Sepsis2020

Sepsis
Dr. Radhwan Hazem Alkhashab
Consultant anaesthesia & ICU
2020

Introduction
• Severe infection is not only a common cause of admission to
intensive care, but also the most common complication
suffered by critically ill patients.
• Nosocomial, or hospital-acquired infections result in
significant morbidity and mortality. Nosocomial infections
have been reported to affect approximately 2 million
hospitalized patients in the United States annually,

Definition of infection
The invasion and multiplication of microorganisms such as
bacteria, viruses, and parasites that are not normally present
within the body. An infection may cause no symptoms and
be subclinical, or it may cause symptoms and be clinically
apparent. An infection may remain localized, or it may
spread through the blood or lymphatic vessels to become
systemic. Microorganisms that live naturally in the body are
not considered infections. For example, bacteria that
normally live within the mouth and intestine are not
infections.

Definition of inflammation
• The inflammatory response is an extremely complicated
process that is triggered by a physical, chemical, or
infectious insult to the host. The presumed role of the
inflammatory response is to protect the host from the
damaging effects of the insult

Old Clinical definitions
The relationships between infection, inflammation is as following points :
1) The condition characterized by signs of systemic inflammation (e.g., fever
and leukocytosis) is called the systemic inflammatory response syndrome
(SIRS).
2) When SIRS is the result of an infection, the condition is called sepsis.
3) Severe sepsis exists when these features are associated with organ
dysfunction.
4) The term multiple organ dysfunction syndrome (MODS) has been
suggested to describe dysfunction of two or more organs associated with
sepsis.
5) Septic shock is defined as acute circulatory failure in a patient with sepsis
or, more specifically, systolic blood pressure less than 90 mm Hg.

New sepsis definition
• Sepsis is defined as life-threatening organ dysfunction
caused by a dysregulated host response to infection.
• Organ dysfunction can be identified as an acute change in
total SOFA score_2 points consequent to the infection.
• The baseline SOFA score can be assumed to be zero in
patients not known to have preexisting organ dysfunction.

SOFA
Sequential Organ Failure Assessment
• This is a scoring system which was devised in 1994 to describe the
degree of organ dysfunction in sepsis.
The system scores the function of six different organ systems:
- Respiratory system.
- Cardiovascular system.
- Central nervous system.
- Coagulation
- Hepatic
- Renal
Each system is scored (1-4) according to the level of physiological
derangement.
Minimum SOFA score: 0
Maximum SOFA score 24

1. Respiratory system
e.g. PaO2 =100, FIO2 =0.21% , so the ratio is 476

Quick SOFA score
The Quick SOFA Score ( qSOFA) was introduced in February 2016 as a
simplified version of the SOFA Score as an initial way to identify patients at
high risk for poor outcome with an infection.
The score ranges from 1 to 3 points. The presence of 2 or more qSOFA
points near the onset of infection was associated with a greater risk of death
or prolonged intensive care unit stay.

Diagnostic Criteria for the Systemic Inflammatory Response
Syndrome (SIRS)
The diagnosis of SIRS requires at least 2 of the following:
1. Temperature >38°C or <36°C
2. Heart rate >90 beats/minute
3. Respiratory rate >20 breaths/minute Or Arterial PaCO <32
mm Hg
4. WBC count >12,000/mm3 or <4000/mm3

Diagnostic criteria for sepsis
Infection, documented or suspected, and some of the following:
A. General variables:
1) Fever (core temperature >38.3°C)
2) Hypothermia (core temperature <36°C)
3) Heart rate >90/min.
4) Tachypnea
5) Altered mental status
6) Significant edema.
7) Hyperglycemia (plasma glucose >120 mg/dL in the absence of diabetes).

Diagnostic criteria for sepsis cont.
B. Inflammatory variables
-Leukocytosis (WBC count >12,000/µL)
-Leukopenia (WBC count <4000/µL)
-Normal WBC count with >10% immature forms
C. Hemodynamic variables
-Arterial hypotension (SBP <90 mm Hg, MAP <65 mmHg).

