Anaesthesia
Final Professional MBBS — Anaesthesiology. Explanation-first answers covering the principles and conduct of anaesthesia, the anaesthesia machine, airway, drugs, regional techniques, monitoring, fluids, complications and resuscitation, with classifications, comparison tables, drug doses, clinical pearls and key-point recaps from Morgan & Mikhail and Miller's Anesthesia.
Definition & Role
Intravenous (IV) anaesthetic agents are drugs injected into a vein to produce a rapid loss of consciousness. They are used chiefly for the induction of anaesthesia (a smooth, quick transition through the excitement stage) and, by infusion, for maintenance (total intravenous anaesthesia) and sedation. Their speed of onset reflects rapid delivery to the well-perfused, lipid-rich brain.
Onset & Offset — Redistribution
After a single induction dose, consciousness is lost within one arm–brain circulation time (~30 s), as the drug reaches the brain. Recovery from that single dose is due mainly to redistribution of the drug from the brain to other tissues (muscle, then fat), not to its metabolism — so awakening is rapid even for drugs (like thiopentone) that are slowly metabolised. Repeated doses or infusions saturate the tissues and prolong recovery.
Agent Induction dose (IV) Key feature Propofol 1.5–2.5 mg/kg Smooth; anti-emetic; TIVA; pain on injection, hypotension Thiopentone 3–5 mg/kg Barbiturate; fast; avoid in porphyria; harmful if extravasated/intra-arterial Ketamine 1–2 mg/kg (IV) Dissociative; analgesic; maintains BP/airway; emergence phenomena Etomidate 0.3 mg/kg Cardiostable; adrenal suppression; myoclonus Midazolam 0.05–0.1 mg/kg Benzodiazepine; sedation/co-induction; amnesia The Ideal IV Agent
An ideal IV agent would be: water-soluble and stable; rapid, smooth onset in one circulation time; rapid recovery without hangover; cardiovascularly and respiratorily stable; non-irritant (no pain on injection, safe if extravasated); without histamine release or hypersensitivity; analgesic; anti-emetic; and cheap. As with inhalational agents, none is ideal, so the choice is individualised.
💡A key exam concept: waking after a single induction dose is due to redistribution, not metabolism. This is why thiopentone — slowly metabolised — still gives rapid initial recovery, but why repeated doses accumulate and cause a prolonged ‘hangover’.Mechanism (Brief)
Most IV agents (propofol, thiopentone, etomidate, benzodiazepines) act by potentiating the inhibitory neurotransmitter GABA at the GABA_A receptor, enhancing chloride influx and neuronal inhibition. Ketamine is the exception — it acts mainly by antagonising the excitatory NMDA receptor, producing ‘dissociative’ anaesthesia.
Combining Drugs — the Balanced Technique
In modern practice the intravenous induction agent is almost never used alone but as one element of a balanced technique: the hypnotic (propofol, thiopentone, etomidate or ketamine) provides unconsciousness, an opioid provides analgesia and blunts the pressor response to laryngoscopy, and a muscle relaxant is added when intubation or surgical relaxation is required. Because these drugs interact — often synergistically — the dose of each is reduced when they are combined, which improves cardiovascular stability and smoothness of induction but also means that respiratory depression and hypotension can be additive, so the drugs are titrated to effect rather than given in fixed doses.
Speed of Onset & the Effect-Site
The rapidity of an intravenous induction depends on how quickly the drug reaches its site of action in the brain, which is why the induction dose is delivered as a bolus into a flowing intravenous line and takes effect within an arm–brain circulation time. There is, however, a short delay between the peak blood concentration and the peak brain (effect-site) concentration — the drug must cross from plasma into the central nervous system — so the experienced anaesthetist injects and then waits for this equilibration before judging the effect, avoiding the error of giving a second dose too soon. A slow circulation time, as in the shocked or low-cardiac-output patient, prolongs the arm–brain time and a given dose reaches a higher peak concentration, so induction agents are given more slowly and in reduced dose in such patients.
Redistribution, not metabolism, terminates the effect of a single dose. 🔑KEY POINTS TO REMEMBER- IV agents: rapid loss of consciousness for induction; also infusion (TIVA) & sedation.
- Onset in one arm–brain circulation time; recovery from a single dose is by REDISTRIBUTION, not metabolism.
- Ideal agent: rapid smooth on/off, cardiostable, non-irritant, analgesic, anti-emetic, cheap — none is ideal.
- Most act via GABA_A potentiation; ketamine is an NMDA antagonist (dissociative).
