Page 851 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

582 PART 5: Infectious Disorders

Biomarkers: Physicians have used biological markers of infection, studies. Subsequently, several other scoring systems, including
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such as the white blood cell count, to help guide clinical decisions CURXO, SMART-COP, REA-ICU, and CAP-PIRO, were devel-
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for a long time, so biomarkers are hardly a new concept. The last oped to specifically address the need for ICU care. The CURXO and
decade has seen an explosion of interest in the potential for the levels SMART-COP criteria were developed with multivariate techniques but
of a number of inflammatory proteins to help guide clinical decision surprisingly are very similar to the IDSA/ATS minor criteria. Table 65-5
making in CAP. Possible applications for biomarkers that have been lists criteria from the various SCAP scoring systems. In general, three or
put forward include guiding antibiotic therapy (both initiation of more of these minor criteria are almost always found in patients who
treatment and duration of therapy) and more accurate stratification are either admitted directly to the ICU or who have deterioration on the
of patients into high- or low-risk groups. floor and subsequent transfer to the ICU. Unfortunately many patients
Procalcitonin (PCT), a calcitonin precursor that is elevated in infection safely managed on the floor have three criteria as well. None of the scor-
as well as in patients with trauma, burns, and neuroendocrine tumors, ing systems have been prospectively demonstrated to avoid late transfers
is probably the best-validated “new” marker. Interferons released in or to lower mortality. However, clearly demonstrated in all of the studies
response to viral infection appear to suppress PCT levels, enhancing a is that the greater the number of these criteria seen at presentation, the
gradient between active bacterial and viral infections. While proposed as more likely the need for ICU care.
a relatively specific marker of bacterial infection (as distinct from viral), Biomarkers: The deficiencies of the existing clinical scoring systems
the clinical discriminating value of PCT remains unclear.
In a randomized trial of patients with a variety of lower respiratory discussed above directly correlate with the interest in biomarkers to
tract infections, only 15% of CAP patients were recommended to with- risk stratify, as probably does the desire for simple decision making
hold antibiotics based on PCT levels. This rate may be very close to the tools that remove the need for the time-consuming process of exam-
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ining patients. Precedence for biomarker use to triage patients comes
incidence of true viral pneumonia. Although the number of patients in
whom antibiotic therapy was withheld increased significantly, more than from the successful use of lactate levels to detect occult hypoperfusion
in sepsis and respond more aggressively. Many of the other minor
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50% of physicians chose to override the PCT-guided recommendations,
giving antibiotics despite the recommendation to withhold them. A criteria listed in Table 65-5 are in essence biomarkers as well.
Biomarkers have been proposed to either simplify or add greater
subsequent study found inadequate sensitivity and specificity to reliably
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differentiate between bacterial or viral CAP. Acute and convalescent predictive power to the clinical predictive tools already discussed. PCT
levels clearly correlate with increasing severity of CAP based on the PSI
serologies also indicate that some high-PCT CAP cases were caused by 73-75
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viral pathogens. Anecdotal experience with primary novel 2009 H1N1 or CURB-65. A PCT <0.1 ng/mL is associated with a good prognosis
regardless of the PSI score, and a PCT >0.5 ng/mL increases the likeli-
influenza pneumonia confirms this observation. Although bacterial 74
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infections are generally associated with higher PCT levels in children, hood of mortality in patients with a PSI grade V. However, PCT did not
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predict development of severe sepsis either acutely or after 24 hours, sug-
the ability to discriminate between bacterial and viral etiology in indi-
vidual cases is highly questionable and likely less accurate than in adults. gesting that PCT may correlate with nonsepsis-related deaths. Another
study found that PCT did not increase the accuracy of the PSI for
Therefore, a high PCT is unlikely to be helpful in patients admitted 75
to the ICU since even severe viral pneumonias may result in increased predicting mortality, although small improvements were found when
C-reactive protein was added to the PSI, CURB-65, or CRB-65 scores.
PCT as a nonspecific inflammatory biomarker. Conversely, a low PCT
Although PCT also correlates with the need for ICU care, adjunctive
in a critically ill patient is suggestive of nonbacterial infection or a CAP use of PCT specifically for the decision to admit to the ICU was not
mimic (Table 65-4). found to be helpful. An elevated serum PCT level did not add any
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■ CRITERIA FOR ICU ADMISSION discriminating value to the IDSA/ATS minor criteria. A small number
of patients with three minor criteria and a low PCT appeared to do well
Patients initially admitted to a non-ICU setting but subsequently requir- when admitted to a non-ICU setting. At this time, a clear role for PCT as
ing ICU transfer (up to 50% of CAP patients ultimately receiving ICU an adjunct to existing clinical scoring systems remains unproven.
care) have a very high mortality rate, exceeding that of patients who have A number of other biomarkers have been suggested to be useful in
equivalent illness at presentation but who are admitted directly to the the setting of CAP. C-reactive protein (CRP) appears to be even more
ICU. 63,64 High degrees of variability in ICU admission for CAP between generic for inflammation, rather than only infection, than PCT and is
hospitals and individual physicians have also been found. This has led likely to have all the issues discussed above for PCT. Given the high
to attempts to standardize the ICU admission decision with a variety of prevalence of acute cardiac complications in patients with CAP, 77,78 the
tools, including scoring systems and biomarkers. In patients who pres- association of markers of cardiac stress, such as troponin-I and B-type
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ent to hospital already severely ill, requiring mechanical ventilation or natriuretic peptide, with CAP outcomes is interesting.
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vasopressor support at the outset, decision support for ICU admission
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is clearly not needed. Therefore, the critical criterion to evaluate these
decision support tools is the ability to identify patients likely to dete- TABLE 65-5 Minor Criteria for Consideration of ICU Admission for Severe CAP
riorate if admitted to a non-ICU situation. A limitation in all of these IDSA/ATS Criteria Other Criteria
decision support tools is the frequency of limitation of care decisions in
patients with CAP. These decisions are not always represented by a clear- Confusion Lactic acidosis
cut do-not-resuscitate order. Institutions also vary in the availability of Uremia (BUN >20 mg/dL) pH <7.30-7.35
ICU beds and the willingness to admit patients with limitations of care Tachypnea (RR >30/min) Low albumin
to the ICU. One solution is to use the need for intravenous vasopressors
and mechanical ventilation as the end point. 66 Bilateral radiographic infiltrates Hyponatremia (<130 mEq/L)
Hypoxemia (P/F <250) Leukocytosis >20,000/mm 3
Scoring Systems: A variety of clinical scoring systems have been devel-
oped that reliably predict 30-day mortality risk for patients with CAP, Thrombocytopenia a Hypoglycemia a
including the pneumonia severity index, CURB-65 and CRB-65, and Hypotension requiring aggressive fluid resuscitation
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the ATS criteria. None of these mortality-based scores were adequate Hypothermia a
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to define the need for ICU care. Therefore, the most recent IDSA/ a
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ATS guideline committee proposed a set of minor criteria to define Leukopenia
patients at risk for the need for ICU care. These IDSA/ATS guideline BUN, blood urea nitrogen; P/F, PaO 2 /FiO 2 ; RR, respiratory rate.
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minor criteria have demonstrated good predictive value in retrospective a Not validated in any multivariate analysis.
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