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 ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2019

Open Access 01-12-2019 | Heart Surgery | Study protocol

Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial

Authors: Carmen A. Pfortmueller, Anna S. Messmer, Benjamin Hess, David Reineke, Laura Jakob, Stefanie Wenger, Jan Waskowski, Patrick Zuercher, Frederik Stoehr, Gabor Erdoes, Markus M. Luedi, Stephan M. Jakob, Lars Englberger, Joerg C. Schefold

Published in: Trials | Issue 1/2019

Login to get access

Abstract

Background

Intraoperative and postoperative management of cardiac surgery patients is complex, involving the application of differential vasopressors and volume therapy. It has been shown that a positive fluid balance has a major impact on postoperative outcome. Today, the advantages and disadvantages of buffered crystalloid solutes are a topic of controversy, with no consensus being reached so far. The use of hypertonic saline (HS) has shown promising results with respect to lower total fluid balance and postoperative weight gain in critically ill patients in preliminary studies. However, collection of more data on HS in critically ill patients seems warranted. This preliminary study aims to investigate whether fluid resuscitation using HS in patients following cardiac surgery results in less total fluid volume being administered.

Methods

In a prospective double-blind randomised controlled clinical trial, we aim to recruit 96 patients undergoing elective cardiac surgery for ischaemic and/or valvular heart disease. After postoperative admission to the intensive care unit (ICU), patients will be randomly assigned to receive 5 ml/kg ideal body weight HS (7.3% NaCl) or normal saline (NS, 0.9% NaCl) infused within 60 min. Blood and urine samples will be collected preoperatively and postoperatively up to day 6 to assess changes in renal, cardiac, inflammatory, acid-base, and electrolyte parameters. Additionally, we will perform renal ultrasonography studies to assess renal blood flow before, during, and after infusion, and we will measure total body water using preoperative and postoperative body composition analysis (bioimpedance). Patients will be followed up for 90 days.

Discussion

The key objective of this study is to assess the cumulative amount of fluid administered in the intervention (HS) group versus control (NS) group during the ICU stay. In this preliminary, prospective, randomised controlled clinical trial we will test the hypothesis that use of HS results in less total fluids infused and less postoperative weight gain when compared to the standard of intensive care in cardiac surgery patients.

