palliative care in end-stage lung disease rebecca colman, md, frcpc respirology, university heath...

Palliative Care in End-Stage Lung Disease

Rebecca Colman, MD, FRCPCRespirology, University Heath Network

James Downar, MDCM, MHSc, FRCPCRespirology/Critical Care and Palliative Care, University Health Network

Canadian Hospice Palliative Care Association Learning InstitutePalliative Care in Advanced Lung Disease

Presenter Name Rebecca Colman, James Downar

Relationships with commercial interests:

No relationships with commercial interests

2

Faculty/Presenter Disclosure

• There is no financial or in-kind support for this program

Potential for Conflict(s) of Interest

• None of the presenters have received payment for the presentation of this program

• None of the products or programs discussed in this program made financial or in-kind contributions

3

Disclosure of Commercial Support

Canadian Hospice Palliative Care Association Learning InstitutePalliative Care in Advanced Lung Disease

• There are no biases to be mitigated.

Mitigating Bias

• Be familiar with End-Stage Lung Diseases and their treatment

• Understand the pathophysiology and treatment of dyspnea in patients with End-Stage Lung Disease.

• Appreciate the boundaries to PC in these pts

• Initiate useful advance care planning for patients with End-Stage Lung Disease.

Objectives

Non-malignant Lung Diseases

Four main non-malignant lung diseases

1. Chronic Obstructive Pulmonary Disease (COPD)

2. Interstitial Lung Disease - Idiopathic Pulmonary Fibrosis (IPF) and

others

3. Cystic Fibrosis (CF)4. Pulmonary Hypertension (PH)

Case 1 - Mr. L

• 64 M. Retired construction worker• Lives in subsidized housing

• Appearance: thin, muscle wasting, barrel chest

• 45 pack year smoker • Quit 2/12 months ago

• Over past year: 3 admissions for bronchitis. Last admission 2 months ago

• Pulmonary function testing 1 year ago: • FEV1 22% predicted

• Exercise capacity: • Cannot ambulate short distances

without SOB• Difficulty with household chores and

self care

• Daily cough productive of grey sputum ¼ cup

Case 1 - Mr. L

Case 1 - Mr. L

• Rx: tiotropium (long acting anti-cholinergic), salmeteral/fluticasone (inhaled corticosteroid/long acting beta-agonist, daily azithromycin

• PaO2 <55mmHg: prescribed O2 therapy

• Referred for pulmonary rehabilitation• Returns 2 months later with ongoing

dyspnea

COPD

• Respiratory disorder largely 2° smoking

• Pathophysiology:• Progressive • partially/irreversible airway obstruction• lung hyperinflation• Mucous hypersecretion• Systemic manifestations• increasing frequency and severity of

exacerbations.

O’Donnell et al. Can Respir J. 2007 14:Suppl B 5B-32B

COPD

• Disease trajectory: gradual decline in health status, increasing symptoms, punctuated by acute exacerbations that are associated with an increased risk of dying.

• Causes of death: progressive respiratory failure, cardiovascular diseases, malignancies

• Prognosis: variable. Multimodal assessment (BODE index) better than degree of obstruction

Celli et al. NEJM 2004: 350; 1005-12GOLD guidelines 2013 update. Available at http://www.goldcopd.org/

Management


Management• Smoking Cessation• Bronchodilators (SABA, SAAC, LABA,

LAAC)• ICS/LABA



LAAC)• ICS/LABA

• Exercise and Pulmonary Rehabilitation



LAAC)• ICS/LABA


• Vaccinations• Steroids• Antibiotics• ICS/LABA• Phosphodiesterase-4 inhibitors• Chronic Azithromycin



LAAC)• ICS/LABA


• Vaccinations• Steroids• Antibiotics• ICS/LABA• Phosphodiesterase-4 inhibitors• Chronic Azithromycin

OxygenSurgery (Lung Volume Reduction, Lung Transplantation)


