ASSociAtE EditorS
Luciano Gattinoni
vol. 2 • n° 2 • 2010
EditorS in chiEf
Alberto Zangrillo
Università Vita-Salute San Raffaele
Milano, Italia
roland hetzer
Deutsches Herzzentrum Berlin, Germany
Official Journal of
School of Anesthesiology
and Intensive Care
Cattedra di Anestesia e Rianimazione
Università Vita-Salute San Raffaele
Milano, Italia
Endorsed by
ITACTA
(Italian Association
of Cardiothoracic Anaesthesiologists)
www.itacta.org
Deutsches Herzzentrum Berlin, Germany
WEb Site
www.itacta.org
Editore
Edizioni Internazionali srl
Divisione EDIMES
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Via Riviera 39 - 27100 Pavia
Tel. 0382526253 r.a. - fax 0382423120
E-mail: edint.edimes@tin.it
Università degli Studi di Milano,
Policlinico di Milano, Italia
Massimo Antonelli
Università Cattolica Sacro Cuore,
Policlinico Gemelli, Roma, Italia
Antonio Pesenti
Università degli Studi di Milano Bicocca,
Ospedale San Gerardo, Italia
SEction EditorS
n intEnSivE cArE
Luciano Gattinoni
Università degli Studi di Milano, Policlinico di Milano, Italia
n AnESthESiA
Fabio Guarracino
Azienda Ospedaliera Universitaria Pisana, Pisa, Italia
n vASculAr SurgEry
Roberto Chiesa
Università Vita-Salute San Raffaele, Milano, Italia
n cArdiAc SurgEry
Ottavio Alfieri
Università Vita-Salute San Raffaele, Milano, Italia
n cArdiology
Giuseppe Biondi-Zoccai
Università degli Studi di Torino, Italia
n clinicAl cArdiology
Alberto Margonato
Università Vita-Salute San Raffaele, Milano, Italia
n invASivE cArdiology
Stephan Dreysse
Deutsches Herzzentrum Berlin, Germany
n intErvEntionAl pEdiAtric cArdiology
Peter Ewert
Deutsches Herzzentrum Berlin, Germany
n EchocArdiogrAphy
Michele Oppizzi
Università Vita-Salute San Raffaele, Milano, Italia
n mEtAboliSm
Dionisio Colella
Università degli Studi di Tor Vergata, Roma, Italia
n nEw tEchnologiES
Federico Pappalardo
Università Vita-Salute San Raffaele, Milano, Italia
n in hoSpitAl EmErgEnciES
Luca Cabrini
Università Vita-Salute San Raffaele, Milano, Italia
n nurSing
Mariano Fichera
Università Vita-Salute San Raffaele, Milano, Italia
n hEmAtology
Andreas Koster
Deutsches Herzzentrum Berlin, Germany
n pEEr-to-pEEr communicAtion
Michael John
Università Vita-Salute San Raffaele, Milano, Italia
n imAging
Antonio Grimaldi
Università Vita-Salute San Raffaele, Milano, Italia
n futurE EvEntS
George Silvay
The Mount Sinai School of Medicine

Segreteria di redazione
Lara Sussani
Cattedra di Anestesia e Rianimazione
Università Vita-Salute San Raffaele, Milano
Via olgettina, 60 - 20132 Milano
Tel. +39 02 26436158
fax +39 02 26436152
sussani.lara@hsr.it
wEb Site
www.itacta.org
direttore responsabile
Paolo E. zoncada
Registrazione Tribunale di Milano
n. 532 del 26 novembre 2009
The Journal is indexed in
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E-mail: edint.edimes@tin.it
EXEcutivE Editor
Massimiliano Nuzzi
Università Vita-Salute San Raffaele, Milano, Italia
EditorS
John T. Apostolakis
Cleveland Clinic, OH, US
Elena Bignami
Università Vita-Salute San Raffaele, Milano, Italia
Tiziana Bove
Università Vita-Salute San Raffaele, Milano, Italia
Maria Grazia Calabrò
Università Vita-Salute San Raffaele, Milano, Italia
Nicola Colangelo
Università Vita-Salute San Raffaele, Milano, Italia
Michele De Bonis
Università Vita-Salute San Raffaele, Milano, Italia
Francesco De Simone
Università Vita-Salute San Raffaele, Milano, Italia
Gian Franco Gensini
Università degli Studi di Firenze, Italia
Giuseppe Giardina
Università Vita-Salute San Raffaele, Milano, Italia
James L. Januzzi
Harvard University, Massachusetts General Hospital, US
Giovanni Landoni
Università Vita-Salute San Raffaele, Milano, Italia
Kevin Lobdell
Sanger Heart and Vascular Institute, Charlotte, NC, US
Giovanni Marino
Università Vita-Salute San Raffaele, Milano, Italia
Andrea Morelli
Università degli Studi “La Sapienza”, Roma, Italia
Stefano Romagnoli
Ospedale Careggi, Firenze, Italia
Antonio Emilio Scala
Dean, Università Vita-Salute San Raffaele, Milano, Italia
Anna Mara Scandroglio
Università Vita-Salute San Raffaele, Milano, Italia
Luigi Tritapepe
Università degli Studi “La Sapienza”, Roma, Italia
Emiliano Vitalini
Ospedale San Camillo Forlanini, Roma, Italia
 proceedings
in Intensive Care
Cardiovascular Anesthesia

Endorsed by

ConTEnTS 3

n EditoriAl
preventing mortality in cardiac surgery with anesthetic drugs and techniques.
there is need for a consensus conference ...................................................................................................................................................................5
G. Landoni, A. Zangrillo

n rEviEw ArticlE
the edge-to-edge technique for mitral valve repair ..................................................................................................................................7
M. De Bonis, O. Alfieri

glucose metabolism in cardiovascular surgery ............................................................................................................................................ 19

C. Lazzeri, S. Bevilacqua, F. Ciappi, C. Pratesi, G. F. Gensini, S. Romagnoli

n originAl ArticlE
high-sensitivity c-reactive protein (hs-crp) and tumor necrotizing factor-alpha
(tnf-α) after on- and off- pump coronary artery bypass grafting ..................................................................... 27
H. Javadzadegan, N. Nezami, K. Ghobadi, A. Sadighi, A.A. Abolfathi, N.D. Nader

A new method for managing emergency calls................................................................................................................................................. 35

G. Landoni, L. Cabrini, O. Fochi, A. Zangrillo

day admission for thoracic aortic surgery ........................................................................................................................................................... 40

G. Silvay

transoesophageal echocardiography during coronary artery bypass procedures:

impact on surgical planning............................................................................................................................................................................................................... 43
F. Guarracino, C. Cariello, L. Tritapepe, L. Doroni, R. Baldassarri, A. Danella, M. Stefani

n cASE rEport
bullet embolisation from injured inferior cava vein to the right ventricle ...........................................51
A. Zenelaj, M. Brati, M. Kerci

n imAgES in mEdicinE
penetrating chest trauma: the role of emergency echo.................................................................................................................. 55
F. Guarracino, R. Baldassarri, C. Vullo, M. Stefani

n pApErS, poStErS, prESEntAtionS:

communicAting thE biomEdicAl SciEncES
once upon a time there was a congress................................................................................................................................................................... 57
M. John
LA SOLUZIONE IDEALE PER:
Arresto cardiaco
Ictus
HIE Encefalopatia Ischemica Ipossica
Danno vertebrale traumatico
Sepsi
Chirurgia
Emergenza
Danno celebrale traumatico
Mantenimento organi per donazione

SEDA S.P.A. Telefono +39 02 48424.1

Via Tolstoi, 7 Fax +39 02 48424290
20090 Trezzano sul Naviglio (Mi) www.sedaitaly.it - sd@sedaitaly.it

Certificato UNI EN ISO 9001:2000

 proceedings
in Intensive Care
Cardiovascular Anesthesia

Endorsed by

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 77-79

77
Ethics and methodology,
Editorial
not bureaucracy
G. Landoni, A. Zangrillo
Department of Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milan, Italy

we have a dream that within ten years, patients admitted to teaching

hospitals will long to be enrolled in “researcher driven”*randomized
clinical trials. Patients will be fully aware of the reduced complica-
tion rates and the improved outcomes that occur in patients invol-
ved in randomized clinical trials, the so-called “Hawthorne effect”.
we have a dream that within ten years scientists will not have to
spend months waiting for ethics committee approval and will not
have to raise thousands of Euros in funds to carry out their research.
on the contrary, they will have a 50% salary increase as they are
spending their creative and enthusiastic energies to perform clinical
trials (at present, hospitals receive several thousand Euros from the
Ministry of Health for each published article, yet the clinical scienti-
st generally knows nothing about it).
Although both “company driven” and “researcher driven” research
are important and useful, the differences are striking. Unfortunate-
ly, patients, medical doctors and legislators do not seem to be fully
aware of these differences. one reason for this might be the influen-
ce of international insurance, pharmaceutical and quality-control
lobbies.
Today, a clinical scientist who wants to compare two forms of treat-
ment that have routinely been used in clinical practice for around 20

*for this editorial the following definitions will be used: “company driven” trials include
phase I, II (III) trials on new drugs with safety issues and economical implications; “rese-
archer driven” trials include phase (III) IV trials on “old” drugs (“generics”) or techniques
used in various combinations, or for new indications with no safety issues or economical
implications. The clinical scientist has no conflict of interest with the drug company. Patient
management is carried out using the best available treatment, the only difference being ran-
domization to treatment or control; “in between” trials include phase (II) III (IV) trials that
resemble the “researcher driven” type, but are actually “company driven”.

Corresponding author:
Giovanni Landoni, M.D.
Department of Cardiothoracic Anesthesia and Intensive Care
Università Vita-Salute San Raffaele
Via olgettina, 60 - 20132 Milano, Italy
e.mail: landoni.giovanni@hsr.it

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 EditoriAl

78 years, two slightly different dosages of the same drug, or use a safe
drug at a lower dosage with slightly different indications is obliged
to:
1) prepare hundreds of pages of documentation (most of the time
not in English, but in a language not generally used by the scien-
tific community);
2) wait from six to twelve months for ethics committee approval
(which at times never arrives);
3) pay a Contract Research organization (CRo) for the quality mo-
nitoring of the study;
4) pay a CRo for the pharmacovigilance of the study (even if the
drug has been used in clinical practice for 20 years on millions of
patients);
5) pay specific insurance for all patients enrolled in the study.

Considering that it can take from one to two years to receive a grant
(from its ideation to its funding) and that protocol approval takes a
year, we are generally forced to observe our ideas while they agonize
under the weight of bureaucracy and fundraising requirements.
we have a dream that within ten years the same clinical scien-
tist will have his idea approved by an ethics commission made up
of peers and patients after only a few weeks and will randomize
hundreds of patients in just a few days using established multicen-
ter networks without costs or bureaucracy. In Italy, for example, we
have more than 100 cardiac surgery centers that perform around
40,000 cardiac surgery operations every year. It would be simple and
cheap to compare inotropic or vasoconstrictor agents in perioperati-
ve cardiac failure; to identify if the widespread use of diuretics in the
management of acute renal failure is useful, useless, or dangerous, to
compare anesthesia techniques and drugs, or investigate preventive
measures or curative drugs for the prevention or treatment of car-
diological, nephrological, or neurological complications. We would
need networking, a simple national web-based database and regular
meetings (either online or in person).
In intensive care the situation is almost grotesque. Most patients are
unconscious and therefore cannot provide written informed con-
sent, which means they cannot benefit from inclusion in researcher
driven randomized clinical trials according to the interpretation of
many ethics committees. As a result, critically ill patients have no
evidence-based medicine guidelines to support the life-saving treat-
ment they are receiving.
Hospitals that carry out clinical research perform better than those
that do not. Patients (and Patients’ Associations) should ask to be-
come involved in “researcher driven” trials. They should go to those
hospitals where “researcher driven” trials are performed and ask to

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 Ethics and methodology, not bureaucracy

be enrolled in ongoing trials. In fact, patients enrolled in “researcher 79

driven” clinical trials have improved outcomes, irrespective of the
assigned treatment or control. This so-called “Hawthorne effect”
can be explained, in part, by the superior knowledge and skill of
the medical doctors/departments where research is performed and
by the additional attention that all the medical and nursing staff
dedicates to these patients. “Research driven” trials should involve
every patient that is admitted to a high-standard hospital. There is
so much to discover and each patient should be studied and benefit
from inclusion in randomized protocols.
Two factors limit this extraordinary opportunity: bureaucracy and
ignorance. International and European laws in this field are excel-
lent where “company driven” trials are concerned, but limit “rese-
archer driven” trials and thus, indirectly, kill thousands of patients
every year.
of course, clinical research has to be studied at Universities and Ma-
ster Courses and clinical scientists need to possess strong methodo-
logy and should receive incentives to disclose any conflict of interest.
What we all need is Ethics and methodology, not bureaucracy.
our dream is to reach this objective within 10 years. We believe we
can do it and we are certain that all of our patients will benefit gre-
atly from it.

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

Papers, Posters,
Presentations:
Communicating
the biomedical sciences

Enrolment for one-day courses

organised on a weekly basis from September 2010

• Methodology and basic statistics

• Impact Factor, H index, Scopus, Pubmed and Google Scholar
• The point of view of the author, reviewer, editor
• How to review a paper
• Without publication your discoveries will remain in your laboratory or in your ward and will be
unknown to the rest of the biomedical community. Remember that it is your duty to contribute to the
construction of an ever-growing biomedical database that will hopefully develop clinical and surgical
techniques, therefore improving the health and lives of your patients.
• How is it possible to be captivating and interesting when communicating scientific data? Science is
serious, but there is no reason why it should be boring.

Prof. Michael John · Università Vita-Salute San Raffaele, Milan

Prof. Giovanni Landoni · Università Vita-Salute San Raffaele, Milan

For details contact Lara Sussani (sussani.lara@hsr.it)

 proceedings
in Intensive Care
Cardiovascular Anesthesia

rEviEw ArticlE
Endorsed by

81
major themes for 2009 in
cardiothoracic and vascular anesthesia
J. Fassl¹, H. Riha², H. Ramakrishna³, N. Singh4, T. Wyckoff4, C. Roscher4,
J.G.T. Augoustides4
¹Department of Anesthesiology and Critical Care, University of Basel; Switzerland;
²Department of Anesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech
Republic; ³Department of Cardiac Anesthesia, Mayo Clinic, Scottsdale, Arizona, USA;
4
Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 81-91

AbStrAct
The hybrid operating room is the venue for transcatheter therapy with the convergence of three specialties:
cardiac surgery, cardiovascular anesthesiology, and interventional cardiology. Transcatheter aortic valve re-
placement is proof that cardiac specialists have embraced the endovascular revolution. Since pharmacologic
and ischemic myocardial conditioning are safe and effective, they are currently the focus of multiple trials.
Angiotensin blockade, anemia and endoscopic saphenous vein harvesting worsen outcome after coronary
artery bypass grafting (CABG). Although off-pump CABG is equivalent to on-pump CABG, it may improve
outcomes in high-risk groups. Although percutaneous coronary intervention (PCI) significantly decreases
mortality after myocardial infarction, the evidence is less convincing for intra-aortic balloon counterpulsa-
tion. Even though prasugrel was recently approved for platlet blockade in PCI, it may be superceded by ti-
cagrelor. Although PCI and CABG appear equivalent for multivessel coronary disease, CABG lowers revascu-
larization rates and also has superior outcomes in diabetics and the elderly. Hetastarch and n-acetylcysteine
both increase bleeding and transfusion in cardiac surgery. factor VII can treat life-threatening bleeding, but
its safety requires further evaluation. Since eltrombopag and romiplostim stimulate platelet production, they
may have a future role in hemostasis after cardiac surgery. Even though fenoldopam, atrial natriuretic peptide
and sodium bicarbonate are nephroprotective, further trials must confirm these findings. Intensive insulin
therapy offers no further outcome advantage and significantly increases hypoglycemic risk. The past year has
witnessed the advent of a new clinical venue, new devices, and new drugs. The coming year will most likely
advance these achievements.

