EMBASE Cardiac Update AutoAlert: EPICORE Cardiac Surgery Blogger2

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<1>
Accession Number
2010443462
Authors
Klamt J.G. Vicente W.V.D.A. Garcia L.V. Ferreira C.A.
Institution
(Klamt, Garcia) Department of Biomechanics, Medicine, and Rehabilitation
of the Locomotor System, FMRP-USP, Brazil
(Vicente) Department of Surgery and Anatomy, FMRP-USP, Brazil
(Vicente) Cardiothoracic Surgery Department, FMRP-USP, Brazil
(Garcia) FMRP-USP, Brazil
(Ferreira) Hospital Das Clinicas, Brazil
(Ferreira) Surgery and Anatomy Department, FMRP-USP, Brazil
Title
Hemodynamic effects of the combination of dexmedetomidine-fentanyl versus
midazolam-fentanyl in children undergoing cardiac surgery with
cardiopulmonary bypass.
Source
Revista Brasileira de Anestesiologia. 60 (4) (pp 350-362), 2010. Date of
Publication: July-August 2010.
Publisher
Sociedade Brasileira de Anestesiologia (R. Prof. Alfredo Gomes 36, Rio de
Janeiro 22251-080, Brazil)
Abstract
Background and objectives: To evaluate the efficacy of the combined
infusion of dexmedetomidine and fentanyl on the hemodynamic response
during cardiac surgery with cardiopulmonary bypass (CPB) in children.
Methods: Thirty-two children, ages 1 month to 10 years, scheduled for
cardiac surgery with cardiopulmonary bypass were randomly divided in two
groups: the MDZ Group received midazolam 0.2
mg.kg^-1.h^-1, while the DEX group received
dexmedetomidine 1 mug.kg^-1.h^-1 during one hour
followed be a reduction by half in the rate of infusion in both groups.
Both groups received fentanyl 10 mug.kg^-1, midazolam 0.2 mg.h
^-1, and vecuronium 0.2 mg.kg^-1 for anesthesia
induction. The same doses of fentanyl and vecuronium used during induction
were infused during the first hour after induction, followed by a
reduction to half. Infusions were initiated immediately after induction
and maintained until the end of the surgery. Isoflurane was administered
for a short time to control the hyperdynamic response to incision and
sternotomy. Results: In both groups, systolic blood pressure and heart
rate reduced significantly after one hour of anesthetic infusion, but the
increase in systolic and diastolic pressure and heart rate to skin
incision were significantly lower in the DEX Group. A significantly lower
number of patients demanded supplementation with isoflurane in the DEX
Group. After CPB, patients in both groups had similar hemodynamic
responses. Conclusions: Infusion of dexmedetomidine without bolus seems to
be an effective adjuvant to fentanyl on the promotion of sedation and
control of hemodynamic responses during surgery for congenital
cardiopathies in children. Elsevier Editora Ltda.

<2>
Accession Number
2010456621
Authors
Ali N. Rizwi F. Iqbal A. Rashid A.
Institution
(Ali, Iqbal, Rashid) Department of Cardiac Surgery, Armed Forces Institute
of Cardiology, National Institute of Heart Diseases, Rawalpindi, Pakistan
(Rizwi) Department of Community Medicine, Islamabad Medical and Dental
College, Islamabad, Pakistan
Title
Induced remote ischemic pre-conditioning on ischemia-reperfusion injury in
patients undergoing coronary artery bypass.
Source
Journal of the College of Physicians and Surgeons Pakistan. 20 (7) (pp
427-431), 2010. Date of Publication: July 2010.
Publisher
College of Physicians and Surgeons Pakistan (7th Central Street, Karachi
755000, Pakistan)
Abstract
Objective: To determine the role of remote ischemic pre-conditioning
(rIPC) on myocardium, against ischemia reperfusion injury in patients
undergoing coronary artery bypass graft (CABG) surgery by measuring CKMB
levels. Study Design: A randomized controlled trial. Place and Duration of
Study: The Surgical Department of Armed Forces Institute of
Cardiology/National Institute of Heart Diseases, Rawalpindi, from January
to June 2008. Methodology: One hundred patients with double and triple
vessels coronary artery disease were randomized in two groups of 50 each.
rIPC protocol consisted of 3 x 5 minutes of forearm ischemia, induced by a
blood pressure cuff inflated to 200 mmHg, with an intervening 5 minutes of
reperfusion, during which the cuff was deflated. Patients in the control
group were not subjected to limb ischemia. The protocol of induced
ischemia was completed before placing patients on extracorporeal bypass
circuit. At the end of surgery serum CKMB levels were measured and
compared at 8, 16, 24 and 48 hours from both the groups. Written informed
consent was taken from patients. Study was approved by the hospital
ethical committee. Results: Remote ischemic pre-conditioning significantly
reduced CKMB levels at 8, 16, 24 and 48 hours after surgery with p-values
of 0.026, 0.021, 0.052 and 0.003 respectively. There was mean reduction of
3 iu/l in CKMB levels, in patients who underwent rIPC protocol prior to
CABG surgery, compared to control group. Conclusion: This study showed a
significant reduction of enzyme marker CKMB in patients subjected to rIPC
prior to CABG surgery. This suggests lesser degree of myocardial damage
compared to control group in CABG patients.

<3>
Accession Number
2010461414
Authors
Block A.J. McQuillen P.S. Chau V. Glass H. Poskitt K.J. Barkovich A.J.
Esch M. Soulikias W. Azakie A. Campbell A. Miller S.P.
Institution
(Block, Chau) Department of Pediatrics, University of British Columbia,
Vancouver, BC, Canada
(Poskitt, Soulikias, Campbell, Miller) Department of Radiology, University
of British Columbia, Vancouver, BC, Canada
(McQuillen, Glass, Esch) Department of Pediatrics, University of
California, San Francisco, 505 Parnassus Ave, San Francisco, CA
94143-0106, United States
(McQuillen, Glass, Barkovich, Miller) Department of Neurology, University
of California San Francisco, San Francisco, CA, United States
(Barkovich) Department of Radiology, University of California San
Francisco, San Francisco, CA, United States
(Azakie) Department of Surgery, University of California San Francisco,
San Francisco, CA, United States
Title
Clinically silent preoperative brain injuries do not worsen with surgery
in neonates with congenital heart disease.
Source
Journal of Thoracic and Cardiovascular Surgery. 140 (3) (pp 550-557),
2010. Date of Publication: September 2010.
Publisher
Mosby Inc. (11830 Westline Industrial Drive, St. Louis MO 63146, United
States)
Abstract
Objective: Preoperative brain injury, particularly stroke and white matter
injury, is common in neonates with congenital heart disease. The objective
of this study was to determine the risk of hemorrhage or extension of
preoperative brain injury with cardiac surgery. Methods: This dual-center
prospective cohort study recruited 92 term neonates, 62 with transposition
of the great arteries and 30 with single ventricle physiology, from 2
tertiary referral centers. Neonates underwent brain magnetic resonance
imaging scans before and after cardiac surgery. Results: Brain injury was
identified in 40 (43%) neonates on the preoperative magnetic resonance
imaging scan (median 5 days after birth): stroke in 23, white matter
injury in 21, and intraventricular hemorrhage in 7. None of the brain
lesions presented clinically with overt signs or seizures. Preoperative
brain injury was associated with balloon atrial septostomy (P = .003) and
lowest arterial oxygen saturation (P = .007); in a multivariable model,
only the effect of balloon atrial septostomy remained significant when
adjusting for lowest arterial oxygen saturation. On postoperative magnetic
resonance imaging in 78 neonates (median 21 days after birth), none of the
preoperative lesions showed evidence of extension or hemorrhagic
transformation (0/40 [95% confidence interval: 0%-7%]). The presence of
preoperative brain injury was not a significant risk factor for acquiring
new injury on postoperative magnetic resonance imaging (P = .8).
Conclusions: Clinically silent brain injuries identified preoperatively in
neonates with congenital heart disease, including stroke, have a low risk
of progression with surgery and cardiopulmonary bypass and should
therefore not delay clinically indicated cardiac surgery. In this
multicenter cohort, balloon atrial septostomy remains an important risk
factor for preoperative brain injury, particularly stroke. 2010 by The
American Association for Thoracic Surgery.

