In either, the development of ARDS is of key importance, though ARDS is the earliest manifestation in all cases.
Dr Kaushal Deep Singh
Lecturer, Department of Surgery
Systemic inflammatory response syndrome (SIRS) → sepsis → severe sepsis
→ septic shock → multiple organ dysfunction syndrome (MODS) → death
Sepsis → septic shock → organ dysfunction/multiple organ dysfunction
syndrome (MODS) → multiple organ failure syndrome → death
■ SIRS is defined as 2 or more of the following variables
– Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)
– Heart rate of more than 90 beats per minute
– Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide
tension (PaCO 2) of less than 32 mm Hg
– Abnormal white blood cell count (>12,000/µL or < 4,000/µL or >10%
immature [band] forms)
■ New 2016 definition, also called Sepsis-3, eliminates the requirement for the
presence of systemic inflammatory response syndrome (SIRS) to define sepsis, and
it removed the severe sepsis definition. What was previously called severe sepsis is
now the new definition of sepsis.
■ Sepsis is defined as life-threatening organ dysfunction due to dysregulated host
response to infection.
■ Bacteremia is defined as the presence of viable bacteria within the liquid
component of blood.
– May be primary (without an identifiable focus of infection) or, more often,
secondary (with an intravascular or extravascular focus of infection).
– Although sepsis is associated with bacterial infection, bacteremia is not a
necessary ingredient in the activation of the inflammatory response that results
in severe sepsis.
– Septic shock is associated with culture-positive bacteremia in only 30-50% of
■ Septic Shock is defined by persisting hypotension requiring vasopressors
to maintain a mean arterial pressure of 65 mm Hg or higher; and a serum
lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume
■ Organ Dysfunction is defined as an acute change in total Sequential
Organ Failure Assessment (SOFA) score greater than 2 points secondary to
the infectious cause.
■ For screening purposes, a shorter version of the SOFA score, termed quick SOFA
(qSOFA), demonstrated to have reasonable accuracy in the settings outside the
■ qSOFA is defined by two or more of a total of the following three components:
– altered mental status,
– respiratory rate of 22 or higher, and
■ Multiple organ dysfunction syndrome (MODS) is defined as the
presence of altered organ function in a patient who is acutely ill and in
whom homeostasis cannot be maintained without intervention.
■ MODS may eventually lead to multiple organ failure syndrome (MOFS) and
■ Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are
common manifestations of MODS or MOFS.
■ However, other conditions besides sepsis can cause MODS, including
trauma, burns, and severe hemorrhagic shock.
■ Acute lung injury and acute respiratory distress syndrome : Berlin
Definition of ARDS classifies ARDS as mild, moderate, or severe :
– Mild ARDS – An oxygenation abnormality with a PaO2/FIO2 ratio of 200-300
and a positive end-expiratory pressure (PEEP) or continuous positive airway
pressure (CPAP) of 5 cm H2O or higher
– Moderate ARDS – A PaO2/FIO2 ratio of 100-200 and a PEEP of 5 cm H2O or
– Severe ARDS – A PaO2/FIO2 ratio of 100 or less and a PEEP of 5 cm H2O or
– Bilateral opacities on chest radiographs that are not fully explained by
effusions, lobar/lung collapse, or nodules
– Edema not of cardiac origin or caused by fluid overload – In the absence of
risk factors for ARDS, this requires objective assessment (eg, via
– Occurrence within 1 week of a known clinical insult or worsening respiratory
■ MODS staging : Two well-defined forms of MODS exist.
1. In the more common form of MODS, the lungs are the predominant, and often the only,
organ system affected until very late in the disease.
– Present with a primary pulmonary disorder (eg, pneumonia, aspiration, lung contusion, near-
drowning, chronic obstructive pulmonary disease [COPD] exacerbation, hemorrhage, or
pulmonary embolism [PE]).
– Pulmonary dysfunction may be accompanied by encephalopathy or mild coagulopathy and
persists for 2-3 weeks. At this time, the patient either begins to recover or progresses to
develop fulminant dysfunction in other organ systems.
– Patients who develop another major organ dysfunction often do not survive.
2. In the second, less common, form of MODS, the presentation is quite different.
– Inciting source of sepsis in organs other than the lung; the most common sources are intra-
abdominal sepsis, extensive blood loss, pancreatitis, and vascular catastrophes.
– Not only does ARDS develop early, but dysfunction also develops in other organ systems,
including the hepatic, hematologic, cardiovascular, and renal systems and central nervous
– Patients remain in a pattern of compensated dysfunction for several weeks, then either
recover or deteriorate further.
■ Before the introduction of antibiotics, gram-positive bacteria were the principal organisms that
■ Subsequently, gram-negative bacteria became the key pathogens causing severe sepsis and septic
■ Currently, however, the rates of severe sepsis and septic shock due to gram-positive organisms are
rising again because of the more frequent use of invasive procedures and lines in critically ill
■ As a result, gram-positive and gram-negative microorganisms are now about equally likely to be
causative pathogens in septic shock.
