Palliative Management Of: Nausea And Vomiting Dyspnea Secretions Delirium Mike Harlos MD, CCFP, FCFP Medical Director, WRHA Palliative Care Professor, University of Manitoba Faculty of Medicine

MECHANISM OF NAUSEA AND VOMITING vomiting centre in reticular formation of medulla activated by stimuli from: Chemoreceptor Trigger Zone (CTZ) area postrema, floor of the fourth ventricle outside blood-brain barrier (fenestrated venules) Upper GI tract & pharynx Vestibular apparatus Higher cortical centres

Cortex CTZ GI VOMITING CENTRE Vestibular

Chemoreceptor Trigger Zone Stimuli Of Vomiting Pathways Chemoreceptor Trigger Zone Vestibular Cortical Peripheral drugs opioids chemoTx etc... biochemical ­ Ca++ renal failure liver failure sepsis radiotherapy tumor anxiety association ­ ICP chemotherapy GI irritation inflammation obstruction paresis compression

PRINCIPLES OF TREATING NAUSEA & VOMITING Treat the cause, if possible and appropriate Environmental measures Antiemetic use: anticipate need if possible use adequate, regular doses aim at presumed receptor involved combinations if necessary anticipate need for alternate routes

Chemoreceptor trigger zone Stimulus Area Receptors Drugs, Metabolic Chemoreceptor trigger zone Motion, Position Vestibular Visceral Organs ? Non-specific CNS ↑ ICP Cerebral cortex D 2 5HT M 5HT H1 M H1 VOMITING CENTRE D 2 5HT CB1 H1 Effector Organs D 2 5HT H1 M CB1 Dopamine Serotonin Histamine Muscarinic Cannabinoid

E S Antonarakis and R D W Hain From: Nausea and vomiting associated with cancer chemotherapy: drug management in theory and in practice Arch. Dis. Child. 2004;89;877-880 E S Antonarakis and R D W Hain

Dyspnea In Palliative Care

An uncomfortable awareness of breathing DYSPNEA: An uncomfortable awareness of breathing

“...the most common severe symptom in the last days of life” DYSPNEA: “...the most common severe symptom in the last days of life” Davis C.L. The therapeutics of dyspnoea Cancer Surveys 1994 Vol.21 p 85 - 98

National Hospice Study Dyspnea Prevalence Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest 1986;89(2):234-6.

Approach To The Dyspneic Palliative Patient Two basic intervention types: Non-specific, symptom-oriented Disease-specific

Simple Non-Specific Measures In Managing Dyspnea calm reassurance patient sitting up / semi-reclined open window fan

Non-Specific Pharmacologic Interventions In Dyspnea Oxygen - hypoxic and ? non-hypoxic Opioids - complex variety of central effects Chlorpromazine or Methotrimeprazine - some evidence in adult literature; caution in children due to potential for dystonic reactions Benzodiazepines - literature inconsistent but clinical experience extensive and supportive

TREAT THE CAUSE OF DYSPNEA - IF POSSIBLE AND APPROPRIATE Anti-tumor: chemo/radTx, hormone, laser Infection Anemia CHF SVCO Pleural effusion Pulmonary embolism Airway obstruction

DISEASE-SPECIFIC MEDICATIONS FOR DYSPNEA Corticosteroids obstruction: SVCO, airway lymphangitic carcinomatosis radiation pneumonitis Furosemide CHF Antibiotics Anticoagulation – pulm. embolus Bronchodilators Transfusion

Opioids in Dyspnea Uncertain mechanism Comfort achieved before resp compromise; rate often unchanged Often patient already on opioids for analgesia; if dyspnea develops it will usually be the symptom that leads the need for titration Dosage should be titrated empirically; may easily reach doses commonly seen in adults May need rapid dose escalation in order to keep up with rapidly progressing distress

A COMMON CONCERN ABOUT AGGRESSIVE USE OF OPIOIDS IN THE FINAL HOURS How do you know that the aggressive use of opioids for pain or dyspnea doesn't actually bring about or speed up the patient's death?

