Online Supplement
Title: Transfusion triggers for guiding red blood cell transfusion for
cardiovascular surgery: A systematic review and meta-analysis
Authors:
Gerard F. Curley1, MB, MSc, PhD, FCARCSI
Nadine Shehata3, MD, MSc, FRCPC
C. David Mazer1, MD, FRCPC
Gregory MT Hare1, MD, PhD, FRCPC
Jan O. Friedrich2, MD, MSc, D Phil, FRCPC
Affiliation: Departments of Anesthesia1, Critical Care and Medicine2,
Medicine and Laboratory Medicine and Pathobiology (Mount Sinai Hospital) 3,
Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto,
Toronto, ON, Canada.
Risk of bias in included studies
A summary of judgements about each methodological quality item for each
included trial is shown in Figure S1 (Supplemental Digital Content 3,
http://links.lww.com/CCM/B29) and Figure S2 (Supplemental Digital Content
3, http://links.lww.com/CCM/B29) and Table S1 (Supplemental Digital Content
2, http://links.lww.com/CCM/B28).
Sequence generation
We judged the risk of bias for this item to be low for four trials (1-4), three of
which used computer randomization and one of which used a table of random
numbers (2) to generate the allocation sequence for the patients. One trial
based the randomisation sequence on hospital record number (5) and we
judged it to be at high risk of bias, while the remaining two trials (6, 7)
presented insufficient information to assess the adequacy of sequence
generation and we rated them as unclear.
Allocation (selection bias)
We judged the risk of bias for this item to be low for four trials that used
central allocation (1, 3, 4, 6). We rated two trials as unclear (2, 7) as they did
not present any information regarding allocation concealment. We rated one
trial as being at high risk of bias for this domain (5).
Blinding (performance bias and detection bias)
The nature of the intervention means that blinding of clinicians involved in the
care and administration of blood transfusions would not have been feasible.
The extent to which this could have biased the results is unclear, thus we
have rated none of the studies as being at low risk of bias for this domain.
However, blind outcome assessment was reported as being used in one trial
(1).
Incomplete outcome data (attrition bias)
We rated all seven trials as being at low risk of bias for this domain as they
either had no missing data or performed intention-to-treat analyses.
Selective reporting (reporting bias)
We could not find any evidence of reporting bias. Although we did not have
access to the trial protocols for the majority of trials, the results for the primary
and secondary outcomes, as described in the methods sections of each trial,
were clearly and concisely reported.
Other potential sources of bias
We identified no other sources of bias.
Appendix 1: Search criteria
The literature search incorporated words such as “cardiac/heart/valve
surgery”, “coronary artery bypass graft”, “valve replacement/repair”,
“cardiopulmonary/heart bypass”, “vascular/carotid/aortic/femoral/iliac/popliteal
artery surgery/bypass/repair/graft/aneurysm”,
“blood/transfusion/hemoglobin/hematocrit’ and “threshold/protocol/trigger”,
and variations of these terms.
CENTRAL
#1
MeSH descriptor: [Femoral Artery] explode all trees
#2
MeSH descriptor: [Iliac Artery] explode all trees
#3
MeSH descriptor: [Popliteal Artery] explode all trees
#4
MeSH descriptor: [Renal Artery] explode all trees
#5
MeSH descriptor: [Tibial Arteries] explode all trees
#6
MeSH descriptor: [Pulmonary Artery] explode all trees
#7
MeSH descriptor: [Iliac Vein] explode all trees
#8
MeSH descriptor: [Popliteal Vein] explode all trees
#9
MeSH descriptor: [Pulmonary Veins] explode all trees
#10 MeSH descriptor: [Femoral Vein] explode all trees
