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What tests can help diagnose and estimate the
severity of sepsis?
All critically ill patients with a systemic
inflammatory response syndrome or a multiple
organ dysfunction syndrome look septic; in spite
of this, only half of them are infected.1 Giving
antibiotics to all these patients may seem a
good thing to do, at least at first glance.
There are indeed data suggesting that the
outcome of septic critically ill patients who
received antibiotics sooner is better. On the
other hand, giving too many antibiotics
increases the “antibiotic pressure” in a given
intensive care unit, which could result in the
development of multiresistant bacteria. There
are data suggesting that the administration of
more antibiotics increases the risk of
contracting a nosocomial infection caused by a
multiresistant bacterium2 and doubles the risk
of death.3,4 Therefore, there is a trade-off
here: it is possible that giving antibiotics
sooner improves the outcome of infected
patients, but it can also increase their risk of
contracting an infection caused by a
multiresistant bacterium. The best strategy
could be to prescribe antibiotics as soon as
possible, but only if there is a great a priori
chance that a critically ill patient who looks
septic will really become infected, and to
postpone such prescription if the a priori
chance is small. Therefore, a test able to
rapidly differentiate infected from non-infected
patients could be of great interest. Bacterial
culture remains the gold standard to do so, but
the results are available only 1 or 2 days after
the question about a possible infection is
raised at the bedside. In practice, the
physician estimates the chance that a patient
will become infected on clinical grounds and on
rapid tests, such as white blood cell count,
C-reactive protein, and procalcitonin.
C-reactive protein and procalcitonin are two
acute-phase reaction proteins of the
inflammatory process. Their blood concentrations
increase rapidly after the onset of an
inflammation; this increase is usually much more
important if the inflammation is caused by an
infection and/or if the pathology is severe.
Procalcitonin seems to be a more reliable
diagnostic marker of inflammation caused by a
bacterial infection than C-reactive protein.5
The normal procalcitonin blood level is lower
than 0.1 ng/mL. With a cutoff point of 1 or 2 ng/mL,
its sensitivity in diagnosing a bacterial
infection ranges between 65% and 100%, and its
specificity is between 61% and 100%. The overall
sensitivity and specificity, as measured in a
systematic review, are 88% (95%CI 80-93) and 81%
(95%CI 67-90), respectively.5 A blood level
higher than 10 ng/mL is almost always associated
with severe sepsis (a systemic inflammatory
response syndrome caused by an infection and
associated with at least one organ
dysfunction).6
Most available data on procalcitonin come from
adults, but there are some pediatric
studies.7-12 These data may look better than
they are. In many studies, procalcitonin was not
measured when practitioners needed to know
whether the patient was infected or not: it was
sometimes measured days after the infection was
suspected, and such time lag may have allowed
its further increase in blood, which could
increase its apparent diagnostic validity.
Actually, the picture could be different if only
measurements on blood drawn immediately when the
infection was suspected are analyzed. There are
very few data addressing this specific question:
is procalcitonin a good diagnostic marker of
bacterial infection in critically ill children
when sepsis is suspected for the first time?
Only one study of 61 children provided data on
this: St-Louis et al.13 reported that the
positive predictive value of a blood level over
1.8 ng/mL was 67% (it was only 50% for the
C-reactive protein).
Another clinically significant question would
be: is there a relationship between the severity
of infection and serum procalcitonin level? The
study conducted by Fioretto et al.14 and
published in this issue of the Jornal de
Pediatria was designed to answer this question.
They enrolled 90 children with a clinical
picture of severe sepsis or septic shock. In all
instances, procalcitonin was measured soon after
the patients were seen for the first time for
their possible infection, i.e. right at their
admission to the pediatric intensive care unit
and 12 hours later. They found that the blood
concentration of procalcitonin was significantly
higher in cases of septic shock in both
instances. Actually, with a cutoff of 2 ng/mL,
the positive diagnostic value to detect cases of
septic shock was 60%, and the negative
predictive value to exclude septic shock was
81%; with a cutoff of 10 ng/mL, they were
respectively 68 and 72%.
The available data suggest that procalcitonin
has some diagnostic value in detecting cases of
sepsis among critically ill children. Two
questions remain: what is the added value of
this information over clinical data, and can it
change the outcome of patients? Stated
differently, the question could be: is
procalcitonin useful, given the clinical
information already available at the bedside?
The results of one study suggest that using
procalcitonin to guide the prescription of
antibiotics in children with lower respiratory
tract infection can decrease antibiotic pressure
without influencing the outcome of patients.15
Nonetheless, more data are required, and a
randomized clinical trial should be undertaken
to assess test effectiveness before strongly
recommending the use of procalcitonin.
Meanwhile, we agree with Dr. Fioretto and
colleagues that procalcitonin can be used to
estimate the severity of illness in septic
critically ill children, but only if the
clinical data are taken into account.
(Pediatr (Rio J). 2007;83(4):297-8.)
References
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