الفهرس 
Hemodynamic monitoring during sepsis and septic shock
Pulmonary Artery CatheterOnly 14 pages are availabe for public view
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Abstract
Depression of LV intrinsic contractility is constant in patients with
septic shock. Because most parameters of cardiac function are strongly
dependent on afterload, especially in this context, cardiac performance
evaluated at the bedside reflects intrinsic contractility but also
thedegree of vasoplegia. Recent advances in echocardiography have
allowed better characterization of septic cardiomyopathy. Unlike
classic cardiomyopathy, it is not associated with high filling pressures
for two reasons: increased LV compliance and frequently associated
RV dysfunction. It is always reversible. Although it is unclear how
septic cardiomyopathy affects outcome, a hyperkinetic state is
indicative of profound and persistent vasoplegia associated with a high
mortality rate. Preliminary data suggest that the hemodynamic response
to dobutamine challenge has a prognostic value, but large studies are
required to establish whether inotropic drugs should be used to treat
this septic cardiac dysfunction.
Reversible myocardial depression in patients with septic shock was
first described in 1984 by Parker et al. using radionuclide
cineangiography. In a series of 20 patients, they reported a 65%
incidence of left ventricular(LV) systolic dysfunction, defined by an
ejection fraction<45%. In 1990, using transthoracic echocardiography,
Jardin et al. reported the same results. In a canine model simulating
human septic shock, Natanson et al. demonstrated that intrinsic LV
performance was actually depressed in all animals and not corrected by
volume expansion. Finally, more recently, Barraud et al. confirmed the
presence of severe depressed intrinsic LV contractility using LV
pressure/ volume loops in lipopolysaccharide-treated rabbits.
All of these studies, and many others not cited in this introduction,
demonstrate the reality of the impairment of intrinsic LV contractility
in septic shock. For many years, septic cardiac dysfunction was largely
underestimated because the hemodynamic device used, i.e., the
pulmonary artery catheter, was not appropriate for establishing such a diagnosis. Development of new hemodynamic tools at the bedside,
such as echocardiography, allowed better characterization of the septic
cardiomyopathy.
Our essay explains the mechanisms of such a depression, its
characteristics, incidence, and finally its impact on treatment and
prognosis. We decided not to deal with the place and the role of
biomarkers, which will be presented in a future review of the journal.
Mechanisms
Many factors may contribute to cardiac depression during sepsis.
Studies performed in humans have ruled out coronary hypoperfusion
requiring coronary intervention as a cause of LV systolic dysfunction
in sepsis. Of course, patients with coronary disease may behave
differently. On the other hand, the role of cytokines has been strongly
advocated in the genesis of septic cardiomyopathy. In 1985, Parrillo et
al. demonstrated in vitro that myocardial cell shortening is reduced by
exposure to the serum of septic patients. Later, the same team showed
that the circulating factor responsible for this was tumor necrosis factor
a (TNF-a), even though later studies have implicated other cytokines,
such as interleukin-1b. Kumar et al. suggested that the effect of
cytokines on cardiac myocytes results from an increase in intracellular
cGMP and in nitric oxide. In addition, direct alteration in cellular
respiration with mitochondrial dysfunction also was advocated, and,
finally, Tavernier et al. suggested that increased phosphorylation of
troponin I was involved by reducing myofilament response to Ca2+.
Main characteristics of septic cardiomyopathy:
The first characteristic of septic cardiomyopathy is that it is acute
and reversible, providing the patient recovers. it is acute and reversible,
providing the patient recovers. In 90 patients during a 5-year period,
Jardin et al. reported that LV ejection fraction is normalized in a few
days, as also reported more recently by Bouhemad et al. The second characteristic, which is crucial to full understanding, is
that depressed LV systolic function is associated with normal or low
LV filling pressure, unlike the “classic” pattern of cardiogenic shock
where LV pressures are elevated. This may explain why the pulmonary
artery catheter has for many years underestimated the incidence of LV
systolic dysfunction. Jardin et al. and Bouhemad et al. reported an
average pulmonary capillary wedge pressure close to 11 mmHg in
patients with decreased LV ejection fraction, which is not significantly
different from that found in patients with a preserved ejection fraction.
