Palliative Medicine & Oncology
Faculty of Medicine
Cairo University
(( Notes for Undergraduates ))
Table of Contents
Introduction to cell Biology ............................................................................................ 1
Cell reproduction:.............................................................................................................. 1
Phases of the cell cycle...................................................................................................... 1
Radiation damage to DNA ................................................................................................ 3
DNA Strand Breaks........................................................................................................... 3
Double strand breaks: ........................................................................................................ 3
DNA repair........................................................................................................................ 3
Basis of cancer and its systemic therapy ....................................................................... 4
What is Cancer .................................................................................................................. 4
Staging and early detection of cancer ................................................................................ 4
Aim and intent of cancer therapy: ..................................................................................... 5
Basics of multidisciplinary management of cancer ........................................................... 5
Systemic therapy for cancer ........................................................................................... 5
Chemotherapy ................................................................................................................... 6
Mechanisms of actions of Chemotherapeutic agents: ....................................................... 7
Targeted therapy ............................................................................................................... 8
Immunotherapy ................................................................................................................. 9
Endocrine therapy ............................................................................................................. 9
Adverse effects of cancer systemic therapy .................................................................... 10
Management of main problems caused by cancer disease itself and/ or
CancerTherapy ...................................................................................................... 11
Cytopenias...................................................................................................................... 12
1-Anemia ........................................................................................................................ 12
2- Thrombocytopenia...................................................................................................... 12
3.
Leutropenia .............................................................................................................. 13
Afebrile patients .............................................................................................................. 13
Febrile neutropenia.......................................................................................................... 13
Gastrointestinal Effects................................................................................................. 14
1- Anorexia ..................................................................................................................... 14
2- Diarrhea.................................................................................................................... 15
3- Mouth lesions ........................................................................................................... 16
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4- Nausea and vomiting ................................................................................................ 17
5- Constipation. ............................................................................................................ 18
6. Hypercalcemia............................................................................................................. 22
7. Dyspnea ....................................................................................................................... 23
8.
Fatigue...................................................................................................................... 24
9.
Delirium ................................................................................................................... 25
Basis of Radiation oncology .......................................................................................... 26
Aim of radiation therapy: ................................................................................................ 26
Biologic basis for Radiation therapy ............................................................................... 26
Indications of radiation therapy: ..................................................................................... 26
Side effects of radiotherapy: ........................................................................................... 27
Ionizing Radiations ......................................................................................................... 27
The types of radiation commonly used clinically ............................................................ 28
Radiotherapy techniques: ............................................................................................. 28
External beam radiotherapy: Which include: .................................................................. 28
Types of Internal Radiation Therapy: ............................................................................. 30
Pain Management: Basic Principles ............................................................................ 30
DEFINITIONS ................................................................................................................ 30
Classification of Pain ...................................................................................................... 31
Assessment of Pain .................................................................................................... 33
Essential elements of Pain History –Basics ................................................................. 34
Adult Scales .................................................................................................................... 37
Principles of Pharmacotherapy .................................................................................. 39
Nonopioid Analgesics ..................................................................................................... 40
Weak Opioid Analgesics................................................................................................. 41
Strong Opioid Analgesics................................................................................................ 42
Management of Adverse Effects of Opioids ................................................................ 45
Opioid Rotation ............................................................................................................. 47
Co-analgesics ................................................................................................................. 47
Non pharmacologic Managementof pain .................................................................... 50
1. Nerve blocks and neuro-destructive procedures: ........................................................ 50
2.
Radiotherapy ............................................................................................................ 50
3. Surgery ........................................................................................................................ 51
4. Transcutaneous electrical nerve stimulation (TENS) .................................................. 51
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5. Physiotherapy .............................................................................................................. 51
6. Occupational therapy................................................................................................... 51
7. Cognitive behavioural therapy and behaviour therapy ................................................ 51
Introducing Palliative Care .......................................................................................... 52
Definitions....................................................................................................................... 52
Integration of palliative care into the care of life-threatening illness .............................. 52
Dimensions of palliative care .......................................................................................... 53
Models and levels of palliative care delivery ............................................................... 53
Assessment in Palliative Care ...................................................................................... 54
Assessment of Performance Status ............................................................................... 54
Assessment of quality-of-life ....................................................................................... 54
Assessment of prognosis ................................................................................................ 55
End-of-Life Care ........................................................................................................... 56
Identifying the Dying Phase ............................................................................................ 56
Goals of End-of-Life Care .............................................................................................. 56
Management .................................................................................................................. 56
Communication ............................................................................................................. 58
Breaking Bad News......................................................................................................... 58
Ethical and Legal Issues ............................................................................................... 59
Euthanasia and Physician-Assisted Suicide .................................................................... 59
Non-treatment decisions (NTD) are not euthanasia ....................................................... 59
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Introduction to cell Biology
Cell reproduction:
Cells must reproduce else they die. The "life of a cell" is termed the cell cycle. Thecell cycle
has distinct phases, which are called G1, S, G2, and M.
Cells that have temporarily or reversibly stopped dividing are said to have entered astate of
quiescence called G0 phase.
Phases of the cell cycle
Interphase
Interphase was once referred to as the “resting phase” of the cell cycle; we now
knowthis statement is incorrect. During interphase the cell is busy. The cell
grows in size, new organelles are made, and the DNA of the chromosomes are
copied in preparationfor mitosis and cytokinesis. Interphase is subdivided into
3 phases: G1, S, and G2.
Stages of Interphase:
G1 phase
During the (G1) phase, the cell grows larger and the number of organelles increases.
S phase or synthesis phase
During S phase, the cell replicates its DNA. DNA replication only occurs if the cell is
programed to proceed beyond G1. At this point the cell possesses twice as much DNAas it
normally does and will need to divide. This video from the DNA Learning Centerexplains
the process.
G2 phase
After more growth occurs in the (G2) phase, the cell is ready to divide and entersmitosis.
The G0 Phase of the Cell Cycle
Most cells that differentiate will do so during this phase.
Cells arrested in G1 may no longer have the capability of reproducing and aresaid to be in
G0.
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Certain cells in G0, however, when given some external or internal cues mayrevert back to
G1 and enter the cell cycle again.
Nerve and muscle cells are usually arrested in G0.
These cells are considered very resistant to X-rays and gamma rays
What Controls the Cell Cycle?
How do cells know when to divide?
Through cell communication signals
chemical signals in cytoplasm give cue
Signals mean proteins which may be either activators or inhibitors.
Frequency of cell division varies by cell type
−Embryo, cell cycle < 20 minute
−skin cells, divide frequently throughout life 12-24 hours cycle
−liver cells, retain ability to divide, but keep it in reserve divide once every year or two
−mature nerve cells & muscle cells, do not divide at all after maturity, permanently in G0
Mutations in cells can be triggered by:
− UV radiation
− chemical exposure
− radiation exposure
− heat
− cigarette smoke
− pollution
− age
− genetics
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Radiation damage to DNA
DNA Strand Breaks
1) Single strand breaks:
Can take place at the phosphodiester bond, or at the bond between the base and the
sugar.
A large proportion of the single strand breaks are caused by hydroxyl radicals (OH•).
2) Double strand breaks:
Involves breakage of both strands at points less than 3 nucleotides apart.
Production by single particle crossing both strands?
Production by two independent events?
Can be measured by various techniques (e.g., sucrose gradient centrifugation)
Double strand breaks have shown a direct proportionality to radiation dose.
X-ray dose of ~1 Gy produces about 1000 single strand breaks and about 50-100 double
strand breaks in a typical mammalian cell. This dose causes about 50% cell death.
DSBs are not necessarily lethal.
DNA repair
Repair of damage to DNA is of central importance to all cells, and is an ongoing process.
Existing repair mechanisms eliminate most radiation-induced lesions.
• Restores viability
• But viable cells may still harbor mutations or chromosomal aberrations
Distinguish repair as
• Error-free: restores DNA to its original state
• Misrepair: non-lethal errors are incorporated and passed on to daughter cells. This
could lead to genomic instability and carcinogenesis.
DNA repair is governed by a multitude of genes, and executed by DNA repair enzymes.
Mutants deficient in DNA repair genes have helped elucidate these complex systems and
their control
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Basis of cancer and its systemic therapy
What is Cancer
•
A tumor is an uncontrolled growth in a specific cell type.
•
A malignant tumor (cancer) is an uncontrolled cell growth that acquired many
potentials suchas angiogenesis, immortality, invasiveness, and metastatic potentials.
Staging and early detection of cancer
•
Many staging systems are used to classify cancer into several stages which is important for
prognosis and to guide the treatment strategy.
•
The most commonly used system is the TNM staging system. There is a specific TNM
staging criteria for each type of cancer. However, as a general rule the following applies:
T stands for Tumor stage (T1, T2, T3 or T4) where T1 is the earliest stage
(smallest tumor) and T4 is the most locally advanced stage.
N stand for Nodal stage (N0, N1, N2, or N3) where N0 represents no spread to LNs,
N1is the earliest or minimal spread and N3 is the most advanced nodal spread.
M stands for Metastatic stage (M0 or M1) where M0 represents no distant
metastatic spread and M1 represents distant metastatic spread (also commonly
named stage IV disease).
•
A simpler stage grouping system classifies cancer into 3 stage groups:
Local: where cancer is localized into the organ of origin
Regional: where cancer has spread to the regional LNs or nearby structures.
Distant: Where cancer has spread to distant organs.
•
Early detection of cancers
One of the most important factors for cancer prognosis is the stage in which cancer
is discovered. This means that early detection of most cancers can improve the
cure rates.
Paying attention to any persistent symptom or sign that is progressive and doesn’t respond
to routine treatment can help in early detection of many cancers (e.g., persistent
progressive cough or chest symptoms could indicate lung cancer).
Examples of successful strategies of early detection include:
1. Regular annual Mammography or breast examination for early detection of breast cancer.
2. Pap smear for early detection of cervical cancer.
3. Abdominal ultrasound screening for hepatocellular carcinoma in cirrhotic patients.
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4.
Low dose CT chest for chronic heavy smokers to detect early lung cancer.
Aim and intent of cancer therapy:
•
Radical:
This is the main strategy of therapy used aiming to cure cancer (The commonest is surgery as in
breast cancers and sarcomas, etc… but radiation can also be gives as a radical treatment in head
and neck cancers and chemotherapy can be used to cure hematological malignancies.
•
Adjuvant (after surgery):
In patients at relatively high risk for recurrence after surgery, another line of treatment
may begiven to decrease the risk of recurrence.
• Neoadjuvant (before surgery):
In patients with large or locally advanced cancers, a line of treatment may be used to reduce the
sizeof the tumor before surgery
• Palliative:
In metastatic patients, treatment is given to relieve cancer related symptoms and improve survival.
Basics of multidisciplinary management of cancer
•
Cancer is a complex disease that always needs several specialties to complete adequate
treatment. Using one treatment strategy (e.g., surgical resection alone) is not sufficient to
cure most cancer patients.
•
Therefore, cancer is best treated in the setting of a multi-disciplinary team (MDT) or a
tumor board where physicians from different specialties meet and discuss what is the best
treatment plan or strategy for each patient.
•
A typical MDT should include a surgical oncologist, a medical oncologist, a radiation
oncologist, a radiologist, and a pathologist. Additional specialties like a nutritionist, a
molecular biologist, a psychiatrist, and a social worker might also be needed.
Systemic therapy for cancer
•
Definition and rationale:
Systemic therapy refers to any type of cancer treatment that targets the entire body
and circulates throughout the blood stream to destroy cancerous cells in multiple
locations.
Once the medications enter the blood stream, they disperse and destroy abnormal cells in
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various locations. As a result, systemic therapy is often used to treat cancers that have spread
to distant sites (metastatic).
−Usually, a combination of several systemic treatment options may be combined to
ensure all malignant cells are destroyed.
•
1.
2.
3.
4.
Types of systemic therapies include:
Chemotherapy
Hormone therapies
Immunotherapies
Targeted therapies
Chemotherapy
•
The goal of cancer therapy is to achieve a cure or at least remission.
•
Cytotoxic Chemotherapy is the most common and oldest form of systemic cancer
treatment. It can be administered through different methods: intravenous infusions, IV
shot or oral as pills.
•
Although chemotherapy can impact cancerous and noncancerous cells throughout the
entire body, it usually causes more damage to cancer cells, hence the concept of the
therapeutic ratio.
•
Chemotherapy is most effective in treatment of rapidly dividing cells. The most chemosensitive cancers are: Leukemias, Lymphomas, Germ cell tumors, and to lesser extent
breast and ovarian cancers.
I. Types of Cytotoxic drugs:
•
•
•
•
Alkylating agents
Anti-metabolites
Natural products/Plant alkaloids
Antitumor Antibiotic
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Mechanisms of actions of Chemotherapeutic agents:
1.
