Anesthetic Management of Carcinoid Syndrome
Carcinoid tumors are slow growing neuroendocrine cells that usually originate from primitive stem cells in the GI tract (67%), usually in the small intestine, rectum/appendix, and stomach, but may also be found in the lung, pancreas, and, rarely, gonads. They release a variety of mediators, including serotonin (abdominal cramps, diarrhea, bronchospasm), kallekrein (which converts kininogen to bradykinin, causing flushing), and histamine (vasodilation, bronchospasm). Other mediators include dopamine, prostaglandins, neurotensin, corticotrophin, and substance P. These mediators are usually metabolized by the liver before they reach the rest of the body, so by the time symptoms appear, hepatic metastases are likely. Pulmonary or ovarian carcinoid tumors also release mediators into the circulation that bypass hepatic metabolism. Carcinoid is the #1 tumor of the appendix, peaking in the 4th to 5th decade, primarily in women.
The diagnosis of carcinoid syndrome is suspected by the classic symptoms of flushing, abdominal cramping or diarrhea, and rarely, wheezing. Flushing may be induced by exercise or alcohol ingestion, or consumption of foods high in tyramine content (cheese, chocolate). However, only 10% of patients with carcinoid tumors have symptoms. The nonspecific complaint of only vague upper or lower GI symptoms can lead to a delay in diagnosis averaging 9 years from the time of symptom onset.
Chronic exposure to serotonin may produce right-sided endocardial fibrosis, leading to tricuspid insufficiency (TI) and pulmonic stenosis (PS) (TI+ PS = TIPS). Left-sided lesions are rare because serotonin is metabolized by the lungs. A pellagra-like syndrome may also occur from niacin deficiency (tryptophan may be diverted to serotonin production by the tumor). The presence of metastatic disease decreases 5-year survival from >90% to <35%.
Confirmation of the diagnosis is made by elevated urinary levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). Provocative test with Ca gluconate, catecholamines, pentagastrin, and alcohol to induce flushing are no longer used. Angiography, CT scan, or MRI can be used to localize the tumor. Metastases can occur anywhere in the body, and I-123 metaiodobenzylguanidine or indium-111 labeled octreotide scan can localize metastases. The differential diagnosis includes mastocytosis, idiopathic anaphylaxis, niacin, menopause, ethanol ingestion, and other tumors (vipoma, renal cell carcinoma, medullary thyroid carcinoma).
Symptomatic treatment can be achieved with the somatostatin analog octreotide, which inhibits release of most carcinoid hormones. Octreotide is the drug of choice for flushing and diarrhea. Flushing can also be treated with chlorpromazine or antihistamines. Corticosteroids may be used for flushing from bronchial carcinoids. Codeine, loperimide, diphenoxylate, or cyproheptadine may be used for diarrhea. Cyproheptadine is a serotonin analog. Niacin may be needed for pellagra. Surgery may be curative for isolated tumors. Metastatic disease can be treated with transarterial chemoembolization, bland embolization, radioembolization, and radiofrequency ablation. Chemotherapy is usually unsuccessful but may be attempted.
Anesthetic care begins with preoperative assessment, focusing on possible GI obstruction, malnutrition, bronchospasm, liver dysfunction, right-sided fibrosis/dysfunction, tricuspid insufficiency, and pulmonic stenosis. Intraoperatively, both hypo- and hypertension are possible, thus an arterial line should be strongly considered. Adequate IV access is also important since surgery often involves hepatic resection, with bleeding and clamping of the portal vein and hepatic artery. Portal hypertension and TI (leading to hepatic venous pulsations) may predispose to major blood loss. If severe TI exists, valve repair should be considered prior to liver surgery.
When choosing anesthetics, histamine-releasing drugs should be avoided. Vasopressors such as phenylephrine should be used to treat hypotension. Beta-agonists like epinephrine and norepinephrine have been associated with mediator release with paradoxical hypotension, and should be reserved for situations when hypotension is thought to be unrelated to tumor release. Octreotide should also be available as bolus treatment for suspected mediator release from the tumor (20-50 mc IV). It is also sometimes given as an infusion at a rate of 50 mc/hr 12 hrs preop. Side effects of octreotide include QT prolongation, bradycardia, conduction defects, abdominal cramps, nausea, and vomiting. For cases of refractory hypotension, vasopressin may be useful.
Careful postoperative monitoring should be employed, especially if tumor debulking, not complete resection, were performed. Continuous labetolol and alpha-agonists to treat hypertension, as well as IV and SQ octreotide for residual tumor release, have been used.