PALLIATIVE CARE SYMPTOM MANAGEMENT Patricia Ford MD Medical Director Community Hospice of Saratoga

OBJECTIVES: Review common non-pain symptoms experienced by patients with chronic, progressive and life-limiting illnesses Identify causes of those symptoms Learn interventions to treat symptoms using both drug and non-drug treatment modalities

COMMON SYMPTOMS Dyspnea Nausea/Vomiting Excess Secretions Agitation/Delirium Constipation

DYSPNEA Definition: A subjective sensation of difficulty breathing; an abnormally uncomfortable awareness of breathing 25% of ambulatory patients and over 50% of inpatients have dyspnea

Mr Jones 78 yo with ES COPD on home hospice. Bed to chair with marked dyspnea. Dyspneic with conversation. Meds: Advair, Spiriva, Combivent, prednisone 10 mg daily Albuterol nebulizer was added – using this about 5 times/day with some relief Continuous supplemental O2 at 2 lit/NC

Mechanism of Dyspnea Hypoxemia, bronchoconstriction, hyper-inflation stimulate sensory receptors CNS processes information – sends impulse to respiratory muscles Mismatch between afferent information from various receptors and the respiratory motor activity - dyspnea

Causes of Dyspnea tracheal obstruction, asthma, COPD, aspiration, diffuse primary or metastatic cancer, lymphangitic metastases, pneumonia, pleural effusion, pneumothorax, pulmonary drug reaction, radiation pneumonitis

Treating the Underlying Cause COPD - MDI’s not effective in severe cases Aerochambers may help Nebulizers are preferred Inhaled steroids may be stopped in patients on chronic oral steroids CHF – titrate nitrates/diuretics

DYSPNEA in Palliative Care Non-Drug Treatments Positioning - sitting up Bedside fan Pursed lip breathing Humidified air Noninvasive positive pressure mask

DYSPNEA Treatment with Oxygen Think of oxygen as any other drug - not all dyspneic patients benefit Pulse oximetry will generally not be of benefit in decision-making for treating terminal dyspnea Masks and positive pressure devices are poorly tolerated; use nasal cannula or nasal high flow For end of life, use 2-4 liters of oxygen; for continued dyspnea use drug therapy rather than using higher flow rates or face mask

High Flow O2 vs BiPAP for Dyspnea in Advanced Cancer HFO: Delivers up to 40L/min humidified heated O2 Provides naso-pharygneal washout and positive distending pressure Decreases airway resistance and the metabolic cost of breathing BiPAP: Also assists ventilation and unloads respiratory muscles – may stimulate trigeminal nerve

Study Results Dyspnea improved with both – lasted for two hours Non-significant decrease in resp rate BiPAP – decreased heart rate HFO – decreased BP and improved O2 No adverse effects – less trouble sleeping on HFO vs BiPAP

DYSPNEA Drug therapy – mainstay is opioids Acutely increase exercise tolerance Reduce minute ventilation Reduce subjective sense of breathlessness Small doses can be effective: 5-10 mg of oral morphine in opioid naïve patients; for severe dyspnea or when patients are unable to swallow, 1-5 mg morphine IV q 10 minutes Other opioids are also useful for dyspnea

Opiate Titration As with pain, titrate to comfort. (tachypnea may persist) May use long acting preparations ex. Morphine sulfate extended release or fentanyl patch with short acting opiate for breakthrough dyspnea

Morphine and Respiratory Depression Sedation precedes respiratory depression. Low dose opioids can be used in advanced COPD to enhance quality of life. Opioid dose can be titrated up at the end of life when needed for symptom control. This is not euthanasia or assisted suicide. Ethically, the use of these drugs is appropriate and essential, as long as the intent is to relieve distress, rather than shorten life. There is no justification for withholding symptomatic treatment to a dying patient out of fear of potential respiratory depression.

