A 2017 consensus guideline from the European Neuroendocrine Tumor Society (ENETS) explored the optimal pre- and perioperative management of patients with neuroendocrine tumors (NETs), emphasizing the prevention of complications like carcinoid syndrome and carcinoid crisis. The optimal dosing of octreotide to prevent carcinoid crisis remains unclear. Intravenous (IV) octreotide reverses rapid crisis and is the cornerstone of prophylaxis, replacing older therapies. For patients on long-acting somatostatin analogs, these should be continued. No standard regimen exists, but for minor procedures, subcutaneous octreotide (100–200 mcg, 2–3 times/day) may suffice, with IV infusions available if needed. For major operations, subcutaneous octreotide (100 mcg, 3 times/day for 2 weeks) or IV octreotide starting at 50–100 mcg/h (mean 100–200 mcg/h) is commonly used, initiated 12 hours before surgery and continued for 48 hours postoperatively. Doses up to 500 mcg/h may be required for severe symptoms. Studies indicate lower complication rates with intraoperative octreotide, though data are limited by small sample sizes and inconsistent terminology. In atypical carcinoid syndrome, octreotide is recommended before and during surgery, with higher doses (100–200 mcg/h) and saline infusion for severe cases. [1]
Per the 2024 National Comprehensive Cancer Network (NCCN) guidelines on neuroendocrine and adrenal tumors, octreotide should be available as needed during surgical procedures for patients with carcinoid syndrome who develop hemodynamic instability that could indicate carcinoid crisis. Doses of octreotide (100–500 mcg IV) can be used, potentially followed by IV infusion of octreotide (50–300 mcg/h). Prophylactic administration of octreotide (dose unspecified) prior to surgery can be utilized although intraoperative complications can still arise, and the routine use of prophylactic octreotide has been called into question. [2]
A 2004 consensus report provided a detailed framework for the clinical use of somatostatin analogs in managing NETs of the gastroenteropancreatic system. During surgery, carcinoid crisis with hypotension is managed with IV boluses of 500–1000 mcg octreotide repeated every 5 minutes until symptoms are controlled. Alternatively, continuous IV infusion at 50–200 mcg/h can follow a bolus dose. Postoperatively, patients requiring supplemental dosing during the procedure should receive 50–200 mcg/h for 24 hours, then resume their preoperative regimen. [3], [4]
A 2013 systematic review analyzed the evidence for employing high doses of IV octreotide to manage carcinoid crises. The systematic review included 18 articles, comprising 17 case reports and one retrospective chart review, and aimed to evaluate the efficacy and safety of octreotide doses exceeding 1,500 mcg. Articles included described patients treated with IV octreotide for suspected or confirmed carcinoid crisis. Findings from the review highlighted that carcinoid crises were effectively managed in case reports with IV bolus doses ranging from 25 to 500 mcg and infusion rates between 50 and 150 mcg/h. No deaths were reported during any crisis event, and most crises were resolved promptly following octreotide administration. However, patients with prior prolonged exposure to octreotide for carcinoid syndrome or those with carcinoid heart disease appeared to require higher doses during crises. However, adverse events related to high-dose octreotide were not well-documented, and the review underscored the inconsistent use of the term "carcinoid crisis" and the paucity of outcomes data as major limitations. Although doses exceeding 1,500 mcg were used in a subset, the clinical justification and outcomes for these higher doses require further elucidation through robust investigations. [5]
A 2013 abstract reports use of higher dosing patterns beyond label recommendations for intramuscular octreotide long-acting release (LAR) in patients treated for carcinoid or pancreatic NETs (pNETs). Of 1,886 patients across 7 NCCN institutions, a total of 271 patients received octreotide LAR, of which 40% and 23% of carcinoid and pNET patients, respectively, received dosing greater than 30 mg q4w. Rationale for above-label dosing included uncontrolled symptoms, tumor progression, high urine 5-HIAA, and unknown. Dosing regimens among carcinoid patients were 40 mg q4w, 40 mg q3w, and 30 mg q2w, while dosing regimens among pNET patients include 40 mg q4w, 30 mg q2w, and 60 mg q4w. Prospective studies are still required to validate these dosing strategies, as well as to determine the most optimal dosing schedule. [6]