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Palliative Potpourri Edward (Ted) St. Godard MA MD CCFPConsulting PhysicianWRHA Palliative Caretstgodard@wrha.mb.ca

Robert Pope. Visitors1I am funded as an independent contractor by the WRHA

Disclosure I. Delirium at end-of-life

Name it, claim it, tame it3At the end of session, participants willBe able to identify the medical condition known as delirium;Appreciate the importance of this recognition;Have an approach to delirium management

objectives

Nurses are in an optimal position to detect fluctuating symptoms of delirium Agar et al. Palliative Medicine. September, 2011.Delirium and nursesSilent, unspoken piece of nursing practice, impacting on workloadNurses deal with the unpredictable and fluctuating condition of delirious patients, which may be a signal of impending chaos

Agar et al. Palliative Medicine. September, 2011.Delirium and nursesUnder-detection of delirium relates to a lack of knowledge of the criteria for identifying deliriumfailure to relay or communicate detected symptoms at onsetAgar et al. Palliative Medicine. September, 2011.Delirium and nursesGlobal cerebral dysfunctionBrain FailureEarly signs often mistaken asanger, anxiety, depression, psychosis

What is delirium ?10A) Change in consciousness with reduced ability to focus, sustain or shift attentionB) Change in cognition (e.g., memory, disorientation, change in language, perceptual disturbance) that is not dementia

Dsm-iv criteria 11C) Abrupt onset (hours to days) with fluctuationD) Evidence of medical condition judged to be etiologically related to disturbance

Dsm-iv criteria 12a disturbance in consciousness with inattention and problems in cognition and/or a disturbance in perception that develop over hours to days with organic causes.Dsm-iv criteria 13DeliriumImpaired memoryImpaired judgementImpaired thinkingDisorientationDementiaImpaired memoryImpaired judgementImpaired thinkingDisorientationDelirium vs dementia 14DeliriumAbrupt onsetDecreased LOCSleep/wake cycle

DementiaInsidious, progressiveAlert, LOC intactMinimal Delirium vs dementia 15DeliriumReversible?PREVENTABLE?DementiaIrreversible

Delirium vs dementia 16In up to 50 % of patients with advanced cancer, delirium can be reversedDelirium is reversible Kang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev(2012)

Lawlor P, Gagnon B, Mancini I, Pereira J, et al. Arch Intern Med 2000Reversed vs non-reversed 1819Hypoactive confusion, somnolence, alertnessHyperactiveagitation, hallucinations, aggressionMixed (>60%)features of bothDelirium sub-types 19

Lawlor P, Gagnon B, Mancini I, Pereira J, et al. Arch Intern Med 2000Delirium sub-types 2080 % in medical intensive care units (ICU) 28 % in patients following hip fracture22 % in general medical inpatientsPrevalence/incidence Partridge et al. The delirium experience: what is the effect on patients, relatives and staff and what can be done to modify this? Int J Ger Psych. October 2012 (online)21Most frequent neuropsychiatric complication in patients with advanced CAUp to 85 % of patients delirious prior to deathIncidence/prevalenceBruera et al. JPSM 2010; 39;2: 186-196~ 42% patients in PC program delirious on admission50% of episodes reversibleTerminal delirium in 88 %

Lawlor et al. Arch Intern Med 2000; 160:786Incidence/prevalence23Palliative sedation requestsDelirium/terminal restlessness (55%)Dyspnea (27%)Pain (18%)Nausea/vomiting (4%)Eisenchlas. Current Opinion in Supportive and Palliative Care 2007, 1:207212Impact Palliative sedation requestsDelirium number one reason for requestsImpact Fainsinger RL et al. A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients. Palliat Med 2000;14:25765.Wed rather see dad dead than like this.S/he would be horrified by this.Impact 73/99 patients (74%) remembered delirious episodeOf these, 81 % recalled experience as distressingFamily stress > patients recalled stressimpactBruera et al. JPSM 2010; 39;2: 186-196Interferes with Sx assessment and TxIncreases morbidity and mortalityHinders communication within familiesimpactBruera et al. JPSM 2010; 39;2: 186-196Sx difficulty and distress Pain Dyspnea Delirium D/D29Sx difficulty and distress Worsening Delirium Ax/Tx Challenges

30Delirium mediated by failure in central cholinergic transmission?Acetylcholine final common neurotransmitter pathway leading to delirium?

