Dr. Çiğdem Biber Atatürk Chest Disease and Chest Surgery Center APROACH TO PATIENT WITH LUNG CANCER AT THE END OF LIFE HOW TO MANAGE DYSPNEA AND PAIN
Jan 08, 2016
Dr. Çiğdem BiberAtatürk Chest Disease and Chest Surgery Center
APROACH TO PATIENTWITH LUNG CANCER AT THE END OF LIFE
HOW TO MANAGE DYSPNEA AND PAIN
Supporting patients, families and caregivers
Ensuring on-going support
Sustaining functions
Making critical treatment decisions with conviction
Extending survival
The symptoms that most benefit from the treatment at the end of life
Pain – Dyspnea – Depression Ann Intern Med. 2008; 148: 147 - 159
Supportive Treatment Plan
Pain related to cancerAffects 50% of patients at any given disease stage
Rate at the end of life: 75 – 97%
Causes of painNeoplastic disease: 60 – 70%
Treatment: 20 – 25%
Not associated with either disease or therapy: 5 – 10%
Based on pathophysiological characteristicsNociceptive: 50 – 70%
Neuropathic: 10 – 30%
Mixed: 20 – 40%
PAIN
Severe pain: 30%
Pain areasIn one area: 20%
In 2 – 4 areas: 60%
In more than 4 areas: 20 %
Ann Oncol 2008; 19: 5 - 7
PAIN
WHO - Three-Step Analgesic Ladder
Non-opioids±
Adjuvant drugs
Weak opioids ± Non-opioids
± Adjuvant drugs
Strong opioids± Non-opioids
± Adjuvant drugs
1- Mild pain
2- Moderate pain
3- Severe pain
90% success rate in pain management 10% inadequate pain control
Step 1 NSAİD ± Adjuvant therapyNon-steroid anti-inflamatory drugs
Acetaminophen, diclofenac, ibuprofen, Cox 2 inhibitors, naproxen
Adjuvant therapyAnti-depressants
Nortriptyline, Amitriptyline, doxsepine, desipramine, duloxetine, venlafaxine
AnticonvulsantsGabapentin, pregabalin, phenitoin, carbamazepin
Step 2 Weak opiods ± NSAİD ± Adjuvant therapyWeak opioids
Codeine, hydrocodeine, tramadol
Step 3 Strong opioids ± NSAİD ± Adjuvant TherapyStrong opioids
Morphine, oxycodone hydrocodone, hydromorphone, methadone, fentanyl
5% patients with pain refractory to treatment = Patients at the end of life
WHO - Three Step Analgesic Ladder
Pain intensity rating scalesNumerical rating scale
0 1 2 3 4 5 6 7 8 9 10 No pain Worst imaginable pain
Categorical scale
0 1 – 3 4 – 6 7 – 10 No pain Mild Moderate Severe
Wong – Baker Faces Pain Rating Scale
Pain treatments at the end of lifeUncontrollable pain treatment
Breakthrough pain treatment
Interventional strategies (4th step pain treatment ) NCCN 2007
Uncontrollable moderate and severe pains category 4–6 or 7–10
Patients in the 2nd or 3rd step of the Three-Step Analgesic Ladder treatment proposed by WHO
In patients who are at the end of life and continuing to experience moderate, severe or increasing pain despite receiving treatment, the first step is to treat
short-acting opioids
PAIN
OralPeak effect 60 min.
IVPeak effect 15 min.
Used opioids5 – 15 mg oral rapid releasing
morphine or equivalent
Not used opioids10 – 20% of the previous
24 h total dose
Not used opioids1 – 5 mg IV morphine
sulfate
Used opioidsIncrease previous total
dose by 10%
Pain> 4
Pain score unchanged or
increases
Pain score decreases
4 – 6
Pain scoredecreases
0 – 3
Pain score unchanged or
increases
Pain score decreases
4 – 6
Pain scoredecreases
0 – 3
- Administer double dose- If no response after 2 – 3 dosing cycles, proceed
with IV titration
- Repeat same dose - Reassess after 60
min.
- Repeat same dose- Reassess after 2 – 3 h
- After 24 h, proceed withlong-acting opioids
- Administer double dose- Monitor for 2-3 dosing
cycles
- Repeat same dose - Monitor
After monitoring for 2 – 3 h, determine
effective dose
Seen in 89% of the patients at the end of life
Usually develops in previous pain areas
Severe, sudden attacks
Reaches peak intensity in 5 minutes, ends in 30 minutes
Attacks occur more than 2 – 3 times a day at the end of life
Tumoral invasion of visceral organs or nerve roots
Ectopic activity of afferent nerves independent of stimulus
Bone metastasis
Tied to KT and RT
May occur with neuropathic pain
Breakthrough Pains
Primarily recommended treatment: WHO pain guidelines
The opioid rescue dose must always be considered in these patients
Other agents used in breakthrough pains
Lidokain - Meksiletin: Antiarithmic – local anesthetic
In dire cases, sc or iv infusion
Ketamine: NMDA receptor antagonist
Prevents opioid tolerance, effective against neuropathic pains
0.1 – 0.4 mg/kg/h iv or sc dose results in significant analgesia Anest Analg 2005; 101:175 – 181
J Pain Symptom manage 2000; 4: 256 – 251
Am J Hosp Palliat care 2007; 24: 430
Breakthrough Pains
Oral transmucosal fentanyl citrate Initial dose: 200 – 400 mcg
Titrated based on patient’s pain condition
Fentanyl buccal tabletRapid and effective palliation !!