Trial registration

ClinicalTrials.gov, NCT03280745. Registered on 12 September 2017.
Appendix
Available only for authorised users
Literature
1.
Sponholz C, Schelenz C, Reinhart K, Schirmer U, Stehr SN. Catecholamine and volume therapy for cardiac surgery in Germany—results from a postal survey. PLOS One. 2014;9(8):e103996.CrossRef
2.
Schumacher J, Klotz KF. Fluid therapy in cardiac surgery patients. Appl Cardiopulm Pathophysiol. 2009;13:138–42.
3.
Challand C, Struthers R, Sneyd JR, Erasmus PD, Mellor N, Hosie KB, et al. Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery. Br J Anaesth. 2012;108(1):53–62.CrossRef
4.
Magder S, Potter BJ, Varennes BD, Doucette S, Fergusson D. Fluids after cardiac surgery: a pilot study of the use of colloids versus crystalloids. Crit Care Med. 2010;38(11):2117–24.CrossRef
5.
Verheij J, van Lingen A, Raijmakers PG, Rijnsburger ER, Veerman DP, Wisselink W, et al. Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery. Br J Anaesth. 2006;96(1):21–30.CrossRef
6.
Jacob M, Fellahi JL, Chappell D, Kurz A. The impact of hydroxyethyl starches in cardiac surgery: a meta-analysis. Crit Care. 2014;18(6):656.CrossRef
7.
Bayer O, Schwarzkopf D, Doenst T, Cook D, Kabisch B, Schelenz C, et al. Perioperative fluid therapy with tetrastarch and gelatin in cardiac surgery—a prospective sequential analysis*. Crit Care Med. 2013;41(11):2532–42.CrossRef
8.
Hans GA, Ledoux D, Roediger L, Hubert MB, Koch JN, Senard M. The effect of intraoperative 6% balanced hydroxyethyl starch (130/0.4) during cardiac surgery on transfusion requirements. J Cardiothorac Vasc Anesth. 2015;29(2):328–32.CrossRef
9.
10.
Bellomo R, Raman J, Ronco C. Intensive care unit management of the critically ill patient with fluid overload after open heart surgery. Cardiology. 2001;96(3–4):169–76.CrossRef
11.
Ogbu OC, Murphy DJ, Martin GS. How to avoid fluid overload. Curr Opin Crit Care. 2015;21(4):315–21.CrossRef
12.
Mitchell KH, Carlbom D, Caldwell E, Leary PJ, Himmelfarb J, Hough CL. Volume overload: prevalence, risk factors, and functional outcome in survivors of septic shock. Ann Am Thoracic Soc. 2015;12(12):1837–44.CrossRef
13.
Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009;76(4):422–7.CrossRef
14.
Brandstrup B, Svendsen PE, Rasmussen M, Belhage B, Rodt SA, Hansen B, et al. Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance? Br J Anaesth. 2012;109(2):191–9.CrossRef
15.
Brandstrup B, Tonnesen H, Beier-Holgersen R, Hjortso E, Ording H, Lindorff-Larsen K, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg. 2003;238(5):641–8.CrossRef
16.
Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet. 2002;359(9320):1812–8.CrossRef
17.
Oda J, Ueyama M, Yamashita K, Inoue T, Noborio M, Ode Y, et al. Hypertonic lactated saline resuscitation reduces the risk of abdominal compartment syndrome in severely burned patients. J Trauma. 2006;60(1):64–71.CrossRef
18.
Schefold JC, Filippatos G, Hasenfuss G, Anker SD, von Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 2016;12(10):610–23.CrossRef
19.
Shimizu K, Kurosawa T, Ishikawa R, Sanjo T. Vasopressin secretion by hypertonic saline infusion during hemodialysis: effect of cardiopulmonary recirculation. Nephrol Dial Transplant. 2012;27(2):796–803.CrossRef
20.
Fang ZX, Li YF, Zhou XQ, Zhang Z, Zhang JS, Xia HM, et al. Effects of resuscitation with crystalloid fluids on cardiac function in patients with severe sepsis. BMC Infect Dis. 2008;8:50.CrossRef
21.
Liszkowski M, Nohria A. Rubbing salt into wounds: hypertonic saline to assist with volume removal in heart failure. Curr Heart Failure Rep. 2010;7(3):134–9.CrossRef
22.
Jarvela K, Koobi T, Kauppinen P, Kaukinen S. Effects of hypertonic 75 mg/ml (7.5%) saline on extracellular water volume when used for preloading before spinal anaesthesia. Acta Anaesthesiol Scand. 2001;45(6):776–81.CrossRef
23.
Jensen JM, Mose FH, Bech JN, Nielsen S, Pedersen EB. Effect of volume expansion with hypertonic- and isotonic saline and isotonic glucose on sodium and water transport in the principal cells in the kidney. BMC Nephrol. 2013;14:202.CrossRef
24.
Lavu H, Sell NM, Carter TI, Winter JM, Maguire DP, Gratch DM, et al. The HYSLAR trial: a prospective randomized controlled trial of the use of a restrictive fluid regimen with 3% hypertonic saline versus lactated Ringers in patients undergoing pancreaticoduodenectomy. Ann Surg. 2014;260(3):445–53 discussion 53-5.CrossRef
25.
