Full HSR proceedings Vol. 1

Transcript

ASSociAtE EditorS
Luciano Gattinoni
Università degli Studi di Milano. Policlinico di Milano, Italia
Massimo Antonelli
Università Cattolica Sacro Cuore,
Policlinico Gemelli, Roma, Italia
Fabio Guarracino
Azienda Ospedaliera Universitaria Pisana
Vol. 1 • n° 2 • 2009
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
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 Pisana, Pisa, Italia
n VASculAr SurgEry
Roberto Chiesa
Università Vita-Salute San Raffaele, Milano, Italia
n cArdiAc SurgEry
Ottavio Alfieri
n cArdiology
Giuseppe Biondi-Zoccai
Università degli Studi di Torino, Italia
n clinicAl cArdiology
Alberto Margonato
n inVASiVE cArdiology
Stephan Dreysse
n intErVEntionAl pEdiAtric cArdiology
Peter Ewert
WEb Site
www.itacta.org
Editore
n EchocArdiogrAphy
Michele Oppizzi
n mEtAboliSm
Dionisio Colella
Università degli Studi di Tor Vergata, Roma, Italia
n nEw tEchnologiES
Federico Pappalardo
n in hoSpitAl EmErgEnciES
Luca Cabrini
Edizioni Internazionali srl
Divisione EDIMES
EDIzIonI MEDICo SCIEnTIfICHE - PAVIA
Via Riviera 39 - 27100 Pavia
Tel. 0382526253 r.a. - fax 0382423120
E-mail: [email protected]
n nurSing
Mariano Fichera
n hEmAtology
Andreas Koster
EXEcutiVE Editor
Massimiliano Nuzzi
EditorS
Elena Bignami
Tiziana Bove
Segreteria di redazione
Lara Sussani
Cattedra di Anestesia e Rianimazione
Università Vita-Salute San Raffaele, Milano
Via olgettina, 60 - 20132 Milano
Tel. +39 02 26437164
fax +39 02 26437178
[email protected]
Maria Grazia Calabrò
Nicola Colangelo
Michele De Bonis
Francesco De Simone
wEb Site
www.itacta.org
Gian Franco Gensini
Università degli Studi di Firenze, Italia
Giuseppe Giardina
direttore responsabile
Paolo E. zoncada
James L. Januzzi
Harvard University - Massachusetts General Hospital, US
Giovanni Landoni
Registrazione Tribunale di Milano
in corso
Kevin Lobdell
Carolinas Heart and Vascular Institute, Charlotte, NC, US
Stampa
Jona Srl
Paderno Dugnano (MI)
Editore
Giovanni Marino
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
Edizioni Internazionali srl
Divisione EDIMES
EDIzIonI MEDICo SCIEnTIfICHE - PAVIA
Via Riviera 39 - 27100 Pavia
Tel. 0382526253 r.a. - fax 0382423120
Anna Mara Scandroglio
Luigi Tritapepe
Università degli Studi “La Sapienza”, Roma, Italia
Emiliano Vitalini
Ospedale San Camillo Forlanini, Roma, Italia
proceedings
in Intensive Care
Cardiovascular Anesthesia
ConTEnTS
n EditoriAl...........................................................................................................................................................................................................................................................................5
n rEViEw ArticlES
cardiac Anesthesia and Surgery in geriatric patients:
Epidemiology, current Surgical outcomes, and future directions ..........................................................................6
J.G. Castillo, G. Silvay, J. Chikwe
most care®: a minimally invasive system for hemodynamic monitoring
powered by the pressure recording Analytical method (prAm) ......................................................................... 20
S. Romagnoli, S. Bevilacqua, C. Lazzeri, F. Ciappi, D. Dini, C. Pratesi, G.F. Gensini, S.M. Romano
n originAl ArticlES
percutaneous aortic valve implantation: the anesthesiologist perspective............................................ 28
R.D. Covello, G. Landoni, I. Michev, E. Bignami, L. Ruggeri, F. Maisano, M. Montorfano,
O. Alfieri, A. Colombo, A. Zangrillo
can timing of tracheal extubation predict improved outcomes after cardiac surgery..... 39
S.L. Camp, S.C. Stamou, R.M. Stiegel, M.K. Reames, E.R. Skipper, J. Madjarov,
B. Velardo, H. Geller, M. Nussbaum, R. Geller, F. Robicsek, K.W. Lobdell
where are italian anesthesiologists and intensive care specialists publishing?
A quantitative analysis of publication activity ........................................................................................................................................... 48
L. Buratti
n pApErS, poStErS, prESEntAtionS:
communicAting thE biomEdicAl SciEncES
communicating biomedicine at congresses:
a general introduction to posters and oral presentations........................................................................................................ 53
M. John
3
LA SOLUZIONE IDEALE PER:
Arresto cardiaco
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Danno vertebrale traumatico
Sepsi
Chirurgia
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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 - [email protected]
Certificato UNI EN ISO 9001:2000
proceedings
Editorial
in Intensive Care
Cari colleghi, cari amici soci di ITACTA,
desidero condividere con voi l’entusiasmo ed il piacere che l’inizio di
questa affascinante avventura del nuovo Journal mi suscita. Prima
di esprimere i miei pensieri al riguardo desidero rivolgere un ringraziamento sincero al Prof. zangrillo per avere pensato e concretizzato
un’iniziativa così importante per la nostra comunità scientifica.
Credo che questa rivista rappresenti un momento proficuo per i medici coinvolti nella gestione della terapia intensiva e della anestesia
cardiovascolare, perché presenta un forte significato di “arruolamento” dei più giovani verso una partecipazione ad una comunità che si
propone di aggiornarsi attraverso lo studio e la ricerca per offrire ai
pazienti livelli di assistenza sempre più eccellenti.
Da tempo ITACTA (Italian Association of CardioThoracic Anesthesiologists), quale braccio italiano di EACTA (European Association
of CardioThoracic Anesthesiologists), propone iniziative tese a favorire la partecipazione a studi e ricerche, e promuove la formazione
spontanea di gruppi di interesse “under 40” nei vari campi della anestesia e rianimazione cardiovascolare e toracica (www.itacta.org).
In questa ottica il nuovo Journal acquisisce un significato davvero
importante, orientato ad offrire anche ai più giovani una motivazione a condividere i propri risultati di studio e di ricerca.
Sono grato al Prof. zangrillo per avere arricchito ITACTA, di cui mi
onoro di essere presidente, del prestigio di una rivista ufficiale.
Desidero inoltre esprimere la mia riconoscenza al dr. Landoni, vicepresidente di ITACTA, per l’enorme lavoro che sta svolgendo nella
cura editoriale di questa iniziativa e nella motivazione straordinaria
a partecipare che riesce a suscitare nei colleghi.
Avendo lavorato presso l’ospedale San Raffaele di Milano, adesso
anche Università Vita-Salute San Raffaele, non posso non ricordare
l’atmosfera congeniale allo studio che respiravo nei reparti e nelle
sale operatorie dove ho trascorso gli anni tra i più belli della mia vita
professionale.
I primi numeri del Journal promettono davvero soddisfazioni future
a tutti coloro che vorranno contribuire al suo successo.
Ed è per questo che desidero invitare tutti i soci ITACTA a sostenere
questa esperienza con il loro usuale instancabile entusiasmo.
Buon lavoro.
fabio Guarracino
ITACTA President
5
proceedings
in Intensive Care
rEViEw ArticlE
6
cardiac Anesthesia and Surgery
in geriatric patients: Epidemiology,
current Surgical outcomes,
and future directions
J.G. Castillo1, G. Silvay2, J. Chikwe1
Department of Cardiothoracic 1Surgery and 2Anesthesiology Mount Sinai Medical Center New York, NY, United States
AbStrAct
The mean life expectancy of the population of the United States is projected to increase from 78.3 years at
present to over 81 years in 2025, with a concomitant increase in the percentage of the population over the age
of 75 years. Elderly patients are more likely to present with valvular and coronary artery disease than younger
patients, and as better perioperative management contributes to improving post-operative outcomes and lower
referral thresholds, very elderly patients form an increasingly large proportion of the cardiac surgical population. This article summarizes the impact of age-related pathophysiologic changes on patients’ response to cardiac surgery and anesthesia, outlines useful perioperative strategies in this age group, and reviews the literature
on outcomes after valvular and coronary in elderly patients.
Keywords: surgery, elderly, anesthesia, cardiac anesthesia, octogenarians.
bAcKground
In 2007, average life expectancy in the
United States was 78.3 years and the
Census Bureau estimated that this will increase to 81 years in 2025 (1).The number
of people older than 65 years is projected
to grow 50% from 35 to 71 million in the
United States alone, eventually representing 19.6% of the overall population (2, 3).
The prevalence of cardiovascular disease,
which remains the leading cause of death
in the West, and which is responsible for
Corresponding author:
Joanna Chikwe, MD fRCS
Assistant Professor
Department of Cardiothoracic Surgery
Mount Sinai Medical Center
1190 fifth Avenue, Box 1028
new York, nY, 10029 United States
[email protected]
a third of all mortality or about 17.5 million deaths annually in the US, is higher in
older individuals and appears to be increasing. An updated analysis of data from the
national Health and nutritional Examination Survey, found that those individuals
who are 65 years or older are substantially
more likely than younger patients to present with cardiovascular disease, cerebrovascular accidents, chronic lower respiratory tract disease, and diabetes (3-5). An
increasing number of elderly patients are
therefore likely to require cardiac anesthesia and surgery.
The definition of “geriatric”, “aged”, “elderly” and “advanced age” varies widely in
the medical literature. Medicare, the state
health insurance for older patients in the
United States, sets its current eligibility
threshold at 65 years of age, and in the car-
cardiac Anesthesia and Surgery in the elderly
diac surgical literature elderly patients have
traditionally been defined as those aged 65
years and above.
not only does this cut-off seem relatively
low in the context of the increasing mean
age of patients undergoing cardiac surgery,
but there is also a trend towards evaluating
patients based on the physical examination
and comorbid conditions rather than just
their chronological age (4). It has been suggested that older adults should be categorized as “young-old” (65-74 years), “midold” (75-84 years), and “oldest-old” (≥85
years) but for the purposes of this review
article “elderly” patients refers to those
aged 75 years and above (4, 6).
AgE-rElAtEd
functionAl dEclinE
A gradual diminution in functional capacity over time is one of the hallmarks of aging, and impacts on the choice of therapy
and surgical planning in elderly patients
undergoing cardiac surgery (7-9). optimizing care in this increasing pool of older patients mandates that cardiovascular professionals become familiar with age-associated
changes in organ physiology and their impact on treatment and recovery. Cardiovascular changes primarily lead to reduction of
the cardiac functional reserve, with a consequent increase in the risk of congestive
heart failure (10, 11).
A reduction in pulmonary reserve has implications for the postoperative stay, and a decline in renal function leads to an increased
potential for the occurrence of renal insufficiency requiring postoperative dialysis (12,
13). Changes in gastrointestinal physiology
increase the risk of mucosal damage (14).
Loss of neurological and muscular skeletal
function is particularly important predictors of post-operative morbidity and mortality (15-17). All these changes impair the
ability of older patients to tolerate surgical
procedures and increase their risk of mortality, and morbidity leading to an overall
decline in functional status, higher frailty
scores, and poorer quality of life. It is clear
that becoming familiar with age-related
physiologic changes is the cornerstone for
cardiovascular care givers in achieving better tailored treatments when possible.
Cardiovascular function
Decrease in cardiac functional reserve (systolic or diastolic dysfunction) considerably
limits both the capacity to develop any kind
of physical activity and the ability to tolerate pathophysiologic stressors such as surgery and sepsis (18). furthermore, most
patients will have coexisting hypertension
and marked atherosclerotic disease which
increases the risk of coronary artery disease and secondary myocardial ischemia
(19). The changes in ventricular compliance involve a significant reduction in early
diastolic filling due to diastolic dysfunction
(20-22).
There may be no baseline change in the
ejection fraction or cardiac index, but during stress the increase in ejection fraction is
blunted and older patients, even those with
normal systolic function, are more prone to
heart failure (23-25). In addition to these
ventricular changes, the aging heart provides a 1% yearly decline in aerobic capacity due to a decrease in the maximum volume of oxygen usage (23).
Although heart rate remains constant with
age, there is a decrease in maximal heart
rate in response to stress (26).
This effect may be caused by a combination of decreased catecholamine responsiveness and an age-related decrease in the
intrinsic sinus rate. In addition, the aging
cardiac conduction system is characterized
by increasing fibrosis, calcification, and a
decrease in the number of sino-atrial pacemaker cells and of bundle branch fibers
7
J.G. Castillo, et al.
figure 1 - Proportion
of patients over the age
of 70 years referred for
cardiac surgery in the
United Kingdom during the last decade (The
Society of Cardiothoracic Surgeons of Great
Britain and Ireland,
national Adult Cardiac
Surgical Database report).
8
(27). These factors may contribute to sick
sinus syndrome, atrio-ventricular block,
and intraventricular conduction delays;
hence cardiac rhythm management devices
are increasingly encountered in patients
presenting for cardiac surgery, and may be
required after valvular heart surgery (28).
Pulmonary function
Pulmonary changes are primarily due to
multiple factors such as smoking, air pollution, heart failure, or skeletal system
changes like kyphosis. Aging additionally
affects the function and structure of the
pulmonary system as well (29, 30). The
most common finding is decreased lung
compliance caused by a marked decrease in
elastic recoil (31).
This progressive cease in elasticity decreases respiratory reserve and the area of alveolar gas exchange surfaces. These changes
have mechanical, functional and anatomical consequences, and lead to an increase
in residual volume and functional residual
capacity both increase of 5-10% and 1-3%
per decade, respectively.
The physiologic response to hypercapnia
and hypoxia are dampened with age, probably due to a decline in sensitivity of these
centers to chemical stimuli. finally, there
is decreased clearance of mucus from the
airways due to diminished function or the
lack of mucociliary structures, which in
combination with age-related immune dysfunction, mean elderly patients are more at
risk of respiratory tract infections (32). Recently, we conducted a retrospective analysis of 5798 patients undergoing all types of
cardiac surgery in order to determine the
predictors of respiratory failure following
cardiac surgery (33, 34). Multivariate analysis revealed that age >70 years was an independent predictor of respiratory failure
(oR=1.6).
Renal function
Several morphologic and histological
changes occur in the renal system with age;
including a decrease in cortical area and
characteristic vascular changes (35-37).
Although there are wide individual differences in the decline of the glomerular filtration rate (GfR) and renal plasma flow,
GfR declines by 4 mL/min/year in individ-
uals older than 50 years of age compared
to a decline of 1 mL/min/year in healthy
younger individuals (38). As renal mass
diminishes, renal blood flow decreases at a
rate of approximately 10% per decade with
a resultant overall decrease in GfR. By the
eighth decade, only 70% of the nephrons
are functioning and free of sclerotic changes, leading to a decreased filtration area and
decreased permeability of glomerular basement membranes (39).
The elderly are at increased risk of developing hyperglycemia before the onset of end
stage renal disease. This may be due to decreased in renin synthesis and impairment
of renin release (40). Dysregulation of the
renin-angiotensin system is characterized
by decreased plasma renin activity under
basal, stimulated, and suppressed conditions; renal vasoconstriction; increased angiotensin
II activity; increased renal nerve activity;
increased endothelin; and decreased vasodilatory prostacyclins (41).
Renal dysfunction is particularly common
after cardio-pulmonary bypass in the setting of prolonged perfusion time and transfusion of multiple blood products (12, 42).
Patients at the highest risk of post-operative
renal failure include those with aneurysmal
involvement of the renal arteries, renal dysfunction indicated by elevated creatinine,
and those with congestive heart failure (41,
43). After retrospectively analyzing 6449
patients to determine the incidence and
predictors of renal failure requiring dialysis in patients undergoing cardiac surgery,
we observed an overall incidence of postoperative renal failure of 2.2%.
Although multivariate analysis confirmed
that age >70 years was an independent
risk factor for preoperative renal dysfunction (oR 1.6 95% CI 1.2-2.3, P=0.003),
age was not found to be an independent
predictor of post-operative renal dysfunction.
Gastrointestinal function
A variety of physiologic gastrointestinal
changes are related to age, ranging from decreased basal gastric blood flow, to diminished blood flow and prostaglandin response
to injury (44). The increased prevalence of
atherosclerotic disease in older patients,
who may be undergoing more complex reoperative procedures, potentially increases
the risk of abdominal organ hypoperfusion
and thromboembolic events, resulting in
ischemic gastrointestinal complications.
Gastrointestinal hemorrhage has been reported in several studies to be the most
frequent cause of post-cardiopulmonary
bypass gastrointestinal complications with
an incidence of 2% following cardiac surgery (45). In contrast, in a more recent
study, Mangi et al reported mesenteric
ischemia as the dominant cause of postoperative gastrointestinal complications
(46). our data from 5188 consecutive patients showed that postoperative gastrointestinal complications after cardiac surgery
occurred in 1.1% of the patients, with the
predominant etiology being intestinal ischemia (59%) followed by gastrointestinal
bleeding (41%), and revealed that age over
65 was an independent predictor of this
complication (oR 2.1, p<0.001) (47).
Neurological function
Rudolph et al. recently published a key paper on the derivation and subsequent validation of a scoring system or rule to predict
delirium after cardiac surgery (48). They
enrolled 122 elderly (≥60 years of age)
cardiac surgery patients that underwent a
delirium assessment pre- and postoperatively beginning on postoperative day 2.
Delirium, defined according to the confusion assessment method, occurred in 52%
of the patients and multivariate analysis
identified 4 independent variables associated with delirium: previous stroke, MMSE
scores, abnormal serum albumin, and the
9
10
geriatric Depression Scale scores. After assigning points to each variable they were
able to accurately predict risk of postoperative delirium in cardiac surgery patients,
further validating the scoring system in a
sample of 109 patients.
Musculoskeletal function
Aging may influence negatively the physiological response to exercise and prolonged
training, mainly due to the loss of muscular mass. Additionally cachexia, defined as
a complex syndrome including weight loss,
diminished muscle and adipose tissue, anorexia, and generalized weakness, is a significant problem in the elderly population
(49). Although not exclusively limited to
the elderly, there are several reasons why
cachexia is more prevalent in geriatric patients, particularly its strong association
with chronic diseases such as cancer, chronic obstructive pulmonary disease, heart failure, and renal insufficiency. In the context
of cardiovascular disease, every physician is
familiar with the classical “skin and bone”
appearance with secondary heart failure. In
a pioneer study on the role of wasting syndrome as an independent risk factor form
mortality in chronic heart failure (CHf),
Anker and coinvestigators showed that at
least 16% of patients with CHf present
with cachexia defined as a weight loss of
7.5% over 6 months.
When the cut-off point is risen to a 6%
weight loss, the prevalence of cachexia increases to 36% with a consequent threefold
increase in mortality rates (50, 51).
Aging and the Metabolic Syndrome
It is widely accepted that cardiovascular
risk factors (hypertension, hyperlipidemia,
obesity, diabetes mellitus, and impaired glucose tolerance) play a major role not only as
a cause of cardiac surgical disease but also
in the development of perioperative complications (52, 53).
In the United States the estimated rate of
the metabolic syndrome in patients aged 60
to 70 years is 43.5% (54).
Accordingly, the impact of diabetes on the
adverse outcome in cardiac patients, particularly in the geriatric population, is well
recognized. However, most recent literature
suggests that diabetes mellitus is not an independent risk factor for increased risk of
wound infection, length of stay, or mortality after open-heart surgical procedures. It
is rather the presence of perioperative hyperglycemia that affects biochemical and
physiologic functions which in turn impacts surgical outcomes (55).
furnary et al reported that the Portland
CII Protocol based on insulin infusions is
a safe and effective method of eliminating
hyperglycemia, contributing to reduced
postoperative mortality from 5.3% to 2.5%
(p<0.001) (56, 57).
doES AgE rEAlly mAttEr?
Despite technological advancements, openheart operations still carry a significant risk
of mortality and morbidity and it is a reality that currently age still prevents many
patients from being referred for cardiac surgery (58, 59).
Potential explanations include the elderly
not being accurately represented in randomized trials and a resultant lack of clear
data on criteria for referral, skepticism
among physicians about postoperative
quality of life, and the impact of preoperative mortality risk calculators on surgical
decision-making.
More recent data suggests improving outcomes in terms of survival and quality of
life in elderly patients undergoing cardiac
surgery (60, 61). Although these studies
may not be representative of the wider
unselected elderly surgical population, the
American College of Cardiology has re-clas-
sified age as a minor clinical predictor of
increased perioperative cardiovascular risk
in the latest update of the guidelines. The
need for separate surgical type-based risk
stratification models for hospital mortality
is increasingly recognized as is the importance of including postoperative variables
in risk stratification models (62).
Recently, zingone and coauthors conducted
a retrospective study on patients 80 years
or older undergoing all types of cardiac surgery in order to determine the independent
predictors of operative mortality.
After multivariate analysis, they created
2 different Cox proportional hazard models, including postoperative variables in
the latter. Interestingly, when postoperative variables were included in the hazard
model, age was no longer considered as a
predictor of mortality, demonstrating that
postoperative complications were stronger
risk factors for hospital deaths than preoperative comorbidities and procedural variables confirming findings reported by our
institution (59).
gEnErAl conSidErAtionS
And prEopErAtiVE EVAluAtion
Elderly patients classically present with
age-specific comorbidities such as multiorgan functional decline, depression, alterations of mental status, cachexia, and
absence of social or familiar support. These
problems are seen with different grades
of severity in this subpopulation and, as
mentioned above, that is why chronological age by itself cannot be the only criterion
for surgical planning and the biological age
should be defined individually, based on comorbidities and performance status. Several publications have reported on the impact
of comorbidities as a predictor of surgical
outcome and survival in elderly patients
(63, 64).
Concurrent comorbidities have an important prognostic impact and play a major
role when trying to achieve an accurate assessment of geriatric patients. Ideally, every
elderly patient should receive a comprehensive geriatric assessment (CGA) for different reasons including an accurate estimation of life expectancy, early identification
of risk factors and predictors (dementia,
delirium, malnutrition, or inadequate social support), and helps to create a warm
and clear environment when consenting
the patient to undergo surgery (65). Additionally, a correct CGA is crucial in classifying patients with functional limitations and
may assist the surgeon in making the most
appropriate surgical planning and decision
for each patient.
pEriopErAtiVE mAnAgEmEnt
And SurgicAl rESultS
Currently, admission to the hospital on the
day of surgery has become standard for
most elective surgery, including the geriatric population. Preoperative assessment
of the patient is mandatory to assure there
have been no interval changes (dehydration, fever, mental disturbance or other
acute medical symptoms) from the time of
the initial anesthetic evaluation (63, 66,
67). In addition, it is prudent to establish
continuous arterial pressure recording before induction of anesthesia. The pulmonary artery catheter is inserted on an individual basis.
Anesthesia and endotracheal intubation
should be induced, performed, and maintained with consideration of the pharmacokinetic and pharmacodynamic changes
associated with aging with particular
care to maintain hemodynamic stability.
Transesophageal echo is a useful monitor
of cardiac function, may confirm supplement preoperative diagnostic information
11
12
and to assist with the deairing of the cardiac chambers (6).
furthermore, epiaortic echocardiography
to detect any atherosclerotic lesions prior
to manipulation or cannulation of the ascending aorta may help reduce embolic incidents particularly in elderly patients. An
aggressive surgical approach after optimal
perioperative preparation offers elderly patients prognostic and symptomatic benefit,
particularly in coronary artery bypass and
valvular heart surgery.
Coronary Artery bypass Grafting
Studies have historically shown high operative mortality in very elderly cardiac surgical patients. In-hospital mortality rates of
over 10% were reported in octogenarians
undergoing CABG or isolated aortic valve
replacement during the 1980’s, (68, 69)
with one study reporting early mortality as
high as 24% (70).
Recent studies suggest results are improving: octogenarians who underwent isolated
CABG experienced mortality rates of 5-10%
(71-74). We described an operative mortality of 1.9% our for coronary artery bypass
grafting in a large cohort of octogenarians
(75). This overall low mortality occurred
despite the prevalence of diabetes, peripheral vascular disease, severely depressed
Ef, left main stem disease, previous stroke,
renal dysfunction and chronic obstructive
pulmonary disease in our patient population, and indicates that patient selection
was not the primary reason for our low
mortality.