■ Respiratory tract and abdominal infections are the most frequent causes of sepsis, followed by
urinary tract and soft-tissue infections.
■ Lower respiratory tract infections cause septic shock in 35-50% of patients. The following are the
– Streptococcus pneumoniae
– Klebsiella pneumoniae
– Escherichia coli
– Legionella spp
– Haemophilus spp
– Staphylococcus aureus
■ Abdominal and GI tract infections cause septic shock in 20-40% of patients.
The following are the common pathogens:
– E coli
– Enterococcus spp
– Bacteroides fragilis
– Acinetobacter spp
– Pseudomonas spp
– Enterobacter spp
– Salmonella spp
– Klebsiella spp
■ Urinary tract infections cause septic shock in 10-30% of patients. The
following are the common pathogens:
– E coli
– Proteus spp
– Klebsiella spp
– Pseudomonas spp
■ Infections of the male and female reproductive systems cause septic shock in 1-
5% of patients. The following are the common pathogens:
– Neisseria gonorrhoeae
– Gram-negative bacteria
■ Soft-tissue infections cause septic shock in 5-10% of patients. The following are
the common pathogens:
– S aureus
– Staphylococcus epidermidis
– Clostridium spp
■ Infections due to foreign bodies cause septic shock in 1-5% of patients. S aureus,
S epidermidis, and fungi (eg, Candida species) are the common pathogens.
■ Miscellaneous infections, such as CNS infections, also cause septic shock in 1-5%
of patients. Neisseria meningitidis is a common cause of such infections.
A 72-year-old woman comes to you 52 hours following uncomplicated
laparoscopic cholecystectomy for gallstone disease. She was found
unconscious on the ward with generalized tonic-clonic seizures, requiring 20
mg diazepam. Her sodium level is 112 mmol/L. During surgery she received
3 L of 5% dextrose with 20 mmol/L potassium chloride. Her potassium and
urea and creatinine are within normal limits. There are no signs of heart
failure. Her plasma osmolality is 265 mOsm/kg and her urinary osmolality is
566 mOsm/kg. Which of the following is the most likely cause for her low
A. Excess 5% dextrose
B. Addison's disease
C. Syndrome of inappropriate antidiuretic hormone secretion
D. Nephrotic syndrome
E. Congestive cardiac failure
■ Extremes of age (< 10 years and >70 years)
■ Primary diseases (eg, liver cirrhosis, alcoholism, diabetes mellitus,
cardiopulmonary diseases, solid malignancy, and hematologic malignancy)
■ Immunosuppression (eg, from neutropenia, immunosuppressive therapy [eg, in
organ and bone marrow transplant recipients], corticosteroid therapy, injection or
IV drug use, complement deficiencies, asplenia)
■ Major surgery, trauma, burns
■ Invasive procedures (eg, placement of catheters, intravascular devices, prosthetic
devices, hemodialysis and peritoneal dialysis catheters, or endotracheal tubes)
■ Previous antibiotic treatment
■ Prolonged hospitalization
■ Underlying genetic susceptibility
■ Other factors (eg, childbirth, abortion, and malnutrition)
Signs and symptoms
■ Signs and symptoms of sepsis are often nonspecific and include the
– Fever, chills, or rigors
– Difficulty breathing
– Fatigue, malaise
– Nausea and vomiting
■ Typical symptoms of systemic inflammation may be absent in severe
sepsis, especially in elderly individuals.
■ Identify any potential source of infection.
■ Complete blood count with differential count
– WBC count higher than 15,000/µL or a neutrophil band count higher than
1500/µL has about a 50% correlation with bacterial infection.
– WBC counts higher than 50,000/µL or lower than 300/µL are associated with
significantly decreased survival rates.
– Hemoglobin concentration dictates oxygen-carrying capacity in blood, keeping
the hemoglobin concentration above 7 g/dL is usually practiced.
– Platelet count will fall with persistent sepsis, and disseminated intravascular
coagulation (DIC) may develop.
■ Coagulation studies (eg, prothrombin time [PT], activated partial
thromboplastin time [aPTT], fibrinogen levels)
– PT and the aPTT are elevated in DIC, fibrinogen levels are decreased, and
fibrin split products are increased.
■ Blood chemistry (eg, sodium, chloride, magnesium, calcium, phosphate,
– Sodium and chloride levels are abnormal in severe dehydration.
– Decreased bicarbonate can point to acute acidosis - sodium bicarbonate
therapy is not recommended to improve hemodynamics or replace
vasopressor requirements in patients with metabolic acidemia from
hypoperfusion whose pH level is 7.15 or greater.
– Hyperglycemia is associated with higher mortality.
– Serum lactate is perhaps the best serum marker for tissue perfusion. Lactate
levels > 2.5 mmol/L are associated with an increase in mortality. Lactate
levels higher than 4 mmol/L in patients with suspected infection have been
shown to yield a 5-fold increase in the risk of death and are associated with a
mortality approaching 30%.
