• Sepsis is a life-threatening organ dysfunction

that results from the body’s response to

infection. It requires prompt recognition,
appropriate antibiotics, careful hemodynamic
support, and control of the source of infection.
• With the trend in management moving away
from protocolized care in favor of appropriate
usual care, an understanding of sepsis
physiology and best practice guidelines is
critical
• Tools such as the Systemic Inflammatory
Response Syndrome criteria and the quick
version of the Sequential Organ Failure
Assessment can help with early diagnosis and
triage.
• The initial antibiotic should be broad-
spectrum, based on local sensitivity patterns,
with daily assessment of appropriate
antibiotic de-escalation and cessation
• Resuscitation with initial fluid boluses should
be followed by weighing benefits and risks of
additional fluid administration based on
dynamically assessed volume status, and then
aggressive fluid removal during recovery.
• During resuscitation, a goal mean arterial
pressure of 65 mm Hg is preferred, using
norepinephrine (with vasopressin if needed)
to achieve it.
• Sepsis and particularly septic shock should be
recognized as medical emergencies in which time
matters, as in stroke and acute myocardial infarction.
• Early recognition and rapid institution of
resuscitative measures are critical.
• But recognizing sepsis can be a challenge, and best
management practices continue to evolve.
• This article reviews guidance on the diagnosis and
management of sepsis and septic shock, with
attention to maximizing adherence to best practice
statements, and controversies in definitions,
diagnostic criteria, and management.
• In 1991, sepsis was first defined as a systemic
inflammatory response syndrome (SIRS) due to a
suspected or confirmed infection with 2 or more
of the following criteria:
• Temperature below 36°C or above 38°C
• Heart rate greater than 90/minute
• Respiratory rate above 20/minute, or arterial
partial pressure of carbon dioxide less than 32
mm Hg
• White blood cell count less than 4 × 109/L or
greater than 12 × 109/L, or more than 10% bands.
• Severe sepsis was defined as the progression
of sepsis to organ dysfunction, tissue
hypoperfusion, or hypotension.
• Septic shock was described as hypotension
and organ dysfunction that persisted despite
volume resuscitation, necessitating vasoactive
medication, and with 2 or more of the SIRS
criteria listed above.
 In 2016, the Sepsis-3 committee issued the
following new definitions:
• Sepsis—A life-threatening condition caused by a
dysregulated host response to infection, resulting
in organ dysfunction
• Septic shock—Circulatory, cellular, and metabolic
abnormalities in septic patients, presenting as
fluid-refractory hypotension requiring
vasopressor therapy with associated tissue
hypoperfusion (lactate > 2 mmol/L).
• The classifi cation of severe sepsis was eliminated
 TOOLS FOR IDENTIFYING HIGH RISK:
SOFA AND qSOFA
• SOFA is an objective scoring system to determine major
organ dysfunction, based on oxygen levels (partial pressure
of oxygen and fraction of inspired oxygen), platelet count,
Glasgow Coma Scale score, bilirubin level, creatinine level (or
urine output), and mean arterial pressure (or whether
vasoactive agents are required).
• It is routinely used in clinical and research practice to track
individual and aggregate organ failure in critically ill patients.
• But the information needed is burdensome to collect and
not usually available at the bedside to help with clinical
decision-making.
• qSOFA is simpler…
• Singer et al8 compared SOFA and SIRS and identified 3
independent predictors of organ dysfunction associated
with poor outcomes in sepsis to create the simplified
qSOFA:
• Respiratory rate at least 22 breaths/minute
• Systolic blood pressure 100 mm Hg or lower
• Altered mental status (Glasgow Coma Scale score < 15).
• A qSOFA score of 2 or more with a suspected or confirmed
infection was proposed as a trigger for aggressive
treatment, including frequent monitoring and ICU
admission.
• qSOFA has the advantage of its elements being easy to
obtain in clinical practice
• Although qSOFA identifies severe organ
dysfunction and predicts risk of death in
sepsis, it needs careful interpretation for defi
ning sepsis.
• One problem is that it relies on the clinician’s
ability to identify infection as the cause of
organ dysfunction, which may not be apparent
early on, making it less sensitive than SIRS for
diagnosing early sepsis.
