ORIGINAL ARTICLE

Enhanced Recovery After Elective Coronary Revascularization Surgery WithMinimal Versus Conventional Extracorporeal Circulation:

A Prospective Randomized Study

Kyriakos Anastasiadis, MD, FETCS, Christos Asteriou, MD, Polychronis Antonitsis, MD, Helena Argiriadou, MD,

Vassilios Grosomanidis, MD, Magdalena Kyparissa, MD, Apostolos Deliopoulos, ECCP,

Dimitrios Konstantinou, MD, and Paschalis Tossios, MD

Objective: A minimal extracorporeal circulation (MECC)

circuit integrates the advances in cardiopulmonary bypass

(CPB) technology into a single circuit and is associated with

improved short-term outcome. The aim of this study was to

prospectively evaluate MECC compared with conventional

CPB in facilitating fast-track recovery after elective coronary

revascularization procedures.

Design: Prospective randomized study.

Setting: All patients scheduled for elective coronary

artery surgery were evaluated, excluding those considered

particularly high risk for fast-track failure. The fast-track

protocol included careful preoperative patient selection, a

fast-track anesthetic technique based on minimal adminis-

tration of fentanyl, surgery at normothermia, early post-

operative extubation in the cardiac recovery unit, and

admission to the cardiothoracic ward within the first 24

hours postoperatively.

Participants: One hundred twenty patients were assigned

randomly into 2 groups (60 in each group).

Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month),

Interventions: Group A included patients who were oper-

ated on using the MECC circuit, whereas patients in Group

B underwent surgery on conventional CPB.

Measurements and Main Results: Incidence of fast-track

recovery was significantly higher in patients undergoing MECC

(25% v 6.7%, p ¼ 0.006). MECC also was recognized as a strong

independent predictor of early recovery, with an odds ratio of 3.8

(p ¼ 0.011). Duration of mechanical ventilation and cardiac

recovery unit stay were significantly lower in patients undergoing

MECC together with the need for blood transfusion, duration of

inotropic support, need for an intra-aortic balloon pump, and

development of postoperative atrial fibrillation and renal failure.

Conclusions: MECC promotes successful early recovery

after elective coronary revascularization procedures, even in

a nondedicated cardiac intensive care unit setting.

& 2013 Elsevier Inc. All rights reserved.

KEY WORDS: coronary artery bypass grafting, minimal

extracorporeal circulation, fast-track, cardiopulmonary bypass

From the Cardiothoracic Department, AHEPA University Hospital,Thessaloniki, Greece.

Address reprint requests to Polychronis Antonitsis, MD, Cardio-thoracic Department, AHEPA University Hospital, Sakellaridi 25, 54248, Thessaloniki, Greece. E-mail: antonits@otenet.gr& 2013 Elsevier Inc. All rights reserved.1053-0770/2601-0001$36.00/0http://dx.doi.org/10.1053/j.jvca.2013.01.010

DEMAND FOR CARDIAC SURGICAL PROCEDUREShas increased considerably during the last decades, con-

tributing significantly to rising health care costs.1 A majorproportion of this cost is attributed to coronary artery bypassgrafting (CABG), which remains the most frequently per-formed and well-studied cardiac surgical procedure. Pressureis exerted on surgeons to decrease resource consumptionwhile operating on an increasing-risk aging population, withoutcompromising safety and quality of care.2 The need forintensive care unit (ICU) stay is an important cost componentof the total cost of recovery after CABG. The concept of fast-track cardiac surgery was introduced in an attempt to reduceICU stay and accelerate the patient’s transfer to a step-down ortelemetry unit as well as to the ward.3 Fast-track recoveryprotocols include not only fast-track anesthetics, but alsonormothermic management and weaning protocols that aim toextubate these patients within a few hours after the surgery.4

Safety and efficacy of fast-track protocols have been wellestablished through large cohort studies and meta-analyses ofrandomized trials.4-6

Minimal extracorporeal circulation (MECC) represents anadvanced cardiopulmonary bypass (CPB) circuit, which wasdesigned to dramatically reduce the side effects caused byCPB, thus resulting in a low inflammation response compar-able to off-pump coronary artery bypass grafting surgery

(OPCAB), while at the same time allowing for completemyocardial revascularization.7 Superiority of MECC comparedwith conventional ECC (CECC) regarding clinical outcomehas been investigated by multiple randomized studies andsubsequent recent meta-analyses.8-11 Even though there isincreasing evidence indicating a benefit for MECC in CABGprocedures regarding short-term outcomes, there are a limitednumber of MECC systems used in contemporary clinicalpractice. The aim of this study was to investigate prospectivelythe role of a minimal extracorporeal circuit in facilitating earlyrecovery after elective coronary revascularization procedures.The authors’ hypothesis was that perceived clinical advantagesof the MECC circuit could promote early recovery and transferof patients to the regular cardiothoracic ward within the first 24hours postoperatively.

