10.2 Sepsis, Shock & Resuscitation

10.2 Sepsis, Shock & Resuscitation

Sepsis-3 Definitions & Pathophysiological Concepts

In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) redefined sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. This definition shifted clinical practice away from the non-specific Systemic Inflammatory Response Syndrome (SIRS) criteria (fever, tachycardia, tachypnoea, leucocytosis), which lacked specificity for adverse clinical outcomes.

Organ dysfunction in Sepsis-3 is operationalized as an acute change in total Sequential Organ Failure Assessment (SOFA) score of $\ge 2$ points attributable to the underlying infection. A baseline SOFA score is assumed to be zero in patients without pre-existing organ dysfunction. An acute increase in SOFA score by $\ge 2$ points correlates with an in-hospital mortality rate exceeding $10%$.

To facilitate rapid bedside identification of infected patients at risk of deterioration outside the intensive care unit (ICU), the quick SOFA (qSOFA) tool was introduced. A qSOFA score of $\ge 2$ incorporates three clinical parameters:

1. Respiratory rate $\ge 22\text{ breaths/min}$
2. Altered mental status (Glasgow Coma Scale score $< 15$)
3. Systolic blood pressure $\le 100\text{ mmHg}$

While qSOFA is not a formal diagnostic criterion for sepsis, meeting $\ge 2$ qSOFA criteria indicates a high risk of adverse outcomes and mandates urgent diagnostic evaluation, blood cultures, serum lactate measurement, and close monitoring.

Septic shock represents a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are severe enough to substantially increase mortality. Clinically, septic shock is defined by:

• Persistent hypotension requiring vasopressors to maintain a mean arterial pressure (MAP) $\ge 65\text{ mmHg}$, AND
• A serum lactate $> 2.0\text{ mmol/L}$ despite adequate fluid resuscitation. Patients meeting both criteria carry an in-hospital mortality rate exceeding $40%$.

---

Classification & Hemodynamic Profiles of Shock

Shock is defined as systemic cellular hypoxia resulting from an imbalance between cellular oxygen delivery ($\text{DO}_2$) and oxygen demand ($\text{VO}_2$). Prompt identification of the physiological shock subtype is critical to direct resuscitation therapies.

---

Emergency Resuscitation & The Hour-1 Bundle

The Surviving Sepsis Campaign (SSC) mandates immediate operational execution of the Hour-1 Bundle upon recognizing sepsis or septic shock:

1. Measure Serum Lactate Level: Re-measure within $2-4$ hours if initial lactate is $> 2.0\text{ mmol/L}$ to guide lactate clearance resuscitation goals.
2. Obtain Blood Cultures Prior to Antibiotics: Draw two sets of blood cultures (aerobic and anaerobic) from separate peripheral sites and central venous lines without delaying antimicrobial therapy beyond 1 hour.
3. Administer Broad-Spectrum Antimicrobials: Initiate empirical intravenous coverage targeting likely bacterial or fungal pathogens within 1 hour of presentation.
4. Begin Rapid Fluid Resuscitation: Administer a minimum bolus of $30\text{ mL/kg}$ of IV balanced crystalloid solution within 3 hours for sepsis-induced hypoperfusion (hypotension or lactate $\ge 4.0\text{ mmol/L}$).
5. Apply Vasopressors: Initiate vasopressor therapy during or immediately after fluid resuscitation if MAP remains $< 65\text{ mmHg}$.

Fluid Selection in Sepsis

Balanced crystalloids (Ringer's lactate or Plasma-Lyte) are preferred over $0.9%$ Sodium Chloride. Large volumes of $0.9%$ Saline induce hyperchloraemic metabolic acidosis, renal afferent arteriolar constriction, and an increased incidence of acute kidney injury requiring renal replacement therapy (SMART trial). Human Albumin (5%) should be considered in patients requiring substantial volumes of crystalloids to achieve volume status targets.