White et. al. First Do no Harm JPM. 10 (2); 2007: 345-351pathophysiology31Relative acetylcholine deficiency and dopamine excess could mediate the characteristic symptoms of deliriumDelirium can be evoked by dopamine agonists and anticholinergic medications Moyer. American Journal of Hospice and Palliative Medicine 28(1), 2011. 44- 51pathophysiologyKang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev(2012)Dopamine/acetylcholine inverse relationshipHaloperidol first line treatment for deliriumHaloperidol D2 antagonist:? Haloperidol increase levels acetylcholine?

White et. al. First Do no Harm JPM. 10 (2); 2007: 345-351pathophysiologyKang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev(2012)33Sometimes successfully treated with dopamine receptor antagonists and possibly by cholinesterase inhibitorsHigh serum anticholinergic activity inpatients with deliriumMoyer. American Journal of Hospice and Palliative Medicine 28(1), 2011. 44- 51pathophysiology-aminobutyric acid (GABA)-ergic benzodiazepines seem to cause deliriumNeuroinflammatory processes drives up-regulation of GABA receptorsGABA receptor versus microglial activation versus apoptosis

pathophysiologyC.G. Hughes et al. Future Directions in Delirium Management and Research. Best Practice & Research Clinical Anaesthesiology. 26 (2012) 395405PredisposingPrecipitating

causesPredisposing factors:Prevalence increases with ageMale > femaleVisual impairmentDepression White et. al. First Do no Harm JPM. 10 (2); 2007: 345-351causes37Predisposing factors:Functional dependenceImmobilityHip fractureDehydrationAlcoholismStrokeSeverity of physical illnessWhite et. al. First Do no Harm JPM. 10 (2); 2007: 345-351causes38All of our patients!Whos predisposed?

Fragile? Frail?40

HANDLE WITH CAREFragile? Frail?41Inverse relationship between the preexisting vulnerability of the patient, and the severity of the insult necessary to precipitate deliriumFragile patientsKnock me over with a feather

42Most patients nearing EOL have multiple predisposing factorsMost of these are beyond our controlFragile patientsPredisposingPrecipitating

causesImpractical, given our patient population (frail, usually old)Imperative to minimize precipitating factors

Decrease predisposition?lyte derangements (dehydn, hypo/hypernatremia)Infx (UTI, resp., skin/soft tissue [sacral ulcers])Metabolic (hyper/hypoglycemia, hypercalcemia, uremia)Low perfusion, hypoxiaWithdrawalprecipitatorsBut whats missing?46Anti-cholinergics (Gravol, TCAs, anti-secretories);BZDsOpioidsSteroidsCipro, lasix (?) ranitidine, and on and on.

drugsThe list is longer, but are we recognizing any?47Drug withdrawal:EtOH, Bzd, opioid, street drugs

drugs48Prophylactic haldolProphylactic olanzepineProhylactic cholinesterase inhib.s

Gagnon et al. PsychoOncology 21: 187194 (2012)Prevention?No conclusive literature on meds prophylactically, especially in palliative care, but certain basic no-brainers.49Maintain sensorium: hearing aids, eye glassesOrientation (clocks, calendars, conversation)

Gagnon et al. PsychoOncology 21: 187194 (2012)Prevention?No conclusive literature on meds prophylactically, especially in palliative care, but certain basic no-brainers.50No good evidence for benefit from screening hospitalized patients

Prevention?Greer N et al. Delirium: screening, prevention, and diagnosis a systematic review of the evidence 2011 Internet.No conclusive literature on meds prophylactically, especially in palliative care, but certain basic no-brainers.51Cured yesterday of her disease, she died last night of her doctor.

paraphrasing Jonathon Swift(you know, Gullivers Travels)

Prevention?No conclusive literature on meds prophylactically, especially in palliative care, but certain basic no-brainers.52

Medication sole precipitant of delirium in 12 39 % healthy patients

Alagiakrishnan et al. Postgrad Med J, 2004; 88: 388-393

Dr. Dr. Drugs drugs53Drug toxicity, drug withdrawalStart low, go slowVery often, less is moreDrugs Drugs drugsAnalgesics: Uncontrolled pain is risk factor for deliriumRome wasnt built in a dayBalance pain against doseTitrate gently

Prevention?55Analgesics: Titrate gentlyDont be afraid to decrease

Prevention?56Sx difficulty and distress Worsening Delirium Ax/Tx Challenges

57Sedatives:

A benzodiazepine will never help your thinking.

