Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2020

Open Access 01-12-2020 | Septicemia | Research article

Effect of sedation with dexmedetomidine or propofol on gastrointestinal motility in lipopolysaccharide-induced endotoxemic mice

Authors: Haiqing Chang, Shuang Li, Yansong Li, Hao Hu, Bo Cheng, Jiwen Miao, Hui Gao, Hongli Ma, Yanfeng Gao, Qiang Wang

Published in: BMC Anesthesiology | Issue 1/2020

Login to get access

Abstract

Background

Sepsis often accompanies gastrointestinal motility disorder that contributes to the development of sepsis in turn. Propofol and dexmedetomidine, as widely used sedatives in patients with sepsis, are likely to depress gastrointestinal peristalsis. We queried whether propofol or dexmedetomidine, at sedative doses, aggravated sepsis-induced ileus.

Methods

Sedative/Anesthetic Scores and vital signs of lipopolysaccharide (LPS)-induced endotoxemic mice were measured during sedation with propofol or dexmedetomidine. Endotoxemic mice were divided into 10% fat emulsion, propofol, saline, and dexmedetomidine group. The gastric emptying, small intestinal transit, tests of colonic motility, gastrointestinal transit and whole gut transit were evaluated at 15 mins and 24 h after intraperitoneal injection of sedatives/vehicles respectively.

Results

40 mg·kg− 1propofol and 80 μg·kg− 1 dexmedetomidine induced a similar depth of sedation with comparable vital signs except that dexmedetomidine strikingly decreased heart rate in endotoxemic mice. Dexmedetomidine markedly inhibited gastric emptying (P = 0.006), small intestinal transit (P = 0.006), colonic transit (P = 0.0006), gastrointestinal transit (P = 0.0001) and the whole gut transit (P = 0.034) compared with the vehicle, whereas propofol showed no depression on all parts of gastrointestinal motility 15 mins after administration. The inhibitive effects of dexmedetomidine in these tests vanished 24 h after the administration.

