European Journal of Cardio-Thoracic Surgery 53 (2018) 5–33

doi:10.1093/ejcts/ezx314 Advance Access publication 6 October 2017

2017 EACTS Guidelines on perioperative medication

in adult cardiac surgery

EACTS GUIDELINES
Authors/Task Force Members: Miguel Sousa-Uva* (Chairperson) (Portugal), Stuart J. Head (Netherlands),
Milan Milojevic (Netherlands), Jean-Philippe Collet (France), Giovanni Landoni (Italy), Manuel Castella (Spain),
Joel Dunning (UK), To mas Gudbjartsson (Iceland), Nick J. Linker (UK), Elena Sandoval (Spain),
Matthias Thielmann (Germany), Anders Jeppsson (Sweden) and Ulf Landmesser* (Chairperson) (Germany)

Document Reviewers: Georg Trummer (Germany), David A. Fullerton (USA),

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Alexander Wahba (Norway), Udo Sechtem (Germany), Jorge Ferreira (Portugal), Andreas Koster (Germany)

* Corresponding authors. Department of Cardiac Surgery, Hospital de Santa Cruz, Av Professor Reinaldo dos Santos, 2790-134 Carnaxide, Portugal; Departamento de
Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, Alameda Prof Hernani Monteiro, 4200-319 Porto, Portugal. Tel: +351-21-0431000, fax: +351-
21-4188095; email: [email protected] (M. Sousa-Uva). Department of Cardiology, Charité—Universit€atsmedizin Berlin (CBF), Hindenburgdamm 30, 12203
Berlin, Berlin Institute of Health (BIH), and Deutsches Zentrum für Herz Kreislaufforschung (DZHK), Berlin, Germany. Tel: +49-30-450513702, fax: +49-30-450513999;
email: [email protected] (U. Landmesser)
Keywords: EACTS Guidelines • Cardiac surgery • Perioperative medication • Risk reduction • Secondary prevention • Coronary artery
bypass grafting • CABG • Valve replacement • Transcatheter aortic valve implantation • Antiplatelet • Antithrombotic • Beta-blockers •
Statins • Glucose management • Pain • Steroids • Antibiotics • Atrial fibrillation

TABLE OF CONTENTS 4. Atrial fibrillation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

4.1 Preoperative atrial fibrillation prophylaxis. . . . . . . . . . . . . . . . . . . 15
Table of contents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4.2 Management of postoperative atrial fibrillation . . . . . . . . . . . . . . 15
Abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 4.3 Thromboembolism prevention for postoperative
1. Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 atrial fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 5. Renin–angiotensin–aldosterone system inhibitors . . . . . . . . . . . . . . . 16
3. Antithrombotic management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 5.1 Preoperative discontinuation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.1 Acetylsalicylic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 5.2 Postoperative use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.1.1 Discontinuation before surgery . . . . . . . . . . . . . . . . . . . . . . . . 8 6. Beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.1.2 Restart after surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 6.1 Preoperative beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.2 P2Y12 inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 6.2 Postoperative beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.2.1 Discontinuation before surgery . . . . . . . . . . . . . . . . . . . . . . . . 8 7. Dyslipidaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.2.2 Platelet function testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 7.1 Statins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.2.3 Restart after surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 7.1.1 Preoperative therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.3 Glycoprotein IIb/IIIa inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 7.1.2 Postoperative use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.4 Preoperative anticoagulation and bridging . . . . . . . . . . . . . . . . . . 10 7.2 Non-statin lipid-lowering agents . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.5 Postoperative antithrombotic and bridging . . . . . . . . . . . . . . . . . 12 8. Ulcer prevention and steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.5.1 Mechanical prostheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 8.1 Ulcer prevention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.5.2 Bioprostheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 8.2 Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.5.3 Valve repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 9. Antibiotic prophylaxis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.5.4 Transcatheter aortic-valve implantation . . . . . . . . . . . . . . . . 14 9.1 Dosing of surgical antibiotic prophylaxis. . . . . . . . . . . . . . . . . . . . 20
3.5.5 Other indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 9.2 Duration of surgical antibiotic prophylaxis . . . . . . . . . . . . . . . . . . 20

Disclaimer 2017: The EACTS Guidelines represent the views of the EACTS and were produced after careful consideration of the scientific and medical knowledge
and the evidence available at the time of their dating. The EACTS is not responsible in the event of any contradiction, discrepancy and/or ambiguity between these
Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeu-
tic strategies. Health professionals are encouraged to take the EACTS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and
the implementation of preventive, diagnostic or therapeutic medical strategies; however, the EACTS Guidelines do not in any way whatsoever override the individual responsi-
bility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and, where appropriate and/or necessary, in con-
sultation with that patient and the patient’s care provider. Nor do EACTS Guidelines exempt health professionals from giving full and careful consideration to the relevant
official, updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted
data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to
drugs and medical devices at the time of prescription.

C The European Association for Cardio-Thoracic Surgery 2017. All rights reserved. For permissions please email: [email protected]
V
6 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

9.3 Choice of surgical antibiotic prophylaxis . . . . . . . . . . . . . . . . . . . . 21 recommendations, usually derived from randomized clinical trials
10. Anaesthesia and postoperative analgesia. . . . . . . . . . . . . . . . . . . . . . 22 or large registries.
10.1 Regional anaesthesia for perioperative pain control . . . . . . . . . 22 Quality criteria for developing clinical guidelines require trans-
10.2 Postoperative pain assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 parency on how they are formulated. The methodology manual
11. Blood glucose management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 for the EACTS clinical guidelines was issued to standardize the
12. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 developmental process of evidence-based documents [1].
Members of the task force to develop a clinical guideline on
perioperative medication in adult cardiac surgery were selected
ABBREVIATIONS AND ACRONYMS for their expertise in their respective areas. To increase the cred-
ibility of evidence-based documents, EACTS aims for a collabora-
ACEI Angiotensin-converting enzyme inhibitor tive process with other specialists also involved in the diagnosis
ACS Acute coronary syndrome or treatment of the given condition. For the current clinical
AF Atrial fibrillation guideline, non-cardiac surgeon specialists, known to be experts
AKI Acute kidney injury in their particular domains, were invited to join the task force;
ARB Angiotensin II receptor blocker however, it should be noted that other scientific societies have
ASA Acetylsalicylic acid

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not officially endorsed this clinical guideline.
CABG Coronary artery bypass grafting Task force members undertook an evidence review, assisted by
CAD Coronary artery disease 2 dedicated research fellows. The level of evidence (Table 1) and
CHA2DS2-VASc Congestive heart failure, hypertension, the strength of the recommendations (Table 2) were weighed
age >_ 75 (2 points), diabetes, prior stroke and graded according to predefined scales [1].
(2 points)–vascular disease, age 65–74, In accordance with the methodology manual for the EACTS
sex category (female) clinical guidelines, task force members were asked to complete
CI Confidence interval declarations of interest.
COX Cyclo-oxygenase
CPB Cardiopulmonary bypass
DAPT Dual antiplatelet therapy Table 1: Levels of evidence
DM Diabetes mellitus
EACTS European Association for Cardio- Level of Data derived from multiple randomized clinical trials or meta-
Thoracic Surgery evidence A analyses.

ICU Intensive care unit Level of Data derived from a single randomized clinical trial or large
evidence B non-randomized studies.
INR International normalized ratio
Level of The consensus of expert opinion and/or small studies,
IV Intravenous evidence C retrospective studies, registries.
LDL-C Low-density lipoprotein cholesterol
LMWH Low-molecular-weight heparin
LVEF Left ventricular ejection fraction
MI Myocardial infarction
NOAC Non-vitamin K antagonist oral Table 2: Classes of recommendations
anticoagulant
NYHA New York Heart Association Classes of Definition Suggested
OAC Oral anticoagulant recommendations wording to use
Class I Evidence and/or general Is recommended/is
OR Odds ratio agreement that a given indicated
PCSK9 Proprotein convertase subtilisin/kexin treatment or procedure is
beneficial, useful and
type 9 effective.
POAF Postoperative atrial fibrillation Class II Conflicting evidence
and/or a divergence of
RAAS Renin–angiotensin–aldosterone system opinion about the
RCT Randomized controlled trial usefulness/efficacy of the
given treatment or
SAP Surgical antibiotic prophylaxis procedure.
SAPT Single antiplatelet therapy Class IIa Weight of evidence/opinion Should be considered
is in favour of usefulness/
SSI Surgical site infection efficacy.
TAVI Transcatheter aortic valve implantation Class IIb Usefulness/efficacy is less
well established by
May be considered

UFH Unfractionated heparin evidence/opinion.

VKA Vitamin K antagonist Class III Evidence/general
agreement that the given
Is not recommended

treatment/procedure is not
useful/effective and may
sometimes be harmful.

1. PREAMBLE
The European Association for Cardio-Thoracic Surgery (EACTS) 2. INTRODUCTION
Guidelines Committee is part of the EACTS Quality Improvement
Programme and aims to identify topics in cardiothoracic surgery Adult cardiac surgery is an essential therapeutic approach to reduce
where there is a need for guidance. Clinical guidelines are issued mortality and morbidity in appropriately defined patients. The out-
for areas where there is substantial evidence to support strong come depends on the management of underlying conditions, and
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 7

medical treatment is key in the optimal perioperative and long- illustration (Fig. 1) summarizes what is new and what is essential in
term success of the cardiac surgery. Several studies have suggested these guidelines according to the class of recommendation.
that patients who have had coronary artery bypass grafting (CABG)
benefit the most from risk factor-modifying strategies [2–6].
Medical therapy affects adult cardiac surgery at 3 distinct stages: 3. ANTITHROMBOTIC MANAGEMENT

EACTS GUIDELINES
preoperative, intraoperative and postoperative [7]. Preoperatively,
one might need to introduce or interrupt drugs to decrease the odds Antithrombotic treatment with anticoagulants and platelet inhibi-
of procedural complications. Intraoperatively, control of glycaemia tors reduces the risk for thromboembolic complications but may
and prophylactic antibiotics are essential to reducing the risk for in- increase the risk for intraoperative and postoperative bleeding
fectious complications. Postoperatively, restarting or initiating medi- complications. An individual assessment of the risk for thrombo-
cation to prevent ischaemic events, prevent arrhythmias and manage embolism and bleeding based on the medication, patient condition
cardiovascular risk factors and heart failure is required to impact the (elective, urgent or emergent), imaging results and planned surgical
long-term prognosis in a positive way, especially if the medications intervention is recommended within the heart team conference.
are included in a formal programme of cardiac rehabilitation [8].
Cardiac surgery is always a major life event that is associated with

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increased disease awareness and represents a unique opportunity to Multidisciplinary decision making
introduce optimized medical therapy and stress the importance of
lifestyle modifications, compliance with medication and lifelong
follow-up. Surgical patients are often treated suboptimally [9, 10], al- Recommendation Classa Levelb Ref c
though the benefit of a more intense postoperative patient-based It is recommended that the Heart
medication therapy is established after cardiac surgery [10, 11]. Team discuss the optimal timing of
The surgical community may be somewhat underinformed on stopping antithrombotic preoperative I C
treatment of patients undergoing car-
this topic [12], despite the availability of previously published guide- diac surgery, based on ischaemic and
lines on specific drugs [13–15]. Therefore, the EACTS Clinical bleeding risk.
Guideline Committee determined that there was a need to produce
an updated guideline focusing on the main pharmacological classes a
Class of recommendation.
involved in the perioperative treatment and prevention of adverse b
Level of evidence.
events in patients undergoing adult cardiac surgery. Medications c
References.
used for the treatment of operative complications, such as graft
vasospasm after CABG, perioperative ischaemia, myocardial infarc-
tion (MI), low cardiac output syndrome, renal failure, arrhythmias 3.1 Acetylsalicylic acid
except for atrial fibrillation (AF), pneumonia, wound infection and
neurological complications, have been excluded. The underlying ra- Acetylsalicylic acid (ASA) is one of the cornerstones for the treatment
tionale for excluding these topics from the final document is the of acute and chronic cardiovascular disease. Secondary prevention
fact that they are comprehensively covered in other relevant clinical with ASA has been shown to reduce mortality, MI and cerebrovascu-
guidelines [16–22] or that these surgical complications will be lar events in different subsets of patients with occlusive cardiovascular
included in an upcoming expert document. The following central disease [23], but also to increase the risk for bleeding complications.

