1. Ketamine Facilitator: Barbara Bischoff, BSN, RN

2. Case Study A 51 year old woman presents to ED with right shoulder pain 11/25/14 Stage 4 Breast Cancer Carcinoma of breast/Cellulitis History of left side Mastectomy Port to left side of chest wall Pt weight 70 kilograms

3. Case Study (continued) Initial Medications Duragesic Patch 100 mcg/hr (Fentynal) 1 patch Q72 hr Hydrocodone (APAP) 5 mg/325 mg (Norco) 1 tab PO Q6 hr PRN Morphine Sulfate (MS Contin) 60 mg tab PO Q12 hr Miralax 17 gm 1 time daily PO Ondansetron (Zophran) 8 mg tab PO Q6 hr

4. Case Study (continued) WBC 7.7 ( 3.9–10.7 x 10 3 cells/μL) RBC 3.99 (4.2–5.9 x 10 6 cells/μL) H & H 12.2/36.6 (12–16 g/dL/36–47%) INR 2.6 (2.0–3.0) Na 139 (136–145 mEq/L) K 3.9 (3.5–5 mEq/L) Cl 104 (98–106 mEq/L) BUN 7 (10-20 mg/dl) Creatinine 0.5 (0.7–1.3 mg/dL) Lab Results on Admission

5. Case Study (continued) Patient on Maria Hall 11/25/15-12/2/15 Patient placed in Palliative Care Patient transferred from Maria Hall to ICU @1300 12/2/15 Continuous monitoring Pain management with ketamine drip Ketamine bolus 10 mg with doctor at bedside Ketamine drip initiated Ketamine 12 mg/Dilaudid 10 mg/hr

6. Ketamine Pain Management Mechanism of Action Clinical Effects Therapeutic Administration Use as an analgesic in palliative care (FDA, 2014; Micromedex, 2015)

7. Ketamine NMDA glutamate receptor antagonist Binds to opioid mu and sigma receptors Acts on cerebral cortex and limbic system Release of endogenous catecholamine Reduces polysynaptic spinal reflexes Anesthetic agent used as analgesic to manage complex pain (Micromedex, 2014, NHS, 2013) GOPIXPIC. (n.d.).

8. NMDA Receptor N-methyl-D-aspartate receptor Located in the dorsal horn of the spinal cord Usually inactive Activated by development of persistent pain NMDA receptor antagonists used to block this receptor

9. Problem Description Increasing number of opioid tolerant patients. High Tolerance Usual multimodal regimen: Opioids Non-opioids NSAIDs Gabapentanoids Muscle Relaxers May not manage pain. (Colfer, Wolo & Viscusi, 2013).

10. Goals of Acute Pain Management in Opioid Tolerant Patients Identify at-risk population Prevent withdrawal symptoms/complications Effective analgesic treatment in acute pain Treatment of psychological disorders Rehabilitation to maintenance therapy (Bourne, 2010)

11. Opioid-tolerant patients in practice Three main groups of opioid-tolerant patients : Patients with cancer pain Patients with chronic non-cancer pain Patients with current addiction to opioid drugs Patients on a maintenance drug program (ANZCA, 2010)

12. Opioids Alone Compromise patient safety Cause side effects Nausea Vomiting Dependence Respiratory Depression (Colfer, Wolo & Viscusi, 2013)

13. Chronic Wounds/Chronic Pain A wound that fails to heal within 3 months. Social, psychological, physical and economic cost Consequences: Severe impairment of quality of life Restriction of daily activity Emotional distress Lengthy treatment High treatment expense (Frykberg, 2011; Werdin et al., 2009; Ruttermann et al.,2013)

14. Position Statement Pain Management American Society for Pain Management Nursing Nurses must advocate for optimal Pain management Symptom relief A meta-analysis 52 studies Spanning 40 years Found 64% of advanced cancer patients have pain ( Reynolds, Drew & Dunwoody, 2013, Colfer, Wolo & Viscusi, 2013)