Alkylating Agents:
a.
Transfer of alkyl groups to various cellular constituents. Alkylation of DNA within the
nucleus probably represents the major interaction leading to cell death.
Member examples:
Cyclophosphamide
Chlorambucil
Platinum compounds: cisplatin, carboplatin, oxaliplatin
b.
•
•
•
2.
Antimetabolites
a. Antifolates: methotrexate
• Inhibit/antagonize folic acid metabolism
b. Fluoropyrimidines: fluorouracil, capecitabine
• Inhibition of DNA synthesis
c. Purine Antagonists: Fludarabine
• inhibits several enzymes of de novo purine nucleotide synthesis
3. Natural Product Cancer Chemotherapy Drugs
d. Vinca Alkaloids
•
inhibit the process of tubulin polymerization, which disrupts assembly of
microtubules, especially those involved in the mitotic spindle apparatus inhibition of
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cell division  cell death.
e. Taxanes: pactitaxel
• high-affinity binding to microtubules with enhancement of tubulin
polymerization
f. Epipodophyllotoxins: Etoposide
• forms a complex with topoisomerase II, the enzyme responsible for cutting
religating double stranded DNA, and DNA, leading to inhibition of DNA synthesis and
function
g. Camptothecins: Irinotecan and topotecan
• inhibit the activity of topoisomerase I, the key enzyme responsible for cutting and religating single DNA strands. Inhibition of this enzyme results in DNA damage
• Antibiotic chemotherapy:
h. Anthracyclines:
• inhibition of topoisomerase II
• generation of free radicals and oxygen free radicals
• high-affinity binding to DNA through intercalation,  blockade of the synthesis of
DNA and RNA
• binding to cellular membranes to alter fluidity and ion transport
i. Mitomycin
• DNA alkylation
j. Bleomycin
• binding to DNA, which results in single and double-strand breaks followingfree
radical formation, and inhibition of DNA biosynthesis
Targeted therapy
•
Targeted therapy is a type of cancer treatment that targets proteins that control how
cancer cells grow, divide, and spread while sparing healthy normal cells. This makes
targeted therapies generally less toxic than conventional chemotherapy.
•
-
Most targeted therapies are either small-molecule drugs or monoclonal antibodies.
Small-molecule drugs are small enough to enter cells easily, so they are used for targets
that are inside cells.
Monoclonal antibodies, also known as therapeutic antibodies, are proteins produced in the
lab. These proteins are designed to attach to specific targets found on cancer cells. Some
-
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monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by
the immune system. Other monoclonal antibodies directly stop cancer cells from growing
or cause them to self-destruct. Still others carry toxins to cancer cells.
• Biomarker testing is a way to look for genes, proteins, and other substances
(called biomarkers or tumor markers) that can provide information about cancer.
Each person’s cancer has a unique pattern of biomarkers. Biomarker tests can help
physician select a cancer treatment for patient. Some cancer treatments, including
targeted therapies and immunotherapies, may only work for people whose cancers
have certain biomarkers. For example, people with cancer that has certain genetic
changes in
the EGFR gene can get treatments that target those changes, called EGFR inhibitors.
• Cancer cells can become resistant to targeted therapy. For this reason, they may
work best when used with other types of targeted therapy or with other cancer
treatments, such as chemotherapy and radiation.
Immunotherapy
•
The immune system detects and destroys abnormal cells and most likely prevents or curbs
the growth of many cancers. Cancer cells have ways to avoid destruction by the immune
system For example, cancer cells may:
- Have genetic changes that make them less visible to the immune system.
- Have proteins on their surface that turn off immune cells.
- Change the normal cells around the tumor so they interfere with how the
immune system responds to the cancer cells.
• Immunotherapies are a group of drugs that aim at activating the patient’s immune
system to fight cancer
•
They include immune checkpoint inhibitors (That stops the cancer-induced
immunosuppressive signals), cancer vaccines, cytokine therapies (like interferons and
interleukins).
Endocrine therapy
Some cancers depend on hormones to grow. Because of this, treatments that block or
alter hormones can sometimes help slow or stop the growth of these cancers. Treating
cancer with hormones is called hormonal therapy, or endocrine therapy. Hormone
therapy is mostly used to treat certain kinds of breast cancer and prostate cancer that
depend on sex hormones to grow. A few other cancers can be treated with hormone
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therapy, too.
•
1) Glucocorticoids
Are used in combination with cytotoxic agents in treating of lymphomas, myeloma
and to induce a remission in acute lymphoblastic leukemia.
• Glucocorticoids are also helpful in reducing oedema around a tumor.
• They have antiemetic activity too.
• Hydrocortisone, Prednisone, Dexamethasone, Prednisolone.
2) Female sex hormones
• Progestins suppress endometrial cancer cells (e.g. Medroxyprogesterone.).
3) Hormone antagonists
• Estrogen antagonists (e.g. Tamoxifen - p.o.) suppress breast cancer cells. It
binds competitively to estrogen receptors
• Aromatase inhibitors are used in postmenopausal women with advanced breast
carcinoma. They inhibit the production of estrogen inside the body
• Androgen antagonists suppress prostate cancer cells e.g. cyproterone & flutamide
4) Thyroid hormones
Stop the growth of thyroid tumors after surgery or radiation therapy for thyroid cancer.
Adverse effects of cancer systemic therapy
•
•
•
Side effects result from lysis of normal cells, and they vary according to the type of
drug, the dose, the route of administration and individual response.
Rapidly dividing cells are more affected i.e. bone marrow cells, digestive tract, hair
follicles and reproductive tract cells.
Adverse effects of cancer systemic therapy may be classified according to
their time of occurrence as follows:
Immediate adverse effects:
Occur during or within thirty minutes of administration, the most common include:
•
Local site reactions e.g. Local irritation, thrombophlebitis, extravasation into
surrounding subcutaneous tissues (with subsequent ulceration).
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•
•


Flushing.
Hypotension.
Hypersensitivity.
Anaphylaxis.
Short term adverse effects:
Occur within hours to days of treatment administration, e.g.:
Gastrointestinal side effects e.g. Mucositis, Nausea and vomiting, Anorexia,
Constipation or diarrhea.
Hematopoietic side effects….Myelosuppression i.e. Neutropenia,
Anemia and thrombocytopenia.
Tumor lysis syndrome….It occurs when cancer treatments cause the destruction (or
lysis) of a large number of rapidly dividing cancer cells, overwhelming the body’s
ability to excrete the end products of cell death.
Medium to long term adverse effects:
Occur later than seven days of treatment administration and may be cumulative, e.g.:
o
o
o
o
o
o
o
o
Alopecia
Liver dysfunction
Nephrotoxicity
Cardiac toxicity
Neurological toxicity e.g. Peripheral neuropathy
Pulmonary toxicity e.g. pulmonary Fibrosis
Gonadal damage (may induce Infertility)
Second malignancies.
Management of main problems caused by cancer disease itself and/ or
CancerTherapy
Adverse effects are common in patients receiving any cancer therapy. Successfully
managing these adverse effects is important because it improves quality of life.
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Cytopenias
−
Cytopenias are common in patients with cancer due to a direct effect of the cancer
(especially in blood and bone marrow cancers such as leukemias, lymphomas, and
multiplemyeloma) and from effects of cancer therapy, especially conventional cancer
(chemotherapy) drugs.
1-Anemia
•
Anemia remain as one of the serious and frequent problem of cancer mainly cancer of
the gastrointestinal, liver, head and neck, ovarian ,cervix and leukemia.
• This is mainly caused by cytokines produced by these cancer diseases. These
cytokines caused impairment of erythropoietin (EPO) synthesis, reduce erythrocytes
life span and prevent normal iron utilization.
• Other direct effect of tumor that cause anemia is bone marrow replacement which
is associated with inhibition of the body ability for the production of RBC.
• As the common side effect of chemotherapy especially with the
myelosuppressive type.
− The treatment of anemia will include red blood cell transfusion, corticosteroids, VitB
12 and Epoetin alfa (recombinant human erythropoietin, rHuEPO).
2- Thrombocytopenia
The main causes leading to occurrence of thrombocytopenia are:
• Chemotherapy drugs.
• Solid cancer, Blood cancer (Leukemia), Spleen cancer.
• Hemorrhage which will lead to increases loss of platelets.
Grades of thrombocytopenia
The normal range of the platelets is between 150,000 and 450,000 cells per
microliter of blood (i.e., 150-450×109/ L) while thrombocytopenia could be
classified into three levels asfollows:
• Mild thrombocytopenia if platelets count < 150 and ≥ 100 × 109/ L.
• Moderate thrombocytopenia if platelets count < 100 and ≥ 50 × 109/ L.
• Severe thrombocytopenia if platelets count < 20 × 109/ L.
Options for thrombocytopenia treatments
The selection for thrombocytopenia treatment will mainly depends on the etiology and
severity of thrombocytopenia.
•
If thrombocytopenia incidence is because of spleen enlargement then
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splenectomy will be beneficial.
• if the cause is due to chemotherapy then the decision to either continue the
treatment with low chemotherapy doses or use of alternative drugs or use of
platelets growth factors (i.e., thrombopoietic growth factor) which stimulate
megakaryocytes to produceplatelets should be made.
• In the case of severe thrombocytopenia< 20,000/microL platelet transfusions is
needed but there are some limitations to its use which are: the availability of the
blood products since it must be freshly taken and used within 5 days, cost,
transfusion reaction and diseases transmission
3. Leutropenia
-
A decreased granulocyte concentration is common in patients with cancer.
A granulocyte concentration < 500/microL (0.5 × 109/L) markedly
increases the risk of infection.
- Measures to protect against infection, including hand washing and protective
isolation, are important.
- Oral non-absorbable antibiotics are sometimes given prophylactically.
When a prolonged interval of low granulocytes is anticipated, prophylactic
antifungal and antiviral drugs are sometimes given.
Afebrile patients
-
with neutropenia require close outpatient follow-up for detection of fever and
should be instructed to avoid contact with sick people or areas frequented by
large numbers of people(eg, shopping malls, airports).
- Although most patients do not require antibiotics, patients with severe
immunosuppression are sometimes given trimethoprim/sulfa methoxazole
(one double-strength tablet/day) as prophylaxis for Pneumocystis jirovecii.
− In transplant patients or others receiving high-dose chemotherapy, antiviral
prophylaxis (acyclovir 800 mg orally twice a day or 400 mg IV every 12 hours)
should be considered if serologic tests are positive for herpes simplex virus.
Febrile neutropenia
− Fever> 38.5° C on two or more occasions in a patient with neutropenia is a medical
emergency.
− An extensive evaluation for potential infection sources should be made and include immediate
chest x-ray and cultures of blood, sputum, urine, stool, and any suspect skin lesions. Examination
includes possible abscess sites (eg, skin, ears, sinuses, perirectal area), skin and mucosa for presence
of herpetic lesions….
− Typically, systemic broad-spectrum antibiotics are given before culture results are known and
therapy modified as needed. Typical regimens include cefepime or ceftazidime 2 g IV every 8 hours
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immediately after samples for culture are obtained. If diffuse pulmonary infiltrates are present,
sputum should be tested for P. jirovecii, and if positive, appropriate therapy should be started.
− If fever resolves within 72 hours after starting empiric antibiotics, they are continued until the
neutrophil count is > 500/microL.
− If fever continues, antifungal drugs should be added and sometimes antiviral drugs.
Reassessment for infection, often including CT of the chest and abdomen, is done.
− Granulocyte concentrations can be increased by giving molecularly cloned myeloid growth
factors such as granulocyte (G) or granulocyte/macrophage (GM) colony stimulating factors
(CSFs) such as filgrastim, sargramostim, and peg-filgrastim.
− To shorten the duration of neutropenia. G-CSF 5 mcg/kg subcutaneously once/day up to
14 days and longer-acting forms (eg, pegfilgrastim 6 mg subcutaneously single dose once
per chemotherapy cycle) may be used to accelerate WBC recovery.
− These drugs are begun at the onset of fever or sepsis or, in afebrile high-risk patients, when
neutrophil count falls to < 500/microL.
Gastrointestinal Effects
Gastrointestinal adverse effects are common in patients with cancer. These effects may be
caused by the cancer itself, cancer therapy, or both.
1- Anorexia
− Anorexia is the loss or absence of appetite leading to reduced caloric intake resulting in
loss of weight and fat tissue. Loss of more than 10% of ideal body weight predicts an
adverse prognosis.
Causes :
− Primary
1.
2.
3.
4.
5.
6.
