Advancement in the use of multimodal analgesia for acute postoperative pain

Advancement in the use of multimodal analgesia for acute postoperative pain Ratan K. Banik, M.D., Ph.D. Assistant Professor Department of Anesthesiology University of Minnesota, Minneapolis, USA 4 October 2017

Role of an anesthesiologist - Acute pain service - Chronic pain clinic - Critical care service - Preop clinic - Ambulatory surgery service

The Scope of the Problem Post-Operative Pain Incidence 80% 25% of patients report sufficient post-op pain relief Moderate-Severe Pain 41% on DOS 15% on POD #4 Wu and Raja, Lancet 2011

Post-Op Pain Time Course Brennan TJ Pain (2011) 152:S33

The Mission Pain Minimize post-operative pain and suffering Early return of function Ambulation Feeding Activities of daily living Treatment Course Reduce inpatient length of stay Earliest possible return to normal daily activities Prevention of persistent post surgical pain

A System for the Mission Multimodal Therapy: A method of providing superior analgesia and reduced side-effects by combining interventional techniques and/or medications of different classes.

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques

Perioperative COX Inhibitors Inhibition of cyclooxygenase (COX) COX-1: constitutive COX-2: inducible Caveats to usage: Renal function GI bleeding Platelets function Klabunde cvphysiology.com

Perioperative COX Inhibitors Celecoxib Multiple Perioperative Doses Orthopedic surgery 200 mg BID-TID x 5 d Pain over 5 days Maximal pain intensity Rescue medication Medication adverse events Scott Reuben Controversy At least 12 Coxib related retractions Derry and Moore (2012) Cochrane 3 Gimbel (2001) Clin Ther (2001) 23(2):228.

Perioperative COX Inhibitors Multiple Perioperative Doses Limit to 15 mg IV Q 6 hrs Limit to 2-3 days Joint decision with surgeon Caution Renal dysfunction Single kidney > 65 years old Ketorolac De Oliveira et al. (2012) AA 114(2):424 Storm et al. JAMA (1997) 275(5):376

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques The perioperative Enhanced Recovery System

Perioperative Gabapentinoids GABA analog without significant direct GABAergic activity Bind a 2 d subunit of VG Ca 2+ channels Ca 2+ influx at presynaptic terminals release of Glutamate release sp/cgrp Clinically effective Post-surgical pain Neuropathic pain Melrose et al. Neurosci Lett (2007) 417(2):187

Perioperative Gabapentinoids Gabapentin Meta-analysis of single pre-operative dose static and dynamic pain for 24 hrs MEDD dose has larger in MEDD Sedation Unclear effect of subsequent dosing Hurley et al. RAPM (2006) 31(3) Seib and Paul. Can J Anesth (2006) 53(5): 461

Perioperative Gabapentinoids Pregabalin Meta-analysis of peri-operative dosing Hysterectomy, mastectomy, cholecystectomy, spine surgery, hip arthroplasty, dental extractions Static pain Unclear effect on dynamic pain MEDD Effects more robust for doses > 300 mg/d Dizziness, headache, and visual disturbance Zhang et al. BJA (2011) 106(4):454

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques The perioperative Enhanced Recovery System at MD Anderson

Perioperative Paracetamol Centrally acting analgesic Debated mechanism COX isoenzymes Cannabinoids Vanilloid (TRPA1) Route: IV, PO, PR IV route with double CSF concentration In cancer population Hepatic toxicity Temperature monitoring Andersson et al. Nature Comm (2011) 2: 551

Perioperative Paracetamol Single pre-operative oral dose 500-1,000 mg pain for 4-6 hours NNT 3.5 Poor dose-response curve 50% needed for additional analgesia Few adverse events Multiple IV Doses Q6 hr paracetamol vs placebo (RCT) 24 hrs after laparoscopic surgery pain time to first rescue opioid MEDD McNicol et al. BJA (2011) 106(6):764 Apfel et al. Pain (2013) 154:677 Wininger et al. Clin Ther (2010) 32: 2348 Toms et al. Cochrane (2012) 4

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques The perioperative Enhanced Recovery System at MD Anderson

Perioperative Tramadol Multiple mechanisms of action Weak MOR agonist (relatively selective) Augments release 5-HT NE reuptake inhibition Oral form only in US Caution Previous seizures Brain metastasis Patients taking SSRI and SNRI Neuroendocrine tumors

Perioperative Tramadol Single pre-operative oral dose Abdominal, ortho, gyn, OB, and dental pain with 50-150 mg Excellent dose response curve Increased efficacy when combined with paracetamol Moore and McQuay. Pain (1997) 69:287-294

Perioperative Tramadol Multiple perioperative oral doses Lumbar disc, groin, and laproscopic surgery 200-600 mg/d pain over 24 hrs Similar efficacy to Codeine/APAP 30/500 mg Naproxen 500 mg No RCT with tramadol ER Grond and Sablotzki. Clin Pharma 92004) 43:879

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques The perioperative Enhanced Recovery System

Patient Controlled Analgesia (IV-PCA) Self-administered small doses of IV opioid Lock-out interval for safety Basal infusion for opioid tolerant patients only (if at all) Loading dose necessary Morphine M6G (MOR active) accumulation in renal failure M3G (MOR inactive) accumulation in renal failure neuroexcitatory Hydromorphone and Fentanyl No meaningful active metabolites Renal dysfunction in cancer patients Grass A&A 2005 Viscusi et al. NYSORA.com 2008

Patient Controlled Analgesia (IV-PCA) Traditional Teaching analgesic gaps opioid needed for same level of analgesia opioid related side effects nursing and pharmacy staff time $400 / d in U.S. patient satisfaction sense of control