- Repeated doses/infusions saturate tissues and prolong recovery.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Pharmacology
Propofol is the most widely used intravenous induction agent. It is presented as a white lipid emulsion and acts via GABA_A potentiation. Its induction dose is 1.5–2.5 mg/kg. It has a rapid onset and a rapid, clear recovery (short context-sensitive half-time), which — with its anti-emetic property — makes it excellent for day-surgery and for total intravenous anaesthesia (TIVA) by infusion.
Uses
Propofol is used for induction, maintenance (TIVA/TCI), and sedation (in ICU and for procedures). Its smooth recovery and anti-emetic effect are valued in day-case and in patients prone to postoperative nausea and vomiting.
Adverse Effects
Cardiovascular: dose-dependent hypotension (vasodilatation and myocardial depression) — marked in the elderly, hypovolaemic or cardiovascularly compromised. Respiratory: apnoea and respiratory depression at induction. Injection: pain on injection (reduced by a large vein and adding lidocaine). It has no analgesic effect. Rarely, prolonged high-dose infusion (especially in critically ill patients/children) causes propofol infusion syndrome.
⚠️Propofol causes significant hypotension and apnoea, particularly in the elderly, hypovolaemic or shocked patient — reduce the dose and titrate slowly in these patients, and have vasopressors and airway support ready.💡Propofol’s trio of advantages — rapid clear recovery, anti-emetic effect, and suitability for infusion — make it the agent of choice for day surgery and TIVA. Its main drawbacks are pain on injection and hypotension, and it provides no analgesia.Practical Points
Because it is a lipid emulsion, propofol supports bacterial growth, so strict asepsis and prompt use of opened ampoules are essential. Pain on injection is minimised by using a larger vein and co-administering lidocaine. It is combined with an opioid (for analgesia) and, where needed, a muscle relaxant.
Comparison & Place in Practice
Propofol has become the default induction agent precisely because its profile suits so much of modern, day-case and ambulatory anaesthesia: the recovery is not merely rapid but clear-headed, patients feel well, and the anti-emetic effect reduces one of the commonest causes of delayed discharge and patient dissatisfaction. Its ability to be run as an infusion, alone or as part of total intravenous anaesthesia, extends its usefulness from a single induction bolus to maintenance of anaesthesia and to sedation in the intensive care unit and for procedures, so a single familiar drug covers a very wide range of clinical needs.
Cautions & Special Populations
Propofol’s cardiovascular depression makes dose reduction essential in the elderly, the hypovolaemic and those with limited cardiac reserve, in whom a standard dose can produce profound hypotension; conversely, younger fit and anxious patients may need a larger dose. It should be injected into a running intravenous line in a larger vein to limit the pain on injection, and because the emulsion supports microbial growth, ampoules are drawn up with strict asepsis and used promptly, with any unused drug discarded. It is safe in porphyria, an advantage over thiopentone, and its lack of analgesic action means an opioid or regional technique must supply the analgesic component of the anaesthetic.
💡Sum propofol up as the day-case and TIVA agent: rapid clear-headed recovery, an anti-emetic effect and suitability for infusion — offset by pain on injection, hypotension and a complete lack of analgesia.⚠️Because propofol depresses the circulation and abolishes ventilation at induction, it must be titrated — not given as a fixed weight-based bolus — in the elderly, the hypovolaemic and the cardiovascularly compromised, in whom a standard dose can cause profound hypotension and apnoea; vasopressors and the means to support ventilation are always at hand.Marked hypotension and apnoea — titrate in the elderly. 🔑KEY POINTS TO REMEMBER- Propofol: commonest IV induction agent; lipid emulsion; GABA_A; dose 1.5–2.5 mg/kg.
- Rapid clear recovery + anti-emetic + infusible → ideal for day surgery & TIVA/TCI.
- Adverse: hypotension, apnoea, pain on injection; NO analgesia.
- Lipid emulsion supports bacterial growth — strict asepsis.
- Rare propofol infusion syndrome with prolonged high-dose infusion.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Pharmacology
Thiopentone (thiopental sodium) is an ultra-short-acting barbiturate used for induction (dose 3–5 mg/kg). It acts via GABA_A potentiation, has a very rapid onset (one arm–brain circulation time), and its brief action after a single dose is due to redistribution. It is prepared as an alkaline solution and was for decades the standard induction agent.
Effects & Uses
Thiopentone causes dose-dependent cardiovascular depression (hypotension) and respiratory depression/apnoea. It reduces cerebral metabolic rate and intracranial pressure, and has anticonvulsant properties — hence uses in neuroanaesthesia and in the control of status epilepticus. It is a useful agent for rapid-sequence induction. It has no analgesic action (indeed it may be anti-analgesic at low dose).