Aortic Valve Replacement
Calcified aortic stenosis is the most common structural cardiac disease in the elderly, with an estimated disease prevalence of
20% (76).
Despite published series noting a trend
towards a better in-hospital mortality and
quality of life, physicians remain reluctant to recommend open AVR for patients
greater than 80 years of age, instead pursuing medical treatment providing minimal
symptomatic relief and diminishing survival (77).
It is well recognized that AVR should be
the procedure of choice as it carries a low
operative mortality and morbidity, even in
very elderly patients, and provides excellent long-term outcomes. Thourani and
figure 2 - Unadjusted (A) Kaplan-Meier survival curves after coronary artery bypass grafting surgery
for octogenarians compared to non-octogenarians and (B) for octogenarians after coronary artery bypass
grafting compared to the survival of an age and gender matched US population.
colleagues evaluated 515 patients (88 octogenarians) undergoing isolated AVR over a
10-year period: they did not observe significant differences in surgical outcomes and
concluded that selecting octogenarians for
cardiac surgery should be left at the surgeon’s discretion after interviewing and
examining the patient (78). Percutaneous
valve therapy may offer a useful alternative
in the elderly or debilitated patient.
Rankin et al reviewed 409,100 cardiac surgical procedures performed between 1994
and 2003 (67). of these patients, 216,245
patients had isolated aortic valve replacement, with unadjusted mortality of 5.7%.
nineteen variables independently influenced operative mortality.
The most significant of which were emergency surgery (oR, 2.11), followed by advanced age (oR, 1.88), and re-operation
(oR, 1.16). Brown and co investigators explored the last 10 years of isolated AVR in
the Society of Thoracic Surgery Database
with regard to the patient characteristics
and operative outcomes (79).
They showed that despite gradual increases
in patient age and overall risk profile, morbidity and mortality of isolated AVR has
fallen. In summary, we believe that clinicians should redouble their efforts to emphasize earlier surgical indication to avoid
urgent and emergency surgery in elderly
patients.
Mitral Valve Repair
Mitral regurgitation is the second commonest valvular heart lesion in elderly patients
in industrialized countries (58). Although
the optimal timing of intervention in elderly asymptomatic patients with mitral regurgitation is controversial, the ACC/AHA
guidelines recommend surgical intervention in symptomatic patients who present
with severe MR (80).
In a recent study conducted for the European Society of Cardiology, Mirabel et al
found that mitral valve repair was denied
in 49% of patients with severe symptomatic MR, with older age one of the main
reasons cited (58).
A potential explanation is that the feasibility and efficacy of mitral valve repair in octogenarians remains controversial, as many
surgeons prefer replacement in the interest
in performing expeditious surgery, especially if more complex pathology or comorbidities are present.
We collected data on 79 consecutive octogenarians undergoing mitral valve repair with
or without concomitant CABG or tricuspid
repair from 1/2002 to 12/2008 in our institution. The mean age of patients was 83±5
years).
operative mortality rate was 5% and 2 of
the 4 deaths occurred in patients undergoing reoperation for ischemic MR. overall
90-day mortality for survivors of the initial hospitalization was 5% (n=4). Major
postoperative morbidities included mechanical ventilation >72 hours (n=12,
15%) and renal failure requiring dialysis
(n=5, 6%).
no patient experienced a postoperative
stroke or required re-operation. Postoperative transthoracic echocardiography
showed none-trace MR in 97%. no patient
required mitral re-repair. Actuarial survival
at 1- and 3-years was 86% and 77% respectively, with an unadjusted survival superior
to 60% at 5 years, similar to that of an agematched population.
Therefore, based on our own experience,
mitral valve repair in a reference center
provides excellent results in most octogenarians, with low operative mortality and
postoperative morbidity, and good midterm results.
We can conclude that cardiac surgical procedures can be performed safely and with
therapeutic benefit in elderly patients, regardless of age in those carefully selected
candidates (81).
13
14
figure 3 - Unadjusted (A) Kaplan-Meier survival curves for octogenarians after aortic valve replacement (A) and mitral valve repair (B) compared to the survival of an age and gender matched US population.
long-tErm outcomE
our own experience with octogenarians
undergoing AVR suggested that outcome
and long-term survival can be similar to
that of gender and age matched population.
Previous publications on survival after
AVR in elderly patients have traditionally
reported one, three, and five year survivals ranging from 83-89%, 79-80%, and 6163% respectively. our results in octogenarians are similar: after a mean follow up of
4.0±2.5 years, 1 and 5-year survival rates
were 90.7±1.8% and 66.3±3.6% for octogenarians vs. 96.2±0.4% and 86.8±0.8%
for younger patients. Among predictors of
late death in octogenarians markers for late
post-operative comorbidities with a strong
negative impact on life expectancy including extensive aortic calcification, concomitant CABG, and previous renal failure or
stroke were most significant. Congestive
heart failure at the time of surgery was a
strong independent predictor of late mortality, underlining the need for early, elective
intervention in octogenarians identified as
surgical candidates, and close follow-up of
those who
The institutional results in octogenarians
undergoing CABG are similar to those
achieved with those octogenarians who
underwent AVR, and highlighted that currently long-term survival and quality of life
in these particular patient population can
match that of octogenarians in the general
population.
However, there is a marked difference
when we compare long-term outcomes to
the younger patients undergoing the same
surgical procedures. Besides the granted
difference in age and biological long-term
survival, previous studies have pointed out
that during the last decade survival in octogenarians undergoing CABG can reached
up to 87% at 1 year, 78% at 3 years, and
66% at 5 years. our institutional experience and analysis revealed that after a
mean follow-up time of 3.6±2.5 years, 1and 5-year survival rates were 90.3±2.1%
and 63.8±4.8% for octogenarians versus
96.3±0.6% and 88.8±1.3% in younger
patients (p<0.001), suggesting that the
common comorbidities in the elderly group
may preclude any benefit on long-term survival due to a better surgical outcome and
perioperative management.
futurE dirEctionS
Additional clinical research in cardiac geriatric anesthesia (preoperative optimization
of the patient, brain protection, improvements in surgical and perfusion techniques,
prevention of complications, new discoveries in organ protections) will further contribute to improve surgical outcome, and age
alone should not therefore be a precluding
factor for any indicated cardiac surgery.
The term “frailty” was defined as a state
of multisystem impairment and increased
vulnerability to adverse outcomes. However, how best to generalize its use is debated. The principle is to assess “deficits”
such as symptoms, signs, diseases, disabilities or abnormal laboratory, radiographic or
electrocardiographic findings, which relate
deficit accumulation to the individual risk
of death.
The more deficits a patient presents with,
the more likely that person is to be frail,
independently of age. Therefore, when
expressed as an index, frailty is often expressed as a ratio of deficits present to the
total number of deficits considered. It is
well known that the frailty index is strongly associated with the risk of death, institutionalization and worsening health status,
especially when an increasing number of
variables are included in the scoring system. The standardization and reproducibility of the findings in relation to the frailty
index is of interest because none of the reported systems or calculators considered
the same deficits (82). This finding suggests
that frailty involves a complex network of
biological variables and may be measured
in many ways.
In order to encourage and propose a more
widespread evaluation and application of
frailty indexes, several geriatricians have
attempted to refine the term and validate
an applicable index with potential to be
posterior generalized to any medical field.
In a very recent publication by Ensrud and
colleagues, the authors conducted a prospective multi-center study to compare the
validity of a simple three-variable frailty
index (weight loss, inability to rise from a
chair, and poor energy) with a more complex and specific skills-required one such
as the Cardiovascular Health Study index
(83). After the analysis, they concluded
that parsimonious scores are able to provide an operational definition of frailty
that predicts falls, disability, fracture, and
long-term mortality as accurately as the
more complicated index. Therefore, simple
indexes may provide a useful phenotype of
frailty to identify high-risk older patients
in any clinical practice, suggesting that the
generalization of their applicability must
be expedited, particularly in the setting of
achieving a tailored surgical planning.
furthermore, fillit and Butler recently published a special article on what they called
“The Frailty Identity Crisis” and discussed
about the psychological changes associated
with frailty, especially in light of an upcoming surgical procedure or intervention
(84). As a result of a longer life-expectancy,
maximizing functional independence and
quality of life during the years of frailty has
become the main goal of the current geriatric medicine. The authors proposed that
a better understanding, assessment and
recognition of physical frailty can assist
individuals to anticipate and manage associated social and psychological changes,
transforming passive acceptance into an
adaptive and robust response to frailty and
consequently enabling predisposition to receive an appropriate care.
concluSion
Advanced age is still viewed as a relative
contraindication to cardiac surgery. The
significant improvement in operative out-
15
16
comes in very elderly patients, combined
with the increasing recognition that more
sophisticated markers of frailty than age in
isolation predict adverse results after surgery, mean that this view point is changing.
Very elderly patients therefore continue to
make up a growing proportion of the cardiac surgical population: a clear understanding of the impact of age on perioperative
management and outcomes will be increasingly important to clinicians involved in
their care.
No conflict of interest acknowledged by the authors
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19
proceedings
in Intensive Care
rEViEw ArticlE
20
most care®: a minimally invasive
system for hemodynamic monitoring
powered by the pressure recording
Analytical method (prAm)
S. Romagnoli1, S. Bevilacqua1, C. Lazzeri1, F. Ciappi1, D. Dini1, C. Pratesi2,
G.F. Gensini3, S.M. Romano3
Heart and Vessels Department, Cardiac and Vascular Anesthesia and Post-Cardiac Surgery Intensive Care Unit,
Careggi Hospital, Florence, Italy;
2
Heart and Vessels Department, Vascular Surgery Unit, University of Florence, Careggi Hospital, Florence, Italy;
3
Heart and Vessels Department Critical Care Medicine and Surgery, University of Florence, Careggi Hospital, Florence, Italy
1
AbStrAct
Invasive hemodynamic monitoring is a cornerstone of the care of critically ill and hemodynamically unstable
patients in both intensive care units and operating rooms. The assessment of cardiac output by means of the
pulmonary artery catheter has been considered the clinical gold standard. nevertheless, several concerns have
been raised regarding its invasiveness, usefulness, and associated complications. These disadvantages have led
to the development, during the last years, of a number of less invasive technologies for cardiac output determination. Among them, those based on the analysis of a peripheral arterial waveform have become commonly
used. Most Care® is a minimally invasive arterial pressure based monitor powered by the Pressure Recording
Analytical Method (PRAM), the only algorithm that does not require prior calibration or pre-calculated parameters and which is based of flow. PRAM provides the measurement of the main factors of hemodynamics,
such as systemic blood pressures, stroke volume, cardiac output, and vascular resistances. Moreover, dynamic
indices of fluid responsiveness are continuously displayed. In the present paper, we reviewed the current literature focusing on advantages and limitations of PRAM.
Keywords: most care, PRAM, cardiac output, hemodinamic monitoring.
introduction
The maintenance of adequate organ perfusion is one of the main targets in anesthesia and intensive care settings since it
is mandatory for anesthesiologists and
intensivists to meet the tissue oxygen and
metabolites need in their patients in any
clinical condition (1).
Dr. Stefano Romagnoli
Department of Heart and Vessels - Cardiac and Vascular Anesthesia
and Post-Cardiac Surgery Intensive Care Unit Careggi Hospital
Viale Morgagni, 85 - 50134 florence, Italy
Email: [email protected]
As a consequence, physicians need to continuously monitor hemodynamics in order
to optimize pre-load, after-load, and contractility by titrating fluids, diuretics, inotropes, and vasoactive drugs, as to achieve
the adequate delivery of oxygen and metabolites to tissues (1). Thermodilution
(ThD) by means of the pulmonary artery
catheter (PAC) has always been considered
the clinical gold standard for the measurement of cardiac output (Co) (2).
nevertheless, pulmonary artery catheterization is associated with considerable risk
of morbidities and mortality (arrhythmias,
table 1 - Main characteristics of PCMs (3).
21
picco
lidco
(pulsion medical
(lidco
Systems, munich, group plc,
germany)
london, uK)
Source of the signal
(Artery)
VigilEo
(Edwards
lifesciences
corporation,
irvine,
cA, uSA)
most care
prAm
(Vytech health,
padova,
itAly)
femoral
or Brachial
Radial
Radial
femoral
or Radial
need of dedicated
material
Yes
Yes
Yes
no
External calibration
or preloaded data
Yes
Yes
Yes
no
valvular lesions, rupture of the pulmonary
artery) and its use is declining (2). Currently, various less invasive technologies based
on the analysis of the peripheral arterial
waveform (Pulse Contour Methods, PCMs)
are gaining popularity in critical care settings and operating rooms (3, 4).
They are based on the principle of predicting a flow from an arterial pressure waveform. In fact, the arterial pressure waveform derives from the interaction between
stroke volume (SV), ejected by the left ventricle, and the physical characteristics of
the systemic vascular system during each
cardiac beat. Thus, ventricle contractility,
resistance, compliance, and arterial impedance (dynamic physical properties of the
vascular system) are simultaneously considered when assessing SV and Co (SV
× heart rate, HR). The theory of PCMs,
goes back to the classic Windkessel (air
chamber) model described by otto frank
in 1899 (5). During the XX century, the
researchers attempted the measurement of
dynamic arterial impedance by means of
calibrations and/or tests carried out both
in vitro and in vivo (6).
These studies led to unsatisfactory and
conflicting results (6). Today the most
PCMs use direct calibration by means of
ThD for the estimation of SV (7-10) and
fittings, obtained in vitro, are used to follow the modifications over time (7-10). According to the PCMs, SV can be estimated
dividing the integral of the change in pressure over time (from the beginning of systole to the dicrotic notch) by the value of
aortic impedance. SV is then adjusted taking into account HR, mean arterial pressure, and age. The SV measured by PCM is
then corrected with that measured by the
reference method (e.g. ThD; EXTERnAL
CALIBRATIon; Table 1).
nowadays, several algorithms have been
elaborated and the measurements of SV
and Co have become part of daily practice
in several clinical settings such as major
surgery, emergency department, and Intensive Care Units (ICU) (11, 12).
The major concern about PCMs lies in the
measurement of the total vascular impedance (a dynamic physical property of the
whole arterial tree), key factor for the calculation of SV from the arterial pressure
waveform (13).
Until now, as stated above, PCMs overtake
this important issue by means of an external calibration with an indicator dilution
technique (ThD or dye-dilution methods)
or uploading other pre-estimated parameters such as age, sex, and anthropometric
data (13, 14).
S. Romagnoli, et al.
22
figure 1 - Most-Care®
Most Care (Figure 1, powered by Pressure Recording Analytical Method, PRAM;
Vytech Health, Padova, Italy) is the only
PCM that measures SV without any form
of external calibration and/or pre-loaded
data (4, 15-19).
The purpose of this paper is to review the
current literature in order to focus on advantages and limitations of PRAM in various clinical settings.
Most Care® (PRAM)
PRAM is a method designed for arterial
pressure-derived continuous Co and it is
the only methodology that does not need
any starting calibration, central venous
catheterization, or any adjustments based
on experimental data (15).
As a consequence, PRAM needs only an
arterial line (radial, brachial, femoral) for
working.
PRAM is based on the principle that, in any
given vessel, volume changes occur mainly
because of radial expansion in response to
pressure variations (15, 16).
This process involves the dynamic interplay among a number of physical parameters including the force of left ventricular
ejection, arterial impedance counteracting
the pulsatile blood inflow, arterial com-
pliance, and peripheral small vessel resistance.
These variables are closely interdependent and simultaneously evaluated by
PRAM (15). Thus, any kind of flow that
is perceived at the peripheral arterial level, whether pulsatile and continuous, is
evaluated by PRAM. According to pulse
contour methodology (7) changes in the
area under the pulsatile systolic portion
of the pressure waveform reflect changes
in SV.
In PRAM, otherwise from other PCMs, the
area is computed taking into account both
pulsatile and continuous contributions of
the physical forces underlying the relationship between pressure curve morphology
and blood flow (Figure 2) (15-17).
The entire concept behind PRAM represents the practical application of a theoretical model totally developed a priori differently from other PCMs (15-18). SV is
calculated by pulsatile and continuous area
divided by a factor, system impedance z(t),
determined by the physical characteristics
of the circulatory system of the subject under study (Figure 2).
Using PRAM, it is possible for each subject
to compute z(t) directly from the analysis
of his/her pressure recording signal (15).
figure 2 - Basic algorithm of the PRAM system
(14). See text.
Another peculiar and fundamental characteristic of the PRAM methodology is the
frequency sampling of 1000 Hz whereas the
other PCMs usually use a sampling rate of
100 Hz (3). A so high frequency sampling
allows a high degree of precision which is
of primary importance for the calculation
of the arterial impedance, and the correct
measure of systolic, diastolic, mean, and dicrotic pressure.
Other parameters provided
by Most Care®
Pulse Pressure Variation (PPV)
Stroke Volume Variation (SVV)
Systolic Pressure Variation (SPV)
Most clinicians optimize intravascular volume with the use of fluid loading guided
by blood pressure, central venous pressure,
or pulmonary artery occlusion pressure.
fluid responsiveness is considered to be
present when an increase in cardiac index
of at least 15% after a volume loading can
be documented.
However, several recent lines of evidence
(19) strongly suggest that these markers of
cardiac preload, independently of the methodologies used for their measurement, are
poor predictors of fluid responsiveness.
There is a growing interest, especially on
a clinical ground, in the measurements of
the variations in blood pressure and SV
that result from the interaction between
the heart and the lungs during controlled
mechanical ventilation.
Positive pressure ventilation, when applied
to a patient at rest and with no spontaneous respiratory effort, is associated with a
cyclic increase in right atrial pressure during the inflation. It follows that, since right
atrial pressure is the back-pressure to venous return, if upstream venous pressures
do not simultaneously increase, right ventricular (RV) filling will also decrease in a
cyclic fashion.
In presence of RV and left ventricle (LV)
preload responsiveness, this cyclic variation
in RV filling will induce a cyclic variation
in left ventricular (LV) filling. The latter
phenomenon will induce a cyclic variation
in LV SV and Pulse Pressure (systolic arterial pressure minus diastolic arterial pressure) in presence of preload responsiveness. Therefore, Stroke Volume Variation
(SVV), Pulse Pressure Variation (PPV),
and Systolic Pressure Variation (SPV), are
useful predictors of volume responsiveness
when exceeded 10-15% if some conditions
of cardiac rhythm and ventilator pattern
are respected (19, 21).
Most Care displays SVV, PPV, SPV, and
Dicrotic PV (DicPV), calculated according
to the operator’s needs (default every 15
seconds).
Maximal Pressure/Time ratio (dP/dTMAX)
With a sampling rate of 1000 Hz, PRAM
displays the exact value of dP/dTMAX (the
maximal slope of the systolic portion of the
arterial pressure waveform).
This parameter depends on the relationship between left ventricular function and
arterial tone and stiffiness.
The velocity of transmission and the reflected waves depend on the arterial vessel
characteristics (stiffiness, tone, stenosis,
and so on).
Thus, an accurate value of dP/dTMAX contemporary to the other hemodynamic parameters, helps in depicting the cardiovascular status of the patient.
Systemic Vascular Resistance (SVR)
Systemic Vascular Resistance is calculated
in Dynes* sec/cm5 with the standard formula: SVR = (mean arterial pressure minus central venous pressure)/Co × 80.
The central venous pressure can be measured by means of a second auxiliary cable.
otherwise the operator can set a value of
pressure if a central venous catheter has
not been placed.
23
24
Cardiac Cycle Efficiency (CCE)
CCE (adimensional value) describes the
cardiac hemodynamic performance in
terms of the ratio between hemodynamic
work performed and the energy expenditure (23).
CCE shows the ability of the cardiovascular system to maintain homeostasis at different energy levels.
The clinical significance of this parameter
is still under evaluation.
Validation studies
In 2002, Romano et al. (15), simultaneously estimated Co by direct-oxygen fick
method, PAC-ThD, and PRAM applied to
pressure signals recorded either invasively
from an aortic catheter (PRAMa) or noninvasively, at the finger level, by photoplethysmography (PRAMf) in 22 adult hemodynamically stable cardiac patients submitted to cardiac catheterization.
A good correlation between PRAM and
both fick method and ThD were found
(fick method vs. PRAMf, r2=0.94; fick
method vs. PRAMa, r2=0.88; ThD vs.
PRAMf, r2=0.77; ThD vs. PRAMa,
r2=0.77).
The Bland-Altman analysis confirmed the
agreement between the fick method and
PRAM, and ThD and PRAM.
In 2004, Giomarelli et al. (18) measured
Co in 28 patients undergoing coronary
artery bypass grafting at 15 min after anesthesia induction, 30 min after weaning
from extracorporeal circulation, 1 and 3
h after arrival in the ICU comparing PACThD and PRAM. Co ranged from 2.3 to
7.4 l/min.
A good correlation between methods was
indicated by r2=0.78. The Bland–Altman
analysis demonstrated that the overall estimates of Co measured by PRAM closely
agreed with Co measured by PAC (mean
difference, 0.027; standard deviation, 0.43;
limits of agreement, -0.83 and +0.89). In
2005, Scolletta et al. (17) compared PRAM
with electromagnetic flowmetry (EM-Co)
and ThD (ThD-Co) during various hemodynamic states (dobutamine and hemorrhage) in a swine model. Co ranged from
1.8 to 10.4 l/min.
The authors found close agreement between the techniques. Mean bias between
EM-Co and PRAM-Co was -0.03 l/min
(precision 0.58 l/min). The 95% limits of
agreement were -0.61 to +0.55 l/min. Similar results between ThD-Co and PRAMCo were found.
Romano et al. in 2006 (16) compared
PRAM-Co and ThD-Co in 50 cardiac patients. PRAM-Co was measured invasively in ascending aorta (PRAMa) and non
invasively at the finger (PRAMf). PRAMa
and PRAMf resulted to be accurate when
compared with the gold standard (ThD
vs. PRAMf, r2=0.76 and mean bias 0.05
l/min/m2; ThD vs PRAMa r2=0.73 and
mean bias 0.03 l/min/m2).
In 2008, Co measured by PRAM was
compared with Co measured by Doppler
echocardiography in 48 pediatric patients
(20) showing a good agreement between
methods also in children.
Patients with low cardiac output syndrome
treated with inotropic drugs or with Intra
Aortic Balloon Pump do not represent a
a limitation for PRAM as Maj et al. (22)
recently observed in a prospective study
comparing cardiac index measured with
PRAM and ThD in 20 patients who underwent cardiac surgery.
We recently published an experimental study comparing the Co measured
by means of PRAM (PRAM-Co) with
that measured with two different methods: thermodilution-PAC (ThD-Co) and
Transesophageal Echocardiograpy (TEECo) in a swine model (4).
Dobutamine, vasoconstriction, hemorrhage, and volume resuscitation were induced step-by-step. The Bias resulted from
Most Care®: a minimally invasive system for hemodynamic monitoring
the comparison between PRAM-CO and
ThD-CO was-0.006 l/min and the Percentage Error was 22.8%. The comparison between PRAM-CO and TEE-CO resulted
in: Bias=-0.007 l/min and Percentage Error=22%. Sub-group analysis revealed
disagreement between methods during
the last two steps of hemorrhage (-35 and
-50% of the theoretical volemia): PRAMCO vs ThD-CO: Bias=-0.37 l/min, and
Percentage Error=45%; PRAM-CO vs.
TEE-CO: Bias=0.4 l/min and Percentage
Error=62%. We concluded that PRAM
proved to be accurate in measuring CO
during hemodynamic stability, tachycardia, and vasoconstriction. When volemia
was reduced more than 35%, disagreement
between methods was observed.
Further larger clinical studies are needed
to confirm the reliability of PRAM in measuring hemodynamic parameters during
conditions of hemodynamic instability.
Moreover, studies focusing on the influence
of hemodynamic monitoring, by means of
minimally-invasive tools, on outcome are
still lacking.
Limitations
A primary concern about PCMs reliability
is related to the quality of the recorded arterial pressure signal.
The signal can be inadequate for patientrelated and technical-related reasons.
Patient-related causes of inappropriate signal acquisition may be due to aortic valve
regurgitation or abnormal transmission of
the signal itself such as during aortic dissection or in every vascular condition resulting in obstruction to the transmission
of the signal (thoracic outlet syndrome,
significant stenosis along the arterial
tree from the aortic valve to the sampling
site).