<4>
Accession Number
2010462184
Authors
Post P.N. Kuijpers M. Ebels T. Zijlstra F.
Institution
(Post) Dutch Institute for Healthcare Improvement CBO, PO Box 20064, 3502
LB Utrecht, Netherlands
(Kuijpers, Ebels, Zijlstra) Thorax Centre, University Medical Centre
Groningen, University of Groningen, Groningen, Netherlands
Title
The relation between volume and outcome of coronary interventions: A
systematic review and meta-analysis.
Source
European Heart Journal. 31 (16) (pp 1985-1992), 2010. Date of
Publication: August 2010.
Publisher
Oxford University Press (Great Clarendon Street, Oxford OX2 6DP, United
Kingdom)
Abstract
Aims Although various studies reported better outcomes in centres
performing a high volume of procedures of coronary artery bypass grafting
(CABG) or percutaneous coronary interventions (PCIs), it is unclear how
strong this relation is and whether it pertains to today's practice.
Methods and results Medline, Embase, and conference reports were searched
for studies reporting the effect of high volume of CABG or PCI on
in-hospital mortality, adjusted for differences in case-mix. Of 140
potentially relevant papers, 15 were included, 2 of which reported data on
both CABG and PCI. Meta-analysis of 10 studies on PCI, comprising 1 322
342 patients in 1746 hospitals, indicated an odds ratio (OR) of
in-hospital mortality for patients treated in a high-volume hospital of
0.87 (95 confidence interval (CI) 0.83-0.91) compared to those treated in
a low-volume hospital. The 7 CABG studies taken together, comprising 1 470
990 patients in 2040 hospitals, also revealed a significant effect of high
volume (OR 0.85; CI 0.79-0.92). A differential effect for specific cut-off
points could not be identified. Meta-regression did not show notable
changes in the effect size over the years. Conclusion sPatients undergoing
CABG or PCI in a high-volume hospital exhibit lower in-hospital mortality
than those treated at low-volume hospitals. Our meta-analysis does not
support the view that this relation has attenuated over time. The Author
2010.

<5>
Accession Number
2010462190
Authors
Rubartelli P. Petronio A.S. Guiducci V. Sganzerla P. Bolognese L. Galli M.
Sheiban I. Chirillo F. Ramondo A. Bellotti S.
Institution
(Rubartelli, Bellotti) Dipartimento di Cardiologia, Ospedale Villa Scassi,
Corso Scassi 1, 16149 Genova, Italy
(Petronio) Dipartimento Cardio-Toracico, Ospedale Cisanello, Universit di
Pisa, Pisa, Italy
(Guiducci) Unit Operativa di Cardiologia Interventistica, Ospedale Santa
Maria Nuova, Reggio Emilia, Italy
(Sganzerla) Dipartimento Cardiovascolare, Ospedale Humanitas Gavazzeni,
Bergamo, Italy
(Bolognese) Dipartimento Cardiovascolare, Ospedale San Donato, Arezzo,
Italy
(Galli) Dipartimento Cardiovascolare, Ospedale sant'Anna, Como, Italy
(Sheiban) Divisione di Cardiologia Universitaria, Ospedale San Giovanni
Battista, Torino, Italy
(Chirillo) Dipartimento Cardiovascolare, Ospedale Ca' Foncello, Treviso,
Italy
(Ramondo) Dipartimento di Scienze Cardiovascolari, Universit di Padova,
Padova, Italy
Title
Comparison of sirolimus-eluting and bare metal stent for treatment of
patients with total coronary occlusions: Results of the GISSOC II-GISE
multicentre randomized trial.
Source
European Heart Journal. 31 (16) (pp 2014-2020), 2010. Date of
Publication: August 2010.
Publisher
Oxford University Press (Great Clarendon Street, Oxford OX2 6DP, United
Kingdom)
Abstract
Aims Percutaneous coronary intervention with bare metal stent (BMS) in
chronic total coronary occlusions (CTOs) is associated with a higher rate
of angiographic restenosis and reocclusion than that observed in subtotal
stenoses. Preliminary reports have suggested a better performance of
drug-eluting stents in CTO. In this multicentre, randomized trial, we
compared the mid-term angiographic and clinical outcome of
sirolimus-eluting stent (SES) or BMS implantation after successful
recanalization of CTO. Methods and results Patients with CTO older than 1
month, after successful recanalization, were randomized to implantation of
SES (78 patients) or BMS (74 patients) in 13 Italian centres. Clopidogrel
therapy was prescribed for 6 months. The primary endpoint was in-segment
minimal luminal diameter (MLD) at 8-month follow-up. Secondary clinical
endpoints included death, myocardial infarction (MI), target lesion
revascularization (TLR), and target vessel revascularization (TVR) at 24
months. Patients treated with SES showed, at in-segment analysis, a larger
MLD (1.98 +/- 0.57 vs. 0.98 +/- 0.80 mm, P < 0.001), a lower late luminal
loss (-0.06 +/- 0.49 vs. 1.11 +/- 0.79 mm, P < 0.001), and lower
restenosis (9.8 vs. 67.7, P < 0.001) and reocclusion (0 vs. 17, P = 0.001)
rates. At 24-month follow-up, patients in the SES group experienced fewer
major adverse cardiac events (50.0 vs. 17.6, P < 0.001) mainly due to a
lower rate of both TLR (44.9 vs. 8.1, P < 0.001) and TVR (44.9 vs. 14.9, P
< 0.001). Conclusion In CTO, SES is markedly superior to BMS in terms of
restenosis and reocclusion rate, and incidence of repeat revascularization
at 24 months. The Author 2010.