Figure 1: Central illustration with the main recommendations. ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker; CABG: coronary
artery bypass grafting; EACTS: European Association for Cardio-Thoracic Surgery; LDL: low-density lipoprotein; LVEF: left ventricular ejection fraction: NOACs: non-
vitamin K antagonist oral anticoagulants; POAF: postoperative atrial fibrillation.
8 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

3.1.1 Discontinuation before surgery. A meta-analysis of 13

trials with 2399 patients who had CABG that compared adminis- Recommendations for perioperative acetylsalicylic
tration of ASA preoperatively versus no treatment or treatment acid management
with a placebo [24] showed that treatment with ASA reduced the
risk for perioperative MI [(odds ratio (OR) 0.56; 95% confidence
Recommendations Classa Levelb Ref c
interval (CI) 0.33–0.96] but did not reduce the mortality rate (OR
1.16; 95% CI 0.42–3.22). Postoperative bleeding, red cell transfu- Preoperative period
sions and surgical re-exploration were increased with ASA. In patients on ASA who need to
However, the included studies were of low methodological undergo CABG surgery, continuing IIa C
quality. ASA throughout the preoperative
A recent large randomized controlled trial (RCT) compared the period should be considered.
administration of ASA (100 mg) on the day of the operation ver- Stopping ASA at least 5 days before
sus the use of a placebo in patients having CABG [25] and dem- surgery should be considered in
onstrated no significant effect of treatment with ASA on patients who refuse blood transfu- IIa C
thrombotic and bleeding perioperative events. However, the sions, undergo non-coronary
cardiac surgery or are at high riskd

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included patients were eligible only if they were not using ASA of re-exploration for bleeding.
preoperatively or had stopped ASA at least 4 days before the op-
eration. Therefore, a strategy of discontinuation versus continu- Bridging oral antiplatelet therapy III B
with LMWH is not recommended. [29]
ation was not evaluated.
Another RCT on pretreatment demonstrated that a large dose Postoperative period
(300 mg) of ASA preoperatively was associated with increased It is recommended to (re)start ASA
postoperative bleeding but with a lower rate of major cardiovas- as soon as there is no concern over I B [33, 34]
cular events at a 53-month follow-up [26]. Similarly, a small RCT bleeding, but within 24 hours of
reported that patients pretreated with ASA (300 mg) had signifi- CABG.
cantly more postoperative bleeding (+25%) and that this effect In patients undergoing non-coron-
was more pronounced (+137%) in carriers of the glycoprotein ary cardiac surgery with a pre-
(GP) IIIa allele PlA2 [27]. Similar results were presented in a previ- operative indication for ASA, it is
recommended that treatment is I C
ous meta-analysis [28], where less bleeding was reported in pa-
restarted as soon as there is no
tients receiving <325 mg ASA daily. Of note, stopping ASA 5 days concern over bleeding, but within
before the operation and replacing it with low-molecular-weight 24 hours after surgery.
heparin (LMWH) increases the risk for bleeding complications
and therefore should be abandoned [29]. a
Class of recommendation.
In summary, the continuation of ASA is associated with more b
Level of evidence.
blood loss but fewer ischaemic events during and after CABG sur- c
References.
gery. Recent data suggest that the inhibiting effect of ASA on plate- d
Complex and redo operations, severe renal insufficiency, haematolo-
let aggregability is clearly susceptible to platelet transfusion [30, gical diseases and hereditary deficiencies in platelet function.
31], which also argues for the continuation of ASA in patients ASA: acetylsalicylic acid; CABG: coronary artery bypass grafting;
undergoing elective or urgent CABG. However, in patients who re- LMWH: low-molecular-weight heparin.
fuse blood transfusions, who undergo non-coronary cardiac sur-
gery or who are at high risk of re-exploration for bleeding—such 3.2 P2Y12 inhibitors
as complex and redo operations, severe renal insufficiency, haem-
atological disease and hereditary platelet function deficiencies— Dual antiplatelet therapy (DAPT) with ASA and P2Y12-receptor
stopping ASA at least 5 days before surgery should be considered inhibitors (clopidogrel, ticagrelor and prasugrel) (Table 3) reduces
[32]. The increased risk for bleeding complications if ASA and other the risk for thrombotic complications in patients with acute cor-
antithrombotic drugs are not discontinued must be weighed onary syndrome (ACS) compared to treatment with ASA only
against the potentially increased risk of thrombotic complications [35–37], especially if they undergo percutaneous coronary inter-
during the preoperative cessation period. vention. The risk for thrombotic complications is further reduced
if one of the more potent third-generation P2Y12 inhibitors (tica-
grelor or prasugrel) is used instead of clopidogrel [36, 37], at the
3.1.2 Restart after surgery. In a large prospective observa- expense of increased spontaneous and surgical bleeding compli-
tional trial [33], patients who restarted ASA within 48 h of CABG cations [36–38].
had a mortality rate of 1.3% compared with a rate of 4.0% among
those who did not receive ASA during this period (P < 0.001). ASA
therapy was associated with a 48% reduction in the incidence of 3.2.1 Discontinuation before surgery. Continuing DAPT until
MI (P < 0.001), a 50% reduction in the incidence of stroke the operation increases the risk of bleeding, transfusions and re-
(P = 0.01), a 74% reduction in the incidence of renal failure exploration for bleeding, as shown in RCTs [39–41], observational
(P < 0.001) and a 62% reduction in the incidence of bowel infarc- studies [42, 43] and meta-analyses [44, 45]. It is, therefore, recom-
tion (P = 0.01). A systematic review of 7 studies showed that ad- mended that P2Y12-receptor inhibitors be discontinued before
ministration of ASA within 6 h of CABG was associated with elective surgery whenever possible [7, 46]. Alternatively, elective
improved graft patency without increased incidence of bleeding operations may be postponed until the DAPT treatment period is
complications [34]. Therefore, ASA should be given to all patients completed. In urgent cases—most often in patients with ACS—the
having CABG as soon as there is no concern over bleeding. risk for thromboembolic episodes (stent thrombosis and MI)
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 9

Table 3: P2Y12 inhibitors

Clopidogrel Prasugrel Ticagrelor Cangrelor

EACTS GUIDELINES
Bioavailability 50% 80% 36% 100%

Half-life (active metabolite) 1-2 hours 2-15 hours 7-9 hours 3-6 minutes

Binding reversibility Irreversible Irreversible Reversible Reversible

Onset of action 2-6 hours 30 minutes 30 minutes 2 minutes

Intravenous
Frequency of administration Once daily Once daily Twice daily
infusion
Duration of effect 3-10 days 7-10 days 3-5 days 1-2 hours

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A ntidote No No No No

Discontinuation before At least 5 days At least 7 days At least 3 days 1 hour

non-acute surgery

while waiting for the effect of the P2Y12-receptor inhibitors to discontinuation is unclear (e.g. in unconscious or confused pa-
cease must be weighed against the risk for perioperative bleeding tients) or treatment compliance is unclear.
complications. In patients who are at extreme high risk for Bedside PFT has been suggested as an option to guide
thrombotic events, e.g. recent stent implantation [47], bridging interruption of therapy rather than an arbitrarily specified period
therapy may be considered [7, 46] or surgery may be performed [7, 46]. Preoperative adenosine diphosphate-mediated platelet
without discontinuation of P2Y12 inhibitors. If bridging is war- aggregation predicts CABG-related bleeding complications in
ranted, GPIIb/GPIIIa inhibitors may be used. However, cangrelor, both clopidogrel- [58–61] and ticagrelor- [54] treated patients
a new reversible intravenous P2Y12 inhibitor with an ultrashort with ACS. A strategy based on preoperative PFT to determine the
half-life, has demonstrated a high rate of maintenance for plate- timing of CABG in clopidogrel-treated patients led to a 50%
let inhibition and no excessive perioperative bleeding complica- shorter waiting time compared with an arbitrary time-based dis-
tions [48, 49]. continuation strategy [62]. PFT in patients with ACS eligible for
Safe discontinuation intervals differ according to the pharma- CABG appears to be a valuable approach to refine the timing of
codynamics and pharmacokinetic profile of each P2Y12-receptor surgery. No RCT or observational study has compared periopera-
inhibitor [46]. When P2Y12-receptor inhibitors are discontinued, tive bleeding complications between a fixed versus a PFT-based
ASA therapy should be continued until the operation. time delay from discontinuation to surgery. Furthermore, the
Discontinuation of clopidogrel 5 days or more before CABG did cut-off levels of P2Y12 inhibition to predict perioperative bleed-
not increase the risk for bleeding complications [39]. A longer ing are not available for all PFT devices.
time interval (7 days) is recommended for prasugrel due to
the longer offset of platelet inhibition [50] and a higher incidence
of CABG-related bleeding complications compared with that 3.2.3 Restart after surgery. Current guidelines recommend
for clopidogrel [41]. In patients treated with ticagrelor, discon- DAPT for all patients with ACS independently of revascularization
tinuation of the drug 3 to 4 days, as opposed to 5 days or more treatment [7, 46]. This recommendation also applies to patients
before CABG surgery, is not associated with a higher incidence of having CABG or other non-coronary cardiac operations.
bleeding complications (OR 0.93; 95% CI 0.53–1.64, P = 0.80) [42]. Furthermore, DAPT after CABG has been associated with reduced
This finding has been confirmed in multiple studies [43, 51]. It is all-cause mortality [63, 64] and better vein graft patency (OR
unlikely that the optimal discontinuation period before surgery 0.59; 95% CI 0.43–0.82) [64], although the evidence is conflicting.
of any of the P2Y12 inhibitors will ever be tested in an RCT with The potential benefits of DAPT after CABG are offset by an
clinically relevant end points. increased risk for bleeding complications.
The magnitude of the benefit, i.e. a reduction in the mortal-
ity rate of more than 50% [40, 41], appears to be more
3.2.2 Platelet function testing. Besides the variances in plate- pronounced in patients with ACS than in those with stable an-
let inhibitory effects between different P2Y12 inhibitors, there is gina and with P2Y12 inhibitors that are more potent than clopi-
also a significant individual variation in the magnitude and dur- dogrel [63–65]. It is recommended to restart DAPT after CABG
ation of the antiplatelet effect [52–54]. Residual platelet reactivity as soon as it is considered safe in patients with ACS. There
is a marker of both ischaemic and bleeding events [55], but test- is currently no evidence to support starting routine DAPT after
ing platelet function to adjust P2Y12 inhibition does not improve CABG in patients not receiving DAPT preoperatively, although
clinical outcome in low- and high-risk patients [56, 57]. Platelet starting DAPT may be considered in patients with a higher is-
function testing (PFT) may optimize the timing for surgical pro- chaemic risk due to a coronary endarterectomy or off-pump
cedures, especially in patients in whom the time since surgery.
10 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

The optimal timing for restarting should be as soon as it is 3.3 Glycoprotein IIb/IIIa inhibitors
deemed safe. In patients with a high risk of ischaemia, P2Y12 in-
hibitors should be restarted within 48 h after surgery. In contrast, GPIIb/IIIa inhibitors (abciximab, eptifibatide and tirofiban) are
it may be considered safe to reinitiate P2Y12 inhibitors 3–4 days almost exclusively used in conjunction with percutaneous coron-
postoperatively when the risk for ischaemia is low (e.g. recent ary intervention but may also be used for bridging high-risk pa-
stent implantation >1 month or ACS without stenting). tients taking oral P2Y12 inhibitors to surgery [7, 46, 66]. The
optimal time delay for discontinuation before surgery is based
mainly on pharmacokinetic assumptions. Platelet function recov-
ery is obtained within 24–48 h of discontinuing abciximab and
Recommendations for perioperative P2Y12 inhibitor up to 4–8 h after discontinuing eptifibatide and tirofiban [67].
management However, the pooled analysis of patients from the EPILOG and
EPISTENT trials shows no difference between patients treated
with abciximab and placebo in terms of major blood loss (88% vs
Recommendations Classa Levelb Ref c
79%, P = 0.27) when the study treatment was stopped within 6 h
Preoperative period before the surgical incision [68]. In addition, other clinical studies

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In patients on DAPT who need to suggest that cessation 4 h before surgery is sufficient for all GP
undergo non-emergent cardiac IIb/IIIa inhibitors, including abciximab [66, 69].
surgery, postponing surgery for at
least 3 days after discontinuation IIa B [41, 42]
of ticagrelor, 5 days after clopidog- Recommendation for bridging antiplatelet therapy
rel and 7 days after prasugrel
should be considered.
with GPIIb/IIIa inhibitors

