Intravenous (IV) Induction of Anaesthesia - Detailed Explanation

1. Definition and Purpose

• Scott-Brown's Otorhinolaryngology, p. 388

2. The Triad of Anaesthesia

• Scott-Brown's Otorhinolaryngology, p. 381

3. Mechanism of Action - General Pharmacokinetics

• High lipid solubility allows rapid diffusion across the blood-brain barrier (BBB)
• The brain has very high blood flow, so drug delivery to the CNS is fast
• After a single bolus, redistribution (not metabolism) accounts for the return of consciousness - drug moves from the brain to other lipid-rich tissues (muscle, fat) with lower blood flows
• Hepatic metabolism provides slower background elimination but does not drive emergence from a single-dose induction
• Most agents work via GABA-A receptor agonism, enhancing chloride channel opening and causing neuronal inhibition

"Intravenous induction agents owe their rapid onset and offset of action to rapid diffusion across the blood-brain barrier due to their high lipid solubility. Hepatic clearance is moderately slow and does not play a significant part in the return of consciousness after a bolus dose."

• Scott-Brown's Otorhinolaryngology, Key Points

4. Pre-Induction Preparation

Preoxygenation

• This does not significantly increase blood oxygen saturation (already near 100% on room air)
• Instead, it denitrogenates the lungs, creating an oxygen reservoir in the alveolar compartment
• This reservoir delays the onset of desaturation during the apnoea that follows induction
• Especially important in obese patients and children, who have reduced FRC and desaturate faster

Monitoring and IV Access

• ECG, SpO2 (pulse oximetry), non-invasive blood pressure (NIBP), capnography
• A secure peripheral IV cannula (minimum 18G)

5. Induction Agents - Individual Profiles

5.1 Propofol (2,6-diisopropylphenol) - First-Line Agent

• Smooth, rapid induction - avoids excitement phase
• Low PONV (post-operative nausea and vomiting) - antiemetic properties
• Potent bronchodilator - useful in asthmatics
• Decreases ICP and CMRO2 (cerebral metabolic rate of oxygen) - suitable for head injury/neurosurgery
• Anticonvulsant properties
• Can be used for maintenance (TIVA) via target-controlled infusion (TCI) using Marsh or Schneider pharmacokinetic models
• Short context-sensitive half-time - patients wake up quickly even after prolonged infusions
• Safe in porphyria and malignant hyperthermia

• Hypotension - reduces sympathetic vasomotor tone and cardiac contractility; worse in elderly, dehydrated, or hypovolaemic patients
• Pain on injection - burning at the IV site (reduced by pre-injection of lidocaine or using a larger vein)
• Respiratory depression and apnoea
• Propofol Infusion Syndrome (PRIS) - rare but fatal; mitochondrial dysfunction, metabolic acidosis, cardiovascular collapse; seen with high-dose prolonged infusions in ICU
• Hypertriglyceridaemia and pancreatitis with prolonged use (propofol is in a lipid vehicle)
• Sabiston Textbook of Surgery, p. 331-332

5.2 Thiopentone (Thiopental Sodium)

• Very rapid onset
• Decreases ICP - still used in neurosurgery emergencies in some centres

• Cannot be used for maintenance (context-sensitive half-time increases significantly with repeated doses - "hang-over" effect)
• Cardiovascular depression similar to propofol
• Triggers acute porphyria - absolutely contraindicated in porphyria
• Higher incidence of PONV compared to propofol
• Can cause histamine release and bronchospasm

5.3 Ketamine

• The only IV induction agent that increases blood pressure and heart rate via sympathomimetic (sympathetic stimulation) effects
• Potent analgesic at sub-induction doses - useful adjunct in multimodal pain management
• Bronchodilator - particularly useful in severe asthmatics and for Rapid Sequence Induction in bronchospasm
• Preserves airway reflexes and spontaneous breathing - can be used as a sole agent for brief superficial cases
• Can be given IM - useful in uncooperative patients or those without IV access

• Psychotropic effects - emergence delirium, nightmares, hallucinations (attenuated by co-administering a benzodiazepine like midazolam)
• Increases cerebral blood flow - classically avoided in raised ICP (though recent data suggest this concern may be overstated in traumatic brain injury)
• Copious oropharyngeal secretions - glycopyrrolate (antimuscarinic) often co-administered
• Tachycardia and hypertension - caution in coronary artery disease
• In profound shock with exhausted sympathetic tone, ketamine's direct cardiac depressant effects can unmask