D. Organ dysfunction variables
- Arterial hypoxemia (Pao2/FIo2 < 300)
- Acute oliguria (urine output < 0.5 mL/kg/h)
- Serum Creatinine increase > 0.5 mg/dL over normal reading.
- Coagulation abnormalities (INR > 1.5 or APTT > 60 s)
- Ileus (absent bowel sounds)
- Thrombocytopenia (platelet count < 100,000/µL)
- Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or
70 mmol/L)

E. Tissue perfusion variables
-Hyperlactatemia: is a pathological state in which resting blood
lactate concentration is abnormally high (>1.5 mmol/L).
Moderate to severe hyperlactatemia (>3.0 to >5.0 mmol/L) is
associated with abnormal accumulation of hydrogen ions (H+)
and a resulting tendency to acidosis.
-Decreased capillary refilling.

PATHOPHYSIOLOGY OF SIRS
• A mild systemic inﬂammatory response to an injury,
infection, or other bodily insult may normally have
salutatory eﬀects. However, a marked or prolonged
response, such as that associated with severe infections, is
often deleterious and can result in widespread organ
dysfunction.
• Although gram-negative organisms account for most
cases of infection-related SIRS, many other infectious
agents are capable of inducing the same syndrome. These
organisms either elaborate toxins or stimulate release of
substances that trigger this response

• The central mechanism in initiating SIRS appears to be the
abnormal secretion of cytokines. These low-molecular-weight
peptides and glycoproteins function as intercellular mediators
regulating such biological processes as local and systemic
immune responses, inﬂammation, wound healing, and
hematopoiesis.
• The most important cytokines released during SIRS are
interleukin-6, adrenomedullin, soluble CD, the adhesion
molecules ELAM-1, macrophage inﬂammatory protein-1α,
extracellular phospholipase A2, and C-reactive protein.

• The resulting inﬂammatory response includes release of
potentially harmful phospholipids, attraction of neutrophils,
and activation of the complement, kinin, and coagulation
cascades.
• Attraction and activation of neutrophils releases a variety of
proteases and free radical compounds that damage vascular
endothelium. Activation of monocytes causes them to
express increased amounts of tissue factor, which in turn
can activate both the intrinsic and extrinsic coagulation
cascades

Infection in ICU
Infections are a leading cause of death in ICUs. Serious infections
may be “community acquired” or subsequent to hospital admission
for an unrelated illness.
The term nosocomial infection describes hospital acquired
infections that develop at least 48 h following admission. The
reported incidence of nosocomial infections in ICU patients has
ranged between 10% and 50%, but with recent attention to aseptic
placement of central venous catheters and earlier removal of
bladder catheters the incidence of bloodstream infections has
markedly declined.

Risk factors for nosocomial infections.
1. Advanced age (age more than 70y.)
2. Malnutrition.
3. Drug therapy (corticosteroid therapy, chemotherapy).
4. Loss of integrity of mucosal and skin barriers.
5. Underlying diseases.
6. Prolonged use of invasive devices.
7. Respiratory failure.
8. Kidney failure.
9. Head trauma.
10.Burns involving more than 40% of the body.(Topical antibiotics delay
but do not prevent wound infections. After burns, early removal of the necrotic
eschar followed by skin grafting and wound closure appears to reverse
immunological defects and reduce infections).

Sources & types of bacteria
Most nosocomial infections arise from the patient’s
endogenous bacterial flora. Furthermore, many critically
ill patients eventually become colonized with resistant
bacterial strains.
• Gram negative bacteria (30-60%)
• Gram positive bacteria (25-50%)
• Fungi (2-10%)
• Cultures positive in only 30-50% septic shock.
• E. coli, Staph, Pseudomonas, Strep, Enterococcus,
Enterobacter, Klebsiella.

Common sites affected
1) Infections of the urinary tract.It account about 35 - 40%.
2) Wound infections account about 25 - 30%.
3) Ventilator associated pneumonias are problems in the ICU
& account 20 - 25%.
4) Intravascular catheter-related infections, account 5 -10% .