Technical-related problems may be due to
inadequate dynamic response of the transducer and fluid-filled tubing system cur-
25
Figure 3 - Under-damped resonating arterial–
signal. Note steep systolic upstroke and narrow
systolic peak.
rently used for invasive blood pressure
monitoring.
Under-damped waveforms and resonance
of the signal (Figure 3) are frequently encountered during arterial pressure monitoring in both operating rooms and critical
care settings. An inadequate damping of
the signal (Figure 3 and 4), may lead to an
incorrect estimation of arterial impedance
and hence an incorrect value of SV. As a
consequence, the possibility to correctly
employ a minimally-invasive system for
hemodynamic monitoring like PRAM is
Figure 4 - Over-damped arterial signal. Note the
loss of evidence of the details.
26
influenced by the physician after a careful
observation of the arterial waveform.
The user must be aware that an inadequately damped signal may lead to misinterpretation of hemodynamics, several
devices with different degrees of invasiveness are available for monitoring hemodynamics in critically ill patients and none
fulfils the criteria of optimal monitor.
In this context, PRAM seems to be a feasible and efficient alternative to standard
monitoring systems in particular in those
settings in which a more invasive and
somewhat aggressive monitoring (TEE
and/or PAC) appears not justified or disproportionate.
Since PRAM does not require any calibration, or any additional invasive procedure,
it is not time-consuming and does not expose the patient to potential complications
related to central venous catheterization.
Although PRAM seems to be easy to use,
the understanding of the underlying cardiovascular pathophysiology is of primary
importance to avoid misinterpretation of
the displayed data. finally, a careful observation of the arterial wave morphology
represents the first and key contribution
that the physician has to take into account
when an arterial pressure-based hemodynamic monitoring as PRAM is used before
interpreting the data.
Even a highly sophisticated and accurate
methodology as PRAM cannot replace the
critical mind of the physician.
Conflict of interests
For the potential implications concerning Conflicts of
Interest, the authors wish to inform the Editor that Dr.
SM Romano is the owner of the patent for the Pressure
Recording Analytical Method (PRAM). The other authors declare that they have no competing interests.
rEfErEncES
1. Romagnoli S, Romano SM, Bevilacqua S, et al.
HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2009; 1: 60-64.
2. Pinsky MR. Hemodynamic monitoring over the
past 10 years. Crit Care 2006; 10: 117.
3. funk DJ, Moretti EW, Gan TJ. Minimally invasive cardiac output monitoring in the perioperative setting. Anesth Analg 2009; 108:
887-897.
4. Romagnoli S, Romano SM, Bevilacqua S, et al.
Cardiac output by arterial pulse contour: reliability under hemodynamic derangements.
Interact Cardiovasc Thorac Surg 2009; 8: 642646.
5. frank o. Die Grundform des arteriellen Pilses.
Erste abhandlung. Mathematische Analyse. z
Biol 1899; 37: 483-526.
6. Starr I, Schild A. Studies made by simulating
systole at necropsy. J Appl Physiol 1957; 11:
169-173.
7. Wesseling KH, Jansen JRC, Settels JJ, et al.
Computation of aortic flow from pressure
in humans using a nonlinear, three-element
model. J Appl Physiol 1993; 74: 2566-2573.
8. Jansen JR, Schreuder JJ, Settels JJ, et al.
Single injection thermodilution. A flowcorrected method. Anesthesiology 1996; 85:
481-490.
9. Gödje o, Hoke K, Lamm P, et al. Continuous,
less invasive, hemodynamic monitoring in intensive care after cardiac surgery. Thorac Cardiovasc Surg 1998; 46: 242-249
10. Gödje o, Hoke K, Goetz AE, et al. Reliability of a new algorithm for continuous cardiac
output determination by pulse-contour analysis during hemodynamic instability. Crit Care
Med 2002; 30: 52-58.
11. ospina-Tascòn GA, Cordioli RL, Vincent JL.
What type of monitoring has been shown to
improve outcomes in acutely ill patients? Intensive Care Med 2008; 34: 800-820.
12. Cholley BP, Payen D. noninvasive techniques
for measurements of cardiac output. Curr
opin Crit Care 2005; 11: 424-429.
13. Hamzaoui o, Monnet X, Richard C, et al.
Effects of changes in vascular tone on the
agreement between pulse contour and transpulmonary thermodilution cardiac output
measurements within an up to 6-hour cali-
bration-free period. Crit Care Med 2008; 36:
434-440.
14. Maus TM, Lee DE. Arterial pressure-based
cardiac output assessment. J Cardiothorac
Vasc Anesth 2008; 22: 468-473.
15. Romano SM, Pistolesi M. Assessment of cardiac output from systemic arterial pressure
in humans. Crit Care Med 2002; 30: 18341841.
16. Romano SM, Conti AA, Giglioli C, et al. Blood
flow Assessment by Arterial Pressure Wave
without External Calibration. Comput in Cardiol 2006; 293-296.
17. Scolletta S, Romano SM, Biagioli B, et al. Pressure recording analytical method (PRAM) for
measurement of cardiac output during various
haemodynamic states. Br J Anaesth 2005; 95:
159-165.
18. Giomarelli P, Biagioli B, Scolletta S. Cardiac
output monitoring by pressure recording analytical method in cardiac surgery. Eur J Cardiothorac Surg 2004; 26: 515-520.
19. Monnet X, Teboul JL. Volume responsiveness.
Curr opin Crit Care 2007; 13: 549-553.
20. Calamandrei M, Mirabile L, Muschetta S, et
al. Assessment of cardiac output in children:
a comparison between the pressure recording analytical method and doppler echocardiography. Pediatr Crit Care Med 2008; 9:
310-312.
21. Sorbara C, Romagnoli S, Rossi A, et al. Circulatory failure: bedside functional haemodynamic monitoring. In: Atlee JL, Gullo A,
2nd eds. Perioperative critical care cardiology.
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22. Maj G, Landoni G, Bignami E et al. PRAM
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27
proceedings
in Intensive Care
originAl ArticlE
28
percutaneous aortic valve implantation:
the anesthesiologist perspective
R.D. Covello1, G. Landoni1, I. Michev3, E. Bignami1, L. Ruggeri1,
F. Maisano2, M. Montorfano3, O. Alfieri2, A. Colombo3, A. Zangrillo1
1
Department of Anesthesia, Intensive Care; 2Cardiac Surgery; 3Laboratory of Interventional Cardiology, Università Vita-Salute
San Raffaele, Milano, Italia e Istituto Scientifico San Raffaele, Milano, Italy
AbStrAct
Percutaneous aortic valve implantation is an emergent technique alternative to surgical aortic valve replacement in high risk patients with aortic stenosis. Percutaneous aortic valve implantation techniques are undergoing rapid development and currently represent a dynamic field of research. Perioperative optimal strategies
keep on evolving too. At a review of the literature, only three previous papers on Pubmed focused specifically
on anesthesiological challenges of percutaneous aortic valve implantation. In one of them our first 6 months
experience was reported. In this new paper we describe the anesthesiological management of percutaneous
aortic valve implantation at our Centre, reporting the results of our implantation program from november 2007
to february 2009.
Keywords: percutaneous aortic valve implantation, aortic stenosis, general anesthesia, local anesthesia.
introduction
Rapid progress in interventional cardiology has recently seen the rate of percutaneous coronary intervention overtake that
of coronary artery bypass surgery. now attention is directed towards the treatment
of valvular heart diseases, with exciting
developments in balloon and stent technology having the potential to transform
the management of many common heart
conditions, such as aortic stenosis (1).
Aortic stenosis is the most common form
of valvular heart disease in adults, affecting thousands of patients every year and
causing significant morbidity and mortality in case of advanced disease. Surgical
Landoni Giovanni, MD
Department of Cardiothoracic Anesthesia and Intensive Care
Istituto Scientifico San Raffaele, Milano, Italia
Via olgettina, 60 - 20132 Milano, Italy
aortic valve replacement is the treatment
of choice for a vast majority of patients (2).
However, in a subset of patients, mainly elderly patients with declining overall health
status or severe comorbidities, aortic valve
replacement is considered either too high
risk or contraindicated (3).
The size of this cohort is expected to increase in the next several years, reflecting
the aging population and the improving
therapeutic options in patients with multiple and advanced medical conditions.
Moreover, prognosis with medical management is poor (2), and effects of percutaneous balloon aortic valvuloplasty (BAV)
are modest and short-lived (4, 5). Given
the limited therapeutic options in these
patients, there has been interest in the
development of transcatheter aortic valve
implantation (TAVI) techniques. The rationale is that of minimizing the overall
surgical trauma by avoiding sternotomy,
percutaneous aortic valve implantation: the anesthesiologist perspective
aortotomy, use of cardiopulmonary bypass
(CPB), and by implanting the prosthesis
on the beating heart, thereby avoiding cardiac arrest.
litErAturE rEViEw
To the best of our knowledge, only three
groups focused on the anesthesiological
management of TAVI so far.
Ree et al. (6) described both the evolution
and the main associated complications
in the anesthetic management of the initial 40 patients undergoing percutaneous
retrograde aortic valve replacement at St.
Paul’s Hospital (Vancouver, Canada). The
first four patients received monitored anesthesia care, while the subsequent 36 underwent general anesthesia.
There were no anesthesia-related adverse
events. The prosthetic valve was placed
successfully in 33/40 patients (83%). Median anesthetic time was 3.5 hours (range,
1.25-7.25 hours).
Thirty-two/40 patients required vasopressor support. The most common, serious
procedural complications were myocardial
ischemia and arrhythmia following rapid
ventricular pacing, hemorrhage from vascular injury secondary to the placement
and removal of the large-bore sheath in
the ilio-femoral artery, aortic rupture, and
prosthetic valve maldeployment; 30-day
mortality was 13% (n=5/40).
Behan M et al. (7) described the experience of the Sussex Cardiac Centre (Brighton and Sussex University Hospital, Brighton, UK) performing TAVI procedures in
12 patients Three of them underwent
the procedure under general anesthesia
and nine under remifentanil-based sedation. There were no differences between
the groups in terms of comorbidities and
clinical characteristics. The procedure was
visualized using fluoroscopic aortic calci-
fication coupled with multiple small volume aortograms. one patient converted
from sedation to general anesthesia. one
patient in the general anesthesia group
died from respiratory complications. They
concluded that TAVI can, in the majority
of cases, be performed under remifentanilbased sedation resulting in a shorter implant procedure time, reduced stay in high
dependency areas, and shorter time to hospital discharge
We recently published our initial six
months experience in anesthesiological
management for TAVI (8). In our experience updated to february 2009, 50 patients (79+7.3 years, logistic EuroSCoRE
25.4+15) underwent TAVI using a balloon expandable (34 patients) or a selfexpandable (16 patients) prosthesis.
Valve deployment was visualized by highresolution fluoroscopy and contrast angiography. nineteen patients received
general anesthesia, and 31 received local
anesthesia plus sedation.
Two patients had to be converted from
local anesthesia to general anesthesia (1
refractory ventricular fibrillation and one
pt was resteless). Procedural complications included prosthesis embolization
(1 patient), ascending aorta dissection (1
patient), arrhythmias following rapid ventricular pacing (5 patients) and vascular
access site complications (8 patients). one
valve-in-valve implantation because of severe aortic regurgitation after the first procedure was performed.
five patients in the general anesthesia
group were extubated in the theatre and
mechanical ventilation time in intensive
care unit (ICU) was 12 hours. Mean ICU
stay in the general anesthesia group was
34+3 hours vs 15+3 hours in the local
anesthesia group (p=.009). Postoperative complications included acute renal
failure (7 patients), III° atrio-ventricular
block (12 patients), sepsis (9 patients) and
29
R.D. Covello, et al.
30
stroke (1 patient). All 50 patients were
alive 30 days after the procedure. At the 6
moths follow-up 4 out of 30 patients died
for non-cardiac reasons.
procEdurES
Two technologies, the balloon-expandable
Edwards/Sapien Bioprosthesis (Edwards
Life-sciences Inc., orange, CA), and the
self-expandable CoreValve ReValving System (CRS TM, CoreValve Inc., CA, USA)
have been used in the largest clinical series
(9). These technologies present differences in design and implantation technique.
Several other technologies are being developed and have entered or are expected to
enter an active phase of clinical testing in
the next future.
All current TAVI procedures start with
conventional BAV to provide an enlarged
passageway for the subsequent insertion
of the prosthesis. Although initial procedures were performed using the so-called
“antegrade” approach (10), via transfemoral vein access, this procedure has been
complication-prone and has been largely
abandoned. Most commonly, the preferred
“retrograde” approach requires transfemoral artery access (percutaneously, surgically or hybrid) negotiation of femoral, iliac
and aortic vasculature, retrograde crossing
of the native aortic valve and valve deployment in the subannular region (9, 10). A
vascular access via subclavian artery (11)
and the hybrid “transapical” approach
(12), through the left ventricular apex,
provide an alternative route to retrograde
transfemoral access in patients with diseased femoral, iliac and aortic anatomy.
The positioning of the prosthesis is mostly
aided by high-resolution fluoroscopy, contrast angiography and transesophageal
echocardiography. After the final assessment of device position and function, the
delivering system is removed and vascular
access sites are closed either surgically or
percutaneously. Iliac and femoral angiography is advocated to ensure the integrity
of vessel repair and the absence of vascular
complications such as perforation, dissection and occlusion. Surgical repair of these
complications may be required; endovascular stenting can be beneficial in selected
cases.
pAtiEnt SElEction And
prEopErAtiVE EVAluAtion
A number of predictive risk models have
been employed to ascribe an objective
quantitative risk profile for the purpose of
patients selection for TAVI. The two risk
models most commonly used are the Europen System for Cardiac operative Risk
Evaluation (EuroSCoRE) (13) and the
Society of Thoracic Surgeon (STS) database (14). notably, these predictive tools
for operative risk assessment are imprecise, especially at high levels of risk, not
entirely consistent from model to model,
and generally omit important risk factors,
such as severe thoracic aorta calcification,
previous chest wall radiation or liver cirrhosis (15-17).
Most appropriately, the best characterization of individual risk should be a combination of objective quantitative predictive
models and subjective assessment by experienced surgeons, cardiologists and anesthesiologists.
The therapeutic option of TAVI has to
be discussed extensively for the individual patient and approved on the basis of
a consensus that conventional surgery is
excessively high risk in terms of anticipated mortality and morbidity. The definition of the “inoperable” patient remains
a pivotal consideration. Patients are excluded if a reasonable quality or duration
of life (>1 year) are considered unlikely
despite valve replacement because of comorbidities. A comprehensive evaluation
of patients’overall medical condition and
non-cardiac comorbidities is essential and
follows the same algoritm as used in surgical patients. Besides comorbidities, older
age arises special anesthesiological concerns. Some patients may have unrealistic
expectations regarding the risk and degree
of invasiveness of the procedure.
An honest and appropriate explanation of
the anesthetic management of the procedure and the risks involved is an essential
feature of the preoperative encounter.
A thoughtful management planning requires that the specialist opinion of the
anesthesiologist, and not just that of cardiologists and cardiac surgeons, should
always be sought early. Moreover, it is imperative for the “valve team” to plan preoperative strategies of treatment in case of
procedural complications, determining the
potential for surgical bailout in advance of
the procedure.
monitoring And
AnESthESiologicAl SEtup
The anesthesiologist has to take a participative role in developing monitoring and
standards of care in the cath lab for this
kind of procedures. It is important to note
that physical environment of the cath lab
is mostly designed to accommodate the
needs of cardiologists, having an anesthesiologist taking an active role in patient
care was not a primary concern when designing the cath lab (18).
Basic monitoring equipment and setup
items that are considered standards in operative rooms, may therefore not be present in the cath lab. The cath lab has to be
stocked with additional equipment and
drugs that anesthesia providers typically
require to manage difficult airways and
hemodynamically unstable patients. Ideally, all operations should be performed in
a hybrid operation theatre, i.e. a standard
operative room with an additional angiography system.
Since the risk of hemodynamic instability
and the need of emergent CPB and open
surgery decreases with increasing equipe’s
experience, given the proven feasibility of
performing the procedure under local anesthesia plus sedation, may be a tendency
to simplify the anesthesiological setup.
The perceived excess of prophylactic anesthetic preparations versus a more relaxed,
confident and less complex approach has
to be interpreted in the light of possible severe periprocedural complications.
At our Institution, all patients are monitored with five-electrodes EKG, pulsoxymetry, urinary catheter, bladder temperature, arterial and central venous lines.
Two external adhesive pads are attached
to the patient, for early management of arrhythmias.
Maintenance of normothermia is accomplished by an external convective warming
system, an under body blanket and an intravenous fluid heater system. Pulmonary
artery catheterization is not routinely performed and reserved to specific situations,
such as left ventricular dysfunction and/
or pulmonary hypertension.
A pulmonary artery catheter sheath may
be placed at the time of initial central venous cannulation, allowing for further
monitoring and providing a ready access
to transvenous pacing routes in case of
atrioventricular block, besides an adjunctive access for fluids.
Periprocedural transesophageal echocardiography (TEE) during PAVI may provide
useful informations (19, 20). It aides the
advancement of guidewires and delivery
system and it allows to evaluate the effects
of BAV (leaflet mobility, aortic regurgita-
31
32
tion), the position of the prosthesis at deployment, and post-implant valve assessment (area and gradient, leaflet mobility,
regurgitation grade and location). TEE is
of particular value when valve calcification are mild and fluoroscopic imaging difficult. Moreover it provides informations
about preload and ventricular function,
thoracic aorta anatomy and procedurerelated complications, such as pericardial
effusion and iatrogenic mitral regurgitation, thus guiding a prompt management
of these events.
Drawbacks of periprocedural TEE may be
the fact that it requires general anesthesia, it is sometimes limited in its ability
to clearly distinguish the prosthesis while
crimped on the delivery system and it may
interfere with fluoroscopic imaging, necessitating probe withdrawal at the time
of implantation.
At our Institution, all patients receive a
transthoracic or transesophageal (if general anesthesia is used) echocardiographic
evaluation at the end of the procedure,
while periprocedural TEE evaluation is
usually performed in selected high risk
cases (aortic disease, concomitant heart
valve problems) and when complications
are suspected.
newer modalities including intra-cardiac
and three dimensional echocardiography,
and CT angiography may further assist
these procedures.
hEmodynAmic mAnAgEmEt
Hemodynamic stability is the main objective of anesthesiological management during TAVI. Goals of hemodynamic management are those typical of aortic stenosis.
Intravenous fluid administration should
be carefully titrated to provide adequate
preload to a hypertrophied left ventricle.
Tachycardia should be avoided to allow
adequate diastolic filling time, and sinus
rhythm should be maintained to preserve
the contribution that atrial contraction
adds to ventricular filling.
The systemic blood pressure must be
maintained at a level to ensure coronary
perfusion.
This may be accomplished through the use
of vasopressor drugs, such as ethilephrine
or norepinephrine. Since a significant
proportion of the left ventricular afterload
is produced by the stenostic aortic valve,
vasopressor agents may be used without
concern of adversely affecting ventricular
performance, even in patients with poor
left ventricular function.
Moreover, TAVI poses significant specific
periprocedural challenges. Performing a
BAV first allows easier passage of the prosthesis through the severely stenotic native
aorti valve. furthermore, the dilated aortic
valve permits cardiac ouput circumventing the delivery system and better hemodynamics especially in patients with critical aortic stenosis. During BAV and the
balloon-expandable prosthesis implantation, a transient partial cardiac standstill
is induced to minimize cardiac motion and
pulsatile transaortic flow, which would
otherwise act to eject the inflated balloon,
resulting in balloon slippage and device
embolization and malpositioning. In earlier cases, CPB has been used to unload the
left ventricle and to support the circulation
during the deployment (21).
Pharmacologic agents such as adenosine
and beta-blockers have also been employed;
however, with inconsistent result. At present rapid ventricular pacing (RVP) is the
preferred method to achieve this purpose
(22), with suggested mechanism of action
including induced atrio-ventricular asynchrony, left ventricular dyskinesis, compromised ventricular filling and reduction
in stroke volume and cardiac output. RVP
is performed at 220 bpm, and in case of
the presence of exit block, the rate is lowered by 20 bpm sequentially until reliable
capture is achieved and a reduction in systolic arterial pressure to below 50 mmHg
is observed.
A coordinated approach has been developed wherein one operator observes the
fluoroscopic image and maintain the ideal
valve position, a second operator starts
pacing, and a third confirms reliable pacemaker capture and effective reduction in
arterial pressure before rapidly inflating
and then deflating the balloon.
only when the balloon is fully deflated the
pacing ends. While RVP is advantageous
for valve positioning, the combination of
rapid heart rate, myocardial hypertrophy
and low coronary perfusion pressure produces an ischemic deficit in the myocardium. In most cases this ischemic deficit is
well tolerated, most likely because of the
brief duration of the RVP (12 seconds on
average). However, it is prudent to minimize the number and duration of rapid
pacing episodes during the procedure, and
allow hemodynamic recovery before further pacing.
A bolus dose of a vasopressor such as
etilephrine administered just prior or immediately after the rapid pacing episode
will allow coronary perfusion pressure to
be regained sooner. If the blood pressure
does not recover promptly after an episode of RVP, myocardial ischemia must be
suspected. The ischemic insult is usually
caused by pacing, but coronary artery embolism from disruption of the calcified native aortic valve, or obstruction of one or
both coronary ostia by the prosthetic valve
or the displaced native valve leaflets must
be considered.
Treatment of post-pacing myocardial ischemia is based initially on the restoration
of coronary perfusion pressure through
the use of vasopressor agents. In case of
ischemia-induced ventricular fibrillation
during valve deployment, consideration
should be given to complete valve deployment before electrical cardioversion, thus
avoiding prosthesis malpositioning or embolization when sinus rhythm is restored.
If the hemodynamic status fails to improve
and the valve has not yet been deployed,
the deployment of the prosthesis is the
next step in management.
The main benefit of valve deployment is
that it reduces left ventricular afterload,
ventricular wall tension and myocardial
oxygen demand, as well as it improves
cardiac output. In the patient with acute
aortic insufficiency following BAV, valve
deployment may be the definitive management. If the patient remains unstable following valve deployment, femoral-femoral
CPB can be rapidly instituted.
By intention CPB has been used in some
centres during the first TAVI procedures,
but it has been largely abandoned because
the procedures appear to be well tolerated
without extracorporeal support in most
patients. Still, we suggest that an experienced cardiac surgeon and a perfusionist
should be present or on call, in case of rapid cardiovascular deterioration requiring
emergent CPB.
In case of hypotension during TAVI, besides ischemia ad aortic regurgitation, differential diagnosis must include cardiac
tamponade, acute mitral regurgitation and
major arterial bleeding/rupture.
Cardiac tamponade causing cardiovascular collapse may result from perforation
of the right ventricle during pacing wire
placement, and aortic or left ventricular
perforation by guidewires or catheters. If
tamponade occurs, it is easily detected by
an associated increase in central venous
pressure, visualization of the pericardial
fluid and right-sided collapse on TEE, and
abnormal movement of the heart on fluoroscopy.
The management may consist of percuta-
33
34
neous needle drainage of the pericardial
blood or surgical intervention.
Acute mitral regurgitation may result
from mitral impingement by the delivery
catheters and the valve prosthesis. It can
be readily diagnosed by continuous TEE
monitoring.
Major arterial bleeding/rupture may complicate transfemoral artery procedures. A
steady loss of blood through the valved
sheath may be appreciated when catheters or wires in the vessels compromise
the valve closure. A sudden unexplained
decrease in blood pressure, particularly on
decannulation, should alert to the possibility of a major vascular rupture which may
require prompt intervention, whether by
open or endovascular route.
Blood loss may be not readily apparent, as
significant volumes may be lost retroperitoneally, but it is easily detected by contrast aortography.
An occlusion balloon may be deployed
proximal to the perforation to attenuate
the hemorrhage, and vigorous volume resuscitation with fluid and blood products
may be required in addition to the use of
vasopressor agents to maintain coronary
perfusion. Usually an arterial guide wire
is left in situ during the decannulation
process so that if a vascular damage occurs the defect may be immediately fixed
endoluminally without the need for open
surgery.