Patient Controlled Analgesia (IV-PCA) Recent meta-analysis of 55 RCT s Mixed surgical types pain vs control patient satisfaction nursing and pharmacist staff costs other adverse SE hospital LOS total opioid itching Hudcova et al. Cochrane (2012) 6

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol Intra-Operative Medications Ketamine Lidocaine IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques The perioperative Enhanced Recovery System at MD Anderson

Epidural Recipients Thoracotomies Upper Abdominal Surgery Lower Abdominal Surgery Urological/Gynecological Othropaedic

Epidural Location Target: dermatomal midpoint of surgical site Thoracotomy: T4-7 Upper abdomen: T6-8 Mid abdomen: T8-10 Lower abdomen: T10-L1

Epidural Catheters 2500 Epidurals per Year 9 Average Epidural Days per Year 2000 8 7 1500 6 5 1000 4 3 500 2 1 0 0

Anticoagulation: ASRA Guidelines PLUS Placing Epidural INR < 1.4 and Platelets > 100K No VEGF inhibitors in last 3-4 weeks Removing Epidural INR < 1.7 and Platelets > 70K Check thrombo-elastogram (TEG) 2% patients require transfusion

Epidurals and Health Outcomes Analgesia Lower pain score vs systemic opioids Improved static and dynamic pain scores Gastrointestinal Decreased duration of postoperative ileus Pulmonary Decreased duration of mechanical ventilation Less atalectasis and hypoxemia Decreased overall post-op pulmonary complications Metabolic Attenuates post-op nitrogen excretion sparing muscle mass Cardiovascular May lower risk MI or dysrhythmias Mortality Small reduction at 30-days Popping DM et al. Arch Surg (2008) 143:990-99. Nishimori M et al. Cochrane Database Syst Rev (2006) 3: CD005059 Joshi GP et al. Anesth Analg (2008) 107:1026-40 Wijeysundera DN et al. Lancet (2008) 372:562-69. Latterman et al. Pain Med (2007) 32: 227 Wu CL et al. RAPM (2004) 29:525-33. Liu SS and Wu CL. Anesth Analg (2007) 689-702 Marret E et al. Br J Surg (2007) 94: 665-73. Fischer HB et al. Anaesthesia (2008) 63: 1105-23.

Splitting Difficult clinical scenario Pain + Hypotension Patchy epidural Unilateral epidural Pain at non-surgical site Solution is splitting Local anesthetics alone in the epidural Provide systemic opioids through IV PCA or PO route Clinical rule: Do not mix neuraxial and systemic opioids Too difficult for patient Provider may forget about other source

Surgery Specific Duration of Catheter Thoracic Surgery After chest tube removed Pneumonectomy POD #5 Esophagectomy POD #7 Abdominal Surgery After tolerating full liquid diet OR tube feeds at 40 ml/hr Ortho When PT goals achieved

Epidural Misadventures No block Not in epidural space Migration Missing segments Unilateral block (catheter depth) Patchy block Wrong level Pain somewhere else Hypotension Fluid sparing anesthesia Motor block Sedation Dural puncture ~1% Post-Operative radicular pain 0.3%

Overview Components of Multimodal Analgesia Pre/Post-Operative Medications COX inhibitors Gabapentinoids Paracetamol Tramadol Intra-Operative Medications Ketamine Lidocaine IV PCA Epidurals Regional anesthesia with emphasis on ultrasound guided techniques The perioperative Enhanced Recovery System

Peripheral Nerve Blocks Rapidly expanding and changing Ultrasound guidance Catheters Mostly orthopedic surgeries in studies pain compared to systemic opioids MEDD Earlier mobilization Possible length of stay Viscusi et al. NYSORA.com 2008

Supraclavicular Plexus Block Neuraxiom.com NYSORA.com

Femoral n. Block Neuraxiom.com NYSORA.com

Transversus Abdominis Plane Block Nerves blocked: Anterior rami of T7-L1 Best block generally T10-L1

Transversus Abdominis Plane Block NYSORA.com

Further Learning USRA.ca NYSORA.com

Innovative Medications Extended release local anesthetics Liposomal bupivacaine Long acting single shot technique Unknown safety

Epidural/Peripheral Bupivacaine Na + Channel Block Gabapentinoids N-type Ca 2+ channel inhib Dexmedetomidine a 2 agonist NSAIDs Cyclooxygenase inhib Tramadol SNRI + weak MOR agonist POST-OP ANALGESIA Ketamine NMDA-R antagonism Paracetamol TRPA1 agonist (?) Lidocaine (infusion) Systemic Na + channel inhib Opioids Strong MOR agonists

Difficult Clinical Scenario #1 Obstructive Sleep Apnea Higher risk of respiratory complications post-op Strongly push for neuraxial or regional technique if applicable Utilize home CPAP/BiPAP immediately after extubation Maximize non-opioid medications Minimum effective opioid dose Vigilant post-op monitoring

Difficult Clinical Scenario #2 Opioid tolerant patient Often misunderstood by physicians Continue pre-operative opioid MORE opioid needed in the perioperative period Strongly push for neuraxial or regional technique if applicable Patient must have access to opioids to prevent perioperative withdrawal IV PCA to determine new opioid requirement Pain score will be higher than the average patient Remember careful titration

Difficult Clinical Scenario #3 The Unhappy Triad Maximize non-opioid medications Consider regional techniques Eliminate other sedating medications Benzodiazepines, antiemetics, anti-histamines Ensure adequate fluid status Safety first

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