#11 MeSH descriptor: [Saphenous Vein] explode all trees
#12 infrainguinal or (infra near inguin*)
#13 *femor* or *popliteal
#14 saphenous
#15 *renal
#16 iliac or tibial or *inguinal
#17 ("vascular surgery" near/3 (low* or leg or periph* or extremit*))
#18 MeSH descriptor: [Vascular Surgical Procedures] explode all trees
#19 MeSH descriptor: [Blood Vessel Prosthesis] explode all trees
#20 MeSH descriptor: [Vascular Patency] explode all trees
#21 bypass or surgery or construct* or reconstruct* or re-construct* or revasculari* or revasculari* or graft* or endovascular
#22 occlu* or reocclu* or re-occlu*
#23 MeSH descriptor: [Graft Occlusion, Vascular] explode all trees
#24 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 #10 or #11 or #12 or
#13 or #14 or #15 or #16
#25 #18 or #19 or #20 or #21 or #22 or #23
#26 #24 and #25
#27 MeSH descriptor: [Aortic Aneurysm] explode all trees
#28 MeSH descriptor: [Aneurysm, False] explode all trees
#29 aneurysm* near/4 (abdom* or thoracoabdom* or thoraco-abdom* or
aort*)
#30 (aort* near/3 (ballon* or dilat* or bulg*))
#31 AAA*
#32 MeSH descriptor: [Aorta, Abdominal] explode all trees
#33 EVAR or EVRAR or RAAA or TEVAR
#34 #27 or #28 or #29 or #30 or #31 or #32 or #33
#35 #17 or #26 or #34
#36 MeSH descriptor: [Cardiac Surgical Procedures] explode all trees
#37 MeSH descriptor: [Cardiopulmonary Bypass] this term only
#38 MeSH descriptor: [Coronary Artery Bypass] explode all trees
#39 heart near bypass*
#40 heart near surgery
#41 cardiac near surgery
#42 CABG
#43 coronary near surgery
#44 coronary near bypass*
#45 coronary near surgical
#46 cardiac near surgical
#47 valv* near surgery
#48 valv* near surgical
#49 valv* near replac*
#50 #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or
#46 or #47 or #48 or #49
#51 MeSH descriptor: [Blood Transfusion] explode all trees
#52 transfus* near/5 (polic* or practic* or protocol* or trigger* or threshold*
or indicator* or strateg* or criteri* or standard*)
#53 (Red blood cell* or RBC) near/5 (polic* or practic* or protocol* or
trigger* or threshold* or indicator* or strateg* or criteri* or standard*) and
(therap* or transfus*)
#54 (H?emoglobin or h?emocrit or HB or HCT) near/5 (polic* or practic* or
protocol* or trigger* or threshold* or indicator* or strateg* or criteri* or
standard*)
#55 transfus* near/5 (restrict* or liberal*)
#56 (blood transfus*) near/3 (management or program*)
#57 #51 or #52 or #53 or #54 or #55 or #56
#58 #35 or #50 in Trials
#59 #57 and #58 in Trials
EMBASE
1 *Blood Transfusion/ (33098)
2 ((Red blood cell* or RBC) adj3 (therap* or transfus*)).mp. (6366)
3 1 or 2 (38595)
4 exp standard/ (354077)
5 3 and 4 (1063)
6 (transfus* adj5 (polic* or practic* or protocol* or trigger* or threshold* or indicator* or
strateg* or criteri* or standard*)).mp. (6439)
7 ((Red blood cell* or RBC) adj5 (polic* or practic* or protocol* or trigger* or threshold* or
indicator* or strateg* or criteri* or standard*)).mp. (1255)
8 ((H?emoglobin or h?emocrit or HB or HCT) adj5 (polic* or practic* or protocol* or trigger*
or threshold* or indicator* or strateg* or criteri* or standard*)).mp. (4991)
9 (transfus* adj5 (restrict* or liberal*)).mp. (711)
10 ((blood or transfus*) adj3 (management or program*)).mp. (6123)
11 5 or 6 or 7 or 8 or 9 or 10 (18315)
12 exp heart surgery/ (238886)
13 (cardiopulmonary adj4 bypass$).tw. (28017)
14 (heart adj4 (surgery or surgical)).tw. (21380)
15 (cardiac adj4 (surgery or surgical)).tw. (39735)
16 (coronary adj4 bypass$).tw. (43744)
17 (heart adj4 bypass$).tw. (2805)
18 (coronary adj4 (surgery or surgical)).tw. (25088)
19 (valv* adj4 (surgery or surgical or replac*)).tw. (34829)
20 CABG.tw. (17574)
