Diagnosis and Management of Sepsis and Septic Shock: An Evidence-Based Review

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. The definition of sepsis was updated in 2016 following publication of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The 2016 consensus definitions recommend that the Sequential (Sepsis-related) Organ Failure Assessment (SOFA) criteria and “quick” (q)SOFA criteria be used to identify sepsis, in place of the currently used systemic inflammatory response syndrome (SIRS) criteria, which were the basis for the previous definition of sepsis. SOFA is an ICU-based mortality score, and qSOFA is a rapid, shortened version of SOFA designed for use outside the ICU. The SOFA scores are no clinical predictors of sepsis; they rely on clinical suspicion for the scores to be assessed. There are as many as 750,000–900,000 cases of sepsis per year, resulting in around 200,000 deaths per year. It is likely that there are as many as 30.5 million cases of sepsis annually worldwide, with an estimated 5.3 million deaths annually. Sepsis is a spectrum of disease, where there is a systemic and dysregulated host response to an infection. Risk of progression to fulminant disease is determined by various factors: magnitude and nature of the infective focus, timing and quality of interventions and genetic and acquired predisposition of the patient. Early recognition and diagnosis is essential because early treatment is associated with significant short- and long-term benefits in outcome. There is ongoing debate about the most appropriate criteria for diagnosing sepsis in clinical practice, with several different approaches suggested: SIRS criteria in the presence of infection, SOFA score, and use of risk stratification system as recommended by guideline groups. Strong risk factors are underlying malignancy, age > 65 years, immunocompromise, hemodialysis, alcoholism, diabetes mellitus, recent surgery or other invasive procedures, breached skin integrity, indwelling lines or catheters, intravenous drug misuse and pregnancy. Early recognition and treatment of sepsis is key to improving outcomes. Treatment guidelines have been produced by the Surviving Sepsis Campaign and remain the most widely accepted standards. Current best practice is based upon evidence for care bundles in sepsis. They include the following: obtain blood cultures prior to administration of antibiotics; administer broad-spectrum antibiotics that target the suspected pathogen(s); administer 30 mL/kg crystalloid for hypotension or lactate ≥36 mg/dL (≥4 mmol/L); obtain serial measurement of blood lactate; use vasopressors to maintain a mean arterial pressure (MAP) ≥65 mmHg in patients refractory to fluid therapy, in patients with an initial lactate ≥36 mg/dL (≥4 mmol/L), or who are persistently hypotensive (i.e. MAP < 65 mmHg); and assess volume status and perfusion using either a repeat focused exam or two of the following methods—measurement of central venous pressure, measurement of central venous oxygen saturation (ScvO2), bedside cardiovascular ultrasound and dynamic assessment of fluid responsiveness with passive leg raise or fluid challenge. One bundle dealing with basic therapies, the “Sepsis Six”, has been shown to improve outcomes in septic patients. If the six factors are completed within the first hour following recognition of sepsis, the associated mortality has been reported to reduce by as much as 50%. The six factors are the following: administer high-flow oxygen to maintain target oxygen saturations greater than 94% (or 88–92% in people at risk of hypercapnic respiratory failure), take blood cultures, give intravenous antibiotics, start intravenous fluid resuscitation, check lactate level and monitor hourly urine output. Patients who are refractory to initial treatments, in particular those with septic shock, may require invasive monitoring and consideration for organ support, so management on a High Dependency Unit or ICU may well be required. Patients who fail to respond to the rapid delivery of adequate volumes of intravenous fluids are in septic shock. The immediate priority in this group of patients is the restoration of the circulation and oxygen delivery. Monitoring of vital signs and response to fluid therapy is essential. Assessment of oxygenation via pulse oximetry and serial lactate measurements should be performed, along with monitoring of urinary output. A failure of lactate to improve with therapy is indicative of a poor outcome. Lactate clearance has been shown to correlate positively with survival. All patients receiving vasopressors should have an arterial catheter inserted as soon as it is practical to do so to aid more accurate monitoring of arterial blood pressure.