Transcript cancer

Management of anesthesia In
cancer
Dr Abdollahi
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4/6/2016
Cancer is the second most frequent cause of death in the United
States, exceeded only by heart disease. Cancer develops in
one of every three Americans. The number of deaths is
increasing, reflecting the growing elderly population and a
decrease in the number of deaths from heart disease.
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Stimulation of oncogene formation by carcinogens
(tobacco, alcohol, sunlight) is estimated to be
responsible for 80% of cancers in the United States.
Tobacco use accounts for more cases of cancer than
all other known carcinogens combined. The
fundamental event that causes cells to become
malignant is an alteration in the structure of DNA.
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Drugs administered for cancer chemotherapy may produce
significant side effects including interstitial pneumonitis,
peripheral neuropathy, renal dysfunction, cardiomyopathy,
and hypersensitivity reactions. These side effects may have
important implications for the management of anesthesia
during surgical procedures for cancer treatment as well as
operations unrelated to the presence of cancer.
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MECHANISM
Cancer results from an accumulation of mutations in genes that
regulate cellular proliferation.
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Cancer cells must evade the host's immune surveillance system,
which is designed to seek out and destroy tumor cells. Most
mutant cells stimulate the host's immune system to form
antibodies. In support of a protective role of the immune
system is the increased incidence of cancer in
immunosuppressed patients, such as those with acquired
immunodeficiency syndrome and those receiving organ
transplants.
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DIAGNOSIS
Cancer often becomes clinically evident when tumor bulk
compromises the function of vital organs. The initial diagnosis
of cancer is often by aspiration cytology or biopsy (needle,
incisional, excisional). Monoclonal antibodies that recognize
antigens for specific cancers (prostate, lung, breast, ovary)
may aid in the diagnosis of cancer.
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TNM
A commonly used staging system for solid tumors is the TNM
system based on tumor size (T), lymph node involvement (N),
and distant metastasis (M). This system further groups
patients into stages ranging from the best prognosis (stage I)
to the poorest prognosis (stage IV).
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TREATMENT
Treatment of cancer includes chemotherapy, radiation, and
surgery. Surgery is often necessary for the initial diagnosis of
cancer (biopsy) and subsequent definitive treatment to
remove the entire tumor or distant metastases or to decrease
the tumor mass. Adequate relief of acute and chronic pain
associated with cancer is a mandatory part of treatment.
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Chemotherapy
Drugs administered for cancer chemotherapy may produce
significant side effects . These side effects may have important
implications for the management of anesthesia during surgical
procedures for cancer treatment as well as operations
unrelated to the presence of cancer.
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Angiogenesis Inhibitors
Cancer cells secrete proteins that facilitate angiogenesis
(creation of new blood vessels) and tissue invasion, such as
vascular endothelial growth factor, fibroblast growth factors,
and matrix metalloproteinases. Drugs that prevent
angiogenesis, such as endostatin, may be useful in the
treatment of cancer.
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Acute and Chronic Pain
Cancer patients may experience acute pain associated with
pathologic fractures, tumor invasion, surgery, radiation, and
chemotherapy. A frequent source of pain is related to
metastatic spread of the cancer, especially to bone. Nerve
compression or infiltration may be a cause of pain. Patients
with cancer who experience frequent and significant pain
exhibit signs of depression and anxiety.
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Multimodal analgesia with local anesthetics and gabapentin may
be effective in preventing both acute and chronic
postmastectomy pain and reducing analgesic consumption
after breast surgery. Recently gabapentin has been shown to
reduce analgesic requirements for acute postoperative pain
but does not significantly affect the development of chronic
pain.
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Drug Therapy
Drug therapy is the cornerstone of cancer pain management
because of its efficacy, rapid onset of action, and relatively
low cost. Mild to moderate cancer pain is initially treated with
NSID and acetaminophen. NSID are especially effective for
managing bone pain, which is the most common cause of
cancer pain.
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The next step in management of moderate to severe pain
includes addition of codeine or one of its analogues. When
cancer pain is severe, opioids are the major drugs used.
Morphine is the most commonly selected opioid and can be
administered orally. When the oral route of administration is
inadequate, alternative routes (intravenous, subcutaneous,
epidural, intrathecal, transmucosal, transdermal) are
considered.
