1. Management of anesthesia In cancer
Dr Abdollahi
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2. 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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3. 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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4. 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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5. MECHANISM
Cancer results from an accumulation of mutations in genes that regulate cellular proliferation.
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6. 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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7. 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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8. 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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9. 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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10. 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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12. 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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13. 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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14. 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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15. 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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16. 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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17. Fentanyl is available in transdermal and transmucosal delivery systems
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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18. 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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19. Anticonvulsants are useful for management of chronic neuropathic pain
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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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. Dorsal rhizotomy involves interruption of sensory nerve roots and is used when pain is localized to specific dermatomal levels.
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27. 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 life-threatening medical emergencies.
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28. Pathophysiologic Manifestations of Paraneoplastic Syndromes
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29. 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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30. 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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31. 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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32. Acute hemolytic anemia may accompany lymphoproliferative diseases
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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33. 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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34. 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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35. 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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36. 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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37. Ectopic Hormone Production
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38. 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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39. 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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40. 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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41. 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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42. 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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43. 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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44. 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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45. 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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46. 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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47. 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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48. 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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49. 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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50. 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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51. 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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52. 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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53. Hoarseness may reflect edema of the vocal cords
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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54. 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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55. 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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56. 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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57. 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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58. 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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59. 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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61. 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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62. 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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63. 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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64. Neurotoxicity
Anticancer chemotherapy can cause a number of neurotoxic side effects including peripheral neuropathy and encephalopathy.
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65. 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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66. 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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67. Severe diffuse brachial plexopathy has been described following an interscalene block in a patient receiving cisplatin.
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68. 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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69. 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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70. 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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71. 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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72. 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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73. 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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74. 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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75. 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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