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Edward (Ted) St. Godard MA MD CCFP Consulting Physician WRHA Palliative Care Robert Pope. “Visitors”

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Presentation on theme: "Edward (Ted) St. Godard MA MD CCFP Consulting Physician WRHA Palliative Care Robert Pope. “Visitors”"— Presentation transcript:

1 Edward (Ted) St. Godard MA MD CCFP Consulting Physician WRHA Palliative Care Robert Pope. “Visitors”

2 I am funded as an independent contractor by the WRHA

3

4 At the end of session, participants will  Be able to identify the medical condition known as delirium;  Appreciate the importance of this recognition;  Have an approach to delirium management

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7  Nurses are in an optimal position to detect fluctuating symptoms of delirium Agar et al. Palliative Medicine. September, 2011.

8  Silent, unspoken piece of nursing practice, impacting on workload  Nurses 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.

9  Under-detection of delirium relates to a lack of knowledge of the criteria for identifying delirium…  failure to relay or communicate detected symptoms at onset… Agar et al. Palliative Medicine. September, 2011.

10  Global cerebral dysfunction  “Brain Failure”  Early signs often mistaken as anger, anxiety, depression, psychosis

11  A) Change in consciousness with reduced ability to focus, sustain or shift attention  B) Change in cognition (e.g., memory, disorientation, change in language, perceptual disturbance) that is not dementia

12  C) Abrupt onset (hours to days) with fluctuation  D) Evidence of medical condition judged to be etiologically related to disturbance

13 …a disturbance in consciousness with inattention and problems in cognition and/or a disturbance in perception that develop over hours to days with organic causes.

14  Delirium  Impaired memory  Impaired judgement  Impaired thinking  Disorientation  Dementia  Impaired memory  Impaired judgement  Impaired thinking  Disorientation

15  Delirium  Abrupt onset  Decreased LOC  Sleep/wake cycle   Dementia  Insidious, progressive  Alert, LOC intact  Minimal 

16  Delirium  Reversible?  PREVENTABLE?  Dementia  Irreversible

17  In up to 50 % of patients with advanced cancer, delirium can be reversed Kang JH et al. “Comprehensive approaches to managing delirium in patients with advanced cancer.” Cancer Treat Rev (2012)

18 Lawlor P, Gagnon B, Mancini I, Pereira J, et al. Arch Intern Med 2000

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

20 Lawlor P, Gagnon B, Mancini I, Pereira J, et al. Arch Intern Med 2000

21  80 % in medical intensive care units (ICU)  28 % in patients following hip fracture  22 % in general medical inpatients 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)

22  Most frequent neuropsychiatric complication in patients with advanced CA  Up to 85 % of patients delirious prior to death Bruera et al. JPSM 2010; 39;2:

23  ~ 42% patients in PC program delirious on admission  50% of episodes reversible  “Terminal delirium” in 88 % Lawlor et al. Arch Intern Med 2000; 160:786

24 Eisenchlas. Current Opinion in Supportive and Palliative Care 2007, 1:207–212

25 Fainsinger RL et al. “A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients.” Palliat Med 2000;14:257– 65.

26  “We’d rather see dad dead than like this.”  “S/he would be horrified by this.”

27  73/99 patients (74%) remembered delirious episode  Of these, 81 % recalled experience as distressing  Family stress > patients’ recalled stress Bruera et al. JPSM 2010; 39;2:

28  Interferes with S x assessment and T x  Increases morbidity and mortality  Hinders communication within families Bruera et al. JPSM 2010; 39;2:

29 Pain Dyspnea Delirium D/D

30 Worsening Delirium Worsening Delirium A x /T x Challenges

31  Delirium 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:

32  Relative acetylcholine deficiency and dopamine excess could mediate the characteristic symptoms of delirium  Delirium can be evoked by dopamine agonists and anticholinergic medications Moyer. American Journal of Hospice and Palliative Medicine 28(1), Kang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev (2012)

33  Dopamine/acetylcholine inverse relationship  Haloperidol first line treatment for delirium  Haloperidol D 2 antagonist:  ? Haloperidol increase levels acetylcholine? White et. al. “First Do no Harm…” JPM. 10 (2); 2007: Kang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev (2012)

34  Sometimes successfully treated with dopamine receptor antagonists and possibly by cholinesterase inhibitors  High serum anticholinergic activity in patients with delirium Moyer. American Journal of Hospice and Palliative Medicine 28(1),