<6>
Accession Number
2010462301
Authors
Cruz F.D.D. Issa V.S. Ayub-Ferreira S.M. Chizzola P.R. Souza G.E.C.
Moreira L.F.P. Lanz-Luces J.R. Bocchi E.A.
Institution
(Cruz, Issa, Ayub-Ferreira, Chizzola, Souza, Moreira, Lanz-Luces, Bocchi)
Heart Institute (InCor), Sao Paulo University Medical School, Sao Paulo,
Brazil
(Bocchi) Rua Dr Melo Alves 690 apto 41, Sao Paulo CEP 01410-010, Brazil
Title
Effect of a sequential education and monitoring programme on
quality-of-life components in heart failure.
Source
European Journal of Heart Failure. 12 (9) (pp 1009-1015), 2010. Date of
Publication: September 2010.
Publisher
Oxford University Press (Great Clarendon Street, Oxford OX2 6DP, United
Kingdom)
Abstract
Aims Trials of disease management programmes (DMP) in heart failure (HF)
have shown controversial results regarding quality of life. We
hypothesized that a DMP applied over the long-term could produce different
effects on each of the quality-of-life components. Methods and results We
extended the prospective, randomized REMADHE Trial, which studied a DMP in
HF patients. We analysed changes in Minnesota Living with Heart Failure
Questionnaire components in 412 patients, 60.5 male, age 50.2 +/- 11.4
years, left ventricular ejection fraction 34.7 +/- 10.5. During a mean
follow-up of 3.6 +/- 2.2 years, 6.3 of patients underwent heart
transplantation and 31.8 died. Global quality-of-life scores improved in
the DMP intervention group, compared with controls, respectively: 57.5 +/-
3.1 vs. 52.6 +/- 4.3 at baseline, 32.7 +/- 3.9 vs. 40.2 +/- 6.3 at 6
months, 31.9 +/- 4.3 vs. 41.5 +/- 7.4 at 12 months, 26.8 +/- 3.1 vs. 47.0
+/- 5.3 at the final assessment; P < 0.01. Similarly, the physical
component (23.7 +/- 1.4 vs. 21.1 +/- 2.2 at baseline, 16.2 +/- 2.9 vs.
18.0 +/- 3.3 at 6 months, 17.3 +/- 2.9 vs. 23.1 +/- 5.7 at 12 months, 11.4
+/- 1.6 vs. 19.9 +/- 2.4 final; P < 0.01), the emotional component (13.2
+/- 1.0 vs. 12.1 +/- 1.4 at baseline, 11.7 +/- 2.7 vs. 12.3 +/- 3.1 at 6
months, 12.4 +/- 2.9 vs. 16.8 +/- 5.9 at 12 months, 6.7 +/- 1.0 vs. 10.6
+/- 1.4 final; P < 0.01) and the additional questions (20.8 +/- 1.2 vs.
19.3 +/- 1.8 at baseline, 14.3 +/- 2.7 vs. 17.3 +/- 3.1 at 6 months, 12.4
+/- 2.9 vs. 21.0 +/- 5.5 at 12 months, 6.7 +/- 1.4 vs. 17.3 +/- 2.2 final;
P < 0.01) were better (lower) in the intervention group. The emotional
component improved earlier than the others. Post-randomization quality of
life was not associated with events. ConclusionComponents of the
quality-of-life assessment responded differently to DMP. These results
indicate the need for individualized DMP strategies in patients with HF.
2010 The Author.

<7>
Accession Number
2010463040
Authors
Schellings D.A.A.M. Dambrink J.-H.E. Hoorntje J.C.A. de Boer M.J. van't
Hof A.W.J. Suryapranata H.
Institution
(Schellings, Dambrink, Hoorntje, de Boer, van't Hof, Suryapranata)
Department of Cardiology, Isala Klinieken, Zwolle, Netherlands
Title
Long-term comparison of balloon angioplasty with provisional stenting
versus routine stenting in patients with non-ST-elevation acute coronary
syndrome.
Source
Netherlands Heart Journal. 18 (6) (pp 307-313), 2010. Date of
Publication: June 2010.
Publisher
Bohn Stafleu van Loghum (P.O. Box 246, Houten 3990 GA, Netherlands)
Abstract
Background. In patients with unstable angina or non-ST-elevation acute
coronary syndrome (NSTE-ACS) who are eligible for PCI, routine stenting is
the recommended treatment strategy, based on the opinion of experts.
Provisional stenting may provide a viable alternative by retaining the
early benefits of stenting without its potential late hazards. Method.
Patients with NSTE-ACS were randomized to provisional or routine stenting
after coronary angiography. Patients were followed for up to ten years.
The occurrence of major adverse cardiac events (MACE) was recorded.
Results. 237 consecutive patients with NSTEACS were randomly assigned to
routine stenting (n=116) or provisional stenting (n=121). No difference in
the incidence of MACE at 30 days was observed. At six months, angiographic
restenosis was lower in the routine stenting group (41 vs. 20%, p=0.02),
paralleled by more MACE in the provisional stenting group at one year
(40.5 vs. 27.6%, p=0.036). At complete follow-up the difference in MACE
was not significant (61.2 vs. 50%, p=0.084) because of relatively more
target lesion revascularizations in the routine stent group. There was no
difference in the incidence of very late stent thrombosis (1.7 vs. 3.4%,
p=0.439). The only independent predictor of MACE was beta-blocker use (RR
0.62 [0.431; 0.892] p=0.010). Conclusion. In selective patients with
NSTEACS, routine stenting was more beneficial than provisional stenting
for a period of up to five years, driven by a reduction in repeat
revascularization procedures. After this period, the benefit was no longer
significant. Beta-blocker use was the only independent predictor of MACE
throughout the complete follow-up period.

