Tezko dihanje - Dyspnea in patients with advanced...
Transcript of Tezko dihanje - Dyspnea in patients with advanced...
Tezko dihanje -
Dyspnea in patients with advanced disease
Ljubjana, 20.102017
Gudrun Kreye
Division for Palliative Care, 2. Medizinische Abteilung, University Hospital Krems
Patient F. M., 10.5.1975
• Osteosarcoma of the right hip
• Lung metastases
• Multiple chemotherapies
• Fluidopneumothorax right side
• Surgical procedure for fluidopneumothorax
• Pneumonia both sides
Patient F. M., 10.5.1975 –Treatment options in
this acute situation?
• Immediate 6th-line chemotherapy
• Therapy with checkpoint-inhibitor therapy
• Opioids
• Palliative sedation
• Another surgical procedure
Patient F. M., 10.5.1975 –Treatment options in
this acute situation?
• Immediate 6th-line chemotherapy
• Therapy with checkpoint-inhibitor therapy
• Opioids
• Palliative sedation
• Another surgical procedure
Patient O.K. ,81 years
• Advanced lung cancer
• Acute dyspnea
• Symptoms of angina pectoris
• X-ray of the lung: stable, no new lesions
• Hb 5,6 g/dl
• Patient wants every treatment possible
Therapy??
Patient O.K. ,81 years -Therapy
• Immediate start of chemotherapy
• Furosemide
• Opioids
• Immediate blood transfusion
• Benzodiazepines
Patient O.K. ,81 years -Therapy
• Immediate start of chemotherapy
• Furosemide
• Opioids
• Immediate blood transfusion
• Benzodiazepines
Female patient A.S., 63
• Advanced breast cancer
• ECOG 3
• Lymphangiosis carcinomatosa
• Chronic dyspnea
Therapy??
Female patient A.S., 63
• Another chemotherapy
• Opioids
• Corticosteroids
• Furosemide
• Blood transfusion
Female patient A.S., 63
• Another chemotherapy
• Opioids
• Corticosteroids (although low
evidence)
• Furosemide
• Blood transfusion
Definition of Dyspnea
American Thoracic Society defines dyspnea
as an individual’s sensation of breathing
discomfort arising from various physiological,
psychological, social, and environmental
circumstances
Dyspnea ATSCo. Dyspnea. Mechanisms, assessment, and management: aconsensusstatement. AmJRespirCritCareMed.
1999;159(1):321–40
Physiology of breathing
• Defined as the movement of oxygen from the outside
environment to the cells within tissues, and the transport of
carbon dioxide in the opposite direction
• Most important internal impulse : pCO², pH - blood
• Less important: pO² in arterial blood
Receptors for pH-value and hypoxemia
• Less important as breathing stimulator
• Localisation:
– Aortic arch
– Bifurcation of carotis
– Breathing center in the brain
Other stimuli for breathing: :
• Expansion of the lung (Hering-Breuer-Reflex)
• Consciousness
Physiology of breathing
Quantification of Dyspnea
Goldstandard: ?
*JR Thomas and v Gunten C, Lancet Oncology 2002
Respiratory rate?
Quantification of Dyspnea
• Goldstandard:
– Subjective report of the patient
• Respiratory rate, oxygensaturation, blood
gas analysis:
– Do not correlate with severity of dyspnoea
– No measurement tool for patients
*JR Thomas and v Gunten C, Lancet Oncology 2002
• Visual analogue scale*
•
• Borg Scale**
•
• Edmonton Rating Scale***
* Adams L et al, Clin Sci 1985
** Med Sci Sports Exerc 1982
*** Driver LC et al, MD Anderson Palliative Care Handbook 2002
Quantification of dyspnea for palliative care patients
Dyspnoea in palliative care
• Cancer
• Neurologic diseases
• Pneumologic diseases
• Cardial diseases
Prevalence of dyspnea in palliative care patients
• COPD: 90–95 %
• Chronic heart failure: 60–88 %
• Advanced cancer: ca. 50 %.1, 2 according to stage 19-
76%
• Pulmonal hypertension
• Increasing with disease progression 49-94%3, 4
Ripamonti et al. Supp Care Cancer 1999
Muers MF et al, Thorax 1993,
Higginson I et al, JR Soc Med 1989;
Reuben DB et al. Chest 1986)
Solano JP et al., J Pain Symptom Manage 2006
Altfelder N et al., Palliative Medicine 2010
Currow DC et al., J Pain Symptom Manage 2010
Bausewein C et al., Palliat Med 2010
Physician attitudes toward palliative care for patients with pulmonary
arterial hypertension: results of a cross-sectional survey
Fenstad ER et al. Pulm Circ. 2014
Physician attitudes toward palliative care for patients with pulmonary
arterial hypertension: results of a cross-sectional survey
Fenstad ER et al. Pulm Circ. 2014
“The most frequent reasons for not referring patients to PC included nonapproval
by the patient/family (51%) and concern that PC is "giving up hope" (43%)”
• Present in 70% of all patients in their last weeks of life
• Severe in 25 % of all cancer patients *
• Dyspnea = independent prognostic parameter for shorter
survival*
* Reuben DB et al, Archives of Internal Medicine 1988
Prevalence of dyspnea in cancer care patients
Dyspnea: independent prognostic parameter for shorter survival *
Arrieta O et al., Lung Cancer 77, 2012, 205–211
Investigations in palliative care patients with dyspnea
suggested by medical students
G. Pohl, WMW 2011
Non-pharmacological treatment of dyspnoea
• Try to be calm
• Prepare emergency plan in advance
• Psychological help
• Physiotherapy
• Change position
• Breathing
• Relaxation techniques
• Stay with the patient- avoid isolation
• Technical aids: ventilator, fan,
• Open window
Nava S. et al. Lancet Oncol. 2013
Pharmacological treatment of dyspnea
Opioids
Benzodiazepines?
