ARTICLE IN PRESS

Journal of Cardiothoracic and Vascular Anesthesia 000 (2019) 1
2

Contents lists available at ScienceDirect

Journal of Cardiothoracic and Vascular Anesthesia

journal homepage: www.jcvaonline.com

Letter to the Editor

Cardiopulmonary Bypass Priming with Hydroxyethyl
Starch 6% 130/0.4 or Sodium Chloride 0.9%: A
Preliminary Double-Blind Randomized Controlled Study
in Cardiac Surgery
To the Editor:
THE CHOICE OF cardiopulmonary bypass (CPB) priming
solution and the use of hydroxyethyl starches (HES) are both
controversial topics in cardiac surgery.1 Perioperative fluid
overload is associated with increased transfusion require-
ments and worse outcomes in the cardiac surgical setting,
and the use of colloids rather than crystalloids for CPB prim-
ing could reduce fluid balance significantly.2-4 However,
high-quality studies comparing HES 130/0.4 with usual crys-
talloids for CPB priming are lacking. In December 2013, the
European Medicine Agency declared that HES should no lon-
ger be used in critically ill patients. In elective surgical
patients, the European Medicine Agency restrained HES to
acute hypovolemia, for which crystalloids alone are not con-
sidered to be sufficient, and stipulated that additional studies
should be performed.5
Therefore, we conducted a double-blind randomized con-
trolled study aiming to compare HES 6% 130/0.4 with sodium
chloride (NaCl) 0.9% for CPB priming in elective
conventional adult cardiac surgery. The hypothesis was that
HES would reduce additional fluids needed to maintain hemo-
dynamic stability during CPB. The local ethics committee
(EudraCT 2015-001965-65-19) and the French National Drug
Agency (ANSM 160545A-42) approved the study protocol,
which was registered at ClinialTrials.gov (NCT02906514).
All patients gave informed written consent. For safety reasons,
the French regulatory authorities limited the number of
patients to a maximum of 30 with an interim safety analysis
after inclusion of 15 patients. The study was in accordance
with the CONSORT 2010 statement.6
Patients scheduled for elective conventional cardiac surgery
with CPB were included. Exclusion criteria were age younger
than 18, weight <33 kg, preoperative glomerular filtration rate
<60 mL/min/1.73 m2, redo surgery, heparin-induced thrombo-
cytopenia, preexisting hemostasis disorders, and HES allergy.
All patients were enrolled at Louis Pradel Hospital (Lyon,
France) between December 6, 2016, and January 17, 2017,
(before the interim safety analysis) and between March 23,
2017, and May 25, 2017 (after the interim safety analysis).
Pharmacists not involved in data registration or patient care
randomly assigned patients in a 1:1 ratio following simple ran-
domization procedures (computerized random numbers) to the
HES or NaCl group. The trial fluid was delivered in identical
bags (Opabag; B. Braun, Germany), which were fully covered

Table 1
Main Outcomes in Both Groups of Patients (n = 30)

HES Group (n = 15) NaCl Group (n = 15) p

Additional fluids needed during CPB (mL) 0 [0-300] 100 [0-3,815] 0.031
Intraoperative fluid balance (mL) 2250 [954-3,450] 2600 [1,499-5,715] 0.395
Length of stay in intensive care unit (d) 1.1 [0.6-11.2] 1.1 [0.6-8] 0.950
Length of stay in hospital (d) 9 [7-35] 12 [7-22] 0.251
Length of surgical drainage (d) 3 [2-5] 3 [1-4] 0.744
All blood products administration during hospital stay 3 (20) 4 (27) 1.000
Surgical revision for bleeding during the 12 first postoperative hours 0 1 1.000
Serum creatinine level on postoperative day 5 (mmol/L) 74 § 18 73 § 19 0.846
Serum creatinine level on postoperative day 28 (mmol/L) 78 § 12 82 § 27 0.895
Serum creatinine level on postoperative day 90 (mmol/L) 83 § 16 90 § 37 0.328
Acute kidney injury during follow-up period* 1 4 0.400
Renal replacement therapy during follow-up period 0 (0) 0 (0) -
Mortality during follow-up period 0 (0) 0 (0) -