• Also, preexisting chronic diseases may infl
uence accurate qSOFA and SOFA
measurement.
• In addition, qSOFA has only been validated
outside the ICU, with limited utility in patients
already admitted to an ICU.
• Studies have suggested that the SIRS criteria
be used to detect sepsis, while qSOFA should
be used only as a triaging tool
ANTIMICROBIAL THERAPY
• Delay in giving appropriate antibiotics is
associated with a significant increase in
mortality rate.
• Appropriate antimicrobials should be initiated
within the first hour of recognizing sepsis,
after obtaining relevant samples for culture—
provided that doing so does not significantly
delay antibiotic administration.
• The initial antimicrobial drugs should be broad-
spectrum, covering all likely pathogens.
• Multidrug regimens are favored to ensure sufficient
coverage, especially in septic shock.
• The empiric choice of antimicrobials should consider
the site of infection, previous antibiotic use, local
pathogen susceptibility patterns, immunosuppression,
and risk factors for resistant organisms.
• Double coverage for gram-negative organisms and for
methicillin-resistant Staphylococcus aureus (MRSA)
should be considered for patients with a high
likelihood of infection with such pathogens.
• Appropriate dosing is also important, as
efficacy depends on peak blood level of the
drug and on how long the blood level remains
above the minimum inhibitory concentration
for the pathogen.
• An initial higher loading dose may be the best
strategy to achieve the therapeutic blood
level, with further dosing based on
consultation with an infectious disease
physician or pharmacist, as well as therapeutic
drug monitoring if needed
 Consider antifungals
• The last few decades have seen a 200% rise in
the incidence of sepsis due to fungal
organisms.
• Antifungals should be considered for patients
at risk, such as those who have had total
parenteral nutrition, recent broad-spectrum
antibiotic exposure, perforated abdominal
viscus, or immunocompromised status, or
when clinical suspicion of fungal infection is
high.
 De-escalation and early cessation
• Antibiotics are not harmless: prolonged use of broad-
spectrum antibiotics is associated with antimicrobial
resistance, Clostridium difficile infection, and even death.
• A robust de-escalation strategy is needed to balance an
initial broad-spectrum approach.
• A pragmatic strategy may involve startingwith broad-
spectrum antimicrobials, particularly in the setting of
hypotension, and then rapidly de-escalating to an
antimicrobial with the narrowest spectrum based on local
sensitivity patterns.
• If the clinical course suggests the illness is not actually due
to infection, the antibiotics should be stopped immediately.
• Antibiotic de-escalation should be discussed
daily and should be an essential component of
daily rounds.17 A 7- to 10-day course or even
shorter may be appropriate for most
infections, although a longer course may be
needed if source control cannot be achieved,
in immunocompromised hosts, and in S
aureus bacteremia, endocarditis, or fungal
infections.
• FLUID RESUSCITATION
• Sepsis is associated with vasodilation, capillary leak,
and decreased effective circulating blood volume,
reducing venous return.
• These hemodynamic effects lead to impaired tissue
perfusion and organ dysfunction.
• The goals of resuscitation in sepsis and septic shock
are to restore intravascular volume, increase oxygen
delivery to tissues, and reverse organ dysfunction.
• A crystalloid bolus of 30 mL/kg is recommended
within 3 hours of detecting severe sepsis or septic
shock
• Some have cautioned against giving too much
fluid, especially in patients who have limited
cardiorespiratory reserve.
• Overzealous fluid administration can result in
pulmonary edema, hypoxemic respiratory
failure, organ edema, intra-abdominal
hypertension, prolonged ICU stay and time on
mechanical ventilation, and even increased
risk of death
• With this in mind, fluid resuscitation should be
managed as follows during consecutive phases
• Rescue: During the initial minutes to hours, fluid boluses
(a 1- to 2-L fluid bolus of crystalloid solution) are
required to reverse hypoperfusion and shock
• Optimization: During the second phase, the benefits of
giving additional fluid to improve cardiac output and
tissue perfusion should be weighed against potential
harms
• Stabilization: During the third phase, usually 24 to 48
hours after the onset of septic shock, an attempt should
be made to achieve a net-neutral or a slightly negative
fluid balance
• De-escalation: The fourth phase, marked by shock
resolution and organ recovery, should trigger aggressive
fluid removal strategies