• Inflammation scarring and fibrosis of lung interstitium

• Idiopathic (IPF) or secondary to systemic disease/exposure

• IPF Prevalence 2-29/100 000• Presentation: chronic exertional

dyspnea, cough, crackles, clubbing

Interstitial Lung Disease

Raghu et al. AJRCCM. 2011 183;788-824

• Prognosis variable• Median survival 2-3 yrs. from time of diagnosis

IPF



• Idiopathic (IPF) or secondary to systemic disease/exposure

• Presentation: chronic exertional dyspnea, cough, crackles, clubbing



• Prognosis variable• Median survival 2-3 yrs. from time of diagnosis

IPF


• Lung transplantation• Pirfenidone• N-acetylcysteine?• Pulmonary rehabilitation

• Improved 6MWD, QOL• Inconsistent benefit on dyspnea

• Co-trimoxazole?• Improved dyspnea, QOL scores

• Sildenafil?• Inconsistent evidence for improving 6MWD,

QOL

IPF Management

Bajwah et al. Thorax 2013;68:867-79. Spruit et al. Respirology 2009;14:781-7.Ryerson et al. JPSM 2012;43:771-82. Holland et al. CDSR 2008(4):CD006322King et al. NEJM May 2014 (epub) IPFNET. NEJM May 2014 (epub)

• Defect in CFTR gene leading to impaired chloride channel functioning

• Multisystem disease• Median survival ~46 yrs• Natural history: progressive decline in

lung function +/- exacerbations• Death due to chronic lower

respiratory tract infection leading to respiratory failure

Cystic Fibrosis

Brady et al. AJRCCM. 2013 187;680-689http://www.torontoadultcf.com

• Airway clearance• Exercise• Inhaled Mucolytics• Chronic azithromycin (anti-

inflammatory & mucolytic)• Inhaled antibiotics• Oral antibiotics• IV antibiotics• Bronchodilators

CF management

• Non-pulmonary treatment: • Nutritional supports • Diabetes management• Osteoporosis prevention• Psychosocial support

• Burden of Treatment• Mean 7 treatments, 108 min per day

• Lung transplantation

CF Management

Fusar-Poli P et al. Lung 2007;185:55-65.

• Mean pulmonary artery pressure ≥25mmHg• Pulmonary arterial hypertension• PH due to: left heart disease, hypoxic

lung disease, chronic thrombo-embolic disease, other (metabolic disease, sarcoidosis, myeloproliferative disorders…)

• Mean age at dx: 36

Pulmonary Hypertension

Gaine & Lewis. Lancet 1998. 352; 719-725Galie et al. Eur Heart J. 2009. 30; 2493-2537

• Presentation: progressive dyspnea, fatigue, weakness, chest pain, syncope, signs of right heart failure

• Prognosis: untreated PAH• WHO IV – 6 months• WHO III – 2.5 years• WHO I-II – 6 years

Pulmonary Hypertension

Gaine & Lewis. Lancet 1998. 352; 719-725Galie et al. Eur Heart J. 2009. 30; 2493-2537

• Diuretics, oxygen, supervised rehabilitation, psychosocial support

• Medical therapy: • Ca2+ channel blockers • phosphodiesterase-5 inhibitors (oral)• endothelin antagonist (oral)• Prostacyclin analogues (IV or SC)

• Lung Transplantation

PH Management

• Up to 10% of PC consultations• 4th most common reason for ER

visit in PC• Up to 89% of patients at EOLC,

~100% of patients with lung disease

• Strong association with poor QOL, prognosis

• Refractory in ~1/2 of end-stage COPD

Dyspnea

Karmal et al. J Pall Med 2011;14:1167-72.Currow et al. JPSM 2010;39:680-90.Ikington et al. Respir Med 2004;98:439-45.

Dyspnea

• Symptoms• Air hunger• Exertional shortness of breath• Chest tightness• Suffocation/panic

• Measurement• Dyspnea scores (ESAS, VAS, Borg)• HRQOL (St George’s Respiratory Questionnaire)• Exercise tolerance (6MWD)• Blood gas measurements

• Improvement vs. Stabilization of symptoms

• Main contributors• Increased load• Increased proportion of respiratory muscle

use• Increased ventilatory requirements• Spritual/existential distress• Anxiety

Dyspnea

Kamal et al. JPM 2011;10:1167-72.

