members. For this purpose, care facilities must
have protocols in place to identify patients at risk
and assess compliance with the current practice
guidelines. 3
Initial resuscitation, source control,
diagnosis, and antimicrobial treatment
The primary objective of resuscitation is to
correct hypovolaemia and restore perfusion
pressure. The key aspect is to begin resuscitation
and empiric administration of antibiotics as soon
as possible. Clinicians should make efforts to
promptly identify the site of the infection (for
example, an intravascular access catheter or
a contaminated device) in order to implement
measures to control its spread right after
a diagnosis is made. Therefore, the administration
of combinations of broad-spectrum intravenous
(IV) antibiotics of different classes (at least two
antimicrobial agents) should preferentially be
initiated within one hour after the diagnosis and
maintained until the pathogen is identified and/or
symptoms improve, with daily assessments in
order to achieve an adequate de-escalation.
Routine microbiologic cultures before initiating
antimicrobial therapy, including aerobic and
anaerobic blood cultures, are recommended
provided they do not delay treatment initiation. 3
The
multidisciplinary
medical care
team should
discuss the
goals, which
should include
palliation when
needed, with
patients and
family members
The 2016 SSC guidelines recommend dosing
antibiotics based on the pharmacokinetic and
pharmacodynamics profile of the drugs,
considering that the increased volume
distribution and renal excretion seen in some
patients may render the initial doses ineffective. 2
The National Institute for Health and Care
Excellence quality standard for sepsis, on the
other hand, provides specific information about
the agents to be used according to the patients
symptoms and age. In presence of fever and
purpuric rash, which is suggestive of
meningococcal disease, parenteral penicillin or IV
ceftriaxone should be used, whereas patients
without a confirmed diagnosis who need
empirical IV treatment can be prescribed
antimicrobials that are available through the
local formulary. For patients up to 17 years old,
ceftriaxone is recommended, but small children
under three months of age can receive ampicillin
or amoxicillin and neonates can be treated with
penicillin and gentamicin. 4
Additionally, fluid therapy is essential to
prevent pulmonary oedema and volume overload;
a crystalloid bolus (>30ml/kg) should be
administered within the first three hours of
presentation. Reassessments of the hemodynamic
status (for example, vital signs, cardiopulmonary
and skin findings as well as non-invasive or
invasive haemodynamic monitoring), with
preference for dynamic over static parameters,
might warrant further fluid therapy with
crystalloids, and subsequent intravascular volume
replacement may be implemented if needed. 3,5 It
must not be ignored though that fluids may also
result in adverse outcomes, increasing mortality,
hence judicious fluid administration is needed,
with careful evaluation of response to treatment. 2
Although blood culture remains the standard
method of diagnosis of bloodstream infections,
it takes a long time to obtain the results (12–72
hours), and the rate of false negative results is
higher than what is desirable. A more rapid
diagnosis can potentially be achieved through
molecular-based point-of-care testing and
detection of biomarkers. For example, direct
detection of DNA from the pathogen in the blood
of patients with positive blood cultures is
relatively fast, with a turnaround of 3–12 hours.
Several molecular diagnostic tests based on DNA
amplification are currently available to detect
bacterial agents, and quantitative assays can also
be used to determine bacterial load, which can
indicate the degree of sepsis severity. However,
false-positive results can result from
contamination with bacterial or fungal DNA from
the environment or present in the reagents used
for amplification. Moreover, these tests are not
very informative in regard to antimicrobial
susceptibility. 6
Biomarkers, on the other hand, can assist in
both establishing a diagnosis and in determining
the prognosis for specific patients, who may
present similar symptomatology but distinct
comorbidities and/or predisposing factors as well
as heterogeneous responses to treatment.
Whereas diagnostic biomarkers enable clinicians
to distinguish between sepsis and other serious
conditions of a non-infectious nature and to
determine the severity of sepsis, prognostic
biomarkers allows them to divide patients into
subgroups according to risk. 6 The biomarker
procalcitonin, for example, can provide
information on the duration and dosing of
antibiotics in sepsis management and is
mentioned in the 2016 guidelines as one of the
approaches to inform de-escalation. 3
Blood pressure, glucose control and
prophylaxis of venous thromboembolism
and stress ulcers
Initially, physicians should aim to correct blood
pressures to a value of 65mmHg in those patients
suffering from septic shock who require
vasopressors (mainly norepinephrine). In cases
of patients with hypertension, intra-abdominal
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