Keywords: hybrid operating room, transcatheter aortic valve replacement, transcatheter mitral valve repair, isch-
emic preconditioning, pharmacologic conditioning, levosimendan, volatile anesthetics, angiotensin-converting en-
zyme inhibitors, anemia, hetastarch, coronary artery bypass grafting, endovascular saphenous vein graft harvesting,
percutaneous coronary intervention, intra-aortic balloon counterpulsation, sodium bicarbonate, atrial natriuretic
peptide, fenoldopam, intensive insulin therapy, prasugrel, ticagrelor.

introduction

This article is the first of its kind for this

journal, and we thank the editorial board
Corresponding author:
John G.T. Augoustides MD, fASE, fAHA for the invitation to review the highlights
Associate Professor of 2009 in cardiothoracic and vascular an-
Cardiothoracic Section
Anesthesiology and Critical Care esthesia. The dominant themes for 2009
Dulles 680, HUP
3400 Spruce Street
will initially be outlined in the introduc-
e.mail: yiandoc@hotmail.com tion of this article and then subsequently
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
 J. Fassl, et al.
82 explored in depth in the in the body of the
article. Transcatheter valve therapy in the
emerging environment of the hybrid op-
erating room (oR) will likely disseminate
even more globally, as further approvals
from regulating agencies are obtained in
new countries and for new devices. The
venue for these breakthrough technologies
will likely increasingly be the hybrid oR,
best understood as merging the advantages
of the cardiac catheterization laboratory
and the operating room. This new peri-
operative venue will continue to facilitate
novel interventions as specialists embrace
the unfolding endovascular revolution in
cardiovascular medicine.
Perioperative myocardial conditioning of
the myocardium has gained increasing at-
tention as trials consistently demonstrate
enhancement of clinical outcomes after
cardiac surgery with exposure to volatile
anesthetics, levosimendan and ischemia,
both local and remote. It is likely that these
perioperative techniques will gradually be
integrated into the conduct of cardiotho-
racic and vascular procedures, as the out-
come advantages are demonstrated in ad-
equately powered trials with meaningful
clinical end-points. In contrast, periopera-
tive exposure to angiotensin blockade and
anemia independently predict adverse out-
come after coronary artery bypass graft-
ing (CABG). The outcome advantages of
off-pump CABG appear to be confined to
high-risk patients. Endoscopic saphenous
vein harvesting may increase the risks of
coronary graft thrombosis to worsen clini-
cal outcomes after CABG. In contrast, the
aggressive management of ST-elevation
myocardial infarction (STEMI) with per-
cutaneous coronary intervention (PCI)
consistently improves outcomes across
multiple trials. The indications for intra-
aortic balloon counterpulsation in STEMI
have recently been questioned as the out-
come advantages are not substantial in
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
recent trials. Although prasugrel appears
likely to replace clopidogrel, the future of
oral thienopyridine platelet blockade may
be moving to direct and reversible blockade
with ticagrelor, pending the results of large
trials currently in progress.
With these advances in platelet blockade,
the role of PCI may continue to expand in
the management of multivessel coronary
artery disease (CAD). Although PCI ap-
pears equivalent to CABG for multivessel
CAD in select groups, it still has a signifi-
cantly higher risk of revascularization and
adverse outcomes in diabetics and patients
>65 years old. It is likely that the inter-
ventional management of CAD will be
integrated in the hybrid oR in the future
search for the best combined approach to
CAD.
Since bleeding and transfusion after car-
diac surgery independently predict adverse
outcome, the impaired hemostasis associ-
ated with hetastarch and n-acetylcysteine
is concerning. The perioperative safety
of factor VII in severe bleeding requires
further study. The advent of the throm-
bopoeitin agonists such as eltrombopag
and romiplostim offers the opportunity
to boost preoperative platelet levels which
may have a clinical niche in the cardiac
surgical patient.
Similarly to bleeding and transfusion, re-
nal dysfunction independently predicts ad-
verse outcome after cardiac surgery. Pilot
data suggest that fenoldopam, atrial natri-
uretic peptide and sodium bicarbonate may
be nephroprotective after cardiac surgery.
Although further trials are indicated to ex-
plore their efficacy and safety, the search
for nephroprotective agents in our special-
ty is a priority, given the outcome impor-
tance of maintaining renal function peri-
operatively.
In a similar fashion, ongoing trials have ex-
plored the safety and efficacy of periopera-
tive glucose management. Although goal
 major themes for 2009 in cardiothoracic and vascular anesthesia
glucose level ≤180 mg/dL enhance clinical
outcome after adult cardiac surgery, these
outcome advantages are not universal.
Tighter glucose control for levels in the
range of 80-110 mg/dL not only does not
offer any clinical advantage but substan-
tially increases the risk of hypoglycemia.
trAnScAthEtEr vAlvE
intErvEntionS
Aortic valve
Transcatheter aortic valve implantation
(TC AVI) is a major innovation in our
specialty and consequently has received
considerable attention (1-4). This technol-
ogy will generalize further in the USA if
the landmark PARTnER trial (Placement
of AoRTic TranscathetER Valve Trial:
full details available at www.clinicaltrials.
gov, last accessed March 2nd 2010) demon-
strates significant outcome improvement.
It is essential that the anesthesia team
thoroughly understands the entire TC AVI
procedure as their focused and integrated
participation is essential for the success
of this challenging procedure, including
transesophageal echocardiography (TEE)
(5-8). The major phases in the conduct of
TC AVI each have their complications (9-
11). Vascular access may be complicated by
arterial rupture, apical tearing, and aortic
dissection. Malsizing of the aortic prosthe-
sis may be complicated by valve emboliza-
tion, aortic annulus rupture and aortic dis-
section. Errors in rapid transvenous ven-
tricular pacing may allow ventricular ejec-
tion to interfere with balloon valvuloplasty
and subsequent valve deployment. Errors
in aortic prosthesis positioning may be
complicated by valve prolapse, valve embo-
lization, coronary occlusion as well as rup-
ture of the aortic root and left ventricular
outflow tract. The successful management
of complications depends on rapid and ef-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
fective multidisciplinary teamwork in the 83
hybrid oR setting (9-13).
The hybrid oR will likely also significantly
impact the interventional management of
CAD (14). A recent trial (n=366) demon-
strated that completion angiography after
CABG in a hybrid oR allowed diagnosis of
graft inadequacies in 12% of cases. These
lesions were all corrected there and then
in the hybrid oR with either PCI or sur-
gical revision. The hybrid oR has brought
advanced fluoroscopy to the intraoperative
management of CAD with significant ef-
fect. This is analogous to the effect of TEE
on the conduct of cardiac surgery, where
the ability to image the structures of inter-
est and receive immediate feedback has
fundamentally altered our specialty for-
ever (15, 16).
Mitral valve
Transcatheter mitral valve therapy has re-
cently progressed far beyond balloon val-
vuloplasty for mitral stensosis and these
many of the novel therapies are currently
in clinical trials (17-19). Transcatheter
Alfieri mitral valve repair is now possible
with an array of technologies that enable
leaflet edge-to-edge union. Percutane-
ous mitral annuloplasty is also possible
through stenting of the coronary sinus that
is closely related to the mitral annulus. It is
likely that these 2 therapeutic approaches
may be combined in the future to signifi-
cantly enhance the durability of the repair,
as evidenced by the surgical approach (20).
furthermore, the hybrid operating room
will likely become their natural venue as
cardiothoracic surgeons master these in-
novative approaches that have established
their safety and efficacy in clinical trials
(21). Indeed, it is logical that dual trans-
catheter aortic and mitral valve interven-
tions will be possible in the near future
once the individual technologies have en-
tered clinical practice.
 J. Fassl, et al.
84 pEriopErAtivE conditioning
for myocArdiAl protEction
Volatile anesthesia
Volatile anesthetics have been demonstrat-
ed to condition the myocardium protec-
tively to better tolerate ischemia-reperfu-
sion (22, 23). The outcome importance of
this important characteristic of our volatile
anesthetics was investigated in a massive
multicenter Italian CABG cohort study
(n=34 310: 64 centers) (24). Exposure
to volatile anesthesia significantly low-
ered perioperative mortality (P=0.035),
especially if there was prolonged duration
(P=0.022) or if the volatile agent was iso-
flurane (P=0.039). These positive findings
add more weight to the argument that the
contemporary cardiac anesthetic should
include a volatile component for optimal
outcome (25).
Levosimendan
Levosimendan is a calcium-sensitizing ino-
dilator that may exert beneficial outcome
effects when administered as soon as pos-
sible after anesthetic induction, including
reduced troponin release (P=0.0003) and
hospital stay (P=0.05) (26, 27). A recent
meta-analysis (cumulative n=440: 10
trials) confirmed that levosimendan ex-
posure significantly reduced mortality af-
ter cardiac surgery (odds ratio 0.35; 95%
confidence interval 0.18-0.71; P=0.003)
(28). These encouraging observations have
spawned multiple clinical randomized tri-
als across both in adult and pediatric heart
surgery to more fully explore perioperative
benefits due to levosimendan (full details
available at www.clinicaltrials.gov, last ac-
cessed March 17th 2010).
Ischemic conditioning
Although ischemic preconditioning con-
fers significant ischemic tolerance to the
myocardium, its perioperative application
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
has mostly been evaluated in small trials.
Recent meta-analysis (cumulative n=933:
22 trials) confirmed its outcome benefits
after cardiac surgery: protection against
ventricular arrhythmias (odds ratio 0.11;
95% confidence intervals 0.04-0.29;
P=0.001) and inotrope sparing (odds ratio
0.34; 95% confidence interval 0.17-0.68;
P=0.002) (29).
Given the cumulative benefits of this in-
tervention, its perioperative safety and
efficacy should be further evaluated in ad-
equately powered clinical trials (29, 30).
Remote ischemic conditioning
Remote ischemic preconditioning is de-
fined as ischemic myocardial protection
following brief ischemia of a remote tissue
and has mainly been studied in small clini-
cal trials (31). Recent trials have confirmed
that this technique significantly reduced
the release of cardiac injury biomarkers
after PCI as well as both noncardiac and
cardiac surgery (32-36).
These promising data have generated the
mandate for a family of perioperative tri-
als (n=40: full details available at www.
clinicaltrials.gov, last accessed March 15th
2010). If the promise from the pilot trials
is consistently demonstrated across this
latest trial set, then this technique will
gradually enter the mainstream of clinical
practice.
SurgicAl mAnAgEmEnt
of coronAry ArtEry diSEASE
The dangers of perioperative
angiotensin blockade
Angiotensin-converting enzyme inhibitor
(ACEI) therapy has already been highlight-
ed as an independent predictor for signifi-
cant perioperative hypotension (37-39).
A large observational study (n=10 023
CABG patients: 1996-2008) demonstrated
that preoperative ACEI exposure signifi-
 major themes for 2009 in cardiothoracic and vascular anesthesia
cantly increased mortality (P=0.04), re-
nal dysfunction (P=0.0002), atrial fibril-
lation (P<0.0001), and inotropic support
(P<0.0001) (40) furthermore, recent data
indicate that the perioperative vasoplegia
associated with ACEI is dose-dependent
(41). Based on these recent observations,
it is reasonable to discontinue ACEI be-
fore CABG, as is currently recommended
in noncardiac surgery (42). The vasoplegia
associated with ACEI exposure has been
managed successfully with vasopressin
given either prophylactically or therapeuti-
cally (43, 44).
The dangers of preoperative anemia
A massive observational trial (n=10 025:
1998-2007 demonstrated that preoperative
anemia independently predicts mortality
after elective CABG (45). furthermore, it
also independently predicts postoperative
renal dysfunction (46).
These observations should trigger a great-
er focus with a new set of trials in cardiac
surgery to test the safety and efficacy of
preoperative hemoglobin augmentation
with interventions such as erythropoietin.
The controversy about endoscopic
saphenous vein graft harvesting
Endoscopic saphenous vein harvesting has
entered mainstream clinical practice due to
its cosmetic and wound advantages. Since
there may be more manipulation with this
technique, there is conceptually the dan-
ger of venous endothelial trauma and pos-
sible loss of long-term patency (47). In a
large observational CABG study (n=1753
in endoscopic harvest group; n=1247 in
open harvest group) endoscopic venous
harvesting significantly increased the risks
of death, myocardial infarction or repeat
revascularization (hazard ratio 1.22; 95%
confidence interval 1.101-1.47; P=0.04)
(48). In contrast, a larger single center
study (n=5825: 1998-2007) demonstrat-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
ed that this technique was safe and effec- 85
tive as it did not independently predict ad-
verse outcomes (49).
Consequently, adequately powered ran-
domized trials are required to resolve this
controversy. These trials may have limited
subject enrollment as patients may be re-
luctant to be randomized to endoscopic
saphenous vein harvesting, given its well-
known outcome disadvantages.
The controversy about the pump
in CAbG
Since the maturation of off-pump CABG,
its comparison with on-pump CABG has
been an ongoing question (50). A mas-
sive cohort comparison (n=63.047:
n=48.658 on-pump CABG; n=14.389 off-
pump CABG) demonstrated no significant
differences in perioperative mortality and
stroke with the off-pump cohort experienc-
ing clinically marginal increases in hospi-
tal length of stay and cost (51).
A second cohort comparison (n=14.766
from 1997-2007: n=7.083 off-pump CABG;
n = 7.683 on-pump CABG) demonstrated
that the off-pump technique preferential-
ly reduced mortality in high risk patients
(P=0.005) (52). These ‘real-world’ analy-
ses suggest that the CABGtechniques ap-
pear equivalent, except in high-risk subsets
where the off-pump technique may offer
outcome advantages.
The controversy in CABG was further ex-
plored in a recently published randomized
trial (n=2203) (53). This trial demon-
strated that after one year, the off-pump co-
hort had significantly worse outcomes and
graft patencies.
This trial has multiple limitations in its de-
sign, including multiple confounders such
as surgical inexperience, operative risk, and
aprotinin exposure (54-56). In summary,
this randomized trial reflects the off-pump
learning curve and its findings should be
confined to that domain.
 J. Fassl, et al.
86 pErcutAnEouS coronAry
intErvEntion
PCI for myocardial infarction
Although primary PCI is effective in STE-
MI, its efficacy in ‘real-world’ settings is
still debated. (57). To address this concern,
a recent meta-analysis included random-
ized trials (n=8140: 23 trials) and obser-
vational studies (n=185.900: 32 studies)
(58). Compared to fibrinolysis, primary
PCI reduced mortality in randomized tri-
als (odds ratio 0.66; 95% confidence inter-
val 0.51-0.82) and in observational studies
(odds ratio 0.77; 95% confidence interval
0.62-0.95). In the set of observational stud-
ies, primary PCI had no significant long-
term clinical outcome benefits. This meta-
analysis suggests that the substantial ben-
efits of PCI in STEMI are relevant in clini-
cal practice beyond the domain of strictly
controlled randomized trials.
furthermore, PCI should be routinely un-
dertaken within 6 hours after fibrinolyis. A
recent randomized trial (n=1.059) dem-
onstrated that this approach significantly
decreased the incidence of an adverse out-
come endpoint (relative risk 0.64; 95%
confidence interval 0.47-0.87; P=0.004),
defined as a composite of death, reinfarc-
tion, recurrent ischemia, congestive heart
failure, or cardiogenic shock within 30
days (59).
Intra-aortic balloon pump therapy
in myocardial infarction
Although intra-aortic balloon counter-
pulsation (IABP) has been recommended
for STEMI with cardiogenic shock, the
evidence supporting this recommendation
was examined in a recent meta-analysis
(60). In the analysis of 7 randomized tri-
als (n=1.009), IABP did not improve out-
come, and significantly increased stroke
and bleeding. In the analysis of 9 obser-
vational studies (n=10.529), IABP only
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
decreased mortality in STEMI managed
with primary fibrinolysis (95% confidence
interval 16%-20%; P<0.0001). The evi-
dence supporting IABP in STEMI is weak
at best.
The new platelet blockers prasugrel
and ticagrelor
Prasugrel is a novel thienopyridine that
blocks platelets more reliably than clopdo-
grel. Both these agents block the adenos-
ine diphosphate P2Y12 receptor and both
requires biotransformation in the liver to
form the active drug metabolites (61). In
acute coronary syndromes, prasugrel was
superior to clopidogrel for ischemic reduc-
tion (hazard ratio 0.81i; 95% confidence
interval 0.73-0.90; P<0.001), but at the
expense of bleeding risk (hazard ratio
1.32; 95% confidence interval 1.03-1.68;
P=0.03) (62).
A multicenter global randomized trial
(n=3534) also demonstrated the superior-
ity of prasugrel over clopidogrel in STEMI,
based on the composite endpoint of cardio-
vascular death, MI or stroke (hazard ratio
0.68; 95% confidence interval 0.54-0.87;
P=0.0017) (63). An important periopera-
tive observation from this trial was that
prasugrel significantly increased bleeding
after CABG (P=0.0033).
The thienopyridines, clopidogrel and
prasugrel, bind irreversibly to the plate-
let ADP P2Y12 receptor after hepatic bio-
transformation and are therefore indirect
irreversible platelet inhibitors (64). The
novel thienopyridine, ticagrelor, binds di-
rectly to the platelet ADP P2Y12 receptor
and requires no hepatic activation (64). In
acute coronary syndromes (n=18.624),
ticagrelor was superior to clopidogrel,
based on the composite endpoint of cardio-
vascular death, MI or stroke (hazard ration
0.84; 95% confidence interval 0.77-0.92;
P<0.001) (65). Ticagrelor did not signifi-
cantly increase bleeding after CABG in this
 major themes for 2009 in cardiothoracic and vascular anesthesia
large trial. Given these positive outcome
effects, this drug will likely disseminate
throughout clinical practice.
PCI or CAbG for multivessel coronary
artery disease
A large single center observational trial
(n=3.720: 2004-2005) demonstrated that
at 3 years PCI significantly increased death
(hazard ratio 1.62; 95% confidence inter-
val 1.07-2.47) and MI (hazard ratio 1.65;
95% confidence interval 1.15-2.44) (66).
In a larger pooled analysis (n=7.812:
10 trials), CABG was superior to PCI for
mortality reduction only in 2 subgroups,
namely diabetics (hazard ratio 0.70; 95%
confidence interval 0.56-0.87; P=0.014)
and the elderly (hazard ratio 0.82; 95%
confidence interval 0.70-0.97; P=0.002)
(67). further trials are required to explore
the survival benefits of CABG in multives-
sel CAD.
Perioperative bleeding and transfusion
Excessive bleeding after cardiac sur-
gery significantly increases the risks of
prolonged mechanical ventilation, pro-
longed stay in the intensive care unit stay
(P<0.001), and death (P<0.001) (68).
Volume resuscitation with the artificial
colloid hetastarch in off-pump CABG
(n=156: I liter of hetastarch versus I liter
of albumin) significantly increased medias-
tinal bleeding (P<0.001), transfusion risk
(P=0.012), and transfusion dose (packed
red blood cells P=0.017; fresh frozen plas-
ma P=0.009; and, platelets (P=0.013)
(69). Although n-acetylcysteine can be
nephroptotective perioperatively, it can
significantly increase mediastinal bleed-
ing (P=0.008), red blood cell transfusion
P=0.02) and the risk of receiving≥5 units
of red blood cells (P=0.005) (70).
A recent meta-analysis (cumulative n=298:
5 trials) explored the safety and efficacy of
factor VII therapy for hemostasis in cardiac
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
surgery (71). This trial demonstrated no 87
significant reduction in surgical re-explora-
tion (P=0.42), mortality (P=0.90), and a
trend towards increased stroke (P=0.09).
In a randomized adult cardiac surgical trial
(n=172), exposure to factor VII significant-
ly reduced surgical re-exploration (P=0.03)
and allogeneic transfusion (P=0.01) with
no significant increase in serious adverse
events (72). further trials are required to
more adequately explore the safety and ef-
ficacy of this hemostatic intervention in car-
diac surgery with massive bleeding.
Can the kidney be protected after
cardiac surgery?
The search for nephroprotective strategies
in cardiac surgery is ongoing. In a small
randomized trial (n=92), fenoldopam sig-
nificantly reduced the risk of renal replace-
ment therapy (P=0.037) (73). A larger
randomized trial (n=504) demonstrated
that perioperative atrial natriuretic peptide
is nephroprotective (P<0.0001) and sig-
nificantly reduces postoperative complica-
tions (P=0.0208) (74). In a pilot random-
ized trial (n=100), perioperative sodium
bicarbonate infusion significantly reduced
renal injury after on-pump cardiac surgery
(odds ratio 0.43; 95% confidence interval
0.19-0.98; P=0.043) (75). These promis-
ing nephroprotective agents are currently
being further evaluated in more than 50
randomized trials (full details available
at www.clinicaltrials.gov, last accessed
March 19th 2010).
In contrast, a large trial (n=563) impli-
cated pentastarch exposure as a significant
predictor of renal dysfunction after cardiac
surgery (odds ratio per mL/kg 1.08; 95%
confidence interval 1.04-1.12; P=0.001).
This trial also demonstrated that this
nephrotoxicity is dose-dependent with a
threshold value of 14 ml per kilogram body
weight (76). Given the current focus on
the importance of renal function in adult
 J. Fassl, et al.
88 cardiac surgery, it is likely that the ongo-
ing clinical development of perioperative
nephroprotective interventions will re-
main a priority.
Does tight glucose control matter?
Tight perioperative management of glucose
remains controversial in cardiac surgery
(77). In a recent large randomized trail in
critically ill adults (n=6.014), intensive
insulin therapy significantly increased
mortality (odds ratio 1.14; 95% confidence
interval 1.02-1.28; P=0.02) and severe hy-
poglycemia (P<0.001) (78).
Recent meta-analysis of intensive insulin
therapy in the intensive care unit (n=13
567: 26 trials) has demonstrated that this
intervention decreased mortality in the
surgical intensive care unit (relative risk
0.63; 95% confidence interval 0.44-0.91)
but not in medical (relative risk 1.0; 9%%
confidence interval 0.78-1.28) or mixed in-
tensive care units (relative risk 0.99; 95%
confidence interval 0.86-1.12) (79). The
Society of Thoracic Surgeons recommends
insulin infusion to maintain perioperative
glucose levels below 180 mg/Dl (80).
concluSionS
The hybrid operating room is likely to be-
come the ideal venue for transcatheter car-
diovascular therapy. Transcatheter aortic
valve implantation will gradually encour-
age further innovations as the revolution
in transcatheter management of cardiovas-
cular diseases matures. Myocardial condi-
tioning with volatile anesthetics and levo-
simendan significantly protect the heart
against ischemia to improve perioperative
outcomes. Remote ischemic conditioning
appears is not only safe and effective but
also is the subject of multiple ongoing peri-
operative trials. Perioperative angiotensin
blockade and anemia significantly worsen
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
outcome after CABG. off-pump CABG
with experienced perioperative teams may
improve outcomes in high-risk patients.
Endoscopic saphenous vein harvesting
may compromise graft patency. The man-
agement of STEMI should almost always
include PCI, but the evidence for IABP in
this important disease is far less conclu-
sive.
The novel platelet blockers prasugrel and
ticagrelor are likely to transform current
practice of antiplatelet therapy in cardio-
vascular diseases. Although PCI is a rea-
sonable option in multivessel CAD, CABG
offers a survival advantage in diabetics and
the elderly. Hetastarch and n-acetylcyste-
ine may worsen bleeding and transfusion
in cardiac surgery. Although factor VII can
arrest massive bleeding, further trials are
required to explore its safety. Recent ran-
domized trials have shown that fenoldo-
pam, atrial natriuretic peptide and sodium
bicarbonate are significantly nephropro-
tective in cardiac surgery. Although peri-
operative glucose management (goal glu-
cose level ≤180 mg/dL) improves outcome
in adult cardiac surgery, this benefit is not
universal across all hospital settings. More
intensive insulin therapy is not indicated
since it does not improve outcome and car-
ries a significant hypoglycemic risk. The
year 2009 has witnessed major advances
cardiothoracic and vascular anesthesia
with new devices, new clinical venues, and
new drugs.
No conflict of interest acknowledged by the authors.
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 proceedings
in Intensive Care
Cardiovascular Anesthesia