Problem Note Porphyria Absolutely contraindicated — may precipitate an acute attack Intra-arterial injection Severe pain, arterial spasm, thrombosis, distal ischaemia/gangrene Extravasation Tissue necrosis (alkaline solution) Accumulation Repeated doses/infusion → prolonged recovery (‘hangover’) ⚠️Thiopentone is absolutely contraindicated in porphyria (it can trigger a life-threatening acute attack). Accidental intra-arterial injection causes intense pain and arterial spasm that can lead to thrombosis and distal gangrene — a serious emergency.💡Remember thiopentone’s dangers: porphyria (absolute contraindication), intra-arterial injection (spasm, gangrene), and extravasation (necrosis, alkaline). Its virtues — rapid onset, reduced ICP and anticonvulsant action — give it a role in neuroanaesthesia and status epilepticus.Comparison with Propofol
Compared with propofol, thiopentone has a similarly rapid onset but a less clear recovery (more hangover, accumulation), is not suitable for maintenance infusion, and is not anti-emetic — which is why propofol has largely replaced it for routine induction, though thiopentone retains niche roles.
Pharmacokinetics & Cautions
Thiopentone illustrates the principle of redistribution more clearly than any other agent: a single dose wakes the patient within minutes as the drug moves from brain to muscle and fat, yet the drug is only slowly metabolised and eliminated, so repeated doses or an infusion saturate the tissues and produce a prolonged ‘hangover’ and delayed recovery. It is highly protein-bound and its free (active) fraction rises in hypoalbuminaemia, and its cardiovascular depression is exaggerated in the hypovolaemic or shocked patient, so the dose is reduced in the elderly, the frail and the haemodynamically compromised, in whom an over-large dose can cause dangerous hypotension.
Uses Beyond Routine Induction
Although largely displaced from routine induction, thiopentone retains value where its particular properties matter: its ability to lower cerebral metabolic rate and intracranial pressure makes it useful in neuroanaesthesia and in the management of raised intracranial pressure, and its anticonvulsant action underlies its use in the control of refractory status epilepticus. It also remains a familiar, inexpensive and rapidly-acting agent for rapid-sequence induction in settings where propofol is unavailable, so a sound understanding of its pharmacology and its dangers — porphyria, intra-arterial injection and extravasation — remains clinically relevant.
💡Carry three dangers of thiopentone into any answer: it is absolutely contraindicated in porphyria, intra-arterial injection threatens the limb through spasm and thrombosis, and extravasation of the alkaline solution causes tissue necrosis — while its virtues (reduced ICP, anticonvulsant action) keep it useful in neuroanaesthesia and status epilepticus.Contraindicated in porphyria. 🔑KEY POINTS TO REMEMBER- Thiopentone: ultra-short-acting barbiturate; GABA_A; induction 3–5 mg/kg; offset by redistribution.
- Reduces cerebral metabolic rate/ICP & is anticonvulsant → neuroanaesthesia, status epilepticus.
- Causes hypotension & apnoea; no analgesia; accumulates with repeat dosing.
- Absolute contraindication: PORPHYRIA; danger: intra-arterial injection (gangrene), extravasation (necrosis).
- Largely replaced by propofol for routine induction (less clear recovery, not infusible/anti-emetic).
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Pharmacology & ‘Dissociative’ Anaesthesia
Ketamine is unique among the IV agents: it acts mainly by antagonising the NMDA (glutamate) receptor and produces ‘dissociative anaesthesia’ — a trance-like, cataleptic state with profound analgesia and amnesia in which the eyes may remain open. It can be given intravenously (1–2 mg/kg) or intramuscularly (useful where IV access is difficult, e.g. children, field/disaster settings).
Distinctive Effects
Unlike other IV agents, ketamine is sympathomimetic — it tends to maintain or raise blood pressure and heart rate and to bronchodilate — and it relatively preserves airway reflexes and respiration. This makes it valuable in the shocked/hypovolaemic or asthmatic patient, in trauma and burns (dressings), and in paediatric and resource-poor settings. It provides potent analgesia even at sub-anaesthetic doses.
Adverse Effects
The main drawbacks are emergence phenomena — vivid dreams, hallucinations, delirium on waking (reduced by benzodiazepines and a quiet recovery) — increased secretions (an antisialagogue helps), and rises in intracranial and intra-ocular pressure and in heart rate/blood pressure, which limit its use in some patients. It can cause hypertension and tachycardia.