Pain med 2005; 4: 305 – 14
J Pain 2006; 7:35
Breakthrough Pains
Inerventional Pain Strategies
Hemiarthroplasty – intramedullary stabilizationTheir effectiveness at the end of life is debatable – unnecessary
Radiotherapy and radioisotope therapiesAre being used with increasing frequency
Complete treatment with RT success rate: %30
Radioisotopes: radioactive agents administered through iv Active in multiple metastatic areas
Most frequently used two isotopes: Stronsium-89, Samarium-153
Easily administered and can reach all metastasized areas
Gives better results when combined with other treatment
Complete pain remission rate of 10 – 30%, decrease in opioid use
Breakthrough Pains
Interventional Pain Strategies
Spinal anesthesia
Intrathecal Neuraxial
Epidural AnalgesiaShould be administered in 5% of all cancer patients – but only done so in 2%
Epidural analgesia Focal pain
Less than 3 months’ life expectancy
Intrathecal analgesiaExtensive pain
Longer than 3 months’ life expectancy
Breakthrough Pains
VertebroplastyPerformed in pain attacks caused by vertebral fractures
Increases the quality of life in patients at the end of life
A filling substance containing percutan is injected in the problem vertebra
Prevents spinal cord compression caused by fracture
J Pain Symptom Manage 2005; 30: 87 – 95
Am J Hosp Palliat Care 2007; 24: 430 - 7
CordotomyPerformed in terminal patients when medical treatment and minimal invasive interventions fall short
Successfully performed in one-sided, localized pains Am J Hosp Palliat Care 2007; 24: 430 - 7
Breakthrough Pains
Awareness of breathing
Air hunger DYSPNEA
Breathlessness
Psychological factors
Social factors
Emotional factors
Environmental factors
Cultural factors
Dyspnea
As effective as physical factors
Rate dyspnea in cancer patients: 21 – 70%
Dyspnea early indication of shortened life expectancy
Life expectancy of patients coming emergency room with dyspnea: 12 weeks
Median time in lung cancer patients: 4 weeks
Cancer and Dyspnea
Most frequently seen
Primary or metastatic lung tumor load
Pleural or pericardial effusion
Lymphangitic carcinomatosis
Pulmonary emboli
VCSS
Depression – Anxiety
Pneumonia
Muscular dysfunction
Pre-existing KOAH – asthma combination
Anemia
Congestive heart failure
Pain
Reasons for Dyspnea Related to Cancer - 1
Related to treatment
Radiation pneumonia
Fibrosis related to chemotherapy
Surgical resection
Reasons for Dyspnea Related to Cancer - 2
Rarely seenAtelektasis
Phrenic nerve paralysis
Tracheal – bronchial obstruction
Tumoral invasion of the chest wall
Abdominal distension
Pneumothorax
Metabolic acidosis
Paraneoplastic syndromes
Reasons for Dyspnea Related to Cancer - 3
Treatment for the underlying disease causing dyspnea and its complications: Primary Treatment
Treatment for the symptom and the pathophysiologic factors that contribute to it
Dyspnea Treatment
Oxygen treatment
Pharmacologic treatments
General support approaches
Symptomatic Treatment of Dyspnea Related to Cancer
Most frequently performed medical support treatment at the end of life
Performed when cancerous tissue is widespread in the respiratory system and there is an underlying obstructive disease
Few studies are done on the benefits of oxygen support – Its effectiveness in treating dyspnea related to cancer is debatable
Semin Oncol Nurs 2008: 24: 57 – 67 Curr Treat Opt Oncol 2005; 6:61 - 8
Oxygen Treatment - 1
Conflicting opinions about its benefits in cancer patients
Some patient groups decrease in dyspnea perception, improvement in hypoxemia
Some patient groups no change
Some patients groups, there is a decrease in dyspnea perception but no improvement in hypoxemia (Placebo effect)
Chest 2007; 132: 368 – 403
Nature Clinical Practise Oncology 2008; 2: 90 - 100
Oxygen Treatment - 2
Supporting Viewpoint Prescribe if the oxygen treatment improves the hypoxemia parameters in patients with cancer
Opposing Viewpoint Prescribe not based on oxygen saturation, but on patient’s comfort level
Oxygen is a prominent symbol of medical treatment and care
Oxygen Treatment - 3
Breathing effort decreases
Alveolar ventilation improves
Helioks 28 (72% helium – 28% oxygen)Improvement in dyspnea during exerciseIncrease in exercise capacityImprovement in oxygen saturation
Nature Clinical Practise Oncology 2008; 2: 90 – 100 Br J Cancer 2004; 90: 366 - 71
Heliox
Central point of dyspnea treatment
Pharmaceutical treatment
Opioids
Adjuvant Treatments
Benzodiazepines
Phenothiazines
Pharmaceutical Treatment
Their effectiveness have been shown in randomised controlled studies done in dyspnea cases related
to both malign and non-malign lung cancer
Opioids
CONCLUSION
Oral or parental opioid use is vital and the first step in the treatment of dyspnea related to
cancer, especially in advanced cases
Opioids
What is the optimal dose in opioid treatment?