In the study by Parker et al., the pulmonary capillary wedge pressure
was 14 mmHg on average in patients with LV ejection fraction <45%.
Two mechanisms may explain this absence of elevated LV
pressures. The first relates to the frequent association with right
ventricular (RV) dysfunction. Vincent et al. in a group of 93 patients
with septic shock reported a decreased RV ejection fraction compared
with a “control” group. Similar results were found by Kimchi et al. and
Parker et al. Using transesophageal echocardiography, we reported that
almost 30% of patients have RV dilatation, which is highly suggestive
of significant RV dysfunction. RV dysfunction is related to acute
pulmonary hypertension, which is frequently associated in this situation
because of the acute lung injury, or depressed intrinsic contractility due
to circulating cytokines. It protects the pulmonary circulation and
avoids significant elevation of LV pressures. The second mechanism
relates to LV compliance alteration, which usually occurs. In their
original work, Parker et al. suggested a huge increase in LV
compliance; they found a dilatation of the left ventricle of more than
100%. This very impressive LV “preload adaptation” was actually
never confirmed and was probably explained in part by technical errors
related to the use of the pulmonary artery catheter. Most studies using
echocardiography only report a slight increase in LV size in patients
with decreased LV ejection fraction compared with patients with
preserved ejection fraction, suggesting a true but slight increase in LV
compliance in these patients. In 12 normal healthy volunteers,
Suffredini et al. demonstrated that injection of endotoxin induces a
depression of LV systolic function associated with a significant decrease in the ratio of pulmonary capillary wedge pressure to LV
enddiastolic volume index. A limited but significant increase in LV
end-diastolic volume was reported after volume loading with a
pulmonary capillary wedge pressure less augmented than in the control
group .
Diagnosis:
In studies of septic shock lasting ≥ 48 hours, 24% to 44% had
systolic LV dysfunction while 44% showed features of diastolic
dysfunction. Myocardial depression is a reversible phenomenon that
subsided in 7–10 days if the patient survived. The characteristics of
myocardial depression in septic shock are reduced ventricular ejection
fraction and biventricular dilatation, although the marked dilatation has
not been confirmed in some studies.
Diastolic dysfunction is not as clearly defined. Poelart et al.
demonstrated that cardiac dysfunction in septic shock is a continuum
from isolated diastolic dysfunction to both diastolic and systolic
ventricular failure. The impact of septic myocardial dysfunction on the
outcome has been controversial. Some studies have found an initially
lower LVEF and more dilated LV in patients who survived while some
have noticed decreased cardiac function in non-survivors. Different
mechanisms in evaluation of cardiac function and fluctuation of the
loading conditions probably explain these differences.
Elevated circulating concentrations of Natriuretic peptides are
clinical hallmarks of cardiac dysfunction. The Serum levels of BNP are
elevated in heart failure. Therefore, plasma BNP concentrations are a
good diagnostic indicator of congestive heart failure. The role of
neurohormonal markers of myocardial dysfunction in sepsis has been
reported in both animal and human models. Hartemink et al. found that
right and left systolic dysfunction correlated with an increase in plasma
levels of atrial Natriuretic peptide (ANP) during the first 72 hours after
the diagnosis of septic shock.Cardiac troponins; and natriuretic peptides. These biomarkers were
initially introduced for use in diagnosis and risk stratification in
patients with acute coronary syndrome (ACS) and congestive heart
failure (CHF) respectively but their spectrum of application is
widening. The aim of the present review is to provide clinicians with a
summary of the current evidence about the prognostic and diagnostic
impact of cardiac troponins and natriuretic peptides in patients with
sepsis-associated myocardial dysfunction.
Echocardiography is unique as it offers an instantaneous, bedside,
comprehensive assessment of cardiac function in septic patients.
Echocardiography allows qualitative and quantitative assessment of
global and regional left and right ventricular systolic function, diastolic
function, left and right ventricular preload, regional wall motion
abnormalities, and cardiac output.
