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A Randomized Porcine Study in Low Cardiac Output of Vasoactive and Inotropic Drug Effects on the Gastrointestinal Tract
Örebro University, School of Medical Sciences. Department of Cardiothoracic and Vascular Surgery.
Örebro University, School of Medical Sciences. Department of Cardiothoracic and Vascular Surgery.
Department of Anaesthesiology and Intensive Care, Skaraborg Hospital, Skövde, Sweden.
Örebro University, School of Medical Sciences. Department of Surgery.ORCID iD: 0000-0003-2789-8001
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2021 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 56, no 2, p. 308-317Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Splanchnic vasodilation by inodilators is an argument for their use in critical cardiac dysfunction. To isolate peripheral vasoactivity from inotropy, such drugs were investigated, and contrasted to vasopressors, in a fixed low cardiac output (CO) model resembling acute cardiac dysfunction effects on the gastrointestinal tract. We hypothesized that inodilators would vasodilate and preserve the aerobic metabolism in the splanchnic circulation in low CO.

METHODS: In anaesthetized pigs, CO was lowered to 60% of baseline by partial inferior caval vein balloon inflation. The animals were randomized to placebo (n = 8), levosimendan (24 μg kg-1 bolus, 0.2 μg kg-1 min-1, n = 7), milrinone (50 μg kg-1 bolus, 0.5 μg kg-1 min-1, n = 7), vasopressin (0.001, 0.002 and 0.006 U kg-1 min-1, one hour each, n = 7) or norepinephrine (0.04, 0.12 and 0.36 μg kg-1 min-1, one hour each, n = 7). Hemodynamic variables including mesenteric blood flow were collected. Systemic, mixed-venous, mesenteric-venous and intraperitoneal metabolites were analyzed.

RESULTS: Cardiac output was stable at 60% in all groups, which resulted in systemic hypotension, low superior mesenteric artery blood flow, lactic acidosis, and increased intraperitoneal concentrations of lactate. Levosimendan and milrinone did not change any circulatory variables, but levosimendan increased blood lactate concentrations. Vasopressin and norepinephrine increased systemic and mesenteric vascular resistances at the highest dose. Vasopressin increased mesenteric resistance more than systemic, and the intraperitoneal lactate concentration and lactate/pyruvate ratio.

CONCLUSION: Splanchnic vasodilation by levosimendan and milrinone may be negligible in low CO, thus rejecting the hypothesis. High dose vasopressors may have side effects in the splanchnic circulation.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2021. Vol. 56, no 2, p. 308-317
National Category
Surgery
Identifiers
URN: urn:nbn:se:oru:diva-88534DOI: 10.1097/SHK.0000000000001726ISI: 000708515100018PubMedID: 33443363Scopus ID: 2-s2.0-85112126056OAI: oai:DiVA.org:oru-88534DiVA, id: diva2:1518947
Available from: 2021-01-18 Created: 2021-01-18 Last updated: 2022-08-24Bibliographically approved
In thesis
1. The gastrointestinal tract in cardiac anaesthesia and intensive care: Clinical and experimental studies
Open this publication in new window or tab >>The gastrointestinal tract in cardiac anaesthesia and intensive care: Clinical and experimental studies
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gastrointestinal (GI) complications after cardiac surgery have a substantial impact on outcome. The aims were to investigate the frequency of, and methods for detecting, GI dysfunction after cardiac surgery and its relation to outcome, and the impact of vasoactive drugs on the GI tract in experimental cardiogenic shock. Paper I investigated the intraabdominal metabolism, using intraperitoneal microdialysis, during and after routine cardiac surgery in six patients. The results imply that, even during a normal perioperative course, the GI tract may be subjected to a subclinical anaerobic state. In Paper II the impact of stepwise reductions of cardiac output (CO) on the metabolism and circulation in the GI tract was studied in anaesthetised pigs using cardiac tamponade (n=6) or partial inflation of a caval vein balloon (n=6). The two models had similar haemodynamic effects and the intraabdominal metabolism became increasingly anaerobic when the CO was reduced by 50%. In Paper III the caval vein balloon model was utilised to examine the GI effects of two inodilators (levosimendan and milrinone) and two vasoconstrictors (vasopressin and norepinephrine) at 40% CO reduction (n=7/group). Negligible splanchnic vasodilation by the inodilators in fixed low CO, and possible GI specific side effects of high dose vasopressors, were demonstrated. Paper IV included 501 cardiac surgery patients assessed using the Acute Gastrointestinal Injury (AGI) grade. Only 32.7% were asymptomatic during the first three postoperative days. At least GI dysfunction, i.e. AGI grade ≥2, developed in 2.2% and was associated with more complex surgeries and higher postoperative frequencies of GI complications and mortality. In Paper V a biomarker for enterocyte damage, intestinal fatty acid-binding protein (IFABP), was investigated in relation to AGI grade. The group with AGI ≥2 (n=11) was compared to a matched group without GI symptoms (n=22). An I-FABP concentration in the fourth quartile on day one was associated with higher frequencies of organ dysfunction and 365-day mortality. In conclusion, this thesis provides evidence for an association between intraoperative GI injury, postoperative GI dysfunction and manifest complications, and that the effects of inodilators and vasoconstrictors must be considered.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2021. p. 81
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 233
Keywords
Acute Gastrointestinal Injury grade, biomarkers, extracorporeal circulation, splanchnic perfusion, inotropic drugs, vasoactive drugs, lactate, lactate/pyruvate ratio
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-88642 (URN)978-91-7529-378-3 (ISBN)
Public defence
2021-04-23, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
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Available from: 2021-01-19 Created: 2021-01-19 Last updated: 2022-08-26Bibliographically approved

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Seilitz, JennySandblom, IsabelleOikonomakis, IoannisAxelsson, BirgerNilsson, Kristofer F.

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