⚠️Ketamine raises intracranial pressure, intra-ocular pressure and blood pressure, so it is used cautiously (or avoided) in raised ICP, penetrating eye injury, and severe hypertension/ischaemic heart disease. Conversely, its cardiovascular stability makes it valuable in the shocked patient.💡Ketamine is the anaesthetist’s friend in the shocked, asthmatic or field patient: it provides analgesia, maintains blood pressure and airway, and bronchodilates. Its price is emergence phenomena (cover with a benzodiazepine) and rises in ICP/IOP.Practical Use & Combinations
Ketamine’s unusual profile makes it useful in situations that defeat other agents: it can be given intramuscularly when no vein is available, it provides analgesia and anaesthesia while largely maintaining ventilation and airway reflexes, and its bronchodilating, blood-pressure-supporting properties suit the asthmatic and the shocked trauma patient. In practice its unwanted effects are managed by co-administering a benzodiazepine to reduce emergence phenomena and an antisialagogue to control the increased secretions, and by recovering the patient in a calm, quiet environment; at low, sub-anaesthetic doses it is increasingly used purely for its analgesic and opioid-sparing effects.
Contraindications & the Balance of Effects
The decision to use ketamine is a balance between its valuable cardiovascular stability and analgesia and its unwanted rises in intracranial pressure, intra-ocular pressure, heart rate and blood pressure. It is therefore used cautiously or avoided in patients with a raised intracranial pressure, a penetrating eye injury, severe systemic or pulmonary hypertension, or significant ischaemic heart disease, in whom the sympathetic stimulation could be harmful, while it is positively indicated in the hypovolaemic, shocked, asthmatic or trauma patient in whom its blood-pressure-supporting, bronchodilating and airway-preserving effects are exactly what is wanted — a striking example of the same drug being contraindicated in one patient and ideal in another.
💡Ketamine is the drug that breaks the usual rules: an NMDA antagonist rather than a GABA drug, it supports rather than depresses the circulation and airway, provides analgesia, and can be given intramuscularly — at the cost of emergence phenomena and rises in intracranial and intra-ocular pressure.⚠️The same sympathomimetic effect that makes ketamine so valuable in shock makes it hazardous elsewhere: its rises in intracranial and intra-ocular pressure and in heart rate and blood pressure argue against its use in raised ICP, penetrating eye injury and severe cardiac or hypertensive disease, so the patient, not the drug’s reputation, decides whether it is the right choice.Preserves airway reflexes and cardiovascular stability — useful in shock. Effect Detail Mechanism NMDA receptor antagonist State produced Dissociative anaesthesia with analgesia Cardiovascular BP and heart rate rise — useful in shock Respiratory Airway reflexes preserved; bronchodilator Adverse Emergence delirium, ↑ secretions, ↑ ICP and IOP Uses Trauma, burns dressing, asthma, field anaesthesia 🔑KEY POINTS TO REMEMBER- Ketamine: NMDA antagonist → ‘dissociative’ anaesthesia with profound analgesia & amnesia; IV or IM.
- Sympathomimetic: maintains BP/HR, bronchodilates, preserves airway/respiration.
- Ideal in shock/hypovolaemia, asthma, trauma/burns, paediatric & field settings.
- Adverse: emergence phenomena (cover with benzodiazepine), secretions, ↑ICP/↑IOP, tachycardia/hypertension.
- Cautious/avoid in raised ICP, penetrating eye injury, severe hypertension/IHD.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Definition
Total intravenous anaesthesia (TIVA) is a technique of providing general anaesthesia entirely with intravenous drugs — with no inhalational agent. Typically a continuous propofol infusion provides hypnosis and a short-acting opioid (e.g. remifentanil) provides analgesia, with a muscle relaxant if needed. Infusions are often controlled by a target-controlled infusion (TCI) pump.
Target-Controlled Infusion (TCI)
A TCI pump uses pharmacokinetic models to calculate and continuously adjust the infusion rate needed to achieve and maintain a chosen target blood (or effect-site) concentration of the drug, which the anaesthetist titrates to clinical effect. This makes running an intravenous anaesthetic as controllable as adjusting a vaporiser.
Advantages & Indications
TIVA offers a smooth, clear recovery with less postoperative nausea and vomiting (propofol is anti-emetic), avoids the environmental pollution and the triggers of malignant hyperthermia associated with volatile agents, and gives a stable anaesthetic where inhalational agents are unsuitable. Specific indications: patients susceptible to malignant hyperthermia, those with severe PONV, neuroanaesthesia, procedures needing a shared airway (rigid bronchoscopy) or tubeless field, and transfers.
