Coronary artery bypass grafting with a minimized cardiopulmonary bypass circuit: a prospective, randomized trial
Coronary artery bypass grafting with a minimized cardiopulmonarybypass circuit: A prospective, randomized trial
Marc P. Sakwa, MD,Robert W. Emery, Francis L. Shannon, Jeffrey M. Altshuler, MD,Dawn Mitchell, RN,
Objective: The study was designed to determine differences in blood loss and transfusion associated with a min-imized cardiopulmonary bypass circuit versus a standard bypass circuit.
Methods: From February 2005 through April 2006, 199 patients were randomized to undergo coronary arterybypass grafting with a standard cardiopulmonary bypass circuit (Medtronic, Inc., Minneapolis, Minn) or a min-imized bypass circuit, the Medtronic Resting Heart Circuit. Laboratory perimeters (hemoglobin and plateletcount), were measured at baseline, after initiation of cardiopulmonary bypass, and on intensive care unit admis-sion. Lowest values recorded were noted. Blood administration was controlled by study-specific protocol orders,(transfusion for hemoglobin<8mg%). Patient demographic data were retrieved from the Society of Thoracic Sur-geons database. Blood product administration was recorded during hospital admission, and chest tube drainage astotal output collected from operating room to discontinuation. Continuous variables were tested with a Wilcoxinrank test, and categoric variables with X2 and Fisher’s exact tests.
Results: Hematocrit, equivalent at baseline, was higher in minimized circuit cohort at lowest point during cario-pulmonary bypass (31.5% Æ 3.9% vs. 25.5% Æ 3.7%), after protamine (31.6% Æ 3.9% vs 29.2% Æ 3.7%), and onintensive care unit arrival (35.2% Æ 4.1% vs 31.8% Æ 3.5%, P < .001). Similarly, platelet count was higher inminimized circuit group on intensive care unit arrival, as was lowest platelet count recorded (170 3 103 Æ 48cells/mm3 vs 107 3 103 Æ 28 cells/mm3, P<.0001). Time to extubation was shorter in minimized circuit group(848 Æ 737 minutes vs. 526 Æ 282 minutes, (P<.01), and total chest tube drainage was lower (1124 Æ 647 mL vs.
506 Æ 214 mL, P<.01). Fewer red blood cells (148 vs 19 units) were given in minimized circuit group (P<.0001).
Conclusions: A minimized cardiopulmonary bypass circuit provides less hemodilution, platelet consumption,chest tube output and lower post-operative blood loss than standard cardiopulmonary bypass. Red blood cellusage was also less. All differences are advantageous.
Since its introduction in the 1950s, cardiopulmonary bypass
some of these concerns, surgeons initially began doing cor-
(CPB) has allowed the development of heart surgery, which
onary artery bypass grafting (CABG) procedures without the
has become the most common of surgical procedures per-
use of CPB (off-pump CABG, or OPCDuring the
formed on a global basis.Even though CPB has been
1990s, OPCAB became popular; because of the technical
used in millions of cases during the past 56 years, there
difficulties encountered in this procedure, however, as well
are still unsolved problems, many of which have been eluci-
as a questionable effect on long-term graft patency, OPCAB
dated in the past decade. These problems include but are not
is currently performed in fewer of 25% of CABG proce-
limited to hemodilution, complement and white cell activa-
dures.A further means of combating the side effects of
tion with systemic inflammatory response, platelet activa-
CPB has been the development of minimized circuits.