<8>
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Accession Number
2010461756
Authors
Ettema R.G.A. Peelen L.M. Schuurmans M.J. Nierich A.P. Kalkman C.J. Moons
K.G.M.
Institution
(Ettema, Schuurmans) University of Applied Science Utrecht, Faculty of
Health Care, Bolognalaan 101, 3584 CJ Utrecht, Netherlands
(Peelen, Moons) Julius Center for Health Sciences and Primary Care,
Nursing Science and Sports, Utrecht, Netherlands
(Schuurmans, Kalkman) Division of Perioperative Care and Emergency Aid,
Nursing Science and Sports, Utrecht, Netherlands
(Kalkman) Department of Rehabilitation, Nursing Science and Sports,
Utrecht, Netherlands
(Nierich) University Medical Center Utrecht, Utrecht, Netherlands
(Nierich) Department of Anesthesiology and Intensive Care, Isala Clinics,
Zwolle, Netherlands
Title
Prediction models for prolonged intensive care unit stay after cardiac
surgery: Systematic review and validation study.
Source
Circulation. 122 (7) (pp 682-689), 2010. Date of Publication: 17 Aug
2010.
Publisher
Lippincott Williams and Wilkins (530 Walnut Street, Philadelphia PA
19106-3621, United States)
Abstract
Background: Several models have been developed to predict prolonged stay
in the intensive care unit (ICU) after cardiac surgery. However, no
extensive quantitative validation of these models has yet been conducted.
This study sought to identify and validate existing prediction models for
prolonged ICU length of stay after cardiac surgery. Methods and Results:
After a systematic review of the literature, the identified models were
applied on a large registry database comprising 11 395 cardiac surgical
interventions. The probabilities of prolonged ICU length of stay based on
the models were compared with the actual outcome to assess the
discrimination and calibration performance of the models. Literature
review identified 20 models, of which 14 could be included. Of the 6
models for the general cardiac surgery population, the Parsonnet model
showed the best discrimination (area under the receiver operating
characteristic curve=0.75 [95% confidence interval, 0.73 to 0.76]),
followed by the European system for cardiac operative risk evaluation
(EuroSCORE) (0.71 [0.70 to 0.72]) and a model by Huijskes and colleagues
(0.71 [0.70 to 0.73]). Most of the models showed good calibration.
CONCLUSIONS-: In this validation of prediction models for prolonged ICU
length of stay, 2 widely implemented models (Parsonnet, EuroSCORE),
although originally designed for prediction of mortality, were superior in
identifying patients with prolonged ICU length of stay. 2010 American
Heart Association, Inc.

<9>
Accession Number
2010442309
Authors
Locali R.F. Matsuoka P.K. Cherbo T. Gabriel E.A. Buffolo E.
Institution
(Locali, Matsuoka, Cherbo, Gabriel, Buffolo) Universidade Federal de Sao
Paulo, Sao Paulo, SP, Brazil
Title
Should biatrial heart transplantation still be performed? A meta-analysis.
Source
Arquivos Brasileiros de Cardiologia. 94 (6) (pp 829-840+778-788), 2010.
Date of Publication: June 2010.
Publisher
Arquivos Brasileiros de Cardiologia (Rua Beira Rio, 45, 3.o andar, Sao
Paolo SP 04548-050, Brazil)
Abstract
The outcomes of total and bicaval heart transplantation techniques are
better than those of the biatrial technique; however, the latter is still
considered the gold-standard. The objective of this study was to determine
whether the total and bicaval heart transplantation techniques are, in
fact, better than the biatrial technique. A systematic review with
meta-analysis was carried out. Studies were retrieved from Pubmed, Lilacs,
Web of Science, Scirus, Scopus, Google Scholar, and Scielo databases,
identified by sensitive strategy. Randomized, prospective, and
retrospective controlled studies were selected for inclusion. Intra and
postoperative parameters were assessed. A total of 11,602 studies were
identified and 36 were included in our review. The number of atrial
arrhythmias, tricuspid valve regurgitation, deaths, and embolic events, as
well as bleeding volume; temporary and permanent pacemaker requirement;
and length of stay in the intensive care unit are significantly lower for
the total and bicaval techniques than for the biatrial technique. Also,
hemodynamic variables such as pulmonary capillary pressure, mean pulmonary
artery pressure, and right atrial pressure are lower in total and bicaval
transplantation. In prognostic terms, total and bicaval orthotopic heart
transplantations are better, than the biatrial transplantation. Therefore,
indication of the biatrial technique for transplantation should be the
exception, not the rule.

<10>
Accession Number
2010442769
Authors
Berger K. Sander M. Kohlar A. Meisel C. Konertz W. Volk T.
Institution
(Berger, Sander, Kohlar) Department of Anesthesiology and Intensive Care
Medicine, Charite-Universitatsmedizin Berlin, Campus Charite Mitte,
Berlin, Germany
(Meisel) Department of Immunology, Charite-Universitatsmedizin Berlin,
Campus Charite Mitte, Berlin, Germany
(Konertz) Department of Cardiovascular Surgery,
Charite-Universitatsmedizin Berlin, Campus Charite Mitte, Berlin, Germany
(Volk) Department of Anaesthesiology, Intensive Care and Pain Therapy,
Saarland University Hospital, Universitatsklinikum des Saarlandes,
Kirrberger Strase 100, Homburg, Saarland 66424, Germany
Title
Inadequate cytoplasmatic calcium signals in alveolar macrophages after
cardiac surgery.
Source
Inflammation Research. 59 (9) (pp 767-773), 2010. Date of Publication:
September 2010.
Publisher
Birkhauser Verlag Basel (Klosterberg 23, P.O. Box 133, Basel CH-4010,
Switzerland)
Abstract
Objective and design: Patients undergoing cardiac surgery have an elevated
risk for pulmonary complications. A dysfunction of alveolar macrophages
(AM) might promote postoperative infections. Therefore intracellular
calcium [Ca ²⁺]_i as an important second messenger in
cellular signaling was assessed in AM. Materials and methods: Twelve
patients undergoing elective coronary artery bypass graft surgery (CABG)
were enrolled in this clinical trial. After anesthesia induction and 2 h
after cardiopulomary bypass (CPB) declamping, the bronchoalveolar lavage
(BAL) fluid was collected preoperatively from the right middle lobe and
postoperatively from the left lingula of the lung. Cell subpopulations and
[Ca²⁺]_i signals were assessed via flow cytometry. To
express the changes of [Ca ²⁺]_i signals the
Fluo4/FuraRed-Ratio was used. Results: After surgery the
[Ca²⁺]_i baseline in unstimulated AMs were
significantly reduced (p < 0.001). A significant signal reduction after
fMLP (p = 0.021) and C5a (p = 0.028) stimulation was found in FSC high AMs
after surgery, even though all populations showed a trend of less
responsiveness. Conclusion: We suggest that the reduced
[Ca²⁺]_i signaling in postoperative AMs is caused by
a reduced coupling to membrane channels. These preliminary data suggest an
inadequate [Ca²⁺]_i signal of AM after surgery, which
may contribute to a local immune dysfunction in the lung. 2010 Springer
Basel AG.