Metabolic disturbances: dehydration, uremia, hypokalemia, …
Inflammatory processes: infection, cachexia, …
Neuro-hormonal: gastric stasis, …
Co-morbid conditions: COPD, CHF, diabetes, …
Neurological disorders: cerebral tumors, autonomic failure, …
Structural/functional abnormalities: GI obstruction, dysphagia, …
− Secondary
Uncontrolled symptoms: pain, dyspnea, nausea/vomiting, xerostomia, …
1. General: advanced age, inactivity, depression, dementia, ….
2. Iatrogenic: many medications belonging to antibiotics (erythromycin, …),
anticonvulsants (valproic acid, …), antidepressants (citalopram, …), antipsychotics
(haloperidol, …), diuretics (furosemide, …), opioids (tramadol, …)
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− Management
Treatment of underlying causes (examples)
− Dysphagia due to oral moniliasis: antifungal.
− Nausea & vomiting: antiemetic.
− Gastro paresis: metoclopramide.
− Uncontrolled symptoms: optimize symptom management.
• Symptomatic management:
Non-pharmacological
− Exercise, Dietary interventions.
− Efforts should be made to maintain reasonable nutrition. Sometimes partial or total
parenteral nutrition (TPN) is needed.
− Patients with surgical interruption of the gastrointestinal tract may need a
feeding gastrostomy.
• Pharmacological
- Corticosteroids: for short-term appetite stimulation, unless contraindicated.
- Megestrol acetate.
- Androgenic steroids
2-Diarrhea
− Diarrhea is defined as the frequent passage of loose stools(more than three unformed stools in
24 hours) with urgency .
− Causes:
• Several types of malignant tumors like Gastroentero-pancreatic and lung
neuroendocrine tumors(NETs) and colo-rectal cancer are the most frequent
diarrhea-associated tumors(20% of the cases).
• Diarrhea is a common side effect of many chemotherapy agents, targeted therapy and
immunotherapy drugs,
• Radiation therapy, especially if the abdomen and/or pelvis is included in the radiation
field.
• Surgery: resection of part of the digestive tract.
• Others, Clostridium difficile diarrhea, Enteral feeding (Tube feeding, either by
nasogastric tube, gastrostomy or jejunostomy), Coeliac plexus block.
− Management of chemotherapy -related diarrhea
•
Patients with grade 1 or 2 diarrhea:
Oral hydration
Dietary modifications (e.g. eliminating all lactose-containing products and high-osmolar
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dietary supplements)
Loperamide should be started at an initial dose of 4mg followed by 2mg every 4 hours or
after every unformed stool(not to exceed 16mg/day) .
•
Patients with high grade diarrhea
Hospital admission and involves i.v. fluids;
Octreotide at a starting dose of 100–150 mg s.c. three times a day (tid) or i.v.
(2550mg/h) if the patient is severely dehydrated, with dose escalation up to 500mg s.c.
tid until diarrhoea is controlled
Administration of antibiotics (e.g. fluoroquinolone).
These patients should be evaluated with complete blood count, electrolyte profile and a
stool work-up evaluating for blood, Clostridium diff icile, Salmonella, Escherichia coli,
Campylobacter and infectious colitis
3-Mouth lesions
− Causes
− Such as inflammation and ulcers are common in patients receiving chemotherapy drugs
and/or radiation therapy.
Ulcers can cause pain and preclude sufficient oral intake, leading to under nutrition and
weight loss.
Management
− Rinses with analgesics and topical anesthetics (2% viscous lidocaine 5 to 10 mL every 2
hours) before meals.
− A bland diet without citrus food or juices, and avoidance of temperature extremes may
allow patients to eat and maintain weight. If not, a feeding tube may be helpful if the
small intestine is functional.
For severe mucositis and diarrhea or an abnormally functioning intestine, parenteral
alimentation may be needed.
− Sometimes these lesions are complicated by infection, often with Candida albicans.
Candidiasis is usually treated with nystatin oral suspension 5 to 10 mL 4 times a day or
fluconazole 100 mg orally once/day.
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4- Nausea and vomiting
• Nausea: is the unpleasant subjective sensation of being about to vomit. It may occur in
isolation or in conjunction with other gastrointestinal symptoms.
• Vomiting: is the forceful expulsion of the gastric contents through the mouth or nose.
Nausea and vomiting are common in patients with cancer whether or not they are receiving
cancer therapy and decrease quality of life.
− Causes
• Chemical: drugs, metabolic and toxins.
• Impaired gastric emptying: drugs, ascites and hepatomegaly.
• Visceral / serosal: bowel obstruction, severe constipation, liver capsule stretch, …
• Cranial: raised intracranial pressure, meningeal infiltration, …
• Vestibular: drugs, motion sickness, …
• Cortical: anxiety, pain.
− Types of Nausea and vomiting induced by anti-cancer agents:
• Acute: starts minutes to hours from anti-cancer agent administration and lasts less than 24
hours.
• Delayed: starts after > 24 hours and can last for days; with cisplatin it starts after 2-3 days
and lasts for 6-7 days
• Anticipatory: occurs even before the dose because of a previous sever vomiting experience;
more common in younger patients
• Breakthrough: occurs in spite of prophylactic anti-emesis and requires rescue therapy
• Refractory: occurs in spite of prophylactic and rescue therapy
Management
• Prevention (examples)
− Anticipatory prescription of antiemetics for patients receiving chemotherapy.
− Prescribing laxatives to prevent constipation in patients receiving opioids.
• Treatment of underlying causes (examples)
− Hypercalcemia: hydration and bisphosphonates.
− Cerebral metastases: corticosteroids ± radiotherapy.
− Malignant ascites: tapping of ascites.
− Medications: discontinue / switch to an alternative if possible.
• Symptomatic management
• Non-pharmacological
Near the end-of-life, families frequently force patients to eat and drink which may cause
nausea/vomiting. Education is important in this situation and include:
17
The deterioration in patients’ condition is principally due to the progression of cancer.
− Forcing patients to eat at this stage doesn’t improve their quality of life of prolong survival
and may cause physical and psychological distress.
− Avoid spicy, fatty and salty foods or ones with strong odour.
− Depend on fluids and semi-solid food.
− East small frequent meals
• Pharmacological
− Several drugs are effective in controlling and/or preventing nausea and vomiting:
− Serotonin-receptor antagonists are the most effective drugs but are also the most
expensive. A 0.15-mg/kg dose of ondansetron ( Zofran) before chemotherapy. Doses of
ondansetron can be repeated 4 and 8 hours after the first dose.
− The efficacy against highly emetogenic drugs can be improved with coadministration of
dexamethasone 8 mg IV given 30 minutes before chemotherapy with repeat doses of 4 mg
IV every 8 hours.
− Other traditional antiemetics, including metoclopramide ( primpran) 10 mg orally or IV
given 30 minutes before chemotherapy with repeated doses every 6 to 8 hours, is alternative
restricted to patients with mild to moderate nausea and vomiting.
5-Constipation.
Constipation is defined as “the slow movement of faeces through the large intestine,
resulting in infrequent bowel movements and the passage of dry, hard stools”.
• Prevalence of constipation in cancer patients;
− A total of 43% to 58% of patients with cancer report constipation.
− It is the third most common symptom (after pain and anorexia) in those with advanced
disease.
− In terminally ill patients, bowel dysfunction may occur in ≥ 80% of patients and in 90%
of patients taking opioids.
Causes:
Usually multifactorial in advanced cancer.
1. Organic factors:
− Metabolic: dehydration, hypercalcemia, hypokalemia, …
− Neuromuscular: myopathy.
− Neurological: autonomic dysfunction, spinal cord involvement, …
− Structural: pelvic mass, peritoneal carcinomatosis, …
− Pain: cancer pain, anorectal pain (anal fissure, hemorrhoids), …
18
2. Functional factors:
− Diet: anorexia, poor food and fluid intake, …
− Environment: lack of privacy, need for assistance during toileting, …
− Other: inactivity, age, depression, sedation…
3. Drugs that are implicated in the development of constipation:
• cancer chemotherapy: alkylating agents like cisplatin and cyclophosphamide due to
their effect on the nerve ending in the gut
• opioid analgesics
• 5HT3 antagonists e.g ondansetron
• drugs with anticholinergic load
• Anti-depressants: MAO inhibitors and tricyclic antidepressants
• Anti-psychotics
• Anti-convulsant e.g. carbamazepine
• Concurrently administrated Antihypertensives: Ca channel blockers or diuretics
Management
1- Prevention
• Non pharmacological management :
− Ensuring privacy and comfort.
− Increased fluid intake.
− Increase dietary fiber intake (with adequate fluid intake and mobility).
− Encourage activity within patient limits.
− Attempts at defecating 30 - 60 minutes following a meal to take advantage of the gastrocolic reflex.
• Pharmacological
− Treatment of underlying causes (examples)
− Hypercalcemia: hydration and bisphosphonate.
− Painful anorectal conditions: medical / surgical management.
− Medications: discontinue / switch to an alternative.
Current Pharmacological therapy :
• Step 1 : Oral laxative:
products are the mainstay and first line in treating constipation in cancer provided that
there is suspected organic bowel obstruction.
Oral laxative osmotic (lactulose or polyethylene glycol) and / or stimulant (senna, bisacodyl
or sodium picosulfate) laxatives.
19
• Step 2 : Rectal laxatives:
Osmotic (glycerin suppositories) or stimulant (bisacodyl suppositories/enema or
sodium phosphate enema).
•
Step 3 : Methylnaltrexone:
A peripherally-acting μ- opioid receptor antagonist (PAMORA) for severe
intractable opioid- induced constipation(OIC) in cancer patients not responded
to titrated dosed of laxatives.
Promising emerging therapy for CIC:
CHLORIDE SECRETION ACTIVATORS
Lubiprostone : It acts by stimulating the type 2 chloride channel (ClC2) in the small intestine. This increases chloride rich fluid secretion into
the intestine, which stimulates intestinal motility and shortens intestinal
transit time.
GUANYLATE CYCLASE-C ACTIVATORS
Linaclotide and plecanatide stimulate intestinal chloride secretion
through a different mechanism by binding to and activating guanylate
cyclase-C on the luminal surface. Prevention of opioid-associated
constipation
20
Current Pharmacological therapy
Drug category
• Bulking agents
Fiber supplements
Psyllium and methyl
cellulose (Stretch intestinal
• Stool softeners
1-Decosate sodium
2-Oral mineral oil(paraffin oil)
Adverse effects /contraindications
Flatulence and distension
Avoid in patients with advanced disease, esophageal
cancer, stenosis, ulcers or intestinal adhesions
Ineffective if used alone
Intestinal cramping
• Not given in patients with risk of aspiration
(lipid pneumonia)
• Decrease absorption of fat-soluble vitamins
• Add it to juice (bitter taste)
• Pruritis ani (delay healing of anal fissure or polyp)
•
•
•
Stimulants 1-Senna
2-Bisacodyl
(the most widely used
• Osmotic agents
1-Mg sulphate (Epson ‘s salt) 2lactulose
Abdominal cramping and Watery diarrhea
No medications are used within 2 hours before or
after bisacodyl
Bitter taste add it to juice and
Excessive use is associated with hypermagnesemia,
hyperphosphatemia, hypokalemia and
hypoalbuminemia Bloating and flatulence
Local
rectal
products
 Stimulant
s 1Biascodyl
2enema
mediate water retention and softens
the impacted hard fecal mass
Must touch rectal wall to produce peristalsis
Elderly with comorbidities may at a risk of
water and electrolytes imbalance
Local irritation
21
6. Hypercalcemia
− Hypercalcemia is a life threatening situation that caused a significant morbidity and mortality.
− Normal level of calcium in the blood ranges between 8.7 – 10.4 mg/ dl. Correct calcium level in the
blood could be determined by using the following equation:
Corrected calcium (mg/ dl) = measured calcium + ([4- albumin (g/ dl)] × 0.8).
• Serum calcium ranging between 10.5 – 12.0 mg/ dl indicates mild hypercalcemia.
−
Moderate hypercalcemia is being diagnosed when serum calcium is between 12.0 – ≤ 14.0 mg/ dl.
Severe hypercalcemia (hypercalcemia crisis) occurs when serum calcium is higher than 14.0 mg/ dl
and is associated with acute signs and symptoms.
− Causes of hypercalcemia
The main causes of hypercalcemia during solid or hematological malignancy are as follows:
1. The direct effect of cancer diseases on the bone by causing bone destruction.
2. Some cancers diseases lead to production of parathyroid hormone-related protein (PTHrP) which
is mainly associated with solid cancer.
3. Some cancer diseases decrease the ability of the kidneys to remove excess calcium also leading
to decreases in the urination.
4. Dehydration due to nausea and vomiting which will lead to difficulties of the kidneys to remove
excess calcium from the blood.