35  Υ-aminobutyric acid (GABA)-ergic benzodiazepines seem to cause delirium  Neuroinflammatory processes drives up- regulation of GABA receptors  GABA receptor versus microglial activation versus apoptosis C.G. Hughes et al. “Future Directions in Delirium Management and Research.” Best Practice & Research Clinical Anaesthesiology. 26 (2012) 395–405

36  Predisposing  Precipitating

37  Predisposing factors:  Prevalence increases with age  Male > female  Visual impairment  Depression White et. al. “First Do no Harm…” JPM. 10 (2); 2007:

38  Predisposing factors:  Functional dependence  Immobility  Hip fracture  Dehydration  Alcoholism  Stroke  Severity of physical illness White et. al. “First Do no Harm…” JPM. 10 (2); 2007:

39 All of our patients!

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41 HANDLE WITH CARE

42  Inverse relationship between the preexisting vulnerability of the patient, and the severity of the insult necessary to precipitate delirium

43  Most patients nearing EOL have multiple predisposing factors  Most of these are beyond our control

44  Predisposing  Precipitating

45  Impractical, given our patient population (frail, usually old)  Imperative to minimize precipitating factors

46  ‘lyte derangements (dehyd’n, hypo/hypernatremia)  Infx (UTI, resp., skin/soft tissue [sacral ulcers])  Metabolic (hyper/hypoglycemia, hypercalcemia, uremia)  Low perfusion, hypoxia  Withdrawal

47 Anti-cholinergics (Gravol, TCAs, anti-secretories); Anti-cholinergics (Gravol, TCAs, anti-secretories); BZDs BZDs Opioids Opioids Steroids Steroids Cipro, lasix (?) ranitidine, and on and on…. Cipro, lasix (?) ranitidine, and on and on….

48  Drug withdrawal:  EtOH, Bzd, opioid, “street drugs”

49  Prophylactic haldol  Prophylactic olanzepine  Prohylactic cholinesterase inhib.s Gagnon et al. Psycho ‐ Oncology 21: 187–194 (2012)

50  Maintain sensorium: hearing aids, eye glasses  Orientation (clocks, calendars, conversation) Gagnon et al. Psycho ‐ Oncology 21: 187–194 (2012)

51  No good evidence for benefit from screening hospitalized patients Greer N et al. Delirium: screening, prevention, and diagnosis – a systematic review of the evidence 2011 Internet.

52 “Cured yesterday of her disease, she died last night of her doctor.” paraphrasing Jonathon Swift (you know, Gulliver’s Travels)

53  Medication sole precipitant of delirium in 12 – 39 % healthy patients Alagiakrishnan et al. Postgrad Med J, 2004; 88:

54  Drug toxicity, drug withdrawal  Start low, go slow  Very often, less is more

55  Analgesics: Uncontrolled pain is risk factor for delirium  “Rome wasn’t built in a day”  Balance pain against dose  Titrate gently

56  Analgesics: Titrate gently  Don’t be afraid to decrease

57 Worsening Delirium Worsening Delirium A x /T x Challenges

58  Sedatives: “A benzodiazepine will never help your thinking.” Dr. Mike Harlos

59  Lorazepam is an independent risk factor for delirium, increasing risk by ~ 20 % (not to mention falls, etc.) Panpharpande et al. Anesthesiology. 2006; 104:21 Kang JH et al. Comprehensive approaches to managing delirium in patients with advanced cancer. Cancer Treat Rev (2012)

60  Sedatives:  Try not to be the one who starts bzd, but don’t be the one who abruptly stops it  Better a tired patient in AM than a delirious patient in AM

61  “Anxiety,” “restlessness?” -- how about company? Going for a walk-about?  More staff, fewer sedatives, less delirium?  Drugs cheap, one-on-one expensive  Value?

