"There is no perfect induction agent — there is only the right agent for this patient. The whole skill is matching a drug's cardiovascular personality to the cardiovascular reserve in front of you."
Synthesised from Miller's Anesthesia; Morgan & Mikhail's Clinical Anesthesiology; Stoelting's Pharmacology & Physiology in Anesthetic Practice.What we want (and never fully get)
The theoretical ideal: rapid smooth onset, quick predictable offset, cardiovascular and respiratory stability, no pain on injection, no histamine release, analgesia, anti-emesis, organ-independent clearance and no toxicity. Every real agent trades some of these away — which is why we keep several on the trolley.
Most IV induction agents (propofol, thiopentone, etomidate, benzodiazepines) work by potentiating GABA-A inhibition. Ketamine is the exception — an NMDA antagonist — which is why its profile (sympathomimetic, analgesic, airway-sparing) is so different.
Doses and defining features
| Agent | Induction dose | Mechanism | Defining feature |
|---|---|---|---|
| Propofol | 1.5–2.5 mg/kg | GABA-A | Smooth, antiemetic; hypotension & apnoea; pain on injection |
| Thiopentone | 3–5 mg/kg | GABA-A (barbiturate) | Fast onset; anticonvulsant; dangerous if extravasated/intra-arterial |
| Ketamine | 1–2 mg/kg IV (4–6 IM) | NMDA antagonist | Sympathomimetic, analgesic, bronchodilator; emergence phenomena |
| Etomidate | 0.2–0.3 mg/kg | GABA-A | Cardiostable; adrenal suppression; myoclonus |
| Midazolam | 0.1–0.3 mg/kg | GABA-A (benzodiazepine) | Slow onset; amnesia; reversible with flumazenil |
The default — but respect its haemodynamics
A lipid emulsion (2,6-di-isopropylphenol). Rapid onset (~one arm–brain circulation), rapid offset by redistribution, and no accumulation for short cases. It is the agent of choice for TIVA and offers useful anti-emetic and anticonvulsant properties.
With high-dose (>4 mg/kg/h), prolonged (>48 h) infusions — especially in children and the critically ill: lactic acidosis, rhabdomyolysis, hyperkalaemia, lipaemia, arrhythmia, cardiac failure. Stop propofol; supportive care ± dialysis/ECMO.
The classic barbiturate
Ultra-short-acting barbiturate; very fast onset. Reduces cerebral metabolic rate and is a potent anticonvulsant (a role in refractory status/raised ICP). Offset by redistribution — but a long context-sensitive half-time, so it accumulates with repeat dosing.
Intra-arterial injection → severe vasospasm, thrombosis and tissue necrosis. Extravasation is tissue-toxic (alkaline pH ~10.5). Contraindicated in porphyria (induces ALA synthase). Histamine release; laryngospasm if given light.
The haemodynamically friendly dissociative
Non-competitive NMDA-receptor antagonist producing dissociative anaesthesia — a cataleptic state with analgesia and amnesia while largely preserving airway reflexes and respiratory drive.
- Sympathomimetic: raises HR, BP and cardiac output — useful in haemorrhagic/septic shock (unless catecholamine-depleted).
- Bronchodilator: a good choice for the severe asthmatic.
- Analgesia at sub-anaesthetic doses; used for procedural sedation and chronic/opioid-tolerant pain.
Emergence phenomena/hallucinations (attenuate with a benzodiazepine), hypersalivation, raised HR/BP (caution in ischaemia/aortic disease); historically avoided where a rise in ICP is undesirable, though modern data are reassuring with controlled ventilation.
Cardiostable — at a price
An imidazole that gives the most haemodynamically stable induction (minimal effect on BP/contractility) — attractive for the shocked or cardiac patient. It also lowers cerebral metabolic rate.
Reversibly inhibits 11β-hydroxylase → cortisol synthesis falls; even a single induction dose transiently suppresses the adrenal axis — a particular concern in sepsis. Also causes myoclonus, pain on injection and a high incidence of PONV.
The adjuncts
| Agent | Role | Notes |
|---|---|---|
| Dexmedetomidine | Central α₂-agonist; "cooperative" sedation, analgesia, opioid-sparing | Preserves respiration; bradycardia/hypotension; useful for awake fibreoptic intubation and ICU sedation (less delirium) |
| Midazolam | Co-induction/premed; amnesia, anxiolysis | Slow onset; synergistic hypotension with propofol/opioids; reversible with flumazenil |
Match the drug to the patient
| Scenario | Preferred induction | Why |
|---|---|---|
| Haemorrhagic / hypovolaemic shock | Ketamine (or etomidate) | Maintains BP; reduce all doses in shock |
| Cardiac / poor LV / fixed output | Etomidate (or careful ketamine) | Cardiostable; avoid propofol's vasodilation |
| Severe asthma / bronchospasm | Ketamine | Bronchodilation |
| Sepsis | Ketamine/propofol (titrated); caution with etomidate | Etomidate's adrenal suppression is a concern |
| Day-case / PONV-prone | Propofol | Antiemetic, clear-headed recovery |
| Status epilepticus / raised ICP | Thiopentone / propofol | Anticonvulsant, lower CMRO₂ |
Golden rule in shock: whatever you choose, reduce the dose (often by half or more) and give it slowly — a normal induction dose can cause cardiovascular collapse in the under-filled patient.
Where it goes wrong
- Giving a full propofol dose to a shocked/elderly patient → profound hypotension.
- Choosing etomidate in sepsis without weighing adrenal suppression.
- Forgetting ketamine is a sympathomimetic — it can still cause collapse in the catecholamine-depleted.
- Thiopentone intra-arterial/extravasation, or using it in porphyria.
- Assuming any IV agent provides analgesia (only ketamine does).
High-yield one-liners
Q: Which induction agent is not a GABA agonist?
Ketamine (NMDA antagonist).
Q: Etomidate's notable adverse effect?
Adrenal suppression via 11β-hydroxylase inhibition.
Q: Features of propofol infusion syndrome?
Lactic acidosis, rhabdomyolysis, hyperkalaemia, lipaemia, cardiac failure (high-dose/prolonged).
Q: Induction agent contraindicated in porphyria?
Thiopentone (barbiturate).
Q: Best induction for the severe asthmatic?
Ketamine (bronchodilator).
Side-by-side comparisons
Propofol vs Thiopentone
| Feature | Propofol | Thiopentone |
|---|---|---|
| Class | Phenol (GABA-A) | Barbiturate (GABA-A) |
| Recovery | Clear-headed, antiemetic | Hangover; accumulates |
| Airway reflexes | Well suppressed (good for LMA) | Less; laryngospasm if light |
| Extravasation/IA | Relatively benign | Tissue-toxic; IA disastrous |
| TIVA | Yes | No |
Ketamine vs Etomidate (for the shocked patient)
| Feature | Ketamine | Etomidate |
|---|---|---|
| Blood pressure | Rises (sympathomimetic) | Stable (neutral) |
| Analgesia | Yes | No |
| Airway/bronchi | Reflexes preserved; bronchodilator | Neutral |
| Main drawback | Emergence phenomena; tachycardia | Adrenal suppression; myoclonus |
References
- Gropper MA, Cohen NH, Eriksson LI, et al. (eds). Miller's Anesthesia. 9th ed. Elsevier; 2020.
- Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 7th ed. McGraw-Hill; 2022.
- Flood P, Rathmell JP, Urman RD. Stoelting's Pharmacology & Physiology in Anesthetic Practice. 6th ed. Wolters Kluwer; 2022.
- Bruder EA, Ball IM, Ridi S, et al. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database Syst Rev. 2015;(1):CD010225.