Acute sepsis in the emergency department

Acute sepsis in the
emergency

department

LO 1

LO 1

LO 1

The Case






• A 19 year-old female college student living in dormatory, presents acutely unwell to the ED

• Acute sepsis is part of the differential diagnosis

• ED has a ‘sepsis bundle’ for urgent management of acute sepsis

• How do we recognize such cases?

LO 1


The History






• Fit and well until last night then

• Non-specifically unwell, fever & chills

• This morning felt acutely unwell with fever, severe

headache, nausea, weakness, general muscle aches, abdominal pain and eye pain on exposure to light (photophobia)

• Friend thought she looked ‘dreadful’ and brought her to hospital

LO 1

On examination






• Pale, cool extremities

• Temp 39.5 O C, pulse 110/min BP 80/50 mmHg

• Respiratory rate 35/min

• Widespread purpuric (non-blanching) rash noted

• Neck stiffness is noted

• Mentally alert, Glasgow Coma Scale 15

• Immediately recognized as severe sepsis + probable meningitis

LO 2


Bacteraemia, sepsis and septicaemia


LO 2




• Bacteraemia is the presence of viable circulating bacteria in the blood (+/- clinical features)

• Septicaemia is a clinical term meaning generalized sepsis

• 1-Acute Sepsis (1st stage)is the systemic inflammatory response to infection and can be defined as:

SIRS + documented or presumed infection

LO 3

Clinical features of sepsis





Systemic inflammatory response syndrome (SIRS)



• SIRS is a systemic response to a non-specific insult – e.g. ischaemia, trauma, burn, pancreatitis, infection, etc

• Presence of two or more of the following signs and symptoms indicates SIRS :


– Temperature



<36 °C or >38 °C


– Heart rate


>90/min


– Respiratory rate


>20/min (or PaCO2 < 4.3kPa)


– WBC


> 12,000/mm 3 or < 4,000/mm 3

LO 2 & 3

Severe sepsis & septic shock


• 2-Severe sepsis (2nd stage)= sepsis (SIRS + infection) + organ hypoperfusion.

–organ hypoperfusion (decreased urine output, hypoxaemia, lactic acidosis and acute alteration in mental status).

-A hypotensive patient has a mean arterial pressure < 70 mm Hg. -Resuscitation with IV fluids increases blood pressure to normal levels.

• 3-Septic shock (3rd stage)= severe sepsis + persistently low blood pressure despite administration of intravenous fluids

• 4-Multiorgan dysfunctions (MODS) (4th stage)

-Presence of altered organ functions that cannot be normalized without intervention including major target organs such as the kidneys, lungs, and liver, and disseminated intravascular coagulation.

LO 4



Sepsis with Meningococcal meningitis
- the likely diagnosis



• Bacterial pathogen Neisseria meningitidis

• Spread by direct contact with (or droplets spread) respiratory secretions

• Most people are harmlessly colonized in nasopharynx

• In the unlucky few - rapidly progressive (and potentially fatal) disease if not recognized and treated promptly

LO 4

LO 4

ETIOLOGY of SEPSIS






Most cases of sepsis occur as the result of an infection of the urinary tract, lungs, or the peritoneum. Other sources of sepsis include skin, soft tissue, and central nervous system (CNS) infections.

Approximately 50% of cases of sepsis are due to gram-negative bacteria, and slightly less than 50% are caused by gram-positive bacteria. Less common causes of sepsis include fungi, viruses such as the human immunodeficiency virus (HIV), and protozoa.

LO 4



-Various microbial triggers cause the white blood cells to produce large amounts of proinflammatory cytokines.


Gram-negative bacteria produce endotoxin, also known as lipopolysaccharide (LPS). LPS is the most common gram-negative bacterial trigger of cytokine release.



-The peptidoglycan of S. aureus has endotoxin-like properties (i.e., it can stimulate macrophages to produce cytokines and can activate the complement and coagulation

cascades). This explains the ability of Sta. aureus to cause the clinical findings of septic shock yet not possess endotoxin.

LO 4

Lipooligosaccharide










































Cytoplasmic membrane & Cell wall of Neisseria meningitidis

LO 4

Clinical outcomes of endotoxin (LPS) activities
1• Activation of macrophage and dendritic cells ?

Massive production of proinflammatory cytokines (e.g., IL-1, TNF, IL-6, prostaglandins)

? fever.

? Increase in capillary permeability ? hypotension and shock.

