Transcript Opioids for Dyspnea

DYSPNEA
IN ADVANCED DISEASE
Porter Storey MD, FACP, FAAHPM
CONFLICT OF INTEREST DISCLOSURES - NONE
NOT FDA APPROVED (OFF – LABEL USES)
• Haloperidol for agitated
delirium
• Lorazepam for sedation
of the ventilated patient
• Clonazepam for anxiety
• Trazodone for insomnia
• Morphine, oxycodone,
hydromorphone, and
fentanyl (sl or iv) for
• Cancer pain in children
• Postoperative pain in
children
• Delivery via PCA pump
• Relief of dyspnea in
advanced disease
LEARNING OBJECTIVES
• At the conclusion of this talk, you should be able to:
1) Describe 4 components of the physiology of dyspnea,
2) Explain 3 ways opioids may increase ventilatory
efficiency, and
3) Name several ways effective teamwork can help
relieve dyspnea in advanced disease.
DYSPNEA
• Old
Misinformation
• Must improve
heart or lungs
to help
• Opioids
contraindicated
“HELP ME, I CAN’T BREATHE!”
Breast cancer with lung mets,
radiation toxicity, pleural
effusion, + pneumothorax
Worried about what this means
Now unable to work and support
her children
Why me?
DAME CICELY SAUNDERS
“Total” Pain or Breathlessness
Physical causes – often multiple,
e.g. airway obstruction, pleural
effusion, CHF, PE, pneumothorax
Psychological – anxiety, depression
Social issues – isolation, anger
Financial – care costs, unable to work
Spiritual – meaning, purpose, hope
Staff – efficiency, burnout, prof mask
“TOTAL BREATHLESSNESS”
• End-stage COPD refusing
oxygen and medications
• “I did this to myself!”
• “I don’t deserve them.”
• Wife frantic
• “Help us! He’s dying!”
• Her diabetes out of
control.
• Illegal immigrant with no
insurance.
• Strong faith, but prayers not
being answered now.
RESEARCH IN MULTIDIMENSIONAL DYSPNEA
Meek PM, Banzett R, et al. Eur Respir J. 2015 Jun; 45(6): 1681–1691.
RESEARCH IN PSYCHOLOGICAL
ASPECTS OF RESPIRATORY DISEASE
• Likelihood of COPD hospitalization
• Higher if more depression and anxiety
• Pooler A, Int J Chron Obstruct Pulmon Dis 2014;9:315-330.
• Higher if sleep and mental disorder
• Ohayon MM, J Psychiatr Res 2014; epub
• Lower if self-management program utilized
• Zwerink M, Cochrane database Syst Rev 2014: epub
• Dyspnea relief w acupuncture
• Suzuki M Arch Intern Med 2012; 172 (11):878-86.
• Romeo MJ, Explore (NY). 2015 Sep-Oct;11(5):357-62.
PROPOSED PHYSIOLOGY OF DYSPNEA
“A subjective experience
of breathing discomfort
that consists of qualitatively
distinct sensations that vary
in intensity.”
American Thoracic
Society 2012
OPIOIDS INCREASE EXERCISE TOLERANCE
• Opioid reduced breathlessness and increased
exercise tolerance in severe COPD patients.
• Woodcock AA, NEJM 1981; 305:1611-1616.
• Oral morphine increased exercise tolerance in COPD pts
by reducing breathlessness for a given level of ventilation
and allowing an elevation in pCO2 so less ventilation
required for a given workload.
• Light RW Am Rev Resp Dis 1989; 139:126-133.
PROPOSED MECHANISMS FOR OPIOIDS
INCREASE IN VENTILATORY EFFICIENCY
• Reduced bronchoconstriction
• Improved gas exchange due to higher CO2 and
lower O2 concentrations
• Reduction in responses to hypoxia and
hypercapnia
• Reduction in the drive to breath
• Reduction in total ventilation
• Less oxygen required at rest or to exercise
• Vasodilation of pulmonary vasculature
• Increased inspiration
• Attenuate limbic responses to dyspnea
RESEARCH ON OPIOIDS AND DYSPNEA
• Neuroimaging studies suggest that the emotion-related
structures involved in pain and dyspnea are shared.