2013: pp ]]]–]]] 1

ANASTASIADIS ET AL2

METHODS

Patient Selection

The study was approved by the institutional research ethicscommittee, and all patients gave written informed consent. The fast-track protocol for the study included the following steps: (i) carefulpreoperative patient selection, (ii) a fast-track anasthetic technique,(iii) surgery at normothermia, (iv) early postoperative extubation in thecardiac recovery unit (CRU), and (v) admission to the cardiothoracicward within the first 24 hours postoperatively. Independent predictorswere used for fast-track failure as identified by Constantinides et al asexclusion criteria for the study,12 namely emergency surgery, redo-surgery, cardiogenic shock, preoperative serum creatinine levels42 mg/dL, concomitant surgery, left ventricular ejection fraction(LVEF) on echocardiography o30%, and history of severe debilitatingdisease (extracardiac arteriopathy, chronic obstructive pulmonary dis-ease, or mental illness). One hundred twenty patients scheduled forelective CABG surgery were randomized between January 2010 andDecember 2011. The patients were assigned randomly into 2 groups:Group A(n ¼ 60 patients) involved patients who used the MECC circuit,whereas patients in Group B (n ¼ 60 patients) underwent surgery underCECC (Fig 1). Patients were blinded to the type of circuit used.Randomization was performed in a 1:1 ratio using computer-generatedrandom allocations. The study is registered at ClinicalTrials.gov,number NCT01603589.

Anesthetic Management and HemodynamicMonitoring

In the operating room, 5 electrocardiogram leads were attached, andleads II and V5 were monitored continuously. A 20-G radial arterycatheter was inserted to measure arterial blood pressure and arterialblood gas. A thermodilution pulmonary artery catheter (Swan-GanzCCOmbo CCO/SvO2, Edwards Lifesciences LLC, Irvine, CA) forcontinuous cardiac output and mixed venous oxygen saturationmonitoring was inserted into the right internal jugular vein via a9.0-F introducer (AVA HF, Edwards Lifesciences LLC, Irvine, CA).

All patients received standardized anesthetic management aiming tofacilitate early recovery. Oral premedication with lorazepamwas administered the evening before and bromazepam on theday of surgery, combined with intramuscular injection of 0.1 mg/kg

Fig 1. Flow chart depicting trial phases.

of morphine 30 minutes before entering the operating room. Generalanesthesia was induced with 1 to 3 mg of midazolam, 5 to 10 mg/kg offentanyl, and 2 to 3 mg/kg of propofol. Tracheal intubation wasfacilitated with 1 mg/kg of rocuronium, which was employed also forintraoperative neuromuscular blockade as necessary. During CPB,analgesia was maintained with low-dose fentanyl (5-10 mg/kg) andanesthesia with sevoflurane (0.5-2 minimum alveolar concentration).After sternal closure, fentanyl and sevoflurane were stopped, a bolusdose of morphine (0.1 mg/kg) was administered, and a continuousinfusion of propofol (3-5 mg/kg/h) and morphine (40 mg/kg/h) wasinitiated and maintained for the first hours in the CRU until initiation ofthe weaning protocol. The total dose of fentanyl administered did notexceed 15 mg/kg. Patients were ventilated to achieve normocapnia withair and oxygen (fraction of inspired oxygen, 0.4-0.45).

Perfusion Technology

MECC Group

The MECC system (Maquet Cardiopulmonary, Hirlingen, Germany)acts as a closed, self-regulated circuit, which resembles a mechanicalcirculatory assist device rather than an ECC. The rationale is to increasebiocompatibility by using a heparin-coated short circuit, reduce foreignsurfaces requiring low priming volume, and avoid air-blood interac-tion.13 Venous blood returns through active drainage with a centrifugalpump instead of a roller pump to a membrane diffusion oxygenator.No venous reservoir and cardiotomy suction of shed blood are used.Oxygenated blood enters the circulation with minimized hemodilutionand mechanical trauma, reducing systemic inflammatory response(SIRS) and preserving coagulation.14 The MECC circuit used in theauthors’ institution consisted of a preconnected closed CPB circuitcontaining a RotaFlow centrifugal pump and a Quadrox-i hollow-fibermicroporous membrane oxygenator. A flowmeter and a bubble sensorwere integrated to the drive unit. The system featured tip-to-tip heparincoating (Bioline Coating, Maquet Cardiopulmonary). No arterial orvenous line filters were included. Priming volume of the system was500 mL. Retrograde autologous priming was utilized in all patientsundergoing MECC intraoperatively.