tion, the need for intensive anticoagulation, systemic organ
These circuits minimize foreign surface–blood interaction
dysfunction, and the frequent need for blood and blood prod-
and are heparinized from tip to tip. The tubing length has
ucts to control postbypass bleeding or blood Atrial
been shortened to decrease crystalloid prime. Importantly,
fibrillation (AF), the most common untoward event after
the use of cardiotomy suction is eliminated or minimized,
heart surgery, has also been related to CPB.To address
and an active air-removal device is added to this closed cir-cuit. To evaluate the potential advantages of a minimizedcircuit relative to a standard CPB (SCPB) unit, a prospective,
From the Division of Cardiovascular Surgery, William Beaumont Hospital, Royal
Oaks, Mich,a and the Division of Cardiovascular Surgery, St Joseph’s Hospital,
Supported by an unrestricted grant from Medtronic Inc to the Beaumont Research
Received for publication April 17, 2008; revisions received Aug 4, 2008; accepted for
After investigation review board approval was received, 199 patients
older than 40 years who were to undergo first-time CABG were randomly
Address for reprints: Robert W. Emery, MD, 640 Jackson St, MS: 11503K, St Paul,
assigned to the use of a Medtronic Resting Heart (RHC) minimized circuit
(Medtronic, Inc, Minneapolis, Minn) or a standard Medtronic CPB circuit
(SCBP) at the time of surgical scheduling by means of computer-generated
0022-5223/$36.00Copyright Ó 2009 by The American Association for Thoracic Surgery
randomization cards sealed in envelopes. The study was conducted from
February 2005 through April 2006. Exclusionary criteria included
The Journal of Thoracic and Cardiovascular Surgery c Volume 137, Number 2
CABG ¼ coronary artery bypass graftingCPB
coagulopathy (international normalized ratio >2), emergency surgery, andsurgery expected to last longer than 6 hours. Additionally excluded were pa-tients who received 11b/111a platelet inhibitors, clopidogrel, or thrombo-lytic therapy within 5 days of surgery; those who showed evidence ofventricular or aortic aneurysm or ventricular thrombus; and those who re-quired other concomitant therapy. Aprotinin was not used.
Operating personnel could not be blinded to circuit randomization. Ex-
tubation was carried out by intensive care unit (ICU) intensivist staff accord-ing to the Beaumont Hospital protocol for all patients undergoing heartsurgery. The ICU physicians were aware that the patients were in theCPB study, but did not know which circuit had been used. The study pa-tients represented fewer than 20% of the heart operations conducted during
FIGURE 1. Medtronic Resting Heart circuit (Medtronic, Inc, Minneapolis,
Transfusion of red blood cells was controlled intraoperatively and post-
operative by a study-specific protocol to administer blood if hemoglobin fell
tip to tip with a Carmeda heparin surface. Our circuit included a Trillium-
below 8 mg/dL in both groups. There were no protocol violations.
coated (BioInteractions Ltd, Reading, UK) reservoir limited to aortic root
Intraoperative fluids were limited by protocol, and perfusion pressure
was maintained during retrograde autologous priming (RAP) by pressor ad-
Heparin was administered (350 units/kg) to maintain activated clotting
ministration. RAP was discontinued if patient hypotension related to hypo-
time greater than 400 seconds. Standard aortic and venous cannulations
were undertaken, and in the RHC group kinetic assistance was used for ve-nous drainage (40–50 mm Hg suction). After cannulation, RAP was used to
displace all but 300 mL of crystalloid prime in the RHC to a bag reservoir,
Laboratory parameters recorded included hematocrit on entry to the op-
which was separated from the circuit and reinfused to the circuit after CPB,
erating room, after the administration of heparin, at its nadir during CPB,
displacing blood from the tubing. All salvaged cells were washed and rein-
after protamine administration and, on arrival at the ICU. Platelet count
fused. In contrast, the Medtronic SCPB circuit, as noted, used the same bio-
was measured at baseline, on admission to the ICU, and as the lowest plate-
pump and oxygenator but did not have an active air-removal system. The
let count recorded during the hospital stay.
SCBP membrane oxygenator and reservoir were Trillium coated. RAP
During the hospital stay, the total numbers of units of blood and blood prod-
was also used in the SCBP cohort; because of patient hypotension, however,
ucts were recorded, and the timing of product administration was noted. Chest
only about half of the 1850-mL volume could be displaced.
tube drainage was recorded as total output collected from the operating roomdrainage initiation to chest tube discontinuation, and extubation time was mea-
sured from arrival at the ICU until the endotracheal tube was removed.