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Fentanyl is available in transdermal and transmucosal delivery
systems. There is no maximum safe dose of morphine and
other μ-agonist opioids. Tolerance to opioids does occur but
need not be a clinical problem. Unnecessary fear of addiction
is a major reason opioids are underused despite the fact that
addiction is rare when these drugs are correctly used to treat
pain in cancer patients.
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Tricyclic antidepressant drugs are recommended for those who
remain depressed despite improved pain control. These drugs
are also effective in the absence of depression and appear to
have direct analgesic effects and cause potentiation of
opioids.
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Anticonvulsants are useful for management of chronic
neuropathic pain. Corticosteroids can decrease pain
perception, have a sparing effect on opioid requirements,
improve mood, increase appetite, and lead to weight gain.
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Neuraxial Analgesia
Neuraxial analgesia is an effective way to control pain in cancer
patients undergoing surgery and may play a role in providing
preemptive analgesia. Neuraxial analgesia with local
anesthetics provides immediate pain relief in patients whose
pain cannot be relieved with oral or intravenous analgesics
and is frequently used for the treatment of cancer pain.
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Neuraxial analgesia is not performed in patients with local
infection, bacteremia, and systemic infection because of the
increased risk of epidural abscess. However, in the presence
of intractable cancer pain, there may be a role for the use of
epidural analgesia despite meningeal infection.
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Patients are typically considered for neuraxial opioid
administration when systemic opioid administration has failed
as a result of the onset of intolerable adverse (systemic) side
effects or adequate analgesia cannot be achieved. Neuraxial
administration of opioids is usually successful, but some
patients require an additional low concentration of local
anesthetic to achieve adequate pain control.
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Neurolytic Procedures
Neurolytic procedures intended to destroy sensory components
of nerves cannot be used without also destroying motor and
autonomic nervous system fibers. Important aspects of
determining the suitability of destructive nerve blocks are the
location and quality of the pain, the effectiveness of less
destructive treatment modalities, life expectancy, the
inherent risks associated with the block, and the availability of
experienced anesthesiologists to perform the procedures
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In general, constant pain is more amenable to destructive nerve
blocks than is intermittent pain. Neurolytic celiac plexus block
(alcohol, phenol) has been used to treat pain originating from
abdominal viscera, for example, pancreatic cancer. The block
is associated with significant side effects, but analgesia usually
lasts 6 months or longer.
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Neurosurgical procedures (neuroablative or neurostimulatory)
for managing cancer pain are reserved for patients
unresponsive to other less invasive procedures. Cordotomy
involves interruption of the spinothalamic tract in the spinal
cord and is considered for treatment of unilateral pain
involving the lower extremity, thorax, or upper extremity
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Dorsal rhizotomy involves interruption of sensory nerve roots
and is used when pain is localized to specific dermatomal
levels.
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PARANEOPLASTIC SYNDROMES
Paraneoplastic syndromes manifest as pathophysiologic
disturbances that may accompany cancer . Certain of these
pathophysiologic disturbances (superior vena cava
obstruction, increased intracranial pressure, pericardial
tamponade, renal failure, hypercalcemia) may manifest as lifethreatening medical emergencies.
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Pathophysiologic Manifestations of
Paraneoplastic Syndromes
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Fever and Weight Loss
Fever may accompany any type of cancer but is particularly likely
with metastases to the liver. Increased body temperature may
accompany rapidly proliferating tumors, such as leukemias
and lymphomas. Fever may reflect tumor necrosis,
inflammation, the release of toxic products by cancer cells, or
the production of endogenous pyrogens.
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Anorexia and weight loss are frequent occurrences in patients
with cancer, especially lung cancer. In addition to the
psychological effects of cancer on appetite, cancer cells
compete with normal tissues for nutrients and may eventually
cause nutritive death of normal cells. Hyperalimentation is
indicated for nutritional support when malnutrition is severe,
especially if elective surgery is planned.
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Hematologic Abnormalities
Anemia is usually a direct result of the effects of cancer, such as
gastrointestinal bleeding or tumor replacement of bone
marrow. Cancer chemotherapy is another common cause of
bone marrow suppression and anemia.