SUBCUTANEOUS MORPHINE IN TERMINAL CANCER Bruera et al. J Pain Symptom Manage. 1990; 5:341-344

Typically, with excessive opioid dosing one would see: pinpoint pupils gradual slowing of the respiratory rate breathing is deep (though may be shallow) and regular

COMMON BREATHING PATTERNS IN THE FINAL HOURS Cheyne-Stokes Rapid, shallow “Agonal” / Ataxic

Palliative Management of Secretions

Secretions - Prevalence At Study Entry And In Last Month Of Life UK Children’s Cancer Study Group/Paediatric Oncology Nurses Forum Survey Goldman A et al; Pediatrics 2006; 117; 1179-1186

Managing Secretions in Palliative Patients Factors influencing approach management: Oral secretions vs.. lower respiratory Level of alertness and expectations thereof Proximity of expected death “Death Rattle” – up to 50% in final hours of life At times the issue is more one of creating an environment less upsetting to visiting family/friends Suctioning: “If you can see it, you can suction it” Suctioning Increased Secretions Mucosal Trauma

CONGESTION IN THE FINAL HOURS “Death Rattle” Positioning ANTISECRETORY: Scopolamine, glycopyrrolate Consider suctioning if secretions are: distressing, proximal, accessible not responding to antisecretory agents

Atropine Eye Drops For Palliative Management Of Secretions Atropine 1% ophthalmic preparation Local oral effect for excessive salivation/drooling Dose is usually 1 – 2 drops SL or buccal q6h prn There may be systemic absorption… watch for tachycardia, flushing

Delirium in Palliative Care

Definition Etiologically non-specific global cerebral dysfunction associated with changes in LOC, attention, thinking, perception, memory, psychomotor behavior, emotion and the sleep/wake cycle

DSM-IV Criteria Change in consciousness with reduced ability to focus, sustain or shift attention Change in cognition (e.g., memory, disorientation, change in language, perceptual disturbance) that is not dementia Abrupt onset (hours to days) with fluctuation Evidence of medical condition judged to be etiologically related to disturbance

Characteristics Abrupt onset Disorientation, fluctuation of symptoms Hypoactive vs.. hyperactive (restlessness, agitation, aggression) vs. mixed Changes in sleeping patterns Incoherent, rambling speech Fluctuating emotions Activity that is disorganized and without purpose

Delirium Types confusion, somnolence,  alertness Hypoactive confusion, somnolence,  alertness Hyperactive agitation, hallucinations, aggression Mixed (>60%) features of both

Prevalence of Delirium 20% - 44% on admission to a palliative care unit (common reason for admission) 28% - 45% of patients developed delirium while on the palliative care unit 68% - 90% prior to death Lawlor et al (J Pall Care 1998) n = 103 pts 50% of episodes reversible Terminal delirium in 88% Hyperactive (5%) vs. hypoactive (47%) Mixed (48%) most common

Delirium versus Dementia Delirium Dementia Abrupt onset Insidious onset Decreased/Fluctuating LOC LOC intact, alert Erratic behaviour Consistent behaviour Sleep/wake cycle change Minimal changes Reversible (theoretically) Irreversible

Causes Of Delirium In Palliative Care Tumour Primary, metastatic, leptomeningeal, paraneoplastic syndrome Metabolic / physiologic hypercalcemia Hyponatremia (hypernatremia less commonly) ↑ or ↓ glucose anemia, hypoxia CO2 Renal or liver failure Infection – UTI, pneumonia, biliary tract, wounds Medication administration – opioids, antiemetics (esp. anticholinergic), sedatives, antisecretory Medication / Drug withdrawal Etc…..

Management Of Delirium In Palliative Care Environmental Quite, private setting: single room if possible Low lighting, calendar, clock, familiar objects Minimal room changes with unnecessary distractions Fix the Fixable – if possible and appropriate Help family navigate complex choices and non-choices, dictated by how the patient would guide care if that were possible Effective sedation – with frank discussion of anticipated course If delirium irreversible, goal of care is sedation Sedation does not hasten the dying process Will facilitate meaningful visiting Encourage communication, even though patient not interactive