rEviEw ArticlE
Endorsed by

93
post cardiac arrest therapeutic
hypothermia in adult patients, state
of art and practical considerations
P.F. Beccaria1, S. Turi1, M. Cristofolini2, S. Colombo1, C. Leggieri1,
F. Vinciguerra1, A. Zangrillo1
Department of Anaesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milano, Italy;
1

Department of Anaesthesia and Intensive Care, Ospedale Santa Chiara, Trento, Italy
2

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 93-103

AbStrAct
The importance of therapeutic hypothermia in selected categories of patients has been widely demonstrated.
Laboratory, animal, and human studies permitted to understand the molecular mechanisms underlying cool-
ing and its importance in preventing the ischemia/reperfusion injury of the brain. The development of new
technologies offered the possibility to reach the desired temperature effectively and rapidly, reducing related
side effects. nevertheless, the application of systematic protocols of cooling has not been adequately reached
in many hospitals. In this paper the most recent findings regarding hypothermia, its physiological bases and
ways of application are reviewed.

Keywords: therapeutic hypothermia, cardiac arrest, ischemia-reperfusion injury, neuroprotection, cooling, re-
warming.

out-of-hospital cardiac arrest claims
225,000 lives each year in the United States
and a similar number in Europe, accounting
for about half of all deaths due to cardiovas-
cular disease (1). Even when resuscitation
efforts are successful, recovery is too often
limited by post-anoxic encephalopathy.
The interest regarding hypothermic thera-
py to protect brain after cardiac arrest start-
ed in late ’50s of the past century and the
first publication dates 1959 (2).
In spite of promising evidences, mostly be-
cause of the absence of simple and reliable
Corresponding author:
Paolo federico Beccaria
Department of Anaesthesia and Intensive Care,
Università Vita-Salute San Raffaele
Via olgettina, 60 - 20132 Milan, Italy
email: beccaria.paolo@hsr.it
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
cooling methods, apart from some farsee-
ing and lonely voices as Peter Safar (3), the
curtain falls over therapeutic hypothermia
(TH) in the following decades.
After almost forty years of oblivion, inter-
est in cooling was rekindled in the early
1980s by the positive results from animal
experiments suggesting that neurological
outcome could be improved by using mild
to moderate hypothermia (31°C-35°C)
rather than deep hypothermia (30°C), with
far fewer and less severe side effects (4-6).
following the promising results obtained
from laboratory and animal models, in
2002 two important randomized multicen-
tric studies on humans were realized (7, 8).
In the first, the European Hypothermia af-
ter cardiac arrest study group enrolled 275
patients, with 137 patients randomly as-
 P.F. Beccaria, et al.
94 signed to the hypothermia group and 138
to the normothermia group. (i.e., the group
that received standard care after resusci-
tation). The study included only patients
who had been resuscitated after witnessed
out-of-hospital cardiac arrest due to ven-
tricular fibrillation (Vf) that were random-
ly assigned to undergo TH (target bladder
temperature, 32°C to 34°C) over a period
of 24 hours or to receive standard treat-
ment with normothermia. The tempera-
ture was maintained at 32°C to 34°C for
24 hours from the start of cooling, followed
by passive rewarming, which was expect-
ed to occur over a period of 8 hours. This
study demonstrated that systemic cooling
increases the chance of survival and of a fa-
vorable neurological outcome, as compared
with standard normothermic life support
without significant differences in terms of
complications in the two groups.
In the second study 77 patients who re-
mained unconscious after resuscitation
from out of hospital cardiac arrest were
randomly assigned to treatment with hy-
pothermia (33° C core body temperature
for 12 hours) or normothermia. In the TH
group 49% survived with a good outcome
(home or rehabilitation facility discharge)
compared with the 26% (P=0.046) of the
normothermia group.
Considering these results, the 2005 Ameri-
can Heart Association guidelines for car-
diopulmonary resuscitation and post resus-
citation support concluded that clinicians
should not actively rewarm hemodynami-
cally stable patients who spontaneously de-
velop a mild degree of hypothermia (33°C)
after resuscitation from cardiac arrest (9).
The same guidelines state that mild hypo-
thermia may be beneficial to neurologic
outcome and is likely to be well tolerated
without significant risk of complications.
In a select subset of patients who were
initially comatose but hemodynamically
stable after a witnessed Vf cardiac arrest
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
of presumed cardiac etiology, active induc-
tion of hypothermia was beneficial (class
IIa). Similar therapy may be beneficial for
patients with non-Vf arrest out of hospital
or for in-hospital arrest (class IIb).
Although eight years passed from the origi-
nal publications and several studies clari-
fied many mechanism of TH and described
feasibility and efficacy of different cooling
methods (10, 11), this therapeutic approach
is far from being extensively and widely
used in everyday practice.
In a survey carried out in 2005 in the US
(12), of 265 physician (practicing emer-
gency medicine, critical care and cardiol-
ogy) who were asked if they had ever used
TH after cardiac arrest, 87% answered
no. Among reasons for non-use they men-
tioned not enough data to support TH,
non-inclusion in ACLS protocol or techni-
cal difficulties.
While a recent survey carried out on all
UK intensive care units showed that 85%
of departments considered TH as a part of
post cardiac arrest management with a ma-
jor implementation in use on the last three
years (13), another recent review under-
lined that an informal online survey of car-
diology conference attendees showed that
20% of respondents were even aware of the
American Hospital Association guidelines
(14).
Many studies tried to identify the reasons
why, despite scientific evidence, TH fa-
tigues to reach a routinely utilization. A
recent study conducted on a 43 Canadian
hospital network identifies some pivotal
elements: lack of familiarity and availabil-
ity of concrete TH protocols, availability
of equipment, equipment costs, and higher
workload demands for emergency nurses
are the most perceived barriers. Awareness
of these general, individual and local bar-
riers may improve adherence to evidence-
based practice (15).
Moreover, the majority of out-of-hospital
 post cardiac arrest therapeutic hypothermia
cardiac arrest patients nowdays are con-
ducted to emergency medical services with
non-Vf (pulseless electrical activity, asys-
tole) as the initial cardiac rhythm, for this
reason, clinicians have to decide whether
or not to use TH in this patient group, con-
sidering the feasibility, possible benefit, and
potential adverse side effects of hypother-
mia in patients with neurological injury
who have been resuscitated from non-Vf
cardiac arrest (16).
Some studies tried to evaluate feasibility and
efficacy of TH in other medical emergency
situations and with cardiac arrest presenta-
tion rhythms different from Vf (17-19), al-
though some authors believe that it will be
difficult to find significant evidence due to
the low incidence and poor outcome of this
condition. As Bernard maintains, these tri-
als would require a very large sample size to
detect a significant change in an important
outcome measure such as survival with
good neurological function.
Bernard et al suggest that, considering the
few adverse effects related to the use of hy-
pothermia and their relatively easy man-
agement, it would appear reasonable for
clinicians to cool most patients with sus-
pected neurological injury following pro-
longed cardiac arrest, whatever the initial
cardiac rhythm (20).
Since a recent retrospective study (21) con-
ducted on 491 patient shows no significant
improvement in neurologic outcomes in
patients whose initial rhythm was different
from Vf, further prospective studies are
needed to clarify whether TH is effective
also in asystole and pulseless electrical ac-
tivity or not.
Another key point for the future is the iden-
tification of poor and good outcome predic-
tors after TH post cardiac arrest. Glasgow
Coma Scale monitoring and particularly
motor response from third day after cardiac
arrest remains a powerful tool to predict
outcome of patients treated with TH (22).
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
Promising data come from the utilization of 95
bispecrtal index (BIS) and suppression ra-
tio during TH as an early predictor of neu-
rologic outcome (23, 24).
for the future, larger prospective studies
are needed to re-assess the validity of tradi-
tional clinical, biochemical and instrumen-
tal outcome predictors in patients treated
with hypothermia and the identification of
good outcome predictors is of paramount
importance.
mEchAniSmS of Action
Animal and laboratory findings during
1980s and 1990s allowed a better knowl-
edge of the molecular mechanisms under-
lying hypothermia, helping to define ad-
equate strategies of cooling and to prevent
possible side effects.
In the 1950s and 1960s, when the first
procedures of cooling were realized, it was
presumed that the beneficial effects of hy-
pothermia were related to the reduction of
brain metabolic requests (25). Although
this statement is correct (a decrease in ce-
rebral metabolism by 6% to 10% for each
grade of body temperature reduction has
been observed) this is not the unique in-
volved mechanism (26).
Brain damages after a cardiac arrest may be
considered as a model of ischemia-reperfu-
sion injury. Animal and laboratory findings
during ’80s and ’90s showed an increase in
apoptosis, a dysfunction in mitochondrial
activity, and an alteration in ion pump
function controlling the influx of calcium
into cells (27). During cooling an inhibition
of caspase enzyme activation, a prevention
of mitochondrial dysfunction, a decreased
overload of excitatory neurotransmitters,
and a modification of intracellular ion con-
centrations were observed, (28, 29). Im-
mune system is also activated in the injured
brain. one hour after the ischemic insult
 P.F. Beccaria, et al.
96 an increase of inflammatory molecules (in-
terleukin-1, tumor necrosis factor alpha)
released by microglia, endothelial cells and
astrocytes is detectable (26). This phe-
nomenon is associated to chemotaxis and
complement system activation facilitating
neutrophil, macrophages and monocytes
passage trough the endothelium (30).
numerous animal experiments and some
clinical studies showed that hypothermia
suppresses ischemia-induced inflammatory
reactions and release of pro-inflammatory
cytokines and decreases the production of
nitric oxide, which is a key agent in the
development of post-ischemic brain injury
(31). In addition, hypothermia can impair
neutrophil and macrophage function, re-
ducing white blood cell count (32).
Another mechanism of damage is related
to the increase of free radicals such as su-
peroxide, peroxynitrite, hydrogen peroxide,
and hydroxyl radicals that play an impor-
tant role in determining whether injured
cells will recover or die (33). Cooling seems
to reduce the production of free radicals and
to mitigate the damage, allowing the cells a
better recovery after injury. This function
and the ability in preserving the integrity of
blood-brain barrier also determine a reduc-
tion of cerebral edema and the consequent
intracranial hypertension (34).
In addition, brain glucose utilization is af-
fected by ischemia-reperfusion, and there
is evidence suggesting that hypothermia
can improve brain glucose metabolism; in
particular the ability of the brain to utilize
glucose (35).
A disruption in equilibrium of vaso-active
substances such as endothelin, thrombox-
ane A2 (TxA2), and prostaglandin I2, fol-
lowing an ischemic or traumatic event, can
lead to vasoconstriction, hypoperfusion,
and thrombogenesis in injured areas of the
brain (36, 37).
Several studies showed how hypothermia
affects the local secretion of these agents in
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
the brain and in other sites reproducing the
natural haemostasis of vasoactive agents
(38).
In some patients, during the post-ischemic
phase, it is also detectable an epileptic ac-
tivity, probably associated to the ongoing
brain damage. Hypothermia is associated to
a reduction in the convulsive activity, pro-
viding an adequate neuro-protection (39).
Hypothermia increases the expression of
the so called immediate early genes, which
are a part of the protective cellular stress
response to injury, and stimulates the in-
duction of cold shock proteins, which can
protect the cell from ischemic and traumat-
ic injury (40). Ischemia-reperfusion also
leads to substantial rises in cerebral lactate
levels that are shown to be reduced during
cooling (41). The importance of the protec-
tive effect of hypothermia on the brain can
also be deduced by the observation that fe-
ver is associated with an increase risk for
adverse outcome, worsening mortality in
brain injures (42).
Cooling strategy
Thanks to a better knowledge of hypother-
mia mechanisms a rationale approach and
management of cooling strategy was es-
tablished and three main phases identified
(43).
The first is the induction phase, with the
target to reach a mild hypothermia (a core
temperature between 32°C-34°C), as soon
as possible. Some animal experiments
suggest that neuro-excitotoxicity can be
blocked or reversed only if the treatment
is initiated in the very early stages of the
neuro-excitatory cascade (44). other stud-
ies have reported somewhat wider time
frames, ranging from 30 minutes to up to 6
hours (45). The possibility of reaching hy-
pothermia in the field for out-hospital car-
diac arrest is still object of debate. one not
adequately powered trial demonstrated a
trend toward a better neurological outcome
 post cardiac arrest therapeutic hypothermia
when cooling was started out-of-hospital
with 4°C saline rapid infusion (17), and
preliminary data from the PRInCE study
showed that cooling before RoSC with a
nasal cooling device is feasible, and in se-
lected groups of patients allowed higher
neurologically intact survival rate when
compared with TH started in hospital (19).
The second phase is the maintenance one,
with the aim to maintain core temperature
as close as possible to the target (maximum
fluctuation 0,2-0,5 0C).
The third phase is the rewarming period,
which consists in a slow and controlled re-
turn to normothermia (0,2-0,3 0C/h). This
phase starts 24 hours after hypothermia in-
duction and ends when the patient reaches
normothermia. Slow de-cooling avoids vio-
lent hemodynamic fluctuations and electro-
lytes disorders and prevent hypoglycemia
due to increased insulin sensitivity. More-
over some studies (46, 47) suggest that rap-
id rewarming could reverse some protective
effects of hypothermia while a significant
decrease in jugular venous oxygen satu-
ration during rapid rewarming of patient
following cardiac surgery is demonstrated
(48, 49), and the incidence and severity of
jugular bulb desaturation may be lessened
by a slower rewarming.
Each TH phase is characterized by physi-
ological changes. Shivering is a protective
strategy activated by human organism in
contrast to temperature loss and leads to an
undesirable increase in metabolic rate and
oxygen consumption (50).
Its prevention and aggressive treatment
requires subsequent steps: a rapid cooling
below 34°C, magnesium administration,
adequate sedation and analgesia, and even-
tually neuromuscular blockade (51). Some
authors describe benefits from skin warm-
ing during cooling (52). Shivering preven-
tion and treatment is of paramount impor-
tance to avoid TH benefits loss.
During mild to moderate hypothermia
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
(32°C-34°C), cardiac output decreases by 97
25% to 40%, mainly due to a decrease in
heart rate; since metabolic decrease exceeds
cardiac output reduction, overall circula-
tory system result unchanged or improved.
At 32°C heart rate usually decrease around
40-45 beats per minute and when heart
rate is allowed to decrease, systolic function
usually increases. Conversely myocardial
contractility decreases when chronotrop-
ic agents are administrated or a pacing is
placed; if an increase in heart rate is nec-
essary rewarming the patient to a slightly
higher temperature may be sufficient. oc-
currence of malignant arrhythmias is de-
scribed only for severe hypothermia (53,
54).
The increase in venous return induced by
hypothermia can lead to activation of atrial
natriuretic peptide and a decrease in the
levels of anti-diuretic hormone leading to
a marked increase in diuresis, which may
lead to hypovolemia, renal electrolyte loss,
and hemoconcentration with increased
blood viscosity (55). Hypovolemia is the
most frequent cause of haemodinamic in-
stability during the induction phase, its pre-
vention and prompt treatment is of pivotal
importance (56).
Hypothermia also induces electrolytic dis-
orders: during the induction phase potas-
sium and magnesium levels decrease due to
urinary loss and intracellular shift. While
electrolytes correction may prevent ar-
rhythmias, it is necessary to consider that
in the rewarming phase electrolytes move-
ment occur in the opposite direction (57).
In cooled patients a reduction in metabo-
lism is also observed. Caloric intake and
mechanical ventilation should be decreased
in order to balance o2 and Co2 and to avoid
alterations that can worse the ischemic/re-
perfusion injury (58).
A decreased insulin secretion and, in many
patients, a moderate (and sometimes se-
vere) insulin resistance is observed. This
 P.F. Beccaria, et al.
98 can lead to hyperglycaemia and/or a signifi-
cant increase in doses of insulin required
to maintain glucose levels within an accept-
able range (59).
Despite standard coagulation tests will
show no abnormalities unless they are per-
formed at the patient’s actual core temper-
ature, due to effects on platelet count and
function, kinetics of clotting enzymes and
other steps in the coagulation cascade, hy-
pothermia produces a mild bleeding diathe-
sis (60-64).
Hypothermia begins to affect platelet func-
tion only when temperature decrease be-
low 35°C, and other coagulation factors are
affected when temperature decrease below
33°C (60-64); the risk of clinically signifi-
cant bleeding induced by hypothermia in
patients who are not already actively bleed-
ing is very low.
Drugs clearance is affected by cooling, the
half-life is increased and higher plasmatic
concentrations are achieved with the same
doses (64). This must be kept on mind
while administrating sedatives, analgesics,
neuromuscular blockade agents or other re-
quired medicaments.
Multiple evidences show that hypothermia
can suppress epileptic activity (65-67), even
if during TH antiepileptic medicaments are
administered for patient sedation, continu-
ous EEG monitoring is recommended when
seizures or non-seizures epileptic activity is
suspected, especially when muscle relaxant
are required for shivering control.
Hypothermia impairs immune functions
and inhibits various inflammatory re-
sponses, increasing the risk of infections
(68). Incidence of pneumonia is described
to increase in some cases, particularly for
prolonged hypothermia and some authors
suggest prophylactic treatments. Appropri-
ate attention must be taken in wound care
(68).
other minor alteration, like transient im-
paired bowel function or amylase count oc-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
curs but they normalize once normothemia
is reached.
In table 2 a list of laboratory and instru-
mental tests we use in our department to
monitor and prevent changes, side effects
and potential complications due to TH.
Cooling methods
After having identified patient to cool and
excluded conditions that contraindicate
TH (Table 1), clinicians should start cool-
ing as soon as possible and should consider
the different options to get the target tem-
perature.
needs for other procedures such as percu-
taneous coronary intervention shouldn’t
delay cooling, as TH during percutanue-
ous transluminal coronary angioplasty is
shown to be feasible and safe (69).
table 1 - Indications and contraindications to thera-
peutic hypothermia.
indicAtionS:
•• Return of Spontaneous Circulation (RoSC) af-
ter cardiac arrest (any rhythm of presentation,
any location)
•• Coma (does not open eyes to pain, does not fol-
low verbal command)
•• Age ≥18
contrAindicAtionS:
•• Time from RoSC >6 h
•• other possible causes for coma (stroke, intoxi-
cation, head trauma, hypoglicaemia, seizures)
•• Significant pre-existing neurologic impairment
•• Systolic arterial pressure <90 mmHg despite
fluids and vasopressors
•• Refractory Ventricular Arrhythmia
•• Pre-existing coagulopaty or severe bleeding
(Disseminated Intravascular Coagulation, se-
vere thrombocytopenia, liver failure)
noTE: anticoagulant and antiplatelet therapy
are not a contraindication
•• Pregnancy
•• Sepsis
•• Known pre-existing terminal illness
SuSpEnd cooling protocol whEn:
•• sepsis or pneumonia
•• refractory haemodynamic instability
•• severe refractory arrhythmia
 post cardiac arrest therapeutic hypothermia