Platelet function testing may be

considered to guide the decision Recommendation Classa Levelb Ref c
on the timing of cardiac surgery IIb B [53, 54,
58, 60] It is recommended to discontinue GPIIb/
in patients who have recently
IIIa inhibitors at least 4 hours before I C
received P2Y12 inhibitors.
surgery.
Bridging P2Y12 inhibitors with
GPIIb/IIIa inhibitors or cangrelor IIb C a
may be considered in high ischae- Class of recommendation.
b
mic risk patients. Level of evidence.
c
References.
Postoperative period GP: glycoprotein.
In patients treated with DAPT after
recent coronary stent implantation 3.4 Preoperative anticoagulation and bridging
(within 1 month) who subsequently
undergo cardiac surgery, it is recom-
mended to resume the P2Y12 inhib- In patients treated with vitamin K antagonists (VKA) (Table 4),
I C
itor postoperatively as soon as there VKAs should be stopped 5 days before planned elective surgery
is no concern over bleeding but to achieve a target international normalized ratio (INR) below 1.5
within 48 hours of surgery, and con-
tinue DAPT until the recommended
on the day of surgery [22, 70]. In patients treated with non-
duration of therapy is completed. vitamin K antagonist oral anticoagulants (NOACs) who are
undergoing elective surgery, NOACs should be discontinued be-
In patients treated with DAPT
fore surgery at various time intervals according to renal function
after coronary stent implantation
(exceeding 1 month) or ACS with- and types of drugs (Table 5). In patients taking direct factor Xa in-
out stenting who subsequently hibitors (apixaban, edoxaban and rivaroxaban), treatment should
undergo cardiac surgery, it is be stopped >_2 days before surgery [71, 72]. In patients treated
recommended to resume the I C with dabigatran with creatinine clearance <50 ml/min/1.73 m2,
P2Y12 inhibitor postoperatively as
soon as there is no concern over NOAC should be stopped >_4 days before surgery.
bleeding but within 96 hours of The decision to bridge oral anticoagulation with unfractionated
surgery, and continue DAPT until heparin (UFH) or LMWH depends on the ischaemic risk for under-
the recommended duration of lying diseases. Preoperative bridging imposes a risk for periopera-
therapy is completed.
tive bleeding; therefore, not all patients on anticoagulation agents
DAPT may be considered after who have cardiac surgery should be bridged [73]. Therefore, bridg-
CABG in selected patients with sta- IIb C ing with oral anticoagulation is recommended in patients with
ble CAD (endarterectomy, off- mechanical prosthetic heart valves, valvular AF (moderate-to-se-
pump).
vere mitral stenosis), AF with a CHA2DS2-VASc score >4 or with a
recent acute thrombotic event within the previous 4 weeks defined
a
Class of recommendation. as ischaemic stroke, ACS or pulmonary embolism. Bridging should
b
Level of evidence. also be considered in patients with left ventricular apex thrombus,
c
References.
antithrombin 3 and proteins C and S deficiencies.
ACS: acute coronary syndrome; CABG: coronary artery bypass grafting;
CAD: coronary artery disease; DAPT: dual antiplatelet therapy; GP: Bridging should be initiated according to the outline in Fig. 2.
glycoprotein. UFH is the only approved bridging method, although there is no evi-
dence from randomized trials. Studies show that patients receiving
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 11

Table 4: Vitamin K antagonists

Coumadine
Acenocoumarol Fluindione Phenprocoumon
(Warfarin)

EACTS GUIDELINES
Half-life 10 hours 35–80 hours 30–40 hours 3–4 days

Steady state 2–3 days 3–6 days 3–4 days 6 days

Initial dose 4 mg 5 mg 20 mg 6 mg

Duration of effect 2–4 days 4–5 days 2–3 days 4–5 days

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Table 5: Different types of direct oral anticoagulant agents

Apixaban Dabigatran Edoxaban Rivaroxaban

Target Factor Xa Thrombin Factor Xa Factor Xa

Bioavailability 51–85% 6–8% 60% 80%

T max 3 hours 2 hours 1–3 hours 2–4 hours

Half-life 9–14 hours 14–17 hours 5–11 hours 9–13 hours

Frequency of administration Twice daily Once or twice daily Once daily Once or twice daily

Renal excretion 25% 80% 36–45% 66% (half inactive)

Antidote Andexanet alfa Idarucizumab Andexanet alfa Andexanet alfa

a
Discontinuation before non-acute surgery At least 48 hours At least 48-96 hours At least 48 hours At least 48 hours

a
Discontinuation >_48 h if creatinine clearance is >80 ml/min/1.73 m2; discontinuation >72 h if creatinine clearance is 50–79 ml/min/1.73 m2 and discontinu-
ation >_96 h if creatinine clearance is <50 ml/min/1.73 m2.

preoperative UFH versus LMWH had fewer postoperative re- prothrombin complex concentrate (25 IU factor IX/kg) should be
explorations for bleeding after cardiac surgery [74]. However, UFH given with an additional dose of 5 mg of vitamin K1 (intravenous,
can only be administered in a hospital, whereas LMWH does not re- subcutaneous or oral) [77]. For patients taking NOACs. The timing
quire hospital admission and continuous intravenous infusion. between the last intake and the procedure should be checked, and
Therefore, LMWH is more practical and user-friendly and should be the treatment concentration should be assessed using specific
considered as an alternative for bridging with dose adjustment ac- diluted thrombin times (HaemoclotV R ) for dabigatran and anti-factor

cording to weight and renal function and if possible with monitoring Xa assays for the FXa inhibitors. The plasma concentration of
of anti-Xa activity with a target of 0.5–1.0 U/ml. The option of bridg- NOACs should be considered the best way to assess the residual ac-
ing with fondaparinux is not recommended due to an extended tivity of the drug and estimate the risk for bleeding [78]. The opera-
half-life (17–21 h) and the lack of an adequate antidote, although it tion may be safely performed if the plasma concentrations of
may have a role in patients with a history of heparin-induced dabigatran and rivaroxaban are below 30 ng/ml; with higher con-
thrombocytopenia [75]. centrations, the operation should be delayed for 12 h (if the concen-
There is no adequate evidence to support specific time intervals tration is 30–200 ng/ml) or 24 h (if the concentration is 200–400 ng/
for stopping preoperative bridging with UFH and LMWH. Based on ml). If plasma concentrations are too high and the operation cannot
the pharmacokinetics of UFH, it is recommended that administra- be postponed, the off-label therapeutic use of both non-activated
tion be discontinued at least 6 h preoperatively. Discontinuation of prothrombin complex concentrate (20–50 U/kg) and activated pro-
LMWH should occur >12 h preoperatively, as suggested by studies thrombin complex concentrate (FEIBAV R , 30 to 50 U/kg) may be

reporting high plasma concentrations if it is given twice daily [76]. considered [79]. Although FEIBAV R and its high potential to over-

Even when the patient’s condition is urgent, surgery should ideally shoot thrombin generation might be more efficient in the case of
be delayed if patients are taking oral anticoagulants. The benefit life-threatening bleeding, this benefit should be balanced against an
associated with allowing a short delay before performing surgery increased risk of thrombosis [80]. Target concentration ranges from
should, however, be balanced against the risk of a major haemor- studies on apixaban/edoxaban are lacking. Idarucizumab has re-
rhage. When VKAs cannot be stopped for an appropriate time, cently been approved for reversing the effect of dabigatran based
12 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

on the Reversal Effects of Idarucizumab on Active Dabigatran 3.5 Postoperative antithrombotics and bridging
(REVERSE-AD) trial, which demonstrated complete reversal of the
anticoagulant effects within minutes [81]. No outcome data are Heart valve replacement or repair increases the risk for thrombo-
available, and treatment duration, as well as monitoring guidelines, embolic complications, requiring antithrombotic therapy. Scientific
is still to be established [81]. The effect of andexanet alfa in reversing evidence for the best antithrombotic strategy and duration is
the effect of FXa inhibitors has shown to be promising, although scarce [88], resulting in a low level of evidence for most recom-
clinical data are currently unavailable [82, 83]. mendations [16].

3.5.1 Mechanical prostheses. Patients undergoing mechanical

Preoperative management of oral anticoagulants valve implantations require lifelong treatment with VKA guided by
INR (Fig. 3, Table 4) [89, 90]. Anticoagulant treatment with UFH
and VKA is started on the first postoperative day and is maintained
Recommendations Classa Levelb Ref c
until the INR is in the therapeutic range. However, special atten-
Preoperative period tion to the coagulation status and potential bleeding events is
required. In the case of bleeding disorders, VKAs should be re-

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It is recommended that VKAs be dis-
continued 5 days prior to surgery to started whenever it is deemed safe, preferably within 48 h. Of
I C
aim for an INR <1.5 on the day of note, similarly to preoperative bridging, UFH administered by the
the elective cardiac surgery. intravenous route remains the only approved bridging treatment
For patients on NOACs, preoperative after the implantation of mechanical heart valve prostheses [91],
discontinuation of therapy is recom- although it has never been evaluated in a randomized trial. Off-
mended at least 48–96 hours prior to I C label bridging with subcutaneous LMWH is widely implemented in
surgery, depending on renal function hospital protocols due to its logistic and cost advantages over
and the agente.
UFH. However, prospective open-label non-randomized studies
Bridging of OAC is recommended in have shown subcutaneous enoxaparin to be suitable for a much
patients with any of the following
indication:
• Mechanical prosthetic heart valve
• AF with moderate to severe mitral I C
stenosis
• AF with a CHA2DS2-VASc score >4
• Acute thrombotic event within
the previous 4 weeks.

Bridging of OACs should be con-

sidered in patients with a high acute IIa C
thromboembolic riskd.

Bridging with UFH is recommended. I B [74, 84]

Bridging with subcutaneous LMWH
should be considered as an alterna- IIa B [85, 86]
tive to bridging with UFH.

Bridging with fondaparinux is not III C

recommended.

In patients who are preoperatively

bridged with UFH, it is recom- I C
mended that UFH be stopped
6 hours before surgery.

In patients who are preoperatively

bridged with therapeutic LMWH, it is I B
recommended that they be given the [76, 87]
last dose 24 hours before surgery.

a
Class of recommendation.
b
Level of evidence.
c
References.
d
Left ventricular apex thrombus, antithrombin 3 deficit and proteins C
and/or S deficit.
e
Table 5 includes the proposition of discontinuation time for specific
agents.
AF: atrial fibrillation; CHA2DS2-VASc: congestive heart failure, hyper- Figure 2: Management of oral anticoagulation in patients with an indication
tension, age >_75 (2 points), diabetes, prior stroke (2 points)–vascular for preoperative bridging. aBridging with UFH/LMWH should start when INR
disease, age 65–74, sex category (female); INR: international normalized values are below specific therapeutic ranges. bDiscontinuation should be pro-
ratio; LMWH: low-molecular-weight heparin; NOACs: non-vitamin K longed to >72 h if creatinine clearance is 50–79 ml/min/1.73 m2 or >_ 96 h if cre-
antagonist oral anticoagulants; OACs: oral anticoagulants; UFH: unfrac- atinine clearance is <50 ml/min/1.73 m2. INR: international normalized ratio;
tionated heparin; VKAs: vitamin K antagonists. LMWH: low-molecular-weight heparin; NOACs: non-vitamin K antagonist oral
anticoagulants; UFH: unfractionated heparin; VKAs: vitamin K antagonists.
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 13

EACTS GUIDELINES
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Figure 3: Proposed antithrombotic algorithm after valvular heart procedures. aIncludes atrial fibrillation, previous thromboembolic events, left ventricular dysfunction
and older generation mechanical AVR; bstands for replacement or repair. ASA: acetylsalicylic acid; AVR: aortic valve replacement; DAPT: dual antiplatelet therapy; INR:
international normalized ratio; LMWH: low-molecular-weight heparin; MVR: mitral valve replacement; OAC: oral anticoagulant; SAPT: single antiplatelet therapy;
TAVI: transcatheter aortic valve implantation; TVR: tricuspid valve replacement; UFH: unfractionated heparin; VKA: vitamin-K antagonists.