1. Urinary infection
Urosepsis is a term used to describe a type of sepsis that is caused
by an infection in the urinary tract. It`s typically associated with
the indwelling catheters or urinary obstruction.
• Urosepsis is a serious complication of a urinary tract infection
that requires immediate medical care to avoid a possible life-
threatening event.

2. Respiratory infection
Nosocomial pneumonias are usually caused by gram-negative
organisms. Gastrointestinal bacterial overgrowth with
translocation into the portal circulation and retrograde
colonization of the upper airway from the gastrointestinal
tract as a result of aspiration are possible mechanisms of
entry for these bacteria. Preservation of gastric acidity
inhibits overgrowth of gram-negative organisms in the
stomach and their subsequent migration into the oropharynx.

Tracheal intubation does not provide effective protection
because patients commonly aspirate gastric fluid
containing bacteria despite a properly functioning cuff ;
nebulizers and humidifiers can also be sources of infection.
Selective decontamination of the gut with non absorbable
antibiotics may reduce the incidence of infection but does
not change outcome.
Elevating the head of the bed more than 30 degree reduces
the likelihood of ventilator-associated pneumonia.
Enteral nutrition reduces bacterial translocation across the
gut and reduces the likelihood of sepsis

3. Wound infections
Wounds are common sources of sepsis in postoperative and
trauma patients; restricting antibiotic prophylaxis to the
immediate perioperative time appears to decrease the
incidence of postoperative infections in some groups of
patients. Although more commonly seen in postoperative
patients, intraabdominal infections due to perforated ulcer,
diverticulitis, appendicitis, and acalculous cholecystitis
can also develop in critically ill patients.

4. Intravascular cannulation sites
Subclavian, jugular, and femoral central venous catheterization
are associated with infections, thrombotic, and mechanical
complications.Catheter-related bloodstream infection has a
significant effect on morbidity, mortality, and health care
costs.
Intravascular catheter-related infections are most commonly
caused by Staphylococcus epidermidis, Staphylococcus
aureus, streptococci, Candida species, and gram-negative
organisms.

Multiorgan Dysfunction and
Failure
The organs most often injured by sepsis and inflammation
are the lungs, kidneys, cardiovascular system, and central
nervous system. The most common of these syndromes is
the acute respiratory distress syndrome (ARDS), which is
associated with 40% of cases of severe sepsis

Septic shock
An infectious process that induces a severe or protracted
SIRS can result in septic shock.
Sepsis associated with hypotension (systolic blood pressure
<90 mm Hg, mean arterial pressure <60 mm Hg) despite
adequate fluid resuscitation. Septic shock is usually
characterized by inadequate tissue perfusion and
widespread cellular dysfunction.

Causes of hypotension
Hypotension is due to:
1. Decreased circulating intravascular volume resulting
from a diffuse capillary leak.
2. Myocardial depression.
3. Systemic venodilation.

Hemodynamic Subsets
The circulation in patients with septic shock is often described as
either hyperdynamic or hypodynamic.
Hyperdynamic septic shock;
is characterized by normal or elevated cardiac output and
profoundly reduced systemic vascular resistance. Mixed
venous oxygen saturation is characteristically increased in the
absence of hypoxemia and likely reflects the increased cardiac
output and the cellular metabolic defect in oxygen utilization.

Hypodynamic shock :
Often occurs early in the course of septic shock. It is more likely
to be seen in severely hypovolemic patients and in those with
underlying cardiac disease. Myocardial depression is
prominent. Mixed venous oxygen saturation is reduced in
these patients. pulmonary hypertension is often prominent.
Elevation of pulmonary vascular resistance, the increase in
pulmonary vascular resistance may contribute to right
ventricular dysfunction.

Clinical Manifestations
Septic shock classically presents with an abrupt onset of
chills, fever, nausea (and often vomiting), decreased
mental status, tachypnea, hypotension, and tachycardia.
The patient may appear flushed and feel warm
(hyperdynamic) or pale with cool and often cyanotic
extremities (hypodynamic).