Other drugs Anxiolytics/Antidepressants
Neuroleptic drugs?
Corticosteroids?
Kamal AH et al. J Palliat. Medicine 2012
Booth S. Palliat. Med. 2013
Ekström et al. BMJ 2015
Opioide-Rationale
• Reduce ventilatory drive to hypercapnia, hypoxia and
exertion
• Activation of µ und d-opioidreceptors reduces
inspiratory volume and volume per minute
*Bianchi A et al. J Pain and Symptom management, 1995)
Opioids – mechanism of action
• Still unclear
• Naloxon enhances dyspnea* - role of endogeneous opioids?
• PET-Scan: cortical areas correlating with dyspnea**
* Akiyama et al., J Appl Physiol 1993
** Peiffer et al. Am J Respir Crit Care Med 2001
Opioids in palliative care patients withs dyspnea
• Pharmacological firstline-therapy
• Only therapy with benefit
• No signs for respiratory depression when adequately
titrated
• No significant chances in oxygen saturation
• No significant elevations of carbon dioxide
Jennings AL et al. Thorax 2002
Abernethy et al. BMJ 2003
Currow DC et al., J Pain Symptom Manage 2011
Ben-Aharon I et al. Acta Oncol 2012
Kamal AH et al. J Palliat. Medicine 2012
Booth S. Palliat. Med. 2013
Abernethy et al. BMJ 2015
Lopez-Saca JM et al. Curr Opp Supp Pall Care 2014
Bausewein C. Internist (Berl). 2016 Oct;57(10):978-982.
Chin C, Booth. Postgrad Med J. 2016 Jul;92(1089):393-400. doi:
10.1136/postgradmedj-2015-133578. Epub 2016 Apr 6.
Opioids for patients with advanced COPD
• Systematic review/meta-analysis (Cochrane)
• 16 studies included
• 271 patients (95% with severe COPD)
• Sigificant reduction of dysnea by using opioids
Ekström M. et al. Effects of Opioids on Breathlessness and Exercise Capacity in Chronic Obstructive Pulmonary Disease: A Systematic
Review. Ann Am Thorac Soc. 2015 Mar 24
Pharmacological treatment of dyspnea with opioids
Opioidnaïve Opioid tolerant*
Mild dyspnea Hydrocodone (5-10 mg) or
Codeine (30 mg) p.o. every 4 h,
Then retarded formulation
Dose escalation 25%
to 50%
Severe dyspnea Morphine 5 mg p.o. every
4h oder
Oxycodone 5 mg every 4 h oder
Hydromorphon 1 mg every 4 h
Dose escalation 25%
to 50%
Parenteral Morphin 2.5 – 5mg s.c. or
i.v. 3-4 h or 10-30 mg/24h s.c. or
i.v.
Dose escalation 25%
to 50%
Titration Dose related escalation 30% Dose related escalation
30%
Jennings AL et al. Thorax 2002
Abernethy et al. BMJ 2003
Currow DC et al., J Pain Symptom Manage 2011
Fentanyl forDyspnoe Simon ST et al., J Pain Symptom Management 2013
622 citations
13! Studies included
88 patients
69 lung cancer 16 COPD
Episodisch-kontinuierlich
Nebulized Fentanyl: 70
OFTC: 9
Intranasal: 5
Transdermal: 3
i.v.-Remifentanyl: 1
Only 2 RCTs!
Fentanyl for dyspnea Simon ST et al., J Pain Symptom Management 2013
• 622 citations
• 13 included
• Only 2 randomized controlled studies
• All studies showed improvement of dyspnea after application
• No respiratory depression by fentanyl!
• Large randomized studies necessary
Pharmacological treatment of dyspnea
Benzodiazepines
• Currently no benefit as firstline therapy
• No signs of respiratory depression
• Second or thirdline after opioid failure
•Simon, Bausewein et al. 2009
•Simon ST et al., Cochrane Database Syst Rev 2010
** JR Thomas and v Gunten C, Lancet Oncology 2002
** Mitchell-Heggs et al, QJM 1980
*** Woodcock AA, BMJ 1981
**** Man CG , Lancet 1993
° Gomutbutra P et al. J Pain Symptom Manag 2013
Pharmacological treatment of dyspnea
Benzodiazepines Dosage
• Lorazepam: 0.5-1mg /h p.o., then every 4-6h
• Diazepam: 5-10mg/h p.o., then every 6-8h
• Clonazepam: 0.25-2 mg p.o. every 12h
• Midazolam: 0.5 mg i .v. 15 min until symptom controllm then
continously
*JR Thomas and v Gunten C, Lancet Oncology 2002
Benzodiazepines for the relief of breathlessness in
advanced malignant and non-malignant diseases in adults.