table 2 - Timetable for laboratory and instrumental tests in use in our institute. 99
time from th induction (h) 0 2 8 12 16 24 36 48 72
Blood Urea nitrogen Creatinine ⊗ ⊗ ⊗ ⊗
Albumin, Proteinaemia ⊗ ⊗ ⊗ ⊗
Creatine Phosphokinase ⊗ ⊗ ⊗ ⊗ ⊗ ⊗
Aspartate Transaminase
Alanine Transaminase Lactate ⊗ ⊗ ⊗ ⊗ ⊗ ⊗
dehydrogenase bilirubin
Creatine Kinase Myocardial
⊗ ⊗ ⊗ ⊗ ⊗ ⊗
Band isoenzyme, Troponin
Coagulation tests ⊗ ⊗ ⊗ ⊗
Amylase, lipase ⊗ ⊗ ⊗
Lactate ⊗ ⊗ ⊗ ⊗
Complete Blood Count ⊗ ⊗ ⊗ ⊗
Arterial Blood Gas
⊗ ⊗ ⊗ ⊗ ⊗ ⊗ ⊗ ⊗
+ electrolytes + glycaemia
Electrocardiography ⊗ ⊗ ⊗ ⊗ ⊗ ⊗
Echocardiography ⊗ ⊗
Chest X-Ray ⊗ ⊗
Electroencephalography
⊗
(continuous when needed)
Evoked potential ⊗
Computed Tomography scan
(if need to exclude other causes ⊗
for coma)

first of all a temperature probe must be po-
sitioned. The site chosen to measure core
temperature is of key importance. Pulmo-
nary artery catheter is the gold standard for
core temperature detection but risks linked
to the procedure must be considered; oe-
sophageal and bladder probes are less pre-
cise and slower in detecting temperature
changes but widely used due high correla-
tion to core temperature, relative simple po-
sitioning and few side effects.
Tympanic probes are also used, particu-
larly indicated for out-of-hospital measure-
ments, they are quick and easy to place,
may reflect brain temperature but readings
sometimes may be inaccurate.
The best way to achieve rapid cooling, tem-
perature maintenance and a slow and con-
trolled rewarming is to integrate different
cooling methods.
Administration of cold fluids in the induc-
tion phase is a common, practical, effective,
safe and cheap procedure. A rapid bolus of
20-30 ml/kg 4°C isotonic saline solution is
effective in decreasing temperature and its
use is supported by multiple evidences in
pre-hospital setting as in emergency depart-
ment (70-74).
Modern cooling devices work in a con-
trolled feedback manner, continuously
measuring patient’s temperature and con-
sequently changing the temperature of the
cooling elements (catheters, pads, or blan-
kets).
Intravascular cooling devices permit to
achieve a tight temperature control but are

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 P.F. Beccaria, et al.
100 affected by risks and complications of cen-
tral venous catheterization (75, 76).
Surface cooling devices allow a good tem-
perature control, are well tolerated and
relative safe because of the infrequency of
overcooling and lack of vascular catheter-
ization complications and are useful for
maintenance of normotermia after cooling
(70). Both this kind of devices represent, at
the moment, the best and preferred choice
for the maintenance and rewarming period.
Preliminary data from the PRInCE study
show that intranasal cooling in feasible and
effective and more studies are needed to
confirm benefits on outcome when used in
out-of-hospital setting (19).
Low cost methods as covering the patient
with ice or placing ice packs on groin, neck
and axillas are also used. Those techniques
are cheap but lack in loop control with the
core body temperature and expose the pa-
tient to an overcooling risk, don’t allow a
tight temperature control, don’t allow a
controlled rewarming and produce an extra
workload for nurses.
other methods like body cavity lavage,
whole-body ice water immersion, cooling
helmets or extracorporeal devices are less
used due to lack in efficacy or higher risks
and costs/effectiveness (77).
concluSionS
Beneficial effects of mild TH in patients
with a witnessed fV cardiac arrest are
clearly demonstrated. However, a wide-
spread use of TH in daily practice is still far
to be reached, as demonstrated by several
surveys. Reasons may be related to general,
individual and local barriers.
Lack of institutional protocols, lack of
agreement with supporting evidence, ab-
sence of adequate instrumentation useful
to reduce nurse work load and optimize
management are the most perceived barri-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
ers. Extensive and rapid diffusion of pro-
tocols and process issues, further training
and more studies in this field are essential
key points for new developments and TH
application increasing.
No conflict of interest acknowledged by the authors.
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hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 proceedings
in Intensive Care
Cardiovascular Anesthesia

rEviEw ArticlE
Endorsed by

105
volatile anaesthetic myocardial
protection: a review
of the current literature
E. Lin, J.A. Symons
Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Monash University; Melbourne, Australia

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 105-109

AbStrAct
Ischaemic preconditioning is a powerful innate adaptive phenomenon whereby brief periods of sublethal isch-
aemia result in marked tolerance to subsequent lethal ischaemia. Halogenated anaesthetics have been shown
to mimic ischaemic preconditioning, modifying and attenuating ischaemia reperfusion injury.
This review aims to present the current animal and human data, discuss the possible mechanisms of action
and review the clinical evidence for volatile anaesthetic-induced myocardial protection.
There is class Ia evidence for the myocardial protective properties of sevoflurane and desflurane in low risk
patients undergoing coronary artery bypass grafting surgery.
These volatile anaesthetics have been shown to improve clinical outcomes and health economics following
cardiac surgery, reducing intensive care and hospital stay. The evidence for the benefit of volatile anaesthetics
in non-cardiac surgery is less robust and further large randomized controlled trials are required to elucidate
this question.

Keywords: volatile anaesthetics, myocardial protection, ischaemic preconditioning, mechanisms, cardiac anaes-
thesia, outcomes.

introduction Mechanism of myocardial protection

There is strong evidence for volatile anaes-
thetic induced myocardial protection in ex-
perimental studies.
Despite this weight of evidence in animal
studies, the translational into human trials
has borne less consistent results.
This review aims to present the current an-
imal and human data, discuss the possible
mechanisms of action and review the clini-
cal evidence.
Corresponding author:
Joel A Symons, MD
Department of Anaesthesia and Perioperative Medicine,
Alfred Hospital, Monash University
Victoria, 3800 - Melbourne, Australia
e.mail: j.symons@alfred.org.au
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
Ischaemic preconditioning is a powerful in-
nate adaptive phenomenon discovered by
Murry and colleagues (1), whereby brief
periods of sublethal ischaemia results in
marked tolerance to subsequent lethal isch-
aemia. Halogenated anaesthetics have been
shown to mimic ischaemic precondition-
ing, modifying and attenuating ischaemia
reperfusion injury (2).
Two periods of ischaemic preconditioning
have been described; early or classical pre-
conditioning that occurs immediately, and
induces potent protection that lasts one to
two hours.
Late preconditioning or the second win-
dow of preconditioning occurs 24 hours
after the initial stimulus, induces a less pro-
 E. Lin, J.A. Symons
106 nounced cardio-protection, but lasts for up
to 72 hours (3).
Early and late preconditioning probably
involves different signalling pathways that
have yet to be fully elucidated. Early pre-
conditioning is thought to involve opening
mitochondrial ATP dependent potassium
channels (4-9), increasing mitochondrial
reactive oxygen species (4, 10, 11), decreas-
ing cytosolic and mitochondrial calcium
loading (12), protection of endothelial
coronary cells by mediating nitric oxide
release (13) and by suppressing neutrophil
activation and the neutrophil-endothelium
interactions that cause myocardial dysfunc-
tion (14, 15).
Pathways of late preconditioning involve
attenuation of nuclear factor kB (nfkB),
activation and reduced expression of tu-
mour necrosis factor k (Tnfk), interleu-
kin 1 (IL1), intracellular adhesion mol-
ecules, enoS, a reduction of the hyper-
contraction that follows reperfusion and
activation of anti-apoptotic kinases (Akt,
ERK 1-2) (2).
Volatile anaesthetics have been shown in a
number of animal ex vivo and in vivo ex-
periments to be able to precondition the
myocardium in a similar way to classical
ischaemic preconditioning. Similarly, vol-
atile anaesthetics have the ability to post-
condition the myocardium whereby ex-
posure to volatiles during the reperfusion
period also protects the myocardium (16).
There is now increasing evidence that vola-
tile anaesthetics can induce late precondi-
tioning, raising the potential of myocardial
protection that persists after the exposure
in the operating theatre (16, 17).
In addition to the ability to precondition
the myocardium, all volatile anaesthet-
ics induce a dose dependent decrease in
myocardial contractility, decrease myocar-
dial oxygen demand and therefore improve
myocardial oxygen balance during isch-
aemia. It is often difficult to experimental-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
ly separate these two protective effects of
volatile anaesthetics on the myocardium.
This is best demonstrated by the fact that
studies have also suggested the maximum
protection is yielded by the administration
of volatile anaesthetics throughout the op-
erative procedure (18).
Clinical evidence in cardiac surgery
Since 1985, when freedman and colleagues
(19) reported that enflurane could im-
prove post-ischemic myocardial recovery,
there has been extensive research into the
potential benefits of anaesthetic myocar-
dial protection in both animal and human
models. The majority have been performed
on patients undergoing CABG (coronary
artery bypass grafting). Unfortunately, to
date, these studies have been observational
in nature or if randomized have been too
small and underpowered to identify effects
on significant outcomes such as myocardial
infarction and mortality. Studies have gen-
erally used surrogate markers for myocardi-
al protection such as the cardiac troponins
as a measure of myocardial injury.
To date there have been 3 meta-analyses
performed including only randomized con-
trolled trials (RCTs) to try and answer the
question does volatile anaesthesia improve
outcomes in coronary surgery?
Yu and Beattie performed the first meta-
analysis in 2006 (20). The authors identi-
fied 32 randomized studies involving 2841
patients. Volatile anaesthetics included hal-
othane, enflurane, isoflurane, sevoflurane
and desflurane and were administered in
any combination of the pre-bypass, during
bypass and post-bypass periods. When com-
pared with intravenous anaesthetics, those
who were exposed to volatile anaesthetics
had an observed reduction in mortality that
did not reach statistical significance (oR,
0.65; 95% CI 0.36-1.18). furthermore, re-
moving studies that used halothane or en-
flurane in their study protocols also failed

to show a statistically significant reduction
in mortality. Similarly, no statistical differ-
ence was seen in the incidence of AMI be-
tween groups. However, post hoc analysis
of patients that received sevoflurane or des-
flurane showed that these patients experi-
enced significantly less Troponin I leakage
than patients receiving intravenous anaes-
thesia.
Symons and Myles performed a similar
meta-analysis in 2006 (21). They identified
27 randomized studies including 2979 pa-
tients comparing volatile with non-volatile
anaesthesia for CABG. Volatile anaesthetics
again included halothane, enflurane, isoflu-
rane, sevoflurane and desflurane and were
administered during pre-bypass, bypass and
post-bypass periods. There was no signifi-
cant difference between volatile and non-
volatile anaesthetic groups with respect to
death, myocardial infarction, myocardial
ischaemia or ICU length of stay. However,
patients randomized to receive volatile an-
aesthetics had significantly higher cardiac
indices, lower troponin I concentrations,
reduced requirement for inotropic support,
shorter duration of mechanical ventilation
and shorter length of hospital stays than
those randomized to receive intravenous
anaesthetics. The results indicated that
volatile anaesthetics may indeed be able to
change outcomes in cardiac surgery.
More recent animal evidence suggests that
sevoflurane and desflurane display more
prominent cardioprotection than the older
halogenated anaesthetics (22-26). This lead
to the most recent meta-analysis performed
by Landoni and colleagues in 2007 (27).
Their group identified 22 randomised stud-
ies involving 1922 patients where compari-
sons of the modern volatile anaesthetics
sevoflurane and desflurane were made with
intravenous anaesthesia in CABG surgery.
Most studies were performed on patients
undergoing on-pump CABG and most au-
thors administered the volatile anaesthet-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
volatile anaesthetic myocardial protection
ics throughout the entire procedure. only 107
a few of the RCTs were of high quality and
all the studies included numbers that were
too small to allow for assessment of impor-
tant clinical outcome variables such as AMI
and death.
Data pooling and analysis showed that
when compared with intravenous anaes-
thesia, sevoflurane and desflurane were
associated with significant reductions in
the rates of all major clinical outcome vari-
ables. Volatile anaesthesia significantly re-
duced the degree of troponin I leakage (oR
0.47; 0.29, 0.76). Importantly, the risk of
all-cause mortality and AMI was also sig-
nificantly reduced by volatile anaesthesia
(oR 0.31; 0.12,0.80 and oR 0.51; 0.32,0.84
respectively). furthermore, the use of sevo-
flurane and desflurane was associated with
a significant reduction in the duration of
mechanical ventilation, length of ICU stay
and time to hospital discharge.
Though this represents strong class Ia evi-
dence for myocardial protection with mod-
ern volatile anaesthetic agents in patients
undergoing CABG, results from a large ob-
servational study published in 2007 are not
quite so conclusive. Data from a retrospec-
tive Danish database of 10,535 patients un-
dergoing cardiac surgery with sevoflurane
or propofol anaesthesia showed no differ-
ence in overall post-operative mortality or
myocardial infarction (28). The group sur-
mise that both propofol and sevoflurane
have different cardioprotective properties.
Sub-group analysis revealed that in patients
undergoing non-coronary cardiac surgery,
sevoflurane was superior to propofol whilst
propofol was superior to sevoflurane in
patients with severe ischaemia, cardiovas-
cular instability or those requiring urgent
surgery. This finding may reflect the anti-
oxidant properties of propofol and the isch-
aemic preconditioning effect of unstable
angina negating the myocardial protection
offered by volatile anaesthesia.
 E. Lin, J.A. Symons
108 Clinical evidence in non-cardiac surgery
Landoni and colleagues performed a meta-
analysis of RCTs comparing sevoflurane or
desflurane anaesthesia with intravenous
anaesthesia in adult patients undergoing
non-cardiac surgery in 2007 (29). Seventy-
nine studies and over 6000 patients were
included in the analysis but firm conclu-
sions could not be made due to the low
incidence of cardiovascular events in both
groups.
nevertheless, the most recent American
College of Cardiology/American Heart As-
sociation Guidelines recommend the use
of volatile anaesthetic agents during non-
cardiac surgery in patients at risk for AMI
(Class IIa, level B) (30).
concluSionS
There is class Ia evidence for the myocardi-
al protective properties of sevoflurane and
desflurane in low risk patients undergoing
coronary artery bypass grafting surgery.
The modern volatile anaesthetics have
been shown to improve clinical outcomes
and health economics following cardiac
surgery, reducing intensive care and hospi-
tal stay.
The evidence for the benefit of volatile
anaesthetics in non-cardiac surgery is less
robust and further large randomized con-
trolled trials are required to elucidate this
question. furthermore, volatile anaesthetic
protection of organs other than the heart
warrants further investigation.
No conflict of interest acknowledged by the authors.
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 C E A SPA

PRESIDI MEDICO-CHIRURGICI
20133 Milano - Piazza Carlo Donegani, 1
DIVISIONE OSPEDALIERA: Viale Europa, 28 - Milano Oltre 2 - 20090 Segrate
Tel. 02.26.92.70.11 - Fax 02.21.39.000
http://www.cea-spa.it/ - E-mail: info@cea-spa.it
 proceedings
in Intensive Care
Cardiovascular Anesthesia

originAl ArticlE
Endorsed by

111
fenoldopam to prevent renal
replacement therapy after cardiac
surgery. design of the fEno-hSr study
G. Landoni¹, T. Bove¹, D. Pasero², M. Comis³, S. Orando4, F. Pinelli4, F. Guarracino5,
A. Corcione6, N. Galdieri6, M. Zucchetti7, E. Maglioni8, B. Biagioli8, G. Pala9,
M. Frontini10, F. Caramelli11, B. Persi12, M. Renzini13, F. Paoletti13, L. Lorini14,
A. Morelli15, G. Alvaro16, R. Bianco17, D. Pittarello17, A. Manzato10, G. Pedersini10,
A. Mizzi¹, N. Lojacono3, P. Leoncini3, T. Iovino6, C. Cariello5, R. Baldassarri5,
A.M. Camata12, G. Padua9, G. Frascaroli11, S. Leonardi7, E. Bignami¹, A. Zangrillo¹
¹ Università Vita-Salute San Raffaele, Milano; ²A.O.U. San Giovanni Battista, Torino; ³A.O. Ordine Mauriziano, Torino;
4
A.O.U. Careggi, Firenze; 5A.O. U. Pisana, Pisa; 6A.O. Vincenzo Monaldi, Napoli; 7A.O. Riuniti Papardo-Piemonte, Messina;
8
A.O.U. Senese Policlinico S. Maria alle Scotte, Siena; 9Ospedale Civile SS. Annunziata, Sassari; 10A.O. Spedali Civili di Brescia,
Brescia; 11A.O.U. Policlinico S. Orsola-Malpighi, Bologna; 12Ospedale Regina S. Maria dei Battuti, Treviso;
13
A.O. di Perugia - Ospedale S. Maria della Misericordia, Perugia, 14Ospedali Riuniti di Bergamo, Bergamo;
15
Università La Sapienza - Policlinico Umberto I, Roma; 16A.O. Mater Domini Germaneto, Catanzaro;
17
A.O. di Padova, Padova

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 111-117

AbStrAct
introduction: Acute kidney injury requiring renal replacement therapy is a serious complication following
cardiac surgery associated with poor clinical outcomes. Until now no drug showed nephroprotective effects.
fenoldopam is a dopamine-1 receptor agonist which seems to be effective in improving postoperative renal
function. The aim of this paper is to describe the design of the fEno-HSR study, planned to assess the effect
of a continuous infusion of fenoldopam in reducing the need for renal replacement therapy in patients with
acute kidney injury after cardiac surgery.
methods: We’re performing a double blind, placebo-controlled multicentre randomized trial in over 20 Italian
hospitals. Patients who develop acute renal failure defined as R of RIfLE score following cardiac surgery are
randomized to receive a 96-hours continuous infusion of either fenoldopam (0.025-0.3 µg/kg/min) or placebo.
results: The primary endpoint will be the rate of renal replacement therapy. Secondary endpoints will be:
mortality, time on mechanical ventilation, length of intensive care unit and hospital stay, peak serum creati-
nine and the rate of acute renal failure (following the RIfLE score).
conclusions: This trial is planned to assess if fenoldopam could improve relevant outcomes in patients un-
dergoing cardiac surgery who develop acute renal dysfunction. Results of this double-blind randomized trial
could provide important insights to improve the management strategy of patients at high risk for postoperative
acute kidney injury.

