The Cancer Patient and Anesthesia

1. The Cancer Patient and Anesthesia Jan Friedman Caroline Kigotho

3. CANCER Second leading cause of death in US. Develops in 1 of 3 Americans. One of every 5 cancer victims die from the effects of their disease. Number of deaths increasing with growing elderly population.

4. Physiology Critical gene related to cancer in humans is the tumor suppressor p53. P53 gene is essential for cell viability, monitors damage to DNA. Inactivation of p53 is an early step in the development of many types of cancer. Genes are involved in carcinogenesis by virtue of inherited traits that predispose to cancer (altered metabolism of potentially carcinogenic components, decreased level of immune system function). Stimulation of oncogene formation by carcinogens (tobacco (#1), alcohol, sunlight) Responsible for 80% of US cancers.

5. Physiology Cancer cells invade the host�s immune system that destroys tumor cells. Mutant cells stimulate the host�s immune system to form antibodies. Some cancer cells are metastatic. Increased incidence of cancer in immunosuppressed patients such as those with AIDS and those receiving organ transplants.

6. Diagnosis Cancer becomes evident when the tumor cells compromise function of vital organs. Initial diagnosis by aspiration cytology or biopsy. A common staging system for solid tumors is the TNM system based on size (T), lymphnode involvement (N), distant metastasis (M). Patients are then grouped into stages from best prognosis (stage1) to poorest prognosis (stage 3 or 4).

7. TreatmentChemo, Radiation , Surgery Surgery Chemo Surgery for initial diagnosis (biopsy) definitive treatment, pallative care, and TX of pain Chemotherapy may produces significant side effects that have important implications for the management of anesthesia.

8. Complications Thrombocytopenia Immunosuppression Leukopenia Anemia Cardiac Toxicity Pulmonary Toxicity Renal Toxicity Hepatic Toxicity CNS toxicity PNS toxicity ANS toxicity Stomatitis Plasma Cholinesterase Inhibition Coagulation defects

9. Management of AnesthesiaPreop tests in patients with Cancer Hematocrit Platelet count WBC PT Electrolytes Liver Function tests Renal Function tests BG, ABG,CXR, EKG

10. Preoperative Preparation Correct Nutritional deficiencies Anemia Coagulopathy Electrolyte abnormalities Control Nausea and Vomiting Metoclopramide Droperidol Zofran Tricyclic antidepressant (potentiate opioids) Opioids may cause preop sedation) Presence of renal/hepatic dysfunction may influence choice of anesthetic drugs and muscle relaxants.

11. Preoperative Preparation 2 Possibility of prolonged responses to succinylcholine is a consideration in patients being treated with alkylating chemo drugs. Attention to anesthesia aseptic technique due to immunosuppression. Immunosuppression produced from anesthesia, surgical stimulation, and blood transfusions may exert undefined effects on the patient�s subsequent responses to cancer.

12. Pulmonary and Cardiac Toxicity Preop pulmonary fibrosis and CHF would influence conduction of anesthesia. -patients on bleomycin have a risk of interstitial pulmonary edema due to impaired lymphatic drainage owing to drug induced pulmonary fibrosis (monitor ABGS and SPO2). Depressant effects of anesthetic drugs on myocardial contractility maybe enhanced in patients with drug induced cardiac toxicity.

13. NeurotoxicityPeripheral neuropathyEncephalopathy Vinca alkaloids(vincristine) causes peripheral neuropathy causing parasthesias in digits. - ANS neuropathy may be affected. Cisplastin causes dose-dependent large-fiber neuropathy by damaging dorsal root ganglia. Corticosteroids dosages at 60 to 100 mg daily may cause a myopathy characterized by weakness causing difficulty standing and sitting and respiratory muscles maybe affected!

14. Encephalopathy High dose cyclophosphamide maybe associated with acute delirium. High dose cytarabine may cause acute delirium or cerebellar degeneration which is reversible. Reversible acute encephalopathy may accompany IV or interthecal administration of methotrexate especially in conjuction with radiation therapy and can lead to dementia.

15. Common Cancers in Clinical Practice Lung Cancer Breast Cancer Colon Cancer Prostate Cancer

16. Lung Cancer Leading cause of cancer deaths among men and women. 1/3 of all cancer deaths. More than 90% related to cigarette smoking. High mortality related to its aggressive biology and advanced state when diagnosis confirmed. Mutagens of carcinogens present in cigarette smoke causes chromosomal damage/CA. Other causes are ionizing radiation, radiation (for breast CA), asbestos and radon gas.