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Acute hemolytic anemia may accompany lymphoproliferative
diseases. Solid tumors, especially metastatic breast cancer,
can lead to pancytopenia. In contrast, an increased amount of
erythropoietin, as produced by a renal cell carcinoma or
hepatoma, can produce polycythemia.
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Thrombocytopenia can be due to chemotherapy or to the
presence of an unrecognized cancer. Disseminated
intravascular coagulation may occur in patients with advanced
cancer, especially when hepatic metastases are present.
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There is an association between venous thromboembolism
and a subsequent diagnosis of cancer. Cancer diagnosed at
the same time as or within 1 year after an episode of
venous thromboembolism is often associated with an
advanced stage of cancer and a poor prognosis. Recurrent
venous thrombosis due to unknown mechanisms may be
associated with pancreatic cancer.
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Neuromuscular Abnormalities
Neuromuscular abnormalities occur in 5% to 10% of patients
with cancer. The most common is the skeletal muscle
weakness (myasthenic syndrome) associated with lung cancer.
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Potentiation of depolarizing and nondepolarizing muscle
relaxants has been observed in patients with co-existing
skeletal muscle weakness, particularly when such weakness is
associated with undifferentiated small cell lung cancer.
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Ectopic Hormone Production
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Hypercalcemia
Cancer is the most common cause of hypercalcemia in
hospitalized patients, reflecting local osteolytic activity from
bone metastases especially breast cancer or the ectopic
parathyroid hormonal activity associated with tumors that
arise from the kidneys, lungs, pancreas, or ovaries.
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Tumor Lysis Syndrome
Tumor lysis syndrome is caused by sudden destruction of tumor
cells by chemotherapy, leading to the release of uric acid,
potassium, and phosphate. This syndrome occurs most often
after treatment of hematologic neoplasms, such as acute
lymphoblastic leukemia. Acute renal failure can accompany
the hyperuricemia.
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Hyperkalemia and resulting cardiac dysrhythmia are more likely
in the presence of renal dysfunction. Hyperphosphatemia can
lead to secondary hypocalcemia, which increases the risk of
cardiac dysrhythmias from hypokalemia and can cause
neuromuscular symptoms such as tetany.
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Adrenal Insufficiency
Adrenal insufficiency caused by complete replacement of the
adrenal glands by metastatic tumor is rare. More often there
is relative adrenal insufficiency owing to partial replacement
of the adrenal cortex by tumor or suppression of adrenal
cortical function by prolonged treatment with corticosteroids.
Adrenal insufficiency is most often seen in patients with
metastatic disease due to melanoma, retroperitoneal tumors,
lung cancer, or breast cancer.
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The stress of the perioperative period may unmask adrenal
insufficiency. Clinical manifestations include fatigue,
dehydration, oliguria, and cardiovascular collapse. Treatment
of acute adrenal insufficiency consists of bolus intravenous
administration of cortisol repeated at 6- to 8-hour intervals or
given by continuous infusion until oral replacement of a
glucocorticoid and mineralocorticoid can be initiated.
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Renal Dysfunction
Renal complications of cancer reflect invasion of the kidneys by
tumor, damage from tumor products, or chemotherapy.
Deposition of tumor antigen-antibody complexes on the
glomerular membrane results in changes characteristic of the
nephrotic syndrome. Extensive retroperitoneal cancer can
lead to bilateral ureteral obstruction and uremia, especially in
patients with cancer of the cervix, bladder, or prostate.
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Percutaneous nephrostomy is indicated if a ureter is totally
obstructed. Chemotherapy can destroy large numbers of
tumor cells. Acute hyperuricemic nephropathy due to
precipitation of uric acid crystals in the renal tubules is
prevented by administration of allopurinol in combination
with hydration and alkalinization of the urine.
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Methotrexate and cisplatin are the chemotherapeutic drugs
most often associated with nephrotoxicity. Acute hemorrhagic
cystitis is a complication of cyclophosphamide therapy.
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Acute Respiratory Complications
The acute onset of dyspnea may reflect extension of the tumor
or the effects of chemotherapy. Bleomycin-induced interstitial
pneumonitis and fibrosis are the most commonly
encountered pulmonary complications of chemotherapy.
