GC001 How Would You Anaesthetise Me - Pharmacology Of Anaesthetic Drugs
The pharmacology of anaesthetic drugs encompasses the mechanisms of action, pharmacokinetics, and pharmacodynamics of intravenous induction agents, inhalational anaesthetics, neuromuscular blocking agents, opioids, and local anaesthetics used to achieve the triad of unconsciousness, analgesia, and muscle relaxation during general anaesthesia.
How Would You Anaesthetise Me? — Pharmacology of Anaesthetic Drugs
Big Idea: This lecture walks through the entire perioperative anaesthetic journey from the patient's perspective — what happens before, during, and after general anaesthesia — while systematically introducing the pharmacology of every drug class used. It also covers regional anaesthesia, its types, and its complications. Think of it as "a guided tour through the operating theatre, with drug names attached to every step."
Learning Objectives (from the lecture): [1]
- Describe the purpose of general anaesthesia and the means to achieve it
- Name and classify commonly used anaesthetic and analgesic drugs
- Name some types of regional anaesthesia
How this fits into exams: This is a GC001 lecture — the very first General Clerkship anaesthesia lecture. Past papers repeatedly test fasting rules, drug classifications (especially muscle relaxants and their reversal), analgesic drugs used perioperatively, local anaesthetic toxicity, and the concept of "balanced anaesthesia." The 2025 MCQ directly asked about which intraoperative analgesic would NOT reduce postoperative pain (remifentanil — because its ultra-short half-life means it's gone before recovery). [2]
General anaesthesia (GA): Reduced level of consciousness and response to stimuli [1]
Regional anaesthesia (RA): Loss of sensation to a body part or region — patient can be fully awake, sedated, or unconscious [1]
Monitored Anaesthetic Care (MAC) / "Conscious Sedation": Patient sedated and should be self-ventilating. Anaesthesiologist should be present at all times. [1]
| Type | Consciousness | Ventilation | Key Feature |
|---|---|---|---|
| GA | Unconscious | Controlled (mechanical) | Full loss of awareness and reflexes |
| RA | Awake → unconscious (spectrum) | Usually spontaneous | Nerve blockade of a region |
| MAC | Sedated but rousable | Self-ventilating | Continuous anaesthesiologist monitoring |
| Combined GA + RA | Unconscious | Controlled | Best of both worlds (e.g., GA + epidural) |
Why combinations? Some surgeries require both muscle relaxation (GA) and excellent regional analgesia (epidural for thoracotomy). Regional techniques also reduce the total dose of systemic drugs needed, improving haemodynamic stability and postoperative pain control.
"Anaesthesia" = without sensation. Reversible (hopefully!). Providing general anaesthesia involves more than just dampening sensation. [1]
From the patient's perspective: "I don't want to feel or remember anything." From the surgeon's perspective: "I want the patient's muscles to be relaxed and don't want any movements."
The Five Objectives of GA
Hypnosis, Amnesia, Analgesia, Areflexia, +/- Muscle Relaxation [1]
| Objective | What it means | Why it's needed | Drug class achieving it |
|---|---|---|---|
| Hypnosis | Loss of consciousness | Patient unaware during surgery | Induction agents, volatile agents, propofol |
| Amnesia | No memory formation | Prevent psychological trauma of awareness | Same as hypnosis agents; midazolam adds amnesia |
| Analgesia | Pain abolition | Body still "feels" surgical trauma even when unconscious → stress response | Opioids, regional techniques, paracetamol, NSAIDs |
| Areflexia | Suppression of autonomic reflexes | Prevent dangerous reflex responses (laryngospasm, bradycardia, hypertension) | Opioids, deeper anaesthesia |
| Muscle relaxation | Paralysis of skeletal muscle | Facilitate intubation, surgical access (abdominal surgery), prevent movement | Neuromuscular blocking agents |
Why Analgesia Matters Even Under GA
Just because the patient is unconscious does NOT mean the body stops responding to surgical pain. Nociceptive signals still travel → sympathetic activation → tachycardia, hypertension, increased oxygen consumption. This "stress response" worsens outcomes. That's why we give opioids and analgesics intraoperatively — not just for the patient's comfort, but to blunt harmful physiological responses.