⚠️The danger of TIVA is awareness if the infusion fails — a disconnected, leaking or tissued IV line delivers no anaesthetic while a co-administered muscle relaxant masks the signs. The infusion line and cannula must be checked and visible, and depth-of-anaesthesia monitoring is often used.💡TIVA’s advantages — clear anti-emetic recovery, no MH trigger, no pollution, good for shared-airway and neuro cases — are balanced against its key risk of awareness if the IV fails; hence a secure, visible line and often processed-EEG monitoring.Context-Sensitive Half-Time
The suitability of a drug for infusion depends on its context-sensitive half-time — the time for its concentration to halve after stopping an infusion, which lengthens the longer the infusion has run. Propofol and remifentanil have short, relatively context-insensitive half-times, giving predictable rapid recovery even after long cases — which is why they are the mainstays of TIVA.
Depth Monitoring & Safe Conduct
Because the classic sign of light anaesthesia — movement — is abolished when a muscle relaxant is used, and because a failed intravenous line delivers no anaesthetic at all, the safe conduct of total intravenous anaesthesia depends on meticulous attention to the delivery system and to depth monitoring. The cannula and the whole length of the infusion line are kept visible and are checked for disconnection, leakage or tissuing; a dedicated cannula or an anti-reflux and anti-siphon valve arrangement is used; and processed-EEG depth-of-anaesthesia monitoring is often employed, particularly when relaxants are given, to reduce the risk of accidental awareness that is the technique’s most feared complication.
Advantages, Disadvantages & Indications Summary
Weighing up the technique, the advantages of total intravenous anaesthesia are a smooth and clear recovery with a low incidence of nausea and vomiting, the avoidance of the environmental pollution and the malignant-hyperthermia trigger associated with volatile agents, and haemodynamic and airway conditions that suit specific procedures; the disadvantages are the need for reliable, secure intravenous access, the greater dependence on equipment (infusion pumps and their programming), the cost, and the risk of awareness if delivery fails. These trade-offs explain its clear indications — the malignant-hyperthermia-susceptible patient, the patient with severe postoperative nausea, neuroanaesthesia, and operations on a shared or unprotected airway such as rigid bronchoscopy — where its benefits outweigh its demands.
⚠️Never forget the awareness risk that is unique to intravenous maintenance: if the cannula tissues or the line disconnects, no anaesthetic is delivered, yet a muscle relaxant can leave the patient paralysed and aware without any outward sign — which is why the line is kept visible and checked, anti-siphon and anti-reflux measures are used, and depth-of-anaesthesia monitoring is strongly advised whenever a relaxant accompanies TIVA.Preferred where malignant hyperthermia risk or PONV is a concern. 🔑KEY POINTS TO REMEMBER- TIVA = general anaesthesia with IV drugs only (no volatile) — usually propofol + short-acting opioid.
- TCI pumps target a chosen blood/effect-site concentration using pharmacokinetic models.
- Advantages: clear anti-emetic recovery, no MH trigger, no pollution; good for MH-risk, PONV, neuro, shared airway.
- Key risk: AWARENESS if the IV fails (relaxant masks signs) — keep line visible; use depth monitoring.
- Suitable drugs have a short context-sensitive half-time (propofol, remifentanil).
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Pharmacology & Use
Etomidate is an intravenous induction agent (dose 0.3 mg/kg) whose outstanding feature is cardiovascular stability — it causes minimal hypotension — so it is valued for inducing haemodynamically unstable, elderly or cardiac patients. It acts via GABA_A and has a rapid onset and recovery.
Adverse Effects
Its drawbacks are notable: pain on injection and involuntary myoclonus, a high incidence of postoperative nausea and vomiting, and — most importantly — adrenocortical suppression (it inhibits 11β-hydroxylase). Even a single induction dose transiently suppresses cortisol synthesis, and infusions are not used for this reason (associated with increased mortality in the critically ill).
💡Etomidate = cardiostable induction for the shocked or cardiac patient, but remember its adrenal suppression (11β-hydroxylase inhibition) — so it is not used as an infusion, and is used cautiously in the septic/critically ill.Why Not Use It as an Infusion
The reason etomidate is confined to single-dose induction, despite its attractive cardiovascular stability, is its effect on the adrenal cortex: by inhibiting the enzyme 11β-hydroxylase it suppresses cortisol synthesis, and studies of continuous etomidate sedation in critically ill patients showed increased mortality attributable to this adrenal suppression. Even a single induction dose causes a measurable, transient fall in cortisol, which is why the drug is used with particular caution in septic and critically ill patients, in whom an adequate stress cortisol response may be important for survival.
💡Etomidate is the induction agent for the haemodynamically fragile patient because it barely touches the blood pressure — but its 11β-hydroxylase inhibition and adrenal suppression are the reasons it is never run as an infusion and is used warily in sepsis.Note
Because even one dose lowers cortisol, etomidate is used thoughtfully in the septic patient, in whom an intact adrenal stress response may matter — and an infusion is never used.