higher proportion of patients within the target anticoagulation (1 month) of triple therapy comprising VKA, low-dose ASA and clo-
range, when compared with UFH, and to provide similar or better pidogrel [16], followed by interruption of either ASA or clopidogrel
safety. It should, therefore, be considered as an alternative bridging should be considered. Ticagrelor and prasugrel are not recom-
strategy to UFH [92, 93]. Once the INR is in the adequate target mended in a triple therapy setting due to the safety hazard [16].
range, bridging should be discontinued.
The INR target in patients with mechanical prostheses depends
on certain patient characteristics (e.g. previous thrombosis and AF) 3.5.2 Bioprostheses. The optimal anticoagulation strategy early
and on the prosthesis thrombogenicity and implantation site (e.g. after implantation of an aortic bioprosthesis remains controversial.
aortic, mitral or tricuspid) [16]. A median target INR of 2.5 (range One should consider either anticoagulation with VKA or single anti-
2.0–3.0) is consistently recommended for aortic prostheses without platelet therapy with ASA during the first 3 months. A large study
additional risk factors for thromboembolism [16, 94], whereas from the Society of Thoracic Surgeons Adult Cardiac Surgery
higher targets are recommended in patients with risk factors (e.g. Database found comparable rates of death, embolic events and
AF, venous thromboembolism, hypercoagulable state and left ven- bleeding in patients treated with ASA alone or with VKAs alone for
tricular ejection fraction [LVEF] <35%) and/or mitral and tricuspid 3 months after bioprosthetic aortic valve replacement, whereas
prostheses (median target INR >3.0). Of interest in patients with combined ASA and VKA therapy reduced the numbers of deaths
mechanical heart valves, the time in the therapeutic range is better and embolic events but significantly increased bleeding [101]. A
associated with safety than the target INR range [95], supporting Danish registry study showed a higher incidence of thrombo-
the use of INR self-management [96–98]. embolic events and cardiovascular deaths in patients discontinuing
The Randomized, Phase II Study to Evaluate the Safety and warfarin during the first 6 postoperative months [102], although this
Pharmacokinetics of Oral Dabigatran in Patients after Heart Valve cannot be directly translated into an increased risk if warfarin treat-
Replacement (RE-ALIGN) trial investigated whether dabigatran ver- ment is not initiated. A recent small RCT of 370 patients found that
sus VKAs was safe and effective in patients with mechanical heart warfarin for 3 months versus ASA therapy significantly increased
valves [99]. The trial was prematurely stopped because of an major bleeding but did not reduce the number of deaths or
increased risk for both thromboembolic complications and major thromboembolic events [103]. There are no data on continuing life-
bleeding with dabigatran. Therefore, NOACs currently have no long ASA after an initial 3 months of treatment in patients with sur-
role in any patient with a mechanical heart prosthesis. gical bioprostheses who do not have any other indication for ASA.
In patients with concomitant atherosclerotic disease, the addition Three months of treatment with VKA is recommended in all pa-
of low-dose (75–100 mg) ASA to VKAs may be considered, al- tients with a bioprosthesis implanted in the mitral or tricuspid
though the evidence is limited. Furthermore, a low dose of ASA position.
may also be added if thromboembolism occurs despite an ad-
equate INR. However, combined antithrombotic therapy is associ-
ated with a significant increase in the risk for bleeding, which 3.5.3 Valve repair. It is recommended to consider oral anticoa-
carries an ominous prognosis [100]. Therefore, it should be reserved gulation with VKA during the first 3 months after valve-sparing
for patients with a very high risk of a thromboembolism. For aortic root surgery and after mitral and tricuspid repair, although
patients who are candidates for triple oral antithrombotic therapy, strong evidence is lacking. As for other indications, the risk for
i.e. patients with a mechanical valve and an absolute indication for thromboembolic and bleeding complications must be taken into
DAPT (e.g. recent stent implantation or ACS), a short period account when the antithrombotic treatment is planned.
14 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

Low-dose ASA (75–100 mg/day)

Postoperative management of oral anticoagulants and should be considered for the first
indications for long-term antithrombotic treatments 3 months after surgical implant- IIa B [101, 103]
ation of an aortic bioprosthesis
or valve-sparing aortic surgery.
Recommendations Classa Levelb Ref c
Oral anticoagulation using a VKA
Postoperative bridging and (re)starting oral anticoagulation should be considered for the first
3 months after mitral or tricuspid IIa C
In patients with an indication for valve repair or bioprosthetic
postoperative therapeutic bridg- I C valve replacement.
ingd, it is recommended to start
UFH 12–24 hours after surgery. TAVI

LMWH should be considered as DAPT should be considered for

an alternative bridging strategy to IIa C the first 3–6 months after TAVI,
UFH 24–48 hours after surgery. followed by lifelong ASA in pa- IIa C
tients who do not need OACs for
It is recommended to (re)-initiate I C other reasons.

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VKAs on the first postoperative day.
ASA monotherapy may be con-
Delaying the restarting of sidered after TAVI in cases where IIb C
NOACs for 72 hours after surgery IIa C there is a high risk for bleeding.
should be considered.
Other indications
Mechanical prostheses
In patients undergoing cardiac
Lifelong oral anticoagulation surgery with a preoperative indi-
using a VKA is recommended for I B [89, 90] cation for oral anticoagulation, it I C
all patients. is recommended that the pre-
operative regimen of VKAs or
NOACs are not recommended NOACs be restarted after surgery.
in patients with a mechanical III B [99]
valve prosthesis.
a
Class of recommendation.
The addition of low-dose ASA b
(75–100 mg/day) to VKA should Level of evidence.
IIa C c
References.
be considered in the case of con-
d
comitant atherosclerotic disease. Patients with a mechanical prosthetic heart valve; AF with moderate to
severe mitral stenosis; AF with a CHA2DS2-VASc score >4; an acute
The addition of lifelong low- thrombotic event within the previous 4 weeks and, potentially, patients
dose ASA (75–100 mg/day) to with left ventricular apex thrombus, antithrombin 3 deficit, protein C
VKA should be considered after IIa C and/or protein S deficits.
thromboembolism despite an ACS: acute coronary syndrome; AF: atrial fibrillation; ASA: acetylsalicylic
adequate INR. acid; CHA2DS2-VASc: Congestive heart failure, hypertension, age >75
(2 points), diabetes, prior stroke (2 points)–vascular disease, age 65–74,
Triple therapy comprising VKAs,
sex category (female); DAPT: dual antiplatelet therapy; INR: interna-
ASA (75–100 mg/day) and clopi-
tional normalised ratio; LMWH: low-molecular-weight heparin;
dogrel (75 mg/day) should be
NOACs: non-vitamin K antagonist oral anticoagulants; OACs: oral anti-
considered for a duration of IIa C coagulants; TAVI: transcatheter aortic valve implantation; UFH: unfrac-
1 month after ACS or recent stent
tionated heparin; VKAs: vitamin K antagonists.
implantation, followed by VKAs
and low ASA (75–100 mg/day) or
clopidogrel (75 mg/day).

INR self-management is recom- 3.5.4 Transcatheter aortic valve implantation. The decision
mended provided that appropri- I B for (dual) antiplatelet therapy or oral anticoagulation after trans-
ate training and quality control are [96]
catheter aortic valve implantation (TAVI) is complicated due to
performed.
multiple factors associated with (i) a prothrombotic environment
Bioprostheses after valve implantation, (ii) combined TAVI and stent implantation
in 30% of patients and (iii) an elderly patient population that fre-
Oral anticoagulation is recom-
mended on a lifelong basis for quently has comorbidities and frailty characteristics and should be
patients with surgically or trans- considered at high risk for bleeding. DAPT remains the most widely
I C
catheter implanted bioprosthe- used antithrombotic strategy after TAVI, being used in >60% of pa-
ses who have other indications tients, whereas VKAs are used in <20% of patients [104]. However,
for anticoagulation.
subclinical valve thrombosis is another challenging issue, because it
Oral anticoagulation may be may occur soon after TAVI with antiplatelet treatment and may
considered for the first 3 months IIb B only be reversed after exposure to oral anticoagulant (OAC) ther-
after surgical implantation of an [101, 103]
aortic bioprosthesis.
apy [105]. Indeed, recent evidence demonstrates that VKA alone
versus VKA plus ASA produced comparable rates of thrombo-
Continued embolic events and deaths while reducing bleeding events [106].
Which antithrombotic regimen (e.g. antiplatelet, VKA or NOAC) is
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 15

most appropriate after TAVI is currently being tested in several on- rhythm control group and vice versa, limiting the ability of the trial
going trials (NCT02247128, NCT02556203 and NCT02664649). For to show a significant benefit of one strategy over the other.
the moment, there is a consensus that DAPT should be used soon Therefore, in asymptomatic or minimally symptomatic patients, a
after TAVI when there is no indication for OACs. rhythm control strategy should be the preferred strategy, whereas
rate control may also be an option. For rate control, beta-blockers

EACTS GUIDELINES
or diltiazem/verapamil (if beta-blockers are contraindicated) are
3.5.5 Other indications. In patients undergoing any cardiac
preferred over digoxin [17, 120]. The choice of drug depends on
operation with a preoperative indication for OACs other than
patient characteristics, including haemodynamics and LVEF. A
heart valve replacement or repair, the preoperative regimen
combination of beta-blockers and digoxin may be required.
of VKAs or NOACs should be reinitiated after surgery.
Patients with a preoperative indication for bridging should
also receive postoperative bridging, following the same scheme Recommendations for prevention in and treatment of
as that used for mechanical prosthetic heart valves shown in Fig. patients with atrial fibrillation
2. In contrast to VKAs, one should restart NOACs after
surgery with caution due to the more immediate antithrombotic
Recommendations Classa Levelb Ref c
effects and the increased risk for bleeding [99].

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Preoperative period

Perioperative low-dose oral

4. ATRIAL FIBRILLATION beta-blocker therapy, starting
2–3 days before cardiac surgery, IIa B [125–127]
4.1 Preoperative atrial fibrillation prophylaxis should be considered for the
prevention of POAF.
The most common arrhythmia in the period after cardiac surgery is If beta-blockers are initiated pre-
AF. It is associated with a longer hospital stay and with higher rates operatively, careful up-titration,
of strokes and mortality [107–109]. It is also a predictor of the occur- according to blood pressure and I C
rence of AF years after surgery [109]. Since the publication of the heart rate, starting several days
before surgery, is recommended.
previous comprehensive version of the guidelines on the Prevention
and Management of de novo Atrial Fibrillation after Cardiac and Perioperative amiodarone, start-
Thoracic Surgery [110], numerous studies have addressed the safety ing 5–6 days before cardiac sur- IIb A [111, 128,
gery, may be considered for the 129]
and efficacy of medication to prevent postoperative AF (POAF) [17]. prevention of POAF.
Treatment with beta-blockers has been shown to reduce POAF
[107, 111]. Therefore, patients who are already taking beta-blockers Postoperative period
should continue to take them before and after surgery. Patients who In patients with postoperative
are not taking beta-blockers may derive some benefit, i.e. a lower haemodynamically stable POAF, I B [119, 130]
incidence of POAF, from starting beta-blockers 2–3 days before the rhythm control is recommended.
operation (if tolerated) and being carefully up-titrated according to In patients with postoperative
blood pressure and heart rate [112]. Amiodarone taken 6 days pre- haemodynamically stable and IIa B
asymptomatic POAF, rate control [119, 130]
operatively followed by 6 days postoperatively has been shown to
be more effective than beta-blockers, but it is associated with more should be considered.
acute and long-term complications [111, 113]. It may be considered In patients with postoperative
in patients who are unable to tolerate beta-blockers. Studies suggest haemodynamically unstable
that both magnesium and fish oil may prevent POAF, but RCTs POAF, cardioversion and antiar- I B [131, 132]
rhythmic drugs to restore sinus
have shown conflicting evidence [114–116]. Therefore, a clear rec- rhythm are recommended.
ommendation for their use cannot be provided at the moment.
There is currently no evidence from clinical trials to support the use Anticoagulation with therapeutic
doses of UFH or LMWH should
of colchicine, steroids or statins to prevent POAF.
be considered within 12–48 hours IIa C
of AF in patients with POAF, bal-
ancing the risks for stroke and sur-
4.2 Management of postoperative atrial gical bleeding.
fibrillation
In patients with POAF at discharge,
it is recommended to initiate OAC
In patients who are haemodynamically unstable because of therapy and continue for at least I B [17, 122,
POAF, we recommend cardioversion and antiarrhythmic drugs to 4 weeks (or longer), depending on 133, 134]
restore sinus rhythm. Both amiodarone and vernakalant are ef- the CHA2DS2-VASc risk score.
fective for restoring sinus rhythm after POAF [117, 118].
Historically, in haemodynamically stable patients, rhythm con- a
Class of recommendation.
trol of POAF has been the norm because of the assumption that b
Level of evidence.
c
the restoration/maintenance of sinus rhythm would be a superior References.
strategy to rate control. More recent evidence from a randomized AF: atrial fibrillation; CHA2DS2-VASc: Congestive heart failure, hyper-
trial including 523 patients has shown that, in asymptomatic or tension, age >75 (2 points), diabetes, prior stroke (2 points)–vascular
disease, age 65–74, sex category (female); LMWH: low-molecular-
minimally symptomatic patients, there is no benefit in adopting a weight heparin; OAC: oral anticoagulant; POAF: postoperative atrial fib-
rhythm control strategy, even with amiodarone [119]. However, rillation; UFH: unfractionated heparin.
25% of patients in the rate control group crossed over to the
16 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