There were 199 patients randomly allocated, 97 to SCPB and 102 to
Pertinent demographic data, operative data, and postoperative adverse events
RHC. Mean age was 67 Æ 10 years (range 39–86 years). Demographic char-
were retrieved from the Society of Thoracic Surgeons database collection.
acteristics of the patients are shown in and the operative proceduresare shown in . The left internal thoracic artery was used in all cases.
Proximal and distal anastomoses were conducted under aortic crossclamp
The RHC was selected for use after a large experience with routine heart
with the heart stilled by the administration of surgeon-specific cardioplegic
surgery. A closed circuit (containing an active air-removal device) with
solution. There was no 30-day mortality. One SCBP patient was returned to
a centrifugal pump and Carmeda-coated (Carmeda AB, Upplands Va¨sby,
the operating room for surgical bleeding. One patient in each group required
Sweden) high-efficiency oxygenator forms the core of the system (
The tubing consists of a 48 3 0.375-inch arterial line and 84 3 0.375-inchvenous tubing, as opposed to the SCPB circuit, with tubings 80 3 0.375 in-
ches and 120 3 0.5 inches, respectively, thus minimizing crystalloid prim-
Continuous variables were tested with a Wilcoxon rank test, a nonpara-
ing volume to approximately 900 mL versus 1850 mL. Because of the
metric approximation of the t test. Categoric variables were examined with
shorter tubing length, the circuit has to ‘‘nestle’’ closely to the patient, mak-
a c2 test; otherwise, a Fisher exact test was used. Values are expressed as
ing the vertical array an important space-saving feature. The RHC is coated
The Journal of Thoracic and Cardiovascular Surgery c February 2009
TABLE 1. Demographic characteristics by circuit type
TABLE 3. Hematologic parameters by circuit type
Data are mean Æ SD. CPB, Cardiopulmonary bypass; SICU, surgical intensive care
P not significant for all comparisons.
Several models of minimized CPB circuits have been de-
veloped and used on a global basis, although as yet for a mi-
CPB times were similar between groups (76 Æ 20 minutes
exposure for complete revascularization and, in more than
for SCBP and 75 Æ 20 minutes for RHC, P>.05). As shown
1500 cases, found neither systemic injury nor occult air em-
in , the hematocrit was significantly higher at all
bolism, consistent with other A minimized cir-
times after the initiation of CPB with the RHC as opposed
cuit has been used in all forms of heart surgery, including
to the conventional circuit. Similarly, platelet count was
CABG, aortic valve replacement, and robotically enabled
higher in patients in whom the RHC was used at all times
mitral valve surgery.This randomized trial confirms
after baseline. The times to extubation were 848 Æ 737 min-
previous non-American studies indicating that less blood
utes in the SCBP group and 526 Æ 282 minutes in the
administration is needed after minimized circuit use, with
RHC group (P < .01). Total chest tube drainage in the
less blood loss during the immediate postoperative pe-
SCPB group (1124 Æ 647 mL) was greater than that in
riod.This is of particular importance because the ad-
the RHC group (560 Æ 214 mL (P < .001). In addition to
ministration of red blood cells can increase postoperative
the blood count being higher in patients in the RHC group,
morbidity and mortaliEven after a successful surgical
more patients in the SCBP group required the use of red
outcome, red blood cell transfusion has also been shown to
blood cells, and a greater number of red cell units were given
reduce long-term survival.Thus it is important to eliminate
both on bypass and during the hospital stay in the SCBP
group (The use of platelets in the operating room
The salutary effect of the minimized circuit is likely due to
(8 vs 3 patients) and in the ICU (4 vs 3 patients) was not sta-
several factors. First, hemodilution is minimized by the
tistically different (P>.5) for SCBP versus RHC. Similarly,
shortened tubing length and the smaller inner diameter of
the use of fresh-frozen plasma was minimal, with a total of 5
tubing used, thus not only maintaining a higher hematocrit
units versus 1 unit for SCBP and RHC groups, respectively.