17. Lung CAncer Cessation of cigarette smoking decreases incidence of lung cancer to that of non smokers after 10 to 15 years have elapsed. Second hand smoke increases incidence of lung ca and increases childhood respiratory infections. Development of emphysema increases incidence of lung CA. AIDS increases risk of lung CA.

18. Signs and symptoms Cough, hemopysis, wheezing, stridor, dyspnea, or pneumonitis. Mediastinal metastasis causes hoarseness (RLN compression), superior vena cava syndrome, dysrrhythmias, CHF from pericardial effusion and tamponade. Generalised weakness, anorexia and weight loss are common.

19. Diagnosis Cytologic analysis of sputum is often sufficient for diagnosis. Lesions as small as 3.0 mm can be detected by high resolution CT scan. Flexible fiberoptic bronc with biopsy. Video assisted thoracoscopic surgery. Mediatinoscopy to examine lymphnodes.

20. Lung Cancer Healthy lung Lung cancer

21. Management of Anesthesia Evaluate underlying pulmonary and cardiac function when lung resection is planned. If mediastinoscopy, monitor for hemorrhage, pneumothorax, VAE, pressure on right subclavian artery and carotid artery. Prepare to place a DLT for a thoracotomy in order to isolate the lung, keep ETCO2 35-45, PIP <35 cm H2O. Large bore IVS X2, Aline . Standard induction: STP or propofol, succs or Roc. O2, iso and iv opioids. Epidural or intercostal block. Extubate in OR, transfer in head up position to PACU or ICU.

22. Colorectal Cancer Second cause of death after lung cancer. Adults older than 50years. 25% familial. 99% are adenocarcinomas. Polyps greater than 1.5cm are more likely to contain invasive cancer. Diet related, upper socioeconomic, living in urban areas. Direct correlation between calories consumed, dietary fat/oil, and meat protein. IBS, Smoking greater than 35 years.

23. Colon Cancer Colonoscopy: Diagnosis. Colon CA spreads to regional lymph nodes, portal circulation, liver, lungs, bones, brain. Preoperative increases in CEA. (carcinoembryonic antigen), suggest that tumor will reoccur following resection. CEA is also increased in other cancers (stomach, pancreatic, breast, lung) and non malignant conditions such as alocholic liver disease, IBS, smoking and pancreatitis.

24. Colon Cancer

25. Anesthesia Management GETA with epidural for post op pain if possible. If acute abdominal process RSI or awake intubation. Maintenance, combined epidural with GA. Decision to extubate depends on underlying cardiopulmonary status. Anticipate large 3rd space losses, large bore IVS x2, monitor UOP. T&C for 4 units PRBC.

26. Anesthesia Management Disease induced anemia. Metastasis to liver, lungs, bones or brain. Chronic large bowel obstruction does not increase risk of aspiration during induction, but may interfere with V/O. Blood transfusions are associated with decreased survival probably from immunosuppression from transfused blood.

27. Prostate Cancer Second leading cause of death among men. Increased number of reported cases due to using prostate-specific antigen (PSA) testing. Highest in african americans; lowest incidents in asians. Mostly discovered during autopsy as asymptomatic. Hereditary prostate cancer gene (HPC-1) increases the risk.

28. Prostate Cancer Previous vasectomy has been reported as a risk factor to prostate cancer but has not been substantiated Prostate cancer is always an adenocarcinoma Treatments include: -Transurethral resection -Radical prostatectomy or radiation

29. BPH

30. Anesthetic management TURP Regional or GA depends on coexisting disease and patient preference. Regional anesthesia maybe better in order to evaluate mental status to detect TURP syndrome. SAB T9 level is optimal using 0.5% bupivacaine 12mg in dextrose 7.5% solution. TURP should not exceed 2hrs due to absorption of irrigation fluid.

31. More anesthetic management Standard induction. Muscle relaxation is not mandatory but patient movement must be avoided. Anticipate BP drop when legs are dropped from lithotomy position. Blood loss can be large if venous sinuses are entered, difficult to quantify with irrigation. Invasive monitoring depends/patient condition. Signs of bladder perforation, such as shoulder pain in awake patient, maybe unnoticed under GA, may see increased HR and BP, sometimes low BP. Minimal post op pain.

