Anesthesia for cancer patients is more than just mass removals and biopsies. It poses unique challenges that the anesthetist must be prepared for including necessity of alterative pain management techniques, detrimental physiologic changes, and complex procedures to remove the cancer source.
Causes of Pain
Cancer pain can occur due to invasion of tumor cells into tissue, distension and obstruction of internal organs, or from inflammatory processes produced by cancer cells. Types of pain include somatic, visceral, and neuropathic pain. Each act more predominantly on different nerve fibers that are found in the body and create a different nociceptive response depending on the type of stimulus. Somatic pain is a type of nociceptive pain that is also referred to as skin pain, tissue pain, or muscle pain. Visceral pain stems from the activation of nociceptors of the thoracic, pelvic, or abdominal organs. Neuropathic pain arises from damage to the nervous system from trauma, infection, ischemia, systemic cancer, or chemically induced (chemotherapy). Some types of neuropathic pain may develop when the peripheral nervous system becomes damaged, causing the nociceptors to transmit pain signals repeatedly leading to hypersensitivity and peripheral sensitization. This abnormal input causes abnormal central processing and the persistence of hypersensitivity associated with neuropathic pain or chronic pain. Chronic pain persists beyond tissue healing, offers no useful biologic function or survival advantage, significantly affects a patient’s quality of life, and tends to be debilitating and poorly responsive to traditional analgesic therapy.
Pain not only causes patient suffering, which is stressful to both hospital staff and owners, but also affects our patients physiologically. It has been shown that pain produces a catabolic state (energy release), which may lead to muscle wasting. It also causes an increased anesthetic risk because higher doses of anesthetic drugs are required to maintain a stable plane of anesthesia. In addition, pain suppresses the immune response, predisposing the patient to infection or sepsis and increasing hospitalization time and cost. Pain also promotes inflammation which delays wound healing.
Pain Management Techniques
Most patients diagnosed with cancer establish pain early in the disease, which intensifies rapidly as the disease progresses. The intent of pain management in these patients is to minimize peripheral and central sensitization and maintain quality of life. Pain management should therefore be multimodal and centered on chronic pain management. Analgesic medications may include NSAIDs, opioids, NMDA antagonists, alpha-2 adrenergic agonists, anticonvulsants, and tricyclic antidepressants.
NSAIDs: Inflammatory pain, hyperalgesia, and allodynia (pain caused by stimulus that does not normally elicit pain) are often controlled with NSAIDs via COX inhibition. Some tumors overexpress COX-2, increasing prostaglandin generation and inflammation. COX-2 inhibiting NSAIDs may also play an important role in management of these tumors. The most common side effects of NSAIDs include inhibition of platelet aggregation, impairment of renal perfusion, and inhibition of gastrointestinal protection.
Opioids: There is a wide range of narcotic medications that exert their effect on various opioid receptors (µ, δ, and κ). They can be administered IM or IV in the peri-operative period or orally for long term management. These drugs include hydromorphone, morphine, methadone, fentanyl, buprenorphine, codeine, and tramadol. Oral opioids have variable uptake in companion animals and should ideally be used in conjunction with other medications. Common side effects of opioids are nausea/vomiting, constipation, panting, and altered mental state/dysphoria.
NMDA antagonists: Low doses of NMDA antagonists are often used to decrease central sensitization or “wind up” pain in oncology patients. These can be especially helpful in highly painful animals with nerve or bone pain such as osteosarcoma patients. This class of drugs includes medications such as ketamine and amantadine and are safe in most patients. Side effects may include elevated heart rate, elevated blood pressure, increased salivation, and pupil dilation, but these effects are minimized at lower doses.
Alpha-2 adrenergic agonist: Dexmedetomidine and medetomidine have been used as part of sedation protocols for years, but they also have the added effect of analgesia both by acting on the alpha-2 receptors and by synergistic effects with opioid administration. Constant rate infusions can be added as part of a multimodal analgesia protocol in moderate to severe pain management. Side effects may include sedation, vasoconstriction, decreased cardiac output, bradycardia, AV block, nausea, hyperglycemia, and polyuria.
Anticonvulsants: Gabapentin has become a widely used medication in veterinary management especially for the treatment of chronic or neuropathic pain. Side effects of gabapentin are rare and include mild ataxia and sedation. Long-term therapy does not appear to worsen side effects. Pregabalin is a lesser used anticonvulsant that has a higher potency but has been studied less in veterinary medicine.
Tricyclic antidepressants: These medications block the reuptake of norepinephrine and serotonin, allowing these molecules to remain present and act on pathways that modulate pain transmission. These medications include amitriptyline, clomipramine, and imipramine. Studies on safety and efficacy in veterinary medicine are currently limited.
Common Comorbidities in Oncology Patients
Oncology patients presenting for surgery often have one or more comorbidities or paraneoplastic syndromes that need to be taken into consideration by the anesthetist. Tumors can produce and release several biologically active substances that can be more deleterious than the original tumor. Examples of paraneoplastic syndromes include cancer anorexia-cachexia syndrome (CACS), fever, anemia, thrombocytopenia, hyperproteinemia, coagulation disorders, hypoglycemia, hypercalcemia, and other general manifestations.