Dr. Mike HarlosPrevention?58Lorazepam is an independent risk factor for delirium, increasing risk by ~ 20 % (not to mention falls, etc.)

Panpharpande et al. Anesthesiology. 2006; 104:21Prevention?Kang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev(2012)Hold the benzos!

59Sedatives:Try not to be the one who starts bzd, but dont be the one who abruptly stops itBetter a tired patient in AM than a delirious patient in AMPrevention?60Anxiety, restlessness? -- how about company? Going for a walk-about?More staff, fewer sedatives, less delirium?Drugs cheap, one-on-one expensiveValue?Prevention?61Does vigorous hydration decrease delirium incidence?Hydn reversed or improved 30 70 % delirium casesThomson et al. Current Op Supp Pal Care. 2009; 3:72-78hydration?Name itClaim itTame it

nicitiA little fluffyLoopyA little offNot quite rightFruit-cakeDELIRIUMName it!MMSE?CAM?Intuition?Do something;Name it.

Name itWhen we hear about fluffy patients, assess concentration. Can they name the months of the year backwards? Can they attend to a short conversation? If not, consider them, if not delirious, at high risk of becoming so, and do something..65Change in consciousness with reduced ability to focus, sustain or shift attention

Name itDisturbance of consciousness with reduced ability to focus, sustain, or shift attention.66Engage in conversation?Months of year backward?Clinical suspicion

Concentrate, focus?Disturbance of consciousness with reduced ability to focus, sustain, or shift attention.67Drs. cause delirium?Can Drs/nurses prevent it, reverse it, or reduce its impact?Who better?

Claim itTwo simultaneous pathwaysSeek and treat cause (thus reverse?) Manage behaviours (supportive care)Human intervention better than pharmacological

Tame itSupportive measuresHydrate?Avoid restraintsMobilizeReduce noise, etc.OrientReassureOne-on-oneInvestigationsMEDICATION REVIEWBloodworkU/A ImagingTame itMeds:Eliminate any psychoactive med possible:Metoclopramide, cipro? Baclofen? Ranitidine? Lasix? others?

Tame itMeds:Analgesia:Good pain control? Consider dose reduction?Sub-optimal pain control? Opioid rotationTame itIf investigations reveal pathology that can reasonably be thought to be causing delirium; and if the pathology can be treated; and if it is in keeping with goals of care; trial treatment Tame itDoes patient behaviour compromise care, or put patient, staff, or others at risk?If yes, can a bedside sitter safely help?If no, low-dose neuroleptic and/or low-dose bzdTame it Haloperidol remains standard of carePowerfulOral and parenteralLimited anti-cholinergic, sedative properties

White et. al. First Do no Harm JPM. 10 (2); 2007: 345-351Medical management75No significant differences in response in double-blind RCT comparing risperidone and haloperidolSimilar evidence finding minimal differences in efficacy between olanzapine and risperidoneBourne et. al. Drug Treatment of Delirium. Journal Psychosomatic Research. 65; 2008: 273 - 282Medical managementKang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev(2012)76Methylphenidate can improve cognitive and psychomotor function in hypoactive deliriumMethylphenidate can cause agitation, aggravation, psychosisBourne et. al. Drug Treatment of Delirium. Journal Psychosomatic Research. 65; 2008: 273 - 282hypoactive77RecapDelirium is badHard on patients, families, staffOften preventable, often iatrogenicNurses optimally locatedOccasionally reversible

Questions/ commentsII. Pain

80At the end of this session, you willUnderstand the importance of context in the interpretation of painAppreciate at a basic level the physiology of pain and some principles of analgesiaHave an approach to pain management that always bears in mind the above pointsobjectives

11/11 65 %

12/12 91 %

Think about pain.Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.Who definitionthe prevention and relief of suffering..by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.Who

Loeser, JD. Perspectives on Pain. Clinical Pharmacology and Therapeutics. Padgham, ed. Baltimore: University Park Press. 1980. p 314

Loeser, JD. Perspectives on Pain. Clinical Pharmacology and Therapeutics. Padgham, ed. Baltimore: University Park Press. 1980. p 314

Multi-disciplinary Team?

Pain or Suffering? Both? Neither?