4.3 Thromboembolism prevention for (IMAGINE) study did not show any benefit of quinapril compared
postoperative atrial fibrillation to placebo initiated early within 7 days of surgery; greater rates of
morbidity and mortality have been observed at 3 months in the qui-
Anticoagulation therapy is necessary for patients who have had car- napril group [141]. However, the exact timing of the discontinuation
diac surgery who develop AF to avoid early stroke and death [121]. and reinstitution of these drugs is poorly defined [138, 141]. RAAS
OAC reduces postoperative mortality rates in patients discharged inhibitors, including the ARBs and ACEIs, can also increase the risk
with POAF. Nevertheless, there is no clear evidence on when to for perioperative hypotension [142] and vasodilatory shock [143],
start anticoagulation, and the decision has to be made based on causing decreased systemic vascular resistance [138]. Therefore, the
balancing the risks for bleeding and thromboembolisms. Starting use of inotropes and vasopressors is increased, and the time patients
early with a therapeutic dose of UFH or LMWH should be con- spend on ventilators and in the intensive care unit (ICU) is extended
sidered within 12–48 h after surgery. OAC should commence 48 h [137, 144]. For these reasons, there is a consensus on discontinuing
after surgery and be maintained for at least 4 weeks according to RAAS blockers before cardiac surgery (Table 6) [136, 137, 140]. In
the CHA2DS2-VASc score [17, 122]. Most of the evidence for antico- patients with preoperatively uncontrolled hypertension, long-acting
agulation of POAF has been obtained with VKAs. For patients with ACEIs and ARBs may be switched to short-acting ACEIs.
mechanical valve prostheses or moderate-to-severe mitral stenosis, Additionally, patients treated with sacubitril/valsartan should have

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VKAs are highly recommended [17]. There is evidence supporting a the same preoperative assessment as other patients treated with
greater benefit of NOACs over VKA in non-valvular POAF, including RAAS inhibitors. There are currently no data on whether aldosterone
patients with a bioprosthetic valve [123, 124]. receptor antagonists should be stopped or continued until surgery.

5. RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM 5.2 Postoperative use

INHIBITORS
The ideal blood pressure following CABG is not well studied, but a
pressure of less than 140/90 mmHg has been suggested to be opti-
Four classes of drugs may be used to inhibit the renin–angioten-
mal [145, 146]. Therapy for postoperative hypertension frequently
sin–aldosterone system (RAAS): (i) angiotensin-converting en-
involves beta-blockers, because they also reduce the risk for AF/
zyme inhibitors (ACEIs); (ii) angiotensin II receptor blockers
flutter and improve the clinical outcomes of patients with heart
(ARBs); (iii) aldosterone receptor antagonists and (iv) direct renin
failure and reduced LVEF [147]. ACEIs, however, should also be
inhibitors. RAAS blockers are mainly used to treat hypertension
considered, often in addition to beta-blockers, in patients with
and heart failure but also have a protective effect against the de-
postoperative hypertension and/or a reduced LVEF [138, 145, 146].
velopment of nephropathy through their inherent properties,
Furthermore, treatment with sacubitril/valsartan is recommended
which are not directly related to their effects on lowering blood
for patients who remain symptomatic with chronic heart failure
pressure [135, 136]. Nevertheless, the use of RAAS blockers in
[New York Heart Association (NYHA) Class III and IV] and who
some patients is fraught with controversy [136–139]. The role of
have a reduced LVEF (<40%) as a replacement for an ACEI to fur-
newly developed direct renin inhibitors in cardiac surgical pa-
ther reduce the risk for death and readmission [19]. ARBs can be
tients is uncertain, and data are currently lacking.
used as an alternative therapy for blood pressure in patients with
reduced LVEF who are intolerant to ACEIs [148, 149] but should
5.1 Preoperative discontinuation not be used concomitantly with ACEIs due to increased rates of
hypotension, hyperkalaemia and impaired kidney function, espe-
It has been debated whether ACEIs should be discontinued before cially if aldosterone antagonists are also used [150]. For other pa-
CABG [136, 137, 140]. The Ischemia Management With Accupril tients without hypertension or a reduced LVEF, the routine use of
Post Bypass Graft Via Inhibition of the coNverting Enzyme ACEIs is not indicated, because it may potentially lead to more

Table 6: Different types of renin–angiotensin–aldosterone system inhibitors

Captopril Enalapril Lisinopril Ramipril Losartan Valsartan

Mechanism of action ACEI ACEI ACEI ACEI ARB ARB

a
Half-life 2 hours 35-38 hours 12 hours 13-17 hours 6-9 hours 6-9 hours

Frequency of administration Twice or Once or Once daily Once or Once or Once or

thrice daily twice daily twice daily twice daily twice daily

Maximum dose 450 mg/day 40 mg/day 40 mg/day 20 mg/day 100 mg/day 320 mg/day

Renal excretion 95% 61% 100% 60% 4% 13%

Discontinuation before non-acute surgery 12 hours 24 hours 24 hours 24 hours 24 hours 24 hours

a
Including the half-life of its pharmacologically active metabolite.
ACEI: angiotensin-converting enzyme inhibitor; ARB: angiotensin II receptor blocker.
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 17

adverse events [141, 151]. The occurrence of low cardiac output function [138] who have had CABG, mainly for long-term preven-
syndrome in the early postoperative phase may result in a pro- tion of adverse events [153]. In addition to ACEIs and ARBs, aldos-
longed stay in the ICU and the need for inotropes or vasopressor terone receptor antagonists may also benefit patients with chronic
support, which is associated with ischaemia and renal complica- heart failure or a reduced LVEF. This benefit was shown in the
tions [152]. Randomized Aldactone Evaluation Study (RALES) trial, where
aldactone reduced overall mortality rates, heart failure symptoms

EACTS GUIDELINES
After the early postoperative phase, RAAS blockers have pro-
tective effects in patients with reduced LVEF and impaired kidney and readmission due to heart failure [154]. Eplerenone, another al-
dosterone antagonist, has subsequently shown, in the Eplerenone
in Mild Patients Hospitalisation and Survival Study in Heart Failure
Management of patients with renin-angiotensin- (EMPHASIS-HF), to reduce the risk for death and rehospitalization
aldosterone system inhibitors and indications for for heart failure in patients with an LVEF <35% and NYHA Class II
long-term treatment [155]. Aldosterone antagonists can be used together with beta-
blockers and ACEIs in patients following CABG but should be lim-
Recommendations Classa Levelb Ref c ited to patients with reduced LVEF and NYHA Class II–IV heart fail-
ure symptoms [155–157]. They should, however, be avoided in
Preoperative period

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patients with kidney failure (estimated glomerular filtration rate
It is recommended to discon- <30 ml/min/1.73 m2) or hyperkalaemia (>5.0 mEG/l) [157].
tinue ACEIs and ARBs preopera- I C
tively in patients undergoing
cardiac surgeryd.
6. BETA-BLOCKERS
In patients with preoperative un-
controlled arterial hypertension, 6.1 Preoperative beta-blockers
switching long-acting ACEI or IIa C
ARB treatment to short-acting
ACEIs should be considered. Current evidence recommends that patients should continue
beta-blockers before elective and non-elective cardiac surgery
Postoperative period [162–164], because doing so results in a consistent survival bene-
It should be considered to start fit plus a reduction in arrhythmic events in the early postopera-
short-acting ACEIs at a low dose tive period [165]. However, the effectiveness of catecholamine in
no earlier than 48 hours after car- IIa C the early postoperative period may be limited by concurrent
diac surgery in patients with a
reduced LVEF (<40%) and an
treatment with beta-blockers until the day of the operation [166].
eGFR >30 ml/min/1.73 m2. Therefore, it may be cumbersome to control patients with pre-
operative long-acting agents. Therefore, one should consider
In ACEI-intolerant patients, an
switching to short-acting agents to limit adverse events.
ARB is recommended in patients I A
with a reduced LVEF (<40%) and [148, 149] Whether one should initiate a beta-blocker in the preoperative
an eGFR >30 ml/min/1.73 m2. or postoperative period is less clear [167], and such a decision
should be individualized, which involves weighing the risks and
Long-term optimal-dose ACEI or
ARB treatment is recommended benefits. As discussed in the section on AF, initiating beta-
after cardiac surgery in patients I A [158–160] blockers preoperatively may be considered for the prevention of
with reduced LVEF (<40%) and POAF. Whether beta-blockers prevent perioperative MI and
an eGFR >30 ml/min/1.73 m2. death is controversial. Studies have shown that beta-blockers are
Sacubitril/valsartan is recom- particularly beneficial in patients with a recent MI [168]. Indeed,
mended as a replacement for an it is suggested that the benefit of beta-blockers before CABG to
ACEI in ambulatory patients with prevent MI and death is limited only to patients with a recent MI
reduced LVEF (<40%) who remain I B [161] [169]. There is conflicting evidence on whether preoperative
symptomatic despite optimal treat-
ment with an ACEI, a beta-blocker beta-blockers are beneficial in patients with reduced LVEF but
and aldosterone antagonists. without a recent MI [126]. However, if beta-blockers are initiated
preoperatively, careful up-titration of short-acting agents accord-
Long-term aldosterone antagon-
ist addition to beta-blockers and ing to blood pressure and heart rate, starting several days before
ACEI therapy is recommended surgery, is recommended.
after cardiac surgery in patients I A
with HF and a reduced LVEF [154, 155]
(<35%), an eGFR >30 ml/min/ 6.2 Postoperative beta-blockers
1.73 m2 and without hyperkalae-
mia (>5.0 mEG/l). In addition to a preoperative beta-blockade in patients with
reduced LVEF, continuing beta-blockers during the early postop-
a
Class of recommendation. erative phase has also been shown to significantly reduce the 30-
b
Level of evidence. day mortality rate following CABG [170]. Strong evidence sug-
c
References. gests that beta-blockers reduce the number of deaths in patients
d
Table 6 includes the proposition of discontinuation time for specific with a recent MI or reduced LVEF (<35%) [171, 172]. Therefore, it
agents. is crucial that beta-blockers be continued upon discharge for
ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin II re- long-term secondary prevention in patients with a recent MI or
ceptor blockers; LVEF: left ventricular ejection fraction; eGFR: estimated
glomerular filtration rate; HF: heart failure. reduced LVEF [173–175]. Approved beta-blockers are metoprolol
succinate, bisoprolol, nebivolol and carvedilol [19].
18 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

7.2 Non-statin, lipid-lowering agents

Management of treatment with beta-blockers in perio-
perative settings In patients after CABG surgery in whom the LDL-C target <70 mg/
dl (1.8 mmol/l) is not reached, despite an intense or maximally tol-
Recommendations Classa Levelb Ref c
erated statin dose, the addition of a cholesterol absorption inhibi-
tor, ezetimibe, should be considered. In a recent analysis of the
Preoperative period IMProved Reduction of Outcomes: Vytorin Efficacy International
It should be considered to con- Trial (IMPROVE-IT) study, it was observed that patients who had a
tinue beta-blocker therapy prior to IIa B [125, 126, previous CABG operation who received ezetimibe plus a statin ver-
cardiac surgery. 176]
sus a statin alone had a substantial reduction in cardiovascular
Postoperative period events during a 6-year median follow-up period [6].
Although no direct evidence for the use of proprotein conver-
Postoperative long-term beta- tase subtilisin/kexin type 9 (PCSK9) inhibitor after cardiac surgery
blocker therapy is recommended I A [171,
in patients with a recent MI or exists, circumstantial evidence provides enough facts for its bene-
173–175]
reduced LVEF (<35%). ficial effects after CABG surgery [184]. Patients in whom the LDL-