Croft D, Dion YM, Dumont M, Langlois D. Cardiac compliance and effects of hypertonic saline. Can J Surg. 1992;35(2):139–44.PubMed
26.
Cross JS, Gruber DP, Burchard KW, Singh AK, Moran JM, Gann DS. Hypertonic saline fluid therapy following surgery: a prospective study. J Trauma. 1989;29(6):817–25; discussion 25-6.CrossRef
27.
Jarvela K, Kaukinen S. Hypertonic saline (7.5%) decreases perioperative weight gain following cardiac surgery. J Cardiothorac Vasc Anesth. 2002;16(1):43–6.CrossRef
28.
29.
30.
Haase-Fielitz A, Haase M, Bellomo R, Calzavacca P, Spura A, Baraki H, et al. Perioperative hemodynamic instability and fluid overload are associated with increasing acute kidney injury severity and worse outcome after cardiac surgery. Blood Purif. 2017;43(4):298–308.CrossRef
31.
Toraman F, Evrenkaya S, Yuce M, Turek O, Aksoy N, Karabulut H, et al. Highly positive intraoperative fluid balance during cardiac surgery is associated with adverse outcome. Perfusion. 2004;19(2):85–91.CrossRef
32.
Campbell JA, Holt DW, Shostrom VK, Durham SJ. Influence of intraoperative fluid volume on cardiopulmonary bypass hematocrit and blood transfusions in coronary artery bypass surgery. J Extra Corpor Technol. 2008;40(2):99–108.PubMedPubMedCentral
33.
Myburgh JA, Mythen MG. Resuscitation fluids. N Engl J Med. 2013;369(13):1243–51.CrossRef
34.
Hofmann-Kiefer KF, Chappell D, Kammerer T, Jacob M, Paptistella M, Conzen P, et al. Influence of an acetate- and a lactate-based balanced infusion solution on acid base physiology and hemodynamics: an observational pilot study. Eur J Med Res. 2012;17:21.CrossRef
35.
Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012;308(15):1566–72.CrossRef
36.
Pfortmueller CA, Kabon B, Schefold JC, Fleischmann E. Crystalloid fluid choice in the critically ill. Wien Klin Wochenschr. 2018;130(7):273–82.CrossRef
37.
Acheampong A, Vincent J-L. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care. 2015;19(1):251.CrossRef
38.
Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, DeBoisblanc B, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564–75.CrossRef
39.
Boyd JH, Forbes J, T-a N, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality*. Crit Care Med. 2011;39(2):259–65.CrossRef
40.
41.
Veroli P, Benhamou D. Comparison of hypertonic saline (5%), isotonic saline and Ringer's lactate solutions for fluid preloading before lumbar extradural anaesthesia. Br J Anaesth. 1992;69(5):461–4.CrossRef
42.
Paterna S, Fasullo S, Parrinello G, Cannizzaro S, Basile I, Vitrano G, et al. Short-term effects of hypertonic saline solution in acute heart failure and long-term effects of a moderate sodium restriction in patients with compensated heart failure with New York Heart Association class III (Class C) (SMAC-HF Study). Am J Med Sci. 2011;342(1):27–37.CrossRef
43.
Parrinello G, Paterna S, Di Pasquale P, Torres D, Mezzero M, Cardillo M, et al. Changes in estimating echocardiography pulmonary capillary wedge pressure after hypersaline plus furosemide versus furosemide alone in decompensated heart failure. J Card Fail. 2011;17(4):331–9.CrossRef
Metadata
Title
Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial
Authors
Carmen A. Pfortmueller
Anna S. Messmer
Benjamin Hess
David Reineke
Laura Jakob
Stefanie Wenger
Jan Waskowski
Patrick Zuercher
Frederik Stoehr
Gabor Erdoes
Markus M. Luedi
Stephan M. Jakob
Lars Englberger
Joerg C. Schefold
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Trials / Issue 1/2019
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-019-3420-6

Other articles of this Issue 1/2019

Trials 1/2019 Go to the issue

Study protocol

Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? Protocol for a feasibility study

Study protocol

Study protocol: developing, disseminating, and implementing a core outcome set for selective fetal growth restriction in monochorionic twin pregnancies

Study protocol

Acupoint transcutaneous electrical nerve stimulation in hospitalized COPD patients with severe dyspnoea: study protocol for a randomized controlled trial

Study protocol

Paramedic Acute Stroke Treatment Assessment (PASTA): study protocol for a randomised controlled trial

Study protocol

Effects of blood flow restriction exercise with very low load and low volume in patients with knee osteoarthritis: protocol for a randomized trial

Study protocol

Multicenter study of plastic vs. self-expanding metal stents in endoscopic ultrasound-guided drainage of walled-off pancreatic necrosis – PROMETHEUS: a randomized controlled trial protocol