Mr Jones 78 yo with ES COPD on home hospice. Bed to chair with marked dyspnea. Dyspneic with conversation. Meds: Advair, Spiriva, Combivent, prednisone 10 mg daily Albuterol nebulizer was added – using this about 5 times/day with some relief Continuous supplemental O2 at 2 lit/NC

Treatment Modifications Discontinue spiriva/advair/combivent Albuterol/ipratropium nebulizer q 4h Albuterol nebulizer prn +/- increase supplemental O2 to 3 lit/NC Morphine 5 – 10 mg po q 1 hr prn Fan across the face prn/relaxation techniques/ pursed lip breathing

Role of Anxiolytics Anxiolytics- benzodiazepines (e.g. lorazepam) may help relieve the anxiety associated with dyspnea Possibly blunt ventilatory drive When combined with opioids, will produce additive sedative/CNS depressant effects which may or may not be desirable

Nausea/Vomiting Occurs in 62% of cancer patients Present in 40% opioid treated patients Under reported and under treated Anorexia may represent chronic low grade nausea

The Case of Mrs. Rubio 72 yo with lung cancer with metastases to adrenals, bone and brain Disease progression despite treatment Recent whole brain radiation Admitted to hospice – 30 lb weight loss, fatigue and weakness Pain well managed on MS Contin 60 mg bid + MSIR for BTP Occasional nausea – prn promethazine

Common Causes of Nausea and Vomiting in Hospice patients Chemical: metabolic, drugs, infections Visceral and serosal causes: bowel obstruction, GI bleed, enteritis, constipation Increased intracranial pressure, anxiety, meningeal irritation Labyrinth disorders

Mechanisms of Nausea Chemicals Affect D2, 5HT3, NK1 receptors – stimulate the chemoreceptor trigger zone Mechanical/GI Affect 5HT3, mechanoreceptors and chemical receptors in GI tract – peripheral pathways Labyrinth disorders – Achm, H1 – stimulates the vestibular system Cortex – anxiety, meningeal irritation, increased ICP Stimulate the vomiting center in the brainstem

NAUSEA / VOMITING Common causes of nausea Obstruction Gastritis, GERD Gastric stasis GI infection Constipation Abdominal carcinomatosis, extensive liver metastases Acute effect of abdominal radiation or chemotherapy Ascites – squashed stomach syndrome

NAUSEA / VOMITING Other causes of nausea Often multi-factorial CNS - elevated ICP, posterior fossa tumors/bleed, infectious or neoplastic meningitis Drugs - opioids, chemotherapy, antibiotics Metabolic - hypercalcemia, liver failure, renal failure, sepsis Psychological - anxiety, pain, conditioned response (e.g. anticipatory nausea/vomiting) Often multi-factorial

NAUSEA / VOMITING Treatment with Non-Drug Therapy GI drainage for obstruction Fluid management – GI obstruction may improve by reducting parenteral fluids to decrease GI secretions

Non-pharmacologic Interventions Avoid strong food smells Small frequent meals NPO during and for a while after periods of vomiting occur. Wrist bands Relaxation techniques - imagery, music, distraction, games Accupuncture/accupressure

NAUSEA / VOMITING – Drug Therapy Try to match the cause of nausea with the most appropriate drug class If primary cause is Stimulation of CTZ : Start with aD2 receptor antagonist: metoclopramide, prochlorperazine or haloperidol If ineffective, add a 5HT3 antagonist: odansetron, mirtazapine

Other Treatments for Nausea Anxiety – may add benzodiazepine Elevated ICP – glucocorticoid Gastric Stasis – metoclopramide Constipation – treat the constipation Bowel Obstruction – octreotide, venting PEG tube, surgery Vestibular – scopalamine patch

The Case of Mrs. Rubio 72 yo with lung cancer with metastases to adrenals, bone and brain 30 lb weight loss – anorexia may represent chronic low grade nausea Morphine may contribute to nausea Recommendations: Consider dexamethasone Odansetron + prochlorperazine around the clock Consider opiate rotation

