Pain and Symptom Management: What if Anything is New JIM MCGREGOR MD SENIOR MEDICAL DIRECTOR SCAH

Transcription

1 Pain and Symptom Management: What if Anything is New JIM MCGREGOR MD SENIOR MEDICAL DIRECTOR SCAH

2 Objectives List 2 possible situations in which ketamine may be used Outline the appropriate starting dosage for each Describe a medical indication for the use of lidocaine infusion List the pre-opioid check list for use of opioids for refractory COPD patients

3 Case 1 42 yr old woman with widely metastatic breast cancer to lungs, liver, bones, pleura/chest wall Admitted to hospital for uncontrolled pain in sharp right back and intermittent sharp pain across her breast radiating to her back pain 10/10 On admission, SR oxycodone 80 mg twice a day, oxycodone IR 20 mg every hour as needed In hospital hydromorphone 0.5 mg IV PCA Other medications: gabapentin 300 mg q8h, duloxetine 30 mg daily What might you do?

4 Case 1 continued Dexamethasone 6 mg daily added Pain continued to be 8-9/10 in spite of 20 mg of IV hydromorphone in 24 hours Decision to stop oxycodone and start basal infusion of hydromorphone Rate started was 1.5 mg/ hour with 0.5 mg q 15 min PCA Continued pain in spite of 20 mg in bolus over 24 hours Rate increased to 2.5 mg/hour Slight improvement in pain to 7-8/10 Patient c/o lethargy and somnolence

5 Case 1 Continued Neuropathic pain not responding to standard treatment Patient somnolent and wishes to be more alert Possible solutions: increase gabapentin but already somnolent Methadone caused worsening somnolence What to do?

6 Ketamine A dissociative anesthetic Off label indications include pain, depression and others Mechanism of action NMDA receptor antagonism, works on muscarinic cholinergic receptors, serotonin, norepinephrine, dopamine receptors, L-type calcium and sodium channels and opioid receptors

7 Ketamine Pharmaokinetics IV formulation has an onset of action in seconds and last 30 seconds to 5 minutes IV 90% availability Oral formulation has an onset of 15 to 20 minutes and lasts 1 to 2 hours PO 16% availability and is metabolized into norketamine which is equianalgesic and has a T1/2 of 4 hours Oral norketamine levels are 2-3 times higher than IV Conversion of IV ketamine to oral is 3:1 (Amin P et al. Case Report, J of Pain and Pall Care Pharm. 2014)

8 Ketamine for Pain 50 published clinical trials Several case reports show benefit as reported by Amin et al

9 Ketamine Use at UCSD Typical dosing 0.2 to 0.5 mg/kg/hr CIVI with no bolus Switch from IV to oral: 3 to 1 ratio Titrated by 30% daily over 3 days Maximum oral dose 200 mg very 6 hours

10 Case 1 continued PCA infusion stopped continued on PCA 1.5 mg q 15 min Was on 1200mg OME/24 hours Started sustained release oxycodone 260 mg q8h Ketamine infusion started at 0.2 mg/kg/hr = 0.2 x 50 kg= 10 mg/h Based on breakthrough could increase rate by 0.1 mg/kg/hr Final rate 0.4 mg/kg/hr Switch PCA to oral oxycodone dose of 8 mg SR oxycodone decreased to 160 mg 12 h

11 Case 1 Planning for discharge Patient not wanting infusion so switch from IV to oral ketamine IV dose 0.3 mg/kg/hr x 50 kg = 15 mg/hr x 24= 360mg in 24 hours IV to oral 3:1= 120 mg oral ketamine in 24 hours 40 mg q8h accomplished over 3 days 30% each day

12 Guidelines for Using Ketamine Indications: neuropathic pain following a trial of opioids, anticonvulsants, and TVAs Other pains which may respond to ketamine: skin pain, mucosal pain Side effect: dysphoria, hallucinations, vivid dreams, dizziness, palpitations, hypertension, nausea, features of opioid toxicity. Symptoms of cystitis, hematuria and suprapubic pain have been observed at higher doses (400mg/24 hr)

13 Guidelines for Using Ketamine 1. Adjust opioid regimen: switch to short acting opioids reduce total daily opioid dose by 30% prescribe usual opioid rescue medication 2. Relative contraindications: Raised ICP, severe systemic hypertension, raised intra-ocular pressure, recent H/O epilepsy, recent H/O psychosis 3. Caution for patients with intracranial space occupying lesion, cardiac arrhythmia, long acting opioid