■ Renal and hepatic function tests (eg, creatinine, blood urea nitrogen,
bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate
aminotransferase, albumin, lipase)
■ American College of Critical Care Medicine (ACCCM) does not recommend
the routine use of free cortisol measurements in critically ill patients.
■ Blood cultures (Surviving Sepsis Campaign recommends obtaining at
least 2 blood cultures before antibiotics are administered, with 1
percutaneously drawn and the other(s) obtained through each vascular
access) - blood cultures are positive in fewer than 50% of cases of sepsis.
■ Urinalysis and urine cultures - Urinary tract infection (UTI) is a common
source for sepsis, especially in elderly individuals. Adults who are febrile
without localizing symptoms or signs have a 10-15% incidence of occult
■ Gram stain and culture of secretions and tissue
■ Chest, abdominal, or extremity radiography
– Most patients who present with sepsis have pneumonia.
– Chest radiography detects infiltrates in about 5% of febrile adults without localizing
signs of infection.
– Chest radiography is useful in detecting radiographic evidence of ARDS - bilateral hazy,
symmetric homogeneous opacities, which may demonstrate air bronchograms, ground-
– Supine and upright or lateral decubitus abdominal radiographs - bowel obstruction or
– Osteomyelitis, necrotizing fasciitis, gas gasgrene
■ Abdominal ultrasonography
– acute cholecystitis or ascending cholangitis, acute pancreatitis
■ Computed tomography of the abdomen or head
– intra-abdominal abscess or a retroperitoneal source of infection, meningitis (Lumbar
■ Admission to the hospital – responders (general ward); non-responders (ICU)
■ Cardiac monitoring, noninvasive blood pressure monitoring, and pulse
■ Goal-directed therapy VS direct and aggressive individualized care [United
States (ProCESS [Protocolized Care for Early Septic Shock]), Australia (ARISE
[Australasian Resuscitation In Sepsis Evaluation]), and the United Kingdom
(ProMISe [Protocolised Management In Sepsis]).
■ Measuring lactate, targeting ScvO2 values, and insertion of a central venous
catheter were not associated with improved outcomes. What was important
was the direct and aggressive individualized care each patient received,
including early bacteriologic cultures of appropriate sites (eg, blood, urine,
sputum), early and correct institution of broad-spectrum antibiotics,
restoration of blood pressure, and reversal of evidence of end-organ
■ Management principles for septic shock include the following:
– Early recognition
– Early and adequate antibiotic therapy
– Source control
– Early hemodynamic resuscitation and continued support
– Proper ventilator management with low tidal volume in patients with acute respiratory distress
■ Treatment of patients with septic shock has the following major goals:
– Start adequate antibiotics (proper spectrum and dose) as early as possible
– Resuscitate the patient from septic shock by using supportive measures to correct hypoxia,
hypotension, and impaired tissue oxygenation (hypoperfusion)
– Identify the source of infection and treat with antimicrobial therapy, surgery, or both (source
– Maintain adequate organ system function, guided by cardiovascular monitoring, and interrupt the
■ First 6 hours of resuscitation of a critically ill patient with sepsis or septic
shock are critical. The following should be completed within 3 hours:
– Obtain the lactate level
– Obtain blood cultures before administering antibiotics
– Administer broad-spectrum antibiotics
– Administer 30 mL/kg of crystalloid solution for hypotension or for lactate
levels of 4 mmol/L or higher
■ Following should be completed within 6 hours:
– Administer vasopressors for hypotension that does not respond to initial fluid
resuscitation to maintain a mean arterial pressure (MAP) of 65 mm Hg or
– If hypotension persists despite volume resuscitation or the initial lactate level
is 4 mmol/L or higher, then measure central venous pressure (CVP) (aiming
for ≥8 mm Hg), measure central venous oxygen saturation (ScvO 2) (aiming
for ≥70%), and normalize lactate levels
Steps in Management
1. Venous access
2. Urinary catheterization
3. Respiratory support
4. Intubation and mechanical ventilation
5. Circulatory support
6. Correction of anemia and coagulopathy
7. Antimicrobial therapy
8. Temperature control
9. Metabolic and nutritional support
■ Certain conditions will not respond to standard treatment for septic shock
until the source of infection is surgically removed -
– Intra-abdominal sepsis [perforation, abscesses]
– pancreatic abscesses
– pyelonephritis or renal abscess from ureteric obstruction
– infective endocarditis
– septic arthritis
– infected prosthetic devices
– deep cutaneous or perirectal abscess
– necrotizing fasciitis
■ Urgent management is indicated for hemodynamically stable patients
without evidence of acute organ failure, delay of invasive procedures for as
long as 24 hours may be possible if the patient receives very close clinical
monitoring and appropriate antimicrobial therapy.
■ When possible, percutaneous drainage of abscesses and other well-
localized fluid collections is preferred to surgical drainage.
■ However, any deep abscess or suspected necrotizing fasciitis should
undergo drainage in the surgical suite.