What is pain?an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.Merskey H, Bogduk N. 2nd ed Seattle, WA: IASP Press; 1994.93What is pain?what ever the experiencing person says it is, existing whenever s/he says it does.Pain confers a survival benefit; we are hard-wired to experience itMerskey H, Bogduk N. 2nd ed Seattle, WA: IASP Press; 1994.94Pain is subjective. Its what the person experiencing it says it is.Symptoms in Advanced Cancer

Bruera 1992 Why Do We Care? Conference; Memorial Sloan-Kettering95

Seow H et al. Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. J Clin Oncol 2011; 29:1151. Pain ClassificationNociceptivesomaticbonysuperficialdeepvisceralNeuropathicneuralgicdysesthetichyperalgesiaAdapted from Jovey R, 2002Pain is not a diagnosis97

Nociceptors Sensory receptors Preferentially sensitive to noxious stimuli (tissue damaging/threatening) Chemical, thermal, mechanical98

Somatic Pain Nociceptive Aching, often constant Often worse with mvt Well localized Tender

bone & soft tissue chest wall post-surgery incision

99

Visceral Pain Constant or crampy Dull, aching Poorly localized Often referred

CA pancreas Bowel obstruction Infiltration/compression/distension

100Neuropathic PainPain initiated or caused by primary lesion or dysfunction in the nervous system

International Association for the Study of Pain101 NP Descriptors

Burning, Itching, Shooting, Shock-like, Electric, Lancinating

Pins and needles, tingling, numb102 NP DescriptorsPins and needles, tingling, numb

103Tx of Neuropathic PainPharmacologic treatmentAnticonvulsants gabapentin, pregabalinTCAs (esp. if depression)NMDA receptor antagonists: ketamine, dextromethorphan, methadoneSteroidsOpioids104Up to 90% of patients with cancer pain could have their pain alleviated by following the treatment guidelines of the WHO analgesic ladderFitzgibbon et al. Parenteral Ketamine as an Analgesic Adjuvant for Severe Pain. J Pall. Med. 8(1) 2005105Mild pain (0-3)Moderate (4-6)Severe (7-10)By the clockBy the ladderAcetaminophen & NSAIDsWeak opioid+ Step 1Strong opioid + Step 2Adjuvant Rx may be added at any stepWHO Analgesic Ladder

106Mild pain (0-3)Moderate (4-6)Severe (7-10)By the clockBy the ladderAcetaminophen & NSAIDsWeak opioid+ Step 1Strong opioid + Step 2Adjuvant Rx may be added at any stepWHO Analgesic Ladder

107Pharmacology ReviewSerum [ drug ] Time TOXICTherapeuticSub-therapeuticSingle dose, prn usage108Pharmacology ReviewSerum [ drug ] Time TOXICTherapeuticSub-therapeuticmultiple dose, prn usage109Pharmacology ReviewSerum [ drug ] TOXICTherapeuticSub-therapeutic4 hours4 hoursIdealized by-the-clock results110PRN alone rarely adequate; Long-acting formulations usually not appropriate until symptoms well-managed

Continuous source of pain requires continuous analgesia111

Life in the Bloodstream

Think about drug, dose, routePoor pain control?Steady decline at homeRapid decline due to illness progression with diminished reserves

Accelerated deterioration begins, pain worsening, pt. admitted, medications changedFamily thinking what?Deteriorating condition119Whats the best approach? Proactive, tell them that of course you wondered about the meds, of course youve reviewed med changes, med usage. HOPEFULLY, youve pre-emptively given them a bit of warning that the meds may precipitate somnolence, and, more importantly, that there likely will be fairly significant deterioration to come. Then theyre not so surprised, ambushed. But dont be defensive. Consider adjusting meds further?

Every family is the Addams family

Too much medicationNot enough.

???????

Its all the morphine youre giving her..its the drugsPopular misconception held by families, lay public, and professionals

Theyre grasping at straws.its the drugsBy the way, palliative care shortens your life, [xxxx] suggested.Theyre grasping at straws.its the drugsAzoulay et al. Opioids, Survival, and Advanced Cancerin the Hospice Setting. J Am Med Dir Assoc. Feb. 2011; 12: 129 -134Increasing overall opioid dosage was associated with improved survival compared with no change or decreasing overall dosage (mean survival 14.0 12.7 days versus 9.3 9.8 versus 9.1 11.4, days respectively, P 5 .01).Theyre grasping at straws.its the drugsAzoulay et al. Opioids, Survival, and Advanced Cancerin the Hospice Setting. J Am Med Dir Assoc. Feb. 2011; 12: 129 -134Opioid usage, even at high dosages, had no effect on survival among advanced cancer patientsin a hospice setting. Theyre grasping at straws.its the drugsTemel et al. Early Palliative Care for Patients withMetastatic NonSmall-Cell Lung Cancer. N Engl J Med. 2010; 363:733 -42

Among patients with metastatic nonsmall-cell lung cancer, As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival.Theyre grasping at straws.