CECC Group

A standard open bypass circuit was used, consisting of uncoatedpolyvinylchloride tubing, a hard-shell venous reservoir, a microporousmembrane oxygenator (Dideco, Mirandola, Italy), and a roller pump(Stockert S3, Munich, Germany). The circuit integrated a 40-mmarterial line blood filter (Dideco, Mirandola, Italy) and was primedwith 1,500 mL of balanced crystalloid/colloid solution (1,000 mLof Ringer’s solution, 200 mL of mannitol 20%, and 300 mL of 6%hydroxyethyl starch). The extracorporeal flow rate for both systems wasset at 2.4 L/min/m2.

Anticoagulation in the CECC group was attained by administrationof 300 IU/kg of heparin to achieve an activated clotting time of longerthan 450 seconds. In MECC group, 150 IU/kg of heparin wasadministered, with a target activated coaglation time of 300 seconds.For both groups, mild hypothermia (351C) and alpha-stat blood gasmanagement were applied. Perfusion pressure was kept at 60 to80 mmHg. During CPB, blood transfusion threshold was a hematocritlevel of less than 21% or a hemoglobin level of less than 7 g/dL.

Surgical Procedure

The same surgical procedure was employed in both groups. Aftermedian sternotomy, the left internal mammary artery and saphenousvein grafts were harvested. Heparinization was followed by standardvenous and arterial cannulation, with a 24-F arterial cannula and a 36/46-F dual-stage venous cannula. Venting through the pulmonary arterytrunk was utilized. Myocardial protection was accomplished using

ENHANCED RECOVERY AFTER ELECTIVE CORONARY REVASCULARIZATION SURGERY 3

antegrade intermittent warm blood Calafiore cardioplegia every 20minutes. After completing distal anastomoses, the aortic cross-clamp wasremoved and the proximal anastomoses were performed using a singleside-clamp on the aorta. The shed blood was collected in both groups, witha cell-saving device (Haemonetics Corp, Braintree, MA). After rewarming,the patient was weaned-off CPB according to the standard criteria andheparin was neutralized with protamine sulfate. An intra-aortic balloonpump (IABP) was inserted when there was inability to wean from CPB orevidence of low-cardiac-output syndrome (cardiac indexo2.2 L/min/m2,pulmonary capillary wedge pressure 425 mmHg, mixed venous oxygensaturation o55%, and increasing lactate levels 430 mg/dL) despitesignificant inotropic support (epinephrine 40.1 mg/kg/min and norepine-phrine4 0.5 mg/kg/min) with impaired contractility of the left ventricle orsigns of myocardial ischemia on the electrocardiogram.

Postoperative Management

All patients were transferred postoperatively intubated to the CRU,which is operated by the surgical and anesthesiology staff that runs thecardiothoracic department, with a 1:1 nurse/patient ratio. In the authors’institution, there is no separate specially designated high-dependencyunit. Extubated patients requiring monitoring are managed in the CRUwith a 1:2 or 1:3 nurse/patient ratio. A standardized protocol forpostoperative care was implemented. A continuous infusion of propofolwas used for postoperative sedation titrated to achieve and maintain aRamsay Sedation Score of 2 to 3, and a continuous infusion ofmorphine at a dose of 40 mg/kg/h was administered for postoperativeanalgesia. Postoperatively, the blood transfusion threshold was ahematocrit less than 24% or a hemoglobin of less than 8 g/dL.Extubation criteria are presented in Table 1.15 Early tracheal extubationwas defined as extubation within 6 hours of arrival in the CRU. Afterextubation, serial arterial blood gases and hemodynamic parameterswere monitored. If hemodynamic and respiratory status remained stablefor a period of 12 to 18 hours, inotropic and vasoactive medicationswere withdrawn, hematologic and biochemical parameters were nor-mal, and there was minimal chest tube drainage (o100 mL for the last5 h), arterial catheter and chest tubes were removed and the patient wastransferred to the cardiothoracic ward with a 1:4 to 1:8 nurse/patientratio depending on the shift. Early recovery was defined as successfulearly tracheal extubation and discharge from the CRU to the wardwithin 24 hours of arrival in the CRU. Early extubation or fast-trackrecovery protocols had not been implemented as routine strategies inthe department before initiation of the study.