Elderly patients and those with co-existing lung disease or
previous radiation therapy receiving large dose of bleomycin
are at greatest risk of pulmonary toxicity..
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Pulmonary toxicity rarely occurs when the total dose of
bleomycin is less than 150 mg/m2. The most common
symptoms of interstitial pneumonitis are the insidious onset
of nonproductive cough, dyspnea, tachypnea, and
occasionally fever 4 to 10 weeks after initiation of bleomycin
therapy. These symptoms appear in 3% to 6% of patients
treated with bleomycin
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Acute Cardiac Complications
Pericardial effusion caused by metastatic invasion of the
pericardium can lead to cardiac tamponade. Lung cancer
seems to be the most common cause of pericardial
tamponade. Malignant pericardial effusion is the most
common cause of electrical alternans on the
electrocardiogram. Paroxysmal atrial fibrillation or flutter
may be an early manifestation of malignant involvement
of the pericardium or myocardium.
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Optimal treatment of malignant pericardial effusion consists
of prompt removal of the fluid followed by surgical
creation of a pericardial window
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Cardiac toxicity manifesting as cardiomyopathy occurs in 1% to
5% of patients treated with doxorubicin or daunorubicin.
Cardiotoxicity may manifest initially as symptoms suggestive
of an upper respiratory tract infection (nonproductive cough)
followed by rapidly progressive congestive heart failure that is
often refractory to inotropic drugs or mechanical cardiac
assistance.
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Cardiomegaly and/or pleural effusion may be evident on chest
radiography. Patients who have undergone radiation therapy,
particularly to the mediastinum, or patients who are on
concurrent cyclophosphamide therapy seem to be more
susceptible to the development of cardiomyopathy.
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Superior Vena Cava Obstruction
Obstruction of the superior vena cava is caused by spread of
cancer into the mediastinum or directly into the caval wall,
most often by lung cancer. Engorgement of veins above the
level of the heart occurs, particularly the jugular veins and
those in the arms. Dyspnea and airway obstruction may be
present. Edema of the arms and face is usually prominent.
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Hoarseness may reflect edema of the vocal cords. Increased
intracranial pressure manifests as nausea, seizures, and
decreased levels of consciousness and is most likely due to
the increase in cerebral venous pressures. Treatment consists
of prompt radiation or chemotherapy, even without a
cytologic diagnosis to decrease the size of the tumor and thus
relieve venous and airway obstruction.
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Bronchoscopy and/or mediastinoscopy to obtain a tissue
diagnosis can be very hazardous, especially in the presence of
co-existing airway obstruction and increased pressure in the
mediastinal veins.
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Spinal Cord Compression
Spinal cord compression results from the presence of metastatic
lesions in the epidural space, most often breast, lung, or
prostate cancer or lymphoma. Symptoms include pain,
skeletal muscle weakness, sensory loss, and autonomic
nervous system dysfunction. Computed tomography and
magnetic resonance imaging can visualize the limits of
compression
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Radiation therapy is a useful treatment when neurologic deficits
are only partial or in development. Once total paralysis has
developed, the results of surgical laminectomy or of radiation
to decompress the spinal cord are usually poor.
Corticosteroids are often administered to minimize the
inflammation and edema that can result from radiation
directed at tumors in the epidural space.
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Increased Intracranial Pressure
Metastatic brain tumors, most often from lung and breast
cancer, present initially as mental deterioration, focal
neurologic deficits, or seizures. Treatment of an acute
increase in intracranial pressure caused by a metastatic lesion
includes corticosteroids, diuretics, and mannitol
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Radiation therapy is the usual palliative treatment, but surgery
can be considered for patients with only a single metastatic
lesion. Intrathecal administration of chemotherapeutic drugs
is necessary when the tumor involves the meninges.
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MANAGEMENT OF ANESTHESIA
Preoperative evaluation of patients with cancer includes
consideration of the pathophysiologic effects of the disease
and recognition of the potential adverse effects of cancer
chemotherapeutic drugs .
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Side Effects of Chemotherapy
Pulmonary and Cardiac Toxicity
The possible presence of pulmonary or cardiac toxicity is a
consideration in patients being treated with
chemotherapeutic drugs known to be associated with these
complications. A preoperative history of drug-induced
pulmonary fibrosis (dyspnea, nonproductive cough) or
congestive heart failure will influence the subsequent conduct
of anesthesia
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In patients treated with bleomycin, it may be helpful to monitor
arterial blood gases in addition to oximetry and to carefully
titrate intravascular fluid replacement, keeping in mind that
these patients are at risk of development of interstitial
pulmonary edema presumably because of impaired lymphatic
drainage from the pulmonary fibrosis.
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Whether bleomycin increases the likelihood of oxygen toxicity in
the presence of high inspired concentrations of oxygen is not
certain, but it seems prudent to adjust the delivered oxygen
concentration to the minimum that provides the desired
SpO2. Depressant effects of anesthetic drugs on myocardial
contractility may be enhanced in patients with drug-induced
cardiac toxicity.
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Neurotoxicity
Anticancer chemotherapy can cause a number of neurotoxic side
effects including peripheral neuropathy and encephalopathy.
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Peripheral Neuropathy
Vinca alkaloids, particularly vincristine, affect the microtubules
causing sensorimotor peripheral neuropathy. Virtually all
patients treated with vincristine develop paresthesias in their
digits. Autonomic nervous system neuropathy may
accompany the paresthesias. These changes are reversible.
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Performance of regional anesthesia in patients being treated
with cisplatin chemotherapy may be influenced by the
realization that subclinical neurotoxicity is present in a large
percentage of patients and cisplatin neurotoxicity may extend
several months beyond discontinuation of treatment.
Administration of local anesthetics and epinephrine in this
situation might produce a clinically significant injury.
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Severe diffuse brachial plexopathy has been described following
an interscalene block in a patient receiving cisplatin.
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The first sign of corticosteroid-induced neuromuscular toxicity is
difficulty rising from the sitting position. Respiratory muscles
may also be affected. Corticosteroid-induced peripheral
neuropathy usually resolves when the drug is discontinued.
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Encephalopathy
Many cancer chemotherapeutic drugs can cause
encephalopathy. High-dose cyclophosphamide may be
associated with acute delirium. High-dose cytarabine may
cause acute delirium or cerebellar degeneration, both of
which are usually reversible. Reversible acute encephalopathy
may accompany the intravenous or intrathecal administration
of methotrexate. Prolonged administration of methotrexate,
especially in conjunction with radiation therapy, can lead to
progressive irreversible dementia.
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Preoperative Preparation
Correction of nutrient deficiencies, anemia, coagulopathy, and
electrolyte abnormalities may be needed preoperatively.
Nausea and vomiting are the most common and distressing
side effects of chemotherapy and, to some extent, of
radiation treatment.
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Serotonin antagonist drugs, such as ondansetron, droperidol,
and metoclopramide may help control nausea in these
patients. Tricyclic antidepressants are useful for potentiating
the analgesic effects of opioids and producing some inherent
analgesia. Opioids used to manage cancer pain may be
responsible for preoperative sedation.
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The presence of hepatic or renal dysfunction may influence the
choice of anesthetic drugs and muscle relaxants. Although not
a consistent observation, the possibility of a prolonged
response to succinylcholine is a consideration in patients
being treated with alkylating chemotherapeutic drugs such as
cyclophosphamide.
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Attention to aseptic technique is important because
immunosuppression occurs with most chemotherapeutic
agents. Immunosuppression produced by anesthesia, surgical
stimulation, or even blood transfusion during the
perioperative period could exert effects on the patient's
subsequent response to cancer. There is concern that,
because of their suppression of the immune response, some
anesthetic drugs may assist in tumor growth or enhance
aggregation of some cancer proteins.
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Cancer patients may have life-threatening airway difficulties and
upper airway obstruction with head, neck, and chest tumors.
Preoperative preparation is required to assess potential
difficulties that may arise in securing the airway. Awake
fiberoptic intubation is the gold standard for difficult airway
management. In some patients, tracheostomy may be
indicated.
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Postoperative Considerations
Postoperative mechanical ventilation may be required,
particularly following invasive or prolonged operations and in
patients with drug-induced pulmonary fibrosis. Patients with
drug-induced cardiac toxicity are more likely to experience
postoperative cardiac complications.
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