💡In short, prize etomidate for a stable induction in the fragile heart, but respect its adrenal suppression.Cardiostable but suppresses cortisol — avoid infusions. 🔑KEY POINTS TO REMEMBER- Etomidate: IV induction agent (0.3 mg/kg); GABA_A; prized for cardiovascular stability.
- Ideal for haemodynamically unstable/cardiac/elderly induction.
- Adverse: pain on injection, myoclonus, PONV, and adrenal suppression (11β-hydroxylase).
- Not used as an infusion (adrenal suppression → harm in critically ill).
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.The Problem
Accidental intra-arterial injection of thiopentone (instead of intravenous) is a serious complication. The alkaline, irritant solution causes intense burning pain, arterial spasm and precipitation of crystals in the arterioles, leading to thrombosis and distal ischaemia that can progress to gangrene and loss of digits/the limb.
Recognition & Management
It is recognised by severe pain radiating distally on injection and blanching/mottling of the hand. Management: stop injecting but leave the cannula in situ (to deliver treatment); give intra-arterial vasodilators (e.g. papaverine), dilute with saline, provide analgesia, consider a sympathetic block (stellate ganglion/brachial plexus) to relieve spasm, and anticoagulation to limit thrombosis.
⚠️Prevent intra-arterial injection by confirming the cannula is venous before injecting an irritant drug. If it occurs, act at once — leave the cannula in, give vasodilators and analgesia, and consider a sympathetic block and anticoagulation to save the limb.💡The immediate step after accidental intra-arterial injection is do not remove the cannula — use it to deliver vasodilators, saline and analgesia — then treat spasm and thrombosis. Propofol and thiopentone should always be given into a confirmed vein.Why It Matters
Although rare now that most induction agents are less irritant and cannulation technique has improved, accidental intra-arterial injection remains a classic examination topic because it can cost a patient their hand: the combination of chemical irritation, arterial spasm and crystal precipitation produces a cascade of thrombosis and ischaemia that is difficult to reverse once established. This is why the emphasis is overwhelmingly on prevention — confirming free venous flashback and the absence of pulsatile flow before injecting — and, if it occurs, on immediate treatment through the cannula that is left in place.
Note
The first move if it happens is counter-intuitive but vital — leave the cannula where it is and treat through it — because it is the route by which vasodilators, saline and analgesia are delivered to the spasming, thrombosing artery.
Leave the cannula in, inject vasodilator, give heparin and block. 🔑KEY POINTS TO REMEMBER- Intra-arterial thiopentone: alkaline/irritant → pain, arterial spasm, thrombosis, distal gangrene.
- Recognise: severe distally-radiating pain + blanching on injection.
- Manage: leave cannula in, intra-arterial vasodilator (papaverine), saline, analgesia, sympathetic block, anticoagulate.
- Prevent: confirm venous placement before injecting irritant drugs.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Pharmacology & Uses
Midazolam is a short-acting, water-soluble benzodiazepine that acts via GABA_A to produce sedation, anxiolysis, amnesia and anticonvulsant effects (but no analgesia). It is used for premedication, sedation (for procedures/ICU), co-induction (reducing the dose of the main induction agent), and to treat seizures. Its amnesic effect is particularly useful.
Effects & Reversal
Midazolam causes dose-dependent respiratory depression (synergistic with opioids — a common cause of over-sedation) and some hypotension. Its effects can be reversed by flumazenil, a benzodiazepine antagonist (used cautiously, as it is short-acting and can precipitate seizures/withdrawal).
💡Midazolam gives sedation, anxiolysis and amnesia but no analgesia; beware synergistic respiratory depression with opioids. Its antagonist is flumazenil — short-acting, so re-sedation can occur.Comparison with Other Benzodiazepines
Midazolam is preferred over older benzodiazepines such as diazepam for anaesthetic use because it is water-soluble in its formulation (so it does not cause the venous irritation of diazepam) yet becomes lipid-soluble at body pH to enter the brain rapidly, and because its short duration suits the perioperative setting. Its powerful amnesic effect is valued for unpleasant procedures, but its respiratory depression is markedly potentiated by opioids, so when the two are combined for sedation the doses are reduced and the patient is monitored closely for airway obstruction and hypoventilation.
💡Midazolam gives sedation, anxiolysis and amnesia with no analgesia, is reversed by the short-acting flumazenil, and its respiratory depression is dangerously additive with opioids — the three facts most worth remembering.Note
Because its respiratory depression combines dangerously with opioids, doses of both are reduced when they are used together for sedation, and the patient is watched closely for hypoventilation and airway obstruction.