Conclusions

Deep sedation with dexmedetomidine, but not propofol, significantly inhibited gastrointestinal peristalsis in endotoxemic mice while the inhibitory effect disappeared 24 h after sedation. These data suggested that both propofol and dexmedetomidine could be applied in septic patients while dexmedetomidine should be used cautiously in patients with cardiac disease or ileus.
Literature
1.
Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K. Assessment of global incidence and mortality of hospital-treated Sepsis. Current estimates and limitations. Am J Respir Crit Care Med. 2016;193(3):259–72.PubMed
2.
Adike A, Quigley EMM. Gastrointestinal motility problems in critical care: a clinical perspective. J Dig Dis. 2014;15(7):335–44.PubMed
3.
Bauer AJ, Schwarz NT, Moore BA, Türler A, Kalff JC. Ileus in critical illness: mechanisms and management. Curr Opin Crit Care. 2002;8(2):152–7.PubMed
4.
Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, et al. The surviving Sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367–74.PubMed
5.
Cawcutt KA, Peters SG. Severe sepsis and septic shock: clinical overview and update on management. Mayo Clin Proc. 2014;89(11):1572–8.PubMed
6.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving Sepsis campaign: international guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304–77.PubMed
7.
Herbert MK, Roth-Goldbrunner S, Holzer P, Roewer N. Clonidine and dexmedetomidine potently inhibit peristalsis in the Guinea pig ileum in vitro. Anesthesiology. 2002;97(6):1491–9.PubMed
8.
Reintam Blaser A, Jakob SM, Starkopf J. Gastrointestinal failure in the ICU. Curr Opin Crit Care. 2016;22(2):128–41.PubMed
9.
Mostafa SM, Bhandari S, Ritchie G, Gratton N, Wenstone R. Constipation and its implications in the critically ill patient. Br J Anaesth. 2003;91(6):815–9.PubMed
10.
McKeage K, Perry CM. Propofol: a review of its use in intensive care sedation of adults. CNS Drugs. 2003;17(4):235–72.PubMed
11.
Diss LB, Villeneuve S, Pearce KR, Yeoman MS, Patel BA. Region specific differences in the effect of propofol on the murine colon result in dysmotility. Auton Neurosci. 2019;219:19–24.PubMed
12.
Inada T, Asai T, Yamada M, Shingu K. Propofol and midazolam inhibit gastric emptying and gastrointestinal transit in mice. Anesth Analg. 2004;99(4):1102.PubMed
13.
Iirola T, Vilo S, Aantaa R, Wendelin-Saarenhovi M, Neuvonen PJ, Scheinin M, Olkkola KT. Dexmedetomidine inhibits gastric emptying and oro-caecal transit in healthy volunteers. Br J Anaesth. 2011;106(4):522–7.PubMed
14.
Kim N, Yoo YC, Lee SK, Kim H, Ju HM, Min KT. Comparison of the efficacy and safety of sedation between dexmedetomidine-remifentanil and propofol-remifentanil during endoscopic submucosal dissection. World J Gastroenterol. 2015;21(12):3671–8.PubMedPubMedCentral
15.
Hong G-S, Zillekens A, Schneiker B, Pantelis D, de Jonge WJ, Schaefer N, Kalff JC, Wehner S. Non-invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice. Neurogastroenterol Motil. 2019;31(3):e13501.PubMed
16.
Li Y, Wu Y, Li R, Wang C, Jia N, Zhao C, Wen A, Xiong L. Propofol regulates the surface expression of GABAA receptors: implications in synaptic inhibition. Anesth Analg. 2015;121(5):1176–83.PubMed
17.
De Winter BY, Bredenoord AJ, Van Nassauw L, De Man JG, De Schepper HU, Timmermans JP, Pelckmans PA. Involvement of afferent neurons in the pathogenesis of endotoxin-induced ileus in mice: role of CGRP and TRPV1 receptors. Eur J Pharmacol. 2009;615(1–3):177–84.PubMed
18.
Nasser Y, Fernandez E, Keenan CM, Ho W, Oland LD, Tibbles LA, Schemann M, MacNaughton WK, Ruhl A, Sharkey KA. Role of enteric glia in intestinal physiology: effects of the gliotoxin fluorocitrate on motor and secretory function. Am J Physiol Gastrointest Liver Physiol. 2006;291(5):G912–27.PubMed
19.
Hoffman JM, McKnight ND, Sharkey KA, Mawe GM. The relationship between inflammation-induced neuronal excitability and disrupted motor activity in the Guinea pig distal colon. Neurogastroenterol Motil. 2011;23(7):673–e279.PubMed
20.
Swaminathan M, Hill-Yardin E, Ellis M, Zygorodimos M, Johnston LA, Gwynne RM, Bornstein JC. Video imaging and spatiotemporal maps to analyze gastrointestinal motility in mice. J Vis Exp. 2016;108:53828.
21.
Moore BA, Manthey CL, Johnson DL, Bauer AJ. Matrix metalloproteinase-9 inhibition reduces inflammation and improves motility in murine models of postoperative ileus. Gastroenterology. 2011;141(4):1283–92 1292 e1281–1284.PubMedPubMedCentral
22.
Nagakura Y, Naitoh Y, Kamato T, Yamano M, Miyata K. Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice. Eur J Pharmacol. 1996;311(1):67–72.PubMed