Although the clinical utility of echocardiography was apparent,
imaging quality was reduced by technological limitations in at least a
third of ventilated ICU patients. Advances in ultrasound technology
have improved the imaging quality obtained by the TTE in the
ventilated critically ill patient. TTE can now be considered the
Echocardiographic modality of first choice for imaging in most ICU
patients, including those with sepsis. It is possible and often relatively
easy to derive or estimate standard hemodynamic data using the
echocardiography. Although the information obtained is not
continuous, repeating a TTE study is relatively easy as long as an
experienced operator is available.
Prognosis and treatment
It is very difficult to establish whether septic cardiomyopathy
independently affects the prognosis of patients with septic shock,
because many other variables are involved, such as age, patient history,
type of microorganisms, and time to resuscitation. Initially, Parker et
al. suggested that development of septic cardiomyopathy was
“protective”. Ten of the 13 survivors had an LV ejection fraction
Summary
115
<40%, but none of the nonsurvivors. In appearance, we found different
results with a mortality rate of 43% in patients with a hypokinetic
profile compared with 24% in patients with a normokinetic profile. We
also found that patients with a hyperkinetic profile (small left ventricle,
supranormal ejection fraction, tachycardia, high cardiac index) had a
100% mortality rate. Actually, rather than a “protective” effect of LV
systolic dysfunction, we can conclude that the prognosis is poor in the
presence of a hyperkinetic state, which reflects persistent and profound
vasoplegia, as explained above. Table 3 summarizes the main studies
and their results in terms of survival and LV systolic function.
Three therapeutic interventions must be discussed. The first is
volume expansion. Parker et al. suggested that “massive” fluid infusion
maintains a normal cardiac index, despite a significantly impaired LV
contractility, through LV preload adaptation. However, we have
learned that this dilatation is limited and that fluid overload is
deleterious for survival. In the study by Ognibene et al., volume
infusion was unable to restore normal left ventricular function and
unmasked a flat Frank-Starling curve in the 21 patients with septic
shock. In our study, LV stroke index and LV end-diastolic volume did
not correlate, whereas LV stroke index and LV ejection fraction were
strongly correlated. Nevertheless, volume expansion must always be
proposed first to restore central blood volume in the case of absolute or
relative hypovolemia.
The second therapeutic option is the infusion of an inotropic drug,
such as dobutamine, a beta-agonist agent. We and others reserve this
treatment for patients with persistent shock, lactic acidosis, and
oliguria. In this situation, dobutamine increases LV ejection fraction
and cardiac index. To which extent such a treatment may improve the
patient’s prognosis is unknown. However, it is well established that the
cardiovascular response to dobutamine stress predicts outcome in
sepsis. Vallet et al. using a dose of 10 μg/kg per min and Rhodes et al.
using a dose of 5 μg/kg per min reported that patients with an increased
oxygen consumption(>15%) in response to dobutamine infusion have a
much higher survival rate. This was related to a significant increase in cardiac index and oxygen delivery. More recently, Kumar et al.
performed a “dobutamine challenge” at 5, 10, and 15 μg/kg per min in
23 patients with septic shock. They also found that survival was
associated with increased cardiac performance and LV contractility
indices. In particular, a cutoff value of 8.5 mL/m2 increase in LV
stroke index in response to dobutamine correctly categorized the
outcome in 21 of 23 patients. Levosimendan, a new calcium sensitizer,
also has been proposed to treat septic cardiomyopathy. It may improve
not only LV but also RV function in the context of sepsis. Barraud et
al. in an endotoxin model in rabbits reported that LV systolic elastance
was restored during levosimendan infusion.
The third and finally, a few words should be mentioned about
norepinephrine administration. As explained above and shown in
Figure 3, norepinephrine infusion may unmask the impairment of LV
contractility. However, some authors recently have suggested that
administration of norepinephrine for restoring mean arterial pressure in
the early phase of septic shock also increased cardiac output through an
increase in both cardiac preload and cardiac contractility. Such findings remain to be confirmed.