Objectives
• Discuss the major chemotherapeutic agent classes.
• Identify effects of chemotherapeutic agents on body systems.
• Review anesthesia considerations.
• Discuss the effects of surgery and anesthesia on cancer recurrence and the immune system.
Cancer Incidence
• 2012 = 1,640,000 new cases/ 577,000 deaths.
• 2nd most common cause of death.
• Breast, prostate, lung, & colorectal cancers.
Chemotherapeutic Agents
• Interfere with cell replication and DNA synthesis.
• Target cells that rapidly replicate.
• Damage healthy cells.
Alkylating Agents
• Essentially these drugs chemically modify the cells DNA.
• Transfer of alkyl group within DNA from one molecule to another.
• Bind to DNA and inhibit both normal and cancer cell DNA processing.
• Intracellular imbalance and cell death.
• Inhibit protein synthesis.
Antimetabolites
• Substitute chemicals that are structurally similar to normal metabolites.
• Interfere with cell growth and division by preventing normal DNA replication.
• Can halt cell growth and cell division.
Antitumor Antibiotics
• Inhibit DNA and RNA synthesis.• Causes structural distortion of
DNA/RNA molecule.
• Block DNA transcription and replication. • Inhibits enzymes that wind and
unwind DNA.
• Damages DNA and cell membranes.• Iron-mediated free oxygen
molecules.
Vinca Alkaloids & Taxanes
• Interfere with the structural components important for cell replication.
• Interacts with and modifies microtubular proteins: • Alters cell division and cytokinesis• Alter microtubule function causing apoptosis
(programmed cell death)
• Made from the sap of the Madagascar Periwinkle.
Miscellaneous Agents
• Biological response modifiers• Interferon-alpha• Monoclonal antibodies
• Hormone therapy
• Mustard gas
• Other chemotherapeutic agents alter cell replication and DNA synthesis.
Cancer Premedications
• Antiemetic medications• Combination therapy
• Histamine blocking agents
• Analgesics• Cancer is associated with significant pain
• Anxiolytics• Psychological aspect of cancer
Toxic Effects of Chemotherapeutic Agents
• Type of drug
• Cumulative dose
• Dosing schedule
• Side effects vary
Myelosuppresion
• Bone marrow suppression
• Anemia
• Leukopenia
• Thrombocytopenia
• Coagulation disorders – anthracyclines & antitumor antibiotics
Central Nervous System
• Seizures – Busulfan
• Peripheral neuropathies – Vinca alkaloids; Taxanes; Alkylating agents
• Loss of deep tendon reflex – Vinca alkaloids
• Extremity weakness – Vinca alkaloids
• Vocal cord paralysis – Vinca alkaloids
• Loss of extraocular muscle function – Vinca alkaloids
Cardiovascular System• Anthracyline
antibiotics can cause cardiotoxicity.
• Risk factors for cardiac dysfunction:• Radiation of mediastinum or left chest
• Age
• Preexisting cardiac disease
• Left ventricular ejection fraction <50%
• Type of surgery
Cardiovascular System
• Signs and symptoms of cardiac damage:• Abnormal ECG findings, ST-T wave changes, QT interval
prolongation, dysrhythmias• Thrombosis, myocarditis, pericarditis, myocardial infarction,
cardiomyopathy
• Chronic manifestations of progressive cardiotoxicity:• Tachycardia • Blood pressure changes• Ventricular dilation• Exercise intolerance• Pulmonary and venous congestion• Poor perfusion
Pulmonary System
• Damage from direct lung injury or indirectly from inflammatory process.
• Bleomycin most associated with pulmonary toxicity.
• Risk factors for pulmonary dysfunction:• Age over 70• Existing pulmonary disease (COPD)• Smoking history• Genetic predisposition• Thoracic radiation therapy
Pulmonary System
• Signs and symptoms of pulmonary dysfunction:• Early inflammatory interstitial
pneumonitis• Acute noncardiogenic pulmonary
edema• Bronchospasm• Pleural effusion• Dyspnea• Cough• Tachypnea• Rales and/or wheezing• Fever
Renal System
• Acute or chronic renal failure.
• Damage to glomerular filtration, proximal tubular function, and distal tubular function.• Cisplatin, methotrexate, & ifosfamide
• Nonsteroidal anti-inflammatory drugs.
• Avoid or decrease the dose of medications that require renal clearance.
Renal System
• Risk factors for renal dysfunction:• Previous renal dysfunction • Decreased renal perfusion
• Signs and symptoms of renal dysfunciton:• Increased serum creatinine and decreased urine
creatinine clearance• Uremia• Electrolyte abnormalities • Filtration abnormalities
Hepatic System
• Signs and symptoms of hepatic dysfunction:• Elevated liver enzymes• Cirrhosis• Coagulopathies• Jaundice • Dark amber urine
• Methotrexate may induce hepatic cirrhosis and fibrosis.
• Anesthetic medications may have prolonged effect.
Gastrointestinal System
• GI mucosa sensitive to cytotoxic agents.
• Increased risk for aspiration.
• Electrolyte imbalances, dehydration, weight loss, and malnutrition.
• Signs and symptoms of GI dysfunction:• Oral mucositis • Decreased appetite• Diarrhea • Nausea and vomiting
Anesthetic Considerations
• Comprehensive preoperative history and physical examination.
• Consult with cancer physician.
• Consider corticosteroid supplementation.
• Aspiration prophylaxis.
• Patients may be taking antiemetic.
• Patients are at increased risk of sepsis.
• Prolonged duration of muscle relaxants.
• Neuromuscular blockade monitoring.
Labs and Tests
• Consider electrolytes, blood count, coagulation studies, cardiac enzymes, renal function, urine creatinine clearance, and liver function tests.
• Chest radiograph.
• Obtain ECG, cardiac echocardiogram, and may consider ejection fraction.
• PFT’s as needed.
• Blood products.
Lines and Monitoring
• IV access may be difficult
• Arterial line
• Central line
• Careful management of intravenous fluids
• TEE
• Temperature
Airway Considerations
• Range of motion
• Hoarseness
• Oral inflammation and ulceration
• Existing airway tumors in or around airway
• Auscultate
• Avoid high FiO2 (bleomycin)
• Post-operative Ventilation
Anesthetic Considerations
• Document existing neuropathies
• Chronic SNS stimulation• Consider non-adrenergic inatropes• Avoid ketamine
• Avoid excessive fluid administration
• Avoid NSAID’s
• Avoid Sevoflurane if evidence of renal disease
• Possible P-450 enzyme induction
• Pain management
Surgery and Anesthesia Effects on Cancer
Recurrence
• Tumor metastases
• Surgery suppresses immune system
• Anesthesia can suppress immune system
• Regional anesthesia
Anesthetic Best Practice for Patients
with Cancer• Cancer pain requires treatment.
• Currently no evidence to justify altering anesthesia techniques.
• Focus should be on good analgesia, decreasing surgical stress, and reducing inflammation.