2.3 Critical Care & Emergency Medicine

Critical Care & Emergency Medicine

Sepsis and Septic Shock (Surviving Sepsis Campaign)

The Surviving Sepsis Campaign (SSC) guidelines outline a time-critical, evidence-based approach to managing sepsis and septic shock, aiming to halt progression to multi-organ failure. The initial "Hour-1 Bundle" demands immediate execution:

1. Measure lactate levels (re-measure within 2-4 hours if initial is > 2 mmol/L to ensure clearance).
2. Obtain blood cultures prior to antibiotic administration, taking care not to delay antibiotics by more than 45 minutes if cultures are difficult to obtain.
3. Administer broad-spectrum empiric IV antibiotics (covering MRSA and Pseudomonas based on local antibiograms).
4. Begin rapid administration of 30 mL/kg of crystalloid fluid for hypotension or lactate ≥ 4 mmol/L.
5. Apply vasopressors if hypotensive during or after fluid resuscitation to maintain a Mean Arterial Pressure (MAP) ≥ 65 mmHg.

Fluid Resuscitation and Vasoactive Agents: Balanced crystalloids (e.g., Lactated Ringer's, Plasma-Lyte) are preferred over 0.9% normal saline, as large volumes of normal saline can cause hyperchloremic non-anion gap metabolic acidosis, leading to renal vasoconstriction and acute kidney injury. Fluid responsiveness should be guided by dynamic measures (e.g., passive leg raise, stroke volume variation) rather than static CVP.

For vasoactive support, Norepinephrine is the undisputed first-line vasopressor in septic shock. It exhibits potent alpha-1 agonism (profound vasoconstriction) with modest beta-1 agonism (inotropic support without excessive tachycardia). If MAP remains < 65 mmHg despite adequate norepinephrine (typically reaching 0.25-0.5 mcg/kg/min), Vasopressin (up to 0.03 units/min) is the recommended second-line agent. Vasopressin acts on V1 receptors and serves a vasopressor-sparing role, replacing endogenous vasopressin stores depleted during shock. Epinephrine is considered a third-line option. Dobutamine (a potent beta-1 agonist) should be added only if there is evidence of persistent hypoperfusion and cardiac dysfunction (e.g., low cardiac output or elevated filling pressures) despite adequate fluid loading and vasopressors. Angiotensin II (Giapreza) is a novel synthetic vasopressor that can be used for refractory vasodilatory shock but carries a significant risk of thromboembolic events, requiring concurrent VTE prophylaxis.

In patients with refractory septic shock (ongoing requirement for vasopressors despite adequate fluid resuscitation), IV hydrocortisone 200 mg per day (typically 50 mg IV every 6 hours) is recommended to treat critical illness-related corticosteroid insufficiency (CIRCI).

Analgesia, Sedation, and Delirium (PADIS Guidelines)

The ICU management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep disruption (PADIS) focuses on achieving patient comfort while facilitating liberation from mechanical ventilation.

• Analgesia-First Approach: Pain must be assessed (using CPOT or BPS tools) and treated prior to initiating sedatives. IV opioids (fentanyl, hydromorphone) are the mainstay of therapy. Fentanyl has a rapid onset and lacks active metabolites, but its extreme lipophilicity causes it to sequester in adipose tissue, leading to prolonged emergence after continuous infusions. Hydromorphone is preferred in patients with renal dysfunction. Morphine is avoided due to histamine release (hypotension) and accumulation of the active neurotoxic metabolite morphine-6-glucuronide in renal failure.
• Sedation Strategies: Light sedation (Richmond Agitation-Sedation Scale [RASS] -1 to -2) is universally recommended over deep sedation, alongside daily spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) to reduce the duration of mechanical ventilation. Non-benzodiazepine sedatives are strongly preferred.
  • Propofol: A highly lipid-soluble, rapid-acting GABA agonist. Provides deep sedation and amnesia but no analgesia. Risks include Propofol-Related Infusion Syndrome (PRIS, characterized by metabolic acidosis, rhabdomyolysis, and cardiovascular collapse), hypertriglyceridemia, and dose-dependent hypotension. Triglycerides must be monitored every 3-4 days; the lipid emulsion provides 1.1 kcal/mL, which must be factored into parenteral nutrition calculations.
  • Dexmedetomidine (Precedex): A selective centrally-acting alpha-2 agonist providing "cooperative sedation" without depressing respiratory drive. It has mild analgesic-sparing properties. The primary adverse effects are bradycardia and hypotension. It is highly effective for facilitating extubation.
  • Benzodiazepines (Midazolam, Lorazepam): Associated with a higher risk of delirium and prolonged mechanical ventilation. Reserved for specific indications such as alcohol withdrawal, status epilepticus, or when propofol/dexmedetomidine are contraindicated. Midazolam has active metabolites that severely accumulate in renal failure.
• Delirium: Routine screening is performed using the CAM-ICU tool. Non-pharmacologic interventions (early mobility, sleep hygiene, reorientation) are first-line. Typical and atypical antipsychotics (haloperidol, quetiapine) may be used for hyperactive delirium to prevent self-harm, but they do not reduce delirium duration or mortality, and they require strict QTc monitoring.

Neuromuscular Blocking Agents (NMBAs)

In critically ill patients with severe ARDS (PaO2/FiO2 < 150), a continuous infusion of an NMBA (e.g., cisatracurium) may be utilized for up to 48 hours to improve patient-ventilator synchrony. Cisatracurium is preferred in multi-organ failure because it undergoes Hofmann elimination (spontaneous degradation in plasma dependent on body temperature and pH) and does not rely on renal or hepatic clearance. Patients receiving NMBAs must be deeply sedated (RASS -4 to -5) and receive adequate analgesia prior to paralysis. Depth of paralysis is monitored using a Train-of-Four (TOF) peripheral nerve stimulator.

Acute Toxicology and Antidotes

Rapid identification of toxidromes and appropriate antidote administration is critical for survival.