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Sepsis: Recognition, diagnosis

and early management

Presentation by:
Dr Muhammad Burhan Pasha
 Bacteremia

 Septicemia

 The systemic response to infection

 SIRS + infection
Systemic inflammatory
response syndrome (SIRS)

Two or more of:

 Temperature >38 *C or <36*C.
 Heart rate >90bpm.
 Respiratory rate >20 breaths/min or PaCO2
<32mmHg (4.3kPa).
 WBC >12,000cells/mm3, <4000/mm3, or >10%
immature forms
Severe sepsis

 Sepsis associated with organ dysfunction or

Septic shock

Sepsis with hypotension, despite adequate fluid

resuscitation, plus presence of perfusion
abnormalities or hyper-lactatemia; shock not
explained by other causes
Incidence (US)

• 3/1,000 population
• Increasing incidence; 750,000 new cases
annually in the United States
• 2% of hospitalized patients; - 75% of ICU
 Imbalance bet pro inflammatory response and
anti-inflammatory response

 Tissue hypo perfusion/ hypoxia

 Loss of membrane barrier function/ inc

 Widespread endothelial dysfunction leads to
maldistribution of blood flow, causing impaired
tissue oxygenation and resultant organ
 Dysregulated nitric oxide production and
activation of the coagulation system causes
maldistribution of organ blood flow and
coagulopathic damage.
 The abnormal inflammatory response can
progress to significant immunosuppression.
Specific etiologic Agents

- Gram-positive (most common) bacteria:

Staphylococcus sp., Streptococcus sp., Enterococcus

- Gram-negative: Escherichia coli, Klebsiella sp., Proteus

sp., Pseudomonas sp. and anaerobic bacteria

- Fungi: Candida sp. (incidence increased 207% from

1976 to 2000)
Common Sources
 Lungs (most common),
 Urinary tract,
 Abdomen (biliary tree, intestine, peritonitis),
 Skin (cellulitis, decubitus ulcer, gangrene),
 Heart valves,
 CNS (meningitis),
 Intravascular catheters

 Unknown site of infection in 20-30% of patients

Risk factors for
 the very young and older people or people who are very frail
 people being treated for cancer with chemotherapy
 people who have impaired immune function (for example, people
with diabetes, who have had a splenectomy, or with sickle cell
 people taking long-term steroids
 people taking immunosuppressant drugs to treat non-malignant
disorders such as rheumatoid arthritis
 people who have had surgery or other invasive procedures in the
past 6 weeks
 people with any breach of skin integrity (for example, cuts, burns,
blisters or skin infections)
 people who misuse drugs intravenously
 People with indwelling lines or catheters.
women who are pregnant, have given birth or had a termination of
pregnancy or miscarriage in the past 6weeks are in a high risk group
for sepsis. In particular, women who:

 have impaired immune systems because of illness or drugs

 have gestational diabetes or diabetes or other co morbidities
 needed invasive procedures (for example, caesarean section,
forceps delivery, removal of retained products of conception)
 had prolonged rupture of membranes
 have or have been in close contact with people with group A
streptococcal infection, for example, scarlet fever
 have continued vaginal bleeding or an offensive vaginal discharge.

 Past medical, surgical, social, occupational, and

travel history to identify risk and potential source
• General symptoms
- Fever, chills, rigors, myalgias
- Mental status changes: restlessness, agitation,
confusion, delirium, lethargy, stupor, coma

• End-organ failure symptoms: shortness of breath,

oliguria/anuria, mottled skin
• Specific symptoms (related to primary source)
- Respiratory: cough, sputum production, dyspnea,
chest pain
- Urinary: dysuria, frequency, urgency, flank pain
- Intra-abdominal: nausea, vomiting, diarrhea,
constipation, abdominal pain
- CNS: stiff neck, headache, photophobia, focal
neurologic signs
Physical Examination

• Assess vital signs: hyper/hypothermia, tachycardia,

tachypnea, hypotension
• Signs of poor perfusion: delayed capillary refill,
• Signs of target organ involvement: jaundice, skin
lesions (erythema, petechiae, embolic lesions,
Diagnostic Criteria for Sepsis,
Severe Sepsis, and Septic Shock
General variables

 Fever (core temperature, >38.3°C)

 Hypothermia (core temperature, <36°C)
 Elevated heart rate (>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) in the
absence of diabetes
Inflammatory variables

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

 Leukopenia (white-cell count, <4000/mm3)
 white-cells with >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, <90 mm

Hg; mean arterial pressure, <70 mm Hg; or
decrease in systolic pressure of >40 mm Hg in
 Elevated mixed venous oxygen saturation (>70%)
 Elevated cardiac index (>3.5 liters/min/square
meter of body-surface area)