Mild-to-moderate aortic regurgitation,
mostly paravalvular, is observed in 50%
of cases (23). However, the availability of
larger prostheses and their careful matching with the size of the aortic annulus led
to the decrease in the incidence of severe
aortic regurgitation to 5%.
further dilatation of the valve stent and
valve-in-valve procedures have been suggested, but a severe periprosthetic aortic
regurgitation with cardiogenic shock may
require emergent surgery (24).
AnESthESiA tEchniQuES
Anesthesia techniques for TAVI may vary
according to patient’s characteristics and
coexisting diseases, and procedural instances. Advantages of general anesthesia
are easily clear. first, general anesthesia
facilitates positioning of the valve prosthesis by maintaining patient immobility during fluoroscopy.
neuromuscolar paralysis allows the anesthesiologist to control respiratory motion
during radiographic filming and program
short periods of apnoea, thus avoiding
breathing artifacts interfering with prosthesis placement.
Moreover, some patients undergoing TAVI
with local anesthesia may become restless
lying completely still for an hour or more,
which is usually the time required for the
procedure.
Thus, general anesthesia may be more favorable when the patient is unable to tolerate the operation secondary to fatigue
or having to maintain the same position
through the entire procedure. Second,
general anesthesia facilitates introducer
sheaths placement and removal and eventual surgical repair of arterial access sites,
which can be potentially complicated and
prolonged. Third, it allows the use of TEE
as an adjunctive imaging modality. finally, it facilitates management of procedural
complications.
Induction of general anesthesia can be
done with a variety of agents. In patients
undergoing TAVI anesthetic requirements
are reduced because of advanced age and
decreased cardiac output due to the severely stenotic aortic valve. The procedure itself does not produce a significant amount
of surgical stimulation.
The choice of induction agents seems to
matter less than the manner in which they
are administered, which should be slowly
and titrated to effect carefully. Mainte-
nance of anesthesia may be accomplished
with inhalational agents, intravenous
agents, or a combination of both. Inhalational agents may have some advantage offering some protection from the ischemic
insult produced during the procedure by
myocardial preconditioning.
Short acting agents that are rapidly cleared
are preferred to facilitate extubation at the
end of the procedure. Airway management
is usually performed by endotracheal intubation. Because of the possible prolonged
procedure and the use of TEE, use of laryngeal mask airway is not advised.
Yet general anesthesia is associated with
important potential complications, particularly respiratory, which high risk patients
who are unfit for surgical aortic valve replacement may tolerate poorly (25). on
the basis of the EURoSTAR data, highrisk patients in particular attain important
advantages from minimally invasive anesthetic techniques during endovascular aortic aneurysm repair: mortality, morbidity,
hospital stay and intensive care unit (ICU)
admission are significantly lower for regional and local versus general anesthesia
in the EURoSTAR registry (26).
Similar benefits could be expected in highrisk patients undergoing TAVI with local
anesthesia.
A trend for shorter procedure time, time
to ambulation, high-dependency unit stay
and overall hospital stay has been observed
in our experience (8). Each of these factors
is of significance both for patient morbidity and satisfaction, and for hospital efficiency and costs.
In our experience, general anesthesia has
been the preferred technique at the beginning of our implantation program, accompanying operator’s learning curve. With
increasing equipe’s experience, since the
technique became straightforward and the
feasibility of local anesthesia plus sedation
became apparent, a shift was seen towards
almost exclusive use of local anesthesia
plus sedation.
At our Institution the anesthetic regimen
for local anesthesia technique consists of
1% lidocaine injected subcutaneously at
the arterial and venous access sites (maximum dose 4 mg/kg). In adjunct, sedation
is accomplished with remifentanil infusion adjusted according to response (target
level: score 2-3 with modified Wilson sedation scale (27); starting dose 0.02 mcg/
kg/min, maximum dose 0.2 mcg/kg/min).
Combined use of remifentanil and propofol (range dose 2-5 mg/kg/h) may be used
according to patient’s and procedural requirements in order to reach the above
mentioned sedation level. operator-delivered sedation is unlikely to be successful
for these patient whose hemodynamics
are brittle and tolerance of invasive procedures may be limited.
A potential advantage of local anesthesia
may be the fact that overstretching the arterial system by the delivery sheath induces discomfort which alerts the physician of
the risk of vascular injury or rupture.
In our experience, the passage of relatively large and stiff deployment catheters
through the arteries is well tolerated with
local anesthesia, and concerns of patients
tolerance for vascular repair with local
anesthesia are perhaps unfounded, since
intravenous sedation is used to maximize
comfort rather than to provide analgesia.
A preoperative ilioinguinal/iliohypogastric block can be performed to reduce the
total dose of infiltration local anesthetics
in patients with reduced metabolic capacity, at increased risk for neurologic and
cardiac toxicity.
If local anesthesia plus sedation is employed, the anesthesiologist must be ready
to institute full general anesthesia at any
moment. This concept of “standby” general anesthesia appears to offer enhanced
flexibility in scheduling patients for these
35
36
procedures. Patients with anticipated difficult airway are obviously unsuitable for
this technique, because the risk of delay in
airway access during emergent situations
may be worse than the potential benefits
of a less invasive anesthetic technique.
notably, fluoroscopy equipment regularly
limits access to patient’s head which may
be difficult once the procedure has started.
We are planning a large randomized trial
of general versus local anesthesia to evaluate whether the choice of anesthetic technique affects the outcome of patients undergoing TAVI.
poSt-procEdurAl courSE
Most patients undergoing TAVI with general anesthesia are able to be extubated in
the theatre at the end of the procedure,
unless they are hemodynamically compromised or difficult airways. It is imperative
to continuously evaluate the patient for
the appropriateness of fast tracking as the
operation progresses.
Patients who require mechanical ventilation postoperatively are usually able to be
extubated within a few hours. Pain management is accomplished in most patients
by nonsteroidal agents/paracetamol and
opioids low rescue doses. It is important
to note that these high risk patients are
prone to complications at any time during
hospital stay, with a pattern of complications substantially different from standard
cardiac surgery.
According to single Institution organization, an early transfer to an intermediate
care unit provided with bedside telemetry,
could be a suitable strategy in selected patients with uneventful operative course.
Ideally, all patients should stay in ICU for
at least 24 hours and be closely monitored
for several days especially as regards he-
modinamics, vascular access, rhythm disturbances and renal function.
In this regard, main concerns may be arised
by atrioventricular block (4-8%), necessitating pacemaker implantation in up to
24% with self-expandable devices (23).
The transvenous pacing lead is routinely
left in situ after the procedure if self-expandable device is implanted. Moreover,
acute renal injury remains a frequent
cause of morbidity in patients undergoing
TAVI. General risk factors include diabetes
mellitus, pre-operative renal insufficiency,
age, volume depletion-hypotension-low
cardiac output, nephrotoxic drugs and
high volume of contrast media.
Among others, specific risk factors comprise transapical access, number of blood
transfusions, post-interventional thrombocytopaenia and severe inflammatory
response syndrome (SIRS). Preventive
measures pre-procedure, as well as careful post-procedure management, should be
routine in all patients.
concluSionS
Six years after the first-in-man, TAVI technique is undergoing rapid development
and dissemination.
As this new procedures is on its way towards clinical practice, perioperative optimal strategies keep on evolving.
Anesthesiologists must be aware of current technologies, playing a participative
role in developing standards of care for
these high risk patients and supporting the
continuous refinement toward a more and
more minimally invasive approach.
Acknowledgments
We’re indebted to Fichera M, RN and Virzo I, RN, and
Zuppelli P, RA, for the careful revision of the manuscript and the support in data entry.
Conflict of interest statement: Maisano, Alfieri and
Colombo acknowledge teaching fee from Edwards.
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proceedings
in Intensive Care
originAl ArticlE
can timing of tracheal extubation
predict improved outcomes
after cardiac surgery?
S.L. Camp1, S.C. Stamou1, R.M. Stiegel1, M.K. Reames1, E.R. Skipper1, J. Madjarov1,
B. Velardo2, H. Geller2, M. Nussbaum1, R. Geller1, F. Robicsek1, K.W. Lobdell1
1
Department of Thoracic and Cardiovascular Surgery; 2Department of Anesthesiology Carolinas Heart and Vascular Institute,
Carolinas Medical Center, Charlotte, North Carolina, US
AbStrAct
Introduction - Early tracheal extubation is a common goal after cardiac surgery. our study aims to examine
whether timing of tracheal extubation predicts improved postoperative outcomes and late survival after cardiac surgery. We also evaluated the optimal timing of extubation and its association with better postoperative
outcomes.
Methods - Between 2002 and 2006, 1164 patients underwent early tracheal extubation (<6 hours after surgery) and 1571 had conventional extubation (>6 hours after surgery). Propensity score adjustment and multivariable logistic regression analysis were used to adjust for imbalances in the patients’ preoperative characteristics. Receiver operating characteristic curves (RoC) were used to identify the best timing of extubation and
improved postoperative outcomes. Cox regression analysis was used to identify whether early extubation is a
risk factor for decreased late mortality.
Results - Early extubation was associated with lower propensity score-adjusted rate of operative mortality
(odds Ratio =0.55, 95% Confidence Intervals =0.31-0.98, p=0.043). Extubation within 9 hours emerged
as the best predictor of improved postoperative morbidity and mortality (sensitivity =85.5%, specificity
=52.7%, accuracy =64.5%). Early extubation also predicted decreased late mortality (Hazard Ratio =0.45,
95% Confidence Intervals 0.31-0.67, p<0.001).
Conclusions - Early extubation may predict improved outcomes after cardiac surgery. Extubation within 9
hours after surgery was the best predictor of uncomplicated recovery after cardiac surgery. Those patients
intubated longer than 16 hours have a poorer postoperative prognosis. Early extubation predicts prolonged
survival up to 16 months after surgery.
Keywords: early extubation, coronary artery bypass, mortality.
introduction
Early tracheal extubation is a common goal
of postoperative recovery after cardiac surgery. It is associated with decreased rates of
pulmonary complications and decreased use
of hospital resources (1-8). Though many
investigations have elucidated the value of
Kevin W. Lobdell, MD
1000 Blythe Blvd
Charlotte, north Carolina 28232
early extubation after cardiac surgery, the
optimal timing has not been determined.
This propensity-matched study was designed to evaluate optimal timing of early
extubation and correlate timing of extubation with early and late outcomes.
mEthodS
The Division of Cardiothoracic Surgery at
Carolinas Heart and Vascular Institute computerized database was utilized to identify
39
S.L. Camp, et al.
40
all patients who had coronary artery bypass
(CABG), isolated valve surgery, or valve/
CABG combination at Carolinas Medical
Center between January 2002 to December
2006; 2735 patients were thus identified.
of those, 1164 were extubated within six
hours (early extubation group) and 1571
were extubated six hours or greater after
surgery (conventional extubation group).
The same group of cardiac surgeons performed all procedures. Data including baseline demographics, procedural data, and
perioperative outcomes were entered prospectively in a pre-specified database by a
dedicated data-coordinating center.
Standard research approval was obtained
via our Institutional Review Board before
data identification, analysis, and study
approval was initiated. Health Insurance
Portability and Accountability Act of 1996
regulations were followed at all times to
maintain personal patient information confidentiality.
The Society of Thoracic Surgeons’ (STS)
national cardiac database definitions were
used for the purposes of the study. Early extubation is defined as removal of breathing
tube <6 hours after arrival to cardiovascular intensive care unit (ICU). Pneumonia
is defined as one of the following: positive
cultures of sputum, blood, pleural fluid, empyema fluid, trans-tracheal fluid or transthoracic fluid; consistent with the diagnosis
and clinical findings of pneumonia (may
include chest x-ray diagnosis of pulmonary
infiltrates). Pulmonary embolism is defined
as diagnosis by study as V/Q scan or angiogram. Septicemia is defined as positive
blood cultures post-operatively. Prolonged
intensive care unit length of stay is greater
than 24 hours. Prolonged hospital length of
stay is defined as hospital stay more than
the 75th percentile of hospital length of stay
(>9 days). Reintubation is defined as reintubation for any reason during hospitalization. operative Mortality is defined as op-
erative death within 30 days of procedure.
Cerebrovascular accident is defined as a
central neurological deficit persisting for
greater than 72 hours. Hemorrhage-related
re-exploration is defined as operative re-intervention required for bleeding or tamponade. Renal failure is defined as an increase
in serum creatinine greater than 2.0 mg/dl,
and a doubling of creatinine over baseline
preoperative value, and/or a new requirement for dialysis/hemofiltration.
Anesthesia and Intra-operative Management. Monitoring included electrocardiography, pulse oximetry, and end-tidal Co2
as well as routine use of pulmonary arterial
and radial arterial catheters. Anesthetic
induction and maintenance routinely included intravenous fentanyl (10-20 micrograms/kg), Midazolam (5-10 mg), Propofol as necessary, and Pavulon (10-20 mg).
Additionally, inhalational anesthesia was
provided with Isoflurane. Anticoagulation
with intravenous Heparin was achieved
and maintained with the aid of the Hepcon
Hemostasis Management System (Medtronic). Transesophageal echocardiography was
routine.
Post-operative Intensive Care Unit Management. Patients were brought to the ICU
immediately after surgery and supported
with mechanical ventilation, with goals of
peak inspiratory pressures less than 30 cm
H2o, pH 7.35-7.45, po2 >80 and pCo2
<50. Bispectral index sedation monitoring (BIS) was utilized to assist the titration of propofol sedation (typically 0-50
mcg/kg/minute intravenously) as needed.
A BIS value of 80 or greater was considered appropriate for extubation. Patients
were warmed for goal temperature >36
°C. Inotropes, vasopressors, vasodilators,
and volume were utilized as needed for
goals of cardiac index >2.2, systemic venous oxygen saturations >65%, and systolic blood pressures from 100-120 mmHg
(unless patient specific characteristics dic-
Early Extubation predicts outcomes after cardiac Surgery
tated otherwise). Post-operative volume
of chest tube drainage, hemodynamics,
temperature, urine output, blood products
transfusion, and analgesics/sedation were
recorded hourly and discussed between
team members with early extubation being continuously considered. Patients
were extubated when consistently hemodynamically stable, tolerating spontaneous
breathing trial, hemostatic, and neurologically appropriate. Contraindications to extubation, without physician approval, included cardiac index <2.2 liters/min/M2,
systolic blood pressure <90 or >160 mm
Hg, heart rate >130, po2 <80 or pCo2
>50 chest tube drainage >100 ml/hour,
urine output <40 ml/hour, and a neurologic deficit. Statistical Analysis. Univariate comparisons of preoperative, operative, and postoperative variables were
performed between groups (early extubation and conventional extubation group).
Dichotomous variables were compared
using a fisher’s exact test and nonparametric variables were assessed with the
Wilcoxon Rank Sum test. All tests were
two-sided and p values 0.05 were considered statistically significant. All analyses
were conducted using SAS (SAS Institute,
Cary, nC). Propensity Score Adjustment.
Propensity score adjustment was used on
the postoperative outcomes to correct for
imbalances between groups at baseline. A
logistic regression model was created with
early extubation/conventional extubation
as the outcome and significant baseline
characteristics (p<0.05) from the bivariate analysis as the covariates. Propensity
scores were generated and included as regression (covariance) adjustments in each
of the logistic regression outcome models
(10). The ability of the propensity score to
effectively balance the compared groups
at baseline was confirmed using separate
logistic models with early-conventional
extubation group type as the dependent
variable and the covariate and propensity
score as the independent variables.
Multivariable Modeling. A multivariable,
stepwise forward logistic regression analysis was used to determine independent
predictors of
1) pneumonia,
2) sepsis,
3) prolonged ICU LoS,
4) prolonged hospital LoS,
5) readmission to the ICU,
6) reintubation,
7) cerebrovascular accident,
8) renal failure,
9) hemorrhage-related re-exploration,
10) operative mortality.
The criterion for variable entry and removal into the logistic models was a univariate
probability level of p<0.05. The quality of
fit of the logistic models was tested with the
Hosmer and Lemeshow goodness-of-fit test.
Survival Analysis A Proportional Hazards
Cox regression model was used to evaluate
the effect of early extubation on survival,
while adjusting for the patients’ baseline
characteristics. Kaplan-Meier curves were
generated to show the survival patterns between the two study groups over 16 months
after surgery.
Timing of Early Extubation. Receiver operator characteristics (RoC) curves were
utilized to evaluate how the timing of extubation affects operative mortality, reintubation, and combined morbidity in cardiac
surgery. Curves were generated at each hour
of extubation up to 30 hours. The specificity and sensitivity of each hour of extubation to predict postoperative outcomes is
reported.
rESultS
Preoperative Characteristics. Univariate
comparisons of patients’ preoperative char-
41
S.L. Camp, et al.
42
acteristics between the early extubation
group (n=1164) and the conventional extubation group (n=1571) are presented
in Table 1. Early extubation patients were
more likely to be males and have multivessel coronary artery disease compared
to conventional extubation group patients.
Conventional extubation group patients
table 1 - Patients’ Baseline Characteristics in Patients with Early (<6 hours) and Late (>6 hours) Extubation.
baseline
characteristics
Gender (male)
Hypertension
Diabetes
Previous Cerebrovascular Accident
Chronic Renal failure
CoPD
Mild
Moderate
Severe
none
Reoperation
Previous CABG
Previous Valve
Congestive Heart failure
Unstable Angina
Recent Myocardial Infarction
Age >75 years
Ejection fraction <40
nYHA Class
I
II
III
IV
Early
Extubation
(n=1164)
conventional
Extubation
(n=1571)
p-value
870 (74.7%)
854 (73.4%)
410 (35.2%)
88 (7.6%)
33 (2.8%)
1102 (70.2%)
1227 (78.1%)
608 (38.7%)
216 (13.8%)
99 (6.3%)
0.008
0.004
0.063
<0.001
<0.001
88 (7.6%)
40 (3.4%)
30 (2.6%)
1006 (86.4%)
361 (31.0%)
50 (4.3%)
17 (1.5%)
137 (11.8%)
196 (16.8%)
234 (20.1%)
91 (7.8%)
229 (19.7%)
119 (7.6%)
84 (5.4%)
59 (3.8%)
1309 (83.3%)
602 (38.3%)
125 (8.0%)
64 (4.1%)
368 (23.4%)
360 (22.9%)
336 (21.4%)
278 (17.7%)
446 (28.4%)
56 (4.8%)
410 (35.2%)
499 (42.9%)
199 (17.1%)
37 (2.4%)
389 (24.8%)
679 (43.2%)
466 (30.0%)
<0.001
166 (14.4%)
70 (6.1%)
619 (53.6%)
299 (25.9%)
227 (14.5%)
98 (6.3%)
975 (62.2%)
267 (17.0%)
< 0.001
0.029
<0.001
.001
<0.001
<0.001
<0.001
0.414
<0.001
<0.001
number of Diseased Vessels
none
one
Two
Three
Case Priority
Elective
Urgent
Emergent
StS risk Score
Median (range)
Mean (SD)
420 (36.1%)
397 (25.3%)
695 (59.7%)
975 (62.1%)
49 (4.2%)
199 (12.7%)
(n = 1081)
(n = 1444)
0.02 (0.002-13.016) 0.03 (0.003-23.990)
0.29 (1.19)
0.44 (1.70)
<0.001
p-value
<0.001
Abbreviations: CoPD - Chronic obstructive Pulmonary Disease; CV - Cardiovascular; nYHA - new York Heart Association, CABGCoronary Artery Bypass Grafting.
were more likely to have hypertension,
chronic renal failure, previous cerebrovascular accident, and reoperation.
Additional characteristics of this group in-
clude unstable angina, depressed left ventricular ejection fraction, advanced age (greater
than 75 years), be in class III/IV by new
York Heart Association (nYHA) functional
table 2 - Patients’ Operative and Postoperative Characteristics in Patients with Early (<6 hours) and Late (>6
hours) extubation.
operative characteristics
Type of Surgery
CABG
Valve
CABG + Valve
Prolonged Pump Time (>125 min)
Prolonged Cross Clamp Time (>78 min)
Prolonged operation (>293 min)
Postoperative outcomes
Cerebrovascular Accident
Sepsis
Renal failure
Hemodialysis
Atrial fibrillation
Cardiac Arrest
Intraaortic Balloon Pump
Hemorrhage-related Re-exploration
Blood Transfusion
Cardiac Tamponade
Mediastinitis
Mortality operative
Cause of Death
Cardiac
Infection
Respiratory failure
Acute Renal failure
other
Unknown
Return to the ICU
Prolonged LoS ICU (>24 hours)
Prolonged Hospital LoS (>9 days)
Reintubation
Pneumonia
Pulmonary Embolism
Multi System organ failure
Early Extubation
(n=1164)
conventional
Extubation
(n=1571)
939 (80.7%)
178 (15.3%)
47 (4.0%)
191 (16.4%)
218 (18.7%)
174 (15.0%)
1177 (74.9%)
247 (15.7%)
147 (9.4%)
462 (29.4%)
446 (28.4%)
493 (31.4%)
<0.001
<0.001
<0.001
7 (0.6%)
15 (1.3%)
25 (2.2%)
3 (0.3%)
269 (23.1%)
16 (1.4%)
1 (0.1%)
14 (1.2%)
296 (25.4%)
4 (0.3%)
7 (0.6%)
18 (1.6%)
50 (3.2%)
72 (4.6%)
162 (10.3%)
48 (3.1%)
534 (34.0%)
64 (4.1%)
4 (0.3%)
143 (9.1%)
760 (48.4%)
26 (1.7%)
16 (1.0%)
89 (5.7%)
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.402
<0.001
<0.001
0.001
0.238
<0.001
15 (1.3%)
0
0
1 (0.1%)
0
1 (0.1%)
1 (0.1%)
61 (5.2%)
542 (46.6%)
124 (10.7%)
39 (3.4%)
30 (2.6%)
2 (0.2%)
4 (0.3%)
52 (3.3%)
4 (0.3%)
13 (0.8%)
13 (0.8%)
4 (0.3%)
3 (0.2%)
0
167 (10.6%)
1111 (70.7%)
471 (30.0%)
122 (7.8%)
148 (9.4%)
8 (0.5%)
52 (3.3%)
Abbreviations: CABG - Coronary Artery Bypass Grafting; LoS - Length of Stay; ICU - Intensive Care Unit
p-value
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.205
<0.001
43
S.L. Camp, et al.
44
classification, and have urgent or emergent
operation. In addition, the STS Risk Scores
for Mortality were significantly higher in
the conventional extubation group.
operative and Postoperative Characteristics. operative and postoperative results
are presented in Table 2.
Early extubation patients were more likely
to have undergone isolated CABG compared to conventional extubation group
patients. Pump, cross clamp and operation
times were longer on average for the conventional extubation group.
had a higher rate of operative mortality,
history of cerebrovascular accident, sepsis,
renal failure, atrial fibrillation, hemodialysis, cardiac arrest, hemorrhage-related reexploration, cardiac tamponade, and blood
transfusion.
were also more likely to be readmitted to
the ICU, had higher reintubation rates,
and had more prolonged ICU and hospital
length of stay.
Propensity Score Adjustment and Multivariable Modeling. Propensity scores were
calculated and shown to balance out the
differences at baseline between the early
extubation and the conventional extubation group patients (onLInE Appendix 1
www.itacta.org) with p <0.05 being statistically significant. The propensity scoreadjusted outcomes are shown in Table 3.
Early extubation was associated with decreased rates of pneumonia (p<0.001),
stroke (p=0.007), acute renal failure
(p<0.001), hemorrhage-related re-exploration (p<0.001), ICU length of stay
(p<0.001) and hospital length of stay
table 3 - Early Extubation and Propensity Score-Adjusted Postoperative Outcomes.
or
ci
0.31
0.13-0.73
0.007
Sepsis
0.56
0.30-1.04
0.066
Renal failure
0.28
0.18-0.45
<0.001
Atrial fibrillation
0.75
0.51-1.11
0.149
Hemodialysis
0.14
0.03-0.60
0.008
Cardiac Arrest
0.60
0.32-1.14
0.118
Intraaortic Balloon Pump
0.64
0.06-6.48
0.702
Hemorrhage-related Re-exploration
0.13
0.07-0.23
<0.001
Blood Transfusion
0.45
0.38-0.54
<0.001
Cardiac Tamponade
0.31
0.09-1.10
0.070
Mediastinitis
0.89
0.34-2.33
0.819
operative Mortality
0.55
0.31-0.98
0.043
Return to the ICU
0.57
0.40-0.79
<0.001
Prolonged Hospital LoS (>9 days)
0.40
0.31-0.51
<0.001
Reintubation
0.58
0.39-0.88
0.009
Pneumonia
0.42
0.27-0.64
<0.001
Multi System organ failure
0.22
0.08-0.64
0.006
Any Infectious Complication
0.49
0.33-0.74
<0.001
Prolonged LoS ICU (>24 hrs)
0.43
0.37-0.52
< 0.001
Conventional extubation treatment is the reference category for the odds ratios.