Cochrane Database Syst Rev. 2016 Oct 20;10:CD007354. Bausewein
C et al.:
• There is no evidence for or against benzodiazepines for the relief of
breathlessness in people with advanced cancer and COPD.
• Benzodiazepines caused more drowsiness as an adverse effect
compared to placebo, but less compared to morphine.
• Benzodiazepines may be considered as a second- or third-line
treatment, when opioids and non-pharmacological measures have
failed to control breathlessness.
• There is a need for well-conducted and adequately powered studies.
Pharmacological treatment of dyspnea
Other drugs
• Anxiolytics/Antidepressants: – E.g. Buspiron, Mirtazapin, Sertralin
– No benefit
• Phenothiazine – e.g. Chlorpromazin, Promethazin oder Levomepromazin
– No benefit
Pharmacological treatment of dyspnea
Other drugs
• Inhaled Furosemid:
– Protective effect against bronchoconstrictionr*
– Reported benefit in review**
– In randomized trial: no benefit ***
• Corticosteroids: anecdotal benefit
– Lymphangitis carcinomatosa
– COPD
*Bianco S et al. Lancet 1988
**Booth S et al. Expert Reviews Resp Med 2009
***Wilcock A et al. Thorax 2008
Pharmacological treatment of dyspnea
Oxygen
• Dyspnea caused by hypoxemia: good response to oxygen (e.g.
COPD)*
• No difference between air and oxygen**
• Maybe placebo effect
• Cold air helps to reduce dyspnea
• Stimulation of N. trigeminus seems to have inhibitory effects
towards dyspnea ** *
• No benefit for oxygen****
• Sometimes „blind activism“ at the end of life*****
*Uronis HE et al. Thorax 2014
**Davis et al.Palliative care and rehabilitation of cancer patients
** * Liss HP et al. Am Rev Respir Dis 1988
*** * Cranston et al, Cochrane Database Syst Rev 2008
**** * Simon ST, Bausewein, 2009
Pharmacological treatment of dyspnea
Oxygen
• Individual attemt:
– 2l/min oxygen
– Titration
– Change to air after three days
– If benefit by oxygen continue
– If not, stop
Simon ST, Bausewein, 2009
Refractory dyspnea
• Dyspnea that can not be resolved after optimal treatment of the
underlying conditions is referred as refractory dyspnea
• *.
*S. T. Simon, V. Weingärtner, R. Voltz, C. Bausewein . Palliativmedizin, UIM 2/2013
Treatment of dyspnea Noninvasive ventilation
• Noninvasive ventilation is more efficient than oxygen and reduces
need for opioids in patients with advanced cancer
Nava S et al. Lancet Oncology 2013
• Patient K.J.
• 1974*, + 2014
• AML, KMT 2004
• Pleuroparenchymale
Fibroelastosis?
• Pulmonal cachexia
Dyspnea
Case report
Noninvasive ventilation, opioids and
benzodiazepines
Terminal dyspnea
• Shallow breathing, quick breathing
• Periods of apnoea
• Cheyne-Stokes-breathing
• Death rattle
Terminal dyspnea*
• Inform relatives about aspects of death rattle
• Low dose opioids and/or benzodiazepines
• Anticholinergic treatment
*JR Thomas and v Gunten C, Lancet Oncology 2002
Terminal dyspnea
• Anticholinergic treatment:
– Scopolamin 0.2-0.4mg s.c. every 4 h
– Or transdermal 1.5mg every 72 h
– oder 0.1-1 mg /h continous infusion
• Suctioning of mucus: often
counterproductive
Palliative Sedation
• If opioids are not enough to control symptoms
• Titration of benzodiazepines, neuroleptic
drugs until symptom control
Wein S, Oncology 2000
Beller EM et al. Palliative pharmacological sedation for terminally ill adults. Cochrane Database Syst Rev. 2015 Jan
Cherny NI et al. EAPC recommended framework for the use of palliative sedation. Palliative Medicine 23, 2009
Dyspnea in terminal heart failure
• Patient H. K.
• NYHA IV
• Several cycles of Simdax
• No HTX possible
• Terminal dyspnea, refractory to
opioids
• Treatment???
Sedierung in der Palliativmedizin - Leitlinie für den Einsatz sedierender Medikamente in der Palliativversorgung - European Association for Palliative Care (EAPC) Recommended Framework for the Use of Sedation in Palliative Care
übersetzt von B. Alt-Epping, T. Sitte, F. Nauck, L. Radbruch
Original von: Nathan I Cherny, Lukas Radbruch. EAPC recommended framework for the use of sedation in Palliative Care. Pall Med 2009; 23 (7): 581-593