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

2. 2 Case 47 yo male, 65 kg 47 yo male, 65 kg Surgery: Wide local incision of squamous cell carcinoma of the lower lip Surgery: Wide local incision of squamous cell carcinoma of the lower lip History: History: HTN HTN Chews tobacco – 30yrs Chews tobacco – 30yrs Medications: Medications: Atenolol Atenolol Cisplatin Cisplatin 5-flurouracil 5-flurouracil Bleomycin 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%

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

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

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

6. 6 Classification of Chemotherapeutic Agents

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

8. 8 Antitumor Antibiotic Cell-cycle Specific Bleomycin : Causes fragmentation of DNA Bleomycin : Causes fragmentation of DNA Clinical uses: Hodgkin’s and non-Hodgkin’s lymphomas, testicular cancer, and squamous cell carcinoma Clinical uses: Hodgkin’s and non-Hodgkin’s lymphomas, testicular cancer, and squamous cell carcinoma mucocutaneous reactions, exacerbation of rheumatoid arthritis and pulmonary toxicity mucocutaneous reactions, exacerbation of rheumatoid arthritis and pulmonary toxicity Pulmonary Toxicity (PT) Pulmonary Toxicity (PT) 5-10% develop PT 5-10% develop PT 1-2% of all patients die from PT 1-2% of all patients die from PT Higher risk for ARDS due to free radicals from hyperoxygenation, which destroy alveolar lining 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 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% Recommendation: Keep FiO2 below 30%

9. 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. 10 Taxanes Alkaloid esters derived from the Pacific and European yew Alkaloid esters derived from the Pacific and European yew Mitotic spindle poison Mitotic spindle poison Paclitaxel: broad range of solid tumors and Kaposi’s sarcoma Paclitaxel: broad range of solid tumors and Kaposi’s sarcoma GI, Sensory neuropathy, myelosuppression GI, Sensory neuropathy, myelosuppression Doxetaxel: second line therapy in advance or refractory cancer of solid tumors Doxetaxel: second line therapy in advance or refractory cancer of solid tumors Neurotoxicity, fluid retention, neutropenia Neurotoxicity, fluid retention, neutropenia

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

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

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

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

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

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

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