5. Decreases in the movement and activity of cancer patients which will lead to breakdown of the
bone and hence increase in the release of the calcium into the blood.
Hypercalcemia treatments and options
There are different types of treatments used for hypercalcemic patients
1. Bisphosphonates (Etidronate, Clodronate and Pamidronate)
2. Calcitonin (Calcimar®)
3. Zoledronic acid (Zometa®)
4. Glucocorticoids (Prednisone)
While for emergency cases with calcium level exceeding 13 mg/ dl the following treatments are
added:
1. Normal saline 200-400 ml/ hour I.V.
2. Furosemide (Lasix®) 200-400 ml/ hour
22
7. Dyspnea
Definition
Dyspnea (shortness of breath / breathlessness) is a “subjective experience of breathing discomfort”.
Causes
−
Cancer itself: primary lung cancer, pulmonary metastases, …
−
Cancer-related causes: pleural effusion, chest wall pain, fatigue/weakness, …
−
Treatment-related causes: lobectomy and radiotherapy-induced pneumonitis.
−
Other conditions: infection, anemia, heart failure, pulmonary embolism, …
−
Co-existing psychological factors: fear and anxiety.
Management
Treatment of underlying causes (examples)
−
−
−
−
−
Pleural effusion: aspiration.
Chest wall pain: analgesics.
Infection: antimicrobials.
Small air way obstruction: bronchodilators.
Panic attack: non-pharmacological / pharmacological (benzodiasepines)
• Symptomatic management
− Non-pharmacological
1. Fan: facial cooling in the areas subserved by the 2nd and 3rd branches of the
trigeminal nerve reduces the sensation of breathlessness.
2. Neuro-electrical muscle stimulation
3. Chest wall vibration
4. Anxiety reduction.
− Pharmacological
1. Opioids: morphine (or an alternative opioid) is the drug of choice.
2. Benzodiazepines: are used when there is anxiety.
3. O2 therapy: in selected patients with hypoxemia after a trial of its benefit
23
8.
Fatigue
Definition
Cancer-related fatigue is “a distressing, persistent, subjective sense of physical,
emotional, and/or cognitive tiredness or exhaustion related to cancer and cancer
treatment that is not proportional to recent activity and interferes with usual
functioning”.
Prevalence
The most common symptom in palliative care. Up to 74% in incurable cancer patients.
Causes : Frequently, multifactorial. Factors contributing to fatigue include:
1. General factors: sleep disturbances, deconditioning (due to reduced activity, fitness
and/or muscle
wasting), psychological factors (anxiety, depression, …), lack of social support, …
2. Condition-related factors: metabolic abnormalities, anemia, infection,
anorexia/cachexia,
uncontrolled symptoms (pain, …),
…
3. Treatment factors: medications (sedatives, opioids, …), surgery, cancer treatment
(radiotherapy, chemotherapy and hormonal therapy).
Management
• Treatment of underlying causes (examples)
1. Uncontrolled symptoms: manage symptoms.
2. Infections: antimicrobials.
3. Medications: discontinue / replace.
• Symptomaticmanagement Nonpharmacological
1. Energy conservation/restoration strategies.
2. Physical activity and exercise.
3. Psychosocial interventions.
Pharmacological
1. Corticosteroids (dexamethasone, …): short-term use.
2. Psycho-stimulants (methylphenidate, …): in selected patients with caution.
24
9.
Delirium
Definition
Delirium is a clinical syndrome characterized by disturbed consciousness, cognitive
function or perception, which has an acute onset and fluctuating course.
Prevalence
Up to 88% of advanced cancer patients in the last 2 weeks of life. Causes :Usually
multifactorial in advanced cancer.
1. Cancer-related: CNS tumors, …
2. Anti-cancer treatment: brain irradiation, …
3. Physical complications in cancer patients: hepatic/renal/pulmonary failure, infections,
dehydration, electrolyte abnormalities,
…
4. Medications: drugs (anxiolytics, opioids, corticosteroids, …), polypharmacy, …
5. Other status / predisposing comorbidities: age >70 years, uncontrolled pain, …
Measurement / Diagnosis
• Screening:
Example: the “Ultra-Brief 2-item Screener” (UB-2) that assesses orientation and
attention. The two items are “please tell me the day of the week”, and “please tell me the
months of the year backwards, say December as your first month”. A positive screen
(either item incorrect) indicates the need for further delirium assessment.
• Diagnosis confirmation:
for instance, by using the “Confusion Assessment Method” (CAM) diagnostic algorithm.
Management
• Prevention
o Non-pharmacological
1. Assistance for cognitive impairment: visible clock and calendar, avoid frequent room
changes, …
2. Assistance with visual / hearing impairment.
3. Encourage mobilization and avoid mobility limitation (physical restraints, …)..
4. Adequate fluid intake.
5. Avoid sleep-wake circadian cycle disturbances.
Treatment of underlying causes (examples)
1. Fever: antipyretic.
2. Infection: antimicrobials
3. Electrolyte abnormalities: correction.
4. Medications: discontinue / switch to an alternative.
5. Drug withdrawal: restart and gradual withdrawal.
25
• Symptomatic management
o Non-pharmacological: As in prophylaxis.
Pharmacological
For patients who have distressing delirium symptoms (such as perceptual
disturbances) or when there are safety concerns.
1. Antipsychotic (haloperidol, …): is the 1st line of choice
2. Benzodiazepines (midazolam, …): as a 1st line if antipsychotics are contraindicated or
as 2nd lin when antipsychotics fail to control delirium.
3. Refractory agitated delirium: consider palliative sedation.
Basis of Radiation oncology
Radiation therapy (RT) is a treatment modality in which high energy ionizing radiation is
used for patients with cancers to kill cancer cells and shrink tumors and for patients with
benign disease like arterio- venous malformation, keloids and orbital pseudotumor.
Aim of radiation therapy:
Among the main cancer treatment modalities, RT and surgery aim to provide local-regional
tumor control. Using chemotherapy and radiotherapy (radiation-sensitizing agent) over the
same treatment period has been shown to be more effective than using the two treatment
modalities separately. Some chemotherapeutic agents, e.g. cisplatinum, appear to sensitize
cells to radiotherapy.
Biologic basis for Radiation therapy
• Radiation therapy works by damaging the DNA of cells and destroys their ability to
reproduce.
• Both normal and cancer cells can be affected by radiation, but cancer cells have
generally
impaired ability to repair this damage, leading to cell death.
• All tissues have a tolerance level, or maximum dose, beyond which irreparable
damage may occur
Indications of radiation therapy:
1- Radical radiotherapy:
• It aims at cure of the patient without use of other local modalities, e.g.
Radical
radiotherapy of nasopharyngeal cancer
2- Adjuvant radiotherapy:
•
It is used following surgical treatment to Kill residual microscopic disease left
26
after surgery or chemotherapy e.g Adjuvant radiotherapy in breast cancer
following mastectomy
•
3- Neo-adjuvant radiotherapy:
It is used before surgical management to help in tumor shrinkage and increase local
control of the tumor.
4- Palliative radiotherapy:
• Commonly used to relieve pain from bone cancers
• Spinal cord compression.
•
Vascular compression, e.g., superior vena cava syndrome
• Bronchial obstruction
• Bleeding from gastrointestinal or gynecologic tumors
• Esophageal obstruction
Side effects of radiotherapy:
Most normal tissue effects of radiotherapy are related to cell killing, such as
nausea, vomiting, fatigue, and drowsiness.
Some late effects may be related to radiation-induced proliferative responses such as
gliosis or fibrosis. It includes:
• Acute effects :
that appear usually within 2 to 3 weeks after treatment commences, such as fatigue,
mucositis, diarrhea, dysphagia and skin changes, are secondary to the depletion of stem
cells and are expected to subside gradually once the treatment course is over.
• Subacute effects:
such as Lhermitte’s syndrome (electric shock-like sensation down the
periphery upon sudden flexion of neck, due to demyelination)
or somnolent syndrome (fatigue, drowsiness, irritability and decrease appetite)
occur several weeks after cranial irradiation and are nearly always transient.
• Late effects
are secondary to the depletion of slowly proliferating cells and are nearly always
permanent.
These side effects can happen months or years after treatment.
These are usually the critical structures that limit the dose prescribed by the
radiation oncologists.
An example is radiation induced fibrosis, menopause and infertility after pelvic or
pituitary gland irradiation, xerostomia and hypothyroidism after head and neck
irradiation.
Ionizing Radiations
Radiations in the energy range used for RT can cause the ejection of orbital
electrons and result in the ionization of atoms or molecules.
The forms of ionizing radiation are either directly ionizing causes direct disruption of
atomic or molecular structure of the tissue ( e.g., a beam of protons, alpha
27
particles, or beta particles) tissues or indirectly ionizing (e.g., electromagnetic
waves and neutron beams) gives up energy as its passes through.
The amount of energy deposited within a certain amount of tissue is defined as the
absorbed dose with a unit of gray (Gy; 1 Gy = 1 joule/kg).
The types of radiation commonly used clinically
•
Photons
The energy range used for RT pertains to either x-rays, which are commonly
produced by a linear accelerator (LINAC), or γ-rays, which are emitted from
radioactive isotopes as cobalt machine.
Photons of different energies interact with matters differently: from low to
high energy. Modern therapeutic machines produce photon beams with energy of
megavoltage (or million electron volt, MeV) range rather than kilovoltage (kilo
electron volt, KeV), as used in diagnostic radiology.
In general, the higher the photon energy, the greater the depth of penetration
into the body and the more “skin-sparing” effect with less radiation dermatitis.
•
Electron beams
− Deposit their energy rapidly as they enter tissue. Thus, they have a relatively
short depth of penetration and generally are used to treat superficial lesions.
− The effective range in tissue also depends on their energy. Each modern LINAC
usually provides one or two energies of photons and several levels of electron
energies.
• Other radiation particles
Used for RT include protons, neutrons, and heavy ions, such as carbon anions.
Charged particles deposits most of their energy at a given depth, minimizing
risk to tissues beyond that point.
Allows for highly specific targeting of tumors located near critical structures
Most commonly used in treatment of pediatric, CNS and intraocular malignancies
Radiotherapy techniques:
External beam radiotherapy: Which include:
1. Two dimension radiotherapy:
It is an old technique with following disadvantages:
Irradiation of large volume of unnecessary tissues
Higher toxicity and side effects
Lack of 3D visualization of the tumor
Uncertainty of dose delivery to the target volume and the risk structures
28
2- Three dimension conformal radiotherapy (3D-CRT):
Is an advanced technique that incorporates the use of imaging technologies,
like CT scan to generate three-dimensional images of a patient’s tumor and
surrounding organs.
Using these detailed images, the treatment team can develop a highly accurate
plan to deliver, the highest radiation dosage to a tumor, with the least dose the
surrounding organs at risk.
3-
Intensity modulated radiotherapy (IMRT):
A highly sophisticated form of 3-D CRT allowing radiation to be shaped more
exactly to fit the tumor
Radiation is broken into many “beamlets,” the intensity of each can be
adjusted individually
IMRT allows higher doses of radiation to be delivered to the tumor while sparing
more healthy surrounding tissue.
4.
Volumetric modulated arc therapy (VMAT):
It uses beams given from a rotating gantry with different MLC shaping so
achieves intensity modulation.
It is more rapid technique than IMRT so has the following benefits:
• Better patient comfort
• Reduced intra-fractional movement
• Higher dose rate to the tumor
• More patients to be treated (better economics)
5- Stereotactic radiotherapy (SRT):
It is a type of radiotherapy, in which radiotherapy dose is given in few
radiotherapy sessions and high dose per fraction.
Only single given radiotherapy session is called Stereotactic surgery (SRS) and
if multiple radiotherapy doses are given, they are called stereotactic body
radiotherapy (SBRT).
Stereotactic radiotherapy can be applied based one of the above mentioned
techniques (IMRT, VMAT), and using either linear accelerator or other machines
as Gamma-Knife or Cyberknife.
Used on the brain , spine, lung, liver, adrenals, pancreas.
6- Image guided radiotherapy (IGRT) :
It is a type of radiotherapy in which images are incorporated in treatment delivery
to ensure high accuracy of radiotherapy. E.g., motion management by respiratory
gating of lung tumor that moves during radiotherapy session.
7. Brachytherapy (implants):
It is another form of radiotherapy where a sealed radiation source is placed inside
or next to the area requiring treatment to deliver high doses of radiation to the
desired target while minimizing the dose to surrounding normal tissues.
29
Temporary treatment involves the placement of radioactive material in or close
to a tumor for a limited period of time before it is removed.
permanent treatment involves leaving the radioactive material in the body and
allowing its levels of radioactivity to diminish naturally. Examples of radioactive
sources are Cs-137, Ir- 192.
