9/20/17. Disclosures. Objectives. Academy of Integrative Pain Management Annual Meeting 2017

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1 Academy of Integrative Pain Management Annual Meeting 2017 Don H. Bivins, M.D. Carilion Clinic October 22, 2017 Disclosures I have no financial conflicts or disclosures to make. Objectives Converse knowledgeably on lidocaine s mechanism of action at the sodium channel Discuss the mechanisms of lidocaine s antiinflammatory properties Explain by case example lidocaine s effectiveness as a systemic analgesic and anti-inflammatory agent Confirm the dosing strategies for systemic lidocaine as proposed by the speaker 1

2 Case Presentation #1 CLB, 39yo male in MVC on 7/12/17; was Gold Alert to our Level I Trauma Center, after having to be intubated in the field; diagnoses included multifocal ICH; multiple pulmonary contusions; avulsion fracture of odontoid process; multiple rib fractures; right clavicular fracture. UDS was positive for unprescribed benzo s and for amphetamine (known methamphetamine user). Case Presentation #1 We were consulted on 7/18/17 for pain control. He was on gabapentin 300mg TID and oxycodone 5 mg q3 hours PRN pain (taking 5-6 per day). We added lidocaine to his regimen, with a bolus of 2 mg/kg; followed by a 1 mg/ min infusion. Within 24 hours, his pain level had dropped from 7-8/10 to 4-5/10. Two days later, IV access was lost, and the lidocaine had to be discontinued. The oxycodone could not control the pain. The IV access was regained within 24 hours, and his pain level dropped to 3-4/10. The patient said that the lidocaine was the agent providing him the best pain control. Parenteral lidocaine administration IV bolus only, dosage based on weight, given in NS over 30 minutes; no constant infusion administered Constant infusion, based on mg/min rate (not weight-based), adjusted according to blood levels IV bolus, dosage based on weight, administered over 30 minutes, followed by constant infusion of mg/min with dose adjusted according to blood levels 2

3 Lidocaine s effect at the sodium channel Blocks action potential generation in healthy nerves Reduces neuronal hyperexcitability and spontaneous firing in injured nerves, whether acutely injured nerves or nerves remaining hyperexcitable after a remote injury With less transmission from the injured nociceptor, then fewer pain signals arrive at the CNS. Gold and Gebhart; van der Wal, et al Case Presentation #2 56yo male presents to PCP with onset over 24 hours of severe left flank, buttock, and proximal hamstring sharp, boring pain Large doses of fentanyl patch, oxycodone, and gabapentin were used to reduce the pain from 9/10 to 6/10 Diagnosed as non-diabetic, vasculitic lumbosacral polyradiculoplexopathy Left with chronic neuropathic pain (1-3/10) and numbness in the area of the pain Case Presentation #2 Same male, now 64yo, presented in 1/14 for elective ACDF, two levels, bilateral Received a 4 mg/kg bolus of IV lidocaine over 30 minutes, 2 hours prior to surgery; No opiates or lidocaine after surgery Same male, now 66yo, presented 7/16 for prostatectomy due to complete urinary obstruction; received lidocaine IV infusion at 1 mg/min prior to, during, and for 2 days post-op; No opiates required post-op Much to his delight, the chronic pain that began in 2006 resolved completely. 3

4 Case Presentation #3 EDR, 52yo male with PMHx of diabetes diagnosed at age 2, PAD, CAD, hyperlipidemia, MI, and testicular cancer Admitted 6/30/17; already had undergone right foot TMA due to PAD ulceration; now has new stump ulceration with infection & pain; no arterial flow to distal limb; had right BKA; Case Presentation #3 We were consulted post-op due to uncontrolled stump pain and phantom limb pain on hydrocodone/apap 10/325 mg q 4 hours PRN We started the patient on a lidocaine IV infusion (2 mg/ kg bolus followed by 1 mg/min constant infusion) The lidocaine infusion was continued for 72 hours (had to be discontinued 24 hours prior to transfer to inpatient rehab unit). During those 72 hours, he used one hydrocodone tablet, had resolution of stump pain; had resolution of phantom pain, but phantom limb sensation persisted. What is inflammation? Most simply defined as the body s reaction to the injury of tissues. It has a protective purpose. However, if left unchecked, it can actually lead to permanent tissue injury. The inflammatory cascade begins with the release of proinflammatory molecules. Leukocytes are stimulated to marginate, adhere, and migrate. Chemokines and cytokines are produced at the injured site. This causes platelets to clump, causing venous occlusion. Free radicals are released, and phagocytosis is enhanced. Leukotrienes lead to increased plasma extravasation into the injured tissues. Lysosomal enzymes lead to aggressive exocytosis of debris. All these steps are inhibited by lidocaine Cassuto 4

5 What is inflammation? The inflammatory cascade begins with the release of proinflammatory molecules. Leukocytes are stimulated to marginate, adhere, and migrate. Chemokines and cytokines are produced at the injured site. This causes platelets to clump, causing venous occlusion. Free radicals are released, and phagocytosis is enhanced. Leukotrienes lead to increased plasma extravasation into the injured tissues. Lysosomal enzymes lead to aggressive exocytosis of debris. Cassuto Case Presentation #4 HEW, 65yo male presented 7/16/17 with a 3 day history of vomiting and increasing LUQ pain; was given morphine in the ED with minimal relief He was on chronic OxyContin 20mg TID at home for chronic pain from spinal DDD. MRI showed 2 pancreatic pseudocysts; serum lipase was 190. The PRN morphine was changed to a hydromorphone PCA. No NSAIDs had been prescribed. Case Presentation #4 We saw him on 7/17/17, and began parenteral lidocaine with a bolus of 2 mg/kg, followed by an infusion of 1 mg/ min. Within 6 hours, his pain level had dropped from 7/10 to 4/10, and he was not using the PCA. On 7/20/17, his pain level was 2/10, the lipase was normal, and he had used no opioids or NSAIDs in 72 hours. The lidocaine was discontinued 1 hour prior to his discharge and he has done well as an outpatient. 5

6 Standard of care in acute pancreatitis Pain control Volume replacement ************************** I propose that parenteral lidocaine become part of the standard of care due to its analgesic and antiinflammatory properties. Lidocaine s Anti-inflammatory effects 1. dose-dependent and reversible inhibition of leukocyte adhesion; 2. dose-dependent and reversible reduction of leukocyte motility from within to outside the vessel wall; 3. inhibition of phospholipase D, and thus reduced leukocyte phagocytosis; 4. reduction of the activity of the enzyme phospholipase A 2, thus reducing the release of inflammatory mediators of the eicosanoid class; 5. reduction of prostaglandin biosynthesis; Lidocaine s Anti-inflammatory effects cont d 6. inhibition of thromboxane B2, thus reducing platelet aggregation; 7. inhibition of leukotriene release; 8. inhibition of histamine release; 9. inhibition of release or secretion of IL-1, IL-β, and IL-8. Cassuto 10. lidocaine blocked inflammatory TNF-α and thus reduced endothelial nitric oxide synthase. Piegeler 6

7 Case Presentation #5 KDL, 45yo male admitted 3/7/17with abdominal pain, nausea, and vomiting of a few hours duration, after having undergone on same day an ERCP due to bile duct stenosis. Studies were consistent with acute pancreatitis. Patient was started on hydromorphone PCA and received no steroids or NSAIDs. Due to persistent pain, we were asked to see him on 3/11/17. We initiated parenteral lidocaine via bolus followed by constant infusion of 1 mg/min. Within 4 hours, pain was substantially reduced and opioid use substantially reduced. Patient discharged on 3/16/17. Case Presentation #5 He was readmitted again on 4/11/17 and 4/25/17 for acute pancreatitis. On these two admissions, he requested that he receive lidocaine infusions in preference to other agents for pain control. He did receive a few injections of hydromorphone, but credited the lidocaine as being the more efficacious. Case Presentation #6 JLJ, 43yo male admitted 7/24/17 with first ever episode of pancreatitis. Lipase 345; abnormal CT of abdomen c/ w pancreatitis. We were asked to see him on 7/26 with uncontrolled pain. 7

8 Case Presentation #6 We began parenteral lidocaine with a 2 mg/kg bolus followed by a 1 mg/min constant infusion. In less than 24 hours, his pain had completely resolved. After initiation of the lidocaine, he received only two doses of fentanyl 50 mcg IV. He received no steroids or NSAIDs during his admission. What causes nociceptor sensitization? The inflammatory soup described above. Case Presentation #7 DSR, 25yo male admitted 5/27/17 after sustaining a crush, degloving injury to left hand, which had been caught in a tire press at the work site. Surgery on admission led to amputation of 3 fingers and extensive soft tissue and ligamentous repair. Additional operations were done prior to discharge on 6/14/17. 8

9 Case Presentation #7 We were asked to see him on 6/1/17 due to uncontrolled pain. Parenteral lidocaine was begun with a bolus of 2 mg/ kg, followed by a constant infusion of 1 mg/min. In less than 24 hours, his pain was much better On 6/1/17, he had used Tylenol 650mg q4hx 2, Fentanyl 25 mcg IV x7; oxycodone 5mg x2; oxycodone 10mg x4; in addition to OxyContin 10mg BID and gabapentin 300mg TID. On 6/3/17, he used OxyContin 10mg BID, gabapentin 300mg TID, and fentanyl 25 mcg IV x2. Parenteral lidocaine protocol EKG, done within the preceding month, must not reveal cardiac dysthymia or conduction block. LFT s must be normal. Seizures Patient must be cautioned about adverse effects that frequently occur during the bolus but resolve within 30 minutes: Dizziness Numbness and tingling of the fingers Hearing changes Confusion Parenteral lidocaine protocol Loading bolus we recommend is 1 or 2 mg/kg in NS over 30 minutes Constant infusion rate we recommend is 1-2 mg/min, and adjusted based on blood levels obtained hours after the initiation of the lidocaine. Infusions can be continued indefinitely When adverse effects occur, they usually resolve within minutes; slowing the rate of the infusion is preferable to stopping the infusion. Ferrini and Paice 9

10 Carilion Clinic Inpa7ent Pain Management Team Bibliography 1. Bartlett EE, Hutaserani Q. Lidocaine (xylocaine) for the relief of postoperative pain. J Am Med Womens Assoc. 1962; 17: Groudine SB, Fisher HA, Kaufman RP, Patel MK. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg. 1998; 86(2): Attal N, Gaude V, Brasseur L, Dupuy M. Intravenous lidocaine in central pain: A double-blind, placebocontrolled, psychophysical study. Neurology. 2000; 54: Bibliography 4. Kvarnstrom A, Karlsten R, Quiding H, Gordh R. The analgesic effect of intravenous ketamine and lidocaine on pain after spinal cord injury. Acta Anaesthesiol Scand. 2004; 48: Kastrup J, Petersen P, Dejgard A, Angelo HR. Intravenous lidocaine infusion a new treatment of chronic painful diabetic neuropathy? Pain. 1987; 28: Viola V, Newnham HH, Simpson RW. Treatment of intractable painful diabetic neuropathy with intravenous lignocaine. J Diabetes Complications. 2006; 20: Rowbothan MC, Reisner Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology. 1991; 41:

11 Bibliography 8. Wallace MS, Dyck JB, Rossi SS, Yaksh TL. Computer controlled lidocaine infusion for the evaluation of neuropathic pain after peripheral nerve injury. Pain. 1996; 66: Baranowski AP, De Courcey J, Bonello E. A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia. Journal of Pain and Symptom Management. 1999; 17: Attal n, Rouaud J, Brasseur L, Chauvin M. Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology. 2004; 62: Wallace MS, Ridgeway BM, Leung AY, Gerayli A. Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. Anesthesiology. 2000; 92: Bibliography 12. Tremont Lukas IW, Hutson PR, Backonja MM. A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain. Clin J Pain. 2006; 22: Grigoras A, Lee P, Sattar F, Shorten G. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. Clin J Pain. 2012; 28: Wu CL, Tella P, Staats PS, Vaslav R. Analgesic effects of intravenous lidocaine and morphine on postamputation pain: A randomized double-blind, active placebocontrolled, crossover trial. Anesthesiology. 2002; 96: Herroeder S, Pecher S, Schonherr ME, Kaulitz G. Systemic lidocaine shortens length of hospital stay after colorectal surgery. Annals of Surgery. 2007; 246: Bibliography 16. Grady P, Clark N, Lenahan J, Oudekerk C. Effect of intraoperative intravenous lidocaine on postoperative pain and return of bowel function after laparoscopic abdominal gynecologic procedures. AANA Journal. 2012; 80: Nguyen NL, Kome AM, Lowe DK, Coyne P. Intravenous lidocaine as an adjuvant for pain associated with sickle cell disease. Journal of Pain & Palliative Care Pharmacotherapy. 2015; 29: Cassuto J, Sinclair R, Bonderovic M. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand. 2006; 50: Piegeler T, Votta-Velis EG, Bakhshi FR, Mao M. Endothelial barrier protection by local anesthetics. Anesthesiology. 2014; 120: