Sepsis and Septic Shock

Septicaemia (Sepsis) is defined as life-threatening organ dysfunction caused by a dysregulated host response to bacterial infection (commonly) and fungal or viral infections (leastly). Organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, with an in-hospital mortality greater than 10%.

Septic Shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than 40%.

Clinical presentation

Temperature of >38^oC or <36^oC; Heart rate of >90/min; Respiratory rate of >20/min or PaCO2 <32 mm Hg
Above features plus evidence of organ dysfunction (hypotension, jaundice, oliguria, or altered state of consciousness from altered sensorium like drowsiness/lethargy)

Note

Septicaemia and septic shock are invariably fatal unless timely investigated and promptly managed using specific antimicrobial therapies and other supportive management.
Identification of the primary source/focus of infection is mandatory to eliminate the infection and ensure favorable treatment outcomes. Neonates may present atypically with inability to feed, respiratory distress/cyanosis or abdominal distension.

Investigations

Blood gases analysis, Bedside ultrasound - accessing the inferior vena cava and the lungs, POC ECG, Urine dipstick, Chest Xray - if suspecting pneumonia, Complete blood count, Qualitative or quantitative CRP or Procalcitonin in centres available, Serum Electrolytes, Creatinine and Urea, Liver function tests - liver enzymes, bilirubin, clotting time, Blood culture and antimicrobial susceptibility testing. Primary source of infection’s clinical sample culture (e.g. urine, pus, sputum, CSF etc) and antimicrobial susceptibility testing and/or RNA/DNA PCR for viral pathogens (where indicated)

Diagnostic criteria

Sepsis: Q-SOFA in settings with limited laboratory infrastructures: two or more SOFA score namely: Respiratory rate ≥22/min, Altered mentation and Systolic blood pressure ≥100 mm Hg) ± bacteria or fungal proven blood culture and susceptibility testing are recommended to make a definitive diagnosis.

Septic shock: Sepsis diagnostic criteria above and vasopressor therapy needed to elevate MAP ≥65 mmHg and lactate >2 mmol/L (18 mg/dL) despite adequate fluid resuscitation.

Non-pharmacological Treatment

Nutritional support
Control measures focused to the primary focus of infection
Perform primary and secondary assessment and provide necessary interventions
Ensure patency of the airway and give oxygen if hypoxic or increased work of breathing
Connect the patient to the cardiac monitor and obtain vital signs

Pharmacological Treatments

A: 0.9% sodium chloride (IV) (ADULT: 2litres; CHILD: 20mls/kg)

A: compound sodium lactate (IV): Adult 2litres; paediatrics 20mls/kg in 20minutes as first bolus followed by second bolus of 2litres/20mls/kg (use small boluses in CCF)

S: dobutamine (IV) 2-20mcg/kg/min can be given for patients in shock not responding to fluids or when there is poor cardiac output

S: noradrenaline (IV) 5-20mcg/min for patients in septic shock not responding after 4litres of IVF to maintain the mean arterial pressure (MAP) of ≥ 65mm Hg

AND

A: hydrocortisone (IV) 200mg stat

Note: Transfuse blood (if hemoglobin is < 7g/dl)

Antimicrobial therapies (broad spectrum antibiotics must be started within the first hour):

A: ampicillin (IV) 150-200mg/kg/day divided 6hourly a day

AND

B: cloxacillin (IV) 50-100mg/kg/day 6hourly a day

AND

A: gentamicin (IV) or (IM) 120mg [For children 7.5mg/kg] 24hourly for 5 days

If no improvement in vital signs within 24 hours (Temp, HR, RR and altered state of consciousness), give:

B: ceftriaxone (IV) 1 gm [For children 100 mg/kg (IV) or (IM)] 24hourly for 4-14 days

AND

A: gentamicin (IV) or (IM) 120mg [For children 7.5mg/kg] 24hourly for 5 days

Refer immediately.

D: ceftriaxone + salbactum (FDC) (IV) or (IM) 75-120 mg/kg 24hourly for 4-14 days

AND

A: gentamicin (IV) or (IM) 120mg [For children 7.5mg/kg] 24hourly for 5days

S**: piperacillin + tazobactum (FDC) (IV) (4g+0.5g) administered 8hourly [For children 100 mg Piperacillin + 12.5mg Tazobactam per kg body weight 8hourly] for 7-10days

AND

A: gentamicin (IV) or (IM) 120mg [For children 7.5mg/kg] 24hourly for 5 days

Alternatively, (for patients who have evidence of not improving on the treatment above and referred to a zonal/tertiary hospital with judicious decision from a medical specialist or medical super-specialist):

S**: meropenem 2g (IV) 8hourly in adults and adolescents [40 mg/kg 8hourly in children] for 7-14 days

S**: vancomycin (IV) 15 to 20 mg/kg body weight 8 - 12hourly (not to exceed 2 g per dose) for 7-14 days.

Note: In renal insufficiency vancomycin can be adjusted for dose and dose interval. These antimicrobial agents are usually reserved for Gram negative and Gram positive pathogen(s), respectively supported by culture and antimicrobial susceptibility testing

For suspected co-existing anaerobic infections, an additional to all regimes above of

B: metronidazole (IV) 500mg 8hourly [In children 7.5 mg/kg 8hourly] for 7 days

S: clindamycin 600mg - 1.2g/day diluted infusion in two or three doses [In children 15-25mg/kg/day in three equal doses] for 7-10days is recommended

For the rare cases of sepsis or septic shock due to carbapenem-resistant Gram negative bacteria or vancomycin-resistant Gram positive bacteria, give:

S**: colistin (IV) 2.5-5mg/kg/day 8-12 hourly for 5days

AND

S**: linezolid (PO/IV) 400-600mg 12hourly for 10-14 days respectively or other non-beta lactam antibiotics may be considered based on culture and antimicrobial susceptibility testing results.

In case there is/are risk factors for invasive Candida infections like in immunocompromised states, prolonged invasive vascular, necrotizing pancreatitis, then antifungal therapies should be added.

C: fluconazole (IV) 800mg 24hourly on the first day then 400mg 24hourly for 14days [In children 6-12mg/kg/day for 14days]