Types of Internal Radiation Therapy:
Intra-cavitary implants:
Radioactive sources are placed in a cavity near the tumor (breast, cervix, uterine)
Interstitial implants:
Sources placed directly into the tissue (prostate, vagina)
Intra-operative implants
Surface applicator is in direct contact with the surgical tumor bed
Pain Management: Basic Principles
DEFINITIONS
Pain “An unpleasant sensory and emotional experience associated with, or resembling that
associated with, actual or potential tissue damage (e.g., tissue ischemia)”. Pain can be purely
nociceptive, purely neuropathic, or mixed.
Nociceptive pain is caused by active tissue damage. It can be visceral (cardiac ischemia, renal
colic) or somatic (skin laceration, fractured bone).
Neuropathic pain is associated with nervous system disease (diabetic neuropathy) or damage
(severed nerves after surgery, compression by tumor).
Myo-fascial pain is either localized in or referred to a muscle. Myofascial pain is
characterized by the presence of trigger points (an area of the muscle that fails to relax,
forming a hard spindle-shaped nodule or band that is tender on palpation). Myofascial pain is
both nociceptive and neuropathic in nature.
Breakthrough pain (incident pain) refers to a sudden and transient exacerbation of pain
that occurs in spite of adequate management of background pain. Breakthrough pain can
be nociceptive or neuropathic in origin.
30
Classification of Pain
Pain
Underlying
etiology
Nociceptive
Inflammatory
Neuropathic
Anatomic
location
Temporal
Acute
Chronic
Acute on chronic
Somatic
Visceral
31
Intensity
Mild
Moderate
Severe
Types of
Mechanism
pain
Underlying etiology
Clinical examples
Pharmacological
treatment
options
Nociceptive
The result of direct
tissue injury from a noxious
stimulus.
Bone fracture, fresh
surgical incision, and fresh burn
injury.
May include both
opiate and nonopiate
medications
depending on
injury.
Inflammatory
The result of released
inflammatory mediators that
control nociceptive input.
Late stages of burn
healing, neuritis, and
arthritis
Antiinflammatory
agents
Neuropathic
The result of direct
injury to nerves leading to an
alteration in sensory
transmission.
Diabetic neuropathy,
peripheral
neuropathic
pain, and post-herpetic
neuralgia.
Tricyclic,
selective
norepinephrine
reuptake inhibitors,
gabapentinoids, or
antidepressants
Idiopathic
Unknown
Chronic back pain without
preceding trauma or
obvious inciting event.
Maybe difficult to
adequately address
pain since underlying
aetiology is
unknown, especially
in emergency
settings.
Somatic
A-delta-fibre activity
located in peripheral
tissues
Superficial lacerations,
superficial burns,
superficial abscess
Topical and/or
local anesthetics,
opiates, nonopiates
Visceral
C-fibre activity located
in deeper tissues such as
organs
Uterine fibroid pain,
pyelonephritis, biliary
colic
Opiates
Acute
A neurophysiological
response to noxious injury
that should resolve with
normal wound healing.
Acute fracture, acute knee
sprain
Opiate, nonopiates
Chronic
Pain that extends
beyond the time for normal
wound healing with resultant
development of multiple
neurophysiological changes
Chronic low back pain,
fibromyalgia, arthritis
Acute-onchronic
An acute exacerbation
of a chronic pain syndrome
Sickle cell disease, cancer,
rheumatoid arthritis, acute
injury in chronic pain patient
Anatomic location
Temporal nature
32
Depends on the
nature of the pain.
Please refer to the
module on chronic pain
for more detailed
Acute-onchronic
CAUSES OF PAIN
TU
1- In patients with cancer causes of pain include:
1) Infiltration or compression of various tissues or organs by tumour.
2) Complications of cancer (e.g., pathologic vertebral fractures due to skeletal metastases).
3) Cancer treatment (e.g., radiation-induced plexopathy, postmastectomy pain syndrome,
chemotherapy-induced neuropathy).
4) Non–cancer-related pain (e.g., primary headache, angina).
2- Non cancer pain is caused by injury or compression of various tissues or organs.
Mechanisms of this include external trauma, ischemia, or toxins (both external, such as
chemical burns, and internal, such as neuropathy caused by uraemia).
Assessment of Pain
1- History
The patient’s history and physical exam can be an invaluable source when it comes to
determining the proper diagnosis and course of treatment.
Essential elements should include a detailed history of the current pain and, for those who suffer
from chronic pain, their previous pain history.
Basics
1.Onset of recent pain
2. Aggravating and alleviating factors
3. Quality of pain experience
4. Location of pain
5. Severity of pain
6. Circumstances of original pain
Functionality
1. How is pain affecting current level of function? 2. Is
patient working?
3. How is patient coping with pain?
Co-morbidities
1. Significant past medical and/or surgical history
2. Chronic diseases (obesity, hypertension, diabetes, etc.)
3. Psychosocial and/or psychiatric co-morbidities
4. Family history of substance abuse
Psychosocial and psychiatric
1. Depression
33
2. Suicidal ideation or past suicide attempts
3. 3. Past psychiatric admissions
4. Physical, sexual and/or emotional abuse.
Essential elements of Pain History –Basics
Basic Elements
1. Onset of recent pain
Description
•When did the pain start and what was the patient doing when it started
•Was the onset sudden, gradual, or an exacerbation of a chronic problem
2. Aggravating and
alleviating factors
3. Quality of pain
experience
•What makes the pain better and what makes it worse?
•How does physical activity or position affect pain?
•Do any non-pharmacological therapies or medications relieve the pain?
•Ask the patient “Can you describe the pain?” Ideally, this will elicit
descriptions of the patient's pain: whether it is sharp, dull, crushing,
burning, tearing, or some other feeling, along with the pattern, such as
intermittent, constant, or throbbing.
4. Location of pain
•Where pain is on the body and whether it radiates (extends) or moves to
any other area?
5. Severity of pain
•Ask the patient to describe the intensity of pain at baseline and during
acute exacerbations, typically done using a pain scale
6. Circumstances of
original pain
•Identify when the pain started, under what circumstances, duration, onset
(sudden/gradual), frequency, whether acute/chronic.
Mnemonics for obtaining pain history
SOCRATS
•Site
•Onset
•Character
•Radiation
U
•Associations
•Time course
•Exacerbating/Relieving factors
•Severity
OPQRST
• Onset of event
• Provocation and palliation of symptom
• Quality
34
• Region and radiation
• Severity
• Timing
S
O
Site
Onset
C
Character
R
A
T
E
Radiation
Associations
Time course
Exacerbating/Relieving
factors
Severity
S
Where is the pain? Or the maximal site of the pain.
When did the pain start, and was it sudden or gradual?
Include also whether if it is progressive or regressive.
What is the pain like? An ache? Stabbing? Burning?
numbness ?
Does the pain radiate anywhere? (See also Radiation.)
Any other signs or symptoms associated with the pain?
Does the pain follow any pattern?
Does anything change the pain?
How bad is the pain?
Medical or surgical issues related to patient’s pain or treatment may
include
Cancer
•Different types of pain may be caused by multiple etiologies:
Tumors: involvement of bone, vessels, nerves, body organs
Diagnostic procedures: may be painful such as biopsies, lumbar
punctures, or venipuncture
Treatment: radiation, chemotherapy, or surgical excision
Recent Surgery
•Incisional pain
•Complications such as anastomotic leak, bleeding, compartment
syndrome, etc.
Other Conditions
•Diabetes which can lead to neuropathic pain
•Herpes zoster which can lead to radicular pain
•Migraines which can lead to mixed etiology
35
Physical Examination
You should be examining the patient’s:
Examples
Appearance
Posture
Gait
Facial Expression
Vital Signs
obese, emaciated, histrionic, flat affect
splinting, scoliosis, kyphosis
antalgic, hemiparetic, using assisting devices
grimacing, tense, diaphoretic, anxious
sympathetic overactivity, temperature
asymmetries
You should be examining the
Painful Area(s):
Inspection
Example
•Skin: colour changes, hair loss, flushing, goose
bumps, sweating
•Muscle: atrophy or spasm
•Edema
Palpation
•Demarcation of the painful area
•Detection of changes in pain intensity within the area
•Trigger points
•Changes in sensory or pain processing
Musculoskeletal system
•Flaccidity: extreme weakness (may be from
paralysis)
•Abnormal movements: neurologic damage or
impaired sense of proprioception, reduced sense of
light touch
•Limit range of motion: disc disease, arthritis, pain
Neurological exam
•Cranial nerve exam
•Motor strength
•Spinal nerve function: deep tendon reflexes, pinprick,
proprioception
•Coordination: Romberg’s test, toe-to-heal, finger-tonose, rapid hand movement
36
Pain Assessment Scales
Pain
Scales*
Adult
Pediatric
Verbal, Alert and Oriented
Non-verbal, GCS <15 or Cognitive
Impairment
1. Adult Non-Verbal Pain Scale (NVPS)
2. Assessment of Discomfort in
Dementia (ADD)
3. Behavioral Pain Scale (BPS)
4. Critical-Care Observation
Tool (CPOT)
1. Verbal Numeric Scale (VNS)/
Numeric Rating Scale (NRS).
2. Visual Analogue Scale (VAS).
3. Defense and Veterans Pain
Rating Scale (DVPRS 2.0)
3 years and older
1. Wong Baker Faces
2. Oucher (3-12yrs)
3. Numerical Rating
(NRS)
Birth–6 months
1. Neonatal Infant Pain Scale (NIPS).
2. Neonatal Pain Assessment and
Sedation Scale (N-PASS)
3. Neonatal Facial Coding System
(NFCS)
4. CRIES
Scale
Infant and older
1.Revised Faces, Legs, Activity, Cry,
and Consolability (r-FLACC)
2.Non-Communicating Children’s Pain
Checklist (NCCPC-R)
3.Children’s Hospital of Eastern
Ontario Pain Scale (CHEOPS) (ages 17)
8 years and older
1.Visual Analogue Scale (VAS)
2.Verbal Numeric Scale (VNS)/
Numeric Rating Scale (NRS)
Adult Scales
Measurement Scale
Verbal Numeric Scale (VNS)/
Numeric Rating Scale (NRS)
Verbal rating scale (VRS)
Visual Analogue Scale
Defense and Veterans Pain Rating
Scale 2.0 (DVPRS)
Description
Self-report scale. Eleven-point scale that requires
understanding of numbers, addition and subtraction.
Five pain levels are indicated in large print on a sheet
give to the patient: no, pain, mild pain, moderate
pain, severe pain, unbearable pain.
A 100-mm rule with a movable cursor: “no pain” is
written at the left end of the horizontal line along
which the cursor is moved, and “maximal pain” at
the right end.
Self-report scale. Eleven-point scale that requires the
patient to identify pain by numerical rating, colour
intensity, facial expression, and pain disruption.
Followed by four supplemental questions evaluating
the biopsychosocial impact of pain.
37
Pain Assessment Scales
U
38
Principles of Pharmacotherapy
1. Use oral analgesics whenever possible, as this route of administration is the least invasive.
If oral treatment is not possible (due to nausea, vomiting, dysphagia), subcutaneous or
transdermal administration should be used.
Transdermal absorption can be unpredictable in patients with edema or reduced peripheral
blood flow (including those actively dying). Initiation of transdermal medications should be
avoided in such situations. However, if patients are already receiving these medications at the
end of life and find them effective, there is no need to stop this therapy.
Subcutaneous injections, when appropriate for selected medication, are preferred over IV
injections for patients at home and for those using long-term parenteral analgesics. Repeated
IM injections are painful and offer no benefits over the subcutaneous or IV route.
2. Use analgesics in accordance with the World Health Organization (WHO) analgesic ladder
(fig. 1).
In patients with mild pain, start treatment with acetaminophen (paracetamol), nonsteroidal
anti-inflammatory drugs (NSAIDs), and other nonopioid medications, unless contraindicated.
If results are unsatisfactory, move up to the next step of the analgesic ladder. Patients with
severe pain generally need an opioid regardless of the underlying mechanism of pain; there is
no reason to start at the bottom step if pain is severe.
On each step of the analgesic ladder co-analgesics and nonopioid medications improve
analgesia, reduce opioid requirements, and inhibit the development of opioid tolerance.
3. In patients with ongoing pain analgesics should be administered on a regular basis
(around the clock) at intervals adjusted to the pharmacokinetics of a specific agent. Regular
dosing provides more consistent pain control than intermittent (as-needed) dosing.
36T
36T
4. Patients with ongoing pain should receive immediate-release breakthrough
analgesics for incident pain . Incident or breakthrough pain is pain that occurs despite the
regular administration of analgesics. Patients receiving analgesics on the around-the-clock
basis should receive immediate-release doses of analgesics to relieve this pain. Patients with
only incident pain may achieve good pain control with a breakthrough analgesic alone.
