Sepsis and septic shock management

Definition

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is most commonly caused by bacterial infections and less commonly by fungal or viral infections. Organ dysfunction is represented by an increase in the Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score of 2 points or more and is associated with an in-hospital mortality greater than 10%.

Septic shock is a subset of sepsis characterized by profound circulatory, cellular, and metabolic abnormalities that are associated with an in-hospital mortality greater than 40%.

Clinical presentation

Patients with sepsis may present with:

• Temperature >38°C or <36°C

• Heart rate >90 beats/minute

• Respiratory rate >20 breaths/minute or PaCO₂ <32 mmHg

• Evidence of organ dysfunction, including:

  • Hypotension

  • Jaundice

  • Oliguria

  • Altered mental status (e.g., drowsiness or lethargy)

Neonates may present atypically with:

• Poor feeding

• Respiratory distress

• Cyanosis

• Abdominal distension

Important notes

• Sepsis and septic shock are potentially fatal unless promptly investigated and treated with appropriate antimicrobial therapy and supportive care.

• Identification of the primary source of infection is essential for source control and improved treatment outcomes.

Investigations

Perform investigations as appropriate to identify organ dysfunction and the source of infection.

Recommended investigations include:

• Blood gas analysis

• Bedside ultrasound (assessment of the inferior vena cava and lungs)

• Point-of-care ECG

• Urine dipstick

• Chest X-ray (if pneumonia is suspected)

• Complete blood count

• C-reactive protein (CRP) or procalcitonin, where available

• Serum electrolytes

• Serum creatinine and urea

• Liver function tests (including liver enzymes, bilirubin, and clotting profile)

• Blood culture and antimicrobial susceptibility testing

• Culture and antimicrobial susceptibility testing of the primary source of infection (e.g., urine, pus, sputum, or CSF)

• RNA/DNA PCR for viral pathogens, where indicated

Diagnostic criteria

Sepsis

In settings with limited laboratory infrastructure, use the qSOFA score.

A diagnosis of sepsis is suggested by two or more of the following:

• Respiratory rate ≥22 breaths/minute

• Altered mentation

• Systolic blood pressure ≤100 mmHg

Blood culture demonstrating bacterial or fungal infection, together with antimicrobial susceptibility testing, is recommended to establish a definitive diagnosis.

Septic shock

Diagnosis requires:

• Fulfilment of the diagnostic criteria for sepsis.

• Requirement for vasopressor therapy to maintain a mean arterial pressure (MAP) ≥65 mmHg despite adequate fluid resuscitation.

• Serum lactate >2 mmol/L (18 mg/dL).

Non-pharmacological treatment

• Perform primary and secondary assessment and provide necessary interventions.

• Ensure airway patency.

• Administer oxygen if the patient is hypoxic or has increased work of breathing.

• Connect the patient to a cardiac monitor and monitor vital signs.

• Provide nutritional support.

• Implement source control measures directed at the primary focus of infection.

Pharmacological treatment

Initial fluid resuscitation

Administer one of the following:

0.9% sodium chloride (IV)

• Adults: 2 litres as the first bolus.

• Children: 20 mL/kg as the first bolus.

OR

Compound sodium lactate (IV)

• Adults: 2 litres.

• Children: 20 mL/kg.

Administer the first bolus over 20 minutes, followed by a second bolus of 2 litres (adults) or 20 mL/kg (children) if indicated.

Use smaller boluses in patients with congestive cardiac failure (CCF).

Inotropic and vasopressor therapy

For patients with shock not responding to fluid resuscitation or with poor cardiac output:

Dobutamine (IV)

• 2–20 micrograms/kg/minute.

For septic shock not responding after 4 litres of intravenous fluids:

Noradrenaline (IV)

• 5–20 micrograms/minute.

• Titrate to maintain a mean arterial pressure (MAP) ≥65 mmHg.

AND

Hydrocortisone (IV)

• 200 mg stat.

Blood transfusion

Transfuse blood if:

• Hemoglobin <7 g/dL.

Antimicrobial therapy

Broad-spectrum antibiotics should be started within the first hour of recognizing sepsis or septic shock.

Initial regimen

Ampicillin (IV)

• 150–200 mg/kg/day divided every 6 hours.

AND

Cloxacillin (IV)

• 50–100 mg/kg/day divided every 6 hours.

AND

Gentamicin (IV or IM)

• Adults: 120 mg every 24 hours for 5 days.

• Children: 7.5 mg/kg every 24 hours for 5 days.

If there is no improvement within 24 hours

If there is no improvement in temperature, heart rate, respiratory rate, or level of consciousness, administer one of the following regimens and refer immediately.

Option 1

Ceftriaxone (IV or IM)

• Adults: 1 g every 24 hours for 4–14 days.

• Children: 100 mg/kg every 24 hours for 4–14 days.

AND

Gentamicin (IV or IM)

• Adults: 120 mg every 24 hours for 5 days.

• Children: 7.5 mg/kg every 24 hours for 5 days.

Option 2

Ceftriaxone + sulbactam (fixed-dose combination) (IV or IM)

• 75–120 mg/kg every 24 hours for 4–14 days.

AND

Gentamicin (IV or IM)

• Adults: 120 mg every 24 hours for 5 days.

• Children: 7.5 mg/kg every 24 hours for 5 days.

Option 3

Piperacillin + tazobactam (fixed-dose combination) (IV)

• Adults: 4 g + 0.5 g every 8 hours.

• Children: Piperacillin 100 mg/kg plus tazobactam 12.5 mg/kg every 8 hours.

Duration: 7–10 days.

AND

Gentamicin (IV or IM)

• Adults: 120 mg every 24 hours for 5 days.

• Children: 7.5 mg/kg every 24 hours for 5 days.

Alternative therapy at zonal or tertiary hospitals

For patients who fail to improve despite the above treatment, and following specialist assessment, consider one of the following:

Meropenem (IV)

• Adults and adolescents: 2 g every 8 hours for 7–14 days.

• Children: 40 mg/kg every 8 hours for 7–14 days.

OR

Vancomycin (IV)

• 15–20 mg/kg every 8–12 hours.

• Maximum dose: 2 g per dose.

• Duration: 7–14 days.

Note: In renal insufficiency, adjust both the dose and dosing interval of vancomycin. Meropenem and vancomycin should generally be reserved for Gram-negative and Gram-positive pathogens, respectively, supported by culture and antimicrobial susceptibility testing.

Additional antimicrobial therapy

Suspected anaerobic infection

Add one of the following to any of the regimens above.

Metronidazole (IV)

• Adults: 500 mg every 8 hours for 7 days.

• Children: 7.5 mg/kg every 8 hours for 7 days.

OR

Clindamycin

• Adults: 600 mg–1.2 g/day by intravenous infusion in two or three divided doses for 7–10 days.

• Children: 15–25 mg/kg/day in three divided doses for 7–10 days.

Carbapenem-resistant Gram-negative or vancomycin-resistant Gram-positive infections

Administer:

Colistin (IV)

• 2.5–5 mg/kg/day divided every 8–12 hours for 5 days.

AND

Linezolid (PO or IV)

• 400–600 mg every 12 hours for 10–14 days.

Alternative non-beta-lactam antibiotics may be selected based on culture and antimicrobial susceptibility testing.

Suspected invasive Candida infection

Patients with risk factors such as immunocompromised states, prolonged invasive vascular access, or necrotizing pancreatitis should receive antifungal therapy.

Fluconazole (IV)

• Adults:

  • 800 mg every 24 hours on Day 1.

  • Then 400 mg every 24 hours for 14 days.

• Children:

  • 6–12 mg/kg/day for 14 days.