15. Policy Statement Oral or IV Ketamine will be initiated upon order from a physician via CPOE. First 24 hours or TBD by MD Administered by nurses in critical care Follow standing order set (NHS, 2013; Zittel, 2011)

16. Signs and Symptoms of Opioid Withdrawal Sweating Restlessness Papillary dilation Irritability Tachycardia Nausea Hypertension Abdominal cramps Vomiting Hyperalgesia Diarrhea Myalgia Yawning Dysphoria Fever/chills Insomnia Rhinorrhea Anxiety Lacrimation Craving for opioids Pilorection ( Adapted from Collett, 1998; Bourne, 2010)

17. Process Patient specific order Infusions prepared by pharmacy Infuse through dedicated line via most proximal port Use portless IV tubing No bolus without anesthesia provider (Zittel, 2011; DRE, 2015)

18. Low-dose Ketamine Defined Bolus < 2 mg/kg intramuscular administration Bolus < 1 mg/kg intravenous administration Continuous IV is < or = 20 microg/kg per min (Schmidt, Sandler & Katz, 1999)

19. Administration Initial ketamine concurrent with opioid. Monitor for sedation or confusion If drowsy notify MD Ketamine side effects (patient not drowsy): Hallucinations or dysphoria Administer as ordered by MD: Haloperidol Midazolam (NHS, 2013)

20. Administration Process Dosing By Pharmacy Prepare new syringe every 24 hours. Dilute ketamine with sodium chloride 0.9%. Check: Syringe is not cloudy Protect it from light. Check: Stability and compatibility. Rotate SC infusion site daily. (NHS., 2013)

21. Monitor Vital signs Alertness Orientation Evidence of: Nystagmus Bad dreams Unpleasant hallucinations. (Zittel, 2011)

22. Report Heart rate > 100 beats per minute Systolic B/P < 90 mmHg Respiratory < 10 breaths per minute Oxygen saturation of < 93% Emergence reaction symptoms: Bad dream Hallucinations Nystagmus (Zittel, 2011)

23. Onset and Duration Rapid Onset: IV within 30 seconds Half-life: 10-15 min (Alpha phase) > 2.5 h (Beta phase) IM within 3-4 minutes. Duration: IV 2 mg/kg lasts 5-10 minutes IM 9 to 13 mg/kg lasts 12-25 minutes (SEMAC, Micromedex, 2015)

24. Common Side Effects Dizziness Tachycardia Altered mental status Anxiety Palpitations Slurred speech Hallucinations Nystagmus Mydriasis Muscular hypertonus Trismus Psychomotor reactions Psychomimetic reactions Emergence delirium Hypertension Chest Pain

25. Converting from IV to Oral Ketamine Oral ketamine is more potent than IV ketamine Dose reduction with change Prescribed in divided doses - four times daily Titrated in 5-10 mg increments per order IV infusion may be stopped with the first dose Or gradually reduced with increase of oral infusion. (NHS., 2013)

26. Contraindications Drug allergy Use of droxidopa Pregnancy Breast-feeding Head trauma or injury Bleeding in the brain Stroke Increased spinal fluid pressure Increased ocular pressure Bladder or urinary problems Congestive heart failure High blood pressure Mental or mood problems Thyroid problems.

27. Pain Management Resource Sites American Society of Regional Anesthesia and Pain Management http://www.asra.com/ American Society for Pain Management http://www.aspmn.org/ American Society of Anesthesiologists http://www.asahq.org/ Food and Drug Administration http://www.fda.gov/Drugs/ Anesthesia Patient Safety Foundation http://www.apsf.org/ Institute for Safe Medication Practices http://www.ismp.org/ ( Colfer, Wolo & Viscusi, 2013).