💡In short, midazolam calms and erases memory but does not relieve pain, and its antidote is flumazenil.Excellent anterograde amnesia — valued for premedication. 🔑KEY POINTS TO REMEMBER- Midazolam: water-soluble short-acting benzodiazepine (GABA_A); sedation, anxiolysis, amnesia, anticonvulsant; no analgesia.
- Uses: premedication, procedural/ICU sedation, co-induction, seizures.
- Respiratory depression (synergistic with opioids) & hypotension.
- Reversed by flumazenil (short-acting → watch for re-sedation).
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Definition
Propofol infusion syndrome (PRIS) is a rare but potentially fatal complication of prolonged, high-dose propofol infusion — classically in critically ill patients and children sedated in intensive care for long periods. It is thought to result from impaired mitochondrial fatty-acid metabolism.
Features & Management
It is characterised by severe metabolic (lactic) acidosis, rhabdomyolysis, hyperkalaemia, acute kidney injury, lipaemia, and cardiac failure/arrhythmias that can be refractory and fatal. Management is to stop propofol immediately, switch to an alternative sedative, and provide supportive care (correct acidosis, cardiovascular and renal support, sometimes haemofiltration). Prevention is by avoiding prolonged high-dose infusion and monitoring for early acidosis.
⚠️Suspect PRIS in any patient on a prolonged high-dose propofol infusion who develops an unexplained metabolic acidosis, rising lactate or arrhythmia — stop the propofol at once. It is largely a syndrome of ICU sedation, not of short operative infusions.Recognition in the ICU
The importance of propofol infusion syndrome lies in recognising it early, because once established it is often refractory and fatal: the warning signs are an unexplained and worsening metabolic acidosis with a rising lactate, new arrhythmias or a widening QRS, and evidence of rhabdomyolysis in a patient who has been receiving propofol at high dose for more than a day or two. The response is to stop propofol immediately and switch to an alternative sedative, alongside aggressive supportive care, which is why sedation guidelines cap the dose and duration of propofol infusions and encourage vigilance for early acidosis.
💡Suspect propofol infusion syndrome whenever a patient on a prolonged, high-dose propofol infusion develops an unexplained metabolic acidosis and rising lactate; the treatment is simple in principle — stop the propofol at once and support the patient — but the syndrome is often fatal once established, so prevention and early recognition are everything.💡In short, a rising lactate on long-term propofol is propofol infusion syndrome until proven otherwise.Limit dose and duration in intensive care sedation. 🔑KEY POINTS TO REMEMBER- PRIS: rare, fatal complication of prolonged high-dose propofol infusion (ICU, children).
- Impaired mitochondrial fatty-acid metabolism.
- Features: metabolic acidosis, rhabdomyolysis, hyperkalaemia, AKI, cardiac failure/arrhythmia.
- Stop propofol immediately + supportive care; prevent by avoiding prolonged high-dose infusion.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Definition
The context-sensitive half-time is the time taken for the plasma concentration of a drug to fall by half after stopping a continuous infusion — where the ‘context’ is the duration of the infusion. Unlike the elimination half-life, it takes account of the drug’s distribution into tissues during the infusion, and for most drugs it increases the longer the infusion has run.
The context-sensitive half-time rises with infusion duration for most drugs (e.g. fentanyl) but stays almost flat for remifentanil — which is why it gives rapid, predictable offset. Clinical Importance
It predicts how quickly a patient will recover after an infusion is stopped, and hence which drugs are suitable for TIVA. Remifentanil has an almost flat, very short context-sensitive half-time (it is broken down by tissue esterases independent of infusion duration), giving rapid offset however long it runs; propofol’s remains short; whereas drugs like fentanyl accumulate, so their half-time lengthens markedly with prolonged infusion.
💡The context-sensitive half-time, not the elimination half-life, tells you how fast someone wakes after an infusion. Remifentanil’s is short and flat (esterase metabolism), which is why it is ideal for infusion.🔑KEY POINTS TO REMEMBER- Context-sensitive half-time = time for concentration to halve after stopping an infusion of given duration.
- Accounts for tissue distribution; usually lengthens the longer the infusion runs.
- Predicts recovery after infusion → which drugs suit TIVA.
- Remifentanil: flat/short (esterase metabolism); propofol short; fentanyl accumulates.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Pharmacology
Fentanyl is a synthetic opioid and a potent μ-receptor agonist, roughly 100 times as potent as morphine. It is highly lipid-soluble, giving a rapid onset and short duration after a bolus (offset by redistribution), which makes it a mainstay of intra-operative analgesia and of blunting the pressor response to laryngoscopy.