<11>
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Accession Number
2010456859
Authors
Weir R.A.P. Murphy C.A. Petrie C.J. Martin T.N. Balmain S. Clements S.
Steedman T. Wagner G.S. Dargie H.J. McMurray J.J.V.
Institution
(Weir, Murphy, Petrie, Martin, Balmain, Clements, Steedman, Dargie,
McMurray) Cardiology Department, Western Infirmary, Glasgow G11 6NT,
United Kingdom
(Wagner) Duke University Medical Center, Durham, NC, United States
Title
Microvascular obstruction remains a portent of adverse remodeling in
optimally treated patients with left ventricular systolic dysfunction
after acute myocardial infarction.
Source
Circulation: Cardiovascular Imaging. 3 (4) (pp 360-367), 2010. Date of
Publication: July 2010.
Publisher
Lippincott Williams and Wilkins (530 Walnut Street, Philadelphia PA
19106-3621, United States)
Abstract
Background-Microvascular obstruction (MO) is associated with large acute
myocardial infarction and lower left ventricular (LV) ejection fraction
and predicts greater remodeling, but whether this effect is abolished by
contemporary antiremodeling therapies is subject to debate. We examined
the influence of several infarct characteristics, including MO, on LV
remodeling in an optimally treated post-acute myocardial infarction
cohort, using contrast-enhanced cardiac magnetic resonance. Methods and
Results-One hundred patients (mean age, 58.9+/-12 years, 77% men)
underwent contrast-enhanced cardiac magnetic resonance at baseline (4
days) and at 12 and 24 weeks. The effects on LV remodeling (ie, change in
LV end-systolic volume index [LVESVi]) of infarct site, transmurality,
endocardial extent, and the presence of early and late MO were analyzed.
Mean baseline infarct volume index decreased from 34.0 (21.2)
mL/m² to 20.9 (12.9) mL/m² at 24 weeks (P<0.001).
Infarct site had no influence on remodeling, but greater baseline infarct
transmurality (r=0.47, P<0.001) and endocardial extent (r=0.26, P<0.01)
were associated with higher LVESVi. Early MO was seen in 69 patients (69%)
and persisted as late MO in 56 patients (56%). Patients with late MO
underwent significantly greater remodeling than those without MO (LVESVi,
+4.1 [13.4] versus 7.0 [12.7] mL/m², respectively, P=0.001);
those with early MO only displayed an intermediate LVESVi ( -4.9 [13.0]
mL/m²). Importantly, late MO was seen frequently despite
optimal coronary blood flow having been restored at angiography.
Conclusions-Late MO on predischarge contrast-enhanced cardiac magnetic
resonance remains an ominous predictor of adverse LV remodeling despite
powerful antiremodeling therapy and may be useful in the risk
stratification of survivors of acute myocardial infarction. 2010 American
Heart Association, Inc.

<12>
Accession Number
2010458738
Authors
Levy M.S. Creager M.A.
Institution
(Levy, Creager) Cardiovascular Division, Brigham and Women's Hospital, 75
Francis Street, Boston, MA 02115, United States
Title
Revascularization versus medical therapy for renal-artery stenosis. The
ASTRAL investigators. The New England Journal of Medicine 2009; 361:
1953-1962.
Source
Vascular Medicine. 15 (4) (pp 343-345), 2010. Date of Publication:
August 2010.
Publisher
SAGE Publications Ltd (55 City Road, London EC1Y 1SP, United Kingdom)
Abstract
Study objective: The objective of ASTRAL was to determine whether
percutaneous revascularization combined with medical therapy compared to
medical therapy alone improves renal function and other outcomes, such as
blood pressure, time to first renal event, time to first major
cardiovascular event, and mortality. Study population: ASTRAL enrolled 806
patients with atherosclerotic renovascular disease from 57 centers.
Patients were screened if treating clinicians felt they had clinical
features suggestive of underlying atherosclerotic renovascular disease
(i.e. hypertension refractory to medical therapy, or renal impairment as
suggested by laboratory measurements). All patients had to have an imaging
modality (i.e. computed tomographic angiography (CTA), magnetic resonance
angiography (MRA) or renal artery ultrasound). This imaging had to convey
that the patient had 'substantial' anatomical atherosclerotic stenosis in
at least one renal artery that was suitable for endovascular therapy.
Also, the treating clinician had to be 'uncertain' that the patient would
benefit from revascularization. Fifty-nine percent of patients were
reported to have renal artery stenosis of > 70%, and 60% had a serum
creatinine of >= 150 mmol per liter. Design and methods: ASTRAL was a
randomized, unblinded study of patients with atherosclerotic renal artery
disease who were assigned to percutaneous revascularization plus best
medical therapy or best medical therapy alone. The primary outcome of the
ASTRAL trial was the change of renal function over time, as determined by
the mean slope of the reciprocal of serum creatinine. Secondary outcomes
included blood pressure, time to first renal event (defined as: new onset
of kidney injury, dialysis, renal transplantation, nephrectomy, or death
from renal failure), time to first major cardiovascular event (defined as:
myocardial infarction, stroke, death from cardiovascular cause,
hospitalization for angina, fluid overload or congestive heart failure,
coronary artery revascularization, or another peripheral arterial
procedure), and all-cause mortality. Randomization was 1:1 via computer
algorithm and was stratified by serum creatinine, glomerular filtration
rate (GFR), severity of renal artery stenosis, kidney length on
ultrasound, and rate of progression of renal impairment. Patients who were
assigned to the revascularization plus medical therapy arm underwent
percutaneous revascularization within 4 weeks. The procedure type
(angioplasty alone or with stenting), was left to the discretion of the
local operator. Distal protection devices were not used. Medical therapy
in both arms consisted of antihypertensive drugs, statins, and
antiplatelet agents. The trial was powered to detect a 20% reduction in
the mean slope of the reciprocal of serum creatinine. Based on low
crossover rates, it was determined that at least 750 patients would have
to be enrolled. Analysis was by intention to treat. Continuous variables
were subject to repeated measures analysis. Time-to-event data were
expressed via Kaplan Meier curves and compared via log-rank testing.
Prespecified subgroup analyses included baseline serum creatinine, GFR,
severity of renal artery stenosis, kidney length, and progression of renal
disease. Results: Of the 806 patients included, 403 were randomized to the
revascularization arm and 403 to medical therapy only. The median
follow-up was 34 months. Only 337 (83%) patients randomized to
revascularization underwent the procedure, whereas 24 patients (6%)
randomized to the medical therapy arm underwent revascularization. The
number of antihypertensive medications used was greater in the medical
therapy group than in the revascularization group at the 12-month
follow-up: 2.97 versus 2.77 (p = 0.03). The mean slope of the reciprocal
of the serum creatinine concentration was -0.07 x 10 ^-3 liters
per micromole per year in the revascularization group versus -0.13 x
10^-3 liters per micromole per year in the medical-therapy group
(difference of 0.06 x 10^-3 liters per micromole per year) (95%
confidence interval [CI], -0.002 to 0.13, p = 0.06) with a trend favoring
revascularization. After 5 years of follow-up, there was a trend toward
lower mean systolic blood pressure (1.6 mmHg lower, p = 0.06) in the
revascularization group. However, the mean diastolic blood pressure was
significantly lower in the medical therapy group at long-term follow-up
(divergence of slope of mean diastolic blood pressure: 0.61 mmHg per year,
p = 0.03). There was no significant difference between renal events, time
to first renal event, acute kidney injury, or development of end-stage
renal disease in either group. Further, there was no difference in major
cardiovascular events or overall survival in either group. The
periprocedural complication rate within the revascularization group was 9%
(31/359 patients). Fifty-five out of 280 patients (20%) had an adverse
event by 1 month post procedure. Overall, there were 31 serious
complications of revascularization in 23 patients. Per protocol analysis
of patients suggested that there was no significant difference in outcomes
between patients who received revascularization versus medical therapy. No
differences between treatment groups were identified in any of the
pre-specified subgroup analyses. Conclusions: Renal artery stenting
combined with medical therapy did not improve renal function compared to
medical therapy alone in patients with atherosclerotic renal artery
disease.