14 Guidelines for Ketamine Use Starting dose (oral route): all patients 10 qid Rate if increase (oral route): mg qid % mg qid 25-33% >100 mg qid 20-25% Example: day 1 10 mg qid day 2 20 mg qid day 3 40 mg qid day 4 60 mg qid day 5 80 mg qid

15 Guidelines for Ketamine Use Subcutaneous route: starting dose frail patient mg infusion/24 hours Fit patient mg infusion/24 hours (max dose 500 mg/24 hours) Rate of increase severe uncontrolled pain: % 8 hourly Other patients: % daily Observations: Pain score, pulse, BP 0 mins, 30 mins, 1 hour and q 4hours on day 1 Once patient comfortable consider reducing oral opioid daily dose by 33% and gradual continue to reduce as able (Northern Regional Palliative Care Physicians)

16 Opioid Overdose If RR >8/min and patient not cyanosed observation If life threatening respiratory depression, dilute 400 mcg of naloxone in 10 ml and inject IV 1 ml/min and repeat until patient s condition improves If relapse (usually in about 20 min) give further mcg IV Aim is to reverse respiratory depression not the analgesic effect

17 Case 2 34 yr old man with pancreatic cancer (neuroendocrine) Stent placed for ascending cholangitis 2 and a half yr old daughter Pain upper abdomen and back without dyspepsia, nausea or vomiting IV hydromorphone 10 mg/h Dexamethasone 8 mg daily Methadone 5 mg bid Metoclopramide 5 mg qid

18 Case 2 Pain worsens and additional characteristic of sharp shooting right abdominal pain Has Pleurx drain for ascetic fluid Methadone increased to 5 mg q8 hr Bolus hydromorphone 25 mg every 10 minutes Pain continues so methadone increased to 10 mg q8 hr Hydromorphone infusion increased to 15 mg/h Pain still not relieved

19 Case 2 Decision to try lidocaine infusion Routine methadone stopped Prn methadone 30 mg q4h prn Hydromorphone basal to 1 mg/h Lidocaine bolus 120 mg over 30 minutes with pain relief Infusion started at 7.8 ml/h By the next day able to ambulate with minimum assistance Developed blurry vision and perioral numbness Infusion decreased to 3.8 ml/h

20 Case 2 Tachycardic, episodes of hallucinations Hydromorphone infusion increased to 3 mg/h Methadone 30 mg tid Following day unresponsive BO 78/54, P 133, T 101.9, RR 26 Dies peacefully

21 Lidocaine Infusion Protocol(Arachoiditis.com/lidocaine) Indications: Severe neuropathic and musculoskeletal pain unrelieved by opioids and adjuvants or patient too sedated by required dose of opioid Lidocaine challenge1-3 mg/kg administered IV in concentration of 8 mg/ml over minutes During infusion careful recording of VS and pain intensity at least every 15 minutes (SC concentration 40 mg/ml over 30 minutes to an hour

22 Lidocaine Infusion (Arachoiditis.com/lidocaine) If challenge effective start infusion SC or IV at mg/kg/h using the lowest dosage that manages pain Over next 72 hours titrate downward to lowest effective dose Reduce opioids rapidly if patient exhibits toxicity If pain exclusively intermittent use bolus Discuss signs and symptoms of toxicity Side effects are sequential and relatively predictable and can be reversed by decreasing or stopping the infusion

23 Lidocaine Side Effects Lightheadedness, numbness around tongue and mouth, and/or dizziness (usually at plasma levels of 4-6 mcg/ml) At higher levels (8 mcg/ml), visual and auditory disturbances, dissociation, muscle twitching, decreased BP At 12 mcg/ml, convulsions At 16 mcg/ml, coma At > 20 mcg/ml, respiratory arrest and cardiovascular collapse Plasma levels when infusion 1-2 mg/kg/h often less than 3 mcg/ml

24 Lidocaine Infusion: Titrating Opioids As pain relieved, necessary to reduce opioids to avoid side effects A previously tolerated opioid dose may result in sedation Rapid downward titration tolerated e.g. 90 mg/h hydromorphone to 1-2 mg/h in 24 hours