This is the concept of balanced anaesthesia: using a combination of drugs at lower doses, each targeting a different objective, to minimize side effects while optimizing all five goals. [3]
3. Perioperative Sequence — Step by Step
History (general, anaesthetic history — especially risk for aspiration), Examination (CVS, Respiratory, Airway, other relevant parts), Investigations [1]
Anaesthetic history is critical: previous difficult intubation, adverse reactions to anaesthetic drugs, family history of malignant hyperthermia, history of PONV (post-operative nausea and vomiting).
Airway assessment: Mallampati score, thyromental distance, mouth opening, neck extension, presence of dentures/loose teeth — all predict difficulty of intubation.
3.2 Preparation of the Patient
Instructions regarding comorbidities, medications, fasting instructions, other preparations (e.g., bringing CPAP machine to hospital) [1]
Minimize the chance of aspiration during induction of and emergence from anaesthesia [1]
| Substance | Fasting Time |
|---|---|
| Clear fluids (water, clear juice without pulp, carbonated beverages, carbohydrate-rich nutritional drinks, clear tea, black coffee) | 2 hours |
| Breast milk | 4 hours |
| Infant formula | 6 hours |
| Solids and non-human milk | 6 hours |
High Yield — Fasting Rules
The 2-4-6 fasting rule is one of the most commonly tested facts in anaesthesia. Remember: "2 clear, 4 breast, 6 solid." Some sources add an 8-hour rule for heavy/fatty meals. The rationale is that during induction and emergence, protective airway reflexes are lost → risk of regurgitation and pulmonary aspiration of gastric contents (Mendelson's syndrome), which causes severe chemical pneumonitis.
Common Mistake
Students often think fasting is only needed for GA. The lecture explicitly states: "Prepare everything for the patient as for general anaesthesia — THAT INCLUDES FASTING — even if regional anaesthesia is planned!!!" [1] Why? Because RA may fail or complications may arise, requiring emergency conversion to GA.
| Drug Class | Action | Rationale |
|---|---|---|
| Anticoagulants (warfarin, NOACs) | Stop 3–4 half-lives before; consider bridging | Risk of surgical bleeding; interaction with neuraxial blocks [3] |
| Antiplatelets (clopidogrel) | Stop 5–7 days before elective surgery | Bleeding risk |
| SGLT2 inhibitors (-gliflozins) | Stop 2 days before | Risk of euglycaemic DKA perioperatively |
| Insulin | Modified regimen based on fasting | Hypoglycaemia risk during fasting |
| Antihypertensives, bronchodilators, anticonvulsants | Usually continue | Abrupt cessation causes rebound |
| ACE inhibitors/ARBs | Often held morning of surgery | Risk of refractory intraoperative hypotension |
Before induction: Pulse oximetry, Blood pressure, ECG. After induction: End-tidal CO₂ monitoring [1]
Why end-tidal CO₂ (ETCO₂)? After intubation, capnography confirms correct ETT placement (CO₂ waveform present = tube in trachea, not oesophagus). It also monitors ventilation adequacy throughout surgery. This is arguably the single most important safety monitor after induction.