Uses & Effects
It is used to provide analgesia during anaesthesia, as part of balanced anaesthesia, and for procedural and postoperative pain. Effects (class effects of μ-agonists): analgesia, respiratory depression (dose-dependent — the main danger), sedation, bradycardia, nausea/vomiting, miosis, and (with large/repeated doses) accumulation. Unlike morphine it causes little histamine release.
⚠️The principal danger of fentanyl (and all opioids) is dose-dependent respiratory depression, potentiated by other sedatives; monitor ventilation and oxygenation, and remember its effect can outlast a single stimulus. Reverse with naloxone if needed.💡Fentanyl — ~100× morphine, fast on/short (redistribution), little histamine — is the workhorse intra-operative opioid; its cardinal risk is respiratory depression, reversible with naloxone. Related agents: alfentanil (faster), remifentanil (ultra-short, esterase-metabolised).Related Opioids
Fentanyl belongs to a family of synthetic opioids that differ mainly in their speed and duration: alfentanil has a faster onset and shorter action, useful for brief intense stimuli, while remifentanil is metabolised by non-specific tissue and plasma esterases so that its effect ends within minutes of stopping an infusion regardless of how long it has run, making it ideal for titratable intra-operative analgesia. All share the μ-agonist effects and the cardinal danger of respiratory depression, and all can be reversed by naloxone, so the choice between them is largely a matter of the required onset and offset.
💡Fentanyl is the intra-operative opioid workhorse: about a hundred times as potent as morphine, quick on and short after a bolus because of redistribution, with little histamine release — and, like every opioid, dangerous chiefly for its respiratory depression, which naloxone reverses.Chest wall rigidity may follow rapid high-dose injection. 🔑KEY POINTS TO REMEMBER- Fentanyl: synthetic μ-agonist ~100× morphine; lipid-soluble → rapid onset, short bolus action.
- Used for intra-operative & procedural analgesia; blunts laryngoscopy pressor response.
- Effects: analgesia, respiratory depression (main danger), bradycardia, nausea; little histamine.
- Reverse with naloxone; relatives alfentanil (faster) & remifentanil (ultra-short).
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.Definition & Use
Naloxone is a competitive opioid (μ-receptor) antagonist used to reverse the effects of opioids — principally life-threatening respiratory depression and sedation, in opioid overdose or excessive perioperative opioid effect. It is given intravenously (also IM/intranasal) and titrated in small doses to restore adequate breathing.
Key Points
Naloxone has a rapid onset but a short duration of action — often shorter than the opioid it is reversing — so re-sedation and respiratory depression can recur, requiring repeated doses or an infusion and continued monitoring. Reversing opioids also reverses analgesia (causing pain, hypertension, tachycardia) and can precipitate acute withdrawal in opioid-dependent patients, so it is titrated carefully.
💡Give naloxone in small titrated doses to reverse respiratory depression while preserving some analgesia, and watch for re-narcotisation — naloxone is often shorter-acting than the opioid, so effects can return and repeat doses/an infusion may be needed.Wider Uses & Cautions
Beyond the operating theatre, naloxone is a cornerstone of the emergency management of opioid overdose, where it is given by any available route to restore breathing, and take-home naloxone programmes have extended its use into the community. The same cautions apply everywhere: it is short-acting relative to many opioids, so the patient must be observed for the return of respiratory depression after the initial response; and in the opioid-dependent patient a large dose can precipitate a distressing acute withdrawal syndrome, so it is titrated to restore adequate ventilation rather than to fully reverse all opioid effect.
💡The trap with naloxone is its short duration: it may wear off before the opioid it reversed, so the patient can become re-narcotised, and it is therefore titrated to restore breathing and the patient kept under observation, with repeat doses or an infusion ready.Note
In opioid overdose naloxone can be given by almost any route to restore breathing, but the same short duration means the patient is never left unobserved after an apparent recovery.
Shorter acting than most opioids — observe or infuse. 🔑KEY POINTS TO REMEMBER- Naloxone: competitive μ-opioid antagonist; reverses opioid respiratory depression/sedation.
- Titrate in small IV doses to restore breathing while preserving some analgesia.
- Short-acting — shorter than many opioids → re-sedation can recur (repeat doses/infusion, monitor).
- Reverses analgesia & can precipitate acute withdrawal in dependence.
📚SOURCES: Morgan & Mikhail’s Clinical Anesthesiology; Miller’s Anesthesia; Ajay Yadav’s Short Textbook of Anaesthesia.