---

Vasoactive Therapeutics & Invasive Hemodynamic Monitoring

When fluid resuscitation fails to restore an adequate MAP, vasoactive drugs must be titrated via continuous infusion through a central venous catheter under invasive arterial line monitoring:

• Noradrenaline (Norepinephrine): The first-line vasopressor in septic shock. Its potent $\alpha_1$-adrenergic agonist activity restores arteriolar tone and SVR, while minor $\beta_1$-adrenergic effects maintain stroke volume without excessive tachycardia.
• Vasopressin: Added as a second-line non-adrenergic vasopressor at a fixed dose of $0.03\text{ units/min}$ to restore MAP and reduce noradrenaline dosage requirements ("noradrenaline-sparing").
• Adrenaline (Epinephrine): Second-line or additive agent when noradrenaline fails to maintain target MAP, though it increases lactate production via skeletal muscle $\beta_2$-stimulation.
• Dobutamine: Added in patients with persistent tissue hypoperfusion despite adequate intravascular volume and MAP, or when myocardial dysfunction (septic cardiomyopathy) causes low cardiac index.

Hemodynamic endpoints include targeting a $\text{MAP} \ge 65\text{ mmHg}$, urine output $\ge 0.5\text{ mL/kg/hour}$, and central venous oxygen saturation ($\text{ScvO}_2$) $\ge 70%$. Dynamic measures of fluid responsiveness—such as passive leg raise (PLR) testing or pulse pressure variation (PPV $> 13%$) on invasive arterial line traces—are superior to static volumetric parameters (CVP).

---

Acute Respiratory Distress Syndrome (ARDS) Management

ARDS is a severe manifestation of sepsis-induced acute lung injury. According to the Berlin Definition, ARDS is diagnosed when acute hypoxaemic respiratory failure occurs within 7 days of a known clinical insult, presenting with bilateral pulmonary infiltrates on chest imaging not fully explained by cardiac failure or fluid overload.

Severity is stratified by the $\text{PaO}_2/\text{FiO}_2$ (P/F) ratio on positive end-expiratory pressure (PEEP) $\ge 5\text{ cmH}_2\text{O}$:

• Mild ARDS: $200 < \text{P/F} \le 300\text{ mmHg}$ ($26.7 < \text{P/F} \le 40\text{ kPa}$)
• Moderate ARDS: $100 < \text{P/F} \le 200\text{ mmHg}$ ($13.3 < \text{P/F} \le 26.7\text{ kPa}$)
• Severe ARDS: $\text{P/F} \le 100\text{ mmHg}$ ($\le 13.3\text{ kPa}$)

Lung-Protective Mechanical Ventilation Strategies

1. Low Tidal Volume Ventilation: Set initial tidal volume to $6\text{ mL/kg}$ of Predicted Body Weight (PBW) (range $4-8\text{ mL/kg}$), rather than actual weight, to prevent volutrauma and biotrauma.
2. Plateau Pressure ($\text{P}_{\text{plat}}$) Restriction: Maintain peak inspiratory plateau pressure $\le 30\text{ cmH}_2\text{O}$.
3. PEEP Titration: Apply higher PEEP levels ($10-18\text{ cmH}_2\text{O}$) using ARDSNet PEEP/$\text{FiO}_2$ titration tables to prevent alveolar collapse (atelectotrauma).
4. Permissive Hypercapnia: Accept respiratory acidosis ($\text{pH} \ge 7.15-7.20$) to adhere to strict volume/pressure limits.

Advanced Rescue Therapies for Severe ARDS

• Prone Positioning: Placing patients prone for $\ge 16\text{ hours/day}$ significantly reduces 28-day mortality in severe ARDS ($\text{P/F} < 150\text{ mmHg}$) by homogenizing transpulmonary pressure gradients and improving ventilation-perfusion matching (PROSEVA trial).
• Neuromuscular Blockade: Short-course continuous cisatracurium infusion ($48\text{ hours}$) reduces ventilator dyssynchrony and metabolic demand in refractory hypoxaemia.
• Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): Indicated for severe refractory hypercapnic respiratory acidosis ($\text{pH} < 7.15$) or severe hypoxaemia ($\text{P/F} < 80\text{ mmHg}$) despite prone positioning and lung-protective ventilation.