Clinical manifestation cont.
Leukocytosis with a left ward shift to premature cell forms is
typical, but leukopenia can be seen with overwhelming sepsis
and is an ominous sign. Progressive metabolic acidosis (usually
lactic acidosis) is typically partially compensated by a
concomitant respiratory alkalosis. Elevated lactate levels reflect
both increased production resulting from poor tissue perfusion
and decreased uptake by the liver and kidneys. Oliguria due to
the combination of hypovolemia, hypotension, and a systemic
inflammatory insult will often progress to kidney failure.
Elevations in serum aminotransferases and bilirubin are due to
hepatic dysfunction

Insulin resistance is uniformly present and produces
hyperglycemia. Thrombocytopenia is common and is often
an early sign of sepsis. Laboratory evidence of disseminated
intravascular coagulation (DIC) is often present but is rarely
associated with a bleeding diathesis, Stress ulceration of
gastric mucosa is common. Respiratory and kidney failure
are the leading causes of death in septic patients.

Monitoring in ICU
1. Non invasive monitoring: this include basic
monitoring :
-Pulse rate :increased , low volume.
-Blood pressure, low BP due to following causes:
Myocardial depression, Vasodilatation, Leaky capillaries,
Decreased circulating volume
-Respiratory rate: metabolic acidosis leading to
hyperventilation (increase in rate & depth).

- pulse pressure : usually narrow before decrease in
the BP, due to slight increase in diastolic pressure due
to vasospasm & due to decrease in systolic pressure
due to decrease in cardiac out put.
-temperature. Patient may appear
• Flushed and feel warm (hyperdynamic)
• Pale with cold and often cyanotic extremities
(hypodynamic)

• SPO2.: low especially when diffusion capacity defect is
occur.
• ETCO2: this measure the concentration of CO2 in exhaled
gases which reflect the intra-alveolar concentration of CO2 at
end of expiration, it's 4-5mmHg less than PaCO2 .
• UOP : patient should be catheterized to measure urine output
every 30-60 minutes, urine output should be at least 25-
30ml/h , or 0.5-1 ml/kg/h.

2. Invasive monitoring :
- Central venous pressure : by putting a catheter in a
major veins by seldenger technique & this connected
to water manometer or transducer.
In septic shock ,there will be a decrease in circulating
volume leading to decrease in CVP .
- Pulmonary arterial pressure.
- PAWP.

- Direct blood pressure .
- Arterial blood gas analysis : essential because in septic
shock there is a big changes in gas tension ( low PaO2,
high PaCO2) , with decrease in pH of the blood due to
metabolic changes & then due to respiratory causes when
ARDS occur.

Management of Severe Sepsis
and Septic Shock

Initial Resuscitation
The following goals have been established for the first 6
hours of management for patients with severe sepsis and
septic shock :
1. Central venous pressure 8–12 mm Hg.
2. Mean arterial pressure =65 mm Hg.
3. Urine output =0.5 mL/kg per hour.
4. SvO2 or ScvO2 =70%.
where SvO2 and ScvO2 are the oxyhemoglobin saturation
in central venous (superior vena cava) blood and mixed
venous (pulmonary artery) blood. In ventilator-dependent
patients, a higher target central venous pressure of 12–15
mm Hg is recommended.

Treatment
(1) Control and eradication of the infection by appropriate
and timely intravenous antibiotics, drainage of abscesses,
debridement of necrotic tissues, and removal of infected
foreign bodies.
(2) Maintenance of adequate perfusion with intravenous
fluids and inotropic and vasopressor agents.
(3) Target organ treatment of complications such as ARDS,
kidney failure, gastrointestinal bleeding, and DIC.
(4) Adjunctive therapy.

1. Choice of antibioics
Antibiotic treatment usually is initiated before pathogens are
identified but only after adequate cultures are obtained ( blood,
urine, wounds, and sputum).
The combination of a penicillin/β-lactamase inhibitor or third-
generation cephalosporin with an aminoglycoside is used.
Vancomycin is added if intravascular catheter-related infection
is suspected. Clindamycin or metronidazole may be given to
neutropenic patients if a rectal abscess is suspected. Antiviral
therapy should be considered in septic patients who are more
than 1 month post–bone marrow or solid organ transplantation.