• Sabiston Textbook of Surgery, p. 332

5.4 Etomidate

• Minimal haemodynamic effects - maintains blood pressure far better than propofol or thiopentone
• Decreases ICP and CMRO2 - suitable for head injury
• Rapid onset and recovery; does not cause apnoea
• Preferred for patients with cardiac contractile dysfunction or severe hypovolemia

• Adrenal suppression - inhibits 11β-hydroxylase (required for cortisol synthesis); even a single induction dose can suppress the adrenal axis for 6-24 hours
• Pain on injection
• Myoclonus - abnormal involuntary muscle movements during induction
• High incidence of PONV
• Concern about worsened mortality in septic patients due to adrenal suppression

5.5 Midazolam

6. Summary Comparison Table (from Sabiston Textbook of Surgery)

7. Dose Titration Principles

• Dose is guided by patient weight but must be titrated to effect (slow injection, watching for loss of consciousness)
• Reduced doses in: elderly, debilitated, hypovolaemic, pre-medicated patients, ASA class III-IV
• Injudicious bolus dosing can cause cardiovascular collapse and respiratory arrest
• Before administering neuromuscular blockers, confirm the ability to ventilate by face mask (except in RSI - see below)

8. Rapid Sequence Induction (RSI)

• Emergency surgery (full stomach)
• Hiatus hernia with active reflux
• Airway or GI haemorrhage
• Bowel obstruction

1. Preoxygenation (3 minutes 100% O2)
2. Bolus of IV induction agent (propofol or thiopentone)
3. Immediately followed by neuromuscular blocker: suxamethonium (1.5 mg/kg) or rocuronium (1.2 mg/kg)
4. Cricoid pressure (Sellick's manoeuvre) applied as soon as consciousness is lost - 40 N force applied to compresses the oesophagus against C6 vertebral body, preventing passive gastric regurgitation
5. No face-mask ventilation between induction agent and intubation
6. Direct laryngoscopy and intubation as soon as muscle relaxation is achieved
7. Confirm placement by capnography (ETCO2)

• Scott-Brown's Otorhinolaryngology, p. 388

9. Total Intravenous Anaesthesia (TIVA)

• Often combined with remifentanil (ultra-short-acting synthetic opioid, metabolised by plasma esterases, context-sensitive half-time of 3 minutes)
• Delivered via target-controlled infusion (TCI) pumps using population-based pharmacokinetic models (Marsh or Schneider models for propofol; Minto model for remifentanil)
• The pumps calculate required infusion rates to maintain a target plasma or effect-site concentration
• Advantages over volatile agents: lower PONV, no environmental pollution, applicable when volatile agent delivery is not possible (e.g., jet ventilation, MRI)
• Useful when nerve monitoring is required, as neuromuscular blockers can be avoided

10. Cardiovascular Effects of IV Induction

• Decreased central sympathetic vasomotor tone
• Reduced cardiac contractility
• Peripheral vasodilation
• This is particularly marked in:
  • Elderly patients
  • Dehydrated or hypovolaemic patients
  • Patients with pre-existing cardiac disease

11. Monitoring During IV Induction

• ECG (continuous)
• SpO2 (pulse oximetry - continuous)
• NIBP (every 5 minutes minimum)
• ETCO2 (capnography) - gold standard for confirming endotracheal tube placement and monitoring ventilation
• Temperature monitoring (when expected changes)
• FiO2 monitoring
• Sabiston Textbook of Surgery, p. 335-336

Key Takeaways

1. IV induction is the standard method because it is rapid (one arm-brain circulation time), smooth, and avoids the dangerous excitement phase of inhalation induction.
2. Propofol is the most widely used induction agent - GABA-A agonist, low PONV, bronchodilator, but causes hypotension.
3. Ketamine uniquely stimulates the cardiovascular system via NMDA antagonism - ideal for haemodynamically unstable patients and asthmatics.
4. Etomidate offers cardiovascular stability but carries adrenal suppression risk.
5. Dose must always be titrated to effect, not given as a rapid bolus, especially in vulnerable patients.
6. RSI with cricoid pressure protects against aspiration in patients with full stomachs.
7. TIVA using propofol + remifentanil by TCI is a complete IV alternative to inhaled maintenance.