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C target <70 mg/dl (1.8 mmol/l) is not reached, despite an intense
a or maximally tolerated dose of statin and ezetimibe, the recently
Class of recommendation.
b
Level of evidence.
developed PCSK9 inhibitors have been shown to reduce
c
References.
LVEF: left ventricular ejection fraction; MI: myocardial infarction.
Management of patients with dyslipidaemia

7. DYSLIPIDAEMIA Recommendations Classa Levelb Ref c

Preoperative period
7.1 Statins
It is not recommended to initiate
statin therapy shortly before car- III A [177–180]
7.1.1 Preoperative therapy. Results from observational studies diac surgery.
and small RCTs have suggested that initiation of preoperative statin
therapy before cardiac surgery reduced mortality, POAF and acute Continuing statin therapy before
cardiac surgery should be IIa C
kidney injury (AKI) [177, 178]. However, in the Statin Therapy in
considered.
Cardiac Surgery (STICS) trial that randomized 1922 patients
undergoing elective cardiac surgery, the initiation of rosuvastatin Postoperative period
therapy (20 mg/day) before cardiac surgery did not prevent peri- LDL-C is recommended as the pri- I A [189]
operative myocardial damage or reduce the risk for POAF [179]. AKI mary target.
was significantly more common among patients who received rosu-
Intense or maximally tolerated
vastatin than among those who received a placebo [179]. In another statin therapy is recommended in
trial of patients undergoing cardiac surgery, initiation of a high dose patients after CABG surgery to
of atorvastatin on the day before surgery that continued periopera- reach the LDL-C target <70 mg/dl I A [20, 182,
tively did show a significantly higher rate of AKI in patients with (1.8 mmol/l) or >50% LDL-C re- 189]
duction if the baseline LDL-C is
chronic kidney disease compared with placebo [180]. The trial was
between 1.8–3.5 mmol/l (70–
later prematurely terminated on the grounds of futility [181]. 135 mg/dl).
In summary, these recent data do not support the preoperative
initiation of statin therapy in statin-naive patients undergoing In patients after CABG surgery in
whom the LDL-C target <70 mg/dl
cardiac surgery. No data are available on whether patients al- (1.8 mmol/l) is not reached by
ready taking statins should continue or discontinue therapy pre- using statin therapy, a combin- IIa B [6, 189]
operatively, although in common practice statins are continued ation of a statin with a cholesterol
perioperatively. absorption inhibitor (ezetimibe)
should be considered.

In patients after CABG surgery

7.1.2 Postoperative use. Intense or maximally tolerated statin who have a persistently high LDL-
therapy is recommended with a low-density lipoprotein cholesterol C (>140 mg/dl or 3.6 mmol/l)
(LDL-C) target of <70 mg/dl (1.8 mmol/l) or >50% LDL-C reduction level, despite treatment with the IIa B [184, 190,
in patients with coronary artery disease. In the Treating to New maximal tolerated statin dose (in 191]
Targets (TNT) trial, which included >4000 randomized patients, in- combination with ezetimibe), a
PCSK9 inhibitor should be
tense lowering of LDL-C [to a mean of 79 mg/dl (2.05 mmol/l)], considered.
with atorvastatin 80 mg/day in patients with previous CABG,
reduced major cardiovascular events by 27% and the need for re- a
Class of recommendation.
peat revascularization by 30%, compared with less intensive lower- b
Level of evidence.
ing of the cholesterol level to a mean of 101 mg/dl (2.61 mmol/l) c
References.
with atorvastatin 10 mg/day [182]. In patients with statin intolerance CABG: coronary artery bypass grafting; LDL-C: low-density lipoprotein
during the follow-up period, the European Atherosclerosis Society cholesterol; PCSK9: proprotein convertase subtilisin/kexin type 9.
has recently developed a scheme for statin re-exposure [183].
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 19

cardiovascular events during follow-up in patients at high cardio- 8.2 Steroids

vascular risk [185, 186]. Therefore, the addition of PCSK9 inhibi-
tors should be considered in selected patients. The use of cardiopulmonary bypass (CPB) initiates a systemic in-
A meta-analysis of 18 RCTs and 45 058 patients showed flammatory response that is associated with adverse clinical out-
that fibrates, agonists of peroxisome proliferator-activated recep- comes such as respiratory failure, bleeding, adverse neurological

EACTS GUIDELINES
tor-alfa, could reduce major cardiovascular events predominantly function and multiple organ failure [199]. Because steroids at-
by preventing coronary events but had no impact on mortality tenuate this systemic inflammatory response, theoretically ster-
rates [187]. However, in recent studies, no additional benefit of oids have a potential benefit for patients undergoing cardiac
treatment with fibrate on top of statin therapy has been demon- surgery with CPB, although steroids may also increase the risk for
strated [188]. Bile acid sequestrants (cholestyramine, colestipol infective complications and MI.
and colesevelam) reduce LDL-C by 18–25% and may be used in A meta-analysis of 44 RCTs (n = 3205) looking at the use of ster-
combination with statins [20]. However, gastrointestinal adverse oids in patients undergoing on-pump CABG showed that steroids
events and drug interactions limit their use. reduced POAF, postoperative bleeding and the duration of the
stay in the ICU but failed to show a reduction in the mortality rate
[200]. Steroids did not increase the rate of MI or infective compli-
8. ULCER PREVENTION AND STEROIDS

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cations. The Steroids in Cardiac Surgery (SIRS) trial was conducted
[201] on the basis of this analysis. In the trial, 7507 patients with a
8.1 Ulcer prevention EuroSCORE >5 who underwent cardiac surgery with CPB were
randomized between methylprednisolone or placebo showed no
Based on older studies, the incidence of upper gastrointestinal ul- difference in the risk for 30-day mortality (4% vs 5%, respectively)
ceration and bleeding is around 1% after cardiac surgery and is or the risk for mortality and major morbidity (24% vs 24%, respect-
associated with significant morbidity and mortality (30–40%) [192]. ively). Although there was no difference in the rate of infections or
However, patients undergoing contemporary cardiac surgery are delirium, there was a safety concern due to significantly higher
aggressively treated with antithrombotic medication, and the inci- rates of myocardial injury. The Dexamethasone for Cardiac
dence may therefore be underestimated. The impact of gastro- Surgery (DECS) trial randomized nearly 4500 patients undergoing
intestinal ulcers and bleeding may be larger due to higher cardiac surgery with CPB and confirmed that no benefit was found
comorbidities and more potent antithrombotic medication. with steroids over placebo in the composite of mortality, MI,
Studies have shown that patients continue to have gastrointes- stroke, renal failure or respiratory failure [202].
tinal complications, despite intraoperative histamine 2 antagonist In summary, the routine use of prophylactic steroids is not indi-
therapy, and that more robust prophylaxis is required [193]. A sum- cated for patients undergoing cardiac surgery. However, a sub-
mary of the available evidence concluded that a proton-pump in- group analysis of the Dexamethasone for Cardiac Surgery trial
hibitor, but not an histamine 2 antagonist, reduced gastrointestinal demonstrated an interaction according to age, suggesting that pa-
complications [194]. Indeed, a large randomized trial of 210 patients tients younger than 65 years may benefit from the preoperative
undergoing cardiac surgery randomly assigned patients to tepre- use of steroids [203]. Indeed, younger patients generally have a
none, ranitidine or rabeprazole and found that patients treated more pronounced inflammatory response than elderly patients;
with a proton-pump inhibitor (rabeprazole) had a significantly therefore, suppression of this effect with steroids could have a po-
lower rate of active ulcers (4.3%) compared with 21.4% and 28.6% tential benefit. Patients on chronic steroid therapy should receive
in patients treated with the histamine 2 antagonist (ranitidine) and their usual preoperative dose of steroids on the day of the oper-
the mucosal protector (teprenone), respectively [195]. Therefore, ation. Additional perioperative stress–dose steroids for these pa-
prophylaxis with a proton-pump inhibitor should be considered, tients are reasonable but are not evidence-based [204].
despite a concern that routine prophylaxis may increase the inci-
dence of postoperative pneumonia [196]. Although, there is con-
flicting evidence to support this statement [197]. Recommendation for routine use of steroids

Recommendations for stress ulcer prophylaxis

Recommendation Classa Levelb Ref c

The routine use of prophylactic

Recommendations Classa Levelb Ref c steroids for patients undergoing III A [200–202]
cardiac surgery is not
The prophylactic use of a PPI for
recommended.
patients undergoing cardiac sur- IIa B [194, 195,
gery should be considered to re- 198]
duce gastric complications. a
Class of recommendation.
b
The prophylactic use of an H2 Level of evidence.
c
antagonist for patients undergo- References.
ing cardiac surgery may be con- IIb B [193–195]
sidered to reduce gastric
complications.
9. ANTIBIOTIC PROPHYLAXIS
a
Class of recommendation. Perioperative infections following cardiac surgery, including
b
Level of evidence.
c
surgical site infections (SSIs), bloodstream infections, pneumo-
References.
nia and Clostridium difficile colitis, dramatically affect survival,
PPI: proton-pump inhibitor; H2 antagonist: histamine 2 antagonist.
are the cause of prolonged hospitalization or readmission and
20 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

Choice
Recommendations for antibiotic prophylaxis
First-line treatment with cefazo-
lin or cefuroxime is I A [230, 231,
recommended. 254]
Recommendations Classa Levelb Ref c

In elective patients undergoing Clindamycin or vancomycin are

cardiac surgery who are S. aureus recommended in patients with a I B [232–235]
carriers, mupirocin twice daily I B [226, 227] documented ß-lactam allergy.
intranasally is recommended,
Vancomycin should be con-
starting 4 days before surgery.
sidered for prophylaxis in patients IIa B [239–241,
In elective patients undergoing known to be colonized with 255]
cardiac surgery with an unknown MRSA.
intranasal S. aureus colonization
status, a strategy of testing well in a
advance of cardiac surgery to Class of recommendation.
IIa C b
Level of evidence.
allow the appropriate preopera-
c
tive duration of mupirocin eradi- References.

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d
cation treatment in colonized Table 7 includes the half-time of the most used antibiotics for SAP.
patients should be considered BMI: body mass index; CPB: cardiopulmonary bypass; MRSA: methicil-
over routine mupirocin treatment. lin-resistant Staphylococcus aureus; SAP: surgical antibiotic prophylaxis.
Primary SAP is recommended to
prevent infectious I A [242–244]
complications. significantly increase costs [205]. Moreover, these major infec-
Timing tions are of particular importance, because they have a rela-
tively high prevalence of nearly 5% in the total cardiosurgical
Administration of the first dose population [206].
of antimicrobial therapy within I B
the 60 min before surgical inci- [243, 246] Surgical antibiotic prophylaxis (SAP) before cardiac surgery is
sion is recommended. recommended to decrease the incidence of major infections. In
addition to the administration of intravenous SAP, the gentami-
Administration of vancomycin
and fluoroquinolones within the
cin–collagen sponge has been developed to keep a high
I B [243, 245] concentration of the agents in the local tissues surround-
120 min before surgical incision
is recommended. ing postoperative wounds. The results from a recent meta-
Dosing
analysis showed significant reduction of the risk for sternal
wound infection after implantation of gentamicin–collagen
It is recommended to use SAP ac- I B [210, 247, sponges [207]. However, the heterogeneity among studies
cording to standardized dosesd. 248] was large, and powerful studies to confirm the benefit of add-
Duration itional local intervention in certain patient populations are
warranted.
It should be considered that the
optimal duration of SAP is IIa A [212, 231,
24 hours and should not exceed 249, 250] 9.1 Dosing of surgical antibiotic prophylaxis
48 hours following cardiac surgery.