Keywords: fenoldopam, cardiac surgical procedures, acute renal failure, cardiac surgery, anesthesia, renal replace-
ment therapy.

Corresponding author:
Giovanni Landoni, M.D.
Department of Anaesthesia and Intensive Care,
Università Vita-Salute San Raffaele
Via olgettina, 60 - 20132 Milan, Italy
e.mail: landoni.giovanni@hsr.it
http://www.metcardio.org/cv/landoni/landoni.html
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
introduction
Acute renal failure (ARf) is a common as
well as life threatening complication in pa-
tients undergoing cardiovascular surgery
(1-3). Despite improvements in intensive
care treatments and dialysis technology,
 G. Landoni, et al.
112 the mortality associated with acute renal
failure requiring renal replacement therapy
(RRT) remains unacceptably high, though
once discharged from hospital long-term
mortality is low with satisfactory quality
of life in patients discharged from hospital
alive (4).
However no drug showed nephroprotective
properties translating into a reduction in
the incidence of renal replacement therapy
and mortality in a cardiovascular setting
(5).
fenoldopam mesylate is a benzazepine
derivative and a dopamine A-1 (DA-1) re-
ceptor agonist that seems to be effective
in improving postoperative renal function
(5). fenoldopam exerts hypotensive effects
characterized by a decrease in peripheral
vascular resistance, with increased renal
blood flow, diuresis and natriuresis; all
these effects are primarily related to acti-
vation of DA-1 receptors. other beneficial
renal effects of fenoldopam could be related
to other pharmacological properties that
are still under investigation such as an anti-
inflammatory effect (6).
A meta-analys (7) of 16 randomized con-
trolled trials including 1290 patients (622
receiving fenoldopam and 668 receiving
placebo or best available treatment, mostly
low dose dopamine) was recently conduct-
ed. five trials were performed in cardiac
surgery, three in vascular surgery, two in
liver and one in renal transplants, while
five trials were performed in the intensive
care unit (ICU) either in selected patients
with sepsis (two studies) or in the overall
ICU population.
fenoldopam dosage varied across studies,
between 0.025 µg/kg/min and 0.3 µg/kg/
min (in one study), mostly being adminis-
tered at a dosage of 0.1 µg/kg/min. All but 2
studies had a >12 h fenoldopam infusion,
with 8 studies reporting ≥2 days infusion
(median duration 48 h).
overall analysis showed that, in compari-
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
son to best medical therapy, fenoldopam us-
age reduces the risk of RRT (34/525 [6.5%]
in the fenoldopam group vs 59/569 [10.4%]
in the control arm, oR=0.54 [0.34-0.84],
p=0.007).
In a second meta-analysis (8) 13 clinical
studies comparing fenoldopam to placebo
or standard treatment in cardiovascular
surgery were included.
The studies enrolled a total of 1.059 patients
(528 received fenoldopam and 531 placebo
or best available treatment). fenoldopam
dosage varied across studies, being always
>0.03 µg/kg/min and most often 0.1 µg/
kg/min, reaching 0.3 µg/kg/min in a single
study.
All but 2 studies had a ≥24 hours fenoldo-
pam infusion, with 5 studies reporting ≥2
days of continuous application. overall
analysis showed that, in comparison to
best medical therapy, fenoldopam was as-
sociated with a significant reduction in the
rates of all major endpoints. Specifically,
fenoldopam usage reduced the risk of RRT
(30/528 [5.7%] in the fenoldopam group
vs 71/531 [13.4%] in the control arm;
oR=0.37 [0.23-0.59], p<0.001, number
needed to treat =13) and of in-hospital
mortality (28/501 [5.6%] in the fenoldo-
pam group vs 55/503 [10.9%] in the con-
trol arm (oR=0.46 [0.29-0.75], p=0.02,
number needed to treat =19).
Several studies suggested that fenoldopam
could have a nephroprotective action in
a cardiac surgery setting, even when it is
used before surgery (9-12), but they were
not powered enough to detect an improve-
ment in clinical relevant outcomes, such as
the need for renal replacement therapy or
mortality.
Scientific literature is not unanimous about
the protective properties of fenoldopam,
and there are also studies which showed
no improvement with administration of
fenoldopam in high-risk patients undergo-
ing cardiac surgery (13).

mEthodS
Study aim
Based on previous concerning the admin-
istration of fenoldopam in patients at high
risk for ARf (14), we are planning to ini-
tiate a large (1000 planned patients) mul-
ticentre, prospective, randomized, double-
blind, placebo controlled clinical study en-
rolling patients undergoing cardiac surgery
who will develop acute renal dysfunction.
our aim is to confirm the promising results
of the cited meta-analyses and to add evi-
dence based medicine to the supposed re-
nal protective properties of fenoldopam in
critically ill patients (7, 8).
Patients selection
We will enroll consecutive patients under-
going cardiac surgery who will develop an
acute renal failure after cardiac surgery.
Candidates for this study meeting the fol-
lowing criteria will be included: patients
who are able to understand and sign an in-
formed consent, aged 18 years or older, un-
dergoing cardiac surgery who will develop,
during the ICU stay an acute renal dysfunc-
tion designed as “R” of RIfLE score (50%
table 1 - RIFLE score for acute renal failure.
gfr* criteria
Risk increased creatinine x1.5
or GfR* decrease >25%
Injury increased creatinine x2
or GfR* decrease >50%
failure increased creatinine x3
or GfR* decrease >75%
or creatinine ≥4 mg/dl
(acute rise of ≥0.5 mg/dl)
Loss Persistent ARf#=complete loss
of renal function >4 weeks
ESRD End-stage renal disease
Abbreviations
* Glomerular filtration Rate
† Urine output
#
Acute Renal failure
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
fenoldopam and renal replacement therapy
postoperative increase in serum creatinine 113
and/or diuresis <0,5 ml/kg/h for 6 hours)
(Table 1).
Conversely, the following exclusion criteria
will be applied: previous unusual response
to fenoldopam, glaucoma, expected ICU
stay less than 24 hours after randomization,
RRT already started or planned before ran-
domization, “do not resuscitate” patients,
participation in other randomized studies
(within the previous 30 days), fenoldo-
pam administration within the previous 30
days, preoperative RRT or dialysis.
Study procedure
All patients planned to undergo cardiac sur-
gery who won’t have exclusion criteria will
be approached by a member of the research
team to sign the informed consent. failure
to obtain a signed informed consent will
make the patient ineligible for the study.
Treatment assignment between fenoldo-
pam and placebo will be determined by a
randomization in a ratio of 1:1. Randomiza-
tion will be performed by centrally provided
sealed opaque envelopes. To ensure that al-
most equal number of patients will receive
either treatment, randomization blocks of
uo† criteria
Uo† <0.5 ml/kg/min
for 6 hours
Uo† <0.5 ml/kg/min
for 12 hours
Uo† <0.3 ml/kg/min for 24 hours
or anuria for 12 hours
 G. Landoni, et al.

114 table 2 - A clinical score to predict acute renal failure urine output greater than 0.5 ml/kg/h, no
after cardiac surgery according to Thakar et al. (15). intravenous inotropic or vasopressor ther-
risk factor points apy aside from dopamine 5 µg/kg/min, and
female gender 1 no seizure activity. Criteria for hospital
discharge will be hemodynamic as well as
Congestive heart failure 1
respiratory recovery, the presence of clean
Left ventricular ejection fraction and dry incisions, afebrile condition, nor-
1
<35%
mal bowel movement, and independent
Preoperative use of Intra Aortic ambulation and regular oral nutrition.
2
Balloon Pump
Preoperative data will be collected according
Chronic obstructive Pulmonary
1 to the clinical score to predict ARf suggested
Disease by Thakar et al. (15) (Table 2), the Continu-
Insulin-requiring diabetes 1 ous Improvement in Cardiac Surgery Study
Previous cardiac surgery 1 score (CICSS) by Chertow et al. (16) (Table
3), the Simplified model to predict postop-
Emergency surgery 2
erative dialysis by Mehta et al. (17) (Table
Valve surgery only 1
Coronary Artery Bypass table 3 - The Continuous Improvement in Cardiac
2
Graft + valve Surgery Study score (CICSS) by Chertow et al. (16).
other cardiac surgeries 2 points
Preoperative creatinine 1.2 to Valvular surgery 3
2
<2.1 mg/dl Estimated creatinine clearance ml/min
Preoperative creatinine ≥2.1 mg/dl 5 ≥100 0
80-99 2
60-79 3
20 patients will be used. fenoldopam and 40-59 5
placebo (normosaline) will be identical in <40 9
shape, color, appearance and size.
Intra aortic ballon pump prior 5
Enrolled patients will be randomized in the to surgery
ICU after the development of an ARf de- Prior heart surgery 3
fined as “R” of RIfLE score, to a placebo or
nYHA* functional class 4 2
fenoldopam (Corlopam - Cephalon, Roma,
Italy) continuous infusion. Starting dose Peripheral vascular disease 2
will be 0.1 µ/kg/min (ranging from 0.025 Left ventricular ejection fraction <0.35 2
to 0.3 µg g/kg/min, according to mean ar- Pulmonary rales 2
terial pressure). Since the renal protective Chronic obstructive pulmonary disease 2
effect of fenoldopam seems to be related to Systolic blood pressure
the dose, it will be suggested to administer
120-139 0
at least 0.1 µg/kg/min.
140-159 0
The infusion will be maintained for 96
<120 and valvular surgery 2
hours or until the patient’s ICU discharge. <120 and CABG† 0
Transfer out of the ICU will be performed ≥ 160 and valvular surgery 0
with Spo2 ≥94% at an fio2 ≤0.5 by face- ≥ 160 and CABG† 3
mask, adequate cardiac stability with no Abbreviations
hemodynamically significant arrhythmias, * new York Heart Association
† Coronary Artery Bypass Graft
chest tube drainage less than 50 ml/h,

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 fenoldopam and renal replacement therapy

table 4 - The Simplified model to predict postoperative 4), and the Simplified Renal Index score 115
dialysis by Mehta et al. (18). by Wijeysundera et al. (18) (Table 5). Tele-
Score phone-based interviews will be performed at
Last serum creatinine (mg/dl) 1 month and 1 year after the procedure.
0.5 5
1.0 10 Study endpoints
1.5 15 The primary endpoint will be the rate of
2.0 20 RRT (continuous venous-venous hemofil-
2.5 25 tration or hemodialysis, according to center
3.0 30 guidelines and protocols). The theoretical
3.5 35 need for RRT will be documented as well as
4.0 and higher 40 defined as the presence of one of the follow-
Age ing parameters and symptoms: serum creati-
<55 0 nine >6 mg/dl during hospital stay; clinical
55-59 1 presentation of uremia, including altered
60-64 2 mental status, itching and/or severe nausea
65-69 3 and vomiting; hypoxia (oxygen saturation
70-74 4 <90% with fio2>=40% unresponsive
75-79 5 to diuretics); wedge pressure >25 mmHg;
80-84 6 hyperkalemia (>6.5 mmol/l or >6.0 after
85-89 7 treatment with cation-exchange resine; met-
90-94 8 abolic acidosis with bicarbonate levels ≤10
95-99 9 mEq/l inspite of endovenous bicarbonates
>100 10 administration. Secondary endpoints will
Surgery be represented by: mortality (in-hospital
CABG* only 0 mortality and telephone follow-up), time
Abbreviations on mechanical ventilation (hours), length
* Coronary Artery Bypass Graft
† new York Heart Association of ICU and hospital stay (days), peak serum
creatinine (mg/dl) and the rate of ARf (fol-
table 5 - A simplified predictive index for renal re- lowing the RIfLE score definition).
placement therapy after cardiac surgery suggested by
Wijeysundera et al. (18). Statistical analysis and sample
variable points size calculation
Estimated glomerular filtration rate 31- 1 An independent clinician investigator with
60 mL/min extensive experience in designing, con-
Estimated glomerular filtration rate 2 ducting and analysing clinical trials, not
≤ 30 mL/min involved in patient management, will be
Diabetes mellitus requiring medication 1 responsible for the statistical analysis. Data
Left ventricular ejection fraction ≤ 40 1
will be stored electronically and analysed
by means of the Epi Info 2002 (CDC), SPSS
Previous cardiac surgery 1
11.0 (SPSS), and STATA 9.0 (STATA) soft-
Procedures other than isolated coronary 1 wares, when appropriate. All data analysis
artery bypass graft or isolated atrial
septal defect repair will be carried out according to a pre-es-
tablished intention-to-treat analysis plan.
non elective procedure 1
Dichotomous data (including the primary
Preoperative intra-aortic balloon pump 1 outcome) will be compared by using a two-

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 G. Landoni, et al.
116 tailed chi2test with the Yates correction or
fisher’s exact test when appropriate. Con-
tinuous measurements will be compared
using the Mann-Whitney U test. Two-sided
significance tests will be used throughout.
Data will be presented as medians (25th and
75th percentiles) or as means (± standard
deviation - SD). Regarding the primary end-
point sample size, with an expected need
for RRT of 5% in the treatment group vs
10% in the control group (7, 8), aiming for a
0.05 alpha and 0.80 power, a total of 870 pa-
tients will have to be enrolled (435 patients
per group). This number will be increased
by 15% (leading to a total of 1000 patients)
in order to take into account potential pro-
tocol deviations. All 1000 patients will be
analysed according to the intention-to-treat
principle, beginning immediately after ran-
domization. Two interim analyses will be
carried out during the course of this study,
after randomizing 250 and 500 patients.
Monitoring of the study
Monitors will verify adherence to required
clinical trial procedures and confirm accu-
rate collection of data and will follow the
Good Clinical Practice (GCP) guidelines.
Study monitoring and follow-up, from the
initial set-up to final reporting, will be ful-
filled according to current national and In-
ternational requirements.
Ethical issues
The drug is safe and has been used as an
antihypertensive drug in clinical practice
for more than 15 years. We might prob-
ably observe more hypotensive episodes in
the treatment group but once being aware
of this potential side effect it shouldn’t be
problematic to detect and manage these
episodes in the ICU. no interference with
the subject privacy is planned. Data will
be stored in an electronic database without
indicating the name of the patients (a nu-
meric code will be used).
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
rESultS
During the present study we will expect
that fenoldopam would reduce the need for
RRT in patients at risk for ARf after cardi-
ac surgery and allow a faster recovery and
a better outcome. our trial should work out
clear recommendations regarding fenoldo-
pam administration in a cardiosurgical set-
ting to improve outcomes and reduce hospi-
tal costs. Improved survival of critically ill
patients undergoing cardiac surgery would
be the most relevant implication of this
study. Reduction in cost per patient will be
striking, since acute renal failure and renal
replacement therapy prolong intensive care
and hospital stay.
diScuSSion
nephroprotection in patients with or at
risk of ARf is a topical matter in cardiac
anesthesia. Many studies (9-12) and meta-
analyses (7, 8) appeared in literature sug-
gesting a protective effect by fenoldopam in
patients undergoing cardiac procedures.
Roasio et al showed that an infusion of 0.1
µg/kg/min of fenoldopam administered for
48 hours in patients with acute renal injury
after cardiac surgery reduced the need for
RRT in a single-center case-matched study.
However, literature is not unanimous and
data from large, multicentre, randomized
trials powered enough to detect a differ-
ence in clinical relevant outcomes are lack-
ing. We will conduct a large multicentre
randomized study comparing fenoldopam
to a placebo in patients undergoing cardiac
procedures who will develop an ARf to ad-
dress the question whether the administra-
tion of this drug might influence patients’
outcome after cardiac surgery.
30.000 cardiac surgical interventions
are performed in Italy every year (and
1.000.000 in the world). Since acute renal

failure develops in 2-10% of this popula-
tion, up to 3000 patients in Italy (100.000
in the world) could benefit from the results
of this study every year. This will be the
first multicentre randomized controlled tri-
al comparing the effects of fenoldopam to
placebo after cardiac surgery.
This study is powered enough to highlight
potential advantages deriving from fenoldo-
pam administration in patients that are at
high risk for postoperative acute renal dys-
function.
Funding, conflicts of interest
The project is funded by the Italian Ministry of Health.
Funding source had no influence on the study design. We
do not have any commercial interest with drug compa-
nies producing the drugs that will be used in this study.
Acknowledgements
A. Vavassori14, D. Colella18, A. Davi2, P. De Vico18,
D. Dini4, A. Gavina11, G. Grillone11, f. Liuzzo16,
R. Lobreglio2, M. Lupo2, L. Marchetti8, G. Marino1,
V. Salandin12, I. Virzo1, R. Vozzo16, P. zuppelli1,
M. Conte19, P. Del Sarto20, B. Martinez21, G. Paternos-
ter22, G. Ricciardi23, M. falco24, A. Gratarola25
14
ospedali Riuniti di Bergamo, Bergamo; 18A.o. Universi-
taria Policlinico Tor Vergata, Roma; 19Città di Lecce Hospi-
tal GVM Care & Research, Lecce; 20ospedale Pasquinucci,
Massa; 21A.o. Universitaria Santa Maria della Misericordia,
Udine; 22Casa di Cura Villa Verde, Taranto; 23A.C.o. San
filippo neri, Roma; 24European Hospital, Roma; 25A. o.
Universitaria S. Martino, Genova
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2. Landoni G, Bove T, Crivellari M, et al. Acute renal
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3. Bove T, Calabrò MG, Landoni G, et al. The incidence
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Cardiothorac Vasc Anesth 2004; 18: 442-445.
4. Landoni G, zangrillo A, franco A, et al. Long-term
outcome of patients who require renal replacement
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2006; 23: 17-22.
5. Schetz M, Bove T, Morelli A, et al. Prevention of
cardiac surgery-associated acute kidney injury. Int J
Artif organs 2008; 31: 179-189.
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7. Landoni G, Biondi-zoccai GG, Tumlin JA, et al.
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V 1.0
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 proceedings
in Intensive Care
Cardiovascular Anesthesia

originAl ArticlE
Endorsed by

119
perioperative evaluation
of primary hemostasis in patients
undergoing mitral valve repair
F. Pappalardo¹, P. Della Valle², G. Maj¹, A. Franco¹, A. Lattuada3,
G. Landoni¹, A. Zangrillo¹, A. D’Angelo²
¹Department of Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milan, Italy;
²Coagulation Service and Thrombosis Research Unit, Università Vita-Salute San Raffaele, Milan, Italy;
³Coagulation Service and Thrombosis Research Unit, Ospedale Sacco, Milan, Italy

