Anesthetic Considerations for Chemo Patients

1. Anesthetic Considerations for Chemo Patients Brett Cavanaugh, RNAI Sacred Heart Medical Center/ Gonzaga University

2. 47 yo male, 65 kg Surgery: Wide local incision of squamous cell carcinoma of the lower lip History: HTN Chews tobacco – 30yrs Medications: Atenolol Cisplatin 5-flurouracil Bleomycin Pre-op VSS: BP 130/88, HR 72, RR 16, SpO2 96% Lungs CTA Heart tones normal Airway: MP1 , TM3, MO3 Labs: CBC & Lytes WNL Chest x-ray, EKG normal Echo: EF 57% Case

3. Intra-op • Induction: • Propofol/Fentanyl/Vecuronium • Nasally intubated, atraumatic • Maintenance: • Isoflurane/N2O/Fentanyl/Vecuronium • FiO2 <30% • Emergence: • Reversal with neostigmine/glycopyrrolate • Immediately, Pt’s sats decreased to 89% on 100% FiO2 • Copious frothy sputum from ETT, bilat rales • Pulm Edema --Lasix 40mg IV • Sats increased to 95% and Pt was taken to ICU intubated

4. Background • In 2005, cancer was the most common cause of death from disease in the USA, causing over 500,000 fatalities • At present, 50% are cured of cancer • Chemotherapy cures 10-15% • Chemotherapy is the best approach to eradication of malignant cells • Total cell-kill • Combination chemotherapy allows the largest possible doses by using different mechanisms, not sharing toxic effects

5. The Cell Cycle • Malignant cells go through normal mitosis, but synthesize DNA and divide at a faster rate • Most chemo drugs exert antineoplastic effects during DNA synthesis (S-phase) or mitosis • Cell Cycle Specific (CCS) drugs • Other chemo drugs sterilize tumor cells whether they are cycling or resting in the Go compartment • Cell Cycle Non-Specific (CCNS)

6. Classification of Chemotherapeutic Agents

7. Antimetabolites • MOA: Inhibition of DNA or RNA synthesis • Methotrexate: Folic acid analog (antagonist) • Acute Lymphoblastic Leukemia • GI tract, myelosuppression and hepatic dysfunction • 5-Fluorouracil: Pyrimidine analog (prodrug) • Breast and GI carcinomas, and skin cancer • Ulcerations of GI tract, myelosuppression • Mecaptopurine: Purine analog (prodrug) • Acute leukemia in children • GI tract, gradual myelosuppression and jaundice

8. Antitumor AntibioticCell-cycle Specific • Bleomycin: Causes fragmentation of DNA • Clinical uses: Hodgkin’s and non-Hodgkin’s lymphomas, testicular cancer, and squamous cell carcinoma • mucocutaneous reactions, exacerbation of rheumatoid arthritis and pulmonary toxicity • Pulmonary Toxicity (PT) • 5-10% develop PT • 1-2% of all patients die from PT • Higher risk for ARDS due to free radicals from hyperoxygenation, which destroy alveolar lining • Signs/Symptoms: Cough, dyspnea, basilar rales, developing into interstitial pneumonitis and fibrosis. Increased A-a gradient and decreased diffusion capacity • Recommendation: Keep FiO2 below 30%

9. Epipodophyllotoxins • Derived from mayapple root extract(podophyllotoxin) • Blocks cell division by damaging DNA strands, causing breakage • Etoposide: germ cell cancer, small cell and non-small cell lung cancer, Hodgkin’s/non-Hodgkin’s and gastric cancer • alopecia and myelosuppression • Tenoposide: acute lymphoblastic leukemia • similar to above

10. Taxanes • Alkaloid esters derived from the Pacific and European yew • Mitotic spindle poison • Paclitaxel: broad range of solid tumors and Kaposi’s sarcoma • GI, Sensory neuropathy, myelosuppression • Doxetaxel: second line therapy in advance or refractory cancer of solid tumors • Neurotoxicity, fluid retention, neutropenia

11. Alkylating Agents • Classified by the different moiety attachments • Bis (chloroethyl) amines (nitrogen mustards) • Nitrosoureas • Aziridines • Alkyl sulfonates • MOA: transfers an alkyl group (carbon with hydrogens) to the DNA causing cell death

12. Alkylating Agents Nitrogen Mustard • Mechlorethamine: Hodgkin’s disease in combination with other chemo drugs • GI, myelosuppression, herpes zoster Nitrourea • Streptozosin: pancreatic cancer • 70% produce renal or hepatic injury Aziridines • Thiotepa: ovarian/bladder/breast cancer • Myelosuppression Alkylsulfonate • Busulfan: chronic granulocytic leukemia • Myelosuppression with an increase in thrombocytopenia

13. Anthracyclines • Antibiotics isolated from Streptomyces • Not only prevent DNA/RNA replication, but also promote free radicals and cell destruction • Daunorubicin: acute lymphocytic and granulocytic leukemia, and wide range of solid tumors • Doxorubicin: metastatic adenocarcinoma and thyroid carcinoma, bladder and lung cancer. • Side effects: acutely: conduction problems, myocarditis, and pericarditis; chronically: dilated cardiomyopathy and CHF. • Myelosuppression with an increase in neutropenia

14. Antitumor AntibioticsCell-cycle non-specific • Derived from Streptomyces • Inhibits DNA/RNA synthesis • Dactinomycin: pediatric tumors; Wilms’ tumor (nephroblastoma), rhabdomyosarcoma, Ewing’s sarcoma (rare bone/soft tissue tumor) • GI, alopecia and myelosuppression • Mitomycin: squamous cell cancers • Myelosuppression

15. Platinum Analogs • Inorganic metal complex • Thought to have cytotoxic effects similar to alkylating agents • Cisplatin: broad range of solid tumors • Nephrotoxicity, ototoxicity, peripheral sensory neuropthy • Carboplatin (second generation): Same spectrum as cisplatin • Less nephrotoxic, myelosuppression

16. Conclusion • There are a variety of chemotherapeutic drugs targeted either at CCS or CCNS • Wide range of toxicities • Evaluate CBC, lytes, renal function, and ECG • Doxo/Daunorubicin = cardiotoxicity • Bleomycin = pulmonary toxicity • Cisplatin = Nephrotoxic • Wise Words: “When in doubt, Palm it out” - B. Engel, CRNA

17. Bibliography • Katsung, B. Basic and Clinical Pharmacology. 2007, 10th Ed. Pp 878-898. • Stoelting, R. Pharmacology and Physiology in Anesthetic Practice. 1987, 2nd Ed. Pp 504-520. • Mathes, D. Bleomycin and Hyperoxia Exposure in the Operating Room, Anesthesia and Analgesia, 1995; 81:624-629. • S. Prakash, H. Suri, G. Usha & A. R. Gogia :Bleomycin Induced Pulmonary Toxicity: A Case Report . The Internet Journal of Anesthesiology. 2008; 16:1