Intraoperative redosing either The incidence of infection after cardiac surgery decreases in pa-
with half a dose or a full dose tients with higher versus lower antibiotic serum concentrations
depending on the antibiotic that
is used, the length of operation,
at the time CPB is started as well as at the end of the operation
BMI and renal function should [208, 209]. To date, because of its safety, effectiveness and user-
be considered to obtain IIa B [222, 243, friendliness, SAP in cardiac surgery is routinely based on stand-
adequate serum and tissue con- 251]
ardized doses rather than on weight-based doses, which avoid
centrations of the antimicrobial
the need for individual patient calculations and therefore clearly
agent if the duration of the pro-
cedure exceeds two half-lives of reduce the risk for dosing errors (Table 7). Nevertheless, based
the antimicrobial treatment.d on the limited evidence that exists for optimal dosing in obese
patients [210, 211], the dose of cephalosporin should not rou-
Intraoperative redosing either
with half a dose or a full dose tinely exceed the usual adult dose. For patients with renal fail-
depending on the antibiotic that ure, dosing should be adjusted according to the creatinine
is used, the length of the opera- clearance.
tion, BMI and renal function
should be considered to obtain IIa B [252, 253]
adequate serum and tissue con- 9.2 Duration of surgical antibiotic prophylaxis
centrations of the antimicrobial
agent if there is haemodilution
Repeat intraoperative dosing is recommended to ensure ad-
during CPB or excessive blood
loss. equate serum and tissue concentrations if the duration of the
procedure exceeds 2 half-lives of the antibiotic agent or when
Continued there is excessive intraoperative blood loss. Indeed, a
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 21

randomized trial of 838 patients comparing a single-dose versus SAP in adult cardiac surgery is 24 h and should not exceed 48 h.
a 24-h multiple-dose cefazolin regimen in patients undergoing Whether intermittent or continuous administration of antibi-
cardiac surgery reported higher SSI rates with the single-dose otics should be preferred remains unclear, although some evi-
regimen [212]. A recent meta-analysis of 12 RCTs with 7893 pa- dence suggests that continuous infusion may reduce
tients showed that SAP administered >_24 h versus <24 h signifi- postoperative infectious complications [219]. For a strategy of

EACTS GUIDELINES
cantly reduced the risk for SSI by 38% (95% CI 13–69%, intermittent administration, the exact timing of redosing de-
P = 0.002) and the risk for deep sternal wound infections by 68% pends on the half-life of the antibiotic agent that is used. It
(95% CI 12–153%, P = 0.01) [213]. Other studies have failed to should, furthermore, be adjusted for a prolonged antibiotic
show the benefit of prolonging SAP to >48 h [214, 215], al- half-life in patients with renal failure [220–223]. Moreover, re-
though this practise does increase the risk of acquired antibiotic peating SAP shortly after initiation of CPB has recently been
resistance compared with shorter prophylaxis [216–218]. shown to ensure adequate drug levels [223].
Therefore, based on current evidence, the optimal length of

9.3 Choice of surgical antibiotic prophylaxis

The majority of pathogenic organisms isolated from patients with

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Table 7: Half-life of the most frequently used antibiotics for
SAPa SSIs after cardiac surgery are Gram-positive bacteria, which are
followed by Gram-negative bacteria. Only a minority of other
bacteria, anaerobes, fungi and parasites have been identified
Antibiotic agent Half-life
[224, 225].
Ampicilline 60 minutes
Ampicilline/sulbactam 60 minutes Particularly due to the rising numbers of methicillin-resistant
Amoxicilline 60 minutes Staphylococcus aureus infections among patients undergoing
Amoxicilline/clavulanate 60 minutes cardiac surgery, the importance of eradicating intranasal S. aur-
Cefazolin 94 minutes
Cefotaxime 60 minutes eus colonization is stressed. There is clear evidence from a large
Cefotiam 45 minutes RCT that intranasal mupirocin twice daily for 4 days prior to car-
Ceftriaxone 7–8 hours
Cefuroxime 70 minutes diac surgery significantly reduces SSIs in patients known to
Ciprofloxacin 3–5 hours be colonized with S. aureus [226, 227]. However, for patients
Clindamycin 2.5 hours in whom the status of colonization is unknown, testing for colo-
Gentamicin 1.5–2hours
Imipenem 60 minutes nization well in advance of cardiac surgery should be con-
Levofloxacin 7–8 hours sidered to allow the appropriate preoperative duration of
Meropenem 60 minutes mupirocin eradication treatment in colonized patients.
Metronidazole 7 hours
Piperacillin 60 minutes Although this practice introduces logistical difficulties and has
Piperacillin/Tazobactam 45 minutes cost implications, such a strategy should be preferred over rou-
Tobramycin 1.5–2 hours
Vancomycin 6 hours
tine mupirocin treatment in patients with an unknown colon-
ization status.
a
For systemic antibiotic prophylaxis, numerous studies have
Repeat intraoperative dosing if the duration of the procedure exceeds
clearly shown that antibiotic prophylaxis with first- and second-
2 half-lives of the antibiotic agent or when there is excessive intraoper-
ative blood loss or haemodilution. generation cephalosporins can effectively reduce the incidence
SAP: surgical antibiotic prophylaxis. of SSI and postoperative infectious complications in patients
undergoing cardiac surgery (Table 8) [228–230], even though a

Table 8: Recommendations for the choice of SAP

Recommended Alternative agents in patients Strength of

Type of procedure
agents with ß-lactam allergy evidence

CABG Cefazolin, cefuroxime Clindamycin, vancomycin A

Cardiac device implantation (e.g. pacemaker) Cefazolin, cefuroxime Clindamycin, vancomycin A

Ventricular assist devices Cefazolin, cefuroxime Clindamycin, vancomycin C

Heart, lung, heart-lung transplant

Cefazolin Clindamycin, vancomycin A

CABG: coronary artery bypass grafting; SAP: surgical antibiotic prophylaxis.

22 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

meta-analysis showed that second-generation cephalosporins Epidural analgesia started before the operation and following
might be superior in reducing SSIs [231]. In patients with an published guidelines for epidural catheter positioning and re-
allergy to ß-lactam who cannot tolerate cephalosporins, clinda- moval [269] is also associated with a possible reduction in the
mycin or vancomycin is sufficient for Gram-positive coverage mortality rate [258] and a low risk for epidural haematoma [275].
[232–235]. However, up to 15% of hospitalized patients reported Intrathecal (‘spinal’) administration of morphine has been dem-
an allergy to penicillin, but after a formal allergy evaluation, be- onstrated to reduce postoperative opioid consumption and may
tween 90% and 99% of these patients were found to be able to be an alternative to epidural analgesia, because it is associated
safely undergo penicillin treatments [236]. Importantly, these pa- with a reduced risk for epidural haematoma [270, 276].
tients are more likely to be treated with vancomycin, clindamycin Administration of intrathecal clonidine, in addition to morphine,
and quinolones with the increased risk for developing drug- may provide additional benefits in terms of pain control and dur-
resistant infections such as vancomycin-resistant Enterococcus ation of mechanical ventilation, but it may also increase the risk
species and C. difficile [237], leading to increased mortality, mor- for hypotension [271, 272, 277].
bidity and prolonged hospital stays. Therefore, implementation The paravertebral block is another alternative to the neuraxial
of hospital protocols, including preoperative skin testing, may be techniques. Compared with epidural analgesia, the paraverte-
effective therapeutic tools to reduce the rates of intrahospital in- bral block showed a similar analgesic efficacy and a lower inci-

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fections, lower the costs of antibiotics and improve the patients’ dence of minor complications in patients undergoing
outcomes [236, 238]. thoracotomy [278]. However, evidence in cardiac surgery pa-
In patients colonized with methicillin-resistant S. aureus in tients is extremely limited. In patients undergoing median ster-
whom cephalosporins are insufficient, the administration of notomy, the bilateral paravertebral block should be performed.
vancomycin is recommended [239–240]. Although this approach appears safe and is probably associated
with fewer complications compared to epidural analgesia, it re-
quires further investigation [279].
10. ANAESTHESIA AND POSTOPERATIVE Infiltration of local anaesthetics along the sternal wound may
ANALGESIA also be effective in reducing postoperative opioid consumption
[280]. However, continuous infusion through a parasternal cath-
Anaesthetic agents and techniques might affect clinically eter has been associated with increased risk of sternal wound in-
relevant postoperative outcomes through pharmacological fection [281]. A single injection may be effective but requires
organ-protective mechanisms [256, 257] and by blunting further investigation [282].
the stress response [258]. Halogenated anaesthetics (isoflurane,
desflurane and sevoflurane) are commonly used anaes-
thetic drugs with hypnotic, analgesic and muscle-relaxant 10.2 Postoperative pain assessment
properties. In addition, halogenated anaesthetics versus total
intravenous anaesthetics result in additional organ protection Routine assessment of pain and its severity improves pain man-
and improvements in clinically relevant end-points after CABG, agement, both in the ICU and on the ward and allows the verifi-
including reduction of mortality rates and perioperative MIs cation of the effectiveness of analgesic medications. It permits
[256, 257, 259–264]. the monitoring of the response to therapy and detection of
Postoperative pain following cardiac surgery still occurs fre- complications and side effects. Multimodal analgesia (e.g. anal-
quently, both in patients in the ICU and in the general ward gesia through different techniques or drugs acting on different
[265]. It is often underdiagnosed and undertreated, especially in pathways) is more effective than analgesia that relies on a single
patients who are unable to self-report pain. Overall, more than technique in the overall surgical population, and there is no
half of the operated patients report pain as the most traumatic reason to doubt that this also applies to the cardiac surgical set-
experience of their postoperative stay [266, 267]. General rec- ting [269].
ommendations for pain assessment developed for general surgi- Several analgesic techniques and drug classes are currently
cal patients and those in the ICU are also indicated in cardiac available. Intravenous opioids are currently considered ‘stand-
surgery patients. Adequate pain relief is associated with im- ard of care’ in the management of significant postoperative pain
proved outcomes through better respiratory function (e.g. an for patients in the ICU after cardiac surgery. In cooperative pa-
effective cough), early mobilization, prevention of delirium and tients, patient-controlled analgesia is superior to nurse-
a reduction of cardiovascular complications, which lead to a controlled analgesia for pain control [283]. Several opioids are
reduced stay in the ICU and lower associated costs. Poorly available, with no clear evidence of the superiority of one
treated pain can have long-term sequelae that negatively affect over the others. A possible exception might be remifentanil,
the patient’s quality of life and increase healthcare-related costs which has shown cardioprotective effects [284] and superiority
[268, 269]. in pain control [285, 286]. Use of paracetamol (acetaminophen)
is safe and reduces opioid consumption [287–290], making it
the best agent to manage postoperative pain after opioid-based
10.1 Regional anaesthesia for perioperative pain cardiac anaesthesia and in combination with postoperative
control opioids.
Non-steroidal anti-inflammatory drugs are still used in
Loco-regional techniques (epidural, intrathecal analgesics, cardiac surgery [291], despite worsening renal function in
paravertebral block, intercostal nerve block and wound infiltra- some patients. The concomitant administration of other non-
tion) provide excellent postoperative pain control with differ- steroidal anti-inflammatory drugs can theoretically diminish
ent documented impacts on clinically relevant outcomes [270– the antiplatelet effects of low-dose aspirin, increasing the
274]. risk for thromboembolic effects (MI and stroke) [292–297].
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 23

Ketamine may be considered

Treatment options in managing perioperative pain a postoperative analgesic IIb B [312–314]
adjuvant.

Recommendations Classa Levelb Ref c

EACTS GUIDELINES
a
Class of recommendation.
Multimodal analgesia is recom- b
Level of evidence.
mended over single-technique I B [269] c
References.
analgesia. d
For example, allergies, ulcer and liver disease.
It is recommended that adult AKI: acute kidney injury; CABG: coronary artery bypass grafting; COX:
patients undergoing cardiac sur- cyclo-oxygenase; ICU: intensive care unit; IV: intravenous; NSAIDs: non-
gery undergo routine assess- I B [268, 269] steroidal anti-inflammatory drugs; PAC: patient-controlled analgesia.
ment of pain presence and
severity for optimal analgesia.

It is recommended that an
anaesthesia plan including a

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halogenated agent (isoflurane, I B [256, 257]
desflurane or sevoflurane) is Nevertheless, RCTs and meta-analyses have shown that the
used in CABG patients. use of low-dose non-steroidal anti-inflammatory drugs in se-
The use of epidural analgesia lected patients at low risk of adverse events is effective in
may be considered after careful reducing pain and opioid consumption and may shorten
IIb B [258]
consideration of benefits and mechanical ventilation time and stay in the ICU [298–302]. A
risks. single propensity-matched study suggested a possible reduc-
Preoperative intrathecal mor- tion in mortality associated with the use of ketorolac [303].
phine administration may be IIb B [276, 309, Therefore, their use as a second-line agent in patients with-
considered to reduce postopera- 310] out contraindications may be considered. On the contrary,
tive opioid consumption.
RCTs showed that selective cyclo-oxygenase-2 inhibitors are
The paravertebral block may be associated with an increase in adverse cardiovascular
considered as an alternative to IIb B [279] events and should, therefore, not be routinely administered
neuraxial techniques.
[304, 305]. Analgesic adjuvants can reduce postoperative pain
Parasternal continuous infusion if given preoperatively (gabapentine or pregabalin) or postop-
of analgesia is not recom- III B [281] eratively (ketamine) [271, 306–308].
mended in cardiac surgery.