?(increase production of Neutrophils and CRP, increase resistance to insulin….etc.)


2• Initiation of complement cascade ? shock
3• Initiation of blood coagulation cascades ? disseminated intravascular coagulation

LO 4

LO 4

Sepsis & Coagulation






• Activation of coagulation cascade : Cytokines initiate production of thrombin and thus promote coagulation

• Cytokines also inhibit fibrinolysis

• Activation of coagulation cascade leads to microvascular thrombosis and hence organ ischaemia, dysfunction and failure

• Microvascular injury is the major cause of

shock and multiorgan failure

LO 4

LO 5

Urgent investigations

• Full blood count.
-leukocytosis, raised neutrophiles with left shift and thrombocytopenia.
-Leukopenia may occur in certain patients (elderly).
• Renal function tests. -BUN , S. creatinine

• Electrolytes (metabolic abnormalities)

• EDTA bottle for PCR (blood & CSF)

• Blood sugar .
-Diabetics can develop hyperglycemia.
• Liver function tests.
-Serum bilirubin and alkaline phosphatase levels can become elevated,
• C-Reactive protein (CRP).
-A nonspecific marker for inflammation.
• Clotting studies (Coagulation profile)

-prolongation of PT and PTT times, decreased fibrinogen suggesting DIC.
• Arteial blood gases.

-ARDS can result in lower O 2 levels in the blood stream.

LO 5

The Sepsis Six (Sepsis bundle) to be delivered within 1 hour



LO 5





1. Deliver high flow oxygen

2. Start IV fluid resuscitation

3. Administer empirical IV antibiotics consider source

control

4. Measure serum lactate

5. Commence accurate urine output measurement

6. Take blood cultures and other cultures

LO 5

Antibiotic treatment






• An agent likely to be:

-active against the pathogens that cause meningitis -cane be used in this age group (different in neonates
and the elderly)

-that penetrates into the CSF

• Empiric choice is CEFTRIAXONE

LO 6

Life-threatening complications






• Irreversible hypotension

• Respiratory failure

• Acute kidney injury (renal failure)

• Raised intracranial pressure

• Ischaemic necrosis of digits/hands/feet

LO 6

Confirming the diagnosis










•Blood aspirate

-Blood culture

-PCR of blood

• Lumbar puncture (if safe)

-Culture of cerebrospinal fluid (CSF)

-PCR of CSF

LO 6

Examination of the CSF





• Lumbar puncture only performed after checking contraindications

• Urgent transport of CSF to laboratory

• Appearance – turbidity and colour

• Microscopy

-WBCs, RBCs

-Gram stain (detection of bacteria)

• Culture in microbiology

• Glucose and protein estimation in biochemistry

• PCR

LO 6

The meningococcus






• Neisseria meningitidis

• Gram-negative diplococcus

• Numerous (13)serogroups (e.g. A, B, C, W-135 & Y)

based on the Polysaccharide capsular antigen

– PS Capsule ?evades immune response by preventing phagocytosis

• Outer membrane antigen acts as an endotoxin as LPS.

LO6

Meningococcal meningitis






• Up to 3o% young adults may be Neisseria meningitidis carriers in nasopharynx .

•Neisseria meningitidis spread by aerosols (droplets spread) and nasopharyngeal secretions (direct contact).

• Acquisition ? clearance, carriage or invasion

• Fatality rate ~10%.

•‘Highest burden of meningococcal disease occurs in the hyperendemic region of sub-Saharan Africa known as the "Meningitis Belt" which stretches from Senegal east to Ethiopia.

LO 6
Prevention 1. vaccination


Meningococcal quadrivalent ACWY conjugate vaccine.

Vaccination is recommended for -risk groups:

1-persons with functional or surgical asplenia.

2-persons with complement deficiencies.

3-travelers to highly endemic areas (eg, sub-Saharan
Africa),

4-“closed populations” such as: a-college students living in dormitories b- the military recruits

c- religious pilgrims

5-populations experiencing a community outbreak.

6-clinical laboratory workers (microbiologists).

LO 6

Prevention 2. antibiotic prophylaxis






• Meningitis is a Notifiable disease

• Cases reported to the local Health Protection Unit of Public Health

• Close contacts can be given antibiotic prophylaxis (rifampicin, ciprofloxacin) & considered for vaccination

Summary






• Recognizing sepsis

• Urgent management & investigations

– Sepsis bundles

• Pathogenesis

• Treatment and prevention











Thank you