Induction → Maintenance → Emergence and Recovery [1]
4. Pharmacology of Induction Agents
Induction: the process of causing general anaesthesia by the administration of pharmaceutics [1]
Most commonly via the intravenous route. Inhalational route can be used. [1]
Propofol, Thiopentone, Etomidate, Ketamine [1]
| Agent | Mechanism | Onset / Duration | Advantages | Disadvantages | Special Notes |
|---|---|---|---|---|---|
| Propofol | Positive modulation of GABA-A receptor → global CNS depression | Rapid onset (15–30s); short duration (5–10 min) | Smooth induction, antiemetic properties, can be used for both induction AND maintenance (TIVA) | Pain on injection, myocardial depression (↓BP, bradycardia), respiratory depression | "The white stuff" — most commonly used (~90% of cases) [3] |
| Thiopentone (thiopental) | Barbiturate — enhances GABA-A | Very rapid onset; ultra-short acting (redistribution) | Rapid, reliable | Cardiovascular depression, tissue necrosis if extravasated, NO analgesic properties, porphyria contraindication | Historically important; less used now |
| Etomidate | GABA-A modulation | Rapid onset | Haemodynamically stable — minimal cardiovascular effects | Adrenocortical suppression (inhibits 11β-hydroxylase), myoclonus, pain on injection | Used when haemodynamic stability is critical (e.g., cardiac patients, hypovolaemia) |
| Ketamine | Non-competitive NMDA receptor antagonist | Onset ~1 min; duration 10–15 min | Stable haemodynamics (↑BP, ↑HR — sympathomimetic), bronchodilation, potent analgesia, can be given IM | Emergence phenomena (hallucinations, nightmares), ↑secretions, ↑ICP, ↑IOP | Does NOT drop BP — useful in trauma/haemodynamic instability [3] |
High Yield — When to Use Which Induction Agent
- Propofol: Default for most patients. Smooth, antiemetic, versatile.
- Etomidate: When you CANNOT afford a BP drop (e.g., shocked patient, severe cardiac disease).
- Ketamine: When you need haemodynamic stability AND analgesia (trauma, paediatrics, asthma — bronchodilation).
- Thiopentone: Niche use; historically for rapid sequence induction. Contraindicated in porphyria.
Sevoflurane, Nitrous Oxide [1]
- Sevoflurane ("the yellow stuff" [3]): Non-irritant to airways → suitable for inhalational induction, especially in children (paediatric patients who can't tolerate IV cannulation before induction)
- Nitrous oxide (N₂O, "laughing gas", Entonox when mixed 50:50 with O₂): Weak anaesthetic on its own, used as an adjunct. Provides mild analgesia and reduces the MAC of volatile agents.
Why gas induction? In children or needle-phobic patients, you can hold a mask with sevoflurane over the face → child breathes in → loses consciousness → THEN establish IV access.
5. Neuromuscular Blocking Agents ("Muscle Relaxants")
Non-depolarising and Depolarising [1]
"This is one reason why we need muscle relaxants when administering general anaesthesia" [1] — referring to the need to pass an endotracheal tube through the vocal cords. Without paralysis, the vocal cords are adducted and intubation is difficult/traumatic. Relaxants also provide the immobility surgeons need.
| Type | Subtype | Examples | Onset | Duration | Key Points |
|---|---|---|---|---|---|
| Non-depolarising | Short-acting | Mivacurium | Slower | ~15 min | Competitive antagonist at nicotinic AChR |
| Intermediate-acting | Atracurium, Cis-atracurium, Rocuronium, Vecuronium | 60–90s (Roc), 3 min (Atr) | 30–45 min | Rocuronium: most commonly used; Atracurium: Hofmann elimination (non-organ dependent — useful in liver/renal failure) | |
| Long-acting | Pancuronium | Slower | 60–90 min | Vagolytic → tachycardia | |
| Depolarising | — | Suxamethonium (succinylcholine / "scoline") | Rapid: 45 seconds | Ultra-short: 9–10 min | Initial fasciculations → depolarisation block. Side effects: hyperkalaemia, ↑ICP, ↑IOP, malignant hyperthermia, suxamethonium apnoea |
High Yield — Suxamethonium
Suxamethonium has the fastest onset of any NMB (45 seconds), making it the drug of choice for Rapid Sequence Induction (RSI) when the airway must be secured immediately (e.g., emergency surgery, full stomach, aspiration risk). However, it has significant side effects:
- Hyperkalaemia: Dangerous in burns (> 24h old), spinal cord injury, neuromuscular diseases, prolonged immobility — due to upregulation of extrajunctional nicotinic receptors → massive K⁺ efflux
- Malignant hyperthermia: Rare but fatal if untreated (treat with dantrolene)
- Suxamethonium apnoea: Patients with pseudocholinesterase deficiency cannot metabolize it → prolonged paralysis
- Fasciculations → muscle pain, ↑IOP, ↑ICP, ↑intragastric pressure
Due to these side effects, avoid suxamethonium unless absolutely necessary [3]
Rocuronium at high dose (1.2 mg/kg) can now be used as an alternative for RSI, especially since sugammadex can rapidly reverse it.
