Prevention of Glucose-Induced Hypotension by the Somatostatin Analogue Octreotide (Sms 201-995) in Chronic Autonomic Failure: Haemodynamic and Hormonal Changes

Abstract

1. The haemodynamic and hormonal changes following glucose ingestion (1 g/kg) were determined before and after pretreatment with either placebo or the somatostatin analogue, octreotide (SMS 201-995, 50 micrograms subcutaneously), in seven patients with chronic autonomic failure. 2. In the placebo phase, after glucose, there was a marked and prolonged fall in blood pressure with no change in cardiac index and peripheral blood flow. Plasma insulin and neurotensin levels increased, whereas glucagon, vasoactive intestinal polypeptide, noradrenaline and adrenaline levels were unchanged. 3. Octreotide transiently raised blood pressure and prevented glucose-induced hypotension. There were no changes in cardiac index or peripheral blood flow. Plasma insulin and neurotensin levels did not rise. Plasma glucose levels increased more slowly but reached a similar level to the placebo phase. 4. We conclude that in autonomic failure patients, glucose-induced hypotension was not accompanied by changes in cardiac index or peripheral blood flow, indicating a lack of compensation to probable splanchnic vasodilatation. The hypotension was prevented by the peptide release inhibitor, octreotide, with no change in cardiac index or in peripheral blood flow, suggesting an effect on the splanchnic vasculature, probably through inhibiting release of vasodilatatory pancreatic and gut peptides.

2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society

“…[484][485][486][487] Octreotide reduces splanchnic blood flow by approximately 20%, 486 which prevents postprandial hypotension, increases blood pressure, and improves orthostatic tolerance. [484][485][486][487] return to the heart drops, with a resultant decrease in cardiac output. 31 Normally, the autonomic nervous system provides compensatory changes in vascular tone, heart rate, and cardiac contractility.…”

Postprandial hypotension. Pathophysiological mechanisms and clinical implications in different disorders.

“…22 " 24 This was first used clinically by Hoeldtke and coworkers, 22 -23 who successfully prevented postprandial hypotension by using somatostatin and later the somatostatin analogue Octreotide (SMS 201-995).…”

“…There is occasionally a modest fall in blood pressure with tachycardia. The 24 pathophysiological basis is the rapid entry of hypertonic solutions into the jejunum, resulting in fluid absorption within the gut, a reduction in plasma volume, and a rise in the hematocrit. 26 There is also an elevation in plasma levels of neurotensin and enteroglucagon, probably stimulated by passage of undigested food into the ileum.…”

“…Octreotide prevents release of insulin, neurotensin, and a range of pancreatic and gastrointestinal hormones in both normal humans and patients with autonomic failure. 24 It abolishes both glucose-( Figure 8A) and food-induced hypotension in autonomic failure. This occurs without an effect on cardiac output or peripheral blood flow, suggesting a major effect on the splanchnic circulation; this has been recently confirmed.…”

Postprandial hypotension in elderly patients with unexplained syncope

“…20 The increase in splanchnic blood volume after the meal was similar for the patients with syncope with PH and the healthy elderly subjects in whom BP remained un changed. Furthermore, two healthy subjects were able to maintain their mean arterial BP despite marked in creases in splanchnic blood volume.…”