Abbreviations: LoS - Length of Stay; ICU - Intensive Care Unit.
p-value
figure 1
Kaplan-Meier Curve for
Late Mortality.
45
(p<0.001), ICU readmission (p<0.001),
reintubation (p=0.009), and operative
mortality (p=0.043). Multivariable models
were used as a supplementary analysis and
confirmed these findings with the exception of sepsis (onLInE Appendix 2 www.
itacta.org).
Specifically, pneumonia (oR=0.35), prolonged ICU LoS (oR=0.43), prolonged
hospital LoS (oR=0.37), readmission to
ICU (oR=0.50), reintubation (oR=0.48),
cerebrovascular accident (oR=0.21), renal
failure (oR=0.24), re-operation for bleeding (oR=0.13), and mortality (oR=0.46)
were all decreased within the early extubation group.
Survival Analysis. Late mortality was assessed out to 16 months after cardiac surgery (Figure 1). Hazard analysis is presented in Table 4. With a hazard ratio (HR) of
0.45, early extubation was associated with
decreased late mortality (p<0.001) when
adjusting for other significant covariates.
Timing of Early Extubation. A sub-analysis was conducted to determine the optimal
timing of extubation to predict improved
postoperative outcomes. Extubation within
9 hours emerged as the best predictor of im-
table 4 - Risk Factors for Late Mortality After Cardiac Surgery.
hr
95% ci
p-value
Early Extubation
0.45
0.31-0.67
<0.001
Diabetes
1.50
1.12-2.03
0.007
Chronic Renal failure
2.46
1.60-3.77
<0.001
CoPD
1.47
1.05-2.08
0.026
Reoperation
1.44
1.07-1.93
0.016
Congestive Heart failure
2.30
1.68-3.15
<0.001
Unstable Angina
1.80
1.31-2.47
<0.001
Age >75
2.96
2.15-4.08
<0.001
Prolonged Pump Time (>125 min)
1.58
1.15-2.15
0.004
STS Risk Score for Mortality
1.06
1.00-1.12
0.036
Abbreviations: HR - Hazard Ratio; CoPD - Chronic obstructive Pulmonary Disease;
STS - Society of Thoracic Surgeons
S.L. Camp, et al.
46
table 5 - Specificity, Sensitivity and Accuracy of Extubation <9 Hours to Predict Postoperative Outcomes.
Extubation <9hrs
combined mortality
and morbidity
mortality
morbidity
reintubation
Sensitivity
85.5%
62.7%
85.6%
62.7%
Specificity
52.7%
80.4%
53.0%
66.5%
Accuracy
64.5%
63.4%
64.9%
63.0%
C-Statistic
0.69
0.73
0.69
0.65
proved postoperative outcomes including
morbidity, mortality and reintubation (Table 5). Detailed analysis is presented within
onLInE Appendix 3 www.itacta.org.
diScuSSion
Mechanical ventilation after cardiac surgery is used to improve oxygenation and
ventilation as well as reduce cardiac workload in the hemodynamically unstable patient (3, 5).
Early extubation has been correlated with
decreased rates of mortality, morbidity, and
resource utilization and may function as
a predictor of an uncomplicated hospital
course (1-9, 11-15).
With this study, we evaluated timing of
early extubation and its relation to post-operative complications, death, and resource
utilization. Additionally, we examined late
mortality in the early versus conventional
extubation groups.
Despite the Society of Thoracic Surgeons’
definition for early extubation being extubation within six hours after surgery, an important finding of our study is that extubation up to nine hours after surgery appears
to be a better predictor of post-operative outcomes (onLInE Appendix 3 www.itacta.
org). operative mortality and cardiac cause
of death were lower in the early extubation group (p<0.001) as were rates of sepsis, cerebrovascular accident, renal failure,
hemodialysis, atrial fibrillation, cardiac ar-
rest, hemorrhage-related re-exploration, and
blood transfusion (p<0.001), (Table 2).
Prolonged intubation and continued hemodynamic instability after cardiac surgery
leads to significantly increased morbidity
and mortality (17). Mechanical ventilatory
support for 16 hours or more demonstrated a
trend towards worse post-operative outcomes
(onLInE Appendix 3 www.itacta.org).
This mirrors the findings from previous
studies where poorer post-operative results
occurred in those extubated in greater than
24 hours (4, 18). Early extubation was associated with improved survival up to 16
months after cardiac surgery (p<0.001)
while chronic renal failure, congestive heart
failure, unstable angina, and advanced age
diminished late survival (Table 4). Similar
findings were demonstrated by Cheng et
al where there were no deaths in the one
year follow-up in those patients extubated
early (1). This study is among the first to
demonstrate early extubation as a predictor
of improved early and late outcomes after
cardiac surgery. Limitations. Limitations of
this study include all those inherent to any
retrospective single-institution analysis.
All data elements, however, were prospectively entered into a cardiac surgery research database with strict definitions, and
the data analysis was performed using appropriately risk-adjusted statistical models
to adjust for differences in preoperative
risk factors. The accuracy of predicting improved outcomes in those patients extubated in <9 hours is 65%.
concluSionS
Early extubation is among the earliest postoperative predictors for those patients who
are more likely to have a smooth post-operative course and decreased complications
after cardiac surgery. further studies are
recommended to confirm the findings of
this study and implement changes in clinical practice.
Disclosure
The authors do not have any disclosure of any personal
or financial support and there is no actual or potential
conflict of interest for the subject manner.
rEfErEncES
1. Cheng DC, Wall C, Djaiani G, et al. Randomized assessment of resource use in fast-track
cardiac surgery 1-year after hospital discharge.
Anesthesiology 2003; 98: 651-657.
2. Reyes A, Vega G, Blancas R, et al. Early vs.
conventional extubation after cardiac surgery
with cardiopulmonary bypass. Chest 1997;
112: 193-201.
3. Hawkes CA, Dhileepan S, foxcroft D. Early
extubation for adult cardiac surgery patients.
The Cochrane Database of Systemic Reviews
Volume (3) 2007.
4. Cheng DC, Karski J, Peniston C, et al. Morbidity outcome in early versus conventional tracheal extubation after coronary artery bypass
grafting: a prospective randomized controlled
trial. Journal Thorac Cardiovasc Surg 1996;
112: 755-764.
5. Guller U, Anstrom KJ, Holman WL, et al. outcomes of early extubation after cardiac surgery
in the elderly. Ann Thorac Surg 2004; 77: 781788.
6. Konstantakos AK, Lee JH. optimizing timing
of early extubation in coronary artery bypass
surgery patients. Ann Thorac Surg 2000; 69:
1842-1845.
7. Myles PS, Daly DJ, Djaiani G, et al. A systematic review of the safety and effectiveness of
fast-track cardiac anesthesia. Anesthesiology
2003; 99: 982-987.
8. London MJ, Shroyer AL, Coll JR, et al. Early
extubation following cardiac surgery in a veterans population. Anesthesiology 1998; 88:
1447-1458.
9. Roosens C, Heerman J, De Somer f, et al. Effects of off-pump coronary surgery on the
mechanics of the respiratory system, lung,
and chest wall. Comparison with extracorporeal circulation. Crit Care Med 2002; 30: 24302437.
10. D’Agostino RB Jr. Propensity score methods
for bias reduction in the comparison of a treatment to a non-randomized control group. Stat
Med 1998; 17: 2265-2281.
11. Rady MY, Ryan T. Perioperative predictors of
extubation failure and the effect on clinical
outcome after cardiac surgery. Crit Care Med
1999; 27: 340-347.
12. Camp SL, Stamou SC, Stiegel MR et al.Quality
improvement program increase early tracheal
extubation rate and decreases pulmonary
complications and resource utilization after
cardiac surgery. Journal of Cardiac Surgery.
In Press.
13. Stamou SC, Camp SL, Stiegel MR et al. Continuous quality improvement program and morbidity after cardiac surgery. American Journal
of Cardiology. 2008; 102: 772-777.
14. Stamou SC, Turner S, Stiegel MR et al. Quality improvement program decreases mortality
after cardiac surgery. Journal of Thoracic and
Cardiovascular Surgery. 2008; 136: 494-499.
15. Lobdell KW, Camp SL, Stamou S et al. Quality
improvement in cardiac critical care. HSR Proceedings in Intensive Care and Cardiovascular
Anesthesia. 2009; 1: 16-20.
16. Wahl GW, Swineburne AJ, fedullo AJ et al.
Long-term outcome when major complications
follow coronary artery bypass graft surgery.
1996; 110: 1394-1389.
17. Cohen AJ, Katz MG, frenkel G et al. A. Morbid
results of prolonged intubation after coronary
artery bypass surgery. Chest 2000; 118: 17241731.
18. Kern H, Redlich U, Hotz H et al. Risk factors
for prolonged ventilation after cardiac surgery
using APACHE II, SAPS II, and TISS: comparison of three different models. Intensive Care
Medicine 2001; 27: 407-415.
47
proceedings
in Intensive Care
originAl ArticlE
48
where are italian anesthesiologists
and intensive care specialists
publishing? A quantitative analysis
of publication activity
L. Buratti
Department of Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milano
AbStrAct
Introduction: With the continuing worldwide shortage of anesthesiologists, the demands of clinical duties allow very little time for research activities. Every dedicated biomedical center should provide doctors and scientists with the proper environment to facilitate education, clinical practice and research activities and promote
publication in international peer-review journals.
Methods: In this observational study, the Scopus database was searched for publications (2004-2009) to identify the most prolific authors among Italian anesthesiologists and intensive care specialists working in Italy. We
then identified the journals that most frequently hosted Italian writers.
Results: The top 20 authors published between 30 and 76 papers each (mean 51) in the last 5 years. Intensive
Care Medicine (112 papers, 14%), Minerva Anestesiologica (92 papers, 11%), Critical Care Medicine (55
papers, 7%), Journal of Cardiothoracic and Vascular Anesthesia (32 papers, 4%), and European Journal of
Anesthesiology (32 papers, 4%) most frequently hosted Italian authors.
Discussion: Despite its obvious limitations such as the choice of a single database (Scopus), the absence of
important qualitative indicators (e.g. impact factor, citation index), the inclusion of any type of publication
(a letter to the editor or reviews counted like a randomized controlled study) and the possible exclusion of
important scholars, this is the most up-to-date and comprehensive attempt to perform a quantitative analysis
of publishing in Italy. Each of the 20 indexed Journals that most frequently hosted Italian authors only accepts
manuscripts in English and has impact factor.
Keywords: anesthesia, intensive care, journals, publications, manuscripts, scopus, publishing, information science
introduction
Education, through the dissemination of
information, is the most obvious reason for
publishing. We want to ‘make a difference’
in our patients’ lives and we can do this
through investigating, analyzing, and publishing. We furthermore teach the methods
behind designing, analyzing, writing, editCorresponding author:
Luca Buratti
Department of Cardiothoracic Anesthesia and Intensive Care
Istituto Scientifico San Raffaele, Milano, Italia.
Via olgettina 60 Milano, 20132 Italy
Tel: ++390226434524 - fax ++390226437178
ing, and publishing to pass on and extend
this dissemination of knowledge. This is
especially true in critical care medicine,
where there is still a paucity of evidence on
how to manage most of the clinical problems commonly encountered in critically ill
patients. (1) It would be remiss of us not
to include the importance of individual or
institutional legitimacy, credibility, visibility, and productivity. Similarly, economics
influence publishing, whether it is the pressure from a professor to ‘publish or perish’,
or an institute that needs to garner funds
for a research project. Reputation is also
an important factor. our literature search
who is publishing in italy?
failed to identify a quantitative evaluation
of publications in Italy. for this reason we
decided to identify the most prolific authors
in the field of Anesthesia and Intensive
Care over the past five years in Italy together with the journals where they published.
mEthodS
Italian anesthesiologists and intensive care
specialists working in Italy were identified
as follows: A) Every Professor of Anesthesiology and Intensive Care Medicine listed
in www.cpoar.org (last accessed March 31st
2009); B) All the first and last names of authors who published in Minerva Anestesiologica from January 2008 To April 2009; C)
All the present SIAARTI (Società Italiana
di Anestesia, Rianimazione e Terapia Intensiva) representatives and all the candidates
for the 2009 elections listed in www.siaarti.
it (last accessed february 28th 2009); D) Coauthors of the previously identified nominees
were identified using Scopus; E) Authors of
papers published in international journals
were also identified. We obtained a total
of 321 names and identified the number of
publications from January 2004 to May 2009
as indexed in the Scopus database (www.
scopus.com) searching for the surname and
initial of the author in the “Health sciences”
section under “Authors”. We then identified
where the 20 most prolific anesthesiologists
were published and the rate of co-authorship.
The homonym problem was not easy to solve.
table 1 - The most prolific 20 Italian anesthesiologists and intensive care specialists of the last 5 years together with
their affiliations.
Author
Affiliation
n of indexed papers
Antonelli, Massimo
Università Cattolica Sacro Cuore, Roma
76
Biancofiore, Gianni
Azienda ospedaliera Universitaria Pisana
40
Casati, Andrea
Università di Parma
65
Citerio, Giuseppe
Azienda ospedaliera San Gerardo, Monza
39
Conti, Giorgio
Università Cattolica del Sacro Cuore, Roma
46
Crescenzi, Giuseppe
IRCCS ospedale San Raffaele di Milano
36
Gattinoni, Luciano
Università di Milano
57
Gullo, Antonino
Università di Catania
56
Iapichino, Gaetano
30
Landoni Giovanni
IRCCS ospedale San Raffaele di Milano
72
Morelli, Andrea
Università La Sapienza di Roma
50
ori, Carlo
Università di Padova
49
Pelosi, Paolo
Università dell’Insubria, Varese
54
Pietropaoli, Paolo
Università La Sapienza di Roma
48
Ranieri, V. Marco
Università di Torino
37
Ranucci, Marco
IRCCS Policlinico San Donato
42
Silvestri, Luciano
Azienda ospedaliera di Gorizia
38
Stocchetti, nino
69
Tufano, Rosalba
Università federico II, napoli
35
zangrillo, Alberto
Università Vita-Salute San Raffaele di Milano
74
49
L. Buratti
50
figure 1
Where are the 20 most
prolific anesthesiologists
working.
our method did not consider the possibility
that there might really be two or more distinct authors publishing in anesthesia and
intensive care with the same surname/name.
Scopus often assigns more than one identity
to the same author, considering them as distinct scholars. In the final table we included
every author publishing in anesthesiology
and intensive care that might not be certainly
separated from the best one.
rESultS
The 20 most prolific Italian anesthesiologists and intensive care specialists of the last
5 years are listed in Table 1 together with
their affiliations (Figure 1). Most of them
are from academic institutes. The complete
top-50 ranking (in which the 50th published
18 papers in the last five years) is available
online on the journal website www.itacta.
org (online table only). one out of 20 and
three out of 50 of the most prolific authors
were female. These 20 authors published
821 manuscripts and only 194 (20%) of
these manuscripts were co-authored by
other “fast publishing” Italian authors, suggesting that collaborative research could be
implemented among Italian researchers.
The 20 International Journals that most
frequently hosted these authors are listed
in Table 2 and include Intensive Care Medicine (112 papers, 14%), Minerva Anest-
who is publishing in italy?
table 2 - The 20 international journals that most frequently host papers from Italian anesthesiologists and intensive care specialists.
ranking
Journal
n of manuscripts
%
1
Intensive Care Medicine
112
13,6
2
Minerva Anestesiologica
92
11,2
3
Critical Care Medicine
55
6,7
4
Journal of Cardiothoracic and Vascular Anesthesia
32
3,9
4
European Journal of Anaesthesiology
32
3,9
6
Critical Care
28
3,4
7
Anesthesia and Analgesia
23
2,8
8
Transplantation Proceedings
22
2,7
9
Anesthesiology
19
2,3
10
Annals of Thoracic Surgery
18
2,2
11
Paediatric Anaesthesia
16
1,9
12
Current opinion in Critical Care
14
1,7
12
American Journal of Respiratory and Critical Care Medicine
14
1,7
12
British Journal of Anaesthesia
14
1,7
15
Journal of Clinical Anesthesia
13
1,6
16
Acta Anaesthesiologica Scandinavica
11
1,3
17
Chest
10
1,2
18
Shock
8
1,0
19
European Journal of Cardio Thoracic Surgery
6
0,7
19
Liver Transplantation
6
0,7
esiologica (92 papers, 11%), Critical Care
Medicine (55 papers, 7%), Journal of Cardiothoracic and Vascular Anesthesia (32
papers, 4%) and European Journal of Anesthesiology (32 papers, 4%). Each of the
20 indexed Journals that most frequently
hosted Italian authors only accepts manuscripts in English and has impact factor.
They deal mostly with anesthesiology (8
journals), intensive care (7 journals) or both
(1 journal), surgery (2 journals) or with
transplants (2 journals). notably, some of
the total 821 papers were published in the
most prestigious journals such as Circulation (5 papers), JAMA (3 papers), nEJM (2
papers), JACC, Internal Medicine and The
Lancet (1 paper each).
diScuSSion
In this study, we identified the most prolific
authors among Italian anesthesiologists
and intensive care specialists over a fiveyear period (2004-2009) using the Scopus
database. We also focused upon where they
published.
new medical information is communicated
through international journals.
The number of published articles might
be considered a reflection of productivity
(2), even though impact factor and citation
indexes are considered to be more reliable
qualitative guides.
If we do not develop the knowledge, both
practical and academic, of anesthesiol-
51
L. Buratti
52
ogy through research, our specialty might
gradually become a simple clinical service
or technical department. More than ever
we need to train and encourage young investigators and educators and provide them
with dedicated mentorship and the necessary resources to allow them to follow
their academic career paths, and avoid an
overly–developed focus on the simple provision of clinical services. The results of
this study suggest that, nowadays, a scholar
could publish one paper per month in a
peer-reviewed international journal while
attempting to publish one paper per year in
a top-ranking journal. The low rate of coauthorship indicated by this study among
Italian scientists from different institutes
highlights the need for more co-operative
research, especially between different academic centers (those publishing more).
Our study has numerous limitations. A) We
only used the Scopus database. Using other
resources, like Web of Science or Pubmed,
we might have obtained slightly different
results. Nonetheless, Scopus is an excellent database with a wide range of journals.
(3) We only identified the most prolific authors without considering impact factor,
citations, H indexes and other important
scores. Letters to the editor, editorials and
review articles had the same importance as
randomized controlled trials and original
articles in our scoring. We also did not identify the position of the scholars’ name (e.g.
first or last names are more important than
names found in other positions). We might
have left out valuable researchers, especially
those working at non-academic institutes.
Unfortunately, it is impossible to include everyone. Furthermore, we decided to exclude
non-anesthesiologists, even when they had
published numerous papers in anesthesiology and intensive care journals.
Andrea Casati, associate professor of anesthesiology and intensive care at the University of Parma, passed away in 2007. He was
the most published medical doctor in Italy
and his death represented a tragic loss for
the anesthesiology community worldwide
(4).
CONCLUSION
Although we acknowledge its limitations,
this is the most up-to-date and comprehensive attempt to estimate the most prolific
authors among anesthesiologists and intensive care specialists working in Italian
hospital or universities over a five-year period. On average these authors published
one paper per month in peer-reviewed international journals with impact factor,
such as Intensive Care Medicine, Minerva
Anestesiologica, Journal of Cardiothoracic
and Vascular Anesthesia, and European
Journal of Anesthesiology.
We confirmed that these authors were
mostly from academic institutes and identified the need for more co-operative research
between Italian centers.
No conflict of interest exists.
Acknowledgments: The author would like to thank Michael John, coordinator of the English courses in the
Faculty of Medicine and Surgery at the Vita-Salute
San Raffaele University, Milan, for the language editing of this paper.
REFERENCES
1. Grasselli G, Gattinoni L, Kavanagh B et al. Feasibility, limits and problems of clinical studies
in Intensive Care Unit. Minerva Anestesiol.
2007; 73: 595-601.
2. Stossel TP, Stossel SC. Declining American
representation in leading clinical-research
journals. N Engl J Med 1990; 322: 739-42.
3. Falagas ME, Pitsouni EI, Malietzis GA, Pappas
G. Comparison of PubMed, Scopus, Web of Science, and Google Scholar: strengths and weaknesses. FASEB J. 2008; 22: 338-42.
4. Fanelli G. Acta Biomed. 2007; 78: 77.
proceedings
in Intensive Care
pApErS, poStErS, prESEntAtionS:
communicAting thE biomEdicAl SciEncES
communicating biomedicine
at congresses: a general introduction
to posters and oral presentations
M. John
Professor of Applied English, Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy
Writing and then publishing a biomedical
manuscript is the natural completion of an
experiment or of a clinical procedure. In
fact, 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.
The publication of your paper can also lead
to something else, however, which is the invitation to present at a congress.
During this kind of venue you will need to
communicate your data using two different
kinds of vector: a poster or an oral presentation.
Posters might be considered as ‘first contact’ between young scientists and their
peers. Indeed, whereas more experienced
professionals can be invited to give oral presentations at congresses, their younger colleagues usually enter this universe through
the poster.
Prof. Michael John
Vita-Salute San Raffaele University
Via olgettina, 60
20132 Milano, Italy
This does not mean, of course, that ‘mature’
clinicians never take a poster to a congress.
What I mean is that poster presentation
can be considered the ideal starting point
for the junior doctor in that it does not put
the inexperienced congress-goer under excessive pressure.
In any case, let’s get back to the poster session. Biomedical posters are large visual
documents that should communicate your
discoveries in a captivating manner.
The title needs to be short and clear; the
introduction has to put your work into
the desired context and stress the objectives, importance and originality of your
own study; the methods section should be
clear, concise and never too long; the results should take up most of the space on
the poster, as this is what most people are
interested in reading; finally, your conclusions have to be concise.
A poster must not be weighed down with
an excessive amount of information and,
ideally, the reader ought to be able to get
through it in around ten minutes.
Dedicated poster sessions at congresses are
a bit like market stalls, so you need to prepare something which is attractive, and not
only informative, if you want it to stand out
in the crowd.
Be sure to use a light-colored neutral background that contrasts with the font and
makes it easy to read. Do not put in too
53
M. John
54
much information when there isn’t room
for it: you do not have to follow the “IMRAD” (Introduction, Methods, Results and
Discussion) format to the letter and you
can go into more detail when the viewers
ask you questions.
There are generally fewer oral presentations than posters at scientific meetings
and they normally tend to be considered
more prestigious.
Good research can benefit enormously if
the presenter is able to put it over to the
audience in an entertaining and convincing
fashion. Yet, good oral presentations cannot
be improvised.
Everyone needs to practise.
Always know what kind of audience you
will have to face: general, specialist or
mixed and always give them what they
want: a good story.
Without the story (your data) you will have
no success, even though you might be the
most entertaining public speaker in the uni-
verse. As we have already seen, presenting
your work to your colleagues can be considered the cornerstone of your scientific
career, so try to do it properly if and when
you get the chance.
Speaking in public is, of course, very difficult and creates a great deal of stress. Remember to prepare good visual aids, without exaggerating with PowerPoint technology, and also consider:
• movement and gestures
• stance and posture
• facial expression
• eye contact
• voice clarity and pace
• pointer use
• interaction and ability to deal with questions
naturally, the situation becomes all the
more complicated when people present in
a language that is not their own. It is obviously, as with everything else, a matter of
practice.
“Questo è il secondo di una serie di articoli sull’argomento.
Potete indirizzare domande (in italiano o in inglese) a [email protected] e vedrete le
risposte pubblicate su questa rubrica”.
‘This is the second of a series of articles on this topic.