Sub-Q MorphineBruera et al. J Pain Symptom Manage. 1990; 5:341-344A Patient 64 woman resents to ED with severe pain; Hydromorph Contin 24 mg PO bid;Hydromorphone IR 6 mg Q1H prn, taking several times daily;Confused per family

A PatientPain everywhere;Poor historian, muddled, family report fairly rapid escalation of opioids past 3-4/7;O/E: vitals unremarkable, dry MM, decreased BS R>L, no adventitia, normal HS. Very tender over R rib cage (without compressing), abdo benign, DTR unremarkable, no tremors or twitches;

A patientACP M;B/W shows creatinine increased from previous, at 195, dry, corrected Calcium 2.5;U/A benign;CXR no obvious rib fractures;AXR abundant stool, no a/f levels, no free air

A few red flags.Pain everywhere (pathophysiology?);Family report fairly rapid escalation of opioids past 3-4/7;Poor historian, muddled;Creatinine up

Opioid-Induced Neurotoxicity (OIN)Potentially fatal neuropsychiatric syndrome of:Cognitive dysfunctionDeliriumHallucinationsMyoclonus/seizuresHyperalgesia / allodyniaEarly recognition is critical134pathophysiology

135

Osborne et al. The Pharmacokinetics of morphine and morphine glucuronides in Kidney Failure. Clin Pharmacol Ther 54:158-167, 1993Normal Renal FcnRenal InsufficiencySeizures,DeathOpioidtoleranceMild myoclonus(eg. with sleeping)Severe myoclonusDeliriumAgitationMisinterpretedas PainOpioidsIncreasedHyperalgesiaMisinterpretedas Disease-Related PainOpioidsIncreasedOpioid-Induced Neurotoxicity (OIN)We should be more clear with our definitions.137Oin: Treatment

Switch opioid (rotation) and/or reduce doseHydrateBzd prn?138Short Re-capNot everyone has pain ;Treating pain with scheduled opioids is appropriate and safe;Avoid long-acting formulations;139Short Re-capWatch out for pain that doesnt make sense, as it might be warning you of OINPain and suffering are distinct, and not always related as closely as we think140PAINPOSSIBLESuffering?

III. Dyspnea

ObjectivesAt the end of the session, you will

Have a basic understanding of respiration Be aware of the complex mechanisms underlying dyspneaHave an approach to the management of dyspneic patients145 DyspneaSubjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.American Thoracic Society. Dyspnea: Mechanisms, Assessment, and Management, a Consensus Statement. Am J Respir Crit Care Med. 1999; 159: 321 - 340

146Under normal circumstances, we are not aware of our breathing DyspneaPhysical and emotional components (anxiety, panic, chronic fear)Often no measurable physical correlates (RR ? SaO2 ? ABG)

Tachypnea dyspneaDudgeon, D. Managing Dyspnea and Cough. Hematology/Oncology Clinics of North America. 2002; 16: 557-577Universal response is to decrease activity to whatever degree necessaryDyspneaWhich pattern shows dyspnea?

ABCD DyspneaSubjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.American Thoracic Society. Dyspnea: Mechanisms, Assessment, and Management, a Consensus Statement. Am J Respir Crit Care Med. 1999; 159: 321 - 340

150Under normal circumstances, we are not aware of our breathingTime till deathMonths

Days

MinutesWithout eating

Without drinking

Without breathing151We can go a long time without eating, a fairly long time without drinking, but a very short time without breathing. Therefore, if our bodies perceive threats in any of these domains, there will be a proportional response. Deranged blood gases, and/or perceptions that the current respiratory status is unsustainable, will lead to very significant concern on the part of the organism.Dyspnea Dyspnea, like pain, is protective. As pain alerts us to actual or impending tissue damage, dyspnea alerts us to threat. Hardwired to protect152 Dyspnea60 % lung Ca patientsNearly 90 % once near death50 % described dyspnea as severeMuers MF, Round CE. Palliation of symptoms in non-small cell lung cancer: a study by the Yorkshire Regional Cancer Organization thoracic group. Thorax 1993;48:339 43.Dyspnea

Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest. 1986; 89(2): 234-6.Abnormality of blood gases, especially hypercapnia (PaCO2 > 50 mmHg) and, to a lesser extent, hypoxia (PaO2 < 60 mmHg);Amount of work that must be performed by respiratory muscles to provide adequate ventilation;State of mind.