• Odonnell DE, Proc Am Thorac Soc 2007; 4(2):145–168.
• Von Leupoldt A, Neuroimage 2009; 48(1):200-206.
• Morphine reduces dyspnea and hypercapnic response in lab
• Less “air hunger” from increased partial pressure of endtidal CO2 w restricted ventilation
• Effectiveness of morphine validates model of dyspnea
• Banzett RB, Am J Respir Crit Care Med. 2011 Oct 15;184(8):920-7.
ENDOGENOUS OPIOIDS AND DYSPNEA
• Opioid receptors are located throughout lungs but especially in
alveoli, where they can modulate respiratory function.
• Zebraski SE, Life Sci 2000; 66: 2221-31.
• Krajnik M, Pharmacol Rep 2010; 62(1):139-49.
• Endogenous opioids reduce dyspnea in exercising COPD pts.
• Ayiyama Y, J Appl Physiol 1993; 74: 590—5.
• Gifford AH, COPD 2011;8:160–166.
• Reduced dyspnea effects reversed with naloxone.
• Mahler DA, Eur Resp J 2009; 33(4): 771-777.
• Mahler DA, Gifford AH, et al. Chest. 2013 May;143(5):1378-85.
JOHN’S ISSUES
-Disabling dyspnea
-Widely metastatic
lung cancer
-Newly divorced
-Marginal insurance
-Upset son
-“This isn’t fair!”
JOHN NEEDS THE FULL TEAM!
SLOW-RELEASE MORPHINE FOR COPD
DYSPNEA
• Randomised, double blind,
placebo controlled crossover
trial of sustained
release morphine for the
management of
refractory dyspnoea.
• Abernethy AP1, Currow DC, Frith
P, Fazekas BS, McHugh A, Bui C.
BMJ. 2003 Sep 6;327(7414):523-8.
• 48 pts w COPD
• Randomized to 4 days of
morphine SR 20mg or placebo +
crossover
• 38 completed study
• Morphine associated with
• Less dyspnea
• Better sleep
• Constipation
LONG-TERM MORPHINE SR FOR DYSPNEA
• Once-daily opioids for
chronic dyspnea: a dose
increment and
pharmacovigilance study.
• Currow DC1, McDonald C, Oaten
S, Kenny B, Allcroft P, Frith P, Briffa
M, Johnson MJ, Abernethy AP J Pain
Symptom Manage 2011 Sep;42(3):38899.
• 83 patients (mean 75yo, 54% COPD)
• Given morphine SR 10mg daily,
• Non-responders increase by 10mg
daily each week.
• 62% responded, for 70% dose was
10mg/d.
• Benefit maintained for 3 mo for 33%.
• Breathlessness significantly better,
constipation worst side-effect (no
respiratory depression or
hospitalization due to morphine)
META-ANALYSES AND SYSTEMATIC REVIEWS
• Marciniuk DD, Managing dyspnea in patients with advanced chronic
obstructive pulmonary disease: A Canadian Thoracic Society
Guideline. Can Respir J 2011; 18(2).
• We recommend that oral (but not nebulized) opioids be used for
the treatment of refractory dyspnea in the individual patient with
advanced COPD. (Grade of recommendation 2C)
• Ben-Aharon I, Interventions for alleviating cancer-related dyspnea: a
systematic review and meta-analysis. Acta Oncol 2012; 51(8):996-1008.
• Our systematic review and meta-analysis demonstrate a beneficial
effect to opioids in alleviating cancer-related dyspnea, and no
advantage for the use of oxygen.
Managing Dyspnea in Advanced COPD
Canadian
Thoracic Society
Guidelines
From Marciniuk D, Goodridge D, Hernandez P, et al. Managing dyspnea in patients with advanced chronic obstructive
pulmonary disease: A Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18(2):69-78.258
Reprinted with permission.
MANAGEMENT OF DYSPNEA IN
PATIENTS WITH ADVANCED LUNG OR
HEART DISEASE
•
patients should be asked to
rate the intensity of their
breathlessness as part of a
comprehensive care plan,
opioids should be dosed
and titrated for relief of
dyspnea in the individual
patient,
American
College of
Chest
Physicians
Mahler DA, Chest. 2010 Mar;137(3):674-91.