Send any questions to [email protected] who will answer them as part of this
column.’
communicating biomedicine at congresses:
a general introduction to posters and oral presentations
Questions from the readers
1
how can we write concise phrases,
without developing articulate ideas
that are difficult to express in a
language we do not have complete
control of?
Very simple. Always write directly in English: do not only use English words.
Try to think in English. Extensive reading
helps a great deal, not only of biomedical
papers but any kind of English writing.
nEVER TRAnSLATE from your own language. You can always get some help from a
mother-tongue reviewer to polish your notso-fantastic English BEfoRE submitting
the paper to your target journal.
By the way, including the reviewer in the
Acknowledgements might make referees
think twice before criticizing your English,
as most referees are not mother-tongue
speakers making an acknowledged reviewer a sort of linguistic ‘guarantee’.
2
Are there books or internet
sites that can help us translate
medical terminology?
Endless Internet sites and online dictionaries can be used for this purpose.
As far as books are concerned, I would
highly recommend:
1. Iles R.L. Guidebook to Better Medical
Writing (Island Press, 2003).
2. Gustavi B. How to Write and Illustrate a
Scientific Paper (Cambridge University
Press, 2003).
3. Day R.A. Scientific English: A Guide
for Scientists and other Professionals
(oryx Press, 1995) and, modestly.
4. John M. English for the Medical Profession: Manuale per Studenti e Professionisti (Masson, 2006).
55
3
is it better to use uK or uSA
English when writing a paper?
naturally this theoretically depends upon
the nationality of the target journal. In fact
a UK journal logically requires UK English
and a USA journal USA English. However,
I feel that writers should not worry about
which form of English to use and should
concentrate instead on uniformity.
This means that if you begin writing using USA English then you must use USA
English throughout the paper. As the main
difference between UK and USA English
lies in the spelling of certain words be sure
to set your computer’s spellchecker to the
form chosen when you start writing. If
various authors are involved then agree beforehand which form of English to use.
furthermore, using USA English can be advantageous as it can be assisted by specialist
biomedical spelling software that is readily
available for purchase online. I personally
always use U SA English when reviewing
papers, unless the Instructions to Authors
state otherwise.
proceedings
in Intensive Care
rEcEnSionE
56
tromboembolia polmonare acuta:
dalla fisiopatologia al follow-up
di Luca Masotti
SEED, 2009, pagine 135
La Tromboembolia Polmonare (TEP) è la terza
malattia cardiovascolare in ordine di frequenza
dopo la cardiopatia ischemica e l’Ictus Cerebri.
non è un processo patologico a sé stante ma,
insieme alla Trombosi venosa profonda (TVP)
e alla Tromboflebite Superficiale, rappresenta la
manifestazione di un unico processo patologico:
la cosiddetta malattia tromboembolica.
La sintomatologia spesso si presenta in maniera aspecifica, con conseguente diagnosi differenziale piuttosto difficoltosa: la percentuale
di casi non diagnosticati è molto alta e si aggira
sul 50-80% (un elevato numero di TEP viene
riconosciuto solo al tavolo autoptico). Questi
dati rendono conto della gravità della patologia
che, se non trattata, può portare a morte fino al
30% dei pazienti.
nonostante il miglioramento della terapia, la
mortalità è rimasta alta e costante negli ultimi
40 anni. È indubbio che è un’entità nosologica
che richiede un approccio multidisciplinare di
tipo pneumologico, cardiologico, ematologico,
vascolare e radiologico. Masotti (dirigente
medico Uo Medicina Interna dell’ospedale di
Cecina, professore presso la Scuola di Specializzazione in geriatria dell’Università degli Studi
di Siena e specialista in Malattie dell’Apparato
Respiratorio) condensa nel suo lavoro gli approcci specialistici alla patologia, delineando in
maniera molto attenta e ordinata tutti i punti
che vertono sulla TEP: dai dati epidemiologici
ai fattori di rischio,dagli indicatori clinici e strumentali alla profilassi e terapia, non tralasciando utilissimi richiami di fisiopatologia. Vengono
presentati gli algoritmi da seguire per la diagnosi o l’esclusione della TEP, elencando anche i
vari scores che godono di maggior credito nella
valutazione del malato e della sua patologia.
nelle pietre miliari della diagnostica,oltre a evidenziare i classici elementi laboratoristici che
possono venire in aiuto del medico (D-Dimero,
BnP, Troponina I) pone anche l’attenzione su
un biomarker oggetto di più ampi studi come
hFABP (hearty type fatty acid binding proteins).
Si tratta di una piccola proteina (14,5 kDa)
non cardiospecifica ma espressa in quantità
relativamente ridotte nell’apparato muscoloscheletrico.
numerosi studi clinici hanno evidenziato
un’elevata sensibilità e specificità della fABP
(significativamente migliore rispetto alla mioglobina) nella rivelazione rapida dell’IMA, per una
valutazione precoce dell’estensione dell’infarto
nonché per rilevare anche un danno cardiaco
minimo (come può accadere nella TEP).
Masotti e la sua equipe sottolineano l’importanza
e l’insostituibilità delle tecniche di imaging,
dove l’angio-tc polmonare spirale rappresenta il
gold standard per la diagnostica. Un breve excursus viene fatto sugli altri esami strumentali
come la scintigrafia polmonare, l’angio-RMn,
l’angiografia polmonare che possono venire in
aiuto nel caso in cui l’angio-tc non fosse disponibile (vedi piccole strutture ospedaliere)
o fosse controindicata (insufficienza renale o
allergia al mezzo di contrasto). Grande spazio
viene dedicato a uno dei passaggi più delicati
nel management della TEP: la profilassi e la
terapia, menzionando i trials clinici più accreditati (MEDEnoX, PREVEnT, ARTEMIS,
EXCLAIM), nonchè le linee guida (ESC 2008,
ACCP VIII).
Il compendio di Masotti è un’opera di immediata comprensione, utile per una rapida consultazione. Può venire in soccorso ad ogni figura
specialistica che, in qualsiasi frangente della
propria professione, può trovarsi a fronteggiare
tale subdola patologia che, non a caso, Braunwald (punto di riferimento della moderna cardiologia) definì “la grande simulatrice”.
Davide Bellantonio
Michele Oppizzi
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59
SUPRANE
®
RIASSUNTO
DELLE CARATTERISTICHE DEL PRODOTTO
RIASSUNTO DELLE CARATTERISTICHE DEL PRODOTTO
1.
DENOMINAZIONE DEL MEDICINALE
2.
COMPOSIZIONE QUALITATIVA E QUANTITATIVA
3.
FORMA FARMACEUTICA
4.
INFORMAZIONI CLINICHE
1Suprane
DENOMINAZIONE
DEL MEDICINALE
liquido per inalazione.
Suprane liquido per inalazione
2Desflurane
COMPOSIZIONE
QUALITATIVA E QUANTITATIVA
100% v/v.
Desflurane 100% v/v
3Liquido
FORMA
perFARMACEUTICA
inalazione.
Liquido per inalazione.
Indicazioni
Terapeutiche
44.1
INFORMAZIONI
CLINICHE
Desflurane
è indicato
come agente inalatorio per l’induzione e il mantenimento del4.1
Indicazioni
Terapeutiche
l’anestesia
in pazienti
adulticome
e per agente
il mantenimento
neonati
Desflurane
è indicato
inalatorio dell’anestesia
per l’induzionein pazienti
e il mantenimento
e bambini.
dell’anestesia
in pazienti adulti e per il mantenimento dell’anestesia in pazienti
Desflurane
è raccomandato
l’anestesia
pazienti
pediatriciin (vedi
neonati non
e bambini.
Desflurane per
non indurre
è raccomandato
perinindurre
l’anestesia
pazienti
anche
sezione(vedi
4.2 anche
“Posologia
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di somministrazione,
paragrafo Induzione
–
pediatrici
sezione
4.2 “Posologia
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paragrafo
Uso Induzione
nei bambini).
– Uso nei bambini).
4.2 Posologia
Posologia
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anche
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anche
sezioni 4.4
4.4 “Speciali
“Speciali avvertenze
e precauzioni
per l’uso”
e 6.6“Istruzioni
“Istruzioni
per l’uso”.
l’uso”.Modo
di somministrazione Desflurane si somministra per inalazione. La concenModo
di somministrazione
trazione
di desflurane richiesta deve essere erogata utilizzando un vaporizzatore specifico
Desflurane
somministra
per l’usosicon
desflurane.per inalazione. La concentrazione di desflurane richiesta
devePremedicazione
essere erogata utilizzando un vaporizzatore specifico per l’uso con desflurane.
Premedicazione
Un’eventuale premedicazione deve essere stabilita in funzione delle necessità indiUn’eventuale
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oggi disponibili
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latoria dell’anestesia.
Posologia
Posologia
La minima concentrazione alveolare (MAC) di desflurane è strettamente correlata all’età
La minima
concentrazione alveolare (MAC) di desflurane è strettamente correlata
deldel
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comecome
segue:
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segue:
–––––––––––––––––––––––––––––––––––––––––––––––––––––
EtàEtà
MAC
MAC
100%
Ossigeno
100%
Ossigeno
MAC
60% Protossido
60% Protossido
d’azoto d'azoto
8,95
- 10,65%
8,95
- 10,65%
7,20 - 9,40%
7,20 - 9,40%
6,35 - 7,25%
5,756,35
- 6,25%
- 7,25%
5,17 + 0,6%
5,75- 7,75%
- 7,75%
5,75
**
5,75 - 7,00% **
5,75 - 7,00% **
3,75 - 4,25%
1,75
- 3,25%
3,75
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1,67 + 0,4%
–––––––––––––––––––––––––––––––––––––––––––––––––––––
1 anno
0 - 01 -anno
1 - 12 anni
1- 12 anni
18 - 30 anni
30 18
- 65- anni
30 anni
oltre 65 anni
30 - 65 anni
5,75 - 6,25%
1,75 - 3,25%
–––––––––––––––––––––––––––––––––––––––––––––––––––––
* = 3-12oltre
mesi65 anni ** = 1-5 anni
5,17 ± 0,6%
1,67 ± 0,4%
*Induzione
= 3-12 mesi
**
= 1-5 anni di desflurane pari a 4-11% producono, in genere, anestesia chirurgiConcentrazioni
ca inInduzione
2-4 minuti. Negli studi clinici, peraltro, sono state impiegate dosi fino al 15%.
Concentrazioni dididesflurane
pariconcorrono
a 4-11% producono,
genere, anestesia chirurgica
in 2-4
Tali concentrazioni
desflurane
a diluire inproporzionalmente
la concenminuti.
studi clinici,
peraltro,
sono state di
impiegate
dosi possono
fino al 15%.
Tali concentrazioni
trazione
di Negli
ossigeno.
Elevate
concentrazioni
desflurane
provocare
effetti
di desflurane
concorrono
a diluire proporzionalmente la concentrazione di ossigeno. Elevate
indesiderati
alle alte
vie respiratorie.
concentrazioni
di desflurane
possono
provocare
indesiderati
alte vie respiratorie.
Bisogna
avere sempre
disponibili
attrezzature
di effetti
rianimazione
e dialle
somministrazione
di ossigeno.
Bisogna avere sempre disponibili attrezzature di rianimazione e di somministrazione di osPuò sigeno.
insorgere
breve periodo
eccitazione
durantedurante
l’induzione
dell’anestesia.
Puòun
insorgere
un brevediperiodo
di eccitazione
l'induzione
dell'anestesia.
Uso Uso
nei bambini
nei bambini
L’usoL'uso
di Suprane
nonnon
è raccomandato
nei bambini
bambinicon
di Suprane
è raccomandatoper
perindurre
indurrel’anestesia
l'anestesia generale
generale nei
con l'uso
l’uso della
della maschera
mascheraaacausa
causadidiun'elevata
un’elevata
incidenza
di laringospasmo,
secre-auincidenza
di laringospasmo,
secrezioni
zionimentate,
aumentate,
difficoltà
di respiro
e tosse.
difficoltà
di respiro
e tosse.
Mantenimento
Mantenimento
LivelliLivelli
adeguati
di anestesia
chirurgica
concentrazionidel
del2-6%
2-6%dididesadeguati
di anestesia
chirurgicasisisostengono
sostengono con
con concentrazioni
desflurane
quandosomministrato
somministratoinsieme
insieme
a protossido
d’azoto.
Concentrazioni
di
flurane quando
a protossido
d'azoto.
Concentrazioni
di desflurane
desflurane
pari al 2,5-8,5%
essere necessarie
quando la somministrazione
pari al 2,5-8,5%
possonopossono
essere necessarie
quando la somministrazione
viene effettuata
vienecon
effettuata
ossigeno
o con inaria
arricchita
in ossigeno.
Sebbene
ossigenocon
o con
aria arricchita
ossigeno.
Sebbene
concentrazioni
finoconcentraal 18% siano
zionistate
fino al
18% siano state
somministrate
per brevi
qualora
fosse necessasomministrate
per brevi
periodi, qualora
fosseperiodi,
necessario
somministrare
alte dosi
rio somministrare
alteprotossido
dosi di desflurane
con protossido
occorreinalata
assicurarsi
di desflurane con
d'azoto occorre
assicurarsi d’azoto
che la miscela
contenga
che la
miscela
inalata
contengaQualora
almenosiil rendesse
25% di ossigeno.
almeno
il 25%
di ossigeno.
necessario un rilassamento muscolare
Qualora
si rendessesinecessario
un rilassamento
muscolare
più pronunciato, si pospiù pronunciato,
possono usare
dosi addizionali
di miorilassanti.
sonoDosaggio
usare dosi
addizionali
di miorilassanti.
in caso
di Insufficienza
Epatica e Renale
Dosaggio
in caso didiInsufficienza
Epatica ine Renale
Concentrazioni
1-4% di desflurane
Protossido d'azoto/ossigeno sono state usate
Concentrazioni
di desflurane
in Protossido
d’azoto/ossigeno
sono trapianto
state
con successodiin1-4%
pazienti
con insufficienza
epatica o renale
cronica e durante
usaterenale.
con successo
in
pazienti
con
insufficienza
epatica o renale cronica e durante
A causa del metabolismo molto ridotto, non è necessario un aggiustamento di
trapianto renale.
dose in pazienti con ridotta attività renale o epatica.
A causa del metabolismo molto ridotto, non è necessario un aggiustamento di dose
4.3 Controindicazioni
in pazienti con ridotta attività renale o epatica.
Desflurane non deve essere usato in pazienti nei quali è controindicata l'anestesia generè inoltre controindicato in pazienti con ipersensibilità agli agenti alogenati
4.3 ale. Desflurane
Controindicazioni
ed in pazienti
con predisposizione,
familiare,
all'insorgenza
di ipertermia
maligna.
Desflurane
non deve
essere usato inanche
pazienti
nei quali
è controindicata
l’anestesia
Desflurane
non èdovrebbe
essere usatoin come
anestetico peraglil’induzione
generale.
Desflurane
inoltre controindicato
pazientiunico
con ipersensibilità
agen-
ti alogenati ed in pazienti con predisposizione, anche familiare, all’insorgenza di
ipertermia maligna.
Desflurane non dovrebbe essere usato come unico anestetico per l’induzione dell’adell’anestesia
quei pazienti
che presentano
patologia
coronariao onei
neicasi
casiinincui
cui va
va
nestesia
in queiinpazienti
che presentano
unauna
patologia
coronaria
evitatoun
unaumento
aumento della
della frequenza
frequenza cardiaca
arteriosa.
evitato
cardiacao odella
dellapressione
pressione
arteriosa.
Desflurane
usatoininpazienti
pazienti
in cui
si siano
manifestate,
a seguito
di sommiDesfluranenon
non va usato
in cui
si siano
manifestate,
a seguito
di somministrazinistrazione
di anestetici
alogenati,
disfunzioni
febbri incerta,
di natura
incerta, leuone di anestetici
alogenati,
disfunzioni
epatiche,epatiche,
febbri di natura
leucocitosi.
cocitosi.
Desflurane, infine, è controindicato in pazienti affetti da turbe convulsive.
infine, è controindicato
pazienti
4.4Desflurane,
Speciali Avvertenze
e Precauzioniinper
l'uso affetti da turbe convulsive.
4.4
Speciali
Avvertenze
e Precauzioni
l’uso specializzato nel praticare
Desflurane
deve essere
somministrato
solo daperpersonale
Desflurane
essere
somministrato
solo da personale
specializzato
nel apraticare
l'anestesiadeve
generale
ed utilizzando
un vaporizzatore
specificatamente
messo
punto e
l’anestesia generale ed utilizzando un vaporizzatore specificatamente messo a
tarato
per
desflurane.
E'
necessario
avere
la
disponibilità
immediata
delle
attrezzature
punto e tarato per desflurane. E’ necessario avere la disponibilità immediata
delle
per il mantenimento
della pervietà delle
aeree del
paziente,
per ladel
ventilazione
attrezzature
per il mantenimento
della vie
pervietà
delle
vie aeree
paziente,forzata,
per la
l'arricchimento
di ossigeno
e la rianimazione
circolatoria.
e lacircolatoria.
depressione
ventilazione
forzata,
l’arricchimento
di ossigeno
e laL'ipotensione
rianimazione
respiratoria aumentano
con l'approfondirsi
dell'anestesia.
di desflurane per
indurre
L’ipotensione
e la depressione
respiratoria
aumentano L'uso
con l’approfondirsi
dell’aneanestesia nei pazienti pediatrici non è raccomandato a causa della frequente insorgenza
stesia.
nei bambini
di tosse,
apnea, laringospasmo
aumentate
DesfluL’uso
di desflurane
perdispnea,
indurre anestesia
nei pazientied
pediatrici
nonsecrezioni.
è raccomandato
a rane,
causaanalogamente
della frequente
neivolatili,
bambini
tosse, dispnea,
apnea,liquorale
laringo-o
agli insorgenza
altri anestetici
puòdiaumentare
la pressione
spasmo
ed aumentate
intracranica
in pazientisecrezioni.
con processi espansivi. In tali pazienti, desflurane deve essere
Desflurane,
analogamente
altri anestetici
volatili,
può aumentare
la pressione
somministrato
a MAC 0,8 oagli
inferiore,
insieme ad
un’induzione
con barbiturici
ed iperliquorale
o
intracranica
in
processialla
espansivi.
In tali pazienti,
ventilazione (ipocapnia) nelpazienti
periodo con
precedente
decompressione
cranica. desflurane
Va prestata
deve
essere
somministrato
a
MAC
0,8
o
inferiore,
insieme
ad
un’induzione
con
barun’adeguata attenzione nel mantenere la pressione di perfusione cerebrale. L'uso
di
biturici ed iperventilazione (ipocapnia) nel periodo precedente alla decompressione
desflurane in pazienti debilitati, ipovolemici ed ipotesi non è ancora stato ampiamente
cranica. Va prestata un’adeguata attenzione nel mantenere la pressione di perfusionesperimentato.
cerebrale. Come per gli altri potenti anestetici generali, si raccomanda in questi pazienti l'uso
di concentrazioni
inferiori
a quelleipovolemici
consigliate.ed
In pazienti
a rischio
di patologie
L’uso
di desflurane
in pazienti
debilitati,
ipotesi non
è ancora
stato
atero-coronariche
è importante
mantenere
emodinamiche
normali per
evitare
ampiamente
sperimentato.
Come
per gli condizioni
altri potenti
anestetici generali,
si raccol’ischemia
miocardica
(vedi
anche
paragrafo 4.3 “Controindicazioni”).
Desflurane ha evimanda
in questi
pazienti
l’uso
di concentrazioni
inferiori a quelle consigliate.
ipertermia maligna.
Se questo mantenere
inavvertitamente
si
Indenziato
pazientilaapossibilità
rischio did'innescare
patologie una
atero-coronariche
è importante
condizioni
emodinamiche
normali
perdievitare
l’ischemia
(vedi questa
anche ipertermia.
paragrafo
presenta,
è allora indicato
l'uso
dantrolene
sodicomiocardica
per far regredire
4.3
“Controindicazioni”).
Desflurane
non deve essere usato in soggetti notoriamente predisposti all’ipertermia maDesflurane
la possibilità
d’innescare
unanon
ipertermia
maligna.inSequesto
queligna. Dataha
la evidenziato
scarsa esperienza
in ostetricia,
desflurane
è raccomandato
sto
inavvertitamente
si presenta,
allora indicato
l’uso dididantrolene
sodico
per far
tipo di interventi chirurgici.
Data laèpossibilità
di comparsa
broncospasmo,
desflurane
regredire
questa ipertermia.
Desflurane
non deve
esseretale
usato
in soggetti
notorianon va somministrato
in pazienti
che possono
sviluppare
condizione.
Poiché
vi è
mente
predisposti all’ipertermia maligna.
scarsa conoscenza nell'anestesia ripetuta non si è in grado di dare delle raccomandazioni
Data la scarsa esperienza in ostetricia, desflurane non è raccomandato in questo
definitive
a questo
riguardo. Come con tutti gli anestetici alogenati l'anestesia ripetuta entipo
di interventi
chirurgici.
tro un
periododidicomparsa
tempo va effettuata
con estrema
cautela. Come
consomministrato
altri anestetici
Data
la breve
possibilità
di broncospasmo,
desflurane
non va
desflurane
indurre sensibilizzazione
inalogenati
pazienti ilche
possonopuò
sviluppare
tale condizione.all'epatite in pazienti che siano stati
sensibilizzati
da precedenti
esposizioni
agli anestetici
alogenati.
Poiché
vi è scarsa
conoscenza
nell’anestesia
ripetuta
non si è in grado di dare delle
4.5raccomandazioni
Interazioni con altri
medicinali
ed altre
forme
di interazione
definitive
a questo
riguardo.
Come
con tutti gli anestetici alogenati
L'azione deiripetuta
miorilassanti
usatidiviene
potenziata
da desflurane.
Nei pazienti
l’anestesia
entro comunemente
un breve periodo
tempo
va effettuata
con estrema
cautela.
trattati con oppioidi, benzodiazepine o altri sedativi sono necessarie dosi ridotte di desfluCome
altritipo
anestetici
alogenati
desflurane
può indurre
sensibilizzazione
all’erane. con
Questo
di interazione
vieneil illustrato
di seguito.
Inoltre,
l'uso concomitante
di
patite
in pazienti
siano
stati di
sensibilizzati
da precedenti
esposizioni
agli“posologia
anesteprotossido
d'azotoche
riduce
le MAC
desflurane, come
spiegato alla
sezione 4.2
ticie modo
alogenati
di somministrazione”. Poiché gli oppioidi possono provocare depressione respira4.5
altri medicinali
ed altre va
forme
di interazione
toria, un Interazioni
eventuale usocon
concomitante
con desflurane
effettuato
con molta cautela.
L’azione dei miorilassanti comunemente usati viene potenziata da desflurane. Nei
Miorilassanti depolarizzanti e non depolarizzanti
pazienti trattati con oppioidi, benzodiazepine o altri sedativi sono necessarie dosi
Nella tabella
1 sono riportate
dosidi diinterazione
pancuronio,viene
atracurio,
suxametonio
e vecuronio
ridotte
di desflurane.
Questo letipo
illustrato
di seguito.
Inoltre,
necessarie
per ottenere
il 95% (ED
) di depressione
nella di
trasmissione
l’uso
concomitante
di protossido
d’azoto
riduce le MAC
desflurane,neuromuscolare
come spiega95
a
differenti
concentrazioni
di
desflurane.
Con
l’eccezione
del
vecuronio,
queste
dosi
sono
to alla sezione 4.2 “posologia e modo di somministrazione”. Poiché gli oppioidi possimiliprovocare
a quelle richieste
con isoflurane.
L’ED95 del
è iluso
14%concomitante
più basso con dessono
depressione
respiratoria,
unvecuronio
eventuale
con
flurane chevacon
isoflurane.
recupero del blocco neuromuscolare è più lungo con
desflurane
effettuato
conInoltre,
moltailcautela.