Empiric Antimicrobial Therapy
Intravenous antibiotics are recommended starting within
one hour of recognition of severe sepsis or septic shock.
Before starting antibiotics, at least 2 sets of blood cultures
should be obtained. Remember that the yield from blood
cultures is directly dependent on the volume of blood
cultured. For an optimal yield from blood cultures, a
volume of 20 to 30 mL of blood should be withdrawn
from each venipuncture site.

2. Circulatory supportive therapy
Tissue oxygenation and perfusion are supported with
oxygen, intravenous fluids, inotropes, and vasopressors.
Central venous pressure is maintained at greater than 8
mm Hg and central venous oxygen saturation is
maintained at greater than 70%. Packed red blood cell
transfusions are given to keep hemoglobin levels greater
than 8 g/dL, especially when central venous pressure and
central venous oxygen saturation are below targets.

Fill the tank Central venous pressure
Insert central venous catheter (Internal Jugular or
Subclavian vein).
Measure central venous pressure:
Goal CVP = 8-12 mmHg
- If < 8 mmHg, 500ml NS Q 30 minutes until 8
- If 8-12 mmHg, NS ( 100ml/hour)
- If > 12 mmHg, hold IV fluids
(Intubated patients may need CVP of 15 mmHg)

Vasopressor therapy is generally initiated if hypotension (mean
arterial pressure <65 mm Hg) or elevated blood lactate levels
persist following administration of intravenous fluids.
Suggested choices are norepinephrine or dopamine; other
positive inotropic drugs (eg, dobutamine) are indicated only
when the SVO2 falls below 70% despite fluids and vasopressor
therapy. Patients with persisting elevations of lactate or
persisting low central venous oxygen saturations , can be
treated by (200–300 mg/d of hydrocortisone).

Dopamine: Usual dose range 5–20 mg/kg/min.
Norepinephrine: Effective dose range in sepsis is 0.2–1.3
mg/kg/min (about 1 to 10 mg/min for a 70 kg patient)

Blood glucose should be controlled with a target value of
less than 180 mg/dL. In patients with hypotension that is
refractory to norepinephrine plus dopamine or
dobutamine, vasopressin may be administered to improve
blood pressure. Severe acidosis may decrease the efficacy
of inotropes and should therefore generally be corrected
(pH > 7.20) with bicarbonate.

Ventilatory support
• The goals of mechanical ventilation include improvement
in gas exchange, reduction in work of breathing, avoiding
oxygen toxicity, minimizing high airway pressures,
avoiding further lung damage, and allowing the injured
lung to heal

A lung protective and pressure-limited ventilatory strategy has
been shown to improve survival rates and lower rates of
barotrauma. Current recommendations are to use a tidal volume of
5-8 mL/kg, a longer inspiratory time, and not to exceed a
transpulmonary pressure of 30 cm H2O. Permissive hypercapnia
may ensue but is tolerated, which may occur with the use of lesser
tidal volumes. The use of PEEP may reduce or prevent ventilator-
induced lung injury. The use of prone positioning and nitric oxide
may prove to be beneficial in the short term; these interventions
have not been shown to improve survival rates

• Patients with sepsis initially are observed on the wards or
in the emergency department. After initial attempts at
stabilization, transfer the patient to the ICU for invasive
monitoring and support
• Ventilatory support and invasive catheters further worsen
the risk of infection. Avoiding the use of catheters or
removing them as soon as possible may prevent severe
sepsis.

4. Adjunctive therapy
• Steroids (Hydrocortisone )
• If hypotension poorly responsive to fluid and
vasopressors
• If adrenally insufficient
• Do NOT use corticotropin stimulation test
• Immunoglobuline therapy

Complication of sepsis
1. Acute lung injury leading to ARDS is a major
complication of patients with severe sepsis and septic
shock. Incidence of ARDS is approximately 18% in patients
with septic shock.
2. Acute renal failure occurs in 40-50% of patients with
septic shock. Acute renal failure complicates therapy and
worsens the overall outcome.
3. DIC occurs in 40% of patients with septic shock.
4. Death occurs in 40-50% of patients with septic shock.

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