Pulmonary Afferents

RespiratoryMuscles

Lung

Airway

(Effectiveness)Cortex

Limbic SystemDLPFCInsula

Brainstem(Chemoreceptors)

(Effort)

(Stimulus)

Dyspnea

• “Neuromechanical Dissociation”• Respiratory demand vs. ability to

ventilate• Current or anticipated

• Mild = reduce activity/metabolism• Severe = panic = increased activity

• Hypoxemia• Exertional dyspnea

• Responsive to O2

• Reduce activity/metabolism

Dyspnea

Hallenbeck. J Pall Med 2012;15:1-6.

• Opioid• Anxiolytic• Antidepressant• Oxygen• Fan• Chest vibration• Meditation, relaxation therapy• (“Disease-modifying therapies”)

Management of Dyspnea

• Mechanism• Decreased sensitivity to

hypoxemia/hypercarbia• Increased ventilatory efficiency • Reduced minute volume (?)• Perhaps greater effectiveness in some

• Anxiety, • Worsening over time• Unpredictable

Opioids

Horton et al. Curr Opin Supp Pall Care 2010;4:92-96.

• Cochrane Review (2001) - WITHDRAWN

• Small (18 RCTs, max 19 pts)• Single dose, usually measuring dyspnea• Small benefit seen

• Crossover trial• 20mg morphine SR per day• VAS 6-10mm lower on 100mm scale

(p<0.02)

Opioids

Jennings et al. CDSR 2001 (CD002066)Abernethy et al. BMJ 2003;327:523-8.

• Dose increment + pharmacovigilance study

• Started morphine SR 10mg/d• Increased to 20, 30mg in nonresponders• 62% had response (avg 35% improvement

in VAS)• 33% maintained at 3 months

• No respiratory depression/hospitalizations

• CTS Recommendations for COPD• Oral opioids for refractory dyspnea (2C)

Opioids

Currow et al. JPSM 2011;42:388-99.CTS Clinical Practice Guidelines 2011

• Appropriate opioid doses do not cause respiratory depression (>10 studies)

• Steady state vs. increases

• Low doses (10-30mg/d) not associated with resp. depression in COPD

Opioids - Fear

Currow et al. Eur J Palliat Care 2009.Gallagher R. Can Fam Physician 2010;56:544-6.

• In advanced illness, no relationship between time of death and

• Opioid dose• Changes in dose• Sedative use

• Clinician discomfort• Cultural stigma• Addiction

• Almost no risk if no hx of addiction, psych history, abuse, >45

Opioids - Fear

Gallagher R. Can Fam Physician 2010;56:544-6.

• CTS Suggested Protocol• Morphine IR 0.5mg BID x2d, increase to

q4h over 1 wk• Increase by 1mg q4h every week until

effective• Switch to Morphine SR q12h when stable

x2wks• Switch to hydromorphone if side effects

• ATS Clinical Policy Statement• Morphine 5-10mg PO Q4H (PRN?)• Hydromorphone 2-4mg Q4H (PRN?)

Opioids – Dosing Guidelines

CTS Clinical Practice Guidelines 2011.ATS Clinical Policy Statement. AJRCCM 2008;177:912-27.

• Start morphine 5mg q1h PRN (2.5mg if naïve)

• Encourage to take 1 dose as test

• If well-tolerated, 2 options• Continue using PRN as above• Encourage to start Morphine CR 10mg BID• Increase morphine CR slowly- add 5mg BID

every few days• ALWAYS titrate to effect.

• Anticipate constipation and nausea• Reassess frequently

• Worsening dyspnea may suggest pneumonia

Opioids – We Suggest

• Intranasal/intrabuccal fentanyl

• Low dose- 25-50mcg

• Good for episodic dyspnea?

• Addiction potential?