36T
36T
5. Controlled-release (long-acting) opioid formulations should be used only after
stable dosing is achieved with immediate-release formulations . Controlled-release
opioids provide analgesia with longer intervals between doses, allowing for patient
convenience. They have a slower onset of action and cannot be titrated as fast as immediaterelease formulations. Pain control may be poor for the first several hours or days of use of
a long-acting opioid and the patient will require an immediate-release breakthrough
medication. The full effect of a controlled-release medication can take several hours or days
to be reached and toxicity can develop if the agent is titrated quickly. Controlled-release
formulations should not be used in opioid-naive patients.
36T
36T
6. Always use lower starting doses in the elderly and those with renal or hepatic
impairment . Opioid metabolism is slower in the elderly, increasing the risk of adverse
events and toxicity. Most opioids and their metabolites are excreted by the kidneys
(hydromorphone
36T
36T
39
and fentanyl are notable exceptions), requiring lower doses in patients with renal failure.
Patients with significant hepatic impairment are particularly sensitive to neurologic adverse
effects of opioids.
Fig. 1 World Health Organization (WHO) analgesic ladder
Nonopioid Analgesics
1. Acetaminophen
has a rapid onset (15-30 minutes) and short duration of action (up to 4-6 hours).
The maximum daily dose in adults (>12 years) who are not at increased risk of hepatotoxicity
is 3 to 4 g/24 h.
Doses ≤2.6 g/d are recommended in the elderly and even lower doses are recommended in
those with liver disease or alcohol abuse.
Be aware that the patient might be taking extra paracetamol in fixed combinations with
opioids or in some OTC preparations.
36T
36T
40
2. NSAIDs ,
Have analgesic and anti-inflammatory properties.
Have the most potent analgesic effect in bone pain, myofascial pain, and pain caused by
inflammation.
The onset and duration of action varies by formulation and includes ibuprofen with a rapid
onset (15-30 minutes) and short duration (4-6 hours) and celecoxib with a slower onset (3
hours) and long duration (14 hours).
Before using NSAIDs, the risk of cardiovascular, gastrointestinal, and renal adverse effects
must be evaluated. Use of selective cyclooxygenase-2 (COX-2) inhibitors, proton pump
inhibitors (PPIs), or both will reduce (but not eliminate) the risks of gastrointestinal bleeding.
There is no evidence that COX-2 inhibitors have a reduced renal or cardiac risk compared
with nonselective COX inhibitors.
Monitor arterial blood pressure and liver and kidney function tests for patients on NSAIDs
Patients above 60 years of age are at more risk of GI and renal toxicities.
36T
36T
Weak Opioid Analgesics
Weak opioids are so named not because they are inherently less effective than other opioids.
At equi analgesic doses, they are just as effective as stronger opioids, such as fentanyl or
morphine. Rather, they are called weak opioids because they are commonly combined with
other medications that limit the maximum daily dose. When used alone (without the doselimiting presence of another drug), weak opioids could be considered strong opioids. The
distinction between weak and strong opioids is thus, to a certain degree, arbitrary.
1. Codeine :
3
Start immediate-release oral codeine 15 mg to 30 mg every 4 to 6 hours.
If necessary, titrate the dose up to a maximum of 240 mg/d.
Immediate-release and controlled-release formulations are available. Immediate-release
formulations contain codeine alone or combined with acetaminophen (marketed as Tylenol
with codeine or Solpadine) or acetylsalicylic acid, limiting the maximum daily dose.
Codeine should not be used in moderate or severe renal failure, as metabolites accumulate,
causing sedation and altered level of consciousness.
2. Dihydrocodeine :
T
Dihydrocodeine is a synthetic opioid.
Start from 60 mg orally every 12 hours.
If necessary, titrate the dose up to 120 mg every 12 hours.
Immediate-release formulations are available as dihydrocodeine alone or combined with
acetaminophen, aspirin, ibuprofen, antihistamines, or decongestants, limiting the maximum
daily dose.
3. Oxycodone :
T
Start from 5 mg every 4 hours.
Titrate the dose to achieve an adequate analgesic effect.
Immediate-release and controlled-release formulations are available. Immediate-release
formulations contain oxycodone alone (in which case it should be considered a strong opioid)
or combined with acetaminophen (marketed as Percocet), limiting the maximum daily dose
41
Oxycodone is available in combination with naloxone (Targin), which helps to minimize the
adverse effect of constipation.
4. Tramadol:
The usual starting dose is 25 to 50 mg every 4 hours in an immediate-release oral formulation.
Titrate the dose as needed at a rate no faster than 25 mg every 3 days up to a maximum of 400
mg/d.
Tramadol works through opioid receptors and serotonin receptors.
Nausea and vomiting are common at the beginning of treatment.
Immediate-release and controlled-release formulations are available. Immediate-release
formulations contain tramadol alone or combined with acetaminophen (marketed as
Tramacet), limiting the maximum daily dose.
Caution and lower initial doses are needed in the elderly and in those with renal or hepatic
failure.
Do not use in patients with poorly controlled seizure disorders. Tramadol is associated with
serotonin syndrome.
Strong Opioid Analgesics
At equianalgesic doses, weak and strong opioids have the same level of effect. Some weak
opioids are actually more potent than certain strong opioids. Table 2
1. Morphin :
T
Start from 5 to 10 mg orally every 4 hours.
Titrate the dose to achieve adequate analgesia or based on adverse effects. Immediate-release
and controlled-release formulations are available.
Oral, rectal, subcutaneous, and IV formulations are available
Morphine and its active metabolites are excreted by the kidneys. Not advised in patients with
renal failure.
2. Hydromorphone:
-Hydromorphone is a semisynthetic (morphine-based) opioid.
Start from 0.5 mg to 1 mg orally every 4 hours.
Titrate the dose to achieve adequate analgesia or based on adverse effect. Immediate-release
and controlled-release formulations are available.
Oral, subcutaneous, and IV formulations are available
Patients with a true allergy to morphine should try a different fully synthetic opiate where
there is no known cross-reactivity.
Hydromorphone has relatively inert metabolites that are excreted by the kidneys. It can be
safely used in patients with renal failure.
3. Buprenorphine:
An intermediate-acting opioid available in transdermal, buccal and sublingual formulations
are available.
Dosing is based on prior exposure to opioids.
Buprenorphine can be used in opioid-naive patients at low doses with caution.
42
All routine dosing of alternative opioids should be stopped when buprenorphine is started.
Intermittent breakthrough opioids can be used to prevent increases in pain or symptoms of
withdrawal.
Buprenorphine is safe for use in patients with renal failure.
a) Transdermal patches:
(up to 20 microg/h) are changed every 7 days.
Dose adjustments should occur only after 3 to 7 days.
Higher-dose preparations of transdermal patches (from 35 microg/h) changed every
4 days are used in some European countries.
3 to
b) Buccal film and sublingual tablets
are taken every 12 hours.
Dose adjustments should occur no quicker than every 4 days.
Lower doses and slower titration are advised in patients with oral lesions.
c) Sublingual tablets that contain both buprenorphine and naloxone are available in 2 dosage
forms which are approved only for use in opioid addiction.
4. Fentanyl :
T
A strong opioid reserved for opioid-tolerant patients.
Immediate-release (buccal and IV) and controlled-release formulations (transdermal patches)
are available.
Starting doses depend on prior opioid use.
Not recommended for patients using <45 mg to 60 mg of morphine (or equivalent) per day.
IV dosing should be reserved for monitored settings, such as operating rooms and intensive
care units.
Patients using controlled-release formulations will need breakthrough analgesics for incident
pain.
Controlled-release formulations should be titrated no quicker than once a week because of
their long half-life.
When a patch is removed, drug levels may be found in blood for up to 1 day.
Conversion from alternative opioids to fentanyl is not as exact as in other opioid conversions.
Deaths have occurred in Canada when opioid-naive patients started using fentanyl patches,
even the smallest doses possible.
Prescription of fentanyl patches should be reserved for practitioners experienced in opiate
dosing.
It is suggested that for critically ill patients, transdermal fentanyl dosing can be converted
directly to IV (and back again when the patient’s condition improves and they are able to take
oral formulations) at a 1:1 ratio. This should be done in a monitored setting.
Fentanyl is safe for use in patients with renal failure.
5. Methadone:
An intermediate-acting opioid used in opioid-tolerant patients.
Only oral formulation is available.
Dosing is based on use of other opioids and goals of therapy (pain management or addiction
therapy).
Methadone may be used in patients with end-stage renal disease.
It is safe for use in patients with renal disease.
43
Methadone prolongs the cardiac QT interval.
It must be used with caution in patients taking other medications.
6. Oxycodone :
T
Described in the weak opioids section (see above), it can be considered a strong opioid when
administered without dose-limiting medications.
The starting doses and rate of titration are the same with and without additional medications.
The opioid conversion table can be used to shift between different opioids or formulations of
the same opioid; for example
The oral dose of morphine is approximately 3 times its parenteral dose because morphine’s
bioavailability is around 30%.
Fentanyl’s dose is about 1/100 that of morphine because fentanyl is around 100 times more
potent. The dose of fentanyl is classically reported in micrograms.
44
Management of Adverse Effects of Opioids
1. Sedation (manifesting as daytime somnolence)
usually occurs at the beginning of opioid treatment or after a considerable dose increase and
resolves within several days. If somnolence persists or worsens, the dose of opioid can be
decreased to the lowest dose that ensures pain control. Other causes of sedation (e.g., other
medications, dehydration, renal failure, disease progression, hypercalcemia) should be
excluded and treated where possible. Persistent somnolence may be an indication for
switching to another opioid. Patients should be advised not to drive or operate heavy
equipment until they are aware how their opioids will affect them (in some countries driving
when using opioids is not allowed).
2. Nausea and vomiting
may develop in the first days of starting an opioid or following a dose increase and usually
resolve spontaneously. Opioids can elicit nausea and vomiting through direct effects on the
vomiting centre in the brain or by way of reduced gut motility (with or without constipation).
Always inform the patient about the risk of nausea or vomiting (or both) and explain these are
likely to be transient (to prevent patients from discontinuing the drug on their own). Consider
providing the patient with an antiemetic agent to be used at home in case of nausea or
vomiting associated with opioid treatment. Other causes of nausea and vomiting (eg, other
medications, renal failure, disease progression, constipation) should be excluded and treated
where possible. Opioid-induced nausea and vomiting respond best to prokinetic antiemetics
(metoclopramide) or dopamine antagonists (haloperidol). If nausea and vomiting cannot be
managed medically, consider rotation to a different opioid or to another form of the
medication (e.g., long-acting, transdermal).
3. Constipation
is the most frequent adverse effect of opioids. Patients using opioids on a regular basis should
be provided with prophylactic laxative therapy. Opioid-induced constipation often requires
a combination of medications. Stimulant (senna) and osmotic (lactulose) laxatives are most
effective.
4. Delirium
may occur with initiation of opioids, dose changes, or accumulation of metabolites (i.e., acute
renal failure). Subtle cognitive changes may occur in the absence of clinically evident
delirium. Cognitive changes are often caused by opioid metabolites rather than the given
opioid itself. Cognitive changes can be reduced by decreasing opioid dose to the lowest dose
that provides adequate pain control. Opioid rotation, particularly to one with minimally active
metabolites (hydromorphone, fentanyl), may reduce cognitive effects. Delirium that does not
resolve or is distressing can be treated with low doses of a dopamine antagonist (haloperidol
0.125-1 mg orally or subcutaneously). Other causes of cognitive impairment (e.g., other
45
medications, renal failure, disease progression, or hypercalcemia) should be excluded and
treated where possible.
5. Hyperalgesia
Opioid-induced hyperalgesia is a poorly understood phenomenon where use of opioids leads
to overstimulation of nociceptors and sensation of pain. Typically, hyperalgesia develops
simultaneously with neurotoxicity. Patients with hyperalgesia experience no pain relief with
increasing opioid doses. Opioid-induced hyperalgesia is a diagnosis of exclusion, and
alternative causes of pain such as disease progression must be ruled out. Hyperalgesia should
be managed urgently by decreasing opioid dose (typically by a third or half) to reduce
stimulation of the opioid receptor. Opioid rotation (including a dose decrease) and careful use
of opioid-sparing analgesics can be helpful as well.