Miorilassanti
non
depolarizzanti
desflurane chedepolarizzanti
con isoflurane. eNon
sono
state evidenziate nelle prove cliniche interazioni
Nella
tabella dal
1 sono
le dosicirca
di pancuronio,
atracurio, suxametonio
e vecusignificative
puntoriportate
di vista clinico
l'uso con miorilassanti
di impiego comune.
ronio necessarie per ottenere il 95% (ED95) di depressione nella trasmissione neuTabella
1
Dosi
(mg/kg)
di
miorilassanti
che
provocano
95%
di
depressione
nella
romuscolare a differenti concentrazioni di desflurane. Con l’eccezione del vecuronio,
trasmissione
queste dosineuromuscolare.
sono simili a quelle richieste con isoflurane. L’ED95 del vecuronio è il
14% più basso con desflurane che con isoflurane. Inoltre, il recupero del blocco
Concentrazione
neuromuscolare è più lungo con
desflurane che
con isoflurane.
Pancuronio
Atracurio
Suxametonio
Vecuronio
diNon
Desflurane
sono state evidenziate nelle prove cliniche interazioni significative dal punto di
vista clinico circa l’uso con miorilassanti di impiego comune.
0,65 MAC/60% N2O/O2
0,026
0,133
*ND
Tabella 1 - Dosi (mg/kg) di miorilassanti che provocano 95%
1,25
MAC/60% N2O/O
0,018
0,119
*ND
nella
di depressione
2 trasmissione neuromuscolare.
*ND
*ND
–––––––––––––––––––––––––––––––––––––––––––––––––––––
Concentrazione
1,25
MAC/O di Desflurane
Pancuronio
0,022
Atracurio
0,120
Suxametonio
0,360
Vecuronio
0,019
0,026
0,133
*ND
*ND
2
–––––––––––––––––––––––––––––––––––––––––––––––––––––
0,65 MAC/60% N2O/O2
*ND1,25
= non
disponibile
MAC/60%
N2O/O2
0,018
0,119
*ND
*ND
Oppioidi
e 2benzodiazepine 0,022
1,25
MAC/O
0,120
0,360
0,019
–––––––––––––––––––––––––––––––––––––––––––––––––––––
La somministrazione di dosi crescenti di fentanil in pazienti anestetizzati con diverse con*ND
= non disponibile.
centrazioni
di desflurane ha reso necessario ridurre la quantità di anestetico o la MAC. La
somministrazione endovenosa di dosi crescenti di midazolam ha comportato una piccola
Oppioidi
e
benzodiazepine
riduzione della MAC. I risultati sono riportati nella Tabella 2.
La somministrazione di dosi crescenti di fentanil in pazienti anestetizzati con diverse
Queste riduzioni di MAC sono simili a quelle osservate con isoflurane. Si può pertanto preconcentrazioni di desflurane ha reso necessario ridurre la quantità di anestetico o la
sumere
anche gli altri oppioidi
e sedativi
influenzeranno
in maniera
analoga.
MAC.
La che
somministrazione
endovenosa
di dosi
crescenti le
di MAC
midazolam
ha compor-
tato una piccola riduzione della MAC. I risultati sono riportati nella Tabella 2.
Queste riduzioni di MAC sono simili a quelle osservate con isoflurane. Si può per-
Tabella 2 - Desflurane 0,6-0,8 MAC/O2
5
% Riduzione MAC
Senza Fentanil
6.33 - 6.35
-
Fentanil (3 μg/kg)
3.12 - 3.46
46 - 51
Fentanil (6 μg/kg)
2.25 - 2.97
53 - 64
Senza Midazolam
5.85 - 6.86
-
Midazolam (25 μg/kg)
4.93
15.7
Midazolam (50 μg/kg)
4.88
16.6
SU
PR
A
N
E
* Comprende i valori della fascia d'età 18-65 anni
4.6 Gravidanza e Allattamento
Non si è osservato alcun effetto teratogenico nei ratti o nei conigli a seguito di una
esposizione durante l'organogenesi con desflurane alla dose approssimativa di 10-13
MAC-ore cumulative.
L'embriotossicità nei confronti delle madri, probabilmente dovuta all'effetto farmacologico del desflurane si è evidenziata a seguito di esposizioni tossiche a livello materno.
In assenza di studi clinici adeguati e ben controllati, pertanto, desflurane non è indicato in
gravidanza. Desflurane, inoltre, non è indicato durante l'allattamento in quanto non sono
disponibili dati sulla sua escrezione nel latte materno.
4.7 Effetti sulla capacità di guidare e di usare macchinari
In assenza di informazioni circa gli effetti che desflurane potrebbe esercitare sulla capacità di guidare ed usare macchinari, è necessario avvisare i pazienti che il grado di attenzione potrebbe essere ridotto dopo un'anestesia generale e, pertanto, devono astenersi
da tali attività per un periodo di 24 ore.
4.8 Effetti Indesiderati
Analogamente agli altri anestetici generali, desflurane può causare ipotensione dosedipendente. Anche una depressione respiratoria dose-dipendente è stata rilevata.
Effetti collaterali dose-dipendenti:
•Cadutadellapressionearteriosa
•Depressionerespiratoria
•Aumento della circolazione cerebrale che può portare ad una accresciuta pressione
cerebrale
•Disturbidelritmocardiaco(tachicardia)
•Ischemiamiocardica
Effetti collaterali non dose-dipendenti
•Aumentodellasalivazionespecieneibambini
•Tosse
•Laringospasmoebroncospasmo
•Nauseae/ovomito
•Leucocitositransitoria
•Epatite
In prove cliniche che hanno incluso 370 pazienti adulti le reazioni avverse associate
al desflurane quando impiegato per indurre l'anestesia per inalazione hanno avuto
l'incidenza seguente: tosse 34%, difficoltà di respiro 30%, apnea 15%, salivazione, laringospasmo, desaturazione dell'ossiemoglobina 3-10%.
Nel periodo postoperatorio sono stati osservati nausea e vomito, normali sequele degli
interventi chirurgici e dell'anestesia generale che possono essere dovuti all'inalazione
dell'anestetico, alla somministrazione di altri farmaci durante l'intervento e nel periodo
postoperatorio e alla risposta del paziente alla procedura chirurgica.
Come per tutti gli altri anestetici generali, è stato osservato un aumento transitorio dei
leucociti anche in assenza di stress chirurgico.
Ipertermia maligna. Analogamente agli altri agenti di questo tipo, l'anestesia con desflurane ha fatto scatenare uno stato di ipermetabolismo dei muscoli scheletrici che ha
portato ad un'alta richiesta di ossigeno ed alla sindrome clinica nota come ipertermia
maligna (MH).
La sindrome presenta sintomi non specifici quali ipercapnia, rigidità muscolare, tachicardia, tachipnea, cianosi, aritmia con sbalzi di pressione ed un aumento generalizzato del
metabolismo che può portare a temperature corporee elevate. Il trattamento comporta
la sospensione degli agenti scatenanti, la somministrazione endovena di dantrolene
sodico, nonché tutte le misure di supporto necessarie. Questo effetto è stato osservato
nell’uomo sottoposto ad anestesia con desflurane in casi molto rari, dunque desflurane
non deve essere usato in soggetti di cui sia nota la tendenza a sviluppare MH.
4.9 Sovradosaggio
Esperienza nell'uomo
Non esiste esperienza di sovradosaggio nell'uomo.
Sintomi e trattamento del sovradosaggio
Si può ritenere che i sintomi di sovradosaggio da desflurane siano simili a quelli osservati
con altri anestetici volatili e comprendano approfondimento dell'anestesia, depressione
cardiaca e/o respiratoria in pazienti che respirano autonomamente, ipotensione in pazienti ventilati nei quali l'ipercarpnia e l'ipossia si possono verificare solo ad uno stadio
avanzato.
In caso di sovradosaggio o di sintomi che potrebbero far pensare ad un sovradosaggio,
occorre adottare le seguenti misure: interrompere immediatamente la somministrazione
di desflurane, assicurare la pervietà delle vie aeree ed iniziare una ventilazione assistita o
controllata con ossigeno puro. Le funzioni emodinamiche devono essere adeguatamente
supportate e mantenute.
5.1 Proprietà farmacodinamiche
Categoria farmacoterapeutica: anestetici generali – idrocarburi alogenati – codice ATC
N01AB07 Desflurano.
Desflurane appartiene alla famiglia dei metiletileteri alogenati che quando vengono
somministrati per inalazione, causano effetti reversibili, dose-dipendenti quali perdita di
conoscenza e di sensazione del dolore, soppressione dell'attività motoria volontaria, riduzione dei riflessi autonomi, sedazione della respirazione e del sistema cardiovascolare.
Appartengono allo stesso gruppo l'enflurane ed il suo isomero strutturale, l'isoflurane,
che sono alogenati sia con cloro che con fluoro. Desflurane è alogenato solo con fluoro.
Come desumibile dalla struttura chimica, il basso coefficiente di partizione sangue/gas
di desflurane (0,42) è inferiore a quello degli altri potenti anestetici generali quali isoflurane (1,4) ed anche inferiore a quello del protossido d'azoto (0,46). Questi dati indicano
che desflurane consente il rapido recupero dall'anestesia. Gli studi nell'animale hanno
dimostrato che l'induzione dell'anestesia ed il ricupero dall'anestesia sono più rapidi con
desflurane di quanto si ottenga con isoflurane pur avendo i due farmaci un profilo cardiorespiratorio simile. Tuttavia gli studi clinici non hanno confermato questi dati. Non sono stati
riscontrati segni di effetti epileptogeni o di altri effetti indesiderati sull'EEG; inoltre i farmaci
coadiuvanti non hanno causato risposte inaspettate o tossiche dell'EEG durante l'anestesia
con desflurane. Studi sui suini resi sensibili all'ipertermia maligna (MH) hanno indicato che
desflurane è un potenziale agente scatenante per l'MH. L'effetto farmacologico è proporzionale alla concentrazione di desflurane inspirata. I principali effetti secondari derivano
dall'azione farmacologica.
5.2 Proprietà farmacocinetiche
a) Caratteristiche generali
Come atteso in base al profilo chimico-fisico, gli studi di farmacocinetica nell'animale e
nell'uomo indicano che desflurane entra più rapidamente nell'organismo rispetto agli altri
anestetici generali, rendendo possibile una più rapida induzione dell'anestesia. Desflurane esce anche più rapidamente dall'organismo, consentendo un ricupero veloce ed una
maggiore flessibilità nella messa a punto della profondità dell'anestesia. Desflurane viene
escreto per via polmonare ed è metabolizzato solo in minima parte (0,02%).
b ) Caratteristiche nei pazienti
La MAC diminuisce con l'aumentare dell'età. Si raccomandano dosi ridotte nei pazienti
ipovolemici, ipotesi e debilitati, come riportato al paragrafo relativo alle Speciali Avvertenze e Precauzioni per l'Uso (4.4).
5.3 Dati preclinici di sicurezza
Nel suino desflurane non sensibilizza il miocardio alla somministrazione esogena di
adrenalina. Desflurane sembra determinare vasodilatazione coronarica a livello arteriolare solo in modelli animali selezionati, analogamente a quanto avviene con isoflurane. In
un modello animale che simuli l'insufficienza coronarica quale il cane sveglio cannulato,
desflurane non sembra produrre deviazione del flusso ematico dalle zone ischemiche a
quelle normalmente perfuse ("furto coronarico"). Studi clinici condotti su pazienti con
patologia coronarica, che valutavano l'evoluzione della malattia in termini di ischemia
miocardica, infarto e decesso, hanno dimostrato che gli effetti coronarici arteriolari di
Suprane non si associano a furto coronarico o ad ischemia miocardica.
Un programma sperimentale dettagliato comprendente studi in vivo ed in vitro non ha
evidenziato proprietà mutageniche di Desflurane in nessuna indicazione.
®
*MAC (%)
PROPRIETA' FARMACOLOGICHE
7
TITOLARE DELL'AUTORIZZAZIONE ALL'IMMISSIONE IN COMMERCIO
Baxter S.p.A. - Viale Tiziano 25 - 00196 Roma
8
NUMERO DELL'AUTORIZZAZIONE ALL'IMMISSIONE IN COMMERCIO
1 Flacone 240 ml: A.I.C. n. 029288014
6 Flaconi 240 ml: A.I.C. n. 029888026
9
DATA DI PRIMA AUTORIZZAZIONE/RINNOVO DELL’ AUTORIZZAZIONE
Dicembre 2005
10 DATA DI (PARZIALE) REVISIONE DEL TESTO
Maggio 2008
hp006ssi - stampato a settembre 2008
6 INFORMAZIONI FARMACEUTICHE
6.1 Lista degli eccipienti
Non ci sono eccipienti.
6.2 Incompatibilità
Nessuna nota.
6.3 Validità
Tre anni.
6.4 Speciali precauzioni per la conservazione
Il prodotto deve essere conservato in posizione verticale con il cappuccio ben chiuso.
6.5 Natura e contenuto del contenitore
Suprane è confezionato in flaconi di vetro ambrato di Tipo III con un rivestimento protettivo in PVC, contenenti 240 ml di desflurane. La chiusura è costituita da una resina
fenolica nera modellata, che si adatta ad un'apposita inserzione conica in polipropilene.
In alternativa, i flaconi di vetro possono essere chiusi con una valvola compatibile con
l'attacco del vaporizzatore di desflurane.
6.6 Istruzioni per l'uso
Rimettere il cappuccio dopo l’uso.
Desflurane deve essere somministrato solo da personale specializzato nel praticare
l'anestesia generale ed utilizzando un vaporizzatore specificatamente messo a punto e
tarato per desflurane. Come per tutti gli anestetici inalatori alogenati, in caso di utilizzo in
circuito chiuso, si raccomanda di verificare la presenza di adsorbitore (es. calce sodata)
fresco o ben umido, in quanto sono stati segnalati casi occasionali di formazione di
monossido di carbonio all'interno del circuito con conseguente carbossiemoglobinemia
per il paziente, dovuta all'interazione tra alogenato ed adsorbente essicato.
BREVIBLOC
®
RIASSUNTO
DELLE
CARATTERISTICHE
DEL
PRODOTTO
RIASSUNTO
DELLE
CARATTERISTICHE DEL
PRODOTTO
1. DENOMINAZIONE DEL MEDICINALE
10 mg/mL, Soluzione
per infusione sacca 250 mL
1. BREVIBLOC
DENOMINAZIONE
DEL MEDICINALE
®
2.
COMPOSIZIONE
QUALI/QUANTITATIVA
BREVIBLOC
Esmololo Cloridrato
10 mg/mL
“100
Ml Soluzione
Infusione”
PerMg/10
gli eccipienti,
vederePer
il punto
6.1 5 flaconcini 10 Ml.
3. FORMA FARMACEUTICA
per infusione QUALITATIVA E QUANTITATIVA
COMPOSIZIONE
2. Soluzione
4.
INFORMAZIONI
CLINICHE
Principio
attivo: Esmololo
cloridrato 100,00 mg
4.1
Indicazioni
terapeutiche
PerBREVIBLOC
gli eccipienti
vedere ilnelpunto
6.1. a breve termine delle: Tachicardie sopraventricolari
è indicato
trattamento
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FARMACEUTICA
3. atriale, FORMA
tachicardia
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brevissima
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Soluzione
perdurata
infusione.
il periodo peri-operatorio.
4.2 Posologia e modo di somministrazione
INFORMAZIONI
CLINICHEpronta all’uso (250 mL), di 10 mg/mL in sodio cloruro,
4. Il medicinale
è una concentrazione,
4.1raccomandata
Indicazioni
per laterapeutiche
somministrazione endovenosa di Brevibloc. Non introdurre additivi a
®
Brevibloc 10èmg/mL
Alla aconcentrazione
10 mg/mL, la dose d’attacco di
indicatopernelinfusione.
trattamento
breve terminedidelle:
BREVIBLOC
mg/kg/min
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Tachicardie
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di mL.
preeccitazione), e particoTachiaritmia
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fibrillazione
atriale,
atriale,
tachicardia
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ed in tutti
i casi in
La
posologia
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deveflutter
essere
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somministrare
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una
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posologico
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Posologia
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di somministrazione
4.2Sequenza
perfusione
di
una dose di mantenimento di 50/mcg/kg/min in 4 minuti. Ricominciare la
ADULTI:
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tacco in 1sopraventricolare
minuto; dose di mantenimento aumentata di 50 mcg/kg/min ad ogni sequenza,
La senza
posologia
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deve essere
titolata
individualmente.
Bisogna
somministrasuperare
200 mcg/kg/min.
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raggiunte
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e la frequenza
cardiaca
mantenere
unicamente
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d’attacco seguita
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ficace,posologico
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tra 50 e 200
Schema
di 5mcg/kg/min.
minuti): La durata della perfusione ai livelli indicati e
la dosedella
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possono
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V. essere
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minuto;
dall’infusione
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mi/kg/min
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Ricominciare con una dose di attacco da
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laterali.
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mentoMantenere
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Aumentare con
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tica
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In caso di comparsa
effetti
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500somministrazione
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150 microgrammi /kg/min.
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effetti la
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di esmololo.
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Nei pazienti
che presentano
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sione.
verapamil,
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digossina® opuò
chinidina.
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Le istruzioni
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caso,o illamedico
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L’interruzione
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Altro antiaritmico
Posologia
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rapida interruzione di betabloccanti
somministrati
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ore ilper
os
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ore
per
os
o
E.V.
tinaVerapamil
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con problemi alle arterie coronariche.
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co La
stabile
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seguenti casi:
prima ora
alla somministrazione
della prima
dose del farmaco,
ridurre Durante
ad una laterapia
consuccessiva
agenti antiaritmici
alternativi quale
propranololo,
digossina,
re della metà
(50%) la
velocità di infusione dell’esmololo.
metoprololo,
chinidina
o verapamil.
Dopo
la
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qui di seguito
ma il medico
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interrompere
l’infusione
deve
considerare con attenzione le istruzioni relative all’agente alternativo scelto.
dell’esmololo.
–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
ATTENZIONE: L’impiego di infusioni di esmololo per periodi superiori alle 24 ore
non èalternativo
stato valutato. Posologia
Agente
Tachicardia e aumenti10-20
di pressione
peri-operatori
Propranololo
mg ogni 4-6
ore per os
In periodo intra-operatorio,
Digossina
da 0,125
mg a 0,5
ogni 6immediato:
ore per osiniezione
o E.V. E.V. di una dose
durante l’anestesia, quando
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unmg
controllo
Verapamil
80
mg
ogni
6
ore
per
os secondi;
d’attacco sotto forma di un bolo di 80 mg in 15-30
infusione di una dose di200
mantenimento
da 150
mcg/kg/min, che potrà essere aumentata
Chinidina
mg ogni 2 ore
per os
fino a 300 mcg/kg/min.
–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
Al momento del risveglio dall’anestesia, per prevenire la scarica adrenergica iniezione E.V.
}
di una dose d’attacco da 500 mcg/kg/min al minuto per 4 minuti; infusione di una dose di
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La posologia didaBREVIBLOC
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In
post-operatorio
1. periodo
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le fasidella
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di infusione
di BREVIBLOC.
lità(50%)
di 50, la
100,
150, 200,
250 e 300
mcg/kg/min somministrati ogni 4 minuti, fermandosi
2. Dopo laterapeutico
seconda desiderato.
dose dell’agente alternativo, monitorare la risposta del paziente
all’effetto
Ricominciare
con la sequenza
di 5 minuti
fino ad ottenere
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e, se un controllo
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ora,terapeutico
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dose
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VIBLOC.
ad
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a
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ore
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arteriosa e la frequenza cardiaca desiderate, mantenere unicamente l’infusione della dose
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24-48 ore
che50
BREVIBLOC
è ben tollerato
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di
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e 300 mcg/kg/min.
Può essere
Tachicardia peri-operatoria
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modulazione
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livelli
di perfusione e della dose di mantenimento in funzione
dell’effetto
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o dell’incidenza
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a) In periodo
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quandodi èeventuali
necessario
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controllo immediato: iniezione
Se leE.V.
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da
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cato un’infusione
utile.
infusione come richiesto fino a 300 microgrammi/kg/min per mantenere la fre4.3 Controindicazioni
a) Assolute
quenza cardiaca desiderata e/o la pressione sanguigna.
Grave
(≤ 50
battiti/min.),
b) Albradicardia
momento del
risveglio
dall’anestesia: iniezione E.V. di una dose d’attacco da
Blocco
atrio-ventricolare
di alto grado
500
microgrammi
/kg/min
per 4 (senza
minuti; apparati)
seguita dall’infusione di una dose di manShock cardiogenico
tenimento
da 300congestizia
microgrammi/kg/min.
Insufficienza
cardiaca
scompensata
c) In periodo
post-operatorio,
Bambini
al di sotto
dei 12 anni quando è possibile la titolazione: iniezione E.V. di una
Gravidanza
e allattamento
sezione 4.6,
“Gravidanza
allattamento”)
dose d’attacco
di 500( vedi
microgrammi
/kg/min
per 1 eminuto;
seguita dall’infusione di
b) Relative:
una dose di mantenimento da 50 microgrammi /kg/min per 4 minuti.
AsmaSebronchiale,
si
ottiene
l’effetto
terapeutico
desiderato,
l’infusione
di mantenimento può
Broncopneumopatia cronica ostruttiva (B.P.C.O.)
essere
continuata
a 50 microgrammi/kg/min.
In caso
di turbe
ventilatorie
ostruttive, ed in presenza di antecedenti di broncospasmo,
Se NON sideve
ottiene
l’effetto
terapeutico
desiderato,
ricominciare
consua
la sequenza
di 5
l’esmololo
essere
utilizzato
con prudenza
tenendo
conto della
relativa cardioselettività
beta 1 e della
sua titolabilità
(vedi anche
“Speciali
e precauzioni
minuti aumentando
la dose
di mantenimento
ogni4.4volta,
finchèavvertenze
non si ottiene
l’effetto
d’impiego”).
terapeutico desiderato:
4.4 Speciali Avvertenze e Precauzioni d’impiego
– stessa dose d’attacco per 1 minuto, per esempio 500 microgrammi/kg/min.
Precauzioni
– seguito
Aumentare
dose di
mantenimento
microgrammi/kg/min
ognidevono
volta, essere
senza
In
al lorolaeffetto
negativo
sul tempodidi50
conduzione,
i beta-bloccanti
somministrati
conmicrogrammi/kg/min.
attenzione nei pazienti
con blocco
superare 300
Infondere
percardiaco
4 minuti.di primo grado. Gli anziani
devono
essere
trattati
con
cautela,
iniziando
con
un
dosaggio
più
basso;
di
solito
la
tolle– Allorchè siano raggiunte la pressione arteriosa e la frequenza cardiaca desiderate,
ranza
degli anziani
èlabuona.
continuare
con
dose
di
mantenimento
efficace
che
si
situa
tra
50
e
300
microI pazienti con malattia broncospastica non devono, in generale, ricevere beta-bloccanti. A
grammi
causa
della /kg/min.
selettività e titolabilità del suo beta1 relativo, Brevibloc deve essere usato con
– Può essere
prevista
una modulazione
della durata
di questo
di trattamento
cautela
nei pazienti
con malattie
broncospastiche.
Tuttavia,
dato cheschema
la selettività
del beta1
none èdella
assoluta,
deve essere
titolato con
attenzione
per ottenere
la dose
efficace
doseBrevibloc
di mantenimento
in funzione
dell’effetto
terapeutico
o della
comparsa
piùdibassa
possibile.
Nel
caso
di
broncospasmo,
l’infusione
deve
essere
immediatamente
effetti collaterali.
sospesa
e, se necessario,
somministrato
un agonistapossibile
beta2. interrompere in qualsiasi
Se lebase
condizioni
delsopra,
paziente
lo richiedono,
Sulla
di quanto
Brevibloc
deve essereèusato
con cautela anche in pazienti con
momentoo asma
l’infusione
e quando necessario riprenderla con una dose di mantenimento
dispnea
pregresse.
inferiore.
Nei
pazienti diabetici i betabloccanti possono nascondere i sintomi premonitori di un’ipoglicemia
come
tachicardia;
tuttavia,dileBREVIBLOC
vertigini ed i sudori
non sono
BAMBINI:
La una
sicurezza
e l’efficacia
nei bambini
nonsignificativamente
è stata stabilita,
modificati.
pazienti
aventi
pressione
arteriosa
sistolica
bassa prima
dunque il Nei
prodotto
non
deveuna
essere
usato
in pazienti
pediatrici
finchèdell’assunzione
sarannoe
dell’esmololo
sarà necessaria
un’attenzione
particolare
durante
il periodo
dinon
titolazione
disponibili
ulteriori dati.
durante
la perfusione
di mantenimento.Tutti i pazienti che ricevano dell’esmololo dovranPAZIENTI
ANZIANI:adIn una
generale
non sono
necessari
di dosaggio
nei
no
essere sottoposti
registrazione
continua
della aggiustamenti
pressione arteriosa
e dell’ECG;
in
caso dianziani.
episodio ipotensivo, con la riduzione del dosaggio o la sua interruzione l’ipopazienti
tensione
è
rapidamente
reversibile.