Table 1. Extubation Criteria

State of

consciousness:Patient following simple commands

(eg, opening eyes and limb movements)Hemodynamic

stability:Normotension, heart rate o100 beats/min,

and no signs of low-cardiac-output

syndrome or myocardial ischemia without

significant inotropic or vasoactive supportSpontaneous

ventilation:Respiratory rate o25 breaths/min with

adequate ventilatory mechanics, tidal

volume 45 mL/kg, oxygen

saturation 495%, a o50% FIO2, and PaO2/

FIO2 4200Normothermia: Temperature 4 361CAbsence of active

bleeding:Chest tube drainage o100 mL/h and

activated clotting time o120 sAnalgesia: No signs indicative of uncontrolled

pain (in a pain scale [0-10] VAS o5)

Abbreviation: VAS; visual analog scale.

Study Endpoints

The primary endpoint of the study was the rate of fast-trackrecovery in both groups. Secondary endpoints included overallmorbidity and mortality (death occurring within 30 d of surgery orduring hospital stay), chest tube drainage, need for perioperative bloodtransfusion, and length of hospital stay. Postoperative acute kidneyinjury was defined as an increase in creatinine levels postopera-tively 42 mg/dL. Stroke was defined as a neurologic deficit of abruptonset caused by disturbance in blood supply to the brain persistingmore than 24 hours.

Statistical Analysis

Power analysis was employed to detect appropriate sample size. Theauthors have calculated that the average successful fast-track recoveryrate in their institution using CECC is about 10%. They supposed thatimplementation of MECC was expected to raise the corresponding ratesup to 30%. Setting the level of type I error (a) at 0.05 and the desiredpower of the study (1-b) at 80%, they calculated that each group shouldinclude at least 60 subjects (G*Power v. 3.1.2, Heinrich-HeineUniversity, Dusseldorf, Germany). Statistical analysis was performedusing the SPSS 17.0 software (SPSS, Chicago, IL) for Windows.Values of continuous data are presented as mean � standard deviation,whereas categoric variables as absolute numbers and percentages.Normal distribution was assessed by the Kolmogorov-Smirnov test.Univariate comparison of means was made using the Student t test andMann-Whitney U test when appropriate. Comparisons between percen-tages were assessed using the chi-square test. Binary logistic regressionanalysis was used for estimating the corresponding odds ratios and 95%confidence intervals of a number of preoperative parameters (age, sex,diabetic status, LVEF, and ECC) in predicting implementation of fast-track cardiac surgery. Level of statistical significance was set at 0.05.

RESULTS

All randomized patients (60 patients in each group) wereincluded in the analysis. Baseline demographic and clinicalcharacteristics are presented in Table 2. Both groups werecomparable in terms of demographic data and preoperativecharacteristics. Perioperative clinical data are presented inTable 3. Total number of bypass grafts constructed was equalin both groups. Although mean aortic cross-clamp time wassimilar in both groups (65.2 v 70.9 min), total CPB time wassignificantly lower among patients who underwent MECC(102.9 v 124.9 min, p o 0.001), which was consistent withthe previous results reported by the authors’ group.14

Regarding the postoperative course, patients who under-went MECC experienced a reduced duration of mechanicalventilation (11.6 � 5.5 v 16.6 � 5.1 h, p o 0.001) andshorter CRU stay (2 � 0.6 v 2.3 � 0.7 d, p ¼ 0.02), whereastotal in-hospital stay was similar in both groups. Mediastinalbleeding did not differ between groups. However, patientsundergoing MECC required significantly fewer blood trans-fusions, either during CPB (0.5 v 1.5 units, p o 0.001) orpostoperatively (2 v 3 units, p ¼ 0.009). The need for an IABPwas significantly lower in the MECC group (3.3% v. 8.3%,p ¼ 0.03), as well as duration of inotropic support (20.4 � 5.4v 35.2 � 6.3 h, p o 0.001), while the incidence of renalfailure also favored patients undergoing MECC (1.7% v8.3%, p ¼ 0.02). Stroke rate was similar between groups.Moreover, incidence of the most common postoperativearrhythmia, atrial fibrillation, was significantly lower among

Table 2. Preoperative Patients’ Demographic and Clinical

Characteristics

MECC

(n ¼ 60)

CECC

(n ¼ 60) p

Age (y) 64.4 � 9.9 65.1 � 7.8 0.67Sex (male) 45 (75%) 47 (78.3%) 0.67Body surface area (m2) 1.87 � 0.22 1.85 � 0.19 0.75Left ventricular ejection

fraction (%)

48.2 � 7.4 46.7 � 7.8 0.28

EuroSCORE II 5.6 � 2.8 5.4 � 3.5 0.79Diabetes mellitus 19 (31.7%) 17 (28.3%) 0.69Hypertension 34 (56.7%) 32 (53.3%) 0.71Peripheral vascular disease 13 (21.7%) 11 (18.3%) 0.65Recent myocardial

infarction (o30 d)

7 (11.7%) 11 (18.3%) 0.31

Clopidogrel o5 d before

surgery

7 (11.7%) 9 (15.0%) 0.59

Atrial fibrillation 1 (1.7%) 1 (1.7%) 0.77

Preoperative creatinine

levels (mg/dL)

0.96 � 0.19 1.01 � 0.19 0.21

Preoperative CK-MB levels

(IU/L)

18.18 � 7.89 16.22 � 4.74 0.11

NOTE. Data are presented as means � standard deviation.