6. Neurotoxicity
Opioid-induced neurotoxicity is a clinical syndrome in which the given opioid or its
metabolites cause neurologic adverse effects. Symptoms can include hallucinations, delirium,
somnolence, myoclonus, dysesthesia, and hyperalgesia. Opioid neurotoxicity does not appear
to be mediated through opioid receptors and thus does not respond to opioid antagonists such
as naloxone. Management of opioid-induced neurotoxicity requires reduction of opioid dosing
and hydration to assist in the clearance of metabolites. Severe cases may require switching to
an alternative opioid. Specific symptoms can be managed with directed therapies, such as
benzodiazepines (myoclonus); these therapies must be used with care as they will contribute
to the altered cognitive status of the patient.
7. Overdose
Features of opioid overdose include depressed respiratory rate, depressed mental status,
decreased bowel sounds, and constricted pupils. Overdose can occur with one large dose or as
metabolites accumulate in patients with dehydration or renal failure. Management of a mild
overdose includes reduction of opioid dosing and IV fluids to assist in the clearance of
metabolites. Low doses of naloxone (0.05-0.1 mg IV, intranasally, or subcutaneously) can be
used if necessary but often this is not needed.
Management of a severe opioid overdose (respiratory depression, airway compromise,
unresponsiveness) requires reduction of opioid dosing, IV fluids, and an opioid antagonist
(naloxone). Initial doses of 0.4 to 1 mg of naloxone IV, intranasally, or subcutaneously are
advised. As the half-life of naloxone is shorter than that of therapeutic opioids, many patients
require a continuous infusion of naloxone to provide support until clearance of all metabolites
is achieved.
Of note, patients at the end of life have symptoms similar to those of opioid toxicity. As long
as death is not related to opioid toxicity, it is important not to give naloxone to actively dying
patients, as this will cause pain and distress and not reverse the symptoms.
8 Other adverse effects
.
Dry mouth, pruritus, urinary retention, and sweating commonly occur and can be treated
symptomatically. With long-term use, suppression of luteinizing hormone, follicle-stimulating
hormone, adrenocorticotropic hormone, and growth hormone secretion can occur and can be
associated with osteoporosis.
46
Opioid Rotation
Opioid rotation (switching from one opioid to another) is used in patients who
develop unacceptable refractory adverse effects to or tolerance of a certain opioid.
when patients are no longer able to swallow opioids that come only in oral formulations.
The method of rotation needs to account for the type of opioid the patient is taking
(controlled-release or immediate-release formulation) and the dose of the opioid. Opioid
receptors have incomplete cross-tolerance for opioids and tend to take up a novel opioid with
greater affinity than the one the patient has been using for some time.
As a result, guidelines suggest calculating equianalgesic doses of the new medication and then
decreasing this dose by as much as a third to a half.
A breakthrough immediate-release opioid can be used to improve analgesia during the
transition period. Consultation with a palliative care or pain medicine specialist is
recommended for opioid rotation.
Co-analgesics
Coanalgesics are agents that are not classified as analgesics but in certain types of pain have
inherent analgesic effects or enhance the effects of analgesics. When appropriate,
coanalgesics should be used at all steps of the WHO analgesic ladder.
1. Antiepileptic drugs:
a) Gabapentin:
Originally designed as an anticonvulsant, gabapentin is now approved for treatment of
neuropathic pain. The usual starting dose is 200 to 300 mg (100 mg in elderly patients and
those with renal impairment) in the evening, with the dose titrated up every 2 to 3 days by 200
to 300 mg/d (100 mg/d in the elderly) until an adequate analgesic effect is achieved or adverse
effects develop. Similarly, to opioids, there is no maximum dose, although benefits from
increases beyond 1200 mg tid are minimal. The goal should be the lowest dose (in a bid or tid
dosing) that achieves pain control and minimizes adverse effects. Somnolence is the most
common adverse effect that limits the rate at which the dose may be increased. Unsteady gait
and falls are common.
b) Pregabalin
Pregabalin is an analgesic designed to mimic the neuropathic analgesic properties of
gabapentin. Start from 75 mg bid (25 mg bid in the elderly and those with renal impairment).
If necessary, titrate the dose up by 25 to 50 mg every 3 to 7 days. The maximum
recommended effective dose is 300 mg bid (total daily doses of 50 mg may be effective in
patients with renal impairment and in the elderly). Common adverse effects include confusion
and volume overload (from sodium and water retention). These effects can be severe and
require discontinuation of the medication. The mechanism of action mimics that of
gabapentin, thus there is no reason to use these two medications at the same time.
c) Carbamazepine:
An anticonvulsant with analgesic effects as a neuropathic agent. Start from 50 to 100 mg bid.
The dose can be titrated up to a maximum of 800 to 1200 mg/d. Lower doses are needed in
47
those with renal impairment and in the elderly. The main adverse effect is sedation, which can
be managed with dose reduction. Carbamazepine is the first-line therapy recommended for
trigeminal neuralgia. The effectiveness of analgesia is not related to drug levels, unlike when
it is used as an anticonvulsant. There is no need to regularly measure drug levels unless
toxicity is suspected (based on the clinical situation or high drug doses).
2. Tricyclic antidepressants (TCAs)
This class of medications has been shown to be effective in the management of migraine,
arthritis, chronic low back pain, postherpetic neuralgia, fibromyalgia, and diabetic
neuropathy. The adverse effect profile of TCAs is that of anticholinergic medications (eg,
sedation, dry mouth, constipation, urinary retention, or confusion) and will often limit dosing.
a) Amitriptyline:
Starting dose 10 mg at bedtime, increased to 25 mg after 3 to 7 days, and then increased by
25 mg/d every 1 to 2 weeks. Effective analgesia (or adverse effects) can often develop with
doses <50 mg/d.
b) Nortriptyline:
Starting dose 10 mg at bedtime, increased to 25 mg after 3 to 7 days, and then increased by 25
mg/d every 1 to 2 weeks. Effective analgesia (or adverse effects) can often develop with doses
<75 mg/d.
3. Other antidepressants:
Other antidepressants have been shown to have coanalgesic effects. They modulate this effect
through management of comorbid mood disorders as well as through mechanisms not yet
understood. Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and
serotonin norepinephrine reuptake inhibitors (SNRIs) have inferior efficacy in neuropathic
pain management when compared with TCAs. However, the adverse effect profile of SSRIs
and SNRIs is better tolerated by most patients, making these agents a suitable option to
consider for the management of neuropathic pain.
Duloxetine: The only SNRI officially approved for management of diabetic neuropathy,
fibromyalgia, and chronic musculoskeletal pain. The starting dose of 30 mg is effective in
some patients. Others need to have their dose increased to a maximum of 60 mg daily after
1 week of treatment with the starting dose. Duloxetine should not be used in patients with
end-stage renal disease or cirrhosis.
4. Other co-analgesics:
There are many other agents used as coanalgesics in specific situations.
a) Glucocorticoids (dexamethasone) provide pain relief in the setting of inflammatory
conditions and when pain is caused by compression, stretch, or infiltration by tumor. They
are useful for pain management in patients with rheumatologic disease, solid tumor, or
lymphoma.
b) Bisphosphonates help to reduce bone pain associated with malignant infiltration through
inhibition of osteoclast activity. Not sufficient as a single analgesic agent.
c) Topical lidocaine and capsaicin are effective in treating localized pain due to
neuropathy, vasculitis, or trauma.
48
*Neuropathic pain or damage to the somatosensory nervous system.
General causes of neuropathic pain variously include:
diabetes, traumatic nerve injuries, autoimmune disorders, genetic disorders, amyloid
depositions, and medications.
Treatment
Neuropathic pain management focuses on treating symptoms, and only in some pathological
condition, the etiological causes can be treated relieving pain.
The Special Interest Group on Neuropathic Pain (NeuPSIG) Proposed:
First-line options for the treatment of chronic pain:
anticonvulsants, serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic
antidepressants (TCAs).
The second-line treatment,
Lidocaine, Capsaicin, and Tramadol
Third-line treatments strong opioids
(Morphine and Oxycodone) and botulinum toxin-A (BTX-A)
1- Pain relievers
a- non-steroidal anti-inflammatory drugs, can relieve mild symptoms.
b- For more-severe symptoms use medications containing opioids, such as tramadol or
oxycodone. They can lead to dependence and addiction, so these drugs generally are
prescribed only when other treatments fail.
2- Anti-seizure medications
Carbamazepine, Gabapentin and pregabalin (Lyrica), may relieve nerve pain.
3- Tricyclic Anti-depressants.
Certain tricyclic antidepressants (TCA) such as amitriptyline, doxepin and nortriptyline can
relieve pain by interfering with chemical processes in brain and spinal cord that cause pain.
4- The serotonin and norepinephrine reuptake inhibitor
Duloxetine (Cymbalta) and the extended-release antidepressant venlafaxine also might ease
the pain of peripheral neuropathy caused by diabetes.
5- Topical treatments.
Capsaicin cream, which contains a substance found in hot peppers, can cause modest
improvements in peripheral neuropathy symptoms. They may produce skin burning and
irritation where the cream is applied, but this usually lessens over the time.
Lidocaine patches are applied to skin may offer pain relief.
Side effects can include drowsiness, dizziness and numbness at the site of the patch.
Non-pharmacological measures
6-Transcutaneous electrical nerve stimulation (TENS)
7- Plasma exchange and intravenous immune globulin
49
8- Physical therapy
9- Surgery to relieve pressure
10- Take care of feet, especially in diabetics
11- Alternative medicine (Acupuncture , Herbs).
Non pharmacologic Management of pain
An in-depth analysis of non pharmacologic interventions of pain management is beyond the
scope of this chapter. However, in many situations they can be an adjuvant to pharmacologic
therapy.
1. Nerve blocks and neuro-destructive procedures:
Use anesthetic agents to temporarily anesthetize or alcohol to permanently destroy the nerve
plexus at the source of pain. Performing such procedures with imaging guidance improves
success rates. The availability of interventional procedures is site-dependent and not all clinics
and hospitals are able to provide such services.
a) Celiac plexus neurolysis may be used in the treatment of pain caused by pancreatic,
gastric, liver, gallbladder, intestinal, or renal cancers; retroperitoneal metastases; or
splenomegaly.
b) Hypogastric plexus neurolysis or blocks may be used in patients with pelvic pain
secondary to malignant and non-malignant causes, tenesmus secondary to radiation therapy to
the rectum, or malignancy-related rectal pain.
c) Blocks of the stellate ganglion, lumbar sympathetic trunk, and ganglion impar (ganglion
of Walther) can be used to ease pain in the limbs, face, and pelvic region.
d) Continuous central neuraxial blocks (subarachnoid and epidural) are most commonly
performed when systemic administration of opioids is ineffective or results in
unacceptable adverse effects. These blocks can be used to treat intractable neuropathic and
nociceptive pain. The most significant benefit of continuous spinal opioid delivery is
typically in the reduction of adverse effects rather than in improved pain control.
e) Peripheral nerve blocks are often used for procedures and interventions. A longterm anesthetic effect could be achieved through alcohol lysis of the same nerves.
f) Trigger point injections are injections of an anesthetic agent with or without glucocorticoid
into a muscle knot (trigger point). The exact mechanism of pain control is not clear but
improvement in local pain has been shown in patients with myofascial pain and
fibromyalgia.
2. Radiotherapy
Is first-line treatment for localized pain associated with metastatic bone disease and direct
nerve injury from solid tumor growth. The number of treatments and total size of radiation
dose varies based on the nature of pain and the type of cancer.
50
3. Surgery
Can be a useful method of pain relief. Prophylactic and post fracture bone fixation provides
rapid and profound pain control. Spinal decompression, vertebroplasty, and kyphoplasty have
shown mixed results in the management of pain from degenerative disc disease and vertebral
compression fractures.
4. Transcutaneous electrical nerve stimulation (TENS)
Uses electrical stimulation applied to the skin to stimulate nerve endings, in this way altering
or eradicating pain. This form of analgesia is easily performed in the outpatient setting. Results
are most beneficial when TENS is used for acute and subacute pain from injury or
surgery.
5. Physiotherapy
Including massage, and exercise are most effective in the management of bone, soft tissue, and
neuropathic pain. Physiotherapy is important in maintaining mobility despite ongoing pain and
disease.
6. Occupational therapy
Does not directly provide analgesia. Thanks to modifications in behavior, gait aids, and tools,
occupational therapy can indirectly reduce pain through altered body mechanics and
minimization of on-going injury.
7. Cognitive behavioural therapy and behaviour therapy
Have been shown to have very small benefits in overcoming disability, managing mood, and
reducing catastrophic thinking associated with chronic pain. It is not clear at this time how long
the therapy should be continued or which patients benefit most from such interventions
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Introducing Palliative Care
Definitions
Palliative Care:
World Health Organization (WHO) definition of Palliative Care: “Palliative care is an
approach that improves the quality-of-life of patients (adults and children) and their
families who are facing problems associated with life-threatening illness. It prevents and
relieves suffering through the early identification, correct assessment and treatment of
pain and other problems, whether physical, psychosocial or spiritual”.
