Sepsis

Sepsis is a medical emergency which, if left untreated, can progress to septic shock, multi-organ failure and death. Pathogens responsible for sepsis can be bacterial, viral or fungal. Any person who acquires an infection is at risk of developing sepsis. Sepsis is the leading cause of death in hospitals and is related to 20% of all deaths.

High levels of lactate in tissue is an indication of tissue hypoxia. Tissue hypoxia for a long time can cause irreversible damage to the tissue resulting in its death and organ failure. Organ failure is a common feature seen in septic shock patients. Multi-organ failure is the last stage of uncontrolled sepsis, which can result in death. Septic shock is a subset of sepsis associated with profound circulatory, cellular and metabolic abnormalities.

Groups at a higher risk of developing sepsis are:

• The very young and old;
• Immunocompromised;
• Hospitalised patients; and
• Pregnant or recently pregnant women.

The following measures can reduce the risk of a person acquiring an infection:

• Vaccination;
• Hand hygiene;
• Sanitation measures;
• Infection control within healthcare; and
• Pandemic response measures.

A delay in the treatment of sepsis or inadequate treatment can reduce the patient’s chance of survival. For every hour of delay in commencing antibiotics, there is a 7.6% decrease in survival over the first 6 hours. The time to initiation of antibiotics is a key factor in patient survival.

Treatment

Evidence-based guidelines (e.g. The Hour-1 Bundle) should be initiated within the first hour of the patient presenting with sepsis. The following is recommended:

• Measure lactate level. Remeasure if initial lactate is >2mmol/L. Serum lactate helps in identifying a patient progressing into septic shock.
• Obtain blood cultures prior to administration of antibiotics. However, antibiotic administration should not be delayed in order to obtain blood cultures.
• Administer broad-spectrum antibiotics.
• Begin rapid administration of a minimum of 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L. A crystalloid solution such as 0.9% sodium chloride is the most frequently used fluid.
• Apply vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain mean arterial blood pressure (MAP) ≥65mmHg

Patients who remain hypotensive despite adequate fluid administration are said to be in septic shock. These patients require vasopressor infusions. Noradrenaline is the first-line treatment in septic shock. Metaraminol and phenylephrine are alternatives. Vasopressin is often administered second-line to replete the relative vasopressin deficiency, which occurs in septic shock and allows for a reduction in noradrenaline requirements.

Steroids may be administered to patients with septic shock. The 2018 ADRENAL trial did not show a mortality benefit with a 200mg daily intravenous infusion of hydrocortisone but did show improvements in secondary outcomes of time off ventilation and length of ICU stay.

If prolonged hypotension occurs, blood flow to the kidneys will reduce, and organ dysfunction will begin. Sepsis is the leading cause of acute kidney injury.

Initial antibiotics used to treat sepsis should be broad-spectrum to cover the potential infecting pathogen. Considerations to be taken into account to determine the most appropriate antibiotic are:

• The most likely source of infection;
• Local antibiotic resistance patterns;
• Recent antibiotic exposure;
• Patient allergies;
• Individual patient factors (e.g. recent hospitalisations, immunosuppression, and overseas travel); and
• Any known multi-resistant organism (MRO) colonisation.

A medication history should be taken with a particular focus on allergies, vaccination history and any recent antibiotics received. If a patient has been taking antibiotics prior to presentation, then antibiotics from a different class, or higher doses, may need to be considered. The antibiotic choice needs to be reviewed and rationalised in response to changes in patient condition and the results of microbiological cultures as they become available. Patients in septic shock can experience pathophysiological changes, which in turn can affect the pharmacokinetics of medicines. Therefore, these changes need to be taken into consideration when dosing. Antibiotic treatment should be reviewed if the patient’s condition deteriorates.

Patients with septic shock may require their regular medicines to be withheld. Other medications may require dose adjustment based on any organ failure. Hospitalised patients should receive venous thromboembolism (VTE) prophylaxis, as septic patients are at a high risk of developing blood clots.

Absorption from the gastrointestinal tract (GIT) is reduced in septic shock, as blood supply is diverted away from the GIT to the essential organs (brain, lungs and heart). Hence, oral administration of antibiotics is less likely to be effective due to delayed or reduced absorption. The Intravenous (IV) route of administration is therefore preferred for septic patients. If unable to obtain IV access, then intraosseous (IO) administration is the second-line option.

Drug metabolism can decrease in septic shock as hepatic blood flow reduces. If liver function is significantly reduced, then dosage adjustments to hepatically cleared medications may be needed.

The Therapeutic Guidelines advise that the following features are indicators of life-threatening organ dysfunction and are associated with a significant risk of deterioration or death:

• Impaired consciousness
• Tachypnoea (respiratory rate 22 breaths/minute or more) or hypoxaemia
• Hypotension (systolic blood pressure less than 90 mmHg)
• Blood lactate concentration more than 2 mmol/L

Life-threatening organ dysfunction is also indicated by the following features:

• Poor peripheral perfusion or mottled skin;
• Acute oliguria or elevated serum creatinine (above baseline);
• Low platelet count; and
• Elevated serum bilirubin (above baseline).