Abbreviations: CECC; conventional extracorporeal circulation,

MECC; minimal extracorporeal circulation.

Fig 2. Percentage of patients achieving fast-track recovery using

minimal (MECC) versus conventional extracorporeal circulation

(CECC).

ANASTASIADIS ET AL4

patients who had surgery using MECC (33.3% v 53.3%, p ¼0.03). There was no 30-day mortality in either group.

The impact of MECC on postoperative fast-track recoverywas proven to be significant, because 15 patients (25%) in theMECC group achieved fast-track recovery as compared to only4 patients (6.7%) of the CECC group (p ¼ 0.006) (Fig 2).

Table 3. Perioperative Clinical Characteristics

MECC

(n ¼ 60)

CECC

(n ¼ 60) p

Number of bypass grafts 2.9 � 0.7 3.1 � 0.9 0.26

Cardiopulmonary bypass

time (min)

102.9 � 25.4 124.9 � 33 o0.001

Aortic cross-clamp time

(min)

65.2 � 17.6 70.9 � 16 0.07

Cardiac recovery unit stay

(d)

2 � 0.6 2.3 � 0.7 0.02

In-hospital stay (d) 10.8 � 2.6 11.5 � 2.8 0.13

Mechanical ventilation (h) 11.6 � 5.5 16.6 � 5.1 o0.001

Chest tube drainage (mL) 731.7 � 238.2 739 � 323.6 0.89

Intraoperative blood

transfusion (units)

0.5 � 0.7 1.5 � 1.1 o0.001

Postoperative blood

transfusion (units)

2 � 1.7 3 � 2.4 0.009

Need for IABP (%) 2 (3.3) 5 (8.3) 0.03

Duration of inotropic

support (h)

20.4 � 5.4 35.2 � 6.3 o0.001

Stroke (%) 2 (3.3) 3 (5) 0.4

Acute kidney injury (%) 1 (1.7) 5 (8.3) 0.02

Postoperative atrial

fibrillation (%)

20 (33.3) 32 (53.3) 0.03

NOTE. Data are presented as means � standard deviation.

Abbreviations: CECC; conventional extracorporeal circulation,

IABP; intra-aortic balloon pump, MECC; minimal extracorporeal

circulation.

Bold is used to denote statistical significance (p o 0.05).

Univariate analysis revealed that implementation of MECCincreased the probability of successful fast-track recovery in theauthors’ institution by 4.7 times (odds ratio, 4.7; 95%confidence interval: lower bound, 1.48 - upper bound, 15.05).After adjustment for a number of confounding preoperativevariables including age, sex, diabetes, and LVEF in a multi-variate analysis, MECC was recognized as an independentpredictor of fast-track recovery compared with CECC (oddsratio, 3.8; p ¼ 0.011; 95% confidence interval: lower bound,1.36 - upper bound, 10.66) (Table 4).

DISCUSSION

A major source of morbidity that complicates and prolongsrecovery after CABG is attributed to CPB, which remains thegold standard perfusion strategy to perform coronary proce-dures worldwide. Induction of SIRS and the coagulationcascade during CPB is related to end-organ injury postopera-tively.16 OPCAB emerged as a promising alternative to con-ventional coronary artery surgery, aiming to reduce resourceutilization and improve short-term outcome.17 The concernsregarding incomplete revascularization and worse long-termoutcome have limited the OPCAB from being performedroutinely.18

Early postoperative extubation and accelerated recovery oflow- to medium-risk patients undergoing uncomplicated CABGis incorporated in the recently published American College ofCardiology Foundation/American Heart Association guidelines

Table 4. Multivariate Predictors for Fast-Track Cardiac Surgery

Covariates Beta OR 95% CI p

Sex (male v female) �0.126 0.882 0.274-2.838 0.83

Age group (465 v r65) 0.338 1.403 0.529-3.717 0.50

LVEF group 0.50

450% – 1 (reference) – –

35%-50% 0.319 1.376 0.236-8.035 0.72

r35% 0.597 1.817 0.668-4.941 0.24

DM (yes v no) �0.677 0.508 0.191-1.352 0.17

ECC (CECC v MECC) 1.336 3.806 1.358-10.664 0.011

Abbreviations: CECC; conventional extracorporeal circulation, CI;

confidence intervals, DM; diabetes mellitus, ECC; extracorporeal

circulation, LVEF; left ventricular ejection fraction, MECC; minimal

extracorporeal circulation, OR; odds ratio.