Pearls in Treating Nausea Make the anti-emetic around the clock Use combination therapy when needed – work on different receptors Promethazine is only a weak anti-emetic Manage constipation if present

EXCESS SECRETIONS Respirations may become congested or gurgling, especially when death is imminent Caused by a decline in the gag reflex function and reflexive clearing of the oropharynx Secretions from the tracheobronchial tree accumulate and the patient is too weak or unable to swallow or expectorate the secretions Often the healthcare professionals and the family members are more affected by the noisy breathing than the patient

EXCESS SECRETIONS Treatments Suctioning the patient is not recommended, as it is ineffective and often uncomfortable for the patient Turn the patient on his/her side Elevate the head of the bed Reassure the family of the patient’s comfort Educate the family about the etiology of the breathing Anticholinergics, such as scopolomine, glycopyrrolate and hyoscyamine can be useful in reducing secretions

Treatment of oral secretions Drug Trade name Route Starting dose Onset Hyoscyca-mine Scopala-mine Trans-dermal 1patch 12 hrs Atropine Multiple Sub-lingual 1 drop 30 min Glycopyr-rolate Robinul Oral 1 mg SC, IV .1 mg

Common Errors Using both scopalamine and atropine Adding an anti-cholinergic then treating subsequent agitation with benzodiazepines Adding atropine for respiratory congestion in a patient that is not terminal.

AGITATION / DELIRIUM Definition - An acute altered level of consciousness associated with: Reduced attention and memory Perceptual disturbances Incoherent speech Altered sleep-wake cycles

The Case of Mr. Coons 45 year old with ESLD secondary to Hepatitis C and alcoholic liver disease Ascites requiring frequent paracentesis Hepatic encephalopathy resistant to lactulose and rifaximin Increased agitation – lorazepam makes it worse

Confusion Assessment Method Digit span-repeat 3, then 4, then 5 numbers Read letters – patient taps with ‘A’ Can a rock float? Are there fish in the sea? Is one pound more than two pounds? Do you use a hammer to pound a nail? “Hold up this many fingers” each hand

AGITATION / DELIRIUM Hyperactive Delirium Hypoactive Delirium Agitated, picking at clothes and bed covers, rambling and loud incoherent speech Hypoactive Delirium Quiet, sleepy, little spontaneous movement, soft incoherent speech

AGITATION / DELIRIUM D – drugs E – eyes and ears L – low flow states I – Intracranial R – retention I – infection U – under – hydration/nutrition/sleep M – metabolic and toxic

AGITATION / DELIRIUM Treatment - Non-Drug Quiet, peaceful room Family member present to relieve anxiety Avoid physical restraints Assess for unresolved psychological or spiritual issues, unfinished business Holistic therapy

AGITATION / DELIRIUM Treatment with Drug Therapy The primary drug class for terminal delirium are the major tranquilizers (e.g. haloperidol) Although benzodiazepines are commonly used, they may lead to paradoxical worsening of the delirium Dosing is similar to opioids for pain – give enough to reduce the target symptom, there is no maximum dose Starting dose of haloperidol is 1-2 mgs, can be given every hour as needed to reduce symptoms until the patient has stabilized, then converted to a dose given every 6-12 hours

Atypical Antipsychotics Risperidone .25-1 mg taken BID to q 6 hrs Caution with renal failure Olanzapine 2.5-10 mg taken daily Not in CNS malignancy, hypoactive, over 70 Quetiapine 12.5 – 50 mg taken bid Dosing 4 pm and hs – most sedating Aripiprazole 5-15 mg taken q am Useful for hyperactive – can cause insomnia

The Case of Mr. Coons 45 year old with ESLD secondary to Hepatitis C and alcoholic liver disease Ascites requiring frequent paracentesis Hepatic encephalopathy ‘resistant to lactulose and rifaximin’ Increased agitation – lorazepam makes it worse