Opioids – Novel Approaches

• Known survival benefit in hypoxemic COPD, IPF

• Reduced minute ventilation, dynamic hyperinflation

• Hypoxemic patients (CTS COPD- 2B)• Inconsistent improvement in dyspnea, exercise

tolerance• Negative Systematic Review- 8 studies, 144 patients

• Normoxemic patients • Not routinely beneficial but heterogeneous studies

• Individualized trial

Oxygen

Cranston et al. CDSR 2008;3:CD004769Uronis et al. CDSR 2011;6:CD006429

• Complex relationship between anxiety, panic and dyspnea

• Benzodiazepines• Inconsistent effect on QOL, dyspnea, exercise tolerance

• Buspirone (GAD)• Inconsistent benefit

• TCAs• Inconsistent benefit, side effects

• SSRIs• Inconsistent benefit, even in depressed pts.

• Not routinely recommended (2B)

Anxiolytics/Antidepressants

Simon et al. CDSR 2010;1:CD007354CTS Clinical Practice Guidelines 2011Kreuter et al. Respiration 2011;82:307-316.

• Pulmonary rehabilitation (COPD, IPF)• Reduce admissions, mortality• Improve HRQOL, exercise capacity

• Neuromuscular Electrical Muscle Stimulation (2B)

• 4-6 weeks, improves dyspnea + performance

• Chest wall vibration (2B)• Integrated disease management

• Reduces admissions• Improves QOL and exercise capacity

Non-Pharmacologic Therapies - COPD

Bausewein et al. CDSR 2008;2:CD005623. Puhan et al. CDSR 2011;10:CD005305CTS Clinical Practice Guidelines 2011 Kruis et al. CDSR 2013;10:CD009437

• Walking aids (2B)• Pursed-lip breathing (2B)• Breathing training

• Improves dyspnea and recovery• http://www.youtube.com/user/ManagingSO

B

• “Insufficient evidence to recommend”

• Acupuncture, pressure, • Distractive auditory stimuli (music),

relaxation• Handheld fans • Counseling and support programs or

psychotherapy

Non-Pharmacologic Therapies - COPD

CTS Clinical Practice Guidelines 2011

http://www.youtube.com/user/ManagingSOB

http://www.youtube.com/user/ManagingSOB

• Etiology• Hypersensiti

ve cough reflex

• GERD• Upper airway

irritation

Cough

• Treatment• Opioids• Antitussive (e.g.

dextromethorphan)• Saline Rinse• Corticosteroids

• Nasal/inhaled/systemic

• Thalidomide?• Inhaled lidocaine?• Gabapentin?

Lee et al. Curr Opp Pulm Med 2011;17:348-54. Hope-Gill et al. AJRCCM 2003;168:995-1002.Horton et al. Thorax 2008;63:749. Lingerfelt et al. J Supp Onc 2007;5:301-2

• Reduces risk of intubation and mortality

• Commonly used for COPD patients with “do not intubate order”

• Symptomatic benefit• Hospital survival rate up to 70% • 1-year survival rate up to 30%

• Survivors report no deterioration in HRQOL at 90 days

Non-Invasive Ventilation

Sinuff et al. Crit Care Med 2008;36:789-94.Schettino et al. Crit Care Med 2005;33:1976-82.Chu et al. Crit Care Med 2004;32:372-7.Azoulay et al. Intensive Care Med 2013;39:292-301.

Noninvasive Ventilation

• Overall mortality of NIV in “DNR” ~50%

• Cardiogenic pulmonary edema 25-39%• COPD 38-48%• Advanced cancer 77-85%

• Mortality of Acute Resp Failure in IPF 80-100%

• Short trial of NIV selects survivors• Treats easily reversible problems• Buys time to make decision• Palliative intervention?

Cuomo et al. Palliative Medicine 2004;18:602-10.Hilbert et al. Crit Care Med 2000;28:3185-90.Sinuff et al. Crit Care Med 2008;36:789-94.Mollica et al. Respiration 2010;79:209-15.

Levy M. CCM 2004;32:2002-7.Schettino G. CCM 2005;33:1976-82.Carillo et al. AJRCCM 2003;A862Nelson et al. CCM 2001; 30:A36

• Need for experienced staff• Clear goals and parameters

Non-Invasive Ventilation

• 15-40 L/min• Increased

ventilation• Positive pressure

3-5 cm H2O• Comfortable

• Heated, humidified• Improves dyspnea

• Little expertise required

High-Flow Nasal Cannula Oxygen

Ricard JD. Minerva Anestesiologica 2012;78:836-41.Image from Ward J. Resp Care 2013;58:98-122.