Palliative Medicine:
Palliative medicine is a branch of medicine defined as “the study and management of
patients with active, progressive, far-advanced disease for whom the prognosis is limited
and the focus of care is the quality-of-life”.
life-threatening illnesses [LTIs]:
Palliative care is required for a wide range of diseases when considered incurable and
life- limiting. These diseases include: cancer, cardiovascular diseases, chronic respiratory
diseases, kidney failure, chronic liver disease, end-stage neurological and
rheumatological diseases, congenital anomalies and drug-resistant tuberculosis.
Note: Although these notes focus on palliative care for cancer patients, it should be noted that
the needs of palliative care cancer and non-cancer patients are very much similar and that the
principles of palliative care described here are, in general, applicable to both.
Integration of palliative care into the care of life-threatening illness
Palliative care should be integrated early into the care of patients with LTIs once a diagnosis
is made (Figure 1). As the LTI progresses, the role of disease-modifying therapy decreases
and that of palliative care increases. Eventually, palliative care becomes the only realistic
treatment approach and continues to the end-of-life. Palliative care extends beyond the death
of patients by providing bereavement care for their families.
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Figure 1. Integration of palliative care into the course of a life-threatening illnes
Dimensions of palliative care
The suffering of patients with LTIs is multidimensional and includes physical, social,
psychological and spiritual components which contribute to the “total suffering”.
In order to relief the multi-dimensional suffering of patients with LTIs and their families,
palliative care is ideally provided by a multidisciplinary team that includes physicians,
nurses, social workers, psychologists / psychiatrists and spiritual advisors. The team may
expand to include other professions when applicable e.g., dietitians, physiotherapist, ...
Models and levels of palliative care delivery
•
•
Different palliative care delivery models exist and include:
Home-based Palliative Care:
For patients with limited mobility.
Outpatient Palliative Care Clinic:
For mobile patients.
− Hospital-based Inpatient Palliative Care Unit:
− Unit within a hospital with dedicated palliative care beds and staff trained in
palliative care.
− Palliative Care Consultation Service:
− Offers consultations to inpatients of other departments of the hospital.
− Palliative Care Day-Care Service:
− Can offer stabilization of symptoms, respite for caregivers and counseling for both
patient and family.
− Hospice / Stand-alone Palliative Care Center:
An inpatient stand-alone facility that admits patients in their last phase of life, when
treatment in a hospital is not necessary and care at home or in a nursing home is
not possible.
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Palliative care should be available at all levels of the health care system:
Primary Palliative Care:
Basic skills and competencies required of all physicians and other health care professionals.
Secondary Palliative Care:
Specialist clinicians and organizations that provide
consultation and specialty care.
Tertiary Palliative Care:
Academic medical centers where specialist knowledge for the most complex cases is
practiced, researched, and taught.
Assessment in Palliative Care
1.
Assessment of Symptoms: ( see pain management).
2. Assessment of Performance Status
−
−
−
−
Performance status is “a global measure of a patient’s functional capacity”.
Assessment of performance status is important for predicting prognosis, treatment
decisions and communication between healthcare professionals and with patients and
families. Example: the Australia-modified Karnofsky Performance Status (AKPS)
(Table 1).
3. Assessment of quality-of-life
Definition
The WHO defines Quality of Life as “an individual's perception of their position in life
in the context of the culture and value systems in which they live and in relation to their
goals, expectations, standards and concerns”.
“Health-related quality-of-Life (HRQoL) refers to how the individual’s wellbeing may
be impacted over time by a disease, a disability, or a disorder”.
Measurement
In health-care, a patient-reported outcome questionnaire (instrument) is used to measure
the quality-of-life which may be:
• Generic (general):
Not specific to any disease, population or treatment. Example: The abbreviated World
Health Organization Quality-of-Life questionnaire (WHOQOL-BREF) which includes
24 questions assessing four domains (physical health, psychological, social relationships
and environment) in addition to two questions for overall quality-of-life and general
health.
• Disease-specific: e.g., specific for cancer patients.
• Disease category-specific (e.g., lung cancer) or a domain-specific (e.g., anxiety,
depression, fatigue … etc.)
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Table 1. The Australia-modified Karnofsky Performance Status (AKPS)
AKPS score
100
90
80
70
60
50
40
30
20
10
0
Description of Performance Status
Normal; no complaints; no evidence of disease.
Able to carry on normal activity; minor signs or symptoms.
Normal activity with effort; some signs or symptoms of disease.
Cares for self; unable to carry on normal activity or to do active work.
Requires occasional assistance but is able to care for most of his needs.
Requires considerable assistance and frequent medical care
In bed more than 50% of the time.
Almost completely bedfast.
Totally bedfast and requiring extensive nursing care by professionals and/or family.
Comatose or barely arousable.
Dead.
4. Assessment of prognosis
Definition
Prognosis is “the likely outcome or course of a disease”.
Importance
• Provide information about the future to patients and families.
• Assist clinicians in decision making.
• Establish patient’s eligibility for care programs and clinical trials.
• Provide a common language for health care professionals.
Factors associated with poor prognosis in incurable cancer
• Clinical prediction of survival: although physicians’ prediction of survival is frequently
inaccurate, a predicted short survival is associated with poor prognosis.
• Poor performance status.
• Symptoms/signs: anorexia, delirium, edema, and dyspnea (especially at rest), …
• Biological parameters: hyponatremia, hypoalbuminemia, leukocytosis, and low
lymphocyte percentage, …
Prognostic scores / models
Incorporate prognostic factors to improve the prediction of prognosis. Example: the Palliative
Prognostic Index (PPI) incorporates performance status, oral intake, edema, dyspnea at rest and
delirium.
Communicating prognosis
• A frequent question asked by patients with LTIs and their families is: “How long have I got?”
The correct answer is: “I do not know”. If it is necessary to make a prediction of survival,
consider the following: o Make it clear that clinical prediction is frequently inaccurate.
o Talk in terms of “days”, “weeks”, or “months” aided by prognostic factors / models.
o NO numbers.
• For poor prognosis patients, avoid phrases like “There is nothing more we can do”.
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End-of-Life Care
Identifying the Dying Phase
Patients with LTIs should be assessed thoroughly when there is a deterioration in their
condition to exclude any potentially-reversible causes for that deterioration (dehydration,
infection, opioid toxicity, delirium, hypoglycemia, …). In the absence
of potentially-reversible causes and with the aid of known prognostic factors / models (see
Assessment of Prognosis) a deteriorating patient may be considered to be in the last days of
his/her life.
Goals of End-of-Life Care
1. Ensure the patient’s comfort physically, emotionally and spiritually.
2. Make the end-of-life peaceful and dignified.
3. Make the memory of the dying process as positive as possible.
Management
1. Discuss the care plan: with the patient, if possible, and the family and explain the
expected changes at this stage.
2. Withhold life-sustaining interventions:
1.
2.
3.
4.
5.
6.
1.
2.
3.
Definition of life-sustaining interventions: “any method, medicine or device used to
prolong life”
Life-sustaining interventions include:
Cardiopulmonary resuscitation
Mechanical ventilation
Nasogastric tube / percutaneous enteral feeding
Parenteral nutrition
Renal dialysis
Vasopressors/inotropes…
Life-sustaining interventions are considered futile at the end-of-life of terminally-ill
patients with no positive impact on the quality-of-life. On the other hand, such
interventions may cause significant physical and psychosocial suffering.
Medications
Stop any medications not consistent with the goals of care.
Continue medications for symptom control as described before.
Anticipatory prescribing: Make as needed medications necessary for the control
of common symptoms at the end-of-life available if not already prescribed.
These include:
▪ Opioid (morphine, …): for pain / dyspnea Anxiolytic (midazaolam, …):
for
anxiety.
• Antipsychotic (haloperidol, …): for agitated delirium
• Antisecretory (hyoscine butylbromide, …): for accumulating secretions.
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
-
Antiemetic (metoclopramide, …): for vomiting.
Route of drug administration:
 Poor oral intake and poor intravenous access are common at the end- of-life
of patients with LTIs.
 Alternative routes of administration are used, e.g., subcutaneous,
rectal, and transdermal, but not intramuscular.
 Medications commonly needed at the end-of-life can be given
subcutaneously (including all anticipatory medications mentioned above).
 Palliative sedation: May be indicated in selected patients with
distressing uncontrolled symptoms after maximizing the usual
pharmacologic management. Only by palliative care specialist.
− Assisted hydration
If the patient is not accumulating fluids (chest secretions, ascites, edema, …), assisted
hydration may be useful in selected patients. The intravenous route is used if already
available, otherwise use the subcutaneous route.
• Investigations
Investigations are unlikely to be of benefit at the end-of-life.
• Other issues
Accumulation of oro-pharyngeal secretions
Occurs due to loss of the gag reflex.
Management: first try postural drainage/repositioning, if no response anti-secretory
medications (hyoscine butylbromide, …) may be used. Oro-pharyngeal suctioning is not
preferred except in selected cases.
Loss of ability to close eyes
Occurs due to loss of retro-orbital fat pad → insufficient eyelid length to close the eyes
→ conjunctival/corneal dryness.
Management: maintain moisture by using artificial tears.
Prevention of bed sores
By turning the patient in bed, skin care and may be air mattresses.
Terminal bleeding
▪ Bleeding may be a terminal event in some malignancies (head & neck,
hematological, …).
▪ Management: make dark sheets available and use anxiolytics (midazolam,
…) for anxiety.
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Communication
Breaking Bad News
Definition
Bad news is “any news that seriously and adversely affects the patient’s view of his or her
future”.
• Protocol for breaking bad news
The SPIKES is a six-step protocol for delivering bad news. The acronym SPIKES stands
for: Setting, Perception, Invitation, Knowledge, Emotions and Strategy and Summary.
1) Setting up the interview:
a) Arrange for some privacy.
b) Review the patient’s medical records
c) Introduce yourself.
d) Sit down.
e) Make connection with the patient.
f) Manage time constraints and interruptions.
2) Assessing the patient’s Perception
− Use an open-ended question to assess patient’s perception: e.g., “What have you
been told about your medical situation so far?”
3) Obtaining the patient’s Invitation
− Assess the willingness of the patient to know the bad news: e.g., “Are you the sort of
person that likes to know everything?”
4) Giving Knowledge and information to the patient before telling the bad news, “warn” the patient
by a “warning shot”: e.g., “Unfortunately, I have got some bad news to tell you”. While giving
knowledge, you should:
Respect patient’s comprehension and vocabulary.
Give information gradually.
Check periodically that the patient is listening to you and understanding.
5) Addressing the patient’s Emotions with empathic response
After delivery of bad news, given the patient a brief period of time to express his/her
feelings.
Observe for and identify the emotional reaction of the patient which may be: silence,
disbelief, crying, denial or anger.
Address the patient’s emotion with an empathic statement like: “I was also hoping
for a better result” …
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Strategy and Summary
Give the patient a clear plan for the future in relation to the bad news.
Summarize the meeting.
Offer the patient to answer any questions he/she has and giver him/her the contact
details for future communication.
Ethical and Legal Issues
The Distinction between Palliative Care and Euthanasia and Physician Assisted Suicide
Euthanasia and Physician-Assisted Suicide
• Euthanasia is defined as: “A physician (or other person) intentionally killing a person
by the administration of drugs, at that person’s voluntary and competent request”.
Euthanasia cannot be non-voluntary, involuntary nor passive.
• Assisted Suicide is defined as: “A person intentionally helping another person to
terminate his or her life, at that person’s voluntary and competent request”.
• Physician Assisted-Suicide is defined as: “A physician intentionally helping a person to
terminate his or her life by providing drugs for self-administration, at that person’s
voluntary and competent request”.
− In the vast majority of countries, including Egypt, euthanasia and assisted-suicide are
illegal.
− Palliative Care should be distinguished from euthanasia and physician-assisted suicide
− According to the WHO definition, palliative care Affirms Life and Regards Dying as a
Normal Process, and it Intends to Neither Hasten nor Postpone Death. Palliative care
offers a support system to Help Patients Live as Actively as Possible Until Death.
Non-treatment decisions (NTD) are not euthanasia
NTDs are: “Withholding or withdrawing medical treatment from a person either because
of medical futility or at that person’s voluntary and competent request”.
NTDs do not intend to hasten death, but allows natural death through omission of
ineffective, futile, or unwanted life-prolonging procedures.
Palliative sedation in not euthanasia. Palliative sedation is “the monitored use of medications
intended to induce a state of decreased or absent awareness (unconsciousness) in order to relieve
the burden of otherwise intractable suffering in a manner that is ethically acceptable to the
patient, family and healthcare providers”. It “intends to neither hasten nor postpone death
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