ENHANCED RECOVERY AFTER ELECTIVE CORONARY REVASCULARIZATION SURGERY 5

(Class I, Level of evidence: B).1 This is the first reported studyaiming to evaluate the impact of MECC on enhancing recoveryafter CABG. The authors demonstrated that implementation of afast-track protocol including MECC as the perfusion circuitpromoted early recovery in patients scheduled for electiveCABG. Although this randomized study was based on carefulpatient selection and excluded patients with a predicted high riskfor fast-track failure, it reflects the real world as many high-riskpatients were included, which resulted in a calculated Euro-SCORE II for both groups of more than 5. Also, a traditionalfast-track anesthetic protocol for both groups was used based onminimal administration of fentanyl (o15 mg/kg) and morphine(40 mg/kg/h for the first hours in CRU), which may havecontributed to the relatively prolonged duration of mechanicalventilation, in combination with the volatile agent sevoflurane.5

Inhalation anesthetics are beneficial in patients undergoingCABG due to a cardioprotective effect attributed to precondi-tioning and attenuation of ischemia/reperfusion injury.19,20

Recognizing MECC in the study as the only significantindependent predictor of early recovery with an odds ratio of3.8 can be justified based on the perceived advantages on thedesign of this contemporary CPB circuit. The major technolo-gic advancement of the MECC system is the integration ofa closed self-regulated circuit without cardiotomy suction.13

A hard-shell venous reservoir is absent; thus, the patients’ ownvascular compartment acts as a natural reservoir. The contact ofblood with air, which is a major trigger of SIRS, is avoidedcompletely. This is further attenuated with the use of fullyheparin-coated tubing.21 Priming volume required for MECC issignificantly lower compared with CECC, resulting in reducedhemodilution. Use of retrograde autologous priming, asemployed in the study, almost eliminates hemodilution. Thisis translated in clinical terms to a significantly reduced needfor blood transfusion, either intraoperatively or postoperatively,as observed in the study and confirmed by recent meta-analyses.8,14 It is well recognized that morbidity after CPB isincreased in parallel to hemodilution severity22; hence, mostmajor complications, including stroke, myocardial infarction,low-cardiac-output syndrome, renal failure, pulmonary edema,redo-surgery due to bleeding, sepsis, and multiorgan failure, areincreased when the nadir hematocrit during CPB decreases.22

Reduced need for blood product transfusion after surgerywith MECC could be attributed not only to minimal hemodilu-tion but also to preservation of coagulation system integrity dueto its biocompatible design. This effect is of utmost importancein achieving early extubation and enhancing recovery, becauseincreased number of blood transfusions has been associatedwith the need for prolonged ventilation.23

An important intrinsic feature of MECC is the increasedperfusion pressure observed during CPB, which subsequentlyreduces the need for vasoconstrictors compared with conventionalcircuits.13,24 This translates into improved cerebral protection andpartially could explain why patients on MECC achieved an earlierstate of consciousness, which readied them for extubation.25-27

MECC is associated with a less complicated postoperative course,resembling OPCAB surgery. Reduced reperfusion time, need forIABP, and inotropic support reflect improved myocardial protec-tion during surgery with MECC. This effect has been confirmedby multiple studies and meta-analyses and greatly facilitates

recovery.8 van Boven et al reported reduced myocardial oxidativestress when using MECC, which was attributed mainly to reducedSIRS together with the fact that there is a slight coronary residualperfusion that reduces air in the coronary system.28 Parallel tomyocardial protection, preservation of renal function, as confirmedin this study, further enhances recovery. Postoperative acutekidney injury has been recognized as a predictor of prolongedmechanical ventilation.29 This effect is attributed also to improvedhemodynamic characteristics during perfusion with MECC.24

A major characteristic of this study was that the percen-tage of patients who achieved early recovery, though sig-nificantly higher in the MECC group, was relatively low inboth arms (25%v 6.7%) as compared to other similar studies.4

This was attributed mainly to the management policy adoptedby the institution and health care authorities guided byrestrictions in resource utilization. There was reluctance inimplementing fast-track extubation and recovery protocols asa routine procedure in the authors’ department, based on theabsence of a dedicated cardiac ICU with specialized medicalstaff. Postoperative recovery was achieved in a CRU, whichis staffed with dedicated nursing personnel, though themedical staff is comprised of the same surgical and anesthe-sia personnel who run the cardiothoracic department. More-over, there is no separate high dependency unit to treatextubated patients who require monitoring. The authors’policy also included that the patients not be discharged fromthe CRU during the night shift that starts at 11:00 PM. Thedecision to transfer patients from the CRU, with a 1:1 to 1:3nurse/patient ratio, to the cardiothoracic ward with a respec-tive ratio of 1:4 to 1:8 without compromising safety, wasbased clearly on early extubation and an uncomplicatedrecovery indicating the absence of literally any complication.This management policy is a common clinical practiceadopted by many low- to medium-operating volume cardiaccenters, especially in Southeastern Europe. Reduction inCRU stay in patients on MECC, as shown in this study,could lead to a significant cost benefit, considering that CRUstay per day in the authors’ institution is 5 times moreexpensive compared with the regular cardiothoracic ward(400h v 80h/d), even though total length of hospital stay issimilar.

The need for inotropic support and postoperative atrialfibrillation were the main complications that contributed toprolonged CRU stay. In this study, the incidence of atrialfibrillation was significantly higher among patients undergoingconventional CPB. Attenuated SIRS, combined with reducedneed for blood transfusion or excessive fluid administrationduring surgery with MECC, contributed to a more physiologiccondition that reduced the possibility of developing post-operative atrial fibrillation.

One limitation of the current study was that it was singleinstitutional with a relatively small number of recruited patientsconducted by a university department with experience in allaspects of surgery with MECC but without facilities thatpromote fast-track recovery. True double-blinding when asses-sing surgical procedures is not considered possible. Moreover,the fast-track anesthetic protocol implemented in this study wasbased on minimal administration of fentanyl and morphine,whereas contemporary protocols that use short-acting opioids,

ANASTASIADIS ET AL6

such as remifentanyl, further accelerate early extubation. Thestrength of the current study was the prospective randomizeddesign, the quality of the randomization, and the uniformity ofboth surgical and anesthetic techniques.

In conclusion, this single-center experience demonstrated, forthe first time, that implementation of MECC could promotesuccessful early recovery after elective coronary revascularization

procedures in a center not dedicated to implementing fast-trackrecovery protocols. Reduced duration of CPB together with a stablepostoperative course contribute to early extubation and acceleratedrecovery even in CRU/non-ICU setting. Financial implications ofthis strategy could be translated into significant cost benefit forhealth care authorities. This needs to be evaluated further with well-designed prospective multi-institutional randomized trials.

REFERENCES

1. Hillis LD, Smith PK, Anderson JL, et al: American College ofCardiology Foundation/American Heart Association Task Force onPractice Guidelines: 2011 ACCF/AHA guideline for coronary arterybypass graft surgery: Executive summary: A report of the AmericanCollege of Cardiology Foundation/American Heart Association TaskForce on Practice Guidelines. J Thorac Cardiovasc Surg 143:4-34, 2012

2. Taggart DP, Altman DG, Gray AM, et al: Randomized trial tocompare bilateral vs. single internal mammary coronary artery bypassgrafting: 1-Year results of the Arterial Revascularisation Trial (ART).Eur Heart J 31:2470-2481, 2010

3. Salhiyyah K, Elsobky S, Raja S, et al: A clinical and economicevaluation of fast-track recovery after cardiac surgery. Heart SurgForum 14:E330-E334, 2011

4. van Mastrigt GA, Maessen JG, Heijmans J, et al: Does fast-tracktreatment lead to a decrease of intensive care unit and hospital length ofstay in coronary artery bypass patients? A meta-regression of random-ized clinical trials. Crit Care Med 34:1624-1634, 2006

5. Myles PS, Daly DJ, Djaiani G, et al: A systematic review of thesafety and effectiveness of fast-track cardiac anesthesia. Anesthesiology99:982-987, 2003

6. Svircevic V, Nierich AP, Moons KGM, et al: Fast track anesthesiaand cardiac surgery; a retrospective cohort study of 7998 patients.Anesth Analg 108:727-733, 2009

7. Mazzei V, Nasso G, Salamone G, et al: Prospective randomizedcomparison of coronary bypass grafting with minimal extracorporealcirculation system (MECC) versus off-pump coronary surgery. Circula-tion 116:1761-1767, 2007

8. Anastasiadis K, Antonitsis P, Haidich AB, et al: Use of minimalextracorporeal circulation improves outcome after heart surgery; asystematic review and meta-analysis of randomized controlled trials. IntJ Cardiol . [Epub ahead of print], 2012

9. Zangrillo A, Garozzo FA, Biondi-Zoccai G, et al: Miniaturizedcardiopulmonary bypass improves short-term outcome in cardiacsurgery: A meta-analysis of randomized controlled studies. J ThoracCardiovasc Surg 139:1162-1169, 2010