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 119-127

AbStrAct
introduction: no data exist on the prevalence of primary hemostatic defects and acquired von Willebrand
disease in mitral valve prolapse with severe regurgitation.
methods: Primary hemostasis was evaluated by PfA-100, von Willebrand factor Antigen (vWf:Ag) and Ris-
tocetin cofactor (vWf:RiCof) assays in a prospective observational trial. Sixty-five consecutive patients with
mitral regurgitation (study group) or aortic stenosis (control group) who were operated for mitral valve repair
or aortic valve replacement were enrolled in the study.
results: There were no differences in Closure Time in the two groups at all time points. The concentration
of plasma vWf: Ag was within normal limits in all patients preoperatively; after surgery, a significant increase
was observed in both groups from baseline (199 +/- 144 mcg/dL vs. 295 +/-141 mcg/dL in the study group,
p=0.002; 243 +/- 141 mcg/dLl vs 338 +/- 154 mcg/dL in the control group, p=0.009).
The ratio of vWf:RiCof to vWf:Ag was slightly decreased preoperatively in both groups (ratio= 0.91) and
showed a marked increase in the postoperative period (ratio=0.22) as, probably, new hemostatically effective
large multimeric forms of vWf were released.
conclusions: Patients who present for surgery with a valvular pathology with high shear stress have some
degree of primary hemostasis defect; nevertheless, the potent stimulus of surgery and the correction of the
underlying disease allow quick restoration of vWf activity and normalization of PfA-100.

Keywords: von Willebrand, mitral surgery, aortic surgery, platelect function, cardiac surgery.

introduction tions. Similarly, patients with other cardiac

Acquired von Willebrand syndrome in high
intracardiac shear stress conditions, such
as aortic stenosis (1-8), ventricular septal
defect (9) and patent ductus arteriosus (10),
has been clearly defined in its epidemiol-
ogy, pathophysiology and clinical correla-
Corresponding author:
federico Pappalardo, MD
Department of Cardiovascular Anesthesia and Intensive Care
Università Vita-Salute San Raffaele
Via olgettina, 60 - 20132 Milan, Italy
e.mail: pappalardo.federico@hsr.it
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
defects might occasionally exhibit such ab-
normality.
Platelet and blood clotting activation has
been shown in patients with mitral valve
prolapse but no data exist on the prevalence
of primary hemostatic defects and acquired
von Willebrand disease in mitral valve pro-
lapse with severe regurgitation (11).
The fluid dynamics of a regurgitant valve
are, in many ways, similar to the fluid dy-
namics of a stenotic valve; however, the
anatomy of the regurgitant orifice and the
 F. Pappalardo, et al.
120 dynamics of the regurgitant flow are com-
plex and not fully understood. The shape
and the direction of the regurgitant jet de-
pends on multiple factors, including the
anatomy and orientation of the regurgitant
orifice, the driving force across the valve,
and the size and compliance of the receiv-
ing chamber.
Given these facts, we hypothesized that pri-
mary hemostasis defects could be a feature
in patients with mitral valve prolapse.
Aim of this study was to evaluate the prev-
alence of primary hemostasis disorders in
patients with severe mitral regurgitation
due to prolapse without an history of path-
ological mucocutaneous bleeding, by means
of PfA-100 and to define their pathophysi-
ology and clinical implications.
mEthodS
65 consecutive patients undergoing open
heart surgery for valve operations were
prospectively evaluated; 41 patients under-
went mitral valve repair for severe mitral
regurgitation (study group), 24 of them un-
derwent aortic valve replacement for severe
aortic stenosis (control group). 5 patients
were excluded from the analysis for postop-
erative re-exploration with evident source
of surgical bleeding.
Patients were not included if operated on
urgency-emergency priority or with a mini-
mally invasive approach or had chronic
atrial fibrillation. no patient received war-
farin or antiplatelet drugs within 7 days
before surgery; patients on intravenous
heparin had it stopped at least 6 hours pre-
operatively. Patients were not considered
eligible if the preoperative platelet count
was <80,000 x 109/l, if they had preopera-
tive PT and/or APTT ratios >1.2 or if they
had a history of hematological or hepatic
disease (e.g., active hepatitis or cirrhosis),
or chronic renal failure requiring dialysis.
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
All patients signed an informed consent,
according to the Declaration of Helsinki,
after approval of the protocol by the Ethics
Committee of our Institution.
PFA-100
The PfA-100 provides an ex vivo quanti-
tative measure of platelet function under
high shear conditions simulating primary
haemostatic events following vascular in-
jury.
The platelet function analyzer (PfA-100,
Dade Behring, Inc, Deerfield, Ill.) performs
analyses on citrated whole blood samples
(Vacutainer tubes, Becton Dickinson; ci-
trate 129 mmol/L; 3.8%) and measures the
time needed for a platelet plug to form after
activation of platelets by collagen and aden-
osin diphosphate (CADP, 50 μg) or collagen
and epinephrine (CEPI, 10 μg). The sample
is aspirated under constant negative pres-
sure through a 200 μm capillary into a small
reservoir, by passing through an 150 μm
opening coated with collagen/epinephrine
(CEPI) or collagen/ADP (CADP). As blood
contacts the collagen-coated membrane,
the platelet agonist (epinephrine or ADP)
is solubilized, resulting in platelet stimula-
tion. The test terminates when the devel-
oped primary hemostatic plug obstructs
the opening. The instrument provides the
Closure Time (CT) parameter, indicating
the time duration of the test: results are ex-
pressed in seconds, with a maximum test
time of 300 seconds. Any value greater
than that is reported as non closure. our as-
says were performed with CADP cartridges
in order to remove the effect of antiplatelets
acting on ADP receptors.
All PfA-100 measurements were performed
within 30 minutes of sample collection.
Patients’ management
Prior to institution of cardiopulmonary by-
pass (CPB), patients received intravenous
porcine heparin (300 IU/kg of body weight)
 primary hemostasis in patients undergoing mitral valve repair
and, during CPB, additional doses (5000
IU), if required, to maintain the activated
clotting time (ACT) >480 sec. (ACT II,
Medtronic, Minneapolis, Mn, USA). ACT
measurements were carried out 2 minutes
after heparin administration and every 20
minutes thereafter. After termination of
CPB and surgical hemostasis, heparin was
neutralized with protamine sulphate (1:1
ratio). All patients received an intraopera-
tive infusion of tranexamic acid (1g in 20
minutes before skin incision, followed by
a continuous infusion of 400 mg/h until
completion of surgery) according to our in-
stitutional protocol.
At the end of the surgical procedure, pa-
tients were transferred to the Intensive
care unit (ICU). Postoperative blood loss
was collected in a graduated reservoir con-
nected to a closed evacuation system (Ar-
gyle, Aqua-seal, Sherwood Medical, Tul-
lamore, Ireland).
Cardiopulmonary bypass circuit
Extracorporeal circulation was instituted
in all patients by draining blood by grav-
ity into an open venous reservoir (Avant
Reservoir, Dideco, Mirandola, Italy), and
by driving it by means of a roller peristal-
tic pump (Caps, Stöckert Instruments, Mu-
nich, Germany) through a heat exchanger
integrated with a hollow fiber membrane
oxygenator (Avant D903, or Avant D903
Ph.i.s.i.o., Dideco, Mirandola, Italy) and
through an arterial filter (D734 MICRo
40, Dideco, Mirandola, Italy) back into the
patient at a mean flowrate of 2.4 l/min/m2.
The same custom pack of PVC/silicone tub-
ing (Dideco, Mirandola, Italy) was used for
all patients. The circuit was primed with
1500-ml Ringer lactate solution, 100 mL
Mannitol 18%, and 5000 IU porcine hepa-
rin. Intermittent cold blood cardioplegia
(4°C) was infused by means of a heat ex-
changer (D720 Helios C, Dideco, Mirando-
la, Italy) and two roller pumps, according
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
to Buckberg’s protocol. Mild-to-moderate 121
hypothermia was employed (mean internal
temperature: 31.4°C).
Shed mediastinal blood suction and left
heart venting were actively performed with
two separated roller pumps. Additionally,
blood was aspirated from the operative
field with a vacuum suction device (D745,
Dideco, Mirandola, Italy), processed in a
cell saver (Compact-A, Dideco, Mirandola,
Italy), and then reinfused after closure of
the chest.
Laboratory assays
Blood samples were collected from a radi-
al arterial catheter by means of a two-sy-
ringe technique. The first syringe was used
to withdraw 10 ml of blood and then the
sample was obtained in the second syringe.
Sample time points were as follows:
A) preoperatively (Baseline);
B) before heparin administration (Pre-hep);
C) after removal of the aortic crossclamp
(Unclamp);
D) 4 minutes after the administration of
protamine (Post-prota);
E) at ICU arrival (ICU-arrival);
f) 4 hours after ICU arrival (ICU-4h);
G) the morning following surgery (ICU-
18h).
Blood samples were collected in siliconized
Vacutainer tubes (Becton Dickinson, Plym-
outh, UK) containing tri-sodium citrate
(0.19 M); within 1 hour from blood collec-
tion, platelet poor plasma was obtained by
centrifugation for 20 minutes at 2000 RPM
at room temperature.
Plasma aliquots of platelet-poor plasma (0.4
mL) were snap-frozen with methanol and
dry ice and finally stored at –80 °C until
assayed.
Assay methods
Von Willebrand factor Antigen (vWf:Ag)
was determinated by commercially avail-
able ELISA assays (Asserachrom vWf, Di-
 F. Pappalardo, et al.
122 agnostica Stago, Asnier sur Seine, france).
Ristocetin cofactor activity (vWf:RiCof)
was measured by commercially available ly-
ophilized platelet reagents (Dade-Behring,
Marburg, Germany) using an automated
coagulometer (ACL 9000; Instrumenta-
tion Laboratory, Lexington, Massachusset,
USA) (12).
All results are the mean of the two determi-
nations and expressed as IU/dL of plasma.
The authors had full access to the data and
take responsibility for its integrity. All au-
thors have read and agree with the manu-
script as written.
Statistical analyses
Descriptive data are expressed as mean
standard deviation or median with inter-
quartile range (IQR) as appropriate ac-
cording to the skewedness of the observed
distribution. Statistical significance of the
difference between continuous variables
was assessed by using a Student t-test or a
Mann-Whitney U-test as appropriate. Com-
parison of proportions was performed by
Chi-Square or fisher Exact tests as appro-
priate. All reported p values are two tailed.
250
P = 0.6
200
P = 0.5
P = 0.9
150
100
50
Baseline Unclamp ICU arrival ICU-4h ICU-18h
figure 1 - Time course of platelet count (t-test) mean ± SD.
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
Differences were considered statistically
significant in case p-values were lower than
0.05.
Statistical analyses were performed using
the SPSS Statistical Package version 11.5.1
(SPSS Inc, Chicago, USA).
rESultS
Patients’ demographics were similar in the
two groups (mitral valve repair/study group
vs aortic valve replacement/control group).
Platelet count and hematocrit did not differ
between the two groups at all time points
(Figure 1 and 2)
There were no differences in Closure Time
in the two groups at all time points (Fig-
ure 3): the median closure time at baseline
was above the normality range (less than
118 sec.) in both groups (146 sec. [106-299,
25th-75th percentile] in the study group vs
183 sec. [128-299, 25th-75th percentile] in
the control group, p=0.22); only three
patients in the control group exhibited a
“normal” CT preoperatively (12%) vs 14
patients (38%) in the study group. five pa-
Control group
Study group
P = 0.7
P = 0.8
 primary hemostasis in patients undergoing mitral valve repair

123
Control group
Study group
50

P = 0.9 P = 0.7
40

P = 0.6
30 P = 0.7 P = 0.4

20
Baseline Unclamp ICU arrival ICU-4h ICU-18h

figure 2 - Time course of hemostasis: (%) (t-test) mean ± SD.

tients in the control group had non closure
(CT >300 sec.) preoperatively.
Preoperative CT increased following hepa-
rin administration and again with initiation
of CPB. fifteen minutes after protamine
sulphate administration, CT returned to
near baseline values.
Median (CT) of all patients significantly
decreased from baseline at ICU arrival and
18 hours postoperatively (163sec. [109.5-
299, 25th-75th percentile] vs 83sec. [66-
112, 25th-75th percentile], p<0.001) (Table
1); similarly the haematocrit and plate-
let count decreased. These variables were
inversely related to CT at all time points
(PLT p<0.001, r=-0.424; Hct p<0.003,
r=-0.353 at ICU arrival (Spearman test).
The concentration of plasma vWf:Ag was

Control group
Study group
P=0.01 P=0.09
300

250
P = 0.2
200
P = 0.7
P = 0.1 P = 0.5
150
P = 0.7
100

50
Baseline Post-epa Post-plegia Unclamp Post-prota ICU arrival ICU-4h

figure 3 - Closure Time (Mann-Whitney) median (25th-75th percentile).

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 F. Pappalardo, et al.

124 table 1 - Time course of Platelet Function Analyzer Closure Time [median (25th – 75th percentile)] in the overall
population.
25th percentile median 75th percentile p
Baseline 109.5 163 299
Pre-hep 132.75 185 299.75 0.389
Post-hep 120 163 299 0.112
Post-CPL 205.5 293 299 < 0.001
Unclamp 151.5 256.5 300 0.009
Post-prota 106 151 247 0.109
ICU arrival 63.5 78 90 < 0.001
4h after ICU arrival 62 79 102 < 0.001
18h after ICU arrival 66 83 112 < 0.001

within normal limits in all patients preop-
eratively. (VWf:Ag) levels did not differ
at all time points in the two groups; after
surgery, a significant increase was observed
in both groups from baseline (199+/-144
mcg/dL vs 295+/-141 mcg/dL in the study
group, p=0.002; 243+/-141 mcg/dL vs
338+/-154 mcg/dL in the control group,
p=0.009) (Figures 4, 5 and 6).
The ratio of vWf:RiCof to vWf:Ag was
slightly decreased preoperatively in both
groups (ratio=0.91; normal range greater
than 0.7) and showed a marked increase in
the postoperative period (ratio= 0.22) as,
probably, new hemostatically effective large
multimeric forms of vWf were released.
The correlations between CT and vWf:Ag
and vWf:RiCof could not be calculated be-
cause of a number of patients had an infi-
nite CT (>300 sec.). However, our results
indicate that, on the whole, the prolonga-
tion of the CT was inversely proportional

600 P < 0.001 600

P = 0.009

500 500
P = 0.155
vWF (mcg/dL)

vWF (mcg/dL)

400 400

300 300

200 200

100 100

Baseline Unclamp ICU-arrival Baseline Unclamp ICU-arrival

figure 4 - von Willebrand Factor Antigen concen- figure 5 - von Willebrand Factor Antigen con-
tration: time course in the overall study population. centration: time course in the control group.