• “sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers’ ability to achieve symptom relief”

Dyspnea Crisis

Annals ATS 2013;10(5) S98-S106

Dyspnea Crisis

Annals ATS 2013;10(5) S98-S106

• Dyspnea, suffocation, hemoptysis

• Action plan• Opioids

• Parenteral morphine/hydromorphone

• Buccal/IN fentanyl

• Sedation• Methotrimeprazine• Midazolam 5mg SC/IV

• Manage the family…

Sudden Events

Challenges in Advance Care Planning for End-Stage Chronic Illness

James Downar, MDCM, MHSc, FRCPCLeah Steinberg, MA, MD, FCFPRebecca Colman, MD, FRCPC

Overview

• Prognostication- Challenges• Advance Care Planning and

Resources• Difficult Conversations

• ICDs• Mechanical Ventilation

• HF patients rarely admitted to PCUs• 79% Cancer • 4.5% “Heart disease”, 2.2% Respiratory disease

• Compared with cancer, “heart disease” patients more disabled, closer to death…

• Lower mean PPS • Shorter median survival • BUT…shorter mean waiting time

• Many HF patients rejected, never referred, or referred too late

HF Patients and Palliative Care Units in Canada – “Prognosis <3

months”

Downar et al. J Pall Med 2012;15:661-6.

• Bidirectional trajectory• Temporal v. Probabilistic survival

estimate• More outliers• Less dependence on oral intake,

bedbound status• Australian-modified KPS

Prognostic Challenges

Performance Status ToolsKPS PPS AKPS

100% Normal, no evidence of disease, no complaints

Normal activity & work, no evidence of disease

Normal; no complaints; no evidence of disease

90% Able to carry on normal activity; minor signs or symptoms

Normal activity & work, some evidence of disease

Able to carry on normal activity; minor signs or symptoms

80% Normal activity w/effort; some signs or symptoms of disease

Normal activity with effort, some evidence of disease

Normal activity with effort; some signs or symptoms of disease

70% Cares for self; unable to carry on normal activity or to do active work

Cares of self, normal or reduced intake

Cares for self; unable to carry on normal activity or to do active work

60% Requires occasional assistance but is able to care for most of his needs

Unable to do hobby/ housework, normal or reduced intake, occ. assistance needed, maybe confused.

Requires occasional assistance but is able to care for most of his needs

50% Requires considerable assistance and frequent medical care

Mainly sit / lie, considerable assistance needed, maybe confused

Requires considerable assistance and frequent medical care

40% Disabled; requires special care and assistance

Unable to do most activity, mainly in bed, mainly assistance, maybe drowsy +/- confused

In bed more than 50% of the time

30% Severely disabled; hospitaliz’n necessary; active supportive treatment is necessary

Unable to do any activity, totally bedbound, total care, maybe drowsy +/- confused

Almost completely bedfast

20% Very sick; hospitalization necessary; active supportive treatment is necessary

Totally bedbound, total care, minimal intake to sips, maybe drowsy +/- confused

Totally bedfast and requiring extensive nursing care by professionals and/or family

10% Moribund; fatal processes progressing rapidly

Totally bedbound, total care, mouth care only, drowsy or coma +/- confusion Comatose or barely rousable

Common Prognostic Indicators

Survival <6m if 2-4 of…• Poor performance status• Advanced Age• Malnutrition• Comorbid illness• Increasing organ dysfunction• Hospitalization for acute

decompensation

Salpeter et al. Amer J Med 2012;125:512 Slide courtesy of A. Weiss

COPD Prognostication Indicators

Ambulatory patients• FEV1 < 35% predicted value =

25% die within 2 years, 55% die within 4 years

Hospitalized patients• PaCO2 >50

• 10% will die on current admission• 33% will die within 6 months• 43% will die within 1 year

Connors et al, Am J Resp Crit Care Med 1996Slide courtesy of A. Weiss

• Factors associated with increased mortality:• FEV1 <30% predicted• Hypoxia (PaO2 <55)• Low BMI• Advanced age• Severe dyspnea with activity limitation• Decreased exercise capacity• Recurrent hospitalizations (esp. with hypercapnic

resp failure)• Depression• Other chronic co-morbid illnesses• Pulmonary hypertension related to COPD• BODE index >7

Prognostication - COPD

• BODE index: BMI, Obstruction, Dyspnea, Exercise

• 4 year survival: 0-2 Points: 80% 3-4 Points: 67% 5-6 Points: 57% 7-10 Points: 18%

Prognostication- COPD

Celli BR et al. N Engl J Med 2004;350:1005-1012.