21 or/12-20 (281158)
22 exp Randomized Controlled Trial/ (337304)
23 exp controlled clinical trial/ (469039)
24 randomi?ed.ab,ti. (434496)
25 placebo.ab. (177547)
26 *Clinical Trial/ (15455)
27 randomly.ab. (233013)
28 trial.ti. (140985)
29 22 or 23 or 24 or 25 or 26 or 27 or 28 (948302)
30 exp animal/ not (exp human/ and exp animal/) (3888039)
31 29 not 30 (867805)
32 11 and 21 and 31 (216)
33 claudica$.ti,ab. (9460)
34 (peripher$ adj3 (occlu$ or arteri$ or vascular)).ti,ab. (36765)
35 (arteri$ adj3 (obstruct$ or occlusi$ or stenos$ or lesion?)).ti,ab. (29291)
36 ((leg or limb) adj3 (isch?emia or occlusi$ or obstruct$ or lesion or stenos$)).ti,ab. (9253)
37 (arteriosclerosis or atherosclerosis).ti,ab. (106616)
38 INTERMITTENT CLAUDICATION/ (7889)
39 PERIPHERAL VASCULAR DISEASE/ (15514)
40 CLAUDICATION/ (3664)
41 BLOOD VESSEL OCCLUSION/ (4875)
42 LEG ISCHEMIA/ (3987)
43 LIMB ISCHEMIA/ (7063)
44 FEMORAL ARTERY/ (22754)
45 POPLITEAL ARTERY/ (7077)
46 ILIAC ARTERY/ (11455)
47 SUPERFICIAL FEMORAL ARTERY/ (1599)
48 INTERNAL ILIAC ARTERY/ (1739)
49 ((femoral or renal or iliac or popliteal) adj3 artery).ti,ab. (43150)
50 ARTERY OCCLUSION/ (15398)
51 (occlu$ or obstruct$ or stenos$ or lesion).ti,ab. (763093)
52 or/44-49 (63904)
53 52 and (50 or 51) (21513)
54 or/33-43 (192822)
55 ABDOMINAL AORTA ANEURYSM/ (17743)
56 AORTA RUPTURE/ (5866)
57 ANEURYSM RUPTURE/ (9486)
58 THORACIC AORTA ANEURYSM/ (5494)
59 (aort$ adj5 aneurysm$).ti,ab. (31930)
60 ((abdominal or thoracic) adj5 aneurysm$).ti,ab. (20742)
61 (thoracoabdominal adj5 aneurysm$).ti,ab. (1653)
62 FALSE ANEURYSM/ and ABDOMINAL AORTA/ (152)
63 FALSE ANEURYSM/ and THORACIC AORTA/ (334)
64 ANEURYSM SURGERY/ and ABDOMINAL AORTA/ (155)
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
ANEURYSM SURGERY/ and THORACIC AORTA/ (129)
or/55-65 (48336)
VASCULAR SURGERY/ (26100)
((vascular or endovascular) adj3 surg$).ti,ab. (24721)
ENDOVASCULAR SURGERY/ (13619)
ANGIOPLASTY/ (16024)
FEMOROFEMORAL BYPASS/ (568)
FEMOROPOPLITEAL BYPASS/ (1477)
SAPHENOUS VEIN GRAFT/ (4395)
SAPHENOUS VEIN/ (11332)
(Femoro$ or popliteal or infra$).ti,ab. (127524)
(graft$ or anastomos$).ti,ab. (320805)
(bypass or surg$).ti,ab. (1561447)
(52 or 74 or 75) and (76 or 77) (48553)
Lower limb amput$.ti,ab. (1398)
exp LEG AMPUTATION/ (6544)
67 or 68 or 69 or 70 or 71 or 72 or 73 or 78 or 79 or 80 (117924)
(peripheral adj5 aneurysm$).ti,ab. (1012)
(femoral adj5 aneurysm$).ti,ab. (940)
(popliteal adj5 aneurysm$).ti,ab. (1135)
(il?ac adj5 aneurysm$).ti,ab. (1889)
or/82-85 (4576)
53 or 54 or 66 or 81 or 86 (334399)
(21 or 87) and 11 and 31 (258)
MEDLINE
1 Cardiopulmonary Bypass/ (18928)
2 (heart adj4 bypass*).tw. (2314)
3 (heart adj4 (surgery or surgical)).tw. (17442)
4 (cardiac adj4 (surgery or surgical)).tw. (28768)
5 exp Coronary Artery Bypass/ (42612)
6 CABG.tw. (10936)
7 (coronary adj4 (surgery or surgical)).tw. (19776)
8 (coronary adj4 bypass*).tw. (34298)
9 exp Cardiac Surgical Procedures/ (155444)
10 (valv* adj4 replac*).tw. (21492)
11 (valv* adj4 (surgery or surgical)).tw. (9239)
12 or/1-11 (204056)
13 exp Vascular Surgical Procedures/ or Peripheral Vascular Diseases/su, th (175377)
14 exp Aortic Aneurysm, Abdominal/su, th (9036)
15 exp Aortic Aneurysm, Thoracic/su, th (5770)
16 exp Endarterectomy, Carotid/ or Amputation/su, th (6391)
17 (Aorta, Abdominal/ or Aorta, Thoracic/) and surgery.ti,ab. (5262)
18 exp Carotid Stenosis/su, th (6087)
19 exp Atherosclerosis/su, th (1653)
20 exp Intermittent Claudication/su, th (2531)
21 ((vascular or aort* or aneurysm or carotid) adj3 (repair or procedur* or surg* or
operat*)).mp. (60477)
22 ((abdominal or thoracic or thoracoabdominal or endovascular) adj3 aneurysm*).mp.
