This document discusses procalcitonin (PCT) as a biomarker for sepsis diagnosis and management. It notes that PCT levels rise rapidly and specifically in response to bacterial infection but not viral infection. PCT can help differentiate bacterial infection from other causes of inflammation. The document also describes how PCT levels correlate with infection severity and can guide antibiotic treatment duration. It presents a case study of how PCT guided management of a patient admitted with shortness of breath potentially due to sepsis.

1. by Dr : MOHAMMAD NOUR AL SAEED

2.  Manifested by two or more of the following:
 Temperature >38°C or <362C
 Heart rate >90 beats/min
 Respiratory rate >20 breaths/min or PaCO2
<32 mm Hg
 WBC >12,000/mm3, <4000/mm3, or >10%
immature (band) forms

3.  Sepsis
Systemic response to infection confirmed
or suspected infection plus >2 SIRS criteria
 Severe Sepsis
Sepsis associated with organ dysfunction,
hypoperfusion, or hypotension
 Septic Shock
Severe Sepsis that cannot be resuscitated
or stabilized with IV fluids alone

5.  Differentiation between sepsis and non-
infectious causes of SIRS is complicated
 The large number of patients presenting to
the ER at the same time can limit the ability
to obtain medical/illness histories and
physical examinations

6.  Scoring systems and commonly available
diagnostic tools provide limited value in
determining which patients will have a poor
outcome
 Initial vital signs can be incomplete, an
accurate core temperature can be lacking
 These limitations often result in the delayed
diagnosis of sepsis which in turn delays
treatment, increases hospital length-of-stay,
increases costs and leads to increased
preventable mortality

7. Integrated use of PCT with other clinical and
laboratory information permits:
 Increased accuracy of clinical diagnosis of
relevant bacterial infection / sepsis
Improved clinical decision making and
patient management

8.  Simple blood test specific for bacterial
infection
 During severe bacterial infections and
sepsis, blood levels rise rapidly (( no
elevation from viral infections ))
 Is the Standard of Care for much of Europe
in the management of infection and sepsis

9.  Alternative synthesis of PCT
1. Bacterial toxins (gram+/-) and cytokines stimulate
production of PCT in all parenchymal tissues
2. PCT is immediately released into bloodstream
3. This process can be blocked during viral
infections
 Interferon gamma released in viral infection, blocks the activation of
PCT production, therefore in viral infection PCT levels remain
normally low .

11.  In critically ill patients, PCT levels elevate in correlation to the
severity of bacterial infection
 In healthy people, PCT concentration are found below 0.05ng/ml
 Concentrations exceeding 0.5ng/ml can be interpreted as
abnormal

12.  PCT levels accurately differentiate sepsis from
noninfectious inflammation
 PCT has been demonstrated to be the best marker
for differentiating patients with sepsis from those
with systemic inflammatory reaction not related to
infectious cause

13.  When PCT is used as a reference, the sensitivity and specificity of
sepsis diagnosis can be significantly increased compared with
conventional clinical parameters.

14.  PCT can aid in the diagnosis and severity in patients suspected of
sepsis, severe sepsis, and septic shock.
 In multiple studies, PCT has demonstrated a high sensitivity and
specificity for the differentiation of sepsis from SIRS (Systemic
Inflammatory Response Syndrome)
 PCT levels can be useful for the management of patients after surgery
or transplant and in peritonitis .

15. 1. Newborn < 48hr - increased PCT values (physiological peak)
On 3" day after birth, normal adult reference ranges apply
2. Primary inflammation syndrome following trauma: multiple
trauma, extensive burns, major surgery (cardiac, transplant,
abdominal) Rapid decrease (half-life 24hr) in the absence of
bacterial infection
3. Medullary C-cell cancers of the thyroid, pulmonary small-cell
carcinoma and bronchial carcinoma
4. Prolonged circulatory failure (e.g.. cardiogenic shock,
hemorrhagic shock, thermal shock)
5. Treatments that can cause a cytokine storm e.g. OKT3, anti-
lymphocyte globulins, etc.