• Factors associated with increased mortality:• Baseline factors

• Level of dyspnea• Diffusion capacity for carbon monoxide

(DLCO) <40% predicted• Desaturation with exercise• Pulmonary hypertension

• Longitudinal factors• Increasing dyspnea• Decline in vital capacity and DLCO over

time• Worsening fibrosis on CT scan

Prognostication - ILD

Slide courtesy of A. Weiss

More than 100 variables have been associated with mortality and re- hospitalization in heart

failure

GeneralAge, diabetes, sex, weight (BMI), etiology of HF, comorbidities (COPD, cirrhosis)

Laboratory markersNa, creatinine (and eGFR), urea, BUN, Hgb, % lymphocytes, uric acidLow HDLInsulin resistance

UrineAbluminuriaNGAL - neutrophil gelatinase associated lipocalin

BiomarkersBNP, NT pro BNP, troponin, CRP, cystatin C, GDF-15 (growth differentiation factor), serum cortisol, TNF, ET, NE, midregional-pro-adrenomedullin (MR-proADM), pro-apoptotic protein apoptosis-stimulating fragment (FAS)

MedicationIntolerance to ACEI, diuretic dose

FC IVEspecially if sustained > 90 days6 minute walk

Cardiopulmonary markersPeak VO2, % predicted, VE/VCO2, AT, workload, systolic BP < 130, HR recovery

Clinical Exam markersBP (admission and discharge), heart rate, JVP, +S3, cachexiaDepressionObstructive sleep apnea

Echo parametersEF, chamber size (LV, LA, RA), sphericity,

RNARVEF, LVEF

Recurrent hospitalizationsECG

IVCDHemodynamic markers

PA pressures, CO, CI, MVO2Endomyocardial biopsies

Microarrays transcriptomic biomarkersMarital status

WHAT SHOULD YOU DO ?????

Increasing age

Lower ejection fraction

Higher NYHA class

Hyponatremia

Elevated and rising BUN

Repeated admissions to hospital

Consistent Predictors- CHF

From Selby, D. 2008

Consistent Predictors- CHF

Significant cardiac dysfunction with:• Marked dyspnea and fatigue• End organ hypo-perfusion at rest• Symptoms with minimal exertion• Maximal medical therapy

AHA Stage D – refractory symptoms

Goodlin et al, Journal of Cardiac Failure Vol. 10 No. 3 2004Hunt SA et al JACC 2001;38:2101–13.

Heart Failure Models

EFFECT model/HFRSS (Lee et al, JAMA 2003)

• Validated in Ontario hospitals• 30 day and 1 –yr mortality• http://www.ccort.ca/Research/

CHFRiskModel.aspx

Seattle HF model (Levy et al, Circulation 2006)

• 1,2,3 yr survival estimate• Clinical, lab, medications and device

therapies• Needs further validation• www.seattleheartfailuremodel.org

Circ Heart Fail. 2013Adler et al. Circ 2009


http://www.seattleheartfailuremodel.org/

• Normalize conversation• Plan A vs. Plan B• Wishing for something vs. planning for

something

• “What is most important to you?”• Explore- fears, concerns• Acknowledge and validate

• Support • Separate message from messenger

• Non-abandonment• Comanagement with respirologist, cardiologist

Advance Care Planning

• Education• Prognosis, fatality of disease• Unpredictable course• Types of acute situations – ACTION PLAN

• Eliciting goals and values• Type of care• Place of care

• Including surrogate DM• More burdened with decisions, less informed by

pt

• Decisional Readiness

Advance Care Planning

palliative care in end-stage lung disease rebecca colman, md, frcpc respirology, university heath...

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