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