16.  Low PCT levels in the presence of bacterial
infection may occur:
Early course of infection: Re-measure in 6-
12hrs
Subacute Endocarditis
Localized infections

17. Elevated / rising PCT levels
 Systemic response to the infection - indicates
that infection is developing or is outside the
control of the immune system
 Risk for further progression
Low PCT levels despite clinical signs and symptoms
 Self-limiting bacterial infection
 Non-infectious cause
 Early phase of infection

19.  Microbiological diagnosis in the patients with
bacteremia is important for effective
antimicrobial therapy. Although blood culture
is known as the gold standard for the
diagnosis of bacteremia, PCT is able to
differentiate bacteremia from both non-
bacteremia and contamination.
 Thus, Necessary treatment can be rapidly
started in case contamination or non-
bacteremia is differentiated from bacteremia,
unnecessary antibiotic use can be prevented
in case of contamination, and resistance can
be prevented by decreasing selective pressure
on microorganisms.>>

20.  Increasing in PCT level in bacterial
infections occurs faster than CRP. Whilst
CRP is increased also in viral infections,
PCT is increased in only bacterial
infections.
 Chronic non-bacterial infections,
autoimmune diseases and other systemic
diseases, and non-infectious and neoplastic
diseases do not induce PCT

21.  Current guidelines recommend blood
culture sampling from hospitalized patients
with suspected CAP.
 PCT levels accurately predicted blood
culture positivity in patients with CAP.
 PCT measurement demonstrated the
potential to reduce the number of blood
cultures drawn in the ED to better
implement resources
 The use of PCT in targeting rational blood
culture utilization allows for more directing
allocation of limited health-care resources.

22. • Low PCT levels identify patients presenting in the ED with
Pneumonia that have a low risk for mortality

23.  Decreasing PCT levels in patients with sepsis indicate effective
treatment of the underlying infection
 Persistently elevated PCT levels indicate a possible treatment failure.
 When integrated into the management of septic patients, PCT can help
clinicians to manage septic patients more efficiently

24.  Effect of PCT-guided management in
patients with sepsis on ICU length of stay

25.  Tailoring of AB treatment using PCT to the
individual patient needs safely led to a reduction of
average treatment duration from 12 to 5 days with
same outcome

26.  PCT guidance gives better outcome in
making decision diagnosing sepsis and
starting the treatment ASAP, and in the
decision of duration, effectiveness or failure
of the treatment .
 In countries with higher antibiotic
prescription rates, PCT guidance may have
clinical and public health implications .

27.  E.P 72 years old male w/ valvular heart disease, sick
sinus syndrome status post pacemaker came to
ED w/ acute SOB on July 8 middle of night shift. Not
known to our system, no old records or previous
imaging available.
 PLAN : O2, bronchodilators, empiric broad spectrum
antibiotics after blood cultures, labs including PCT
 Management : Admitted to intermediate care unit for
high flow O2, antibiotics, monitoring, bronchodilators,
trial of diuretics.
 Note increasing prevalence of elderly patients with pacemakers or on beta-blocker
reduces clinical vital sign effectiveness in diagnosis SIRS and Sepsis since heart rate
may be artificially blunted
CASE STUDY FROM THE EMERGENCY DEPARTMENT

28.  PCT was 3.45 from ED draw, patient was
admitted ICU, immediately Vascular access
was established and blood sent to lab for
Blood culture, full blood count (FBC), U&E,
coagulation profile, venous blood gas (VBG)
and started on :
 High flow O2
 Antibiotic
 IV fluid 0.9% saline 20ml/kg
 And active monitoring

29.  Guidance of therapy
* Decision on antibiotic initiation
* Guidance of duration of therapy
 Risk stratification of patients
* Admission to hospital
* Admission to ICU
* Escalation of therapy
 Guidance of diagnosis
* More appropriate selection of who might need invasive
diagnostic tests
* Rational utilization of advance imaging modalities
 Improved direction in choice of microbiology and
virology studies

31. by Dr : MOHAMMAD NOUR AL SAEED