32. Open prostate operations Usual preop diagnosis is BPH and prostate CA. Regional technique, GA or combined technique is used. Optimal block T8-T10. Under GA standard induction. Moderate blood loss expected with larger glands 30-80g have patient have blood available. Have 2 large bore IVs. CVP for volume status assessment. Arterial lines for continuous BP measurement and labs. Commonly used drugs (digitalis, b-blockers, diuretics, NTG) to prevent cardiovascular complications.

33. Breast Cancer Most women diagnosed with breast cancer do not die from it cure rate is 70%. It is estimated that 2 million in the US people are living with breast cancer. 75% of cases occur in patients older than 50 years of age. Family history (a first degree relative diagnosed when younger than 50 years increases the risk 3 to 4 fold). Reproductive risk factors include early menarche, late menopause, late first pregnancy, nulliparity due to prolonged exposure of breasts to estrogen.

34. Screening and prognosis Self breast exam. Clinical breast exam by a professional. Screening mammography (recommended if older than 40years. 10-15% of breast cancers are not picked up by mammography, MRI, US maybe needed.

35. Breast CA Axillary node status and tumor size determine outcome in patients with breast CA.

36. Treatments Lumpectomy with radiation. Modified radical mastectomy (with removal of breast and axillary nodes). Sentinel node dissection (dominant axillary node). If negative further axillary node dissection can be avoided. Radiation therapy accompanies lumpectomies due to reccurence. Radiation post mastectomy is not recommended due to cardiac toxicity.

37. Breast Cancer

38. Management of anesthesia Side effects of chemotherapy should be evaluated. IV lines should be avoided in ipsilateral arm to avoid exacerbation of lymphedema. Bone pain and pathological fractures should be considered when selecting regional anesthesia. Preop opioids help with pain management prior to surgery. Isosulfan dye used for localization can decrease pulse oximetry transiently. Anesthetic drugs, techniques, and monitoring depends on planned surgical procedure and pts current condition.

39. Anesthesia for breast biopsy and sentinel node biopsy MAC with local anesthesia. GA with local anesthesia for post op pain -Mask, LMA or ETT. Muscle relaxants not necessary. Minimal blood loss.

40. Anesthesia for Breast-conserving surgery, mastectomy and reconstruction GETA or GA with LMA. Regional anesthesia with paravertebral block (PVB) in breast surgery is associated with less PONV, less pain and earlier discharge. Standard induction. Use of muscle relaxants during axillary dissection should be avoided to allow identification of nerves by nerve stimulator. Risk of pneumothorax. High incidence of PONV so medicate appropriately. Minimize coughing on emergence to decrease post op bleeding.

41. Less Common Cancers Encountered in Clinical Practice Cardiac Tumors Cardiac Myxomas Metastatic Cardiac Tumors Primary Malignant Tumors Head and Neck Cancers Thyroid Cancer Esophageal Cancer Bone Cancer Multiple Myeloma Osteosarcoma Ewing�s Tumor Chondrosarcoma Gastric Cancer Liver Cancer Pancretic Cancer Renal Cell Cancer Bladder Cancer Testicular Cancer Uterine Cervix Cancer Uterine Cancer Ovarian Cancer Cutaneous Cancer

42. Less common cancersCardiac myxomas Accounts for � of all benign cardiac tumors in adults. 70% occur in LA and 30% in RA. Symptoms interfere with filling and emptying of involved cardiac chamber. Also release of myxomatous material from the tumor or thrombi that have formed in the tumor. LA myxomas mimic mitral valve disease with development of pulmonary edema. RA myomas mimic tricuspid disease causing impaired venous return and evidence of right heart failure. Embolism occurs in 30 to 40% of patients.

43. Diagnosis and treatment Incidental diagnosis during intraop TEE. Cardiac myxoma tumors are at least 0.5 to 1.0 cm in diameter can be identified by CT and MRI. Surgical resection is curative and should be done ASAP. Mechanical damage to the heart valve or adhesion of tumor to the heart valve necessitates valve replacement.