Guyton and Hall. Textbook of Medical Physiology. 491DyspneaDyspnea

156Under normal circumstances, we are not aware of our breathing

Mahler. Understanding Mechanisms Dyspnea. Current Opinion in Supportive and PalliativeCare .2011, 5:7176CNSIntegrates information about:Degree of effort requiredMechanical response achievedO2/CO2 pH status

In order to answer two questions:CNSIs the mechanical response normal relative to the degree of effort expended?Is the current effort sustainable?If not, dyspnea

DyspneaDyspnea occurs when there is a mismatch between ventilation and the demand set by chemical driveBuchanan and Richerson. Role of Chemoreceptors in Mediating Dyspnea. Respiratory Physiology and Neurobiology. 2009; 167: 9 19160Under normal circumstances, we are not aware of our breathing

OxygenCarbon DioxideCO2 + H2O HCO3- + H+Complex monitoring

With each heartbeat the blood passes through the medulla, where molecular watchmen pay attention to the various gases.Complex monitoring

If O2 drops, or CO2 rises, the watchmen hit the alarm bell, telling the organism to breathe harder, deeper, and to be afraid, to panicTachypneic?Hypoxic?Anxious/afraid?Diaphoretic?Unconscious?

A dyspneic patient DyspneaSubjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.American Thoracic Society. Dyspnea: Mechanisms, Assessment, and Management, a Consensus Statement. Am J Respir Crit Care Med. 1999; 159: 321 - 340

172Under normal circumstances, we are not aware of our breathingAssess the symptomDetermine the causeTreat the causeTreat the symptomApproach to Dyspnea

As is the case with all sx, here is an algorithmAssess the symptomRemember:Tachypnea is not dyspnea;Assess distress, not just apparent intensity

Determine the causeThoracicNon-malignantMalignantParamalignant

Extra-thoracicCachexia;Anemia;Ascites;HepatomegalyLyte derangement

Anti-tumour: chemo/RT, etc.InfectionCHFSVCOPleural effusionPulmonary embolismAirway obstructionTreat the causeTreat the SymptomGoal of interventions:

Minimize production of symptom (pre-medicate, energy mgmt., breathing techniques)Diminish perception of symptom (meds, fan, distraction)Treat the SymptomGoal of interventions:

Modify the experience of the symptom (address meaning, help with mood/fear/anxiety)Dyspnea TherapyNon-pharmacologicalOpen window?Cool facial stimulation (fan)PositioningPulmonary rehab?

Dyspnea TherapyPharmacologicalOxygenOpioids Nebulized furosemideAnti-inflammatory txBenzodiazepines?

Oxygen?Bruera 199314 dyspneic, hypoxic (SaO2 < 90%) cancer inpatientsRCT, 2 x blind, placebo, crossover5 L/min air by NP vs O2no in VAS from baseline with air, significant improvement with O2

Bruera et al. Lancet. 1993; 342: 13 -14Oxygen?Bruera 1993Conclusion: O2 substantial benefit in hypoxic dyspneic cancer patients Bruera et al. Lancet. 1993; 342: 13 -14Oxygen?Bruera 200333 dyspneic, non-hypoxic cancer ptsRCT, single blind, placebo, cross-over5 l/min air vs O2 for 6 MW testNo difference in dyspnea, fatigue, or distance walkedBruera et al. Pall Med. 2003; 17: 659 - 63Oxygen?Bruera 2003Conclusion: O2 of no benefit over air to exercising non-hypoxic cancer pts Bruera et al. Pall Med. 2003; 17: 659 - 63Oxygen?O2 no better than air in non-hypoxic patient

O2 better than air if hypoxicOxygen in COPD?NormalCOPDO2 CO2 Resp. DriveO2 CO2 Resp. Drive

Under normal circumstances, our respiratory drive is controlled by CO2. As CO2 rises, so does our drive to breathe,Oxygen in COPD?COPD O2 CO2 Resp. Drive

