways Synergism of multiple agents Allows for dose reduction of individual agents, reducing the risk for adverse effects MULTIMODAL THERAPY Key Practice Guidelines Recommendations Anesthesiologists who manage perioperative pain should, after thoughtfully considering the risks and benefits for the individual patient, use therapeutic options such as: • Epidural or intrathecal opioids • Systemic opioid patient-controlled analgesia (PCA) • Regional techniques American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. MULTIMODAL THERAPY Key Practice Guidelines Recommendations Unless contraindicated, patients should receive an around-the-clock regimen of nonsteroidal antiinflammatory drugs (NSAIDs), COX-2 inhibitors, or acetaminophen. Dosing regimens should be administered to optimize efficacy while minimizing the risk for adverse events. The choice of medication, dose, route, and duration of therapy should be individualized. American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. PERIOPERATIVE TECHNIQUES IN PAIN MANAGEMENT Technique Examples Advantages Disadvantages Central Regional Analgesia Intrathecal or epidural opioida • Improved pain • Increased relief frequency of pruritus Epidural opioida + local anestheticb • Improved pain • Increased scores motor weakness Epidural opioida + clonidine • None noted • None noted Examples of opioids include morphine, fentanyl, sufentanil b Examples of local anesthetics include bupivacaine, ropivacaine a American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. PERIOPERATIVE TECHNIQUES IN PAIN MANAGEMENT Technique Examples Advantages Disadvantages Systemic opioidsa Staff-administered intramuscular (IM) injections • None noted • Pain on injection • Tissue damage Staff-administered intravenous injections • Similar pain • Peak / trough control to PCA opioid adverse drug reactions (ADRs) PCA without background infusion • Improved pain • None noted scores vs IM PCA with background infusion • Improved pain • Increased scores vs IM analgesic use vs no background a Examples of opioids include morphine, fentanyl, hydromorphone American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. PERIOPERATIVE TECHNIQUES IN PAIN MANAGEMENT Technique Examples Advantages Disadvantages Peripheral Regional Analgesia Peripheral nerve blocksb • Generally, improved • None noted pain relief and lower analgesic consumption compared with saline Intra-articular blocksb or opioidsa • None noted compared with saline Infiltration of incisionsb • Generally, improved • None noted pain relief and lower analgesic consumption compared with saline • None noted Examples of opioids include morphine, fentanyl, sufentanil b Examples of local anesthetics include bupivacaine, ropivacaine a American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. PERIOPERATIVE TECHNIQUES IN PAIN MANAGEMENT Technique Examples Advantages Nonopioid systemic analgesics Acetaminophen (oral, rectal, injectable) • Similar benefit to • None noted intravenous (IV) PCA opioid • Fewer ADRs Injectable NSAIDs • Improved pain scores • Reduced analgesic use • NSAID risks / ADRs Oral NSAIDs (both non- and selective • None noted • NSAID risks / ADRs Gabapentinoids (both gabapentin and pregabalin) When combined w/ opioids • None noted • Improved pain scores • Reduced analgesic use American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. Disadvantages Dual Ascending Pathways Limbic Cortex Sensory Cortex Thalamus Peripheral Nociceptor Descending Pathways Ascending Pathways Mid Brain Sensory Fiber Dorsal Horn Spinal Cord Efferent Fiber Slide courtesy of Raymond Sinatra, MD Limbic Cortex Physiological Pain Sensory Cortex Thalamus Ascending Pathways Nociceptor Mid Brain Sensory Fiber Dorsal Horn Spinal Cord Efferent Fiber Slide courtesy of Raymond Sinatra, MD Postoperative Pain Treatment Multimodal Therapy Opioids 2-Agonists Acetaminophen N-methyl-D-aspartate (NMDA) antagonists Local anesthetics (LA) infiltration Acetaminophen Anti-inflammatory agents, COX-2 inhibitor LA via peripheral nerve catheters Local anesthetics Opioids 2-Agonists NMDA antagonists COX-2 Inhibitors Slide courtesy of Raymond Sinatra, MD and modified for educational purposes MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Acetaminophen (APAP) – oral, single dose Cochrane review1 51 studies, 5762 patients, 3277 active, 2425 placebo 50% in pain with 50% APAP group, 20% placebo group for 4 hours Number needed to treat (NNT) based on dose: 1Toms 2Ong APAP 500 mg: 3.5 APAP 650 mg: 4.6 APAP 1000 mg: 3.6 50% of APAP and 70% of placebo needed additional analgesia A systematic review2 identified 21 studies comparing APAP alone or in combination with NSAIDs and reported increased efficacy with the combination of 2 agents than with either alone L et al. Cochrane Database Syst Rev. 2008;(4):CD004602. CK et al. Anesth Analg. 