What is the protocol for managing sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

The sepsis protocol involves early recognition and immediate intervention, with administration of effective IV antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock as the goal of therapy 1.

Key Components of Sepsis Protocol

• Obtain blood cultures and measure lactate
• Administer broad-spectrum antibiotics within one hour of recognition, covering likely pathogens based on suspected infection source
• Initial antibiotics may include a combination of agents like piperacillin-tazobactam, ceftriaxone, or meropenem, plus vancomycin for MRSA coverage when appropriate
• Administer IV fluids, starting with 30ml/kg crystalloid for hypotension or lactate ≥4 mmol/L
• If hypotension persists after fluid resuscitation, start vasopressors, with norepinephrine as first choice
• Monitor vital signs, urine output, and repeat lactate measurements
• Source control is essential, identifying and addressing the infection source through procedures like abscess drainage or device removal when necessary
• Reassess antibiotic therapy within 48-72 hours based on culture results

Rationale for Protocol

The protocol is based on the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016, which recommends early effective fluid resuscitation and administration of antimicrobials as crucial for stabilization of sepsis-induced tissue hypoperfusion or septic shock 1.

Important Considerations

• The use of dynamic over static variables to predict fluid responsiveness is suggested, where available 1
• An initial target mean arterial pressure of 65 mm Hg is recommended in patients with septic shock requiring vasopressors 1
• Guiding resuscitation to normalize lactate in patients with elevated lactate levels is suggested as a marker of tissue hypoperfusion 1

From the FDA Drug Label

2 DOSAGE & ADMINISTRTION

2.1 Preparation of Solution Inspect parenteral drug products for particulate matter and discoloration prior to use, whenever solution and container permit. Vasopressin Injection Solution for Dilution, 20 units/mL Dilute vasopressin injection in normal saline (0. 9% sodium chloride) or 5% dextrose in water (D5W) prior to use for intravenous administration. Discard unused diluted solution after 18 hours at room temperature or 24 hours under refrigeration. 2.2 Administration In general, titrate to the lowest dose compatible with a clinically acceptable response. The recommended starting dose is: Post-cardiotomy shock: 0.03 units/minute Septic Shock: 0. 01 units/minute Titrate up by 0.005 units/minute at 10-to 15-minute intervals until the target blood pressure is reached.

The protocol for sepsis (specifically septic shock) using vasopressin is as follows:

• Starting dose: 0.01 units/minute
• Titration: increase by 0.005 units/minute at 10-15 minute intervals until target blood pressure is reached
• Maximum dose: limited data available for doses above 0.07 units/minute, with expected increase in adverse reactions at higher doses
• Tapering: after target blood pressure has been maintained for 8 hours without catecholamines, decrease by 0.005 units/minute every hour as tolerated to maintain target blood pressure 2

From the Research

Sepsis Protocol

The protocol for sepsis involves several key components, including:

• Fluid resuscitation: The administration of intravenous (IV) fluids to restore circulating fluid volume and optimize stroke volume 3.
• Choice of fluid: Crystalloids are recommended as the first-line therapy for fluid resuscitation in sepsis, with balanced crystalloids potentially being a safer alternative to normal saline 4, 5.
• Initial fluid resuscitation dose: A dose of 20-30 mL/kg of crystalloid fluid within the first hour may be associated with reduced 28-day mortality in patients with septic shock 6.
• Avoidance of certain fluids: Semi-synthetic colloids and hydroxyethyl starches are not recommended due to their association with decreased survival and increased kidney injury 4, 5.

Key Considerations

• The Surviving Sepsis Campaign recommends rapid administration of 30 mL/kg of crystalloid fluid for hypotension or lactate ≥4 mmol/L in patients with septic shock 6.
• However, there is limited evidence to support this recommendation, and some studies suggest that a more conservative fluid strategy may be beneficial 3.
• The choice of fluid and initial fluid resuscitation dose may vary depending on the individual patient's needs and the clinical setting 4, 5, 6.
• Further research is needed to determine the optimal fluid resuscitation strategy for patients with sepsis and septic shock 3, 6, 7.

Fluid Resuscitation Strategies

• Crystalloids: Recommended as first-line therapy for fluid resuscitation in sepsis 4, 5.
• Balanced crystalloids: May be a safer alternative to normal saline due to their potential to improve patient-centered outcomes 4, 5.
• Albumin: May be associated with reduced mortality compared to crystalloids or starches, but its use is uncertain due to limited evidence 7.
• Semi-synthetic colloids and hydroxyethyl starches: Not recommended due to their association with decreased survival and increased kidney injury 4, 5.