Nerve stimulator used to assess degree of neuromuscular blockade [1]
Train-of-Four (TOF): Four stimuli at 0.5-second intervals applied to the ulnar nerve; count the number of twitches. Typically aim for 2/4 twitches during surgery. Full recovery = TOF ratio ≥ 0.9 (all 4 twitches with < 10% fade). [3]
After induction and muscle relaxation:
Instrument airway → Endotracheal tube (ETT) secured with tape → connected to anaesthetic machine via the circuit → ventilator pumps gases into lungs [1]
- ETT (Endotracheal tube): Gold standard for definitive airway. Cuffed tube placed through the vocal cords into the trachea. Provides airway protection against aspiration.
- LMA (Laryngeal Mask Airway): Supraglottic device. Less invasive, does NOT protect against aspiration. Used for shorter, less invasive procedures.
- Video laryngoscopy: Modern technique allowing visualization of vocal cords on screen → improved first-pass success.
Why ventilate between giving the relaxant and intubation? NMBs take 60–90 seconds (rocuronium) to 3 minutes (atracurium) to work. During this time, the patient cannot breathe → must bag-mask ventilate to maintain oxygenation. [3]
7. Maintenance of Anaesthesia
Continuous administration of a maintenance anaesthetic agent, usually in combination with an analgesic agent. Inhalational or intravenous route. [1]
Isoflurane, Sevoflurane, Desflurane, +/- Nitrous Oxide [1]
| Agent | Key Feature | MAC (% atm) | Blood:Gas Partition Coefficient | Notes |
|---|---|---|---|---|
| Sevoflurane | Non-irritant, pleasant smell | ~2.0 | 0.65 (low → fast onset/offset) | Good for induction AND maintenance |
| Desflurane | Very low blood solubility | ~6.0 | 0.42 (very low → fastest onset/offset) | Pungent — NOT for inhalational induction; excellent for rapid emergence; requires heated pressurized vaporizer |
| Isoflurane | Cost-effective | ~1.15 | 1.46 | Pungent; coronary steal controversy |
| Nitrous oxide | Weak agent; used as adjunct | ~105 (> 100 → cannot produce anaesthesia alone) | 0.47 | Second gas effect; diffusion hypoxia; avoid in closed gas spaces (bowel obstruction, pneumothorax) |
Concept: MAC (Minimum Alveolar Concentration) — The concentration of inhaled anaesthetic at 1 atm that prevents movement in response to a surgical stimulus in 50% of patients. Think of it as the ED50 for volatile agents. Lower MAC = more potent agent. MAC is additive — combining agents reduces the concentration of each needed.
Monitoring volatile agents: The anaesthetic monitor displays both inspiratory (what goes in) and end-tidal (what comes out) concentrations. At steady state, end-tidal concentration approximates brain concentration. The vaporizer dial adjusts the concentration delivered. [1]
Propofol [1]
- Propofol infusion for both induction and maintenance, often combined with remifentanil infusion
- Target-Controlled Infusion (TCI): Computerized pump calculates dose based on patient weight and age to maintain a target plasma or effect-site concentration [3]
- Advantages: No atmospheric pollution, reduced PONV, smooth emergence
- Requires BIS (Bispectral Index) monitoring to titrate depth of anaesthesia (since you can't measure propofol concentration like end-tidal volatile agent)
8. Analgesic Agents Used Perioperatively
"Just because the patient is not aware of the trauma, does your body still 'feel' the pain?" [1] — YES, the surgical stress response occurs regardless of consciousness.
