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SMS 201–995 and Provocation Tests in Preparation of Patients with Carcinoids for Surgery or Hepatic Arterial Embolization

The Departments of Surgery, Anesthesiology, Diagnostic Radiology, and the Institute of Neurobiology, Gothenburg University, Gothenburg, Sweden.

Abstract

Patients with midgut carcinoids undergoing surgical resection or ischemic treatment of hepatic metastases by embolization are at risk for development of carcinoid crises due to release of hormonally active tumor products. Eight such patients were treated on nine separate occasions with increasing subcutaneous doses of a synthetic somatostatin analogue (SMS 201–995) 4 days prior to surgery or hepatic arterial embolization. The patients were tested by pentagastrin provocation and simultaneous measurement of serotonin (5-HT) levels in peripheral blood before and after prophylactic treatment, to evaluate the efficacy of SMS 201–995. The provoked release of 5-HT was markedly diminished, and the basal levels of 5-HT were markedly reduced in patients with high initial levels. During surgery or embolization both SMS 201–995, as well as ketanserin, a 5-HT₂ receptor blacker, were given. With this combined treatment all patients were hemodynamically stable during surgery or embolization. During embolization the arterial levels of 5-HT increased only moderately, while urinary excretion of 5-hydroxyindoleacetic acid remained un-changed despite a proven adequate embolization. Two patients were operated on without previous treatment with SMS 201–995; both developed severe crises at induction of anesthesia, hut IV SMS 201–995 rapidly reversed the bronchoconstriction and facial flush and gradually restored arterial blood pressure, even though cardiac output remained depressed for a prolonged period. The crisis reaction correlated well with high circulating levels of 5-HT, but after treatment with SMS 201–995 these levels were still high. These findings indicate that the acute IV administration of SMS 201–995 can antagonize the peripheral actions of 5-HT and tachykinins, an effect different from the reduced release seen after prophylactic treatment with SMS 201–995. SMS 201–995 may block an intracellular mechanism common for activation of monoamine and tachykinin receptors on both tumor cells and normal cells, which would explain the observed effects. The prophylactic use of SMS 201–995 is recommended prior to surgery or hepatic arterial embolization in patients with disseminated midgut carcinoid tumors, because peripheral blockade of 5-HT, receptors alone is not sufficient to prevent a crisis reaction.

Key Words: SEROTONIN, CARCINOID—5-HT antagonist. • SURGERY, ABDOMINAL—carcinoid. • ANESTHESIA—carcinoid excision.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999