In a certain percentage of COPD patients, their CO2 is chronically high, so their respiratory drive is controlled by dropping O2. That is, as O2 drops, resp. drive increases. In these patients, giving O2 can decrease resp. drive.Oxygen in COPD?Giving pts. with COPD supplementary O2 can actually suppress their resp. drive (and kill them with kindness)

Anxiolytics?Anxiety is significantly correlated with intensity of dyspneaLimited evidence supporting BZD roleBruera, E. et al. The Frequency and Correlates of Dyspnea in patients with Advanced Cancer. J Pain Symptom Mgmt. 2000; 19: 357-62

Milk of the poppyUsed for analgesia for centuriesUsed since at least 19th century for breathlessnessNow a degree of reticence Opioids?Mahler DA, Murray JA, Waterman LA, Ward J, Kraemer WJ,Zhang X, Baird JC: Endogenous opioids modify dyspnoeaduring treadmill exercise in patients with COPD. Eur RespirJ 2009; 33:771. Naloxone versus saline in exercising COPD patients; Naloxone group more dyspnea; Endogenous opioids blunt dyspnea Opioids?Opioids?Cochrane:18 RDBPC crossover trials9 nebulized, 9 systemic, 14 single dosePrimarily COPDConclusion: significant benefit for systemic, but not for nebulized opioids

Jennings et al. Opioids for the Palliation of Breathlessness in Terminal Illness. Cochrane. Database of Systemic Reviews. 2001Early use of opioids may prolong survival, by reducing physical and psychological distress Twycross, R. Morphine and Dyspnea. Pain Relief in Advanced Cancer. New York: Churchill Livingston, 1994. 383- 99Opioids?Opioid mechanism? Medullary sensitivity/response to hypercarbia/hypoxia Cortical resp. awareness Metabolic rate/ventilatory demandVasodilation (improved cardiac fcn)Analgesia: pain-induced resp. driveAnxiolysis

Opioid mechanism?

With each heartbeat the blood passes through the medulla, where molecular watchmen pay attention to the various gases.Opioid mechanism?

If O2 drops, or CO2 rises, the watchmen hit the alarm bell, telling the organism to breathe harder, deeper, and to be afraid, to panicOpioid mechanism?

Opioids tell the watchmen to allow for broader derangements in the blood gases, and to hit the alarm bell with less force when they need to hit itNarrow therapeutic indexWatch: Rate of dose changePrevious exposure? Bruera, E. Effects of Morphine on Dyspnea. J Pain Symptom Mgmt. 1990; 5: 341-4Opioids?

Pinpoint pupilsGradual slowing of the respiratory rateBreathing is deep (though may be shallow) and regularExcessive opioidsits the drugsKamal et al. Dyspnea Review for the Palliative Care Professional. J Pall Med. 2012; 15 (1): 106 - 114

fear has been shown to be largely unfounded. Examining changes in respiratory parametersin dyspneic palliative care patientsdemonstrated significant decrease in respiratory rate and improvement in dyspnea with titration with morphine or hydromorphone but no significant changes in other respiratory parameters, indicating no opioid-induced respiratory depression.Theyre grasping at straws.its the drugsKamal et al. Dyspnea Review for the Palliative Care Professional. J Pall Med. 2012; 15 (1): 106 - 114

demonstrated benefits, and the lack of edvidence of accelerated death, have led the American College of Chest Physiciansto recommend that physicians titrate oral and/or parenteral opioidsTheyre grasping at straws.

Bruera et al. J Pain Symptom Manage. 1990; 5:341-344Sub-q morphineRecapDyspnea cant be measured, and often cant be observedOxygen is a drug; balance benefit vs cost ($ and other)Opioids work

If you want a wise answer, ask a reasonable questionGoetheWho questions much, shall learn much, and retain muchFrancis Bacon

Our solar system consists of one star, and some debris.Carl SaganChart11924223321231613261845

Non RevRev

Sheet1HypoxiaInfectMetabolOtherDehydOpioidsNon Rev19423231318Rev22312162645

Chart1762022

MixedHypoactiveHyperactiveNormal

Sheet1Mixed76Hypoactive20Hyperactive2Normal2

Chart190857668656012

% Patients

Sheet1AstheniaAnorexiaPainNauseaConstipationSedation/ConfusionDyspnea90857668656012