during the operative procedure and after CPB but minimiz-
Cell salvage reinfusion was not different between the RHC
ing the dilution of coagulation factors. Along with minimiz-
and SCBP groups (716 Æ 256 mL and 810 Æ 346 mL,
ing the blood–foreign surface interface, the shortened tubing
P>.05). Postoperative AF occurred in 16% of the patients,
with its tip-to-tip heparin coating also minimizes platelet ac-
14% in the RHC group and 19% in the SCBP group, with
tivation. Because of the previously mentioned factor, less in-
the difference not reaching significance. Cerebrovascular
tensive anticoagulation is necessary during the CPB run,
accidents were equally distributed, with 2 events in each
enabling better postoperative hemosIn our experi-
group, and were all minor, requiring no therapy. There
ence, approximately two thirds of the traditional hepariniz-
were no postoperative sternal wound complications.
ing dose for the SCPB circuit is used.RAP is also an
TABLE 2. Number of grafts per procedure by circuit type
The Journal of Thoracic and Cardiovascular Surgery c Volume 137, Number 2
Second, the effect of the minimal circuit volume and ret-
rograde autologous priming may be obviated if too much
crystalloid volume infusion is administered before and dur-ing the case. In this study, fluid was controlled by protocol,
and perfusion pressure was maintained during RAP by pres-
Finally, because kinetic assistance is necessary, emptying
important factor in red blood cell conservation and minimi-
of the heart with decreased perfusion flow can at times be
zation of hemodilution; however, RAP was used in all cases
difficult. One needs to ensure a complete seal around and
in both groups, yet hemoglobin was higher and red blood
proper positioning of the venous drainage cannulas to prevent
cell use lower with the RHC at all times after the initiation
air entering the circuit. and the surgeon must maintain active
of CPB. Thus RAP alone cannot explain all the salutary ef-
observation on the heart should the right atrium or right
fects of the minimized circuit. Finally, because of the mini-
ventricle dilate with undrained volume, communicating with
mized closed circuit, the heparin coating, and, importantly,
the perfusionist to improve drainageThere are specific
the decreased air–blood interface, the activation of white
instances—including the administration of cardioplegic solu-
blood cells releasing inflammatory factors is minimized.
tion, discontinuation of vent drainage, and, importantly, car-
Earlier extubation is likely related to less hemodilution and
diac manipulation, particularly pulling the heart superiorly
white blood cell activation, consequently resulting in less
and to the right for access to the circumflex coronary artery
system–that can impede venous drainage and lower perfusion
Immer and colleaguesfound improved myocardial pro-
flows. Drainage issues can also occur with vigorous traction
tection in patients undergoing surgery with the minimized
on the left atrium during mitral valve surgery. Active commu-
circuit as opposed to SCBP. In addition to improved protec-
nication among all portions of the surgical team is mandatory.
tion, patients with the minimized circuit had less weight gain,
Air entry to the RHC was not encountered. The active air-
and the authors believed these facts to be primarily responsi-
removal system cleared any air that might enter the venous
ble for the lower incidence of postoperative new-onset AF in
cannula and obviated, even eliminated, the occult air embo-
their minimized circuit patients. Koch and
lization that has been seen with SCBP.
found red blood cell transfusion to be associated with an in-
In summary, the RHC offers a viable alternative to the
creased risk of AF. We found no difference between groups
SCPB circuit. It has been associated with less postoperative
in the incidence of AF. In patients at higher risk for AF, how-
blood loss, lower transfusion rates, and earlier extubation,
ever, the impact of a minimized circuit may be more notice-
while allowing adequate exposure for cardiac surgical pro-
able. Other reports have indicated that the minimized circuit
cedures. This was a series of low-risk CABG surgical pa-
offers similar decreases in all the previously mentioned pa-
tients, and those in populations at higher risk may achieve
rameters, which is more similar to OPCAB surgery than to
SCBP; however, the use of RHC facilitates complete revas-cularization, especially for complex anatomy or unstable
We acknowledge the work of Nicholas A. Tepe, MD, Phillip L.