44. Anesthetic management Possibility of low cardiac output and arterial hypoxemia from obstruction at the tricuspid valve. RA myxoma prohibits placement of RA or PA catheters. SVT dysrhythmias and conduction disturbances may occur.

45. Anesthetic management GETA Aline placement prior to induction. Moderate to high dose narcotic (fentanyl 10-100mcg/kg or sufentanil 2.5-20mcg/kg), midazolam (50-350mcg/kg). Etomidate (0.1-0.3mg/kg), Vecuronium or pancuronium (0.1mg/kg) depending on desired HR to facilitate intubation. Use of fluid to treat low BP ok but consider pulmonary edema. Phenylephrine to maintain SVR. Maintain sinus rhythm. Maintain case with narcotic, low dose isoflurane and oxygen with air as tolerated. Standard monitors: PAC, TEE, foley catheter. T&C patient and have blood in the room.

46. Postoperative Considerations Postoperative mechanical ventilation following invasive or prolonged operations and in patients with preoperative drug-induced pulmonary fibrosis. Drug induced cardiac toxicity patients are more likely to experience postop cardiac complications.

47. Acute and Chronic Pain Acute pain is associated with pathological fractures, tumor invasions, surgery, radiation and chemo. Metastatic cancer pain especially to bone. Nerve compression of infiltration may cause pain. Signs of depression and anxiety.

48. Pathophysiology of pain Norciceptive pain -Somatic and visceral pain due to stimulation of norciceptors in somatic or visceral structures -Somatic pain involves bone or muscle pain described as aching, stabbing or throbbing -Visceral pain is in a hollow or solid viscus described as diffuse, crampy or gnawing. -Responds to opioids and nonopioids Neuropathic pain -Involves peripheral nerves or central afferent neural pathways described as burning or lancinating pain -Respond poorly to opioids.

49. Treatment Drug therapy such as NSAIDS and acetaminophen for mild to mod pain. Codeine for management of mod to severe pain. Opioids for severe cancer pain such as morphine and fentanyl. Tricyclic antidepressants for patients who remain depressed even when pain is controlled. TCAs are useful since they potentiate opioids. Anticonvulsants are useful for management of chronic neuropathic pain. Corticosteroids can lower pain perception decreasing need for opioids, improve mood, increase appetite and weight gain.

50. Treatment Neuraxial administration -Morphine epidurally or intrathecaly. -Implantable infusion devices when systemic infusions have failed. Neurolytic procedures -Destroying sensory component of nerves using nerve blocks. -Celiac plexus blocks for pain originating in abdominal viscera. -Dorsal column stimulators or deep brain stimulators can be used.

51. Paraneoplastic Syndromes Superior Vena Cava Syndromes Increased ICP Pericardial Tamponade Renal Failure Hypercalcemia

52. Pathophysiologic Manifestations of Paraneoplastic syndromes Fever, Anorexia, Weight Loss, Anemia Thrombocytopenia, Coagulopathies Neuromuscular abnormaities Ectopic hormone production Hypercalcemia Hyperuricemia Tumor lysis syndrome Adreneal insufficiency Nephrotc Syndrome Utereral syndrome Pulmonary hypertrphic osteoarthropathy /clubbing Pericardial effusion, Pericardial tamponade Superior vena cava syndrome Spinal cord compression Brain metastasis

53. Fever and Weight Loss Fever with any CA, but is particularly likely with mets to the Liver. Increases body temp, lactic acidosis may accompany rapidly proliferating tumors (leukemias and lymphomas). Fever may reflect tumor necrosis, inflammation, the release of toxic products by CA cells, and production of endogenous pyrogens. Anorexia and wt loss, especially with lung CA.

54. Carcnoid Tumor and Carcinoid Syndrome Slow growing malignancies of enterochromaffin cells usually found in the GI tract. (lung, pancreas, thymus, liver). Increased use of PPI ?cause. GI tract 2/3 of of carcinoids (small intestine 41.8%, rectum 28%,stomach 8.7%). Tumors secrete biologically active substances: serotonin, histamine, prostaglandins, adrenocorticoptropic hormone, gastrin, calcitonin, and growth hormone. 5-10 % develop carcinoid syndrome.