2010;110(4):1170-1179. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Acetaminophen – Parenteral Studied single dose, multiple dose over 24 hours compared with placebo Orthopedic surgery, laminectomy, abdominal, gynecological, cardiac, and thyroidectomy Dosing: 1 gram IV, either single dose or every 6 hours Summary APAP patients: Statistically significant shortened time to meaningful pain relief and in total relief compared with placebo Improved patient satisfaction with pain control, lower morphine consumption (up to 61%) and decreased incidence of vomiting No statistical significant difference in the rates of adverse events including liver function abnormalities compared with placebo Wininger SJ et al. Clin Ther. 2010;32(14):2348-2369. Cakan T et al. J Neurosurg Anesthesiol. 2008;20(3):169-173. Memis D et al. J Crit Care. 2010;25(3):458-462. Macario A, Royal MA. Pain Pract. 2011;11(3):290-296. ACETAMINOPHEN (PARACETAMOL OR APAP) Produces a central analgesic effect, but unknown mechanism of action (MoA) for years New evidence for MoA from extensive research MoA evidence now suggests that the analgesic effect of APAP is partly due to the indirect activation of cannabinoid CB(1) receptors APAP primary amine (p-aminophenol) is conjugated to form N-arachidonoylphenolamine, an endogenous cannabinoid N-arachidonoylphenolamine is an agonist at TrpV-1 receptors and an inhibitor of cellular anandamide uptake, increased levels of endogenous cannabinoids APAP may also work through inhibition of prostaglandin (PG) synthesis via prostaglandin H(2) synthetase, particularly in areas of the brain with high concentrations of fatty acid amide hydrolase Thus, acetaminophen may have multiple MoAs, one of which ultimately acts as a pro-drug, the active one being a cannabinoid Dual effect may be both a direct analgesic effect and modulation effect Bertolini A et al. CNS Drug Rev. 2006;12(3-4):250-275. Graham GG et al. Inflammopharmacology. 2013;21(3):201-232. Anderson BJ. Paediatr Anaesth. 2008;18(10):915-921. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Nonselective NSAIDs Single dose oral ibuprofen1 – Summary 72 randomized clinical trials (RCTs), 9168 patients 50% pain relief in approximately half of patients with moderate to severe postoperative pain, and adverse events were similar to placebo Single dose oral aspirin2 – Summary 50% or greater reduction in pain in 39% of those with moderate to severe pain, compared with 15% of those in the placebo group The efficacy of aspirin was considered equivalent to that of acetaminophen Adverse events were statistically similar for those taking a lower aspirin dose, 600 mg to 650 mg, compared with placebo. However, patients who took 900 mg to 1000 mg experienced adverse events at more than twice the rate of patients receiving placebo (26% vs 12%). The most common events in the aspirin group were drowsiness, dizziness, nausea, vomiting, and gastric irritation 1Derry 2Derry C et al. Cochrane Database Syst Rev. 2009;(1):CD004234. C et al. Cochrane Database Syst Rev. Published Online Jan 2012 MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Selective NSAIDs – Single dose Celecoxib Cochrane review - 10 studies, 1785 patients NNT for 50% decrease in pain over 4 to 6 hours: Celecoxib 200 mg: 4.8 Celecoxib 400 mg: 3.5 Median time for rescue medication use: Celecoxib 200 mg: 6.6 hours Celecoxib 400 mg: 8.4 hours Placebo: 2.3 hours Proportion of patients requiring rescue medications: Celecoxib 200 mg: 74% Celecoxib 400 mg: 63% Placebo: 91% Adverse events mild to moderate in all groups with no difference in frequency Derry S et al. Cochrane Database Syst Rev. Published Online: 22 OCT 2013 MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Injectable NSAIDs Ketorolac and