Simple: Paracetamol (PO, IV, PR), NSAIDs & COX-2 inhibitors (IV, suppositories) [1] Opioids: Fentanyl (IV, SC), Morphine (IV, PO), Oxycodone (IV, PO), Pethidine (IV) [1] Others: Tramadol, Gabapentinoids, Ketamine, Regional Techniques [1]
| Drug | Route | Key Points |
|---|---|---|
| Paracetamol | PO, IV, PR | Central mechanism (likely COX-3 / endocannabinoid pathway); safe, ceiling effect, hepatotoxic in overdose |
| NSAIDs (e.g., diclofenac, ketorolac) | PO, IV, PR | COX-1/2 inhibition → ↓prostaglandin synthesis; risks: GI bleeding, renal impairment, platelet dysfunction |
| COX-2 inhibitors (e.g., celecoxib, parecoxib IV) | PO, IV | Less GI/platelet side effects; CV risk with prolonged use |
| Fentanyl | IV, SC | Potent synthetic opioid; 100× more potent than morphine; rapid onset, short duration; used at induction to blunt intubation response |
| Morphine | IV, PO | Gold standard opioid; longer duration; histamine release → hypotension; active metabolite M6G accumulates in renal failure |
| Oxycodone | IV, PO | Semi-synthetic; less histamine release than morphine |
| Pethidine | IV | Synthetic opioid; less biliary spasm; risk of serotonin syndrome with MAOIs; norpethidine metabolite → seizures |
| Remifentanil | IV infusion | Ultra-short acting (ester hydrolysis, t½ ~3 min); ideal for TIVA maintenance; NO postoperative analgesia |
| Tramadol | PO, IV | Weak µ-agonist + NE/5-HT reuptake inhibition; less respiratory depression; risk of seizures, serotonin syndrome |
| Gabapentinoids (gabapentin, pregabalin) | PO | α2δ calcium channel ligands; reduce opioid requirements; used for neuropathic pain component |
| Ketamine (sub-anaesthetic dose) | IV | NMDA antagonist; anti-hyperalgesic; opioid-sparing; useful in chronic pain patients |
Exam Trap — Remifentanil
Remifentanil is metabolized by plasma esterases with a context-sensitive half-time of ~3 minutes. This means it provides excellent intraoperative analgesia but gives ZERO postoperative pain relief — it's completely gone by the time the patient wakes up. The 2025 MCQ asked: "Which drug given intraoperatively would NOT be useful for reducing pain after surgery?" Answer: Remifentanil (Option C). [2] Morphine, pethidine, and tramadol all have longer durations and provide postoperative analgesia.
Naloxone — pure µ-opioid antagonist. 0.4 mg IV q2min (max 2 mg). Reverses respiratory depression, but also reverses analgesia. Short half-life → may need re-dosing (risk of re-narcotization). [4]
To reverse neuromuscular blockade, NOT hypnosis [1]
| Agent | Mechanism | Reverses | Key Points |
|---|---|---|---|
| Neostigmine + anticholinergic | Anticholinesterase → ↑ACh at NMJ to outcompete non-depolarising NMB | All non-depolarising agents | Must co-administer atropine or glycopyrrolate to block muscarinic side effects (bradycardia, ↑secretions, bronchoconstriction) |
| Sugammadex | Modified γ-cyclodextrin that encapsulates steroidal NMBs | Rocuronium (and vecuronium) ONLY | Rapid, complete reversal; can reverse even deep block; expensive; does NOT work for atracurium or suxamethonium |
| Flumazenil | Competitive antagonist at benzodiazepine receptor | Benzodiazepine sedation | 0.2 mg IV q1min (max 1 mg); risk of resedation and seizures [4] |
| Naloxone | µ-opioid receptor antagonist | Opioid effects | See above |
High Yield — Neostigmine + Atropine, Why Together?
