Sepsis – Current definitions, diagnosis and management

According to the current definition, sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock, on the other hand, is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. The mortality of sepsis is around 10%, and the mortality of septic shock is around 40%.

The definition of sepsis was recently changed after many years of the previous definition – based on the systemic inflammatory response syndrome (SIRS) criteria because a task force realized that the previous definition was inaccurate in many situations since SIRS is present in many patients despite the absence of infection.

CURRENT DEFINITIONS:

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection according to the new consensus, as mentioned before. For this purpose, organ dysfunction can be defined as an acute change on the total Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score >= 2 points consequent to the infection. The SOFA score can be found in the end of this article.

Since the SOFA score is a long assessment that takes time, the quick SOFA (qSOFA) can be used outside the ICU setting (e.g. office, urgent care, ER) to assess the patients with suspected infection and identify sepsis:

qSOFA ( can be memorized with the “HAT” mnemonic)

Hypotension: SBP less than or equal to 100 mmHg
Altered mental status (any GCS less than 15)
Tachypnea: RR greater than or equal to 22

The presence of at least two of the three criteria is considered to be positive (and the patient should be treated according to the sepsis protocol).

Septic shock is clinically defined as sepsis (SOFA >=2 / qSOFA positive) and the presence of both below:

• Persistent hypotension requiring vasopressors to maintain MAP >= 65mm Hg, AND
• Lactate greater than or equal to 2 mmol/L

PREVIOUS DEFINITIONS USED (FOR REFERENCE):

Systemic Inflammatory Response Syndrome (SIRS) definition: The presence of two or more of the following:

• Fever of more than 38°C (100.4°F) or less than 36°C (96.8°F)
• HR > 90bpm
• RR > 20 breaths per minute or PaCO2 < 32mmHg
• White blood cell count > 12.000/µL or < 4.000/µL or >10% immature forms (e.g. bands)

Sepsis definition: SIRS + presumed or confirmed infection.

Severe sepsis definition: Sepsis with organ dysfunction (SpO2 <90% on room air; platelets <100×10(9)/L; creatinine elevation; urine output < 0.5mL/kg/h for 2h; bilirubin > 34umol/L or 2mg/dL; INR > 1.5 or PTT > 60s; SBP <90mmHg or MAP <65mmHg or lactate > 2.0 mmol/L).

Septic shock definition: Sepsis with refractory hypotension (SBP <90mmHg or MAP < 70mmHg that does not improve after 30mL/kg of crystalloid).

TREATMENT:

Regardless of classification imbroglios, sepsis and septic shock are medical emergencies, and the treatment should begin immediately. The patient should be monitored (BP, HR, SatO2) and IV access should be obtained.

The airway and breathing should be assessed. Supplemental oxygen should be provided to all patients with sepsis. Mechanical ventilation may be necessary in patients with decreased consciousness, respiratory failure and/or sepsis-related ARDS.

Blood tests should be ordered (CBC, CMP, ABG, lactate, procalcitonin) as well as Gram-stain and cultures (2 sets of blood cultures, sputum, urine and other relevant cultures). Chest radiography should also be obtained. Other tests such as ECG, echocardiogram may be necessary in a case by case basis.

Broad spectrum antibiotics should be started in the first 60 minutes after sepsis recognition (they should be administered after the collection of cultures if possible). If there is an identifiable source of infection (such as a collection or infected device or prosthesis) it should be controlled as soon as possible (e.g. abscess drained).

Patients with hypotension or lactate >=4mmol/L should receive a fluid challenge consisting of 30mL/kg of IV crystalloid that should be given within the first 3 hours. After this fluid challenge, the patient should be reevaluated with physical examination, noninvasive and invasive methods if present. Such parameters may include BP or MAP and HR response, urine output, echocardiogram, CVP changes, pulse pressure variation, lactate clearance, and passive leg raising response. Further crystalloid infusion may be considered according to the response, but it is important to be careful with the possibility of pulmonary edema.

Patients with hypotension despite adequate fluids should receive vasopressors. The first choice is norepinephrine (NE) 35-90mcg/min. If NE is not enough to reach MAP target (65mmHg), vasopressin (0.03units/min) should be used. If NE and vasopressin are not enough, IV steroids (hydrocortisone 200mg/day) may be used and epinephrine (20-50mcg/min) can be added. If none of the above work, phenylephrine 200-300mcg/min may be added.

RBC transfusion should occur if Hb is < 7.0mg/dL (except in patients with bleeding, heart conditions or severe hypoxemia, in which case this threshold can be higher).

The previous sepsis consensus used the Early Goal-directed therapy strategy, which proposed parameters to be reached in the first 6 hours (these parameters indicate improvement of the perfusion):

• Mean arterial pressure (MAP) >= 65 mm Hg (MAP = [(2 x DBP) + SBP]/3);
• Central venous oxygen saturation (ScvO2, from the superior vena cava) >= 70%, or mixed venous oxygen saturation (SvO2, from a pulmonary artery catheter) >= 65%.
• Urine output = 0.5 mL/kg/hr (35 mL/hr for someone weighing 70 kg or 154 lbs);
• Central venous pressure (CVP) 8-12 mm Hg (12-15 mm Hg in patients receiving mechanical ventilation or with known preexisting decreased ventricular compliance);

Since a central line is needed for the measurement of CVP and ScvO2, it is also reasonable to measure only MAP and urine output if the patient does not need a central line for another reason.

If a patient remains with ScvO2 < 70 % after optimization of fluids, hemoglobin and vasopressors, inotropes may be necessary to increase the cardiac output. Dobutamine (0.5 to 1 mcg/kg/minute to maximum of 40mcg/kg/min) may be used in these scenarios.

A reduction in procalcitonin levels may indicate that the infection is getting better.

Glucose levels should be tolerated up to 180mg/dL and kept in the range 140-180mg/dL.

Patients with AKI should receive continuous or intermittent renal replacement therapy.

Venous thromboembolism prophylaxis with LMWH should be provided in the absence of contraindications.

Enteral feeding should be tried as soon as possible, with IV glucose if necessary. Parenteral nutrition should be avoided over the first 7 days.

The initial antibiotic choice should be reevaluated daily according to culture results and clinical improvement.

ANNEXE:

SEQUENTIAL ORGAN FAILURE ASSESSMENT (SOFA)

(To calculate the SOFA, use the worst value for each physiological variable within the past 24 hours.)

SOURCES & FURTHER READING:

1. Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810.
2. Seymour CW, et al. Assessment of Clinical Criteria for SepsisFor the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762-774.
3. Shankar-Hari M, et al. Developing a New Definition and Assessing New Clinical Criteria for Septic ShockFor the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):775-787.
4. Howell MD, Davis AM.Management of Sepsis and Septic Shock. JAMA. 2017;317(8):847-848.
5. Phillip DR, et al. A Users Guide to the 2016 Surviving Sepsis Guidelines. Critical Care Medicine: March 2017 – Volume 45 – Issue 3 – p 381–385.
6. Andrew R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine: March 2017 – Volume 45 – Issue 3 – p 486–552.