62  Does vigorous hydration decrease delirium incidence?  Hyd’n reversed or improved 30 – 70 % delirium cases Thomson et al. Current Op Supp Pal Care. 2009; 3:72-78

63  Name it  Claim it  Tame it

64  “A little fluffy”  “Loopy”  “A little off”  “Not quite right”  “Fruit-cake” DELIRIUM

65  MMSE?  CAM?  Intuition?  Do something;  Name it….

66  Change in consciousness with reduced ability to focus, sustain or shift attention

67  Engage in conversation?  Months of year backward?  Clinical suspicion

68  Drs. cause delirium?  Can Drs/nurses prevent it, reverse it, or reduce its impact?  Who better?

69  Two simultaneous pathways  Seek and treat cause (thus reverse?)  Manage behaviours (“supportive care”)  Human intervention better than pharmacological

70 Supportive measures  Hydrate?  Avoid restraints  Mobilize  Reduce noise, etc.  Orient  Reassure  One-on-one Investigations  MEDICATION REVIEW  Bloodwork  U/A  Imaging

71  Meds:  Eliminate any psychoactive med possible:  Metoclopramide, cipro? Baclofen? Ranitidine? Lasix? others?

72  Meds:  Analgesia:  Good pain control? Consider dose reduction?  Sub-optimal pain control? Opioid rotation

73 I F 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

74  Does 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 bzd

75  Haloperidol remains standard of care  Powerful  Oral and parenteral  Limited anti-cholinergic, sedative properties White et. al. “First Do no Harm…” JPM. 10 (2); 2007:

76  No significant differences in response in double-blind RCT comparing risperidone and haloperidol  Similar evidence finding minimal differences in efficacy between olanzapine and risperidone Bourne et. al. “Drug Treatment of Delirium.” Journal Psychosomatic Research. 65; 2008: Kang JH et al. “Comprehensive approaches to managing delirium in patients with advanced cancer.” Cancer Treat Rev (2012)

77  Methylphenidate can improve cognitive and psychomotor function in hypoactive delirium  Methylphenidate can cause agitation, aggravation, psychosis Bourne et. al. “Drug Treatment of Delirium.” Journal Psychosomatic Research. 65; 2008:

78  Delirium is bad  Hard on patients, families, staff  Often preventable, often iatrogenic  Nurses optimally located  Occasionally reversible

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81 At the end of this session, you will  Understand the importance of context in the interpretation of pain  Appreciate at a basic level the physiology of pain and some principles of analgesia  Have an approach to pain management that always bears in mind the above points

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83 11/11 65 % 12/12 91 %

84 Think about pain….

85  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.

86 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.

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

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89 Multi-disciplinary Team?

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91 Pain or Suffering? Both? Neither?

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93 “…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.

94 “…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 it Merskey H, Bogduk N. 2nd ed Seattle, WA: IASP Press; 1994.

95 Bruera 1992 “Why Do We Care?” Conference; Memorial Sloan-Kettering

96 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.

97 Nociceptive somatic bony superficialdeep visceral Neuropathic neuralgicdysesthetic hyperalgesia Adapted from Jovey R, 2002 Pain is not a diagnosis

98 N OCICEPTORS Sensory receptors Sensory receptors Preferentially sensitive to noxious stimuli (tissue damaging/threatening) Preferentially sensitive to noxious stimuli (tissue damaging/threatening) Chemical, thermal, mechanical Chemical, thermal, mechanical

99 S OMATIC P AIN Nociceptive Nociceptive Aching, often constant Aching, often constant Often worse with mvt Often worse with mvt Well localized Well localized Tender Tender – bone & soft tissue – chest wall – post-surgery incision

100 V ISCERAL P AIN Constant or crampy Constant or crampy Dull, aching Dull, aching Poorly localized Poorly localized Often referred Often referred – CA pancreas – Bowel obstruction – Infiltration/compression/distension

101 Pain initiated or caused by primary lesion or dysfunction in the nervous system International Association for the Study of Pain

102 NP D ESCRIPTORS NP D ESCRIPTORS Burning, Itching, Shooting, Shock- like, Electric, Lancinating “Pins and needles,” tingling, numb

103 NP D ESCRIPTORS NP D ESCRIPTORS “Pins and needles,” tingling, numb

104 Pharmacologic treatment  Anticonvulsants – gabapentin, pregabalin  TCAs (esp. if depression)  NMDA receptor antagonists: ketamine, dextromethorphan, methadone  Steroids  Opioids 

105 Up to 90% of patients with cancer pain could have their pain alleviated by following the treatment guidelines of the WHO analgesic ladder Fitzgibbon et al. “Parenteral Ketamine as an Analgesic Adjuvant for Severe Pain.” J Pall. Med. 8(1) 2005