Neostigmine is a cholinesterase inhibitor → increases ACh at ALL cholinergic synapses (nicotinic AND muscarinic). At the NMJ (nicotinic), this reverses the paralysis. But at muscarinic receptors (heart, gut, secretory glands), excess ACh causes dangerous bradycardia, excessive secretions, and bronchoconstriction. Therefore, an anticholinergic (atropine or glycopyrrolate) is ALWAYS co-administered to block these muscarinic effects while allowing the nicotinic reversal to occur.
Emergence: process of return to baseline physiologic function of all organ systems after the cessation of administration of general anaesthetic agent(s) [1]
Steps:
- Turn off volatile agent / stop propofol infusion
- Increase fresh gas flow to "wash out" volatile agent
- Reverse NMB (if residual) — assess with nerve stimulator
- Suction oropharynx
- Patient regains consciousness, spontaneous breathing, protective reflexes
- Extubate when criteria met (adequate tidal volume, responds to commands, TOF ≥ 0.9, no residual respiratory depression)
Risks during emergence: Laryngospasm, bronchospasm, aspiration (hence fasting!), awareness, agitation/delirium, PONV, shivering.
11. Postoperative Management
Oral analgesia, Parenteral analgesia, Infusion, Patient Controlled Analgesia (PCA), Continuation of Regional Block (Epidural, Catheters along major plexus & nerves) [1]
Multimodal analgesia is the standard approach: combining paracetamol + NSAID + opioid ± regional technique to target different pain pathways, reduce opioid consumption, and minimize side effects (the WHO analgesic ladder adapted for acute pain).
PCA (Patient Controlled Analgesia): Patient presses a button to self-administer a pre-set bolus of morphine IV. Lock-out interval prevents overdose. Empowers the patient and provides more consistent pain control than PRN dosing.
Home, Ward, High Dependency Unit (HDU), Intensive Care Unit (ICU). If you are not sure, ask the anaesthesiologist. [1]
Factors determining disposition: premorbid status, nature/length of operation, intraoperative events, anticipated postoperative complications, level of monitoring/support needed. [5]
12. Regional Anaesthesia (RA) — Detailed
Established by the deposition of local anaesthetic in close proximity to a nerve or a group of nerve fibres. The local anaesthetic blocks transmission of signals → reduced sensation from the anatomical area supplied by the blocked nerves. [1]
How LAs work: LAs block voltage-gated Na⁺ channels on the intracellular side → prevent depolarization → prevent action potential propagation. Smaller, unmyelinated fibres (pain, temperature) are blocked first, larger myelinated fibres (motor) last. This is why you can have sensory block without complete motor block at lower concentrations.