10. Biancari F, Rimpilainen R: Meta-analysis of randomised trialscomparing the effectiveness of miniaturised versus conventional cardio-pulmonary bypass in adult cardiac surgery. Heart 95:964-969, 2009

11. Harling L, Warren OJ, Martin A, et al: Do miniaturizedextracorporeal circuits confer significant clinical benefit without com-promising safety? A meta-analysis of randomized controlled trials.ASAIO J 57:141-151, 2011

12. Constantinides VA, Tekkis PP, Fazil A, et al: Fast-track failureafter cardiac surgery: Development of a prediction model. Crit CareMed 34:2875-2882, 2006

13. Wiesenack C, Liebold A, Philipp A, et al: Four years’ experiencewith a miniaturized extracorporeal circulation system and its influenceon clinical outcome. Artif Organs 28:1082-1088, 2004

14. Anastasiadis K, Asteriou C, Deliopoulos A, et al: Haematologicaleffects of minimized compared to conventional extracorporeal circulationafter coronary revascularization procedures. Perfusion 25:197-203, 2010

15. Heijmans J, Fransen E, Buurman W, et al: Comparison of themodulatory effects of four different fast-track anesthetic techniques on

the inflammatory response to cardiac surgery with cardiopulmonarybypass. J Cardiothorac Vasc Anesth 21:512-518, 2007

16. Royston D: The inflammatory response and extracorporealcirculation. J Cardiothorac Vasc Anesth 11:341-354, 1997

17. Scott BH, Seifert FC, Grimson R, et al: Resource utilization inon- and off-pump coronary artery surgery: Factors influencing post-operative length of stay—An experience of 1,746 consecutive patientsundergoing fast-track cardiac anesthesia. J Cardiothorac Vasc Anesth19:26-31, 2005

18. Shroyer AL, Grover FL, Hattler B, et al: Veterans AffairsRandomized On/Off Bypass (ROOBY) study group. On-pump versusoff-pump coronary-artery bypass surgery. N Engl J Med 361:1827-1837, 2009

19. De Hert SG, Van der Linden PJ, Cromheecke S, et al:Cardioprotective properties of sevoflurane in patients undergoingcoronary surgery with cardiopulmonary bypass are related to themodalities of its administration. Anesthesiology 101:299-310, 2004

20. De Hert SG, ten Broecke PW, Mertens E, et al: Sevoflurane butnot propofol preserves myocardial function in coronary surgerypatients. Anesthesiology 97:42-49, 2002

21. Fromes Y, Gaillard D, Ponzio O, et al: Reduction of theinflammatory response following coronary bypass grafting with totalminimal extracorporeal circulation. Eur J Cardiothor Surg 22:527-533, 2002

22. Habib RH, Zacharias A, Schwann TA, et al: Adverse effects oflow hematocrit during cardiopulmonary bypass in the adult: Shouldcurrent practice be changed? J Thorac Cardiovasc Surg 125:1438-1450, 2003

23. Alhan C, Toraman F, Karabulut EH, et al: Fast track recovery ofhigh risk coronary bypass surgery patients. Eur J Cardiothorac Surg 23:678-683, 2003

24. Bauer A, Diez C, Schubel J, et al: Evaluation of hemodynamicand regional tissue perfusion effects of minimized extracorporealcirculation (MECC). J Extra Corpor Technol 42:30-39, 2010

25. Liebold A, Khosravi A, Westphal B, et al: Effect of closedminimized cardiopulmonary bypass on cerebral tissue oxygena-tion and microembolization. J Thorac Cardiovasc Surg 131:268-276, 2006

26. Rimpilainen R, Hautala N, Koskenkari JK, et al: Minimizedcardiopulmonary bypass reduces retinal microembolization: A randomizedclinical study using fluorescein angiography. Ann Thorac Surg 91:16-22, 2011

27. Anastasiadis K, Argiriadou H, Kosmidis MH, et al: Neurocog-nitive outcome after coronary artery bypass surgery using minimalversus conventional extracorporeal circulation: A randomised con-trolled pilot study. Heart 97:1082-1088, 2011

28. van Boven WJ, Gerritsen WB, Driessen AH, et al: Myocardialoxidative stress, and cell injury comparing three different techniquesfor coronary artery bypass grafting. Eur J Cardiothorac Surg 34:969-975, 2008

29. Legare JF, Hirsch GM, Buth KJ, et al: Preoperative prediction ofprolonged mechanical ventilation following coronary artery bypassgrafting. Eur J Cardiothorac Surg 20:930-936, 2001