Robinson, MD, Joseph S. Bassett, MD, Goya V. Raikar, MD, Mark
The systemic inflammatory response is the result of the
Pica, RN, and Joan Benedetti, RN, without whose efforts the pro-ject would be incomplete.
activation of both cellular and humoral components.
Although this study did not undertake the measurementof inflammatory markers, others have noted a decrease in
1. Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac
the inflammatory response with minimized bypass cir-
surgery. In: Gibbon JH Jr, ed. Recent advances in cardiovascular physiology
cuits.Inflammatory response activation may con-
and surgery. Minneapolis: University of Minnesota; 1953. p. 107-13.
tribute to myocardial dysfunction, respiratory failure, renal
2. Butler J, Recker GM, Westaby S. Inflammatory response to cardiopulmonary by-
pass. Ann Thorac Surg. 1993;55:552-9.
insufficiency, confusion or stroke, and AF.Eliminating
3. Fromes Y, Gaillard D, Ponzio O, Chauffert M, Gerhardt MF, Deleuze P, et al. Reduc-
or minimizing these effects is desirable.
tion of the inflammatory response following coronary artery bypass grafting with to-
A learning curve is necessary but is not associated with
tal minimal extracorporeal circulation. Eur J Cardiothorac Surg. 2002;22:527-33.
4. Abdel-Rahman U, Ozaslan F, Ristesk P, Martens S, Moritz A, Al Daraghmeh A,
higher riskThere are three drawbacks to the minimized
et al. Initial experience with a minimized extracorporeal bypass system: is there
circuit that become apparent during its use. First, communi-
clinical benefit? Ann Thorac Surg. 2005;80:238-43.
cation between the perfusion, anesthesiology, and surgical
5. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann
teams is more imperative than with SCBP. The blood pres-
6. Immer FF, Pirovino C, Gygax E, Englberger L, Tevaearai H, Carrel TP. Minimal
sure has to be maintained during RAP, and active communi-
versus conventional cardiopulmonary bypass: assessment of intraoperative myocar-
cation when CPB is initiated is necessary to determine
dial damage in coronary bypass surgery. Eur J Cardiothorac Surg. 2005;28:701-4.
7. Edgerton JR, Herbert MA, Prince SL, Horswell JL. Reduced atrial fibrillation in
adequacy of perfusion because the circuit has been primed
patients immediately extubated after off-pump coronary artery bypass grafting.
The Journal of Thoracic and Cardiovascular Surgery c February 2009
8. Puskas J, Cheng D, Knight J, Angelini G, DeCannier A, Dullum M, et al. Off-pump
˚ , Tangen G, Brosstad F, Abdelnoor M, Ringdal ML, et al.
versus conventional coronary bypass grafting: a meta-analysis and consensus state-
Completely heparinized cardiopulmonary bypass and reduced systemic heparin:
ment from the 2004 ISMICS Consensus Conference. Innovations. 2005;1:3-27.
clinical and hemostatic effects. Ann Thorac Surg. 1995;60:365-71.
9. Puskas JD, Steele M. Would you like some cardiopulmonary bypass with your
21. Perthel M, El-Ayoubi L, Bendisch A, Laas J, Gerigk M. Clinical advantages of
coronary revascularization? Circulation. 2007;116:1756-8.
using mini-bypass systems in terms of blood product use, postoperative bleeding
10. Gundry SR, Romano MA, Shattuck OH, Razzouk AJ, Bailey LL. Seven-year fol-
and air entrainment: an in vivo clinical perspective. Eur J Cardiothorac Surg.
low-up of coronary artery bypasses performed with and without cardiopulmonary
bypass. J Thorac Cardiovasc Surg. 1998;115:1273-8.
22. Castiglioni A, Verzini A, Pappalardo F, Colangelo N, Torracca L, Zangrillo A,
11. Wiesenack C, Liebolo A, Philipp A, Ritzka M, Koppenberg J, Birnbaum DE, et al.
et al. Minimally invasive closed circuit versus standard extracorporeal circulation
Four years’ experience with a miniaturized extracorporeal circulation system and
for aortic valve replacement. Ann Thorac Surg. 2004;83:586-91.
its influence on clinical outcome. Artif Organs. 2004;28:1082-8.