25 Case 3 76 yr old man with CAD with heart failure diagnosed 3 yrs ago, Type 2 DM with diabetic neuropathy and nephropathy (CCl 35), COPD C/O severe neuropathic pain in his feet and legs which interferes with his mobility NYHC III, Stage C heart disease Prognosis approximately 18 months

26 Case 3 Meds: hydrochlorothiazide 25 mg daily, Isosorbide 20 mg BID, lisinopril 20 mg daily, metoprolol 50 gm BID, furosemide 40 mg BID, Potassium 20 meq daily, Albuterol MDI ii puffs QID prn, Ipratropium I puffs QID, Tylenol PM, citalopram 10 mg qhs Oxycodone for neuropathic pain had side effects and drowsiness Started gabapentin 300 mg TID and was sedated and had a fall Refusing to take that again Prebabulin caused dizziness What are the options to treat his pain?

27 Methadone What are the considerations when considering methadone for this man?

28 Methadone Guidelines (Chou et al) Baseline ECG if risk factors for QTc prolongation ECG within one yr acceptable

29 Methadone Guidelines (Chou et al) Relative contraindications: H/O ventricular arrhythmia H/O QT prolongation Meds which prolong QTc

30 Meds With Potential to Increase QTc TCAs Fluoroquinolone antbiotics Macrolide antibiotics Anticholinergic drugs and drugs with anticholinergic side effects SSRIs Systemic antifungals (ketoconazole, fluconazole) Cardiac dysrhythmic drugs 5HT3 receptor antagonists Hydrochlorothiazide

31 Risks for This Patient Hydrochlorothiazide Tylenol PM Citalopram

32 Case 3 Presumed prognosis of at least 18 months Was on oxycodone SR 20 mg BID but sedated Dosage of methadone? QTc 425 ms

33 Methadone Dosing In Hospice and Palliative Care (MacPherson ML, AAHPM) OME/day <40 to 60 mg mg QD or BID OME/day 60 to 120 mg- 10:1 morphine to methadone OME/day >200 mg- 20:1 morphine to methadone Do not exceed 30 mg methadone starting dose Adjust in 5-7 days If age > 65 decrease dose by 30 50% Decrease dose of cachectic, on concurrent meds that increase methadone levels (TCAs, antifungals, SSRIs, macrolides), severe ESLD, non-physical pain component

34 Case 3 Oxycodone for this man 20 mg BID OME 60 mg Starting dose of methadone 2.5 mg BID Chou et al would recommend checking ECG in 2-4 weeks or in dose >30 to 40 mg/day, or new risk factors for QTc prolongation If baseline QTc 450 to 500, correct reversible causes If baseline Qtc >500 do not use methadone (Methadone Safety: A Clinical Practice Guideline. Journal of Pain, Apr 2014, Vol 15, Issue4 pages Consensus Guidelines for Methadone Safety and Effectiveness in Hospice and Palliative Medicine, MacPherson ML)

35 Refractory Depression and Anxiety Depression and anxiety are prevalent and undertreated in hospice LOS hospice 18.5 days in 2013 Most antidepressants not effective for 4-6 weeks 28-day open-label proof of concept trial with oral ketamine Received daily oral dosage of ketamine (0.5 mg/kg) Results: Time to response 8.6 +/- 6 days for anxiety (median 7) and /- 19 days for depressive symptoms (median of 10.5) Response rate for depression 57% Response rate for anxiety 100%

36 Case 4 78 yr old woman with metastatic colon cancer with retroperitoneal mets causing hydronephrosis, extensive liver and bone mets C/O constant feeling of nausea worse at times Unrelieved by vomiting She has Parkinson s disease and her movement disorder was worsened with haloperidol How would you manage her nausea?

37 Case 4 constant felling of nausea unrelieved by vomiting points to CTZ Need antidopaminergic drug Olanzapine: atypical antipsychotic with affinity for D1, D2, D4 Fewer extrapyramidal side effects, does not usually cause QT prolongation, weak inhibitor of CYP isoenzymes so less likelihood of drug interactions Dosage 5-10 mg a day Patients over 65 or debilitated mg a day Also dexamethasone 4 mg a day (dosage 4-8 mg/day for nausea Glare et al, Treating nausea and vomiting in palliative care: a review. Clin Interv Aging. 2011; 6:

38 Antiemetics in SNFs CMS Skilled Nursing Facility Regulations F329 has specific language that provides an exception to the specific criteria for antipsychotic drug use(including haloperidol) for hospice patients in SNF Subsection (1) after table of drugs CMS concerned about Exception: When antipsychotic medications are used for behavioral disturbances related to Tourette s disorder, or for nonpsychiatric such as movement disorders associated with Huntington s disease, hiccups, nausea and vomiting associated with cancer or chemotherapy or adjunctive therapy at the end of life Therefore for haloperidol and other antipsychotic drugs being used to manage symptoms related to EOL in SNFs, the regulatory criteria on maximum dose, duration of therapy or related issues do not apply

39 Case 5 78 yr old man with COPD C/O quite severe dyspnea which is not responsive to present meds Using MDIs of albuterol I puffs qid, ipratropium ii puffs qid, beclomethasone dipropionate ii puffs bid How would you manage this?

40 Pre-Opioid Checklist for COPD Accurate diagnosis and severity assessment. Optimal standard treatment. Assessment of factors (renal, hepatic, pulmonary function, current and past opioid use) that impact the dosing of opioid. Understanding and addressing possible psychosocial, spiritual factors that worsen dyspnea. In this regard, dyspnea is analogous to pain. Conversation with patient, family and other healthcare providers involved in the care regarding goals, side effects and allaying concerns of addiction. If advance care planning on end-of-life decisions has not been made, consider whether the time is opportune to discuss these.

41 Opioid Dosing for Dyspnea in COPD Opioid naïve patient 3 mg q6h prn SOB Opiate naïve: no regular opioid for last 2 weeks Already on opioid for pain, increase dose by 25-50%

42 Is Medicine the Only Way to Manage Pain?

43 The Medical Model Fails to explain several observations especially in older adults Pain reported often has a very poor correlation to evidence of tissue pathology Treatments often do not relieve pain Non-biomedical factors may play important roles in the pain experience

44 Biopsychosocial Model Pain is a complex experience influenced by many psychological, social, relational, spiritual factors Treatment directed to these factors can improve management

45 Psychological Context Pain catastrophizing: tendency to focus on and magnify pain sensations It is more associated with increased pan intensity and disability Associated with the affective aspects of pain: anger, anxiety, sadness, depression These patients report higher level of social support Partners express higher levels of stress

46 Social Context Social isolation and socioeconomic status impact pain and disability Pain leads to isolation, difficulty maintaining relationships Patients with lower socioeconomic status are at greater risk of disabling pain

47 Psychosocial Interventions Cognitive Behavioral Therapy help patients alter pain-relevant thoughts, emotions and behaviors Educate patients in skills such as relaxation, distraction, activity pacing, cognitive restructuring, and problem solving Skills such as progressive muscle relaxation, imagery, goal setting, activity pacing, identifying and challenging negative thoughts, and problem solving

48 Emotional Disclosure Premise is that the patient s inability to experience, identify, express and process negative emotions exacerbates pain and psychological distress Write or speak about their deepest thoughts and feelings related to a stressful experience Usually minute sessions Writing about their thoughts and feeling about disease shown to reduce pain and fatigue (as reported in BJA 111 (1): (2013)

49 Mind-body Interventions Mindfulness-based stress reduction and yoga Studies show that these interventions may be helpful MBSR improved pain acceptance and physical functioning Chair-based yoga improved physical functioning is older patients with OA

50 Other Complimentary Therapies Reiki: hand-based techniques to help alleviate physical, mental and emotional illnesses. Healing and calming. PC patients have improvement in pain and suffering Acupuncture: specific points of body stimulated by various techniques. In PC used to ease pain, nausea and fatigue Massage therapy

51 Aromatherapy Human Response Anxiety Nausea Pain Comfort Measure Intervention Listening to music, gentle touch, massage, EOA: lavender, bergamot EOA: Peppermint, lemon Positioning, relaxation training, massage, imagery, EOA: lavender, lemon, bergamot Spiritual distress Listening to story, music, art, relaxation training, EOA: lemon, lavender, bergamot Fear Active listening, relaxation training, EOA: lavender Grieving Listening, story telling, music, art, EOA: bergamot Powerlessness/poor coping Sleep Comfort Listening, art EOA: lavender Music, relaxation, EOA: lavender RT, music, massage, EOA: lavender, lemon, sweet orange, bergamot

52 Questions? I have time?