Neuroaxial Blocks (Spinal, Epidural), Plexus blocks, Nerve blocks, Local infiltration, Topical anaesthesia, Intravenous regional technique [1]
| Type | Site of LA Deposition | Key Features |
|---|---|---|
| Spinal (subarachnoid / intrathecal) | Into CSF | Dense block ("temporary paraplegia"); motor + sensory; single injection; rapid onset; used for lower abdominal/pelvic/lower limb surgery; e.g., C-section |
| Epidural | Epidural space (outside dura) | Variable motor/sensory block; can place catheter for continuous infusion; used for labour analgesia, thoracic/abdominal surgery |
| Plexus block | Near nerve plexus (e.g., brachial plexus) | Arm surgery |
| Nerve block | Near individual nerve (e.g., femoral nerve) | Specific dermatome/myotome |
| Local infiltration | Directly into tissues | Minor procedures (wound suturing, excisions) |
| Topical | Skin/mucosal surface | EMLA cream (lignocaine + prilocaine), lignocaine spray for laryngoscopy |
| IV regional (Bier's block) | IV injection into exsanguinated limb with tourniquet | Short procedures on forearm/hand |
| LA | Class | Onset | Duration | Max Dose (without / with adrenaline) | Key Points |
|---|---|---|---|---|---|
| Lignocaine (Lidocaine) | Amide | Fast (< 2 min) | ~1.5h | 3 mg/kg / 7 mg/kg | Most commonly used; also anti-arrhythmic |
| Bupivacaine | Amide | Slow | 3–4h | 2–2.5 mg/kg | Most cardiotoxic; preferred for spinal/epidural due to long duration |
| Ropivacaine | Amide | Intermediate | 3–4h | 3 mg/kg | Less cardiotoxic than bupivacaine; less motor block |
| Levobupivacaine | Amide | Intermediate | 3–4h | Same as bupivacaine | S-enantiomer of bupivacaine; fewer side effects |
| Prilocaine | Amide | — | — | 6 mg/kg | Risk of methaemoglobinaemia; preferred for Bier's block (less cardiotoxic) |
Role of Adrenaline with LA: [6]
- Causes local vasoconstriction → ↓ absorption → prolongs block duration → ↓ systemic toxicity → ↓ dosage required
- Contraindicated in end-arteries: digits (fingers, toes), penis, ear pinna — risk of ischaemic necrosis
- 70 kg patient, max dose of lignocaine = 70 × 3 = 210 mg
- 1% lignocaine = 10 mg/mL; 0.5% = 5 mg/mL
- Max volume of 0.5% lignocaine = 210/5 = 42 mL
13. Complications of Regional Anaesthesia
Inadvertent intravascular injection, Overdose, Adverse reaction to adjuvant [1]
Spectrum of systemic manifestations: Neurological symptoms → Convulsions → Cardiovascular collapse [1]
The toxicity spectrum progresses in order (CNS before CVS):
| Stage | Manifestations |
|---|---|
| Early CNS | Perioral numbness, metallic taste, tinnitus, dizziness, visual disturbance |
| CNS excitation | Tremors, convulsions |
| CNS depression | Loss of consciousness, respiratory depression |
| CVS toxicity | Hypotension, bradycardia, arrhythmias (VF), cardiac arrest |
Why CNS before CVS? The CNS is more sensitive to LA toxicity because inhibitory cortical neurons are blocked first → unopposed excitatory activity → seizures. Higher concentrations then depress everything including the heart.
Management of LAST: [6]
- Stop injecting LA
- Call for help
- Manage airway — intubate if necessary
- IV benzodiazepine (diazepam/midazolam) for seizures — ↑ seizure threshold
- 20% Intralipid (lipid emulsion) — binds LA in circulation ("lipid sink"), rescues cardiovascular collapse
- Standard ACLS if cardiac arrest (may require prolonged resuscitation)
Prevention of LAST: [6]
- Calculate and respect maximum doses
- Frequent aspiration before injection (check for blood return)
- Inject in small increments
- Use adrenaline as marker (↑HR if intravascular injection)
- Use ultrasound guidance for nerve blocks
Hypotension: Sympathectomy, inadequate intravascular volume, inappropriate patient choice (cardiac/valvular disease) [1] Bradycardia: Blockade of cardiac sympathetic fibres [1]
Why? Spinal/epidural anaesthesia blocks sympathetic nerve fibres → arteriolar vasodilation (↓SVR) + venodilation (↓venous return) → ↓BP. If the block extends to T1–T4 (cardiac accelerator fibres), you also lose sympathetic drive to the heart → bradycardia. Treatment: IV fluids (preloading), vasopressors (ephedrine, phenylephrine), atropine for bradycardia.
Excessive rostral spread of LA — dose too much, position head down, subdural injection [1] Respiratory distress: motor blockade of intercostal muscles → may require ventilatory support [1] "Total Spinal": supraspinal neurons (brain, midbrain, pons, medulla) blocked by LA [1]
Total spinal is an emergency: complete motor/sