9/18/2017. Pharmacology for Advanced Practice Nurses Annual Meeting of the Virginia Association of Clinical Nurse Specialists Richmond, VA

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1 Pharmacology for Advanced Practice Nurses 2017 Annual Meeting of the Virginia Association of Clinical Nurse Specialists Richmond, VA Lidocaine and Ketamine in Pain Management Don H. Bivins, MD Director, Inpatient Pain Management Carilion Clinic September 29, 2017 Disclosures I have no financial obligations or associations to report. 1

2 Objectives Review the mechanisms of action (MOA s) of the more commonly used analgesics Explore the two MOA s of lidocaine, especially with its parenteral administration Investigate the two MOA s of ketamine parenteral administration Discuss the impact of these two analgesics on the opioid epidemic MOA of common analgesics Opioids Block the µ receptors. They are ubiquitous in the PNS and CNS. There are at least 13 types. (Who cares?) Tramadol (partial antagonist) Weakly blocks the µ receptor but also blocks serotonin and norepinephrine re-uptake. NSAID s Work primarily to block the COX-1 and COX-2 receptors. Acetaminophen May inhibit COX-2 pathways. Activates descending serotonergic pathways. Blocks the cannabinoid receptors. The first MOA of lidocaine Blocks action potential generation in healthy nerves at the sodium channel. Reduces neuronal hyperexcitability and spontaneous firing in injured nerves, whether acutely injured nerves or nerves remaining hyperexcitable after a remote injury, again at the sodium channel. 2

3 The second MOA of lidocaine: anti-inflammation 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; The second MOA of lidocaine 5. reduction of prostaglandin biosynthesis; 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 lidocaine blocked inflammatory TNF-α and thus reduced endothelial nitric oxide synthase. Parenteral lidocaine protocol EKG, done within the preceding month, must not reveal cardiac dysthymia or conduction block. LFT s must be normal. Seizures are a relative contraindication. Patient should 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 3

4 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. We recommend a blood level of as appropriate for maintenance. When adverse effects occur, they usually resolve within minutes; slowing the rate of the infusion is preferable to stopping the infusion. Ferrini and Paice Case Presentation #1 JLJ, 43yo male admitted 7/24/17 with abdominal pain, nausea, and vomiting. Lipase 345; abnormal CT of abdomen c/w pancreatitis. We were asked to see him on 7/26 with uncontrolled pain. Case Presentation #1 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. 4

5 Case Presentation #2 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. Case Presentation #2 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. Ketamine Brand name is Ketalar. Is used most often as a general anesthetic. Produces profound analgesia, unresponsiveness to commands, excessive salivation, and amnesia; but patients often will have their eyes open and move their limbs spontaneously. This is known as dissociative anesthesia. As a result, a benzo or thiopental must be administered concomitantly to produce true sedation. 5

6 Ketamine Beneficial effects with its use as an anesthetic: produces analgesia, which most general anesthetics do not. increases cerebral blood flow and intracranial pressure. increases blood pressure, heart rate, and cardiac output. produces significant bronchodilation. Ketamine Adverse effects with its use as an anesthetic: may produce myocardial ischemia. is relatively contraindicated in patients with increased intracranial pressure. is relatively contraindicated in patients with glaucoma or open eye injuries, with schizophrenia or PTSD, or with significant liver or renal dysfunction. may be relatively contraindicated in a patient who has experienced the serotonin syndrome. The MOA s of ketamine Opioid receptor blockade, at µ and δ sites but does not reverse with naloxone. NMDA receptor blockade, thus blocking glutamate activity at this site, it prevents acute physiologic pain to some degree, but exerts a greater effect against pathological pain, such as chronic neuropathic or cancer-related pain. This is probably is the most important site of analgesic activity. Downregulates sodium channels and inhibits serotonin and norepinephrine reuptake, thus making it useful in acute pain this makes it very effective for trauma patients, because it does not lower the BP as do many opioids or other anesthetics. Enhances activity at GABA A receptors 6

7 Ketamine used topically Used as a 5 10 % preparation, applied while wearing gloves, to the area of the incision, laceration, rib fracture, etc. Must be compounded, and some compounding pharmacies charge $$$$ for it. may be mixed with other agents such as amitriptyline, lidocaine, ketoprofen, gabapentin May be used pre-emptively or post-operatively especially useful in amputations, acute or chronic nerve injuries, CRPS, central pain, or depression. Ketamine used IV perioperatively Primary effect is thought to be at the NMDA receptor. Often used immediately pre-op and then during the procedure, but stopping in the post-op unit before transfer to the floor. Now being used more often on the floor as an adjunct to typical pain management with opioids. Typical dosing is 0.02 mcg/kg/hour to 0.5 mcg/kg/hour as a constant infusion. It is not used as bolus pushes by the RN or as a PCA. To prevent the treatment emergent psychotomimetic effects, lorazepam mg IV q 4 hours can be very effective. Can be used as a constant IV infusion of up to 30 mg/hour for several days for varying disorders. 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, placebo-controlled, psychophysical study. Neurology. 2000; 54:

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