55. Carcinoid Syndrome Manifestations Episodic cutaneous flushing (kinin, histamine) Diarrhea Heart Disease Tricuspid regurgitation, pulmonic stenosis SVT Bronchoconstriction Hypotension Abdominal Pain Hypertension Hepatomegaly Hyperglycemia Hypoalbuminemia Vasoactive peptids released from carcinoid tumors in bronchi and ovaries

56. What 2 factors enhance release of carcinoid hormones? Direct physical manipulation of the tumor. Beta Adrenergic stimulation.

57. Anesthesic Considerations in Carcinoid Syndrome Most common clinical signs are flushing, wheezing, Bp & HR Changes, and diarrhea. Preop assessment: CBC, Lytes, Liver function tests, BG, EKG, Urine 5 HIAA levels. Optimize fluid and lytes. Pretreat with Octreotide. Continue in post op period. Both Histamine 1 and 2 receptor blockers must be used fully to block histamine effects. Avoid histamine releasing agents: MSO4,Thiopental, Atracurium. Avoid sympathomimetic agents : ketamine and/or ephedrine. Treat Low BP with alpha-receptor: Neo

58. Carcinoid Syndrome GA over RA. Pts with high serotonin levels have prolonged recovery, use des or sevo for rapid recovery. Aggressively maintain normothermia to avoid catecholamine-induced vasoactive mediator release. Monitor BG intraoperatively, prone to hyperglycemia.

59. Octreotide Somatostanin analog is used to blunt the vasoactive and bronchoconstrictive effects of carcinoid tumor products. TX 2 weeks before OR dose of 100mcg SQ TID 50 to 150 mcg SQ preop. 100mcg/hr infusion. 100 to 200mcg IV for intraop carcinoid crisis. Bronchospasm (histamine or bradykinin) have shown to be resistant to ketamine or inhalation agents. Use Beta 2 agonists for bronchodilitation.

60. Superior Vena Cava Obstruction Engorgement of veins above the waist, particularly jugular veins. Dyspnea, airway obstruction. Facial and arm edema. Hoarseness may reflect edema of the vocal cords.

61. Spinal Cord Compression Metastatic lesions in the epidural space, most often relflecting breast, lung, prostate cancer or lymphoma. Pain, Skeletal muscle weakness, sensory loss, autonomic nervous system dysfunction. Corticosteroids, radiation, MRI, CAT, Myelography.

62. Increased ICP Nausea Seizures Decreased level of consciousness Mental deterioration Focal neuro deficits CAT scan, corticosteroids, diuretics, mannitol Radiation, Intrathecal Chemo

63. Cancer Does Anesthetic Management affect Cancer Outcomes?

64. The Stress Response and CANCER Immune response is controlled by cytotoxic T lymphocytes, NK (natural killer) cells, NK-T-cells, dendritic cells and macrophages. Inflammatory mediators such as interferon (INF) and interleukin (IL) increase the activity of T and NK cells. B-adrenergic stimulation which increases during stress states suppresses NK activity and so promotes metastasis. Low NK activity increases cancer morbidity and mortality.

65. Surgery, Anesthesia and CANcer Metastasis Surgery suppresses immunity and so promotes metastasis. Surgical stress promotes angiogenesis and contributes to neoplastic growth. Minimally invasive procedures might be better for cancer patients.

66. Anesthetic Drugs A study in rats showed that ketamine, thiopental, and halothane reduced NK cell activity and increased lung metastasis. The effect of ketamine might be due to adrenergic stimulating properties. Propofol does not promote metastasis may be due to its weak beta adrenergic antagonist properties.

67. Anesthesia: Animal Studies Morphine promotes angiogenesis and promotes breast tumor growth in rodents. Pain relief decreases metastasis susceptibility due to reduction in stress response. It is now know that opioids inhibit cellular and humoral immune function in humans.

68. Anesthesia: Animal Studies Decreases use of inhaled agents and opioids which decrease NK cells. Opioids administered intrathecally in small quantities do not have the same effect on NK cells. Decreases release of catecholamines which reduce NK cell activity. Epidural anesthesia improves post op outcomes by decreasing surgical stress. In a study of mice a laparatomy procedure using sevo increased liver mets as compared to sevo and spinal anesthesia.

69. Neuraxial Anesthesia: Human Data Use of paravertebral anesthesia and analgesia for breast cancer decreases risk of reoccurence. A study on men undergoing a prostatectomy under GA with morphine compared to GA with epidural anesthesia, epidural technique was associated with a 65% reduction in biochemical recurrence of prostate CA.