23.
De Winter B-Y, De Man J-G. Interplay between inflammation, immune system and neuronal pathways: effect on gastrointestinal motility. World J Gastroenterol. 2010;16(44):5523–35.PubMedPubMedCentral
24.
Yoo JY, Kwak HJ, Kim YB, Park CK, Lee SY, Kim JY. The effect of dexmedetomidine pretreatment on the median effective bolus dose of propofol for facilitating laryngeal mask airway insertion. J Anesth. 2017;31(1):11–7.PubMed
25.
Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clinical Pharm. 2016;7(2):27–31.
26.
Gargiulo S, Greco A, Gramanzini M, Esposito S, Affuso A, Brunetti A, Vesce G. Mice anesthesia, analgesia, and care, part I: anesthetic considerations in preclinical research. ILAR J. 2012;53(1):E55–69.PubMed
27.
Coursin DB, Skrobik Y. What is safe sedation in the ICU? N Engl J Med. 2019;380(26):2577–8.PubMed
28.
Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, et al. Early sedation with Dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506–17.PubMed
29.
Alves HC, Valentim AM, Olsson IA, Antunes LM. Intraperitoneal propofol and propofol fentanyl, sufentanil and remifentanil combinations for mouse anaesthesia. Lab Anim. 2007;41(3):329–36.PubMed
30.
Li Lin A, Shangari N, Chan TS, Remirez D, O'Brien PJ. Herbal monoterpene alcohols inhibit propofol metabolism and prolong anesthesia time. Life Sci. 2006;79(1):21–9.PubMed
31.
Chassard D, Lansiaux S, Duflo F, Mion F, Bleyzac N, Debon R, Allaouchiche B. Effects of subhypnotic doses of propofol on gastric emptying in volunteers. Anesthesiology. 2002;97(1):96–101.PubMed
32.
Freye E, Sundermann S, Wilder-Smith OH. No inhibition of gastro-intestinal propulsion after propofol- or propofol/ketamine-N2O/O2 anaesthesia. A comparison of gastro-caecal transit after isoflurane anaesthesia. Acta Anaesthesiol Scand. 1998;42(6):664–9.PubMed
33.
Lee TL, Ang SB, Dambisya YM, Adaikan GP, Lau LC. The effect of propofol on human gastric and colonic muscle contractions. Anesth Analg. 1999;89(5):1246–9.PubMed
34.
Auteri M, Zizzo MG, Serio R. GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacol Res. 2015;93:11–21.PubMed
35.
Koutsoviti-Papadopoulou M, Akahori F, Kounenis G, Nikolaidis E. Propofol's biphasic effect on GABA(a)-receptor-mediated response of the isolated Guinea pig ileum. Pharmacol Res. 1999;40(4):313–7.PubMed
36.
De Ponti F, Giaroni C, Cosentino M, Lecchini S, Frigo G. Adrenergic mechanisms in the control of gastrointestinal motility: from basic science to clinical applications. Pharmacol Ther. 1996;69(1):59–78.PubMed
37.
Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst. 2000;81(1–3):87–96.PubMed
38.
Fulop K, Zadori Z, Ronai AZ, Gyires K. Characterisation of alpha2-adrenoceptor subtypes involved in gastric emptying, gastric motility and gastric mucosal defence. Eur J Pharmacol. 2005;528(1–3):150–7.PubMed
39.
Scheibner J, Trendelenburg AU, Hein L, Starke K, Blandizzi C. Alpha 2-adrenoceptors in the enteric nervous system: a study in alpha 2A-adrenoceptor-deficient mice. Br J Pharmacol. 2002;135(3):697–704.PubMedPubMedCentral
Metadata
Title
Effect of sedation with dexmedetomidine or propofol on gastrointestinal motility in lipopolysaccharide-induced endotoxemic mice
Authors
Haiqing Chang
Shuang Li
Yansong Li
Hao Hu
Bo Cheng
Jiwen Miao
Hui Gao
Hongli Ma
Yanfeng Gao
Qiang Wang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2020
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-020-01146-z

Other articles of this Issue 1/2020

BMC Anesthesiology 1/2020 Go to the issue

Research article

Effect of sex differences in remifentanil requirements for inhibiting the response to a CO2 pneumoperitoneum during propofol anesthesia: an up-and-down sequential allocation trial

Research article

The fraction of nitrous oxide in oxygen for facilitating lung collapse during one-lung ventilation with double lumen tube

Research article

Analgesic efficacy of ultrasound guided paravertebral block in percutaneous nephrolithotomy patients: a randomized controlled clinical study

Research article

What is the role of locoregional anesthesia in breast surgery? A systematic literature review focused on pain intensity, opioid consumption, adverse events, and patient satisfaction

Research article

Adding dexmedetomidine to morphine-based analgesia reduces early postoperative nausea in patients undergoing gynecological laparoscopic surgery: a randomized controlled trial

Research article

Evaluation of alveolar recruitment maneuver on respiratory resistance during general anesthesia: a prospective observational study