Patient history of prior opioid use is important
If opioid is currently being administered, increase dose by 25 – 50%
Opioids
Opioids
The initial principle in cases without prior opioid use for any reason, elderly patients and when seen together with COPD
‘’START LOW AND GO SLOW’’
Dyspnea treatment related to advanced diseaseFIRST STEP TREATMENT: Opioids and doses
Dose in patients with opioid tolerance: 25 – 50%
Patients without prior Opioid use or elderly patientsHydromorphone: 0.5 – 1 mg po every 4 hours mild
Oxycodone: 2.5 – 5 mg po every 4 hours dyspnea
Morphine sulfate: 2.5 – 5 mg po every 4 hours
To break dyspnea, 10 – 20% of total daily dose is given every hour, or dose is increased by 25 – 50% every 24 hours
May start with twice the total dose in young patients
Opioids
In patients who also have serious COPD and other chronic lung diseases, the dose is reduced by 50%
Opioids
Constipation, nausea
Most important side effects
Tolerance is developed against
all other side effects in 1 – 2 weeks
All patients should be treated simultaneously with effective intestinal diets and laxatives for constipation
Opioids
Can nebulized form be used?
Use of nebulized forms not recommendedRandom controlled studies still needed
Widely used today
Opioids
Nebulized opioid use
2.5 – 10 mg morphine, 0.25 – 1 mg hydromorphone
25 µg fentanyl
Given by adding 2 mL 09% NACL solution with nebulization
Opioids
Anxyolitics SECOND STEP TREATMENT
Neuroleptics No randomised controlled study showing their
effectiveness
Most widely used agent: ChlorpromazineUse in terminal cancer patients is highly emphasized
Chlorpromazine: 7.5 – 25 mg po or subcutan. Every 6 – 8 hours (when necessary or regularly)Methotrimeprazine: 2.5 – 10 mg po or subcutan. Every 6 – 8 hours (when necessary or regularly)Levomepromazine: 6 – 25 mg oral
Adjuvant Treatment: Neuroleptics
No meta-analysis or randomised controlled study showing their effectiveness against dyspnea related to cancer
Widely used for dyspnea caused by cancer
Adjuvant Treatment: Benzodiazepines
Occurs in patients with dyspnea Dyspnea
Anxiety
Even though opioids by themselves break the relation between dyspnea and anxiety, tolerance is quickly developed against anxyolitic effects
They are not the primary option in dyspnea treatment
Anxyolitics
Anxyolitic treatment in dyspneaLorazepam: 0.5 – 1 mg po every 6 – 8 hours Most widely used agent
Diazepam: 5 – 10 mg po every 6 – 8 hours
Clonazepam: 0.25 – 2 mg po every 12 hours
MidazolamEffective when added to opioids at the end of life
With sc infusion 10 – 60 mg/24 hours
Breaks opioid tolerance
Anxyolitics
Lymphangitic carcinomatosisRadiation pneumonia – fibrosisVCSSBOOP developed post-Adjuvant RT COPD – presence of inflammatory component such as asthma
Has negative functional and pathological effects on certain muscle groups starting with the diaphragm
Corticosteroids
Stimulating mecanoreceptors – decrease in the skin surface temperature
Trigeminal nerve is stimulated
Central inhibition
Reduction in dyspnea perception
Fans
Patient is immediately and aggressively treated with parenteral opioids and
sedatives until breathing comfortably
Approach to Terminal Dyspnea
Doctor should attend the patient at all times
Opioids must always be parenterally given2.5 – 5 mg morphine iv or sc is immediately administered to patients without opioid use history. The dose is increased to 50 – 100% right away in patients with opinoid tolerance
Reassessment every 10 minutes if iv is given, and every 20 minutes if sc is given
Parenteral opioid dose is increased by 25% every 10 or 20 minutes until dypsnea starts to improve
In addition to opioids, 2.5 – 10 mg methotrimeprazine can be sc administered immediately
Approach to Terminal Dyspnea
If the patient has severe anxiety or agitation Midazolam 2.5 – 5 mg is iv or sc given and patient is monitored
Lorazepam 0.5 – 1 mg is iv or sc given and patient is monitored
Must be extremely cautious when giving anxyolitics to the patient Risk of death
Opioids alone are not adequate and reliable for sedation
Approach to Terminal Dyspnea
Thank You