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

 primary hemostasis in patients undergoing mitral valve repair
600
P = 0.009
500
P = 0.932
vWF (mcg/dL)
400
300
200
100
Baseline Unclamp ICU-arrival
figure 6 - von Willebrand Factor Antigen con-
centration: time course in the study group.
to the level of vWf:Ag and of vWf:RiCof
(Figure 3).
Postoperative bleeding did not differ in the
two groups (280 ml [220-400, 25th-75th per-
centile] vs 300 ml [180-400, 25th-75th per-
centile]) and no significant correlation was
detected between nor preoperative or post-
protamine CT and postoperative mediasti-
nal drainage. However, among the patients
population, five patients had no formation
of the platelet plug at baseline (CT>300 or
non-closure): this subgroup showed a sta-
tistically significant higher postoperative
bleeding as compared to the rest of other
patients (350 ml [240-400, 25th-75th percen-
tile] vs 220 ml [180-290, 25th-75th percen-
tile]), p=0.05) which was related to CT at
baseline (r=0.441, p=0.035).
no patients suffered of any thromboembol-
ic complication.
diScuSSion
Patients with high intracardiac shear stress
have a certain degree of proteolysis of high
molecular weight vWf and such a condi-
tion may contribute to the increased risk of
postoperative bleeding. PfA-100 has been
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
found to be both sensitive (90-100%) and 125
specific (88-95%) in the detection of von
Willebrand disease (13-16).
our study shows that patients with mitral
valve regurgitation due to prolapse have
high intracardiac shear stress which is re-
sponsible for the development of defects of
primary hemostasis, which can be detected
by means of PfA-100.
Despite these biological alterations, how-
ever, these patients do not show any patho-
logical mucocutaneous or surgical bleed-
ing, confirming the discrepancy between
the low frequency of bleeding symptoms
and the high prevalence of hemostatic ab-
normalities in this setting. This subclini-
cal defect of primary hemostasis is quickly
corrected by valve replacement due to the
quick restoration of vWf levels; however
it is responsible for a higher postoperative
bleeding in those patients with the most se-
vere deficiencies.
The PfA-100, however, is a sensitive, spe-
cific and reproducible test which might be
useful to screen patients preoperatively to
identify those who could benefit from cor-
rect diagnosis and appropriate therapy to
reduce their complications.
High shear rates prevail in stenotic valves:
under these conditions, large molecular
weight multimers of vWf are changed in
shape and exposed to the action of, which
results in their proteolysis. High molecu-
lar weight multimers of vWf are the most
effective in platelet mediated hemostasis.
Platelet adhesion to the subendothelial ma-
trix of injured arterial vessels wall requires
adhesion of platelets to subendothelially lo-
cated vWf and of plasma vWf to subendo-
thelial collagen. In addition, vWf enhances
the adhesion of platelets to fibrin clots and
stabilizes coagulation factor VIII (17-20).
Although aortic stenosis is a relevant in
vivo model of shear stress induced cleav-
age of vWf with resultant loss of its larg-
est multimers, fluid dynamics of mitral re-
 F. Pappalardo, et al.
126 gurgitation are also characterized by high
shear stress.
These anomalies measured with PfA-100
were reversed by surgical correction of the
regurgitant valve on the first postoperative
day, a finding which is consistent with the
12-to-20-hour half-life of vWf in vivo.
The correction of PfA-100 abnormalities
after surgical repair or replacement of the
diseased valve indicates that the passage
of blood through the diseased valve causes
a disturbance of flow, thereby generating
high shear stress and turbulence, may be
responsible, at least in part, for a height-
ened vWf proteolysis. However, the overall
imbalance of primary hemostasis is usually
mild and the PfA-100 abnormalities are not
an accurate predictor of a bleeding tenden-
cy, unless non closure is present (21).
froom et al. (22) reported their evaluation
of vWf in mitral valve prolapse: they con-
clude that there is a relationship between
mitral valve prolapse and low levels of
vWf:Ag. However, vWf:Ag levels are nor-
mal in those patients with mitral valve pro-
lapse and heart failure, as it may account
for an increased release of vWf.
Slaughter et al. (23) have investigated the
PfA-100 in CABG patients: they showed
that an impaired ADP mediated platelet ag-
gregation is not corrected after surgery in
17 of 19 patients. Moreover, they reported
that 80% of patients having CABG with
abnormal chest tube output had prolonged
PfA-100 measurements 15 minutes after
administration of protamine sulphate.
Raman et al. (24) identified 16 bleeders
after CABG: in 15 of those whose bleed-
ing was controlled by platelet transfusion,
PfA-100 after protamine sulphate was pro-
longed. They suggested a potential role for
PfA-100 measurements to help identify
which patient could benefit from platelet
transfusion after CABG.
Several limitations of our study should be
acknowledged. first, plasma concentration
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
of vWf has large variations, as it is influ-
enced by ABo blood type, Lewis blood type
race and age (25).
Moreover, the plasma level of vWf tran-
siently increases in response to a variety
of physiological conditions including trau-
ma, surgery, atherosclerosis, inflammatory
states and β-adrenergic stimulation.
concluSionS
In conclusion, mitral regurgitation second-
ary to prolapse is responsible for a certain
degree of proteolysis of high molecular
weight vWf as shown by abnormal shear
induced platelet aggregation. This defect of
primary hemostasis is quickly corrected by
valve repair due to the prompt restoration
of vWf levels and this condition is not as-
sociated with an increased risk of bleeding,
except for those patients with the most se-
vere deficiencies.
on the basis of these data, postoperative
bleeding after mitral valve repair should
prompt a search for other causes than von
Willebrand disease.
In addition, our observation confirms the
discrepancy between the low frequency of
bleeding symptoms and the high prevalence
of hemostatic abnormalities in the setting
heart valve disease. Although aortic steno-
sis and mitral regurgitation are a relevant
in vivo model of shear-stress induced cleav-
age of vWf with resultant loss of its largest
multimers, the diagnosis of von Willebrand
syndrome should be restricted to those pa-
tients who have bleeding.
Shear induced platelet aggregation is sig-
nificantly increased after cardiac surgery,
but the role that this phenomenon might
play in the development of postoperative
thromboembolic complications remains to
be addressed.
No conflict of interest acknowledged by the authors.
 primary hemostasis in patients undergoing mitral valve repair
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1. Vincentelli A, Susen S, Le Tourneau T, et al. Ac-
quired von Willebrand syndrome in aortic stenosis.
n Engl J Med 2003; 349: 343-349.
2. Yoshida K, Tobe S, Kawata M. Acquired von Wille-
brand Disease Type IIA in patients with aortic valve
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platelet aggregation in patients with aortic valve ste-
nosis. Circulation 2000; 102: 1290-1295.
4. Sadler JE. Aortic stenosis, von Willebrand factor,
and bleeding. n Engl J Med 2003; 349: 323-325.
5. Goldsmith IR, Blann AD, Patel RL, Lip GY. Effect
of aortic valve replacement on plasma soluble P-se-
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6. King RM, Pluth JR, Giuliani ER. The association of
unexplained gastrointestinal bleeding with calcific
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nosis and bleeding gastrointestinal angiodysplasia:
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9. Gill JC, Wilson AD, Endres-Brooks J, Montgomery
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blood clotting activation in patients with mitral
valve prolapse. Thromb Res 1996; 83: 299-306.
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Nei nostri farmaci equivalenti
c’è tanta scienza
quanta negli originatori.
Nei nostri farmaci equivalenti
c’è tanta scienza
quanta negli originatori.
 proceedings
in Intensive Care
Cardiovascular Anesthesia

cASE rEport
Endorsed by

131
inter-hospital extracorporeal
life support
G. Redaelli¹, A. Annoni¹, R. Caruso², F. Formica³, V. Meroni¹, L. Avalli¹
¹Cardiac Surgical ICU, ²Perfusion Service, ³Cardiac Surgical Department, San Gerardo Hospital, Monza, Italy

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 131-134

AbStrAct
A 60-year-old man with history of hypertension and unspecified left ventricular dysfunction had chest pain at
home at 9 am. At 1 pm he was transported to a peripheal hospital and treated for acute myocardial infarction.
At 4.30 pm, despite pharmacological and intra aortic balloon pump support , the extreme hemodynamic insta-
bility and the echocardiographic signs forced the doctors in charge to contact the “extracorporeal membrane
oxygenation team” of our Intensive Care Unit. The team, that in our hospital is composed of an intensivist,
a cardiac surgeon, a perfusionist and a nurse, reached the hospital at 5.15 pm and performed a percutaneous
cannulation of right femoral artery and left femoral vein connecting the patient to the extracorporeal mem-
brane oxygenation circuit. At 6.30 pm the patient on extracorporeal membrane oxygenation was transferred
by ambulance to the Cardiac Surgery Intensive Care Unit of San Gerardo Hospital in Monza. on day 20 he was
transferred back to the original hospital without neurological deficits, with normal renal function and normal
blood gas analysis.

Keywords: extracorporeal membrane oxygenation, cardiogenic shock, cardiac arrest.

introduction vice than by standard treatment with IABP

Cardiogenic shock is the leading cause of
death for patients with acute myocardial
infarction who reach the hospital alive.
It affects about 6 to 8% of patients with
acute myocardial infarction. (1) Despite
the advantages of early intra-aortic balloon
pump (IABP), fibrinolysis, percutaneous
coronary intervention or coronary arterial
bypass graft , once shock is diagnosed, the
mortality remains high (about 50%) with
half of death occurring during the first 48
hours. (2).
Some studies suggested that haemodynam-
ic and metabolic parameters could be more
effectively reversed by ventricular assist de-
Corresponding author:
Gianluigi Redaelli, MD
Cardiac Surgical Intensive Care Unit
San Gerardo Hospital
Via Pergolesi, 33 - 20052 Monza, Italy
e.mail: g.redaelli@hsgerardo.org
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
(3).
In this investigation we report our experi-
ence of using extracorporeal membrane ox-
ygenation (ECMo) to resuscitate a 60-year-
old man with critical left main coronary
artery disease complicated by acute myo-
cardial infarction (AMI) and cardiogenic
shock. The connection of patient to ECMo
circuit was performed in an hospital other
than ours and the patient was then trans-
ported to our hospital on ECMo with an
Advanced Care Mobile Unit.
cASE rEport
A 60-year-old man with history of hyper-
tension and unspecified left ventricular
dysfunction started to have chest pain at
home at 9 am. His medications included
beta-blockers, a sartanic and a tiazidic di-
 G. Redaelli, et al.
132 uretic. He waited more than four hours at
home before calling for help. At 1.30 pm
he alerted the emergency department (118)
and the advanced life support team found
him awake, hypotensive, symptomatic and
with ECG signs of extensive antero-lateral
AMI. Morphine and apirine were admin-
istered, dopamine infusion started and the
patient was transferred to the nearest pe-
ripheral hospital having a coronary care
unit, ten kilometres from our hospital.
At 2 pm during the angiographic study he
developed severe cardiogenic shock unre-
sponsive to catecholamine (dopamine 20
mcg/kg/min) and requiring IABP support
(1:1). The angiographic study showed dis-
tal occlusion of left main coronary artery
and the cardiologist performed angioplasty
on left anterior descending and circum-
flex coronary artery and positioned a bare
metal stent on left main and left anterior
descending arteries administering heparin
bolus 7500 IU and continuous infusion of
reopro.
The procedure was successful and obtained
a good revascularization, but the TIMI
score was 1 (the patient had severe hypo-
tension despite high-dose norepinephrine).
At 3.30 pm the patient had a bradi-asystolic
cardiac arrest treated with 20 minutes ad-
vanced life support algorithms including
tracheal intubation and transvenous pac-
ing.
After the resuscitation manoeuvres, the pa-
tient was still in cardiogenic shock refrac-
tory to high amines dosage (dopamine 16
mcg/kg/min plus adrenaline 0.14 mcg/kg/
min), IABP, pacing, mechanical ventilation:
systolic blood pressure was 90 mmHg, heart
rate 100 beats per minute, anuria, pao2 53
mmHg, paCo2 60 mmHg, pH 7.04, lactates
>6 mmol/L and base excess -14 mmol/L.
An echocardiography examination showed
the presence of contractile reserve (i.e. tem-
porary improvement of ejection fraction
and arterial pressure during epinephrine
bolus). At 4.30 pm the doctors in charge de-
cided to call our extracorporeal membrane
oxygenation (ECMo) team, composed of
four figures (intensivist, cardiac surgeon,
perfusionist and nurse by cardiac surgi-
cal care unit). At 5.15 pm we reached the
peripheral hospital and, being the patient
hemodinamically unstable , we decided for
ECMo implantation. Percutaneous can-
nulation of right femoral artery with a 17
french cannula and of left femoral vein
with a 21 french cannula was performed.
The perfusionist prepared and primed the
circuit and at 5.40 pm the patient was con-
nected to ECMo with blood flow3.5 L/min,
gas flow 3 L/min and fio2 0.6 with rapid
hemodynamic stabilization, reduction of
amines, recovery of diuresis and normal-
ization of blood gas parameters (pao2 457
mmHg, paCo2 29 mmHg, pH 7.48, lactates
1,9 mmol/L, BE -1,2 mmol/L). The reopro
infusion was interrupted at the beginning
of the manoeuvre and we had no hemor-
ragic complications. At 6.30 pm the patient
on ECMo was transferred by ambulance to
the cardiac surgery intensive care unit of
San Gerardo Hospital in Monza. The trans-
port required 20 minutes for a distance of
about 10 kilometres and was uneventful.
The patient was maintained sedated, with
continuous perfusion of muscle relaxant
and, for the first 24 hours therapeutic hy-
pothermia was applied for brain protection.
With total ECMo support he was hemo-
dynamically stable without catecholamine
support. Monitoring included arterial, cen-
tral venous and pulmonary artery catheter.
Hemodynamic data were: arterial blood
pressure 150/60 mmHg, heart rate 80 beats,
sinus rhythm, central venous pressure 12
mmHg, wedge pressure 15 mmHg, pulmo-
nary artery pressure 29/18 mmHg, cardiac
output 2,5 L/min, venous oxygen satura-
tion 72%. A transesophageal echocardiog-
raphy showed an ejection fraction of 10%
under full ECMo blood flow. Dobutamine

5 mcg/kg/min was started to assure aortic
valve opening.
Intravenous infusion of heparin had an ac-
tivated clotting time of 180-200 seconds.
Aspirin and clopidrogel were started with-
out loading dose.
on day 1 echocardiography showed aki-
nesia of apex and anterior wall, severe hy-
pokinesia of septum and lateral wall, no
valvular defects. Daily evaluations of legs
perfusion were performed with clinical pa-
rameters and/or arterial doppler. We never
found any problem of leg perfusion in this
case.
on day 4, because of relative hypertension,
we started infusion of calcium-sensitizer
and weaning from ECMo gradually reduc-
ing blood flow at 2 L/min for 12 hours and
then 1 L/min for others 12 hours while
monitoring hemodinamic parameters and
cardiac performance and dimensions with
Swan-Ganz catheter and echocardiogra-
phy. on day 5 the patient was weaned from
ECMo with IABP (1:1) and dobutamine 10
mcg/kg/min.
The cannulae were removed with only ex-
ternal compression for hemostasis. After
removal of ECMo cannulae the patient de-
veloped hyperdynamic shock (cardiac out-
put 11 L/min, blood pressure 80/40 mmHg)
requiring norepinephrine for 24 hours. We
treated this hyperdynamic shock as a septic
one, performing cultural examination and
starting empiric antibiotic therapy with
meropenem.
on day 6 we removed IABP and started ni-
trates. Echocardiography without ECMo
and IABP support showed persisting aki-
nesia of apex and anterior wall with good
recovery of septal and lateral wall motion
and an ejection fraction of 30%.
on day 7 linezolid was added to meropenem
because of fever and elevation of leukocytes
and inflammation indexes. The same day
the patient had bronchial bleeding and de-
terioration of blood gas parameters, requir-
inter-hospital extracorporeal life support
ing high PEEP and interruption of heparin 133
and clopidogrel. Ecodoppler was performed
to exclude the presence of thrombosis in
the main vessels.
on day 8 the patient developed an hyper-
tensive crisis with pulmonary oedema with-
out changes in ECG or cardiac regional wall
motion with high pulmonary pressures re-
quiring mechanical ventilation with PEEP
15cmH2o, high fio2 and inhalatory nitric
oxide for 48 hours.
negative water balance and infusion of cal-
cium-sensitizer because of the evidence of
diastolic dysfunction at echicardiography-
were performed. ACE-inhibitor and beta-
blockers were introduced. on day 11 the
patient was extubated and on day 13 we in-
troduced digoxin for prevention/treatment
of .congestive heart failure (4).
on day 20 he was transferred back to the
hospital he came from. At discharge from
our unit the patient was awake, without
neurological deficits, hemodynamically
stable, in sinus rhytm, receiving ACE-in-
hibitor and beta-blocker, with normal renal
function and normal blood gas analysis.
The equipment used during the transpor-
tation included: an usual Advanced Care
Mobile Unit coordinated by our 118 depart-
ment; a portable ECMo circuit (Figure 1)
and a transport ventilator “oxylog 3000
(Draeger, Lubeck, Germany). The portable
ECMo circuit is composed by Rotaflow
centrifugal blood pump, Rotaflow console
and permanent life support system (Ma-
quet, Jostra Medizintechnik AG, Hirrlin-
gen, Germany); cannulae Bio-Medicus
(Medtronic inc., Minneapolis, Mn). The
transport of ECMo_system was made with
the “Mobile Heart-Lung Machine (HLM)
holder HKH 8800 (Maquet, Jostra Mediz-
intechnik AG, Hirrlingen, Germany)” (5).
In our Unit we have an “ECMo-bag” con-
taining devices for cannulation and emer-
gency assistance of intensive patients ready
for use.
 G. Redaelli, et al.
134
figure 1 - ECMO circuit with membrane oxygenator and centrifugal pump mounted on a specially
designed multifunctional holder Steering and control unit including battery pack.
diScuSSion
The details of our “ECMo project” are
available online at and are inclusive of in-
clusion and exclusion criteria, flowcharts,
duties of the emergency department (118),
background and reasons that justify the
project that offers to the surrounding hos-
pitals that have no cardiac surgery and no
expertise with ECMo the possibility of a
prompr referral.
Within this project and till July 2009 the
ECMo team was activated 7 times: in five
cases no intervention was needed (we were
on stand-by for elective dangerous proce-
dures in catheter laboratories). The first pa-
tient with cardiogenic shock who received
ECMo in the peripheral hospital and trans-
port to our hospital died in our intensive
care unit on day 2 for intestinal infarction
due to important extracardiac arteriopathy.
The second patient is described in details in
this case report and had good recovery.
overall, before july 2009, our experience
with ECMo for cardiac assistance included
57 cases, 35% of them performed outside
in the emergency department, in the cath-
eterization laboratory or in other hospitals.
and all of them with percutanoeus cannu-
lation performed either by the cardiac sur-
geon or the intensive care specialist.
No conflict of interest acknowledged by the authors.
rEfErEncES
1. Seyfarth M, Sibbing D, Bauer I, et al. A ran-
domized clinical trial to evaluate the safety
and efficacy of a percutaneous left ventricu-
lar assist device versus intra-aortic balloon
pumping for treatment of cardiogenic shock
caused by myocardial infarction: J Am Coll
Cardiol 2008; 52: 1584-1588.
2. Thiele H, Sick P, Buodriot E, et al. Random-
ized comparison of intra-aortic balloon sup-
port with percutaneous left ventricular assist
device in patients with revascularized acute
myocardial infarction complicated by cardio-
genic shock. Eur Heart J 2005; 26, 1276-1283.
3. Baughman KL, JarchoJA. Bridge to life-car-
diac mechanical support. n Eng J Med 2007;
357: 846-849.
4. Hood WB Jr, Dans AL, Guyatt GH, et al. Digi-
talis for treatment of congestive heart failure
in patients in sinus rhythm. Cochraine Data-
base Syst Rev 2004; CD002901.
5. Matthias Arlt, Alois Philipp, Markus zim-
mermenn, et al. first experience with a new
miniaturized life support system for mobile
percutaneous cardiopulmonary bypass. Re-
suscitation 200877; 345-350.
 proceedings
in Intensive Care
Cardiovascular Anesthesia

imAgES in mEdicinE
Endorsed by

HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 137-138

137
A “four-leaf clover” aortic valve
A. Grimaldi, E. Collu, A. Castiglioni, G. La Canna, M. De Bonis, E. Bignami,
G. Melisurgo, O. Alfieri
Department of Cardiothoracic and Vascular Surgery, Università Vita-Salute San Raffaele, Milan, Italy

