Sepsis

Question 1

Definitions in sepsis

Answer 1

Sepsis: systemic inflammatory response to infection

Severe sepsis: sepsis complicated by acute organ dysfunction (often defined by provision of supportive therapy)

Septic shock: sepsis complicated by either hypotension that is refractory to fluid resuscitation or by hyperlactatemia

Question 2

Causes of severe sepsis

Answer 2

Acquisition:

community-acquired

health care - associated infections

Sources:

Pneumonia commonest cause (~50%), then intra-abdominal & urinary tract

Cultures:

Blood cultures positive in only 1/3

Cultures from all sites are negative in 1/3

Question 3

Organisms in sepsis

Answer 3

Gram-positive

• Staph aureus
• Strep pneumoniae

Gram-negative

• Escherichia coli
• Klebsiella species
• Pseudomonas aeruginosa

Question 4

Organ dysfunction in sepsis

Answer 4

Respiratory: ARDS (hypoxia+bilateral non-cardiac infiltrates)

Cardiovascular: hypotension, ↑lactate

CNS: obtundation, delirium,polyneuropathy,myopathy

Renal: ↓output, ↑creatinine

GIT: ileus, ↑ALT, altered glucose

Hormonal: adrenal dysfunction, sick euthyroid

Blood: DIC, ↓plts

Question 5

Risk factors for sepsis

Answer 5

** Patient predisposition**

 *chronic diseases*
       acquired immuno deficiency syndrome
       chronic obstructive pulmonary disease
       many cancers
  *immunosuppressive agents*

Likelihood of acute organ dysfunction

 causative organism
  patient genetic composition (e.g. encoding proteins)
  age, sex, race, ethnic group

 underlying health & organ function
  timeliness of therapeutic intervention

Question 6

Diagnostic criteria in sepsis

Answer 6

Documented or suspected infection + >1 of the following

General variables:

Fever (core temperature, >38.3°C)

Hypothermia (core temperature, 90 beats per min or >2 SD above the upper limit of the normal range for age)

Tachypnea

Altered mental status

Substantial edema or positive fluid balance (>20 ml/kg of body weight over a 24-hr period)

Hyperglycemia (plasma glucose, >120 mg/dl [6.7 mmol/liter]) in the absence of diabetes

Inflammatory variables:

Leukocytosis (white-cell count, >12,000/mm3)

Leukopenia (white-cell count, 10% immature forms)

Elevated plasma C-reactive protein (>2 SD above the upper limit of the normal range)

Elevated plasma procalcitonin (>2 SD above the upper limit of the normal range)

Hemodynamic variables:

Arterial hypotension systolic pressure 40 mm Hg in adults or to >2 SD below lower limit for age Elevated mixed venous oxygen saturation (>70%)

Elevated cardiac index (>3.5 liters/min/square meter of body-surface area)

Organ-dysfunction variables:

Arterial hypoxemia (ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen 0.5 mg/dl (>44 µmol/liter)

Coagulation abnormalities (INR, >1.5 or APTT, >60 sec)

Paralytic ileus (absence of bowel sounds)

Thrombocytopenia (platelet count, 4 mg/dl [68 µmol/liter])

Tissue-perfusion variables:

Hyperlactatemia (lactate, >1 mmol/liter)

Decreased capillary refill or mottling

Severe sepsis → plus organ dysfunction

Septic shock → plus either hypotension [refractory to intravenous fluids] or hyperlactatemia

Question 7

Altered coagulation in sepsis

Answer 7

(may → DIC)

Excess fibrin driven by:

Tissue factor

Impaired anticoagulation

• protein C system
• antithrombin
• depressed fibrinolytic system

Protease-activated receptor-1 (PAR-1)

• protective when stimulated by activated protein C or low-dose thrombin
• destructive (endothelial barrier) when activated by high-dose thrombin

Question 8

Management of sepsis

Answer 8

Initial resuscitation

intravenous fluids

vasopressors

oxygen therapy

mechanical ventilation as necessary

Initial infection control

Ongoing care

monitoring support of organ function

avoidance of complication

de-escalation of care when possible

Question 9

Describe (diagram) the host response in severe sepsis

Answer 9

Question 10

describe (diagram) organ failure in sepsis

Answer 10