What is the role of ketamine in managing septic shock?

Ketamine in Septic Shock: Clinical Utility and Recommendations

Ketamine is the preferred sedative agent for intubation and ongoing sedation in septic shock patients because it maintains cardiovascular stability by preserving endogenous catecholamine release and avoiding the myocardial depression caused by propofol, benzodiazepines, and other traditional sedatives. 1

Primary Indication: Intubation and Procedural Sedation

The American College of Critical Care Medicine specifically recommends ketamine with atropine premedication for sedation and intubation in pediatric septic shock, and this principle extends to adult practice given the shared hemodynamic concerns. 1

Why Ketamine Over Other Agents

• Propofol, thiopental, benzodiazepines, and inhalational agents all cause direct myocardial depression and vasodilation, compounded by blunting of endogenous catecholamine release—effects that are particularly dangerous in septic shock. 1

• Etomidate is explicitly contraindicated even for single-dose intubation in septic shock due to independent association with increased mortality in both children and adults, likely from adrenal corticosteroid biosynthesis inhibition. 1

• Ketamine maintains cardiovascular stability through multiple mechanisms: it blocks nuclear factor-kappa B transcription, reduces systemic interleukin-6 production, and preserves an intact adrenal axis. 1

Dosing Protocol for Intubation

• Bolus dose: 1-2 mg/kg IV with atropine premedication to prevent secretions and bradycardia. 1, 2

• For patients with depleted catecholamine reserves, consider the ketamine-lidocaine combination (0.5 mg/kg ketamine plus 1 mg/kg lidocaine) which shows superior hemodynamic stability compared to full-dose ketamine alone, with significantly lower incidence of post-intubation hypotension (5% vs 77%). 3

Continuous Infusion for Ongoing Sedation

Ketamine can be used as a continuous infusion to maintain cardiovascular stability during mechanical ventilation in septic shock. 1

Infusion Protocol

• Initial bolus: 1-2 mg/kg IV, followed by continuous infusion starting at 5 mcg/kg/min. 2

• Titrate by 2 mcg/kg/min every 30 minutes to achieve Richmond Agitation Sedation Scale (RASS) goal of -1 to -2. 2

• Ketamine infusions reduce adjunctive opioid and propofol requirements, which is particularly beneficial given these agents' hemodynamic liabilities in shock states. 2

Cardiovascular Effects and Mechanisms

• Ketamine is the only IV anesthetic that increases mean arterial pressure without compromising cardiac output, primarily through sympathetic nervous system stimulation and inhibition of ATP-sensitive potassium channels. 4

• Anti-inflammatory properties include inhibition of proinflammatory cytokines (TNF-α, IL-6), with experimental evidence suggesting reduced mortality in sepsis models. 4

• Ketamine acts as an NMDA receptor antagonist, providing both amnesia and analgesia without depressing respiratory drive or blood pressure—critical advantages in septic shock. 2, 5

Critical Caveats and Limitations

Catecholamine Depletion Warning

In patients with severely depleted catecholamine reserves, ketamine can paradoxically suppress myocardial contractility since its cardiovascular benefits depend on intact sympathetic responses. 1 This is most relevant in:

• Prolonged shock states with exhausted endogenous catecholamine stores
• Patients already on maximum vasopressor support
• Cardiogenic shock components overlapping with septic shock

For these high-risk patients, minimize sedative doses overall and have a lower threshold to initiate neuromuscular blockade rather than escalating sedation. 1

Microcirculatory Concerns

• Ketamine inhibits endothelial nitric oxide synthase, which could theoretically worsen impaired regional blood flow in sepsis. 4

• This remains a theoretical concern without clear clinical evidence of harm, but warrants monitoring for signs of tissue hypoperfusion despite adequate blood pressure.

Neuropsychiatric Effects

• Ketamine carries higher risk of delirium compared to dexmedetomidine (though lower than benzodiazepines). 1

• Psychomimetic side effects are the most common limitation, though less relevant in deeply sedated mechanically ventilated patients. 5

Practical Implementation Algorithm

1. For intubation in septic shock:

   • Use ketamine 1-2 mg/kg with atropine premedication 1
   • Consider ketamine-lidocaine combination (0.5 mg/kg + 1 mg/kg) if severe hemodynamic instability 3
   • Avoid etomidate entirely 1

2. For ongoing sedation:

   • Start ketamine infusion at 5 mcg/kg/min after bolus 2
   • Titrate every 30 minutes to RASS -1 to -2 2
   • Expect reduced opioid and propofol requirements 2

3. If cardiovascular instability persists despite ketamine:

   • Consider catecholamine depletion 1
   • Minimize all sedatives and use neuromuscular blockade instead 1
   • Optimize vasopressor support per standard septic shock protocols 6

Special Populations

For neonates with septic shock, insufficient data exists to make firm recommendations for or against ketamine use. 1 In pediatric patients beyond the neonatal period, ketamine is well-supported by guideline recommendations. 1