Mr Coons Haldol 1 mg q 1 hr x 3 doses then 2 mg q 6 hrs around the clock Correct hyponatremia Lactulose – ‘do not hold’ Discontinue diazepam and zolpidem Improve pain management Indwelling Pleurx catheter to manage ascites

Constipation “Constipation” can mean different things to different people Acute: recent decrease in frequency or increase in difficulty starting a bowel movement, duration less than 6 months Chronic: less than 3 BM’s per week, duration more than 6 months

Constipation In addition to complaining of “constipation”, patients also complain of: Stool that is small or hard Stool that is not completely evacuated Increased gas Abdominal or rectal pain Change in stool character Anorexia and early satiety

Causes of Constipation Drugs Opioids Anti-cholinergics: (antidepressants, neuroleptics, anti-emetics, anti-histamines) Metabolic Hypercalcemia, diabetes, hypothyroidism, uremia Neurologic Spinal cord lesions

Causes of Constipation (cont’d) Mechanical Obstruction or pseudo-obstruction (Ogilvie’s) Ascites Carcinomatosis

Causes of Constipation (cont’d) Miscellaneous Pain - generalized or rectal Lack of privacy or awkward positioning (bedpan) Loss of normal bowel routine Lack of fluid intake Delirium

Opioid-Induced Constipation Little tolerance to constipation develops Start bowel protocol when opioids are initiated Optimal dose is unknown Fentanyl and methadone may cause less constipation than morphine Methylnaltrexone (Relistor©) - Sub Q injection to reverse OI constipation

Constipation: Key Assessment Issues Fecal Impaction? Constipation vs. Obstruction? Neurological Process? Fluid/Electrolye problem?

Management of Constipation General measures Increase fluid intake Restore daily bowel routine Ensure privacy Ensure a comfortable position Reverse treatable causes Prophylaxis when possible

Drug Therapy for Constipation Laxatives/Stimulants Bulk agents Lubricants Hyperosmotic agents Prokinetic drugs “Natural” laxatives Enemas

Laxatives / Stimulants Senna Bisacodyl (Dulcolax ®) Detergent laxatives “wetting agents” Colace ®, Surfak ® Castor oil is a detergent laxative that is not recommended for use.

Lubricants Mineral Oil Can be used for fecal impaction or acute constipation Causes malabsorption with prolonged use Do not use with docusate products

Hyperosmotic and Saline Agents Agents that pass through the small bowel and draw water into the colon Sugars: lactulose, sorbitol, mannitol, glycerin Saline agents: Polyethylene glycol (Miralax ®), magnesium, sulfate, and phosphate preparations

Enemas Saline (Fleets®) Tap water or soap suds Oil-retention Other

Natural Laxatives Prunes or prune juice Dates and figs Raisins Apples Senna Other

Pearls in Treating Constipation at the End of Life Do not add fiber in patient with poor fluid intake (soft impaction) Poor motility is common – senna is useful Docusate is generally ineffective alone Miralax works well, but can cause dehydration

REFERENCES Wood GJ et al Mgt of intractable nausea nad vomiting in patients at the end of life JAMA 2007; 298(10) 1196-1207 Breitbart W, Alici Y, Agitation and Delirium at the End of Life JAMA Dec 2008 McPhee et al, Care at the Close of Life: Evidence and Experience, JAMA Archives and Journals 2011 Panke, J., Coyne, P. (2006) Conversations in Palliative Care. Pittsburgh, PA: Hospice and Palliative Nurses Association

References continued Wrede-Seaman, L. (2005) Symptom Management Algorithms A handbook for Palliative Care. Yakima, Washington: Intellicard Weissman, D.(2006) Palliative Care: Presentations for Medical Educators. Medical College of Wisconsin Hui, D et al. (2013) High-Flow Oxygen and Bilevel Positive Airway Pressure for Persistent Dyspnea in Patients with Advanced Cancer: A Phase II Randomized Trial. Journal of Pain and Symptom Management Vol 46 No. 4, October 2013