Nei
pazienti
con
insufficienza
renale
l’esmololo
deve
INSUFFICIENZA RENALE: Poichè il metabolita acido di BREVIBLOC è principalessere
con cautela
poichè deve
il metabolita
acido
è principalmente
mente somministrato
eliminato
immodificato
esserel’eliminazione
postadell’esmololo
cautela
si somminieliminato
immodificato
dai reni.daiIn reni,
questi pazienti
delquando
metabolita
acido è
stra BREVIBLOC diminuita,
per lunghi poichè
periodil’emivita
a pazienti
con insufficienza
renale. alla norma, e i
significativamente
è circa
dieci volte superiore
4.3 di plasma
Controindicazioni
livelli
sono considerevolmente elevati.
In
di insufficienza
epatica
sarà necessaria nessuna ulteriore precauzione per via
– caso
importante
bradicardia
(< 50non
battiti/min.),
della
funzione
precipua svoltadidalle
esterasi(senza
plasmatiche
nel metabolismo dell’esmololo.
–In pazienti
blocco
atrio-ventricolare
alto
grado
pace-maker),
con disordini circolatori periferici (malattia o sindrome di Raynaud, claudicazione
– shock cardiogenico,
intermittente),
i beta-blocanti devono essere usati con grande cautela dato che può sopravve– insufficienza
cardiaca
congestizia
scompensata,
nire
un peggioramento
di questi
disordini.
Sebbene
le interazioni
osservate
in studi
non siano
– ipersensibilità
al principio
attivo
o ad “ad
uno hoc”
qualsiasi
degli clinicamente
eccipienti rilevanti (vedi la
successiva
sezione 4.5
“Interazionie con
altri farmaci
altre forme di interazione”) Brevibloc
4.4
Speciali
avvertenze
precauzioni
peredl’uso
deve
essere
titolato
con
cautela
in
pazienti
trattati
contemporaneamente
con digossina, morAvvertenze:
fina,
succinilcolina o warfarina.
La
sicurezza
e
l’efficacia
di
BREVIBLOC
nei
bambini
non
è
stata
stabilita,
dunque il
Avvertenze
prodotto
deve essere
usato in pazienti
pediatrici
finchè non
sarannoè necessaria
disponibili
In
caso dinon
antecedenti
di insufficienza
cardiaca,
la stimolazione
simpatica
per
sostenere
ulteriori
dati. la funzione circolatoria nell’insufficienza cardiaca congestizia, e il blocco
dei
recettori
ha il rischio
potenziale dicardiaca:
aumentare
la depressione
della contrattilità
Pazienti
conbeta
antecedenti
di insufficienza
ai primi
segni o sintomi
di insuffidel
miocardio
e causare
maggiore insufficienza.
La continua
depressione
del
miocardio
cienza
cardiaca,
la
somministrazione
di
BREVIBLOC
deve
essere
ridotta
o interrotta.
con gli agenti beta-bloccanti per un certo periodo di tempo può, in alcuni casi,
portare ad
Per chi svolge
attività Ai
sportiva:
l’usoodel
farmaco
senza necessità
terapeutica
costituiinsufficienza
cardiaca.
primi segni
sintomi
di insufficienza
cardiaca
imminente,
Brevisce doping
e puòinterrotto.
determinare
comunque
positività
ai test
anti-doping.
bloc
deve essere
Sebbene
l’interruzione
possa
essere
sufficiente, a causa della
rapida
emivita
di
Brevibloc,
considerare
anche
un
trattamento
specifico
(vedi
anche
sezione
Precauzioni:
4.9
“Sovradosaggio”).
Pazienti
con problemi broncospastici: I pazienti con malattie broncospastiche non
I beta-bloccanti possono aumentare il numero e la durata degli attacchi di angina nei
devono, con
in generale,
beta-bloccanti.
Per la sua relativa
beta1 selettività
e titopazienti
angina diricevere
Prinzemetal
dovuta all’alfa-recettore
incontrastato
che funge
da
labilità,
il
deve essere
usato coronarica.
con cautelaInnei
pazienti
coni malattie
bronmediatoreBREVIBLOC
nella vasocostrizione
dell’arteria
questi
pazienti
beta-bloccanti
non
selettivi non
devonodato
essere
ed i bloccanti
vanno
usati solo con
cospastiche.
Tuttavia,
cheusati
la beta1
selettivitàbeta1
non èselettivi
assoluta,
BREVIBLOC
devela
massima
attenzione.
essere titolato
con attenzione per ottenere la dose efficace più bassa possibile. Nel
Icaso
beta-bloccanti
possono indurre bradicardia.
Se laimmediatamente
velocità del polsosospesa;
diminuisce
a meno
di
broncospasmo,
deve essere
Può
essere
50-55dibattiti
al minuto a l’infusione
riposo e il paziente
manifesta
sintomi collegati alla bradicardia,
il
somministrato
un
agente
beta2
stimolante
se
le
condizioni
lo
richiedono
ma
deve
dosaggio deve essere ridotto.
usato con
particolare
attenzione
dato che i verso
pazienti
hanno già
frequenIessere
beta-bloccanti
possono
aumentare
sia la sensibilità
gli allergeni
cherapide
la serietà
delle
reazioni
anafilattiche.
ze ventricolari.
Nei
pazienti
anziani:
non è stata la
rilevata
modifica èdegli
effettia farmacodinamici
Pazienti
diabetici
e ipoglicemici:
gravitànessuna
dell’ipoglicemia
inferiore
quella osservadal
confronto
dei risultati
ottenuti
in pazienti
di età superiore
ai 65 mascherare
anni e pazienti
di età
ta
con
i
betabloccanti
non
cardioselettivi;
i
betabloccanti
possono
la tachiinferiore ai 65 anni.
cardia
che accompagna
l’ipoglicemia,
ma altre non
manifestazioni
come le vertigini ed i
La
sicurezza
e l’efficacia dell’esmololo
sul bambino
sono state accertate.
Per
chipossono
pratica sport
agonistici,
attenzione: questo
prodotto contiene un principio
sudori
non essere
significativamente
modificati.
attivo
può una
introdurre
unaarteriosa
reazionesistolica
positiva
ad alcuni
praticati durante
Pazientiche
aventi
pressione
bassa
prima test
dell’assunzione
dell’econtrolli
antidoping.
saràcon
necessaria
un’attenzione
particolare
durante la somministrazione della
4.5smololo:
Interazioni
altri farmaci
e altre forme
di interazione
dose d’attaccocon
e durante
l’infusione di mantenimento.
Tutti
i pazienti chedell’effetto
ricevano delL’associazione
agenti ganglioplegici
può provocare un
potenziamento
ipol’esmololo
dovranno essere
sottoposti
una registrazione
continua della
tensivo.
L’associazione
dell’esmololo
agli ad
anestetici
volatili può potenziare
i loro pressione
effetti ipotensivi.
La eposologia
altriipotensivi,
potrà essere
modificata
peressere
mantenere
l’effetto
arteriosa
all’ECG; dell’uno
in caso odidegli
episodi
l’infusione
deve
rallentata
e,
desiderato.
se necessario, interrotta.
Farmaci anestetici: in situazioni in cui lo stato del volume plasmatico del paziente è incerto
Bradicardia: Somministrazione endovenosa di atropina o di un altro farmaco anti-colinergico.
Broncospasmo: Somministrazione endovenosa di un beta-2-mimetico e/o di un derivato
teofillinico.
Insufficienza cardiaca: Somministrazione endovenosa di un diuretico e/o di un glicoside
digitalico. Nello shock risultante da un’inadeguata contrattilità cardiaca, somministrazione
endovenosa di un agente inotropico. Possono essere considerati dopamina, dobutamina,
isoprenalina o amrinone.
Ipotensione sintomatica: Somministrazione endovenosa di liquidi e/o agenti pressori.
Shock cardiogenico: Somministrazione endovenosa di dopamina, di dobutamina, di isoprenalina o di amrinone.
5. PROPRIETA’ FARMACOLOGICHE
5.1 Proprietà farmacodinamiche
Categoria farmacoterapeutica: Betabloccanti. Codice ATC C07AB09: Esmololo cloridrato
Brevibloc è un betabloccante cardioselettivo che inibisce i recettori adrenergici con un
rapido attacco, una durata di azione molto breve e senza una significativa attività simpaticomimetica intrinseca o un effetto stabilizzante di membrana alle dosi terapeutiche.
L’esmololo cloridrato, principio attivo di Brevibloc, è chimicamente collegato alla classe dei
beta-bloccanti fenossidici propanolaminici. La molecola ha un gruppo estere labile dal punto
di vista enzimatico che permette un rapido metabolismo ed una emivita plasmatica breve.
Brevibloc, come altri beta-bloccanti, può esercitare effetti inotropi negativi. Le sue proprietà
farmacologiche gli conferiscono rapidità d’azione, breve durata d’azione ed adattabilità
delle dosi terapeutiche. Dopo una dose d’attacco appropriata, la concentrazione plasmatica
allo stato di equilibrio è ottenuta in meno di 5 minuti ed è in correlazione al conseguimento
dell’effetto farmacologico desiderato. La titolazione permette di ottenere la dose terapeutica adatta ad ogni paziente. Una rapida reversibilità del blocco dei beta-recettori è ottenuta
nei minuti che seguono l’interruzione della perfusione.
5.2 Proprietà farmacocinetiche
L’emivita di distribuzione è molto rapida, circa 2 minuti.
L’emivita di eliminazione è di circa 9 minuti dopo la somministrazione endovenosa.
L’esmololo è metabolizzato da esterasi eritrocitarie sanguigne e/o tessutali in un metabolita
acido e in metanolo per idrolisi del gruppo esterificato. L’esmololo è escreto nelle urine
sotto forma immutata (meno del 2% del prodotto somministrato) e sotto forma di un metabolita acido sprovvisto di significativa azione betabloccante.
La cinetica di eliminazione dell’esmololo è indipendente dalla dose nell’intervallo posologico da 50 a 300 mcg/kg/min.
La clearance totale è di 285 mL/kg/min. Essa non dipende dal flusso sanguigno epatico, nè
da alcun altro flusso sanguigno locale.
Il volume di distribuzione è di 3,4 l/kg.
Il legame con le proteine plasmatiche è del 55%.
5.3 Dati preclinici di sicurezza
Non applicabile
6. INFORMAZIONI FARMACEUTICHE
6.1 Lista degli eccipienti
Sodio cloruro, sodio acetato, acido acetico glaciale, sodio idrossido o acido idrocloridrico,
acqua ppi. L’osmolarità è 312 mOsmol/L.
6.2 Incompatibilità
Brevibloc non è compatibile con il bicarbonato di sodio.
6.3 Validità
18 mesi
6.4 Speciali precauzioni per la conservazione
Non conservare al di sopra di 25 °C. Non refrigerare o congelare.
6.5 Natura e contenuto del contenitore
Brevibloc 10 mg/mL soluzione per infusione è fornito in una sacca poliolefinica da 250 mL,
pronta all’uso, priva di lattice con due accessi in PVC.
6.6 Istruzioni per l’uso
Brevibloc 10 mg/mL per infusione è fornito in sacche poliolefiniche da 250 mL, pronte
all’uso, prive di lattice, con due accessi in PVC, uno per il farmaco e l’altro per la somministrazione. Nel caso di Brevibloc 10 mg/mL per infusione, l’accesso per il farmaco deve
essere usato solo per prelevare un bolo iniziale dalla sacca; tale accesso non deve essere
usato per la somministrazione ripetuta di boli. Usare una tecnica asettica quando si preleva
la dose di bolo. Non aggiungere altri farmaci a Brevibloc 10 mg/mL per infusione. Ogni
sacca è monouso e non contiene conservanti. Una volta che il farmaco è stato prelevato, si
consiglia di utilizzare il contenuto della sacca entro 24 ore, dopo le quali il contenuto non
utilizzato deve essere eliminato. Gettare il contenuto non utilizzato. Non riconnettere sacche
parzialmente usate.
Figura 1. Sacca IntraVia® a due accessi
Accesso per il
farmaco
(solo per il prelievo
iniziale del bolo)
Accesso per la
somministrazione
ATTENZIONE
Non usare contenitori in plastica per connessioni in serie. Un simile utilizzo può causare
un’embolia dovuta all’aria residua proveniente dal contenitore primario prima che la somministrazione del liquido dal contenitore secondario sia completata.
PER APRIRE
Non rimuovere l’unità dall’involucro esterno fino all’utilizzo. Non usare se l’involucro esterno è stato precedentemente aperto o danneggiato. L’involucro esterno è una barriera per
l’umidità. La sacca interna assicura la sterilità della soluzione.
Tirare l’involucro esterno dall’incavo e rimuovere la sacca. Si può osservare una certa opacità della plastica dovuta all’assorbimento dell’umidità durante il processo di sterilizzazione.
Ciò è normale e non influenza la qualità o la sicurezza della soluzione. L’opacità diminuirà
gradualmente.
Controllare se ci sono piccole perdite comprimendo con forza la sacca interna. Se si scoprono perdite, gettare la soluzione dato che la sterilità può essere compromessa. Non usare
se la soluzione non è limpida, incolore fino al giallo chiaro, e se il sigillo non è intatto.
Non introdurre additivi a Brevibloc 10 mg/mL per infusione.
PREPARAZIONE PER SOMMINISTRAZIONE ENDOVENOSA
(usare una tecnica asettica)
Appendere il contenitore utilizzando l’occhiello di supporto
Rimuovere la protezione in plastica dal punto di uscita in fondo al contenitore
Collegare il set di somministrazione. Fare riferimento alle istruzioni per l’uso del set
7. TITOLARE DELL’AUTORIZZAZIONE ALL’IMMISSIONE IN COMMERCIO
Baxter S.p.A.
Viale Tiziano 25, 00196 - Roma
8. NUMERO DI AUTORIZZAZIONE ALL’IMMISSIONE IN COMMERCIO
AIC N. 027248032
9. DATA DI PRIMA REGISTRAZIONE/RINNOVO
9 febbraio 2004
10. DATA DI (PARZIALE) REVISIONE DEL TESTO:
Gennaio 2008
HP007SSI - Stampato a settembre 2008
oppure vengono utilizzati in concomitanza farmaci anti-ipertensivi, si può verificare attenuazione della tachicardia di riflesso e un aumentato rischio di ipotensione.
Il blocco continuato dei recettori beta riduce il rischio di aritmia durante l’induzione e l’intubazione. L’anestesista deve essere informato quando il paziente riceve un agente betabloccante in aggiunta a Brevibloc. L’associazione alla succinilcolina non provoca modificazione della velocità di comparsa del blocco neuromuscolare; in cambio, la durata di tale
blocco può risultare leggermente aumentata (passando da 5 ad 8 minuti).
Calcio-antagonisti: L’associazione con verapamil o diltiazem influenza negativamente la
contrattilità e la conduzione atrio-ventricolare. Ai pazienti che presentano turbe della conduzione, l’esmololo non potrà essere somministrato che 48 ore dopo l’interruzione del
verapamil. L’associazione con derivati della diidropiridina, come la nifedipina, può aumentare il rischio d’ipotensione. Inoltre, nei pazienti con insufficienza cardiaca, il trattamento
con agenti beta-bloccanti può portare ad arresto cardiaco. Pertanto, sono raccomandati
un’attenta valutazione della titolazione di Brevibloc ed un appropriato monitoraggio emodinamico. L’associazione di beta-bloccanti con glicosidi digitalici può aumentare il tempo
di conduzione atrio-ventricolare. In uno studio specifico condotto su volontari sani, dove
digossina e Brevibloc sono stati somministrati contemporaneamente per via endovenosa,
si è verificato in alcuni casi un aumento del 10-20% dei livelli ematici di digossina, mentre
quest’ultima non ha influenzato la farmacocinetica di Brevibloc.
Associazione con clonidina: I beta-bloccanti aumentano il rischio dell’ipertensione di “rebound”. Se associato a beta-bloccanti non selettivi, come il propanololo, il trattamento con
clonidina deve essere continuato per un certo periodo successivamente all’interruzione
della somministrazione del beta-bloccante.
L’associazione alla morfina per via endovenosa non provoca alcuna modificazione del tasso
plasmatico di morfina; invece, è stato osservato un aumento del 46% dei tassi plasmatici
d’esmololo allo stato d’equilibrio senza modificazione degli altri parametri farmacocinetici.
L’associazione con farmaci anti-aritmici di classe I (per es. disopiramide, chinidina) e
amiodarone può avere un effetto potenziante sul tempo di conduzione atriale ed indurre
effetto inotropo negativo. L’insulina e i farmaci antidiabetici orali possono intensificare
l’effetto ipoglicemizzante (specialmente nel caso di beta-bloccanti non selettivi). Il blocco beta-adrenergico può prevenire, mascherandola l’apparizione dei segni di ipoglicemia
(tachicardia).I farmaci che inibiscono la sintesi delle prostaglandine possono aumentare gli
effetti ipotensivi dei beta-bloccanti.
Gli agenti simpaticomimetici possono contrastare l’effetto degli agenti bloccanti beta-adrenergici. La somministrazione concomitante di antidepressivi triciclici, barbiturici e fenotiazine, come pure di altri agenti anti-ipertensivi può aumentare gli effetti di abbassamento
della pressione ematica. Il dosaggio di Brevibloc deve pertanto essere regolato conseguentemente per evitare un’ipotensione inattesa.
I dati ottenuti da uno studio di interazione tra Brevibloc e la warfarina hanno dimostrato
che la somministrazione concomitante di Brevibloc e warfarina non altera i livelli di plasma
della warfarina. Le concentrazioni di Brevibloc, tuttavia, sono inequivocabilmente maggiori
se somministrato con warfarina. Le sostanze che esauriscono la catecolamina come per
es. la reserpina, possono avere un potenziamento di effetto se somministrate con agenti
beta-bloccanti. I pazienti trattati contemporaneamente con una di queste sostanze e Brevibloc devono dunque essere osservati attentamente per un’eventuale ipotensione o segni
di bradicardia evidente, che si manifestano con vertigini, sincope o ipotensione posturale.
4.6 Gravidanza e Allattamento
Sebbene non ci siano studi adeguati e ben controllati nelle donne in stato di gravidanza, è
stato riportato che l’uso dell’esmololo nell’ultimo trimestre di gravidanza o durante il travaglio o il parto può causare bradicardia fetale, continuata dopo il termine dell’infusione del
farmaco. L’uso di Brevibloc nelle donne in cui si sospetta o è confermata una gravidanza
deve essere evitato.
Non è noto se Brevibloc è escreto nel latte umano: tuttavia, la somministrazione di Brevibloc
nelle madri che allattano deve essere evitata.
4.7 Effetti sulla capacità di guidare e usare macchinari
Non applicabile
4.8 Effetti indesiderati
Più frequentemente: ipotensione arteriosa (vedi sezione 4.4 “Avvertenze speciali e precauzioni d’impiego”). Meno frequentemente: eccessiva sudorazione, nausea, vomito, ischemia
periferica, cefalea, infiammazione, indurimento al livello del punto d’infusione (vedi sezione
4.4 “Avvertenze speciali e precauzioni d’impiego”), bradicardia e broncospasmo in periodo
perioperatorio. Raramente: ansietà, anoressia, costipazione, ritenzione urinaria, edema, sibili, dispnea, turbe dell’eloquio, disturbi della vista ed episodi febbrili.
Eccezionalmente: in caso di stravaso, possibilità di necrosi cutanea.
In caso di comparsa di effetti collaterali, ridurre o interrompere l’infusione di esmololo. Tutti
questi effetti collaterali scompaiono in al massimo 30 minuti dalla sospensione dell’infusione di esmololo. Le seguenti reazioni avverse sono state registrate in studi clinici condotti su
369 pazienti con tachiaritmia sopraventricolare e su 600 pazienti in fase intra-operatoria e
post-operatoria. Molte reazioni avverse osservate nello studio clinico controllato sono state
leggere e passeggere. La più importante reazione avversa è stata l’ipotensione.
Cardiovascolari
L’ipotensione sintomatica (sudorazione, capogiri) è sopravvenuta nel 12% dei pazienti, e
la terapia è stata interrotta in circa l’11% dei casi, metà dei quali circa erano sintomatici.
L’ipotensione asintomatica è sopravvenuta nel 25% circa dei pazienti. L’ipotensione si è
risolta durante l’infusione di Brevibloc nel 63% di questi pazienti e entro 30 minuti dopo
l’interruzione dell’infusione nell’80% dei pazienti rimanenti. La sudorazione ha accompagnato l’ipotensione nel 10% dei pazienti. E’ sopravvenuta ischemia periferica nell’1% circa
dei pazienti. Pallore, rossore, bradicardia (battito cardiaco minore di 50 battiti al minuto),
dolore al torace, sincope, edema polmonare e blocco cardiaco sono stati riportati in meno
dell’1% dei pazienti. In due pazienti senza tachiaritmia sopraventricolare ma con grave
danno all’arteria coronarica (dopo-infarto del miocardio inferiore o angina instabile), si è
sviluppata grave bradicardia/pausa sinusale/asistolia, reversibile in entrambi i casi con l’interruzione del trattamento.
Sistema Nervoso Centrale: Sono sopravvenuti capogiri nel 3% dei pazienti; sonnolenza nel
3%; confusione, mal di testa ed agitazione in circa il 2%; affaticamento nell’1% circa dei
pazienti. Parestesia, astenia, depressione, pensieri anormali, ansietà, anoressia e vertigini
sono stati riportati in meno dell’1% dei pazienti. Sono state riportate anche convulsioni in
meno dell’1% dei pazienti, con un caso di decesso.
Respiratori: Broncospasmo, asma, dispnea, congestione nasale, sibili e rantoli sono stati
riportati in meno dell’1% dei pazienti.
Gastrointestinali: E’ stata riportata nausea nel 7% dei pazienti. E’ sopravvenuto vomito
nell’1% circa dei pazienti. Dispepsia, costipazione, bocca secca e dolori addominali sono
sopravvenuti in meno dell’1% dei pazienti. E’ stata riportata anche alterazione del gusto.
Epidermiche (punto di infusione): Le reazioni del punto di infusione incluse infiammazione
e indurimento sono state riportate nell’8% circa dei pazienti. Edema, eritema, scolorimento
della pelle, bruciore al punto di infusione, tromboflebiti e locale necrosi cutanea dovuta a
stravaso sono sopravvenute ognuna in meno dell’1% dei pazienti.
Varie: Ciascuna delle seguenti reazioni avverse è stata riportata in meno dell’1% dei pazienti: ritenzione urinaria, disordini del linguaggio, disturbi della vista, dolore tra le scapole,
brividi e febbre. Nel periodo intra-operatorio, sono state osservate anche bradicardia e
broncospasmo.
4.9 Sovradosaggio
I sovradosaggi di Brevibloc possono causare arresto cardiaco. In aggiunta, i sovradosaggi possono causare bradicardia, ipotensione, dissociazione elettromeccanica e perdita di
coscienza. Casi di sovradosaggio accidentale massiccio di Brevibloc sono sopravvenuti in
seguito ad errori di diluizione. Alcuni di questi sovradosaggi sono stati fatali mentre altri
hanno causato invalidità permanente. Dosi in bolo variabili da 625 mg a 2,5 g (12,5-50
mg/kg) sono state fatali. I pazienti si sono ripresi completamente da sovradosaggi di 1,75 g
somministrati in un minuto o dosi di 7,5 g somministrate in un’ora per chirurgia cardiovascolare. I pazienti che sono sopravvissuti sono stati quelli la cui funzione circolatoria poteva
essere supportata fino all’esaurimento degli effetti causati da Brevibloc.
A causa del suo tempo di eliminazione (emivita di circa 9 minuti), il primo passo nel trattamento della tossicità consiste nell’interruzione dell’infusione di Brevibloc. Poi, in base agli
effetti clinici osservati, devono essere considerati anche i seguenti provvedimenti generali.

Full HSR proceedings Vol. 1

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