<13>
Accession Number
19649758
Authors
Woodfield J.C. Beshay N. van Rij A.M.
Institution
(Woodfield) Department of Surgery, University of Otago Medical School, PO
Box 913, Dunedin, New Zealand.
Title
A meta-analysis of randomized, controlled trials assessing the
prophylactic use of ceftriaxone. A study of wound, chest, and urinary
infections.
Source
World journal of surgery. 33 (12) (pp 2538-2550), 2009. Date of
Publication: Dec 2009.
Abstract
BACKGROUND: Ceftriaxone is an effective prophylactic antibiotic. However,
there is no consensus about whether ceftriaxone should be used as a
first-line antibiotic for the prevention of incisional surgical site
infection (SSI). Its role in preventing urinary tract infection (UTI) and
pneumonia also is controversial. METHODS: A meta-analysis of randomized,
controlled trials assessing the prophylactic use of ceftriaxone between
1983 and 2005 was performed. Medline, Embase, and Cochrane registers were
reviewed. Additional references, review papers, and proceedings from
meetings were searched. The Jadad score was used to assess study quality.
A meta-analysis with sensitivity analyses was performed for SSI, UTI, and
pneumonia. RESULTS: Of 231 reviewed papers, 90 were included. Ceftriaxone
prophylaxis was superior to other antibiotics in each category. Sixty-one
studies assessed the prevention of SSI (odds ratio (OR), 0.68; 95%
confidence interval (CI), 0.53-0.7, p < 0.001; Cochran's Q statistic, p =
0.93). The difference was greatest for abdominal surgery. There was no
difference for cardiac surgery. Thirty-five studies assessed the
prevention of UTI (OR 0.53; 95% CI 0.43-0.63, p = 0; Cochran's Q
statistic, p = 0.97). The difference was greatest in obstetric and
gynecological and colorectal surgery. Thirty-seven studies assessed the
prevention of pneumonia (OR 0.66; 95% CI 0.54-0.81, p = 0; Cochran's Q
statistic, p = 0.65). The difference was greatest in upper abdominal
surgery. CONCLUSIONS: The meta-analysis confirms that prophylactic
ceftriaxone is more effective than most other prophylactic antibiotics.
This reduces SSI, UTI, and pneumonia in procedures where there is an
increased risk of these infections. In such procedures, the data support
using ceftriaxone as a first-line prophylactic antibiotic.

<14>
Accession Number
2010454540
Authors
Gagnon J. Laporta D. Beique F. Langlois Y. Morin J.-F.
Institution
(Gagnon) Service of Perfusion, Division of Cardiac Surgery, Department of
Surgery, Australia
(Laporta) Department of Adult Critical Care, Australia
(Beique) Division of Cardiac Anesthesia, Department of Anaesthesia,
Australia
(Langlois, Morin) Department of Surgery, Jewish General Hospital, A Mcgill
University Teaching Hospital, Montreal, QC, Canada
Title
Clinical relevance of ventilation during cardiopulmonary bypass in the
prevention of postoperative lung dysfunction.
Source
Perfusion. 25 (4) (pp 205-210), 2010. Date of Publication: July 2010.
Publisher
SAGE Publications Ltd (55 City Road, London EC1Y 1SP, United Kingdom)
Abstract
The current clinical study is the continuity of previous experimental
findings in which ventilation during cardiopulmonary bypass (CPB)
prevented reperfusion injury of the pulmonary arterial tree as
demonstrated by preservation of vasorelaxation to acetylcholine (ACh) in
swine. The aim of this prospective randomized study is to determine: 1) if
ventilation during CPB prevents the selective endothelium-mediated lung
dysfunction in humans and, 2) the clinical relevance of ventilation during
CPB. Forty patients scheduled for primary coronary artery bypass grafting
(CABG) were randomized into two groups: Group 1: Usual care (defined as no
ventilation during CPB) and Group 2: CPB with low tidal volume ventilation
(3 ml.kg^-1) without positive end expiratory pressure (PEEP). To
evaluate endothelial function, ACh was injected into the pulmonary artery
and the changes in pulmonary vascular resistance index (PVRI) were
measured at: (1) induction of anesthesia prior to surgery, (2) immediately
after weaning from CPB and (3) 1 hour after CPB. In addition, secondary
endpoints, such as PaO₂/FiO₂ ratio, mean pulmonary
artery pressure (MPAP), postoperative length of stay (LOS) and
postoperative pulmonary complications were measured to evaluate the effect
of ventilation during CPB. To assess pulmonary complications, a chest
x-ray was taken on the first and third postoperative days. There were no
statistically significant changes in PVRI, PaO₂
/FiO₂ ratio, MPAP, postoperative LOS and postoperative
pulmonary complications when comparing the non-ventilated and the
ventilated groups during CPB. The ventilated group appears to obtain a
greater vasorelaxation to ACh, as shown by the more pronounced change in
PVRI when compared to the non-ventilated group. However, the difference in
PVRI between the two groups was not statistically significant after
weaning (p= 0.32) and 1hr after CPB (p= 0.28). Contrary to our hypothesis
and due to larger than expected variability in the data, the hemodynamic
and clinical changes seen were not statistically significant. The
Author(s) 2010.