ibuprofen studied in United States Indicated for short-term moderate to severe acute pain that requires analgesia at the opioid level Studies (variety of surgery types) with ketorolac1,2 compared with placebo suggest patients who received ketorolac: Significant reduction in pain Reduction in opioid consumption (~30%) Facilitation of quicker recovery and rehabilitation Studies with ibuprofen in orthopedic and abdominal surgery3 At 800-mg dose, reduced morphine use by 22% in first 24 hours Significant reductions in pain at rest and with movement No significant increases compared with placebo in ADRs 1. Cassinelli EH et al. Spine (Phila Pa 1976). 2008;33(12):1313-1317. 2. Wong HY et al. Anesthesiology. 1993;78(1):6-14. 3. Southworth S et al. Clin Ther. 2009;31(9):1922-1935. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Parenteral Opioids – Patient-controlled Analgesia Cochrane review 55 studies with 2023 patients receiving PCA and 1838 patients assigned to a control group (nurse-administered opioid) PCA provided better pain control and greater patient satisfaction than conventional parenteral 'as-needed' analgesia Patients using PCA: Consumed higher amounts of opioids than the controls Had higher incidence of pruritus (itching), but similar incidence of other adverse effects There was no difference in the length of hospital stay Hudcova et al. Cochrane Database Syst Rev. 2006;(4):CD003348. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Parenteral Opioids – Patient-controlled Analgesia PCA vs nurse-controlled (NCA) after cardiac surgery 10 randomized trials, 666 patients Compared with NCA: PCA significantly reduced visual analogue scale (VAS) at 48 hours, not at 24 hours PCA groups showed significantly increased cumulative morphine equivalents consumed at 24 hours No difference with ventilation times, length of ICU stay, length of hospital stay, patient satisfaction scores, sedation scores, incidence of postoperative nausea and vomiting (PONV), respiratory depression, severe pain, discontinuations, and death Bainbridge D et al. Can J Anaesth. 2006;53(5):492-499. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Epidural Opioids Cochrane Review Abdominal aortic surgery 15 trials with 1297 patients (633 received epidural analgesia and 664 received systemic opioid analgesia) The epidural analgesia group showed significantly lower visual analogue scale scores for pain on movement (up to postoperative day 3) Conclusions: Compared with systemic opioids: Regardless of the site of the epidural catheter and epidural formulation, epidural analgesia provides better pain relief (especially during movement) in the period up to 3 postoperative days Duration of postoperative tracheal intubation is reduced by roughly half with epidural The occurrence of prolonged postoperative mechanical ventilation, myocardial infarction, gastric complications, and renal complications was reduced by epidural analgesia Nishimori M et al. Cochrane Database Syst Rev. 2012;(7):CD005059. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Epidural Local Anesthetics vs Opioid-based Regimens (systemic or epidural) Cochrane Review Abdominal surgery, 8 studies, small numbers of patients Key outcome analysis: Postoperative: Gastrointestinal (GI) function, pain, PONV, and complications Conclusions: Epidural local anesthetics: Reduced time of GI functioning, slight reduction in VAS pain scores on the first postoperative day No significant differences in PONV or complications Jorgensen H et al. Cochrane Database Syst Rev. Published Online: 22 JAN 2001 MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Continuous Epidural Analgesia Cochrane database review1: 9 RCT comparing IV PCA and continuous epidural analgesia (CEA) CEA had better pain control in the first 72 hours after abdominal surgery There was no difference in length of hospital stay and adverse events between the 2 routes Patients with CEA had a higher incidence of pruritus related to opioids Comparing PCA vs CEA in colorectal surgery2 showed that CEA significantly reduced postoperative pain and ileus, but was associated with pruritus, hypotension, and urinary retention 1Werawatganon 2Marret T, Charuluxanun S. Cochrane Database Syst Rev. 2005;(1):CD004088. E et al; Postoperative Pain Forum Group. Br J Surg. 2007;94(6):665-673. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Intrathecal (IT) Morphine + PCA Morphine vs PCA Morphine Alone Major abdominal surgery, 60 patients Summary Analgesia at rest and while coughing was significantly better in the IT+PCA morphine group on the first postoperative day only Morphine consumption was lower in the IT+PCA morphine group during first postoperative day No difference was found in pain relief and morphine consumption between the groups on the second postoperative day Nausea and vomiting were more frequent with IT+PCA morphine on the first postoperative day No respiratory depression occurred in either group Satisfaction was high in both groups Devys JM et al. Can J Anaesth. 2003;50(4):355-361. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Local Anesthetics – Wound Infiltration Useful in a variety of surgeries Cardiothoracic, abdominal, gynecological, colorectal, head and neck, orthopedic General conclusions from studies: Effective in a variety of surgical sites Neither infection nor toxicity appears to be a significant clinical issue Preoperative blockage superior to postoperative Pain is reduced both at rest and on mobilization Opioid requirements are less Decreased occurrence of acute and chronic pain 3 and 6 months after surgery shown in 1 study with breast cancer surgery Scott NB. Anaesthesia. 2010;65(suppl 1):67-75. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Intravenous Lidocaine Meta-analysis after abdominal surgery 8 trials, 161 patients received lidocaine (active arm), 159 saline (placebo arm) Both arms could receive as-needed opioids Lidocaine IV groups showed: Decreased duration of ileus Length of hospital stay Postoperative pain intensity Incidence of PONV 30%–50% reduction in opioid consumption Marret E et al. Br J Surg. 2008;95(11):1331-1338. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Intravenous Lidocaine Systematic review (various surgeries, including: abdominal, tonsillectomy, total hip, coronary bypass) 16 trials, 395 patients received lidocaine (active arm), 369 saline (placebo arm) All could receive as-needed opioids In patients who received IV lidocaine IV: Pain scores were reduced at rest and with cough or movement for up to 48 hours postoperatively in abdominal surgery patients No impact on postoperative analgesia in patients undergoing tonsillectomy, total hip arthroplasty, or coronary artery bypass surgery Decreased duration of ileus Length of hospital stay shortened Postoperative pain intensity lessened Incidence of PONV decreased Up to 85% reduction in opioid consumption McCarthy GC et al. Drugs. 2010;70(9):1149-1163. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Ketamine Intravenous – Systematic Review • 70 studies, 4701 patients (2652 ketamine, 2049 placebo) • Summary Patients receiving ketamine reported a reduction in total opioid consumption and an increase in the time to first analgesic dose needed across all studies (P < .001). o The greatest efficacy of ketamine was found for thoracic, upper abdominal, and major orthopedic surgical subgroups Despite using less opioid, 25 out of 32 treatment groups (78%) experienced less pain than the placebo groups Hallucinations and nightmares were more common with patients receiving ketamine, but there was no association with increased sedation In patients in whom ketamine was reported as efficacious for pain, postoperative nausea and vomiting was less frequent in those patients who received ketamine The analgesic effect of ketamine was independent of the type of intraoperative opioid administered, the timing of ketamine administration, and the ketamine dose administered Laskowski K et al. Can J Anaesth. 2011;58(10):911-23. MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Gabapentinoids - Systematic Review of RCTs • Gabapentin: 22 trials, 1640 patients • Pregabalin: 8 trials, 707 patients • Summary: Gabapentin provided better postoperative analgesia and in sparing rescue analgesics than placebo in the 6/10 RCTs that administered gabapentin as preemptive analgesia only 14 RCTs suggested that gabapentin did not reduce PONV when compared with placebo Pregabalin provided better postoperative analgesia and in sparing rescue analgesics than placebo in 2/3 RCTs that evaluated the effects of pregabalin alone vs placebo 4 studies reported no pregabalin effects on preventing PONV Both agents reduced opioid consumption by ~30% Dauri M et al. Curr Drug Targets. 