Anesthesia and Chemotherapeutic Agents

Introduction

• The number of surgical patients receiving chemotherapy continues to grow, creating a need for anesthesiologists to understand the perioperative impact of anticancer agents.^1,2
• Chemotherapeutic regimens cause dose-dependent and cumulative toxicity across multiple organ systems, influencing responses to anesthetics, hemodynamic management, ventilation strategies, and postoperative outcomes.^1,3,4
• Immunotherapy adds an additional layer of complexity due to immune-related adverse events that may present subtly but progress rapidly.^5,6
• Multidisciplinary collaborative care with oncology and subspecialty services is crucial.^2,7

Cardiovascular Toxicity

• Multiple chemotherapeutic classes, including anthracyclines, HER2-targeted therapies, tyrosine kinase inhibitors, and ICIs, can produce cardiotoxicity ranging from asymptomatic dysfunction to cardiomyopathy, myocarditis, and malignant arrhythmias.^1,3,5,7
• Mechanisms include free radical injury from anthracyclines, reversible HER2 blockade with trastuzumab, and T-cell–mediated inflammation with ICIs.^3,5,7
• Patients who are at risk include extremes of age, prior ischemic heart disease, hypertension, valvular heart disease, and liver disease.⁸

Preoperative Assessment

• A focused physical exam should be performed to assess signs/symptoms of cardiotoxicity, followed by an electrocardiogram (ECG), as arrhythmias are often the first sign of cardiac dysfunction.^1,3
• Echocardiogram (especially for anthracyclines or trastuzumab)^3,7
• Cardiac biomarkers (Troponin/BNP) should be ordered when cardiac dysfunction is suspected or with ICI exposure.^5,6

Intraoperative Considerations

• Myocardial depression should be avoided and anesthetics should be titrated carefully.^1,3
• Consider an arterial line in patients with reduced ejection fraction.¹
• Stable hemodynamics should be maintained.³

Pulmonary Toxicity

• Bleomycin is strongly associated with pneumonitis and pulmonary fibrosis, which can deteriorate with high oxygen concentrations and excessive fluid administration (Figure 1, source link).^4,9
• Patients who are at increased risk are those of old age, cumulative dose >400-450U, poor pulmonary reserves, radiotherapy, uremia, higher inspired oxygen concentrations, and concomitantly administered other anticancer drugs.⁸

Preoperative Assessment

• Patients usually present with symptoms of cough, dyspnea, low-grade fever, and hypoxemia.²
• Computed tomography chest or pulmonary function tests for carbon monoxide diffusion capacity when clinically indicated.^2,4

Intraoperative Considerations

• The lowest possible fraction of inspired oxygen (FiO_₂) should be administered to maintain oxygen saturations greater than 92% to prevent increased morbidity and mortality.^2,4
• Lung-protective ventilation strategies, such as increased positive end-expiratory pressure, are preferred to maintain oxygenation over increased FiO₂.²
• A conservative fluid strategy should be considered and colloid vs crystalloid can be beneficial.^2,4

Hematologic Toxicity

• Myelosuppression from cytotoxic agents causes anemia, thrombocytopenia, and neutropenia, all of which increase infection and bleeding risks. Myelosuppression caused by chemotherapeutic agents is partially or completely reversible within 1-6 weeks of termination of therapy.

Renal and Hepatic Toxicity

• Cisplatin causes nephrotoxicity and electrolyte disturbances, including hypomagnesemia, hypokalemia, and hypocalcemia.¹
• Hepatotoxicity may occur with methotrexate and tyrosine kinase inhibitors.²

Management

• Basic metabolic panel, creatinine, and liver function tests should be ordered to check electrolytes, kidney, and liver function.^1,2
• Electrolyte derangements should be corrected.¹
• Nephrotoxins should be avoided; dosing of renally cleared anesthetics (e.g., morphine, rocuronium) should be adjusted.^1,2

Neurologic Toxicity

• Vinca alkaloids, taxanes, and platinum compounds frequently cause peripheral neuropathy, loss of deep tendon reflexes, vibratory sense, sensory ataxia, and autonomic dysfunction.^1,2

Anesthetic Considerations

• Baseline neuropathy should be documented before regional anesthesia.²
• Careful positioning should be used.¹
• Quantitative neuromuscular monitoring should be applied due to the risk of prolonged blockade.²

Immune Checkpoint Inhibitor Toxicity

• Immune checkpoints are built-in “brakes” in the immune system that prevent overactive T cells from damaging healthy tissue. Cancer cells can exploit these checkpoints to shut down T-cell attacks. ICIs block those “off” signals, reactivating T cells so they can recognize and kill tumor cells.¹¹
• ICIs, such as pembrolizumab, nivolumab, and ipilimumab, may cause myocarditis, pneumonitis, thyroiditis, adrenalitis, hepatitis, and colitis.^5,6 Toxicity may manifest weeks to months after starting medication and long after therapy cessation.^5,6

Preoperative Assessment

• Clinicians should screen for recent ICI exposure and new cardiopulmonary or endocrine symptoms.^5,6
• ECG, troponin, thyroid function, and adrenal testing should be considered as indicated.^5,6

Intraoperative Considerations

• Elective procedures should be delated if active immune-related toxicity is present.^5,6
• Clinicians should coordinate with oncology for steroid or immunosuppressive therapy.^5,6

Drug-Drug Interaction

• Chemotherapy alters cytochrome P450 metabolism, potentially affecting the clearance of opioids, benzodiazepines, and other anesthetic medications.^1,2
• Some agents (e.g., cisplatin, anthracyclines) may increase sensitivity to neuromuscular blockers, requiring dose reduction and close monitoring.¹
• There is no strong evidence that supports a clear benefit of volatile anesthesia versus total intravenous anesthesia for cancer recurrence reduction.^1,2

Summary Table