<15>
Accession Number
2010454541
Authors
Anastasiadis K. Asteriou C. Deliopoulos A. Argiriadou H. Karapanagiotidis
G. Antonitsis P. Grosomanidis V. Misias G. Papakonstantinou C.
Institution
(Anastasiadis, Asteriou, Deliopoulos, Argiriadou, Karapanagiotidis,
Antonitsis, Grosomanidis, Misias, Papakonstantinou) Department of
Cardiothoracic Surgery, AHEPA University Hospital, Thessaloniki, Greece
Title
Haematological effects of minimized compared to conventional
extracorporeal circulation after coronary revascularization procedures.
Source
Perfusion. 25 (4) (pp 197-203), 2010. Date of Publication: July 2010.
Publisher
SAGE Publications Ltd (55 City Road, London EC1Y 1SP, United Kingdom)
Abstract
During the last decade, minimized extracorporeal circulation (MECC)
systems have shown beneficial effects to the patients over the
conventional cardiopulmonary bypass (CECC) circuits. This is a prospective
randomized study of 99 patients who underwent coronary artery bypass
grafting (CABG) surgery, evaluating the postoperative haematological
effects of these systems. Less haemodilution (p=0.001) and markedly less
haemolysis (p<0.001), as well as better preservation of the coagulation
system integrity (p=0.01), favouring the MECC group, was found. As a
clinical result, less bank blood requirements were noted and a quicker
recovery, as far as mechanical ventilation support and ICU stay are
concerned, was evident with the use of MECC systems. As a conclusion,
minimized extracorporeal circulation systems may attenuate the adverse
effects of conventional circuits on the haematological profile of patients
undergoing CABG surgery. The Author(s) 2010.

<16>
Accession Number
70254970
Authors
Wechsler M. Cox G. Niven R. Zoratti E. Hanania N.
Institution
(Wechsler) BostonMAUnited States
(Cox) HamiltonCanada
(Niven) ManchesterUnited Kingdom
(Zoratti) DetroitMIUnited States
(Hanania) HoustonTXUnited States
Source
Annals of Allergy, Asthma and Immunology. Conference: 2009 Annual
Scientific Meeting of the American College of Allergy, Asthma and
Immunology, ACAAI Miami, FL United States. Conference Start: 20091105
Conference End: 20091110. Conference Publication: (var.pagings). 103 (5
SUPPL. 3) (pp A71), 2009. Date of Publication: November 2009.
Publisher
American College of Allergy, Asthma and Immunology
Abstract
Introduction: BT is a procedure designed to improve asthma control by
reducing airway smooth muscle mass. Three randomized controlled trials
(RCT) evaluated the effect of BT in patients with asthma. The most recent
trial was a double-blind, sham-controlled study (AIR2 Trial) to evaluate
the effectiveness and safety of BT for the treatment of severe,
symptomatic asthma. Methods: 297 subjects with severe asthma [symptomatic
despite taking high doses of ICS (>= 1000mcg BDP equiv.) and LABA] were
enrolled with a 2:1 randomization (BT:Sham control) at 30 sites. The
primary endpoint was the difference between groups for the change from
baseline in the AQLQ score. Results: 79% of BT subjects achieved a
statistically significant and clinically meaningful AQLQ improvement of
>=0.5 compared to 64% of the Sham group. This was consistent with findings
from the two prior RCTs. BT subjects with lower AQLQ tended to have
greater improvements in AQLQ. The cumulative rate of ER visits over the
entire study was 0.13/subject in the BT group and 0.45/subject in the sham
group. As in previous RCTs, an increased rate of respiratory AEs was
observed in the BT group compared to Sham during the Treatment period.
3.1% of BT bronchoscopies were associated with a hospitalization in the
Treatment period vs. 0.7% in the sham group (ppsuperiority 99.4%). This
rate was consistent with the previous AIR Trial. The median time to onset
and time to resolution of respiratory AEs were 1 day and 1 week,
respectively. Short-term AEs were related to transient worsening of asthma
symptoms, were reversible, and managed with standard care. During the
post-treatment period out to 12 months, the rate of respiratory AE's was
lower in the BT group than in the Sham group, and resulted in fewer ER
visits for BT subjects. There were no procedure-related pneumothoraces,
cardiac arrhythmias, intubations, or death over the course of the 3 RCTs.
Conclusions: Clinical experience in 3 RCTs demonstrates BT may be an
effective new treatment approach. While the risks of BT include transient
worsening of asthma, patients on high doses of ICS+LABA, with impaired
quality of life, experience meaningful improvements in their overall
asthma status. Referral for BT may be considered when standard medications
are not sufficient to control severe asthma.

<17>
Accession Number
70255331
Authors
Pugh R.J. Rathbone P.
Institution
(Pugh, Rathbone) Glan Clwyd Hospital, Rhyl, United Kingdom
Source
Critical Care. Conference: 30th International Symposium on Intensive Care
and Emergency Medicine, ISICEM Brussels Belgium. Conference Start:
20100309 Conference End: 20100312. Conference Publication: (var.pagings).
14 (pp S30), 2010. Date of Publication: 2010.
Publisher
BioMed Central Ltd.
Abstract
Introduction: This systematic review aims to evaluate evidence from
randomised controlled trials (RCTs) for oral chlorhexidine in preventing
nosocomial pneumonia in intubated mechanically ventilated critically ill
adults. Use of oral chlorhexidine appeals since it should reduce bacterial
aspiration from the orophayrnx. A number of RCTs have recently been
published on this topic. Methods: Search of Medline, Embase, Cochrane
library, grey literature registers, conference proceedings and reference
lists for RCTs comparing chlorhexidine with placebo or standard care for
prevention of pneumonia in the critically ill. Outcomes: episode of
nosocomial respiratory tract infection (RTI), mortality, duration of
mechanical ventilation (MV) and length of ITU stay (ITU LOS). Review
Manager 4.2 (Nordic Cochrane Centre) was used for data synthesis. Effect
estimates (odds ratio for dichotomous and weighted mean difference for
continuous data) were calculated using a random effects model. Results:
Fourteen studies were identified, three involving patients undergoing
cardiac surgery (1,841 patients) and 11 involving patients in
noncardiothoracic ITUs (1,497 patients; see Table 1). Five studies
(including two cardiac studies) found a significant reduction in episodes
of nosocomial RTI in the chlorhexidine-treated group versus placebo or
standard care. Pooled data indicated a significant reduction in nosocomial
RTI in the treatment group among all patients, and among cardiac and
noncardiac sub-groups (odds ratio 0.57 (95% CI 0.42 to 0.77), 0.52 (0.37
to 0.75) and 0.6 (0.4 to 0.89), respectively). However, no significant
differences in mortality, duration of mechanical ventilation or ITU stay
were demonstrated. Significant heterogeneity (I2 statistic >40%) was
detected for all outcomes except mortality. {Table presented}.
Conclusions: Use of oral chlorhexidine is associated with reduction in
nosocomial respiratory tract infection in intubated mechanically
ventilated critically ill adults.