OPIOID FOR DYSPNEA – SAFETY?
68yo with COPD and advanced
lung cancer
Would be on O2 if stopped
smoking
Dyspnea and pain at rest
Wants to stay home with his dog
Highest priority comfort
Safe to administer an opioid?
SC MORPHINE RELIEVES CANCER DYSPNEA
WITHOUT RESPIRATORY DEPRESSION
• Open, uncontrolled trial
• in 20 terminal ca pts, 5mg or 2.5 x reg
• 95% reported less dyspnea
• No change in respiratory rate or effort
• No change in arterial O2 sat or endtidal PaCO2.
• Bruera E J Pain Symptom 1990; 5(6):
341-344.
• Crossover Placebo Controlled Trial
• 10 consecutive ca pts on stable opioid
• Dose increased 50% (avg 34.5 mg sc)
• Good relief, no resp depression
• Bruera E Ann Intern Med 1993; 119:906.
• Randomized double-blind trial
• 9 elderly cancer patients
• Received either 5mg sc or 3.75mg
more than regular dose.
• In 45 min sig lower mean dyspnea by
VAS & Borg scales
• No changes observed in respiratory
effort or rate,
• No change in O2 sats
• Mazzocato C, Ann Oncol. 1999;
10(12):1511-4.
HYDROMORPHONE EFFECTIVE FOR DYSPNEA
WITHOUT RESPIRATORY DEPRESSION
• 14 palliative care patients with dyspnea
• All treated with hydromorphone and carefully monitored
• In 30 minutes, average dyspnea dropped 5.2 to 1.1 on 10
point scale
• Respiratory rate decreased 39 to 35 breaths / min
• peripheral oxygen saturation unchanged
• transcutaneous arterial pressure of carbon dioxide
unchanged
• Clemens KE, Support Care Cancer. 2008; 16(1):93-9.
OPIOIDS SAFE AND EFFECTIVE FOR DYSPNEA
IN ADVANCED
• Cancer dyspnea
• Bruera E, J Pain Symptom Manage
1990; 5(6):341-4.
• COPD
• Abernethy AP, BMJ 2003; 325:523-539.
• Idiopathic pulmonary fibrosis
• Allen S, Palliat Med 2005; 19(2): 128-30.
• Cystic Fibrosis
• Pediatrics 1997 Aug;100(2 Pt 1):205-9.
• Motor Neuron Disease / ALS
• Amyotroph Lateral Scler 2010
Dec;11(6):562-4.
• CHF
• J Palliat Med 2013 Mar;16(3):250-5
COMPONENTS OF RELIEF
Careful assessment for
treatable causes
Teamwork to address
non-physical issues
General measures,
O2, fan, relaxation
Skillful use of opioid
WHICH OPIOID & HOW MUCH ?
• Dyspnea-related History
•
•
•
•
Severity, onset, associations, effective interventions?
Adequate trial of disease-modifying or supportive interventions?
Good response to past use of opioid? Side-effects?
Difficulties controlling use of nicotine, alcohol, sedatives, cannabis,
or opioids?
• Exam and lab studies
• Extent of disease?
• Signs of treatable complication (pneumonia, effusion, etc.)?
• Signs of CNS or GI disease that might predispose patient to sideeffects?
BUILDING TRUST
Do your evaluation in a way
that says,
“Gosh, I see you are
having a tough time!”
“There is more we can
do to help.”
“We are going to be
here when you need us!”
START LOW, TITRATE REGULARLY IF NEEDED
• Starting dose will vary based on symptom severity, frailty, co-morbidities
• Outpatient with moderate symptoms, one possible beginning might be
• hydrocodone or oxycodone 2.5 to 5mg every 4-6 hours as needed
• With regular use of laxative
• Inpatients with more severe symptoms may benefit from
• parenteral doses of morphine or hydromorphone to get relief quickly
and determine effective dosing.
• Remember sleepless patient, finally comfortable, can look
overmedicated
• Family and staff require some educating also.
• Don’t forget the laxative!
USE ORAL MEDS WHEN
POSSIBLE
Patient trust in provider important for
therapeutic success.
IV or SC much less painful than IM.
LIKE TREATING PAIN
-Use regularly scheduled or
slow-release medication for
persistent symptom. (Drug must
be in patient to prevent
distress).
-Breakthrough medication
short-acting and as needed.
Titrate doses regularly for best
balance of relief and sideeffects.
-Don’t forget the laxative!
OPIOID PRESCRIBING CONCERNS
• Side-effects
• Tolerance rapidly develops to
• Sedation
• Confusion
• Itching
• Tolerance rarely develops to
• Constipation
• Addiction and Abuse
• Little evidence that normal
people become addicts
when opioids prescribed
appropriately
• People with addiction
problems (tobacco, alcohol,
drugs) often develop
advanced disease.
• Overdose Deaths at crisis levels
OPIOID OVERDOSE DEATHS
OPIOID OVERDOSE DEATHS
• Prescription painkiller overdoses - a public health crisis
• 116 million people in the US suffer from chronic pain.
• 12 million Americans (age 12 or older) reported nonmedical
use of prescription painkillers in the past year.
• Drug overdose has now surpassed traffic accidents as the
leading cause of unintentional injury in the US.
• 75% of pharmaceutical overdose deaths due to opioid analgesics
like oxycodone, hydrocodone, and methadone.
• Prescription painkiller overdoses killed over 16,600 people in the
US in 2010.
OPIOID OVERDOSE DEATHS
Drug overdose death rates by state per 100,000 people
NON-MEDICAL OPIOID SOURCE
Free from friend or relative 54%
Prescribed by physician(s)
20%
Stolen from friend or relative 5%
Bought from friend or relative 11%
Bought from dealer
4%
Stolen, fake script, etc.
5%
MANAGING OPIOIDS IN PATIENTS
WITH ADDICTION HISTORY
• Engagement – develop a
therapeutic relationship
• Assessment
• Misuse or abuse?
• Dependence?
• Physical and mental health
• Motivation to change?
• Focus on patient’s strengths
• Define Goals
• Controlling Substance Use
• Harm reduction
• Tools to consider
• Colorado Prescription Drug
Monitoring Program
• Opioid Agreement?
• Slow-release preparations
only
JUANITA
-Osteosarcoma widely
metastatic to lungs
-Pain and dyspnea severe
with activity
-Family in crisis
-Trying to be brave
-Mother rarely gives the
hydrocodone,
afraid “of addiction”
WHAT WOULD MAKE A DIFFERENCE NOW?
-On morphine SR
60mg every 12
hours
-Comfortable
enough to really
enjoy the pizza
party for her
friends.
ON HER FINAL DAY
-Now on equivalent of
morphine 180mg IV / hr
-Communicates with family
that she is comfortable
-Able to eat some jello and
smile at jokes.
-Dies quietly when Mom steps
away from room.
THE FINAL HOURS OF LIFE
• Important to recognize
• Patient with very advanced disease
• Has been on a stable dose of symptom management medications
• Now barely arousable, irregular respiration, mottled extremities
• Appropriate actions
• Sit down with family
• Sensitively discuss your concern that time may be short
• Discuss with staff to make sure
• Symptoms remain under control
• Patient and family not abandoned
• Naloxone stays in the pharmacy where it belongs
REJECTING A LUNG TRANSPLANT
-Transferred to inpatient
hospice dyspneic, terrified,
suicidal.
-Full team worked hard on
complex psychosocial
catastrophe.
-Now out enjoying the
sunshine, greeted me with
a smile,
-On hydromorphone
1mg/hr sc + lorazepam
HOPE
• Hope can be measured on 5 point Likert scale
• “I see light ahead”
• “I feel better each day”
• Hope-fostering strategies
•
•
•
•
•
•
Symptom relief
Increase interpersonal connectedness
Lightheartedness, Courage
Serenity, Attainable aims
Uplifting memories
Affirmations of worth
• As patients were referred to a hospice service and
approached the end of their lives, their scores
increased.
• Herth K, J Adv Nurs 1990; 15:1250-1259.
• Buckley J, Herth K, Nurs Stand 2004; 19(10): 33-41.
THERE IS LOTS WE CAN
DO TO HELP