Cancer Anorexia-Cachexia Syndromes: This is the most common paraneoplastic disorder in veterinary patients. CACS is characterized by nausea, anorexia, and weight loss that ultimately lead to severe body fat depletion and muscle wasting. Due to a body composition with less fat and muscle, higher circulating levels of drugs may be present. Drug dosages may need to be altered to avoid overdose, prolonged recoveries, or rough recoveries. These patients may be more prone to hypothermia during the anesthetic period, so the anesthetist should decrease heat loss by insulating from cold surfaces, wrapping the patient, using warm water blankets, and/or using other active heating.
Fever: This occurs in the oncology patient either due to the production and release of pyrogenic cytokines by the tumor or from the patient’s immune system. Severe hyperthermia can cause and increased metabolic rate and oxygen consumption that can lead to dysfunction of multiple organ systems. This may include acute renal failure, disseminated intravascular coagulation, or arrhythmias. This may also cause faster drug metabolism and need for increased inhalant anesthetic concentrations. Patients should be treated for hyperthermia prior to anesthetic induction if possible.
Anemia: In cases where the tumor is causing hemorrhage or hematopoietic suppression, removal of the tumor may be necessary to improve anemia. Acute or severe anemia should be stabilized prior to anesthesia with a whole or packed red blood cell transfusion, especially if hypovolemia or hypoperfusion are a concern. Preoxygenation is vital in these patients to maximize oxygenation and guarantee optimal perfusion to tissues throughout the procedure.
Thrombocytopenia: Surgery and anesthesia may be necessary to remove malignancies triggering thrombocytopenia. The use of cytotoxic drugs may increase risk of thrombocytopenia in oncology patients. A coagulation profile (PT, PTT) can assess clotting function prior to surgery. If indicated, a plasma transfusion may be necessary to prevent excessive hemorrhage intraoperatively.
Hyperproteinemia: Patients with multiple myeloma, lymphoma, or leukemia may have concurrent hyperproteinemia. Bleeding disorders may be present in these patients due to poor platelet aggregation. Other patients may present with hyperviscosity and blood sludging, which can lead to tissue hypoxia, ocular changes, CNS deficits, cardiac disease, or multiorgan failure. In severe cases plasmapheresis may be necessary prior to anesthesia.
Hypercalcemia: Bone reabsorption by osteoclasts and concurrent release of circulating calcium may lead to hypercalcemia in oncology patients. Other diseases can cause hypercalcemia including hypoadrenocorticism and renal failure, so those diseases should be ruled out preoperatively. Signs of hypercalcemia include polyuria, polydipsia, muscle tremors, weakness, vomiting, bradycardia, stupor, and/or coma.
Cardiac arrhythmias: Changes in intracellular signaling pathways may lead to the presence of cardiac arrhythmias in the cancer patient. The most common cardiac arrhythmias seen are premature ventricular complexes and atrial fibrillation. All oncology patients should have an ECG performed prior to anesthesia, and proper treatment initiated if an arrhythmia is present and the patient is clinical.
Procedural Complications
Cancer can be present in almost any part of the body, so surgical oncology procedures can be widely variable. Some complex procedures that can be performed to remove primary tumors include splenectomies, liver lobectomies, amputation, partial pancreatectomies, mandibulectomies, thyroidectomies, and anal sacculectomies to name a few. Management of these procedures should be case-based, and protocols tailored to each patient. Some splenectomies or liver lobectomies may require blood product administration, while others may be straightforward and low risk. Some thyroidectomies may be quick procedures, while others have a risk of swelling, respiratory distress, or hemorrhage. It is the responsibility of the anesthetist to understand potential complications for each procedure and be prepared for them prior to surgery.
Oncology patients can present many challenges that the anesthetist should be prepared for prior to surgery. Pain management in these patients can be tricky, they can have multiple comorbidities, and the surgical procedures may be complicated. Thorough workups, knowledge of multimodal analgesia, understanding of paraneoplastic syndromes, and familiarity with necessary surgical procedures are key elements in successful management of anesthesia for oncology patients.
References
1. Fan TM. Cancer patients. In: Grimm KA, Lamont LA, Tranquilli WJ, Greene SA, Robertson SA, eds. Veterinary Anesthesia and Analgesia: The Fifth Edition of Lumb and Jones. 5th ed. Ames, IA: Wiley-Blackwell; 2015:993–998.
2. Salazar V. Neoplastic disease. In: Johnson RA, Snyder LB, eds. Canine and Feline Anesthesia and Co-Existing Disease. 1st ed. Ames, IA: Wiley-Blackwell; 2015:264–290.
3. John WJ, Patchell RA, Foon KA. Paraneoplastic syndromes. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, PA: Lippincott-Raven; 1997:2397–2422.