2009;10(8):71633.26 MULTIMODAL APPROACHES: EVIDENCE-BASED SUMMARY Systemic 2 Agonist – Meta-analysis of RCTs Summary Moderate analgesic benefit—probably better than paracetamol, but less than that of ketamine and NSAIDs as inferred from nonsystematic indirect comparison Adverse reactions may be significant (hypotension and bradycardia) Provides extra analgesic benefits such as sedation, anxiolysis, analgesia, postoperative shivering, decreased PONV, agitation, mitigation of stress response to surgery and tracheal intubation, anaesthetic-sparing effect, and as supplement to neuraxial and peripheral nerve blocks Decreased perioperative mortality and myocardial infarction, especially in high-risk vascular surgeries Blaudszun G et al. Anesthesiology. 2012;116(6):1312-1322. PERIOPERATIVE PAIN – ANALGESIC ADJUVANTS Pain Intensity Analgesic Opioid Consumption Opioidrelated Side Effects Prevention of Chronic Postsurgical Pain Ketamine Inconsistent Pregabalin Yes Sedation, dizziness Gabapentin Yes Sedation, dizziness IV Lidocaine Possible None noted, but monitor Systemic α2 agonist No data Hypotension, bradycardia Drug Shankar R et al. Anaesth Crit Care Pain. 2013;13(5):152-157. Side Effects Psychomimetic (hallucinations, dreams) SYSTEMIC MULTIMODAL MEDICATIONS – COMMON ADVERSE DRUG REACTIONS Class Examples Opioids Morphine Hydromorphone Fentanyl • • • • NSAIDs (injectable) Ketorolac Ibuprofen • GI bleeds • Nephrotoxicity • May affect wound / bone healing NSAIDs (oral, nonselective) Ibuprofen Naproxen Diclofenac • GI bleeds • Nephrotoxicity • Nausea / Vomiting • May affect wound / bone healing NSAIDs (oral, selective) Celecoxib • Nephrotoxicity • Nausea / Vomiting • May affect wound / bone healing Acetaminophen Acetaminophen • Hepatotoxicity at high doses • No effect on bleeding times • Well tolerated Gabapentinoids Gabapentin • Dizziness • Sedation • Helpful with neuropathic pain (oral and injectable) Pregabalin ADR Risks Sedation Constipation Nausea / Vomiting Dizziness Comments • Sedation may impair postoperative rehabilitation • Constipation may affect time to discharge MULTIMODAL ANALGESIA The state-of-the-art is multimodal therapy with: Opioids IV Intraspinal (IS) Oral route NSAIDs APAP Local anesthetics Wound site infiltration or perfusion Peripheral nerve infusions via catheters Epidural IV Preperitoneal catheters American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273. TEMPORAL PAIN INTENSITY DIFFERENCES BETWEEN ACUTE AND CHRONIC PAIN Acute Surgical Pain Chronic Pain “Ladder” Step 4 (interventional) Step 3 (potent opioids) Step 2 (weak opioids) Step 1 (nonopioids) No analgesics TRANSITION FROM ACUTE SURGICAL PAIN AND THE DEVELOPMENT OF CHRONIC PAIN Surgery Decreasing Pain Intensity Increasing Pain Intensity interventional potent opioids interventional weak opioids non-opioids no medications Time Nerve Injury vs Central Sensitization potent opioids adjuvants TRANSITION FROM ACUTE SURGICAL PAIN TO SUBACUTE (PERSISTENT) PAIN Surgery Decreasing Pain Intensity interventional Pain Intensity Remains High potent opioids weak opioids potent opioids non-opioids adjuvants no medications Time 1 to 12 weeks MULTIMODAL PAIN MANAGEMENT: STEP THERAPY Severe Postoperative Pain Step 3 Step 1 and Step 2 Strategies AND Local Anesthetic Peripheral Neural Blockade (with or without catheter) AND Use of Sustained-release Opioid Analgesics Step 2 Moderate Postoperative Pain Step 1 Strategy AND Intermittent Doses of Opioid Analgesics Mild Postoperative Pain Step 1 Nonopioid Analgesic Acetaminophen, NSAIDs, or COX-2 Selective Inhibitors AND Local Anesthetic Infiltration Reprinted with permission. Copyright © 2002 American Medical Association. All rights reserved. Crews JC. JAMA. 2002;288(5):629-632. PHARMACOECONOMICS Consequences of side effects Consequences of inadequate pain control Consequences of postoperative complications Readmissions TRANSITION FROM ACUTE SURGICAL PAIN TO SUBACUTE (PERSISTENT) PAIN Surgery Decreasing Pain Intensity interventional Pain Intensity Remains High potent opioids weak opioids potent opioids non-opioids adjuvants no medications Time 1 to 12 weeks CLINICAL PEARLS THANK YOU!