Anesthesia for patients with carcinoid tumors

Published on 07/02/2015 by admin

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Anesthesia for patients with carcinoid tumors

Michelle A.O. Kinney, MD, John A. Dilger, MD and Toby N. Weingarten, MD

Evaluation of carcinoid tumors

Carcinoid tumors are the most common gastrointestinal endocrine tumor, with an incidence of 3 per 100,000 per year in the United States. Carcinoid tumors arise from enterochromaffin cells (entero meaning gut and chromaffin because these cells share characteristics with chromaffin cells in the adrenal medulla) derived embryologically from epithelial stem cell precursors. Because these cells are not derived from the neural crest, they are more appropriately termed enteroendocrine than neuroendocrine. The site of origin of carcinoid tumors depends on the number of enterochromaffin cells within different organs—70% to 90% arise in the appendix, ileum, and rectum; up to 20% of tumors arise in the lungs; and less commonly, they can be found in the ovaries, thyroid, and pancreas. Enterochromaffin cells contain numerous membrane-bound neurosecretory granules composed of hormones and biogenic amines. The most prevalent compound is serotonin (80%-90% of the body’s stores), produced from its precursor, 5-hydroxytryptophan, but these cells can also produce corticotropin, histamine, dopamine, substance P, neurotensin, prostaglandins, and kallikrein. Stress of any kind can stimulate tumors to release their contents of these vasoactive substances into the circulation, resulting in mild symptoms to a full-blown carcinoid crisis.

Because the vasoactive substances contained in enterochromatin cells are cleared from the circulation by the liver, carcinoid tumors that are isolated to the gastrointestinal tract usually do not result in the systemic manifestations of the carcinoid syndrome. The carcinoid syndrome occurs when these substances are secreted into the systemic venous system from a tumor that has metastasized to the liver (thus bypassing the portal circulation) or has originated in the lungs, ovaries, or thyroid. Clinical signs and symptoms of carcinoid syndrome include bronchoconstriction, episodic cutaneous flushing, abdominal pain, diarrhea, hemodynamic instability, hepatomegaly, hyperglycemia, and dysthymia.

Laboratory test results that support a diagnosis of carcinoid tumor, either primary or metastatic, include a 24-h urine test with more than 25 g of 5-hydroxyindoleacetic acid (5-HIAA), the metabolite of serotonin, or a positive serum chromogranin A (CgA) test. Serum CgA is a glycoprotein secreted with other hormones by enteroendocrine tumors and is 95% specific and almost 80% sensitive for the detection of carcinoid tumors.

In addition to performing a physical examination and history to identify associated signs and symptoms and conducting appropriate laboratory tests, a thorough heart evaluation is warranted, looking specifically for evidence of tricuspid regurgitation and pulmonary stenosis. Left-sided valvular lesions are uncommon and are usually associated with a bronchogenic tumor. Carcinoid-related valvular fibrosis has been thought to be due to longstanding exposure to elevated levels of serotonin, but other factors must be involved because serotonin inhibitors do not prevent the cardiac valvular fibrosis.

Anesthetic management of patients with carcinoid tumors

Preoperative anesthetic management

Most patients with carcinoid tumors who are presenting for surgery will have had a careful evaluation by an endocrinologist and cardiologist and will be taking octreotide acetate, a long-acting analog of the naturally occurring peptide somatostatin. Octreotide, which inhibits release by tumor cells of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide, can be administered intravenously or subcutaneously, depending on the desired time of onset and duration of treatment. Intravenous administration results in peak serum concentrations within approximately 3 min. Subcutaneous injections of octreotide result in peak concentrations 30 to 60 min after injection; and the plasma half-life is 113 min. The biologic duration of effect may be as long as 12 h.

The usual preoperative dose of octreotide is 50 to 300 μg. Acute administration of octreotide may be lifesaving in an acute carcinoid crisis and is generally given in 50-μg to 300-μg intravenously administered doses. Octreotide doses of 500 to 1000 μg have been reported to have been given to patients undergoing cardiac valvular operations. However, intravenously administered bolus doses of octreotide of 100 μg or greater may result in bradycardia and abnormalities in atrioventricular conduction, presumably by acting directly on the cardiac conduction system. Diluting octreotide, slowly infusing the drug, and continuously monitoring the electrocardiogram may be advisable to minimize potential adverse side effects of octreotide.

Octreotide is also now available as a once-monthly intramuscularly administered slow-release preparation. Patients who are receiving the intramuscularly administered drug who need surgery may have high sustained levels of octreotide that suppress their symptoms but that are not sufficiently high to suppress the potentially higher intraoperatively released levels of vasoactive substances. Therefore, these patients may still require subcutaneously or intravenously administered doses of octreotide in the perioperative period.

The use of preoperative sedation could be justified to minimize sympathetic stimulation, which could result in a carcinoid crisis.

Intraoperative anesthetic management

The presence of hypovolemia or electrolyte abnormalities and the possibility of right-sided cardiac valvular lesions should be taken into account when planning for induction and maintenance of anesthesia. Gentle surgical skin preparation to avoid tumor compression is advised (Box 175-1). The use of histamine-releasing drugs should probably be avoided in patients with carcinoid tumors, although these drugs have been used frequently in the past without complications. Phenylephrine and amrinone have been safely used in patients with carcinoid syndrome. However, even very low doses of β-adrenergic agonists (e.g., 5 μg of intravenously administered epinephrine) have been shown to stimulate the release of vasoactive substances, but the action of these drugs can be blunted if the patient has received an adequate dose of octreotide. In a hypotensive patient, if the cause of hypotension is secondary to carcinoid crisis, additional octreotide and fluid should be administered. β-Adrenergic agonists should be used only when the cause of hypotension is thought to be secondary to decreased systemic vascular resistance or decreased cardiac output from factors unrelated to tumor activity.

Octreotide should be readily available intraoperatively for immediate treatment of carcinoid symptoms and should be administered—along with volume infusion and phenylephrine, as needed—whenever carcinoid symptoms (e.g., bronchospasm, unexpected hypotension, facial flushing) occur. The usual intravenously administered intraoperative bolus dose for the treatment of the signs of carcinoid activity is 50 to 300 μg, which may need to be repeated. The total intraoperative dose of octreotide administered in noncardiac operations may reach 4000 μg, although a dose this high is uncommon. In a study of patients with carcinoid syndrome who were undergoing cardiac operations, the median intraoperative octreotide dose was 1500 μg (mean 3666 ± 6461 μg,).

Postoperative management

The humoral effects of metastatic carcinoid lesions are usually not eliminated by surgery. Thus, octreotide should be continued postoperatively if the patient was using it preoperatively.

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