106 Mild pain (0-3) (0-3) Moderate (4-6) (4-6) Severe (7-10) (7-10) By the clock By the ladder Acetaminophen & NSAIDs & NSAIDs Weak opioid + Step 1 Strong opioid + Step 2 + Step 2 Adjuvant Rx may be added at any step

107 Mild pain (0-3) (0-3) Moderate (4-6) (4-6) Severe (7-10) (7-10) By the clock By the ladder Acetaminophen & NSAIDs & NSAIDs Weak opioid + Step 1 Strong opioid + Step 2 + Step 2 Adjuvant Rx may be added at any step

108 Serum [ drug ] Time TOXIC Therapeutic Sub-therapeutic

109 Serum Time TOXIC Therapeutic Sub-therapeutic

110 Serum TOXIC Therapeutic Sub-therapeutic 4 hours

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113 Life in the Bloodstream

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118  Think about drug, dose, route

119 Steady decline at home Rapid decline due to illness progression with diminished reserves Accelerated deterioration begins, pain worsening, pt. admitted, pain worsening, pt. admitted, medications changed medications changed Family thinking what?

120 Every family is the Addams family

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122 Too much medication Not enough…. ???????

123 “It’s all the morphine you’re giving her…..”

124 Popular misconception held by families, lay public, and professionals

125 “’By the way, palliative care shortens your life,’ [xxxx] suggested.”

126 Azoulay et al. “Opioids, Survival, and Advanced Cancer in the Hospice Setting.” J Am Med Dir Assoc. Feb. 2011; 12: “Increasing overall opioid dosage was associated with improved survival compared with no change or decreasing overall dosage (mean survival days versus versus , days respectively, P 5.01).”

127 Azoulay et al. “Opioids, Survival, and Advanced Cancer in the Hospice Setting.” J Am Med Dir Assoc. Feb. 2011; 12: “Opioid usage, even at high dosages, had no effect on survival among advanced cancer patients in a hospice setting.”

128 Temel et al. “Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer.” N Engl J Med. 2010; 363: “Among patients with metastatic non– small-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.”

129 S UB -Q M ORPHINE Bruera et al. J Pain Symptom Manage. 1990; 5:

130  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

131  Pain “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;

132  ACP “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

133  Pain “everywhere” (pathophysiology?);  Family report fairly rapid escalation of opioids past 3-4/7;  Poor historian, “muddled”;  Creatinine up

134  Potentially fatal neuropsychiatric syndrome of:  Cognitive dysfunction  Delirium  Hallucinations  Myoclonus/seizures  Hyperalgesia / allodynia  Early recognition is critical

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136 Osborne et al. “The Pharmacokinetics of morphine and morphine glucuronides in Kidney Failure.” Clin Pharmacol Ther 54: , 1993 Normal Renal Fcn Renal Insufficiency

137 Seizures, Death Opioid tolerance Mild myoclonus (eg. with sleeping) Severe myoclonus Delirium Agitation Misinterpreted as Pain Opioids Increased Hyperalgesia Misinterpreted as Disease-Related Pain Opioids Increased

138  Switch opioid (rotation) and/or reduce dose  Hydrate  Bzd prn?

139  Not everyone has pain ;  Treating pain with scheduled opioids is appropriate and safe;  Avoid long-acting formulations;

140  Watch out for pain that “doesn’t make sense,” as it might be warning you of OIN  Pain and suffering are distinct, and not always related as closely as we think

141 PAIN

142 POSSIBLE

143 Suffering?

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145 At the end of the session, you will Have a basic understanding of respiration Have a basic understanding of respiration Be aware of the complex mechanisms underlying dyspnea Be aware of the complex mechanisms underlying dyspnea Have an approach to the management of dyspneic patients Have an approach to the management of dyspneic patients

146 “Subjective 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:

147 Physical and emotional components (anxiety, panic, chronic fear)Physical and emotional components (anxiety, panic, chronic fear) Often no measurable physical correlates (RR ? SaO 2 ? ABG)Often no measurable physical correlates (RR ? SaO 2 ? ABG) Tachypnea ≠ dyspnea

148 Dudgeon, D. “Managing Dyspnea and Cough.” Hematology/Oncology Clinics of North America. 2002; 16: Universal response is to decrease activity to whatever degree necessary

149 A B C D

150 “Subjective 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:

151 MonthsDaysMinutes Without eating Without drinking Without breathing

152 Dyspnea, like pain, is protective. As pain alerts us to actual or impending tissue damage, dyspnea alerts us to threat. Dyspnea, like pain, is protective. As pain alerts us to actual or impending tissue damage, dyspnea alerts us to threat. “Hardwired” to protect “Hardwired” to protect

153 60 % lung Ca patients60 % lung Ca patients Nearly 90 % once near deathNearly 90 % once near death 50 % described dyspnea as severe50 % described dyspnea as severe Muers 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.