A 75-year-old man with acute worsening

of heart failure symptoms and a clinical
history of prior rheumatic fever, presented
with blood pressure 150/60 mmHg and a
high-pitched diastolic murmur in the aor-
tic area.
A preliminary Transthoracic exam showed
severe aortic regurgitation (vena contracta
width >7 mm) (Figure 1) and moderate
mitral regurgitation due to rheumatic leaf-
lets retraction.
A three-dimensional reconstruction of
short axis aortic view showed a four leaflets
valve with a significant central tip malcoap-
tation (Figure 2, Panel A).
A Transesophageal exam confirmed a quad- figure 1 - The Standard Transthoracic approach
ricuspid valve with four cusps approximate- shows a severe aortic insufficiency (vena contracta
ly of equal size (Hurwitz and Roberts Type width >7 mm).
A) (Figure 2, Panel B).
The peculiar spatial arrangement allowed
the cusps leading edges to malcoaptate caus-
ing a severe aortic regurgitation.
no anomalous origin of coronary ostia was
found.
The surgical inspection confirmed the di-
agnosis (Figure 3) and the aortic valve was
successfully replaced with a biological pros-
thesis.
normally shaped aortic valve has three
leaflets according to a regular cono-trunkal
embryological ripartition into aortic and
pulmonic valve and development of three

figure 2 - Panel A. Transthoracic Three-Dimen-

Corresponding author:
Antonio Grimaldi, MD
sional echocardiographic reconstruction of the
Department of Cardiothoracic and Vascular Surgery four-leaf clover aortic valve. Panel B. The Stand-
Università Vita-Salute San Raffaele
Via olgettina 60 - 20132 Milan, Italy
ard Transesophageal aortic short axis view shows
e.mail: grimaldi.antonio@hsr.it the symmetrical central tip malcoaptation.
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
 A. Grimaldi, et al.
138
figure 3 - At surgical inspection the quadri-
cuspid aortic valve appears to be made up of four
cusps approximately of equal size. No anomalous
coronary ostia were detected.
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
small pads of mesenchymal tissue. Any
eventual deviation from the symmetric ar-
rangement can lead to leaflets number or
position abnormalities (1).
According to autopsy series the prevalence
of quadricuspid aortic valve ranges be-
tween 0,008 and 0,033% (2) and the valve
malformation can be alone or associated
to other congenital cardiac defects (3); in
10% of cases a displacement of coronary
ostia or a single coronary artery can be de-
tected (4).
rEfErEncES
1. fernandez B, Duran AC, Matire A, et al. new em-
bryological evidence for the formation of quadricus-
pid aortic valves in the Syrian hamster. J Comp Path
1999; 121: 89-94.
2. feldman B, Khandernia B, Warnes C, et al. Inci-
dence, description and functional assessment of iso-
lated quadricuspid aortic valves. Am J Cardiol 1990;
65: 937-938.
3. Suzuki Y, Daitoku K, Minakawa M, et al. Congeni-
tal quadricuspid aortic valve with tetralogy of fal-
lot and pulmonary atresia. Jpn J Thorac Cardiovasc
Surg 2006; 54: 44-46.
4. Robicsek f, Sanger PW, Daugherty HK, Montgom-
ery CC. Congenital quadricuspid aortic valve with
displacement of the left coronary orifice. Am J Car-
diol 1969; 23: 288-290.

pApErS, poStErS, prESEntAtionS:
communicAting thE biomEdicAl SciEncES
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2: 139-141
leave nothing to chance:
using English to navigate
your presentation
M. John
Professor of Applied English, Faculty of Medicine, Università Vita-Salute San Raffaele Milan, Italy
I have already spoken about the need to
prepare attractive slides to transmit your
discoveries, procedures and statistics dur-
ing an oral presentation at a peer-to-peer
congress. I have also already mentioned
the fact that during your presentation you
should not hold notes in your hand and
simply read a written text to your audience.
This would be terribly boring for them and
would not reflect positively upon your abil-
ities as a speaker.
Remember, you do not need notes in any
case as all of your relevant data should be
present in the concise and clear bullet points
written in your slides, which you then ex-
pand upon and develop during your talk.
Let’s be honest, you should know what you
are talking about as far as your medical spe-
cialty is concerned.
However, you might have a few more prob-
lems with the English language. Maybe you
are not a native speaker. Maybe your Eng-
lish is not fluent. Maybe you are convinced
that your English is the worst on the plan-
et! This will make you nervous when you
have to speak in a language that is not your
own to describe complex, maybe even con-
troversial, procedures and theories.
We are therefore going to have a look at some
phrases that will help you get through the
Corresponding author:
Prof. Michael John
Università Vita-Salute San Raffaele, Milan, Italy
Via olgettina 48 - 20132 Milan, Italy
e.mail: michael.john@hsr.it
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
proceedings
in Intensive Care
Cardiovascular Anesthesia
Endorsed by
139
presentation without too many problems.
You have probably ‘borrowed’ words, phras-
es and structures already when you have
written papers. There is nothing wrong
with that. So, let’s start.
1. the polite opening
I am honored to speak here today...
Thank you so much for inviting me to speak...
2. the topic and aim of the presentation
The aim of my presentation is...
My talk mainly deals with...
3. the structure of the presentation
First of all, I’ll give you an overview of our
procedure...
Then, I’d like to touch on...
Following this, we’ll be examining...
Finally, we’ll take a closer look at...
4. navigating forward
So, after my introduction let’s take a look at...
Now this brings me to a very interesting point...
I’d like to proceed with some examples of...
5. branching out
I want to take a moment to talk about...
Another thing we cannot ignore concerning
this topic is...
6. returning to the main theme
I’d like now to return to the main theme of my
presentation...
Now let’s go back to the central theme of my
talk...
 M. John
140 7. in conclusion
Finally, I want to mention...
My presentation is drawing to its close...
We might therefore conclude that...
8. describing your slides
As you can see in this slide...
What we are looking at here is...
In this slide, I want to draw your attention to...
In the upper/lower part of the image you can see...
To illustrate my point I’d like you to focus on
this graphic...
9. Summarizing
To sum up...
In summary, what I have tried to show you is...
Questions from the readers
1 is it better to use the present tense
or the past tense when writing a
paper?
The main tense used in a biomedical paper is
the simple past The word ‘simple’ is impor-
tant as compound tenses, such as the present
perfect, should be avoided unless absolutely
necessary.
However, the simple present is also used as
you can see below.
In the Introduction you should use the pres-
2 how is the medical history inter-
view (anamnesis) carried out in
English?
A doctor typically asks questions to obtain
the following information about the patient:
1. Identification and demographics: name,
age, height, weight
2. The “chief complaint (CC)” - the major
health problem or concern, and its time
course (e.g. chest pain for past 4 hours)
3. History of present illness (HPI) - details about
the complaints, enumerated in the CC
hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2
Taking all of these factors into account...
10. the take-home message
The bottom line of our study is...
What I want you to remember is...
11. thanks and closure
Thank you for your attention...
Thanks for listening...
of course, what comes next is often con-
sidered the most difficult, although in my
opinion it is also the most fruitful, part of
any presentation: ‘What questions do you
have?’
More about that next time!
ent tense to tell your readers what the pa-
per is about. Use the simple past to describe
background information and to give an over-
view of your methods.
The Methods should be written in the simple
past tense.
The simple past should also be used in the
The Discussion uses the simple present to
put your results and conclusions into con-
text, but you will also use the simple past
tense at times when you are referring to pre-
vious work in the field.
4. Past Medical History (PMH) (including
major illnesses, any previous surgery/op-
erations, any current ongoing illness, e.g.
diabetes)
5. Review of systems (RoS) Systematic
questioning about different organ systems
6. family diseases - especially those relevant
to the patient’s chief complaint
7. Childhood diseases - this is very impor-
tant in pediatrics
8. Social history (medicine) - including
living arrangements, occupation, mari-
tal status, number of children, drug use
 “once upon a time there was a congress...”

(including tobacco, alcohol, other recre-
ational drug use), recent foreign travel,
and exposure to environmental pathogens
through recreational activities or pets
9. Regular and acute medications (including
those prescribed by doctors, and others
obtained over-the-counter or alternative
medicine)
10. Allergies - to medications, food, latex, and 141
other environmental factors.
Sexual history, obstetric/gynecological
history etc.*
(* Wikipedia)
for more detailed information visit http://
en.wikipedia.org/wiki/Medical_history

“Questo è il sesto di una serie di articoli sull’argomento.

Potete indirizzare domande (in italiano o in inglese) a michael.john@hsr.it e vedrete le
risposte pubblicate su questa rubrica”.

‘This is the sixth of a series of articles on this topic.

Send any questions to michael.john@hsr.it who will answer them as part of this column’

hSr proceedings in intensive care and cardiovascular Anesthesia 2010, vol. 2

proceedings
in Intensive Care
Cardiovascular Anesthesia
futurE EvEntS
Endorsed by
142
calendar for future meetings
intensive care, Surgery and cardiovascular Anesthesia
2010
June 28th. first Consensus Conference on Reduction of Mortality
in Cardiac Anesthesia and Intensive Care. Milano, Italy. for
information, contact: law.jessica@hsr.it, Website: www.hsrpro-
ceedings.net
June 29 - July 2. The 11th Annual Congress of Asian Society for
Vascular Surgery. Kyoto, Japan. for information, contact:
Asvs2010@inc.co.jp
September 9-11. Czech national Congress Society of Anesthesiolo-
gists in Critical Medicine. zlin, Czech Republic. for information,
contact: Guarant, Ms. R. Somolova, opletolova, 22 11000 Prague
1. Email: csarim2010@guarant.cz
September 11-15. 24th Annual Meeting of the European Association
for Cardio-thoracic Surgery. Geneva, Switzerland. for informa-
tion, contact: EACTS, 3 Park Street, Windsor, Berkshire SL41LU,
UK, Email: info@eacts.co.uk
September 21-24. 12th International Congress of Cardiothoracic and
Vascular Anesthesia. Beijing, China. for information, contact:
Email: ICCVA2010@gmail.com, Website: www.iccva2010.cn
September 30 - october 2. 2nd International Meeting on Aortic Di-
seases. Liege, Belgium. for information contact: Department of
Cardiovascular and Thoracic Surgery CHU Liege, 4000 Liege, Bel-
gium. Email: cardiovasc@chu.ulg.ac.be, Website: www.chuliege.
imaa.be
october 2-5. Australian Society of Anaesthetists 69th national Scien-
tific Congress Melbourne 2010. Melbourne, Australia. for infor-
mation, contact: Website: www.asa2010.com
october 9-13. 23rd Annual Congress European Society of Intensive
Care Medicine. Barcelona, Spain. for information, contact: ESI-
CM, 40 Avenue Joseph Wybran, 1070 Brussels, Belgium. Email:
barcelona2010@esicm.org
october 16-20. American Society of Anesthesiologists Annual Mee-
ting. San Diego, CA. for information, contact: ASA, 520 n. nor-
thwest Highway, Park Ridge, IL 60068, Website: www.ASAhq.
org
December 10-14. Sixty-fourth Postgraduate Assembly, new York
State Society of Anesthesiologists. new York, nY. for informa-
tion, contact: nYSSA, 85 fifth Avenue, new York, nY 10003,
Email: hq@nyssa-pga.org
December 17-18. 4th International Congress: Aortic Surgery and
Anesthesia “How to do it”. Milano, Italy. for information, con-
tact: S. Grassi, San Raffaele Congress Centre, Via olgettina 58,
20132 Milano, Italy, Email: info@aorticsurgery.it; Website: aor-
ticsurgery.it
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia welcomes announcements of interest to physicians, re-
searchers and others concerned with cardiothoracic and vascular anesthesiology, medicine, pharmacology and related areas.
All copies are reviewed and edited for style, clarity and length. Information should be addressed to: George Silvay, M.D.,
Ph.D., Editor, Professor of Anesthesiology, Department of Anesthesiology, Mount Sinai Medical Center, 1 Gustave L. Levy
Place, Box 1010, new York, nY 10029-6574. E-mail: george.silvay@mountsinai.org
2011
January 12-15. Annual Meeting Society for Technology in Anes-
thesia. Las Vegas, nevada. for information, contact: Society for
Technology in Anesthesia, 6737 W. Washington Street, Suite
1300, Milwaukee, WI 53214. Email: STAhq@anestech.org
January 16-21. 29th Annual Symposium: Clinical Update in Anes-
thesiology, Surgery and Perioperative Medicine with Interna-
tional faculty and Industrial Exhibits. St. Martin, french West
Indies. for information, contact: Helen Phillips, The Mount Sinai
School of Medicine, one Gustave L. Levy Place, Box 1010, new
York, nY 10029. Email: helen.phillips@mountsinai.org
January 31 - february 2. 47th Annual Meeting Society of Thoracic
Surgeons. San Diego, CA. for information, contact: Email: sts@
sts.org
february 13-16. 40th Annual Meeting of the German Society for
Thoracic and Cardiovascular Surgery. Stuttgart, Germany. for
information, contact: Executive Secretary GSTCVS Langerbeck-
Virchou Haus Luisenstr 58/59, 10117 Berlin, Germany. Email:
secretariat@dgthg.de
february 24-27. International Conference on Pre-Hypertension and
Cardio Metabolic Syndrome. Vienna, Austria. for information,
contact: Paragon Conventions, 18 Avenue Louis – Casai, 1209
Geneva, Switzerland. Email: marketing@prehypertension.org
March 22-25. 31st International Symposium on Intensive Care and
Emergency Medicine. Brussels, Belgium. for information, con-
tact: Eramus University Hospital, Route de lennik 808, B-1070
Brussels, Belgium, Email: veronique.de.ulaemich@nlb.ac.be,
Website: www.intensive.org
April 29-May 4. 33rd Annual Meeting and Workshops Society of Car-
diovascular Anesthesiologists. Savannah, GA. for information,
contact: SCA, Po Box 11086, 2209 Dickens Road, Richmond, VA
23230, Website: www.scahq.org
May 11-15. 58th Annual Meeting Association of University Anesthe-
siologists. Philadelphia, PA. for information, contact: AUA, 520
n. northwest Highway, Park Ridge, IL 60068, Email: dionne@
asahq.org
october 15-19. American Society of Anesthesiologists Annual Me-
eting. Chicago, Il. for information, contact: ASA, 520 n. north-
west Highway, Park Ridge, IL 60068, Website: www.ASAhq.org
november 7-8. Surgery of the thoracic aorta. Bologna, Italy. for in-
formation contact: noema, Via orefici 4, 40124 Bologna, Italy.
Email: info@noemacon-gresci.it., Website: www.noemacongres-
si.it
2012
March 25-30. 15th World Congress of Anesthesiologists. Buenos
Aires, Argentina. for information, contact: Website: www.
wca2012.com
Somanetics™*
Ossimetro Cerebrale / Somatico InvOS™*
Reflecting the color of life
 Somanetics: un parametro vitale di qualità
Unico ossimetro in commercio al tempo stesso cerebrale e somatico, il Sistema Cerebrale / Somatico INVOS effettua il
monitoraggio delle variazioni di saturazione regionale di ossigeno (rSO2), rivelando in modo semplice e diretto l’insorgere di
complicanze ischemiche. Il Sistema Cerebrale / Somatico INVOS consente di applicare fino a quattro sensori contemporaneamente
su aree specifiche, di rilevare precocemente problemi di ossigenazione in tempi spesso più rapidi rispetto ai parametri vitali
sistemici, e di intervenire tempestivamente.

Modalità di monitoraggio a due o quattro canali:

• R
afforza il monitoraggio cerebrale con l’introduzione
del monitoraggio somatico
• I dentifica e permette di gestire in maniera più precisa
problemi di ossigenazione regionale
• P
ossibilità di posizionare fino a quattro sensori per
ottenere, in modo non invasivo, dati sull’ossigenazione
da zone di maggior interesse
• F
ornisce dati più oggettivi da utilizzare per un
trattamento personalizzato del paziente

Altri vantaggi:
rSO2 cerebrale e somatica: una guida in
• Display più ampio per una più facile lettura
• U
scita video ad un secondo monitor remoto per una
tempo reale alla perfusione e agli interventi
90
Cerebrale sinistro
migliore visibilità da parte dell’intero personale di Intubato Cerebrale destro
Somatico sinistro (peri-renale)
cura 80
Inizio CEC Somatico destro (peri-renale)

Fine CEC
• Download dei dati più facile tramite porta USB 70

• Impostazioni utente migliorate

60
• I ndicatore di potenza del segnale per riflettere meglio
Soglia di desaturazione somatica
le interferenze 50

Raffreddamento, aumento
Vent CO2, FiO2 e anestetici
40
Soglia di desaturazione cerebrale
Indicazioni per l’uso:
Il Sistema INVOS è progettato per monitorare e misurare direttamente, 30
etCO2 etCO2
in modo continuo e non invasivo, le variazioni di saturazione regionale 40 28
cerebrale dell’emoglobina in un individuo. Poiché l’emoglobina nel campo
20 2 unità di CGR
del sensore è costituita dal 75% circa di sangue venoso, dal 20% di
Clampaggio aortico totale Rimozione del clampaggio aortico totale
sangue arterioso e dal 5% di sangue capillare, l’interpretazione clinica Ipotensione
10
delle letture è coerente con quella di una misura venosa.Il dispositivo 16:16 16:46 17:16 17:46 18:16 18:46 19:16 19:46 20:16 20:46
è destinato all’uso per tutti quei pazienti che presentano un rischio di
squilibri nell’ossigenazione cerebrale. Il dispositivo deve essere utilizzato
esclusivamente da personale medico specializzato.Il dispositivo può
inoltre essere utilizzato per il monitoraggio aggiuntivo di supporto della
saturazione di emoglobina in una regione di tessuto muscolare scheletrico
al di sotto del sensore di un individuo a rischio di stati ischemici per flusso
ridotto o assente.

Controindicazioni: Nessuna.
™* Somanetics, INVOS e “Reflecting the color of life” sono marchi registrati di Somanetics Corporation.
COVIDIEN, COVIDIEN con logo e simbolo ™ sono marchi registrati di Covidien AG o delle sue consociate.
© 2007 Covidien AG o sue consociate. Tutti i diritti riservati. C-MN-SurgRealities/IT

Covidien Via Rivoltana, 2/d +39 02 703171 [t] www.covidien.com

Italia SpA 20090 SEGRATE (Mi) +39 02 703 173 17 [f]
Italia
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4 th I N T E R N A T I O N A L C O N G R E S S

DECEMBER
2010
AORTIC SURGERY
AND ANESTHESIA
“ HOW TO DO IT ”

ISTITUTO SCIENTIFICO UNIVERSITARIO SAN RAFFAELE

MILANO - ITALY - DECEMBER 17TH - 18TH, 2010

www.aorticsurgery.it
 Il PPI differente dall’origine

Depositato presso l’AIFA in data 26/01/2010