28. Thank you for your Time Questions? Comments?

29. References ANZCA (Australian and New Zealand College of Anesthetists, Faculty of Pain Medicine). (2010). Acute Pain Management: Scientific Evidence (3 rd ed.). Melbourne, Victoria, Australia. ANZCA. Bourne, N. (2010). Acute pain management in the opioid-tolerant patient. Nursing Standard. 25, 12, 35-39. Chin, M.L. (2014). Multimodal analgesia: Role of non opioid analgesics. American Society of Regional Anesthesia and Pain. Retrieved from https://www.asra.com/pain- resource/article/35/multimodal-analgesia-role-of-non-opioid-analgesics Colfer, K., Wolo, E. & Viscusi, E.R. (2013). Acute pain management: Current trends,technologies, and new agents. Journal of Legal Nurse Consulting, 24(1), 11-19. Collett, B.J. (1998). Opioid tolerance: the clinical perspective. British Journal of Anaesthesia, 81(1), 58-68. Dickenson, A. H. (1997). NMDA receptor antagonists: Interactions with opioids. Acta Anaethesiologica Scandinavica, 41(1), 112-115.

30. References (Cont) Drugs.com. (2015). Droxidopa. Retrieved from http://www.drugs.com/mtm/droxidopa.html http://www.drugs.com/mtm/droxidopa.html FDA (U. S Food and Drug Administration). (2014). "Off-Label" and investigational use Of marketed drugs, biologics, and medical devices - information sheet guidance for institutional review boards and clinical investigators. Retrieved from http://www.fda.gov/regulatoryinformation/guidances/ucm126486.htm http://www.fda.gov/regulatoryinformation/guidances/ucm126486.htm Frykberg, R.G. (2011). The science of advanced wound care: What should you be using in your office? Podiatry Today Supplement: Emerging evidence on advanced wound care for diabetic foot ulcerations. HMP Communications, LLC (HMP), 1-3, 8- 15. GOPIXPIC. (n.d.). Cerebral cortex. Limbic system. Image retrieved from http://www.gopixpic.com/limbic-system-not/ http://www.gopixpic.com/limbic-system-not/ Loftus, R.W., Yeager, M.P., Clark, J.A., Brown, J.R., Abdu, W.A., Sengupta, D.K. & Beach, M.L. (2010). Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology, 113(3), 639-646. doi: 10.1097/ALN.0b013e3181e90914.

31. References (Cont) Medtronic. (2014). Common Types of chronic pain. Retrieved from http://www.medtronicneuro.com.au/chronic_pain_commontypes.html Micromedex. (2014). Ketamine Hydrochloride. DrugPoint Summery. Retrieved from http://www.micromedexsolutions.com/micromedex2/librarian/PFDefaultActionI d/evidence http://www.micromedexsolutions.com/micromedex2/librarian/PFDefaultActionI d/evidence NHS. (2013). Ketamine in palliative care. Lothian. Reynolds, J., Drew, D. & Dunwoody, C. 2013. American Society for Pain Management Nursing Position Statement: Pain Management at the End of Life. Ruttermann M., Maier-Hasselmann, A., Nink-Grebe, B. & Burckhardt, M. (2013). Clinical practice guideline: Local treatment of chronic wounds in patients with peripheral vascular disease, chronic venous insufficiency, and diabetes. Dtsch Arztebl Int; 110(3): 25–31. DOI: 10.3238/arztebl.2013.0025

32. References (Cont) Schmid, R.L., Sandler, A.N. & Katz, J. (1999).Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain, 82(2), 111-125. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10467917 http://www.ncbi.nlm.nih.gov/pubmed/10467917 SEMAC (State Emergency Medical Advisory Committee). (n.d.). Ketamine. Drug Formulary. Retrieved from https://www.health.ny.gov/professionals/ems/pdf/ketamine_formulary https://www.health.ny.gov/professionals/ems/pdf/ketamine_formulary Sigma-Aldrich. (2015). S-(+)-Ketamine hydrochloride. Picture retrieved from http://www.sigmaaldrich.com/catalog/product/sigma/k1884?lang=en&reg ion=US http://www.sigmaaldrich.com/catalog/product/sigma/k1884?lang=en&reg ion=US Werdin, F., Tennenhaus, M., Schaller, H.E. & Rennekampff, H.O. (2009). Evidence-based Management Strategies for Treatment of Chronic Wounds. Open Access Journal of Plastic Surgery, 9(19), 169-179.