154 Reuben DB, Mor V. “Dyspnea in terminally ill cancer patients.” Chest. 1986; 89(2):

155 Abnormality of blood gases, especially hypercapnia (PaCO 2 > 50 mmHg) and, to a lesser extent, hypoxia (PaO 2 50 mmHg) and, to a lesser extent, hypoxia (PaO 2 < 60 mmHg); Amount of work that must be performed by respiratory muscles to provide adequate ventilation;Amount of work that must be performed by respiratory muscles to provide adequate ventilation; State of mind.State of mind. Guyton and Hall. Textbook of Medical Physiology. 491

156

157 Mahler. “Understanding Mechanisms …Dyspnea.” Current Opinion in Supportive and Palliative Care.2011, 5:71–76

158 Integrates information about:Integrates information about: o Degree of effort required o Mechanical response achieved o O 2 /CO 2 pH status In order to answer two questions:

159 1.Is the mechanical response normal relative to the degree of effort expended? 2.Is the current effort sustainable? If not, dyspnea

160 Dyspnea occurs when there is a mismatch between ventilation and the demand set by chemical drive Buchanan and Richerson. “Role of Chemoreceptors in Mediating Dyspnea.” Respiratory Physiology and Neurobiology. 2009; 167: 9 – 19

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168 Oxygen Carbon Dioxide CO 2 + H 2 O HCO H +

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171 Tachypneic? Tachypneic? Hypoxic? Hypoxic? Anxious/afraid? Anxious/afraid? Diaphoretic? Diaphoretic? Unconscious? Unconscious?

172 “Subjective 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:

173 1.Assess the symptom 2.Determine the cause 3.Treat the cause 4.Treat the symptom

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175 Remember:Remember: o Tachypnea is not dyspnea; o Assess distress, not just apparent intensity

176 ThoracicThoracic Non-malignantNon-malignant MalignantMalignant ParamalignantParamalignant Extra-thoracicExtra-thoracic Cachexia;Cachexia; Anemia;Anemia; Ascites;Ascites; HepatomegalyHepatomegaly ‘Lyte derangement‘Lyte derangement

177 Anti-tumour: chemo/RT, etc.Anti-tumour: chemo/RT, etc. InfectionInfection CHFCHF SVCOSVCO Pleural effusionPleural effusion Pulmonary embolismPulmonary embolism Airway obstructionAirway obstruction

178 Goal of interventions:Goal of interventions: o Minimize production of symptom (pre-medicate, energy mgmt., breathing techniques) o Diminish perception of symptom (meds, fan, distraction)

179 Goal of interventions:Goal of interventions: o Modify the experience of the symptom (address meaning, help with mood/fear/anxiety)

180 Non-pharmacologicalNon-pharmacological o Open window? o Cool facial stimulation (fan) o Positioning o Pulmonary rehab?

181 PharmacologicalPharmacological o Oxygen o Opioids o Nebulized furosemide o Anti-inflammatory tx o Benzodiazepines?

182 Bruera dyspneic, hypoxic (SaO 2 < 90%) cancer inpatients14 dyspneic, hypoxic (SaO 2 < 90%) cancer inpatients RCT, 2 x blind, placebo, crossoverRCT, 2 x blind, placebo, crossover 5 L/min air by NP vs O 25 L/min air by NP vs O 2 no ∆ in VAS from baseline with air, significant improvement with O 2no ∆ in VAS from baseline with air, significant improvement with O 2 Bruera et al. Lancet. 1993; 342:

183 Bruera 1993 Conclusion: O 2 substantial benefit in hypoxic dyspneic cancer patients Bruera et al. Lancet. 1993; 342:

184 Bruera dyspneic, non-hypoxic cancer pts33 dyspneic, non-hypoxic cancer pts RCT, single blind, placebo, cross-overRCT, single blind, placebo, cross-over 5 l/min air vs O 2 for 6 MW test5 l/min air vs O 2 for 6 MW test No difference in dyspnea, fatigue, or distance walkedNo difference in dyspnea, fatigue, or distance walked Bruera et al. Pall Med. 2003; 17:

185 Bruera 2003 Conclusion: O 2 of no benefit over air to exercising non-hypoxic cancer pts Bruera et al. Pall Med. 2003; 17:

186 O 2 no better than air in non- hypoxic patientO 2 no better than air in non- hypoxic patient O 2 better than air if hypoxicO 2 better than air if hypoxic

187 Normal COPD O 2 CO 2 Resp. Drive

188 COPD O 2 CO 2 Resp. Drive O 2 CO 2 Resp. Drive

189 Giving pts. with COPD supplementary O 2 can actually suppress their resp. drive (and kill them with kindness)

190 Anxiety is significantly correlated with intensity of dyspneaAnxiety is significantly correlated with intensity of dyspnea Limited evidence supporting BZD roleLimited evidence supporting BZD role Bruera, E. et al. “The Frequency and Correlates of Dyspnea in patients with Advanced Cancer.” J Pain Symptom Mgmt. 2000; 19:

191 “Milk of the poppy…”

192 Used for analgesia for centuriesUsed for analgesia for centuries Used since at least 19 th century for breathlessnessUsed since at least 19 th century for breathlessness Now a degree of reticenceNow a degree of reticence

193 Mahler DA, Murray JA, Waterman LA, Ward J, Kraemer WJ, Zhang X, Baird JC: “Endogenous opioids modify dyspnoea during treadmill exercise in patients with COPD.” Eur Respir J 2009; 33:771. Naloxone versus saline in exercising COPD patients; Naloxone versus saline in exercising COPD patients; Naloxone group more dyspnea; Naloxone group more dyspnea; Endogenous opioids blunt dyspnea Endogenous opioids blunt dyspnea

194 Cochrane:Cochrane: o 18 RDBPC crossover trials o 9 nebulized, 9 systemic, 14 single dose o Primarily COPD Conclusion: significant benefit for systemic, but not for nebulized opioidsConclusion: 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. 2001

195 Early 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,

196 ↓ Medullary sensitivity/response to hypercarbia/hypoxia ↓ Medullary sensitivity/response to hypercarbia/hypoxia ↓ Cortical resp. awareness ↓ Cortical resp. awareness ↓ Metabolic rate/ventilatory demand ↓ Metabolic rate/ventilatory demand Vasodilation (improved cardiac fcn)Vasodilation (improved cardiac fcn) Analgesia: ↓ pain-induced resp. driveAnalgesia: ↓ pain-induced resp. drive AnxiolysisAnxiolysis

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200 Narrow therapeutic indexNarrow therapeutic index Watch:Watch: o Rate of dose change o Previous exposure? Bruera, E. “Effects of Morphine on Dyspnea.” J Pain Symptom Mgmt. 1990; 5: 341-4

201 Pinpoint pupilsPinpoint pupils Gradual slowing of the respiratory rateGradual slowing of the respiratory rate Breathing is deep (though may be shallow) and regularBreathing is deep (though may be shallow) and regular

202 Kamal et al. “Dyspnea Review for the Palliative Care Professional.” J Pall Med. 2012; 15 (1): “…fear has been shown to be largely unfounded. Examining changes in respiratory parameters…in dyspneic palliative care patients…demonstrated 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.”

203 Kamal et al. “Dyspnea Review for the Palliative Care Professional.” J Pall Med. 2012; 15 (1): “…demonstrated benefits, and the lack of edvidence of accelerated death, have led the American College of Chest Physicians…to recommend that physicians titrate oral and/or parenteral opioids”

204 Bruera et al. J Pain Symptom Manage. 1990; 5:

205 Dyspnea can’t be measured, and often can’t be observedDyspnea can’t be measured, and often can’t be observed Oxygen is a drug; balance benefit vs cost ($ and other)Oxygen is a drug; balance benefit vs cost ($ and other) Opioids workOpioids work

206 If you want a wise answer, ask a reasonable question Goethe Who questions much, shall learn much, and retain much Francis Bacon

207 Our solar system consists of one star, and some debris…. Carl Sagan


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