(25117)
23 (femoropopliteal adj3 (bypass or graft)).mp. (792)
24 carotid endarterectomy.mp. (7259)
25 peripheral revascularisation.mp. (14)
26 infrainguinal bypass.mp. (498)
27 amputation.ti,ab. (20174)
28 or/13-27 (234893)
29 *Blood Transfusion/ (28730)
30 ((Red blood cell* or RBC) adj3 (therap* or transfus*)).mp. (3856)
31 29 or 30 (31924)
32 exp Reference Standards/ (31698)
33 standards.fs. (510831)
34 methods.fs. (2407626)
35 32 or 33 or 34 (2795762)
36 31 and 35 (6089)
37 (transfus* adj5 (polic* or practic* or protocol* or trigger* or threshold* or indicator* or
strateg* or criteri* or standard*)).mp. (3803)
38 ((Red blood cell* or RBC) adj5 (polic* or practic* or protocol* or trigger* or threshold* or
indicator* or strateg* or criteri* or standard*)).mp. (831)
39 ((H?emoglobin or h?emocrit or HB or HCT) adj5 (polic* or practic* or protocol* or
trigger* or threshold* or indicator* or strateg* or criteri* or standard*)).mp. (2357)
40 (transfus* adj5 (restrict* or liberal*)).mp. (366)
41 ((blood or transfus*) adj3 (management or program*)).mp. (4043)
42 36 or 37 or 38 or 39 or 40 or ((blood or transfus*) adj3 (management or program*)).mp.
(15292)
43 randomized controlled trial.pt. (340350)
44 controlled clinical trial.pt. (85196)
45 placebo.ab. (135236)
46 clinical trials as topic.sh. (162565)
47 randomly.ab. (174757)
48 trial.ti. (104211)
49 43 or 44 or 45 or 46 or 47 or 48 (713895)
50 (animals not (humans and animals)).sh. (3673440)
51 49 not 50 (662245)
52 (12 or 28) and 42 and 51 (195)
53 12 and 42 and 51 (169)
Conference Proceedings Search
American Society of Anesthesiologists (2000-2013, asaabstracts.com)
Canadian Anesthesiologists Society (2007-2013,
www.cas.ca/English/Archived-Annual-Meetings)
European Society of Anesthesiology, (2004-2013,
http://www.esahq.org/resources/publications/abstract-books)
American Society for Hematology 2004-2013,
http://bloodjournal.hematologylibrary.org/site/misc/ASH_Meeting_Abstracts_In
fo.xhtml)
European Hematology Association (1994-2013,
http://www.ehaweb.org/congress-and-events/annual-congress/previouscongresses-2/)
Society for Critical Care Medicine (2007-2013,
http://www.sccm.org/Education-Center/Annual-Congress/Pages/PastFuture.aspx)
Society of Cardiovascular Anesthesiologists (2006-2013,
http://www.scahq.org/Default.aspx?TabID=407)
European Association of Cardiothoracic Anaestheisologists (2007-2013,
http://www.eacta.org/publications-2/eacta-books/)
References
1.
Hajjar LA, Vincent JL, Galas FR, et al. Transfusion requirements after
cardiac surgery: the TRACS randomized controlled trial. JAMA
2010;304(14):1559-1567.
2.
Johnson RG, Thurer RL, Kruskall MS, et al. Comparison of two transfusion
strategies after elective operations for myocardial revascularization. J Thorac
Cardiovasc Surg 1992;104(2):307-314.
3.
Karkouti K, Wijeysundera DN, Yau TM, et al. Advance targeted transfusion
in anemic cardiac surgical patients for kidney protection: an unblinded
randomized pilot clinical trial. Anesthesiology 2012;116(3):613-621.
4.
Shehata N, Burns LA, Nathan H, et al. A randomized controlled pilot study
of adherence to transfusion strategies in cardiac surgery. Transfusion
2012;52(1):91-99.
5.
Bracey AW, Radovancevic R, Riggs SA, et al. Lowering the hemoglobin
threshold for transfusion in coronary artery bypass procedures: effect on patient
outcome. Transfusion 1999;39(10):1070-1077.
6.
Bush RL, Pevec WC, Holcroft JW. A prospective, randomized trial limiting
perioperative red blood cell transfusions in vascular patients. Am J Surg
1997;174(2):143-148.
7.
Slight RD, O'Donohoe P, Fung AK, et al. Rationalizing blood transfusion in
cardiac surgery: the impact of a red cell volume-based guideline on blood usage
and clinical outcome. Vox Sang 2008;95(3):205-210.