23. Remadi JP, Rakotoarivello Z, Marticho P, Trojette F, Benamar A, Poulain H, et al.
12. Remadi JP, Marticho P, Butoi I, Rakotoarivelo Z, Trojette F, Benamar A, et al.
Aortic valve replacement with the minimal extracorporeal circulation (Jostra
Clinical experience with the mini-extracorporeal circulation system: an evolution
MECC System) versus standard cardiopulmonary bypass: a randomized prospec-
or a revolution? Ann Thorac Surg. 2004;77:2172-6.
tive trial. J Thorac Cardiovasc Surg. 2004;128:436-44.
13. Remadi JP. Invited commentary. Ann Thorac Surg. 2008;85:1000-1.
24. Koch CG, Li L, Duncan AI, Mihaljevic T, Cosgrove DM, Loop FD, et al. Mor-
14. Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA, Angelini GD. In-
bidity and mortality risk associated with red blood cell and blood-component
flammatory response after coronary revascularization with or without cardiopul-
transfusion in isolated coronary artery bypass grafting. Crit Care Med. 2006;
monary bypass. Ann Thorac Surg. 2000;69:1198-204.
15. Beghi C, Nicolini F, Agostinelli A, Borrello B, Budillon AM, Bacciottini F, et al.
25. Koch CG, Li L, Sessler D, Figueroa P, Hoeltge GA, Mihaljevic T, et al. Duration
Mini-cardiopulmonary bypass system: results of a prospective randomized trial.
of red cell storage and complications after cardiac surgery. N Engl J Med. 2008;
16. Mazzei V, Nasso G, Salamone G, Castorino F, Tommasini A, Anselmi A. Pro-
26. Koch CG, Li L, Duncan AI, Mihaljevic T, Loop FD, Starr NJ, et al. Transfusion in
spective randomized comparison of coronary bypass grafting with minimal extra-
coronary artery bypass grafting is associated with reduced long-term survival. Ann
corporeal circulation system (MECC) versus off-pump coronary surgery.
27. Baufreton C, de Brux JL, Binuani P, Corbeau JJ, Subayi JB, Daniel JC, et al. A
17. Emery RW, Raikar GV, Murphy BJ, Rohan A, Nielsen K. The use of the mini-cardio-
combined approach for improving cardiopulmonary bypass in coronary artery sur-
pulmonary bypass circuit in robotic mitral valve surgery. Innovations. 2008;3:16-8.
gery: a pilot study. Perfusion. 2002;17:407-13.
18. Immer FF, Ackerman A, Gygax E, Stalder M, Englberger L, Eckstein FS, et al.
28. Koch CG, Li L, Van Wagoner DR, Duncan AI, Gillinov AM, Blackstone EH. Red
Minimal extracorporeal circulation is a promising technique for coronary bypass
cell transfusion is associated with an increased risk for postoperative atrial fibril-
grafting. Ann Thorac Surg. 2007;84:1515-21.
lation. Ann Thorac Surg. 2006;82:1747-56.
19. Ti LK, Goh BL, Wong PS, Ong P, Goh SG, Lee CN. Comparison of mini-cardio-
29. Just S, Mu¨ller T, Hartrumpf M, Albes JM. First experience with closed circuit cen-
pulmonary bypass system with air-purge device to conventional bypass system.
trifugal pump extracorporeal circulation: cellular trauma, coagulatory, and inflam-
matory response interact. Interact Cardiovasc Thorac Surg. 2006;5:646-8.
The Journal of Thoracic and Cardiovascular Surgery c Volume 137, Number 2
For the quantitative determination of rabbit E2 in serum, plasma, cell culture fluid and other biological fluids For Research Use Only. Not for use in diagnostic procedures. Page 1 of 5 Product Information Cat. No. KT-56058 INTENDED USE This E2 ELISA kit is intended for laboratory research use only and not for use in diagnostic or therapeutic procedures. The stop solu
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