3.5 Anaesthetics and Induction Agents

Anaesthetics and Induction Agents

Rapid Sequence Intubation (RSI) in critical care transport is a high-risk procedure. The selection of the induction agent is a critical decision that directly impacts the patient's hemodynamic stability and cerebral perfusion. Inducing anesthesia in critically ill patients requires agents that act rapidly (within one minute) to facilitate laryngoscopy while minimizing adverse physiological surges.

Ketamine (Ketalar)

Ketamine is a dissociative anesthetic that acts as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It blocks glutamate, the primary excitatory neurotransmitter in the central nervous system, leading to a functional dissociation between the limbic and cortical systems.

• RSI Induction Dose: 1.0 to 2.0 mg/kg IV or IO (commonly 1.5 mg/kg). For intramuscular induction, the dose is 4.0 to 10.0 mg/kg.
• Onset and Duration: Onset is rapid (30 to 60 seconds IV); duration of action is 10 to 20 minutes.
• Cardiovascular Effects: Ketamine stimulates the sympathetic nervous system, causing catecholamine release. This results in transient increases in heart rate, mean arterial pressure (MAP), and cardiac output. This makes ketamine the induction agent of choice for patients in septic, hemorrhagic, or anodic shock.
• Respiratory Effects: It is a potent direct bronchodilator, making it highly effective for patients with severe bronchospasm (status asthmaticus). Unlike most other induction agents, ketamine preserves protective airway reflexes and maintains respiratory drive.
• Clinical Caveats: In patients who are chronically catecholamine-depleted (e.g., end-stage cardiogenic shock, severe septic shock with maximal compensatory response), ketamine's direct myocardial depressant effects are unmasked. When endogenous catecholamine reserves are exhausted, administering ketamine can cause a sudden, profound drop in blood pressure and cardiac arrest. Historically, ketamine was avoided in patients with traumatic brain injury (TBI) due to fears of increasing intracranial pressure (ICP); however, modern clinical evidence has debunked this, showing that ketamine maintains mean arterial pressure and cerebral perfusion pressure ($CPP = MAP - ICP$), making it safe and effective in TBI.

Etomidate (Amidate)

Etomidate is a carboxylated imidazole derivative that acts as a potent GABA-A (gamma-aminobutyric acid type A) receptor agonist. It enhances the inhibitory effects of GABA, producing rapid hypnosis.

• RSI Induction Dose: 0.3 mg/kg IV or IO.
• Onset and Duration: Onset occurs within 30 to 60 seconds; duration of action is 3 to 12 minutes.
• Cardiovascular Effects: Etomidate is hemodynamically neutral. It does not alter heart rate, MAP, stroke volume, or myocardial contractility, making it the gold standard for patients with cardiovascular disease, cardiogenic shock, coronary artery disease, or aortic dissection.
• Cerebral Effects: It decreases the cerebral metabolic rate of oxygen consumption ($CMRO_2$), cerebral blood flow, and ICP while preserving cerebral perfusion pressure.
• Clinical Caveats: Etomidate causes transient, dose-dependent adrenal suppression by inhibiting 11-beta-hydroxylase, an enzyme crucial for the synthesis of cortisol and aldosterone. A single induction dose can suppress adrenal function for 12 to 24 hours. While this has raised concerns regarding mortality in patients with septic shock, large-scale clinical trials have not demonstrated a clear increase in mortality from a single dose, and it remains widely used due to its hemodynamic stability. Etomidate can also cause myoclonus (brief muscle contractions) during induction.

Propofol (Diprivan)

Propofol is an alkylphenol derivative that facilitates inhibitory neurotransmission through GABA-A receptors, leading to rapid sedation and hypnosis.

• RSI Induction Dose: 1.5 to 2.5 mg/kg IV or IO.
• Onset and Duration: Onset is ultra-rapid (15 to 30 seconds); duration is short (5 to 10 minutes) due to rapid redistribution.
• Cardiovascular Effects: Propofol causes profound, dose-dependent systemic vasodilation (reducing preload and afterload) and direct myocardial depression. It blunts the sympathetic response to laryngoscopy, leading to significant hypotension. It is contraindicated in patients with hypovolemia, shock, or severe cardiovascular instability.
• Cerebral Effects: Propofol significantly decreases ICP, cerebral blood flow, and $CMRO_2$. It has potent anticonvulsant properties, making it an excellent choice for patients in status epilepticus who are hemodynamically stable.
• Clinical Caveats: Its use in transport is limited for induction due to the high incidence of hypotension, but it is frequently used as a post-intubation sedative infusion.

Midazolam (Versed)

Midazolam is a short-acting benzodiazepine that enhances the action of GABA-A receptors.

• RSI Induction Dose: 0.1 to 0.3 mg/kg IV or IO.
• Onset and Duration: Onset is relatively slow (1 to 3 minutes); duration is 20 to 60 minutes.
• Clinical Caveats: When used at full induction doses, midazolam causes myocardial depression and vasodilation, leading to hypotension, especially in volume-depleted patients. Due to its slow onset compared to etomidate or ketamine, it is rarely used as a primary RSI induction agent in modern transport protocols. It is, however, widely used for post-intubation sedation and co-induction.

Fentanyl (Sublimaze) as a Sympatholytic Co-Agent

Fentanyl is a synthetic opioid agonist acting on mu-receptors. In the context of RSI, it is used as a pretreatment agent rather than a primary induction agent.

• Pretreatment Dose: 1 to 3 mcg/kg IV/IO administered slowly over 60 seconds, 2 to 3 minutes prior to induction.
• Rationale: Laryngoscopy triggers a profound sympathetic reflex, causing tachycardia, hypertension, and spikes in ICP. Fentanyl blunts this reflex (sympatholysis). It is indicated in patients with intracranial pathology (TBI, hemorrhagic stroke), suspected aortic dissection, or acute coronary syndrome.
• Clinical Caveats: Rapid administration of high doses can cause chest wall rigidity, which impairs ventilation. This is managed with neuromuscular blockade.