Perioperative remifentanil infu-

sion should be considered in all IIa B
11. BLOOD GLUCOSE MANAGEMENT
patients undergoing cardiac [284]
surgery. Hyperglycaemia affects over 40% of patients after cardiac sur-
PAC should be considered over gery, due to stress and the use of inotropes [206]. Controlled
IIa B [283]
a nurse-driven protocol. studies show that patients with diabetes mellitus (DM) have
IV opioids plus IV paracetamol increased rates of morbidity and mortality after cardiac surgery
should be considered as first- [315]. Perioperative hyperglycaemia, per se, even in non-DM pa-
line treatment for postoperative IIa B [287–289] tients, is associated with negative outcomes after cardiac surgery.
pain in the ICU after cardiac Moreover, roughly 20–30% of cardiac surgery patients have pre-
surgery.
existing DM [316]. DM is associated with endothelial and platelet
Routine NSAIDs are not recom- dysfunction, leading to prothrombotic states, adverse vascular
mended as first-line agents in III A events and increased infection risk. The prevalence of unrecog-
unselected cardiac surgical [292–294]
nized DM and pre-DM in patients undergoing cardiac surgery
patients.
contributes heavily to high blood glucose concentrations (BGCs)
Short-term low-dose NSAIDs in the perioperative period [316]. Small increases in perioperative
may be considered as second- BGCs are associated with significant increases in rates of hospital
line agents in selected patients IIb B [298, 299,
with a low risk of postoperative mortality and morbidity [316, 317]. Therefore, preoperative
301, 302]
AKI and no contraindications to documentation in the diagnosis of diabetes and its type should
NSAIDsd. be a universal practice. Patients undergoing adult cardiac surgery
COX-2 inhibitors are not recom-
should have a fast glucose measurement at hospital admission
mended in cardiac surgical III A [304, 305] and if >120 mg/dl (6.6 mmol/l) the level of haemoglobin A1c
patients. (HbA1c) should be determined.
Preoperative and post-ICU glucose management techniques
It may be considered to start
gabapentin or pregabalin before [306, 307,
have no solid scientific evidence and are based on expert
IIb B
surgery as postoperative anal- 311] opinion. ICU data are controversial and should be interpreted
gesic adjuvants. cautiously. However, there is randomized evidence that peri-
operative BGC control reduces the risk for death and adverse
Continued
events in patients having cardiac surgery [318–320]. There is also
24 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery

evidence that blood glucose control should be started before the

Specific recommendations for perioperative blood glu- operation and not deferred until after surgery. The overall ad-
cose management equacy of BGC monitoring in the weeks before surgery, as re-
flected by the preoperative HbA1c level, is associated with
several perioperative complications including death, stroke, renal
Recommendations Classa Levelb Ref c
failure, sternal wound infections, prolonged ICU stays and re-
Preoperative period admission [321].
It is recommended that oral antidia- Perioperative hyperglycaemia is probably a marker of illness
betics and long-acting subcutaneous in- I C severity rather than a cause of poor outcomes [322]. Indeed, the
sulin be omitted the day before surgery. degree of hyperglycaemia is related to the level of activation of
It should be considered that preopera- the stress response. Although mild-to-moderate stress hypergly-
tive short-acting subcutaneous insulin caemia is protective, it is likely that severe stress hyperglycaemia
is used while patients await surgery to IIa C
maintain blood glucose levels between may be deleterious. However, the blood glucose threshold above
120–180 mg/dl (6.7–10 mmol/l), with a which stress hyperglycaemia becomes harmful is still unknown.
check every 4 hours.
Many observational studies have been carried out to find the

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Intraoperative period most reliable approach to blood glucose levels, and a U-shaped
It should be considered that non-DM association between mean blood glucose levels and death was
patients have a small (5 IU) bolus IV of found, with the lowest mortality rate observed for the 125–
insulin if the blood glucose level is IIa C
160 mg/dl range [323].
>180 mg/dl (>10 mmol/l), as well as
hourly checks. Importantly, evidence points towards an increased risk of
hypoglycaemic events with aggressive glycaemic control and
It should be considered that in non-DM
patients a continuous IV insulin infusion suggests that moderate control can achieve clinically relevant
is started to maintain a blood glucose of IIa B [317, 333, improvements [324–327]. The Controlled Trial of Intensive
150–180 mg/dl (8.3–10 mmol/l) during 334] Versus Conservative Glucose Control in Patients Undergoing
surgery if blood glucose is persistently
>180 mg/dl (<10 mmol/l). Coronary Artery Bypass Graft Surgery (GLUCO-CABG) showed
that intensive insulin therapy to achieve the target glucose level
In diabetic patients, it is recommended
that a continuous IV insulin infusion is between 100 and 140 mg/dl in the ICU did not significantly re-
started at the beginning of surgery and I B [326, 335]
duce perioperative complications compared with the target glu-
continued throughout to maintain a
blood glucose level >150 (>8.3 mmol/l)
cose level between 141 and 180 mg/dl after CABG [328].
and <180 mg/dl (<10 mmol/l). Moreover, the Normoglycemia in Intensive Care Evaluation and
Surviving Using Glucose Algorithm Regulation (NICE-SUGAR)
ICU
trial showed that a blood glucose level between 81 and 108 mg/
With diabetic and non-DM patients, dl was associated with a significant increase in all-cause mortal-
continuous IV insulin infusion is rec-
ommended if the blood glucose level ity in ICU patients compared with a target of 180 mg/dl or less,
I B [328–330]
is >180 mg/dl (>10 mmol/l) for a tar- including both surgical and non-surgical patients [329].
get of 150–180 mg/dl (8.3–10 mmol/l)
during the ICU stay.
Observational studies suggest that, particularly in patients with
insulin-treated DM, glucose levels below the recommended
It is recommended that blood glu- threshold of 180 mg/dl are associated with increased complica-
cose levels are checked hourly if not I C
stable and every 4 hours if stable tions. In patients without DM and non-insulin-dependent DM,
during the ICU stay. higher blood glucose levels were associated with more compli-
After ICU cations than lower blood glucose levels [330, 331]. Whether dif-
ferential glucose thresholds should be stratified according to
It should be considered to start a
combination of short-acting and previous diabetic status requires further large prospective
long-acting subcutaneous insulin at IIa C randomized studies.
50% of the total previous 24-hour in- There is high variability in methods of and indications for
sulin dose (in ICU) and then titrated.
insulin therapy, management of non-insulin agents and
Checking the blood glucose level blood glucose monitoring among glucose management guide-
every 4 hours and adjusting insulin IIa C
doses to a target of 150–180 mg/dl lines issued by several professional organizations due to contro-
(8.3–10 mmol/l) should be considered. versial findings and the lack of high-quality studies [332]. A
It may be considered to restart oral anti- multidisciplinary diabetes team should be in charge of continu-
diabetics at 50% of the preoperative IIb C ous intravenous insulin-infusion protocols, treatment algorithms
dose when the patient is on oral feeding. for the transition to subcutaneous insulin after discharge from
At hospital discharge the ICU, nutritional requirements and the reintroduction of oral
It is recommended that patients with
antidiabetic agents, using hospitalization as a ‘window of oppor-
DM or specifically, de novo DM, consult I C tunity’ for patient education, treatment selection and dose adjust-
a diabetic specialist before discharge. ment (Fig. 4).
Before hospital discharge, the patients with a diagnosis of DM
a
Class of recommendation. or pre-DM should have an endocrinology consultation and diet-
b
Level of evidence. ary counselling. Post discharge, plasma glucose and HbA1c levels
c
References. should be followed up regularly, with appropriate adjustments
DM: diabetes mellitus; ICU: intensive care unit; IU: international unit; made in insulin and oral hypoglycaemic therapies with the aim
IV: intravenous.
of keeping HbA1c <7%.
 EACTS Guidelines / European Journal of Cardio-Thoracic Surgery 25

EACTS GUIDELINES
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Figure 4: A recommended bottom-to-top stepwise strategy to implement perioperative blood glucose control (reproduced from Preiser et al. [323] with permission
from Springer).

ACKNOWLEDGEMENTS artery bypass graft surgery: analysis from the post-myocardial infarction
free Rx event and economic evaluation (FREEE) randomized trial.
Circulation 2013;128:S219–25.
The authors would like to thank Alessandro Belletti and Pasquale [3] Zhang H, Yuan X, Zhang H, Chen S, Zhao Y, Hua K et al. Efficacy of
Nardelli, Department of Anaesthesia and Intensive Care, IRCCS San chronic b-blocker therapy for secondary prevention on long-term out-
Raffaele Scientific Institute, Milan, Italy, for their constructive com- comes after coronary artery bypass grafting surgery. Circulation 2015;
ments and assistance with data collection and Rianne Kalkman, ad- 131:2194–201.
[4] Milojevic M, Head SJ, Parasca CA, Serruys PW, Mohr FW, Morice MC
ministrative director of EACTS, who patiently co-ordinated our et al. Causes of death following PCI versus CABG in complex CAD: 5-
conference meetings and other activities during the entire publica- year follow-up of SYNTAX. J Am Coll Cardiol 2016;67:42–55.
tion process. [5] Hlatky MA, Solomon MD, Shilane D, Leong TK, Brindis R, Go AS. Use of
medications for secondary prevention after coronary bypass surgery
compared with percutaneous coronary intervention. J Am Coll Cardiol
Funding 2013;61:295–301.
[6] Eisen A, Cannon CP, Blazing MA, Bohula EA, Park JG, Murphy SA et al.
The benefit of adding ezetimibe to statin therapy in patients with prior
This article was produced by and is the sole responsibility of the coronary artery bypass graft surgery and acute coronary syndrome in
European Association for Cardio-Thoracic Surgery (EACTS). the IMPROVE-IT trial. Eur Heart J 2016;37:3576–84.
[7] Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V et al. 2014
ESC/EACTS guidelines on myocardial revascularization: the Task Force
Conflict of interest: Miguel Sousa-Uva received speaker fees
on Myocardial Revascularization of the European Society of Cardiology
from AstraZeneca and Boheringer Ingelheim. Jean-Philippe (ESC) and the European Association for Cardio-Thoracic Surgery
Collet received speaker fees and honoraria from Sanofi-Aventis, (EACTS). Developed with the special contribution of the European
Bristol-Myers Squibb, AstraZeneca, Medtronic and Bayer. Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J
Giovanni Landoni received speaker fees from Abbvie, Cardiothorac Surg 2014;46:517–92.
[8] Niebauer J. Is there a role for cardiac rehabilitation after coronary artery
Octapharma and Orion. Manuel Castella received honoraria for bypass grafting? Treatment after coronary artery bypass surgery remains
consultacy from Atricure and Medtronic. Joel Dunning received incomplete without rehabilitation. Circulation 2016;133:2529–37.
research funding from Dextera Surgical. Nick Linker received [9] Mohr FW, Morice MC, Kappetein AP, Feldman TE, Stahle E, Colombo A
speaker fees and honoraria from Medtronic, Boston Scientific, et al. Coronary artery bypass graft surgery versus percutaneous coron-
ary intervention in patients with three-vessel disease and left main cor-
Abbott, Boehringer Ingelheim and Pfizer. Anders Jeppsson
onary disease: 5-year follow-up of the randomised, clinical SYNTAX
received speaker fees and honoraria from AstraZeneca, trial. Lancet 2013;381:629–38.
Boeringer-Ingelheim, XVIVO Perfusion, LFB Corporation, CSL [10] Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY et al. Trial of
Behring, Roche Diagnostics, Triolab AB and Octapharma. Ulf everolimus-eluting stents or bypass surgery for coronary disease. N Engl
Landmesser received speaker fees and honoraria from Amgen, J Med 2015;372:1204–12.
[11] Iqbal J, Zhang YJ, Holmes DR, Morice MC, Mack MJ, Kappetein AP
Sanofi, MSD, Bayer, Boehringer Ingelheim, Abbott and Berlin et al. Optimal medical therapy improves clinical outcomes in patients
Chemie. The other authors have no disclosures. undergoing revascularization with percutaneous coronary interven-
tion or coronary artery bypass grafting: insights from the Synergy
Between Percutaneous Coronary Intervention with TAXUS and
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