<18>
Accession Number
70255619
Authors
Hajjar L. Galas F. Sundin M. Nakamura R. Silva C. Mauad T. Pomerantzeff P.
Bueno P. Kalil Filho R. Vincent J.L. Auler J.
Institution
(Hajjar, Galas, Sundin, Nakamura, Silva, Pomerantzeff, Bueno, Kalil Filho,
Auler) Heart Institute, So Paulo, Brazil
(Mauad) So Paulo University, So Paulo, Brazil
(Vincent) Erasme Hospital, Brussels, Belgium
Source
Critical Care. Conference: 30th International Symposium on Intensive Care
and Emergency Medicine, ISICEM Brussels Belgium. Conference Start:
20100309 Conference End: 20100312. Conference Publication: (var.pagings).
14 (pp S126-S127), 2010. Date of Publication: 2010.
Publisher
BioMed Central Ltd.
Abstract
Introduction: There are no prospective studies comparing outcomes between
restrictive or liberal strategies in cardiac surgery. This study is a
double-blind randomized study to determine whether a restrictive strategy
of red cell transfusion and a liberal strategy produced equivalent
Results: in patients submitted to cardiac surgery. Methods: Until November
2009 we enrolled 380 patients undergoing elective cardiac surgery and
randomly assigned 185 patients to a restrictive strategy of transfusion,
in which red cells were transfused if the hematocrit concentration dropped
below 24%, and 195 patients to a liberal strategy, in which transfusions
were given when the hematocrit fell below 30%. Both transfusion strategies
were followed into the operative room and during the ICU stay. We compared
the rates of complications and death from all causes during the hospital
stay and clinical outcomes of patients after 90 days. Adult patients,
after written informed consent, were allocated if they would be submitted
to elective primary surgery or were redone adult cardiac surgical patients
for coronary artery bypass grafting, valve procedure or combined
procedures. Results: Overall, hospital mortality was similar in the two
groups (4.7% vs 5.3%, P = 0.11). The rates of complications were similar
in the two groups (28.3% in the restrictive-strategy group and 26.1% in
the liberal-strategy group, P = 0.33). The ICU stay was significantly
lower in the restrictivestrategy group (2.2 days vs 4.1 days, P = 0.05).
There was no difference in 90-day mortality between groups. Conclusions: A
restrictive strategy of red cell transfusion is at least as effective as
and possibly superior to a liberal transfusion strategy in patients
submitted to cardiac surgery.

<19>
Accession Number
70248879
Authors
Yank V. Logan A.C. Vaughan Tuohy C. Bravata D.M. Staudenmayer K. Eisenhut
R. Sundaram V. McMahon D. McDonald K.M. Owens D. Stafford R.S.
Institution
(Yank) Department of Medicine, Division of General Internal Medicine,
Stanford University, Stanford, CA, United States
(Logan) Department of Medicine, Divisions of Hematology and Blood and
Marrow Transplantation, Stanford University, Stanford, CA, United States
(Vaughan Tuohy, Bravata, Eisenhut, Sundaram, McDonald, Owens, Stafford)
Department of Medicine, Stanford Prevention Research Center, Stanford
University, Stanford, CA, United States
(Staudenmayer) Department of Surgery, Trauma and Surgical Critical Care,
Stanford University, Stanford, CA, United States
(McMahon) Department of Statistics, Stanford University, Stanford, CA,
United States
Source
Blood. Conference: 51st Annual Meeting of the American Society of
Hematology, ASH New Orleans, LA United States. Conference Start: 20091205
Conference End: 20091208. Conference Publication: (var.pagings). 114
(22) , 2009. Date of Publication: 20 Nov 2009.
Publisher
American Society of Hematology
Abstract
Background: Recombinant factor VIIa (rFVIIa) is a potent hemostatic agent
licensed for treatment of bleeding in hemophiliac patients with inhibitors
but has been increasingly used off-label to treat or prevent bleeding,
despite sparse data to support its efficacy and a possible increase in
thromboembolic events. While randomized controlled trials (RCTs) provide
the best evidence regarding efficacy, they may not identify rare but
important adverse events. Observational studies may capture the rate of
such events in clinical practice more accurately. Objectives: To compare
rates of thromboembolic events associated with off-label use of rFVIIa in
RCTs and observational studies. Methods: Studies of off-label application
of rFVIIa were identified by review of 10 literature and clinical trial
databases through February, 2009. The off-label indications examined were
trauma, non-traumatic intracranial hemorrhage (ICH), and adult cardiac
surgery. When an appropriate number and quality of studies were available,
data from RCTs and higher quality comparative observational studies were
combined via meta-analysis using the arc sine statistical method, a method
that characterizes uncommon events more accurately than more conventional
methods. To describe the absolute rate of thromboembolism for patients
treated with rFVIIa in RCTs versus observational studies, we analyzed data
from the interventional arms of RCTs and comparative observational
studies, as well as data from non-comparative observational studies with
15 or more patients. Results: Included Studies Our search identified 4
RCTs and 4 observational studies of rFVIIa use in ICH. Two RCTs and 5
observational studies were identified for trauma. For cardiac surgery, 2
RCTs, 2 higher quality comparative observational studies (included in the
meta-analysis), and 8 additional observational studies were identified.
Meta-analyses The meta-analysis of the RCTs investigating use of rFVIIa in
ICH showed a trend toward increased thromboembolic risk with rFVIIa
(arcsine summary effect size 0.100, 95% CI -0.072-0.272). For trauma, the
two RCTs did not provide sufficient data to perform meta-analysis.
Individually, they did not demonstrate significantly different incidences
of thromboembolic events with rFVIIa compared to placebo but may have been
underpowered to detect such differences. For cardiac surgery, the
meta-analysis of the 4 studies showed a significant increase in
thromboembolic events in the rFVIIa group (arcsine summary effect 0.14;
95% CI 0.038- 0.242). Absolute rates of thromboembolic events in RCTs
versus observational studies In ICH, thromboembolic event rates in the
treatment arms of the RCTs ranged from 0.07-0.11, while those in the
observational studies ranged from 0-0.20. In trauma, thromboembolic event
rates in the RCT treatment arms ranged from 0.03-0.06, whereas those in
the observational studies ranged from 0.02-0.11. In cardiac surgery,
thromboembolic event rates in the RCTs ranged from 0.07-0.22 compared to a
range of 0-0.25 in the observational studies. For all three indications,
Figure 1 shows that the weighted mean thromboembolic event rates
associated with rFVIIa use are higher in the observational studies than in
the RCTs. Patients in the observational studies tended to be older and
have a worse prognosis than those enrolled in the RCTs. (Figure presented)
Conclusions: We identified a trend toward significantly higher rates of
thromboembolic adverse events with off-label use of rFVIIa compared to
placebo in our meta-analyses of ICH and cardiac surgery, but no similar
pattern in trauma trials. For each of these indications, we identified a
higher rate of thromboembolic adverse events associated with the use of
rFVIIa in observational trials compared to RCTs. This finding suggests
that patients receiving off-label rFVIIa for these off-label indications
in real-world practice may be at higher risk of thromboembolic events than
patients enrolled in clinical trials and may caution against widespread
use, especially in the absence of convincing data on efficacy.