NOTE. Values are expressed as median [extremes] or number (%) or mean § standard deviation.
Abbreviation: CPB, cardiopulmonary bypass.
* Defined as an increase of more than 26.5 mmol/L or more than 50% of preoperative creatinine serum level.
 ARTICLE IN PRESS
2 Letter to the Editor / Journal of Cardiothoracic and Vascular Anesthesia 00 (2019) 1
2

in custom-made, green, opaque plastic bags and sealed by 2 Vretzakis G, Kleitsaki A, Stamoulis K, et al. Intra-operative intravenous
pharmacists. Patients received 1,000 mL of nonbalanced HES fluid restriction reduces perioperative red blood cell transfusion in elective
6% 130/0.4 (Voluven; Fresenius Kabi, France) in the HES cardiac surgery, especially in transfusion-prone patients: A prospective, ran-
domized controlled trial. J Cardiothorac Surg 2010;5:7.
group or 1,000 mL NaCl 0.9% (Fresenius Kabi, France) in the 3 Morin J-F, Mistry B, Langlois Y, et al. Fluid overload after coronary artery
NaCl group for the CPB priming solution. No other fluid or bypass grafting surgery increases the incidence of post-operative complica-
medication was added. No additional HES administration was tions. World J Cardiovascular Surg 2011;1:18–23.
allowed during surgery. 4 Himpe D. Colloids versus crystalloids as priming solutions for cardiopulmo-
Demographic and clinical characteristics were similar in nary bypass: A meta-analysis of prospective, randomised clinical trials.
Acta Anaesthesiol Belg 2003;54:207–15.
both groups, except for systolic arterial pulmonary pressure 5 European Medicines Agency. Hydroxyethyl starch solutions for infusion.
(30 mmHg [extremes 15-76] in the HES group v 25 mmHg Available at: https://www.ema.europa.eu/en/medicines/human/referrals/
[extremes 15-30] in the NaCl group; p = 0.017). We found a hydroxyethyl-starch-solutions-infusion. Accessed 30 April 2019.
moderate but significant decrease in additional fluids manda- 6 Schulz KF, Altman DG, Moher D. CONSORT Group. CONSORT 2010
tory to maintain hemodynamic stability and adequate function- statement: Updated guidelines for reporting parallel group randomised trials.
BMJ 2010;340:c332;23.
ing during CPB in the HES group (Table 1). No other
difference between groups was evidenced. Remi Schweizer, MD*
Despite its robust design and encouraging results, the present Maxime Lameche, MD*
preliminary study was largely underpowered to demonstrate Clement Coelembier, MD*
any clinically relevant effect or to draw definite conclusions for Philippe Portran, MD*
clinical practice. Because of the reluctance of French regulatory William Fornier, MD*
authorities to conduct additional well-designed studies assessing Bettina Colombet, PharmDy
Daniel Grinberg, MDz
the efficacy and safety of HES 130/0.4 in elective surgical pro-
Matteo Pozzi, MD, PhDz
cedures, we call for a European or worldwide study to address Matthias Jacquet-Lagr
eze, MD*
these crucial issues in cardiac surgery. Jean-Luc Fellahi, MD, PhD*,x
*
Service d’Anesth
esie-R
eanimation, H^opital Louis Pradel,
Conflicts of Interest Hospices Civils de Lyon, Lyon, France
y
Service de Pharmacie Hospitali
ere, H^
opital Louis Pradel,
The authors have no conflicts of interest to disclose. Hospices Civils de Lyon, Lyon, France
z
Service de Chirurgie Cardiaque, Vasculaire et Thoracique, H^ opital Louis
Pradel, Hospices Civils de Lyon, Lyon, France
References x
IHU OPERA Cardioprotection, Universit e Claude Bernard Lyon 1,
Lyon, France
1 Kingeter AJ, Kingeter MA, Shaw AD. Fluids and organ dysfunction: A nar-
rative review of the literature and discussion of 5 controversial topics. J Car- https://doi.org/10.1053/j.jvca.2019.05.003
diothorac Vasc Anesth 2018;32:2054–66.