4.2 Sepsis and Septic Shock Management

Sepsis and Septic Shock Management

Pathophysiology and Clinical Definitions

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Pathophysiologically, the release of pro-inflammatory mediators triggers widespread endothelial injury, capillary leak, and activation of the coagulation cascade. This results in microvascular thrombosis, tissue hypoperfusion, and cytopathic dysoxia (inability of cells to utilize oxygen).

Organ dysfunction is clinically identified by an acute increase of 2 points or more in the Sequential Organ Failure Assessment (SOFA) score, which evaluates the respiratory, coagulation, hepatic, cardiovascular, central nervous, and renal systems. In out-of-hospital or transport environments, the quick SOFA (qSOFA) is a rapid screening tool. A patient meets qSOFA criteria if they have 2 or more of the following:

• Respiratory rate >= 22 breaths per minute
• Altered mental status (GCS < 15)
• Systolic blood pressure <= 100 mmHg

Septic Shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. It is clinically defined as sepsis requiring vasopressor therapy to maintain a Mean Arterial Pressure (MAP) >= 65 mmHg AND a serum lactate level > 2 mmol/L despite adequate fluid resuscitation.

The Surviving Sepsis 1-Hour Bundle

The Surviving Sepsis Campaign recommends initiating resuscitation and treatment within one hour of recognition. The five key elements of the 1-Hour Bundle are:

1. Measure Lactate Level: A lactate level > 2 mmol/L indicates tissue hypoperfusion. Re-measure lactate within 2–4 hours if the initial level was elevated (> 2 mmol/L) to guide resuscitation.
2. Obtain Blood Cultures: Draw at least two sets of blood cultures (one percutaneous and one from each vascular access device in place for > 48 hours) prior to administering antibiotics. However, do not delay antibiotic therapy if cultures cannot be rapidly obtained.
3. Administer Broad-Spectrum Antibiotics: Initiate empiric broad-spectrum IV antibiotics (e.g., Cefepime, Piperacillin/Tazobactam, or Meropenem, often paired with Vancomycin for MRSA coverage) to target the suspected source.
4. Begin Fluid Resuscitation: Administer 30 mL/kg of IV crystalloid fluid for patients presenting with hypotension (MAP < 65 mmHg) or severe hypoperfusion (lactate >= 4 mmol/L). Balanced crystalloids (such as Lactated Ringer's or Plasma-Lyte) are preferred over 0.9% Normal Saline to reduce the risk of hyperchloremic metabolic acidosis and acute kidney injury.
5. Initiate Vasopressors: Apply vasopressors immediately if the patient remains hypotensive during or after the 30 mL/kg fluid challenge to maintain a MAP >= 65 mmHg.

Early Goal-Directed Therapy (EGDT) and Resuscitation Targets

Although large clinical trials (ProCESS, ARISE, ProMISe) demonstrated that protocolized EGDT does not show a survival benefit compared to usual care when antibiotics and fluids are delivered promptly, the physiological targets of EGDT remain core concepts on the FP-C exam:

• Central Venous Pressure (CVP): Target 8–12 mmHg (12–15 mmHg if mechanically ventilated to account for positive pressure). CVP is a surrogate for right atrial pressure and volume status.
• Mean Arterial Pressure (MAP): Target >= 65 mmHg.
• Urine Output: Target >= 0.5 mL/kg/hour (measured via indwelling Foley catheter).
• Central Venous Oxygen Saturation (ScvO2): Target >= 70% (measured from a central venous catheter in the superior vena cava) or Mixed Venous Oxygen Saturation (SvO2) >= 65%. A low ScvO2 indicates inadequate oxygen delivery (low cardiac output or low hemoglobin) relative to tissue demand.
• Lactate Clearance: Target a decrease of >= 10% in serum lactate every 2 hours until lactate is normalized (< 2 mmol/L).

Vasoactive and Inotropic Therapy in Transport

When fluid resuscitation fails to restore blood pressure and perfusion, vasoactive medications must be titrated to clinical endpoints:

• Norepinephrine (Levophed): First-line vasopressor for septic shock. Potent alpha-1 adrenergic receptor agonist (vasoconstriction) with modest beta-1 agonist activity (increasing heart rate and contractility).
  • Dosing: 0.05–1.0 mcg/kg/min (or 2–30 mcg/min).
• Vasopressin (Pitressin): Second-line adjunct. Stimulates V1 receptors on vascular smooth muscle, causing direct vasoconstriction. Administered at a fixed, non-titratable rate of 0.03–0.04 units/min. Helps reduce norepinephrine dosing and limits beta-adrenergic side effects.
• Epinephrine: Second-line alternative. Strong alpha-1, beta-1, and beta-2 agonist activity, which increases cardiac output and systemic vascular resistance but may increase serum lactate levels due to beta-2 mediated aerobic glycolysis.
• Dobutamine: Inotrope indicated in patients with persistent tissue hypoperfusion (low ScvO2 < 70%) despite achieving an adequate MAP and CVP, indicating myocardial dysfunction. Acts primarily on beta-1 receptors to increase cardiac contractility.
• Hydrocortisone: Indicated at 200 mg/day IV only for patients with septic shock who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy (suspected relative adrenal insufficiency).

Transport Considerations

1. Vascular Access: Central access is preferred for vasopressor infusion. However, do not delay the initiation of vasopressors. Infusing Norepinephrine through a large-bore peripheral IV (18G or larger, located in the antecubital fossa) is safe and recommended during transport until central access is secured.
2. Monitoring: Continuous invasive blood pressure monitoring via an arterial line is the gold standard during transport of patients on vasoactive infusions.
3. Fluid Balance: Avoid aggressive fluid administration beyond the initial 30 mL/kg unless the patient shows clear signs of fluid responsiveness. Positive fluid balance is associated with worsening lung injury (ARDS) and increased mortality.

Vasoactive Comparison Table