70. Neuraxial Anesthesia: Human Data Spinal anesthesia for a TURP resulted in less immunosupression after surgery. If reducing volatile anesthetic requirements or opiates is vital, use of dexmedetomidine or IV lidocaine might be beneficial.

71. Conclusion Our anesthetic drugs and approaches may impact tumor metastasis after cancer surgery. Techniques that prevent stress responses and increase catecholamine, and that limit requirements for volatile anesthetics and opiates, seem effective in reducing the incidence of metastasis. Since 90% of cancer related death is due to metastatic development rather than primary cancer, then potential for improving patient outcome is very significant.

72. Case Study 50 year old female, Ima Goner undergoing primary resection of the small intestine tumor. She has been on Proton Pump Inhibitor for 10 years, and was recently diagnosed at the SDSC via colonoscopy. Labs include: H/H: 9.8/31. Na+ 140, K+ 3.9, BG, 153. During tumor removal the patient becomes hard to ventilate, wheezes are detected, BP goes to 70/40, HR 112, code brown ensues.What is the most common clinical scenario happening?

73. Case Study Preoperative Assessment for this case should have included what 6 to 7 tests? CBC Electrolytes LFTs BG EKG (Echo if indicated) Urine 5-HIAA levels What drug should this patient have been treated with? How long? Octreotide Treatment 2 weeks pre-op 100mcgs SQ Anesthestic drugs of choice for this case include: STP, MSO4, Atricurium, Ketamine, Ephedrine, Halothane, Isoflurane. True or False?

74. Case Study What two drug catagories/blockers must be utilized to fully counteract histamine release? H1 and H2 Receptor Blockers Treat hypotension with what drug? Alpha Receptor Agonist- Neo What temperature should this patient be maintained? Normothermic What lab should be assessed during the case? BG

75. Question 1 An otherwise healthy patient is undergoing a small bowel resection for tumors and develops bronchoconstriction, cutaneous flushing of the face and neck, and supraventricular tachydysrythmias during manipulation. The most likely cause of these signs is: A. Acute asthma attack B. Anaphylaxis reaction C. Carcinoid syndrome D Autonomic hyperreflexia

76. Rationale C: Carcinoid syndrome Manifestations of carcinoid syndrome include: cutaneous flushing (kinins, histamine), supraventricular tachydyshythmias (serotonin), Bronchoconstriction (serotonin, bradykinin, substance P).

77. Question 2 Treatment of hypotension in a patient anesthetized for resection of metastatic carcinoid would be best accomplished with? A: Epinephrine B: Ephedrine C: Somatostatin D: Angiotensin

78. Rationale: C: Somatostatin Suppresses the release of serotonin and other vasoactive substances from the tumor.

79. Question 3 A 55 year old is to undergo a TURP under general anesthesia. The patient has a 40 pack year smoking history and a history of CHF. The patient receives Reglan and Scopolamine preoperatively. General anesthesia is induced with Ketamine the procedure is uneventful. In PACU the patient complains of inability to see objects up close.The most likely cause would be?

80. Question 3 A: Effects of scopolamine B: Emergence delirium from ketamine C: Effects of glycine in the irrigating solution D: Corneal abrasion E: Hyponatremia

81. Rationale: A: Effects of Scopolamine Scopolamine is an anticholinergic that may produce mydriasis and can result in patients inability to accommodate.

82. Question 4 Induction of anesthesia in the cancer patient being treated with alkylating chemo drugs may exhibit one of the following complications: A. Decreased urinary output. B. Increased HR and BP. C. Decreased BP and bradycardia. D. Prolonged response to Succinylcholine.

83. Rationale: D: Prolonged response to Succinylcholine.

84. Question 5 Cancer patients on large doses of corticosteroid may exhibit the following on emergence: A: Respiratory weakness. B: Cardiac dysrrhythmias. C: Prolonged effect of narcotics. D: Decreased sodium and water retention.

85. Rationale: A: Respiratory Weakness. Corticosteroids cause a myopathy characterized by weakness causing difficulty standing sitting and respiratory muscles may be affected.

86. Sing As though no one can hear you. Live As though heaven is on earth. Dance As though no one is watching you. Love As though you have never been hurt before. Mark Twain