 Arterial hypoxemia (ratio of the partial pressure of arterial

oxygen to the fraction of inspired oxygen, <300)
 Acute oliguria (urine output, <0.5 ml/kg/hr or 45 ml/hr, for at
least 2 hr)
 Increase in creatinine level of >0.5 mg/dl (>44 μmol/liter)
 Coagulation abnormalities (international normalized ratio,
>1.5; or activated partial-thromboplastin time, >60 sec)
 Paralytic ileus (absence of bowel sounds)
 Thrombocytopenia (platelet count, <100,000/mm3)
 Hyperbilirubinemia (plasma total bilirubin, >4 mg/dl [68
Tissue-perfusion variables

 Hyperlactatemia (lactate >1 mmol/liter)

 Decreased capillary refill or mottling
Diagnostic tests

 Lab tests

 Blood cultures

 Radiography

 Aspiration, biopsy, drainage


 Begin initial fluid resuscitation with crystalloids

 Consider the addition of albumin when substantial amounts
of crystalloid are required to maintain adequate arterial
 ≥30 ml of crystalloids per kilogram of body weight

 Continue fluid-challenge technique as long as there is

hemodynamic improvement
 Use Norepinephrine as the first-choice vasopressor to
maintain a mean arterial pressure of ≥65 mm Hg
 Use Epinephrine when an additional agent is needed to
maintain adequate blood pressure

 Infuse Dobutamine or add it to vasopressor therapy in the

presence of myocardial dysfunction (e.g., elevated cardiac
filling pressures or low cardiac output) or on-going
hypoperfusion despite adequate intravascular volume
 Avoid the use of intravenous hydrocortisone if adequate
fluid resuscitation and vasopressor therapy restore
hemodynamic stability; if hydrocortisone is used,
administer at a dose of 200 mg/day

 Target a hemoglobin level of 7 to 9 g/dl in patients

without hypoperfusion, critical coronary artery disease/
myocardial ischemia, or acute hemorrhage
 FFPs
Infection control

 Obtain blood cultures before antibiotic therapy is

 Perform imaging studies promptly to confirm source of
 Administer broad-spectrum antibiotic therapy within 1 hr
after diagnosis of either severe sepsis or septic shock
 Reassess antibiotic therapy daily
Quickly identify source of infection and remove septic
foci (within 12hours):
 - Early surgical consultation for acute abdomen,
empyema, necrotizing fasciitis

 - Debride necrotic tissues: Drain or remove

abscesses or other foci of infection.

 - lnterventional radiology consultation for guided

Broad-spectrum antibiotic should be initiated in the first
hour after recognition of sepsis or septic shock
 - Adult (Pseudomonas not suspected): vancomycin +
Gram-negative coverage (3rd-generation cephalosporin
+beta-lactamase inhibitor, or carbapenem)
 - Adult (Pseudomonas suspected): vancomycin + two
agents aimed at resistant Gram-negative bacteria,
ceftazidime/cefepime/carbapenem/ piperacillin-
tazobactam + either fluoroquinolone (ciprofloxacin) or
aminoglycoside (gentamicin/ amikacin) depending on
local hospital sensitivities
General measures

 Use a protocol-specified approach to blood glucose

management, with the initiation of insulin after two
consecutive blood glucose levels of >180 mg/dl,
targeting a blood glucose level of <180 mg/dl

 Use the equivalent of continuous venovenous

hemofiltration or intermittent hemodialysis as needed for
renal failure or fluid overload
 Administer prophylaxis for deep-vein thrombosis
 Administer stress-ulcer prophylaxis to prevent upper
gastrointestinal bleeding
 Administer oral or enteral feedings, as tolerated, rather
than either complete fasting or provision of only
intravenous glucose, within the first 48 hr after a
diagnosis of severe sepsis or septic shock
 Address goals of care, including treatment plans and
end-of-life planning as appropriate
 Despite aggressive treatment, overall mortality
rates are still very high (10-50%) in patients with
severe sepsis/septic shock.
High risk Patients
 objective evidence of new altered mental state
 respiratory rate of 25breaths per minute or above, or new need
for 40% oxygen or more to maintain oxygen saturation more
than 92% (or more than 88% in known chronic obstructive
pulmonary disease)
 heart rate of more than 130beats per minute
 systolic blood pressure of 90mmHg or less, or systolic blood
pressure fall more than 40mmHg below baseline
 not passed urine in previous 18hours (for catheterised patients,
passed less than 0.5ml/kg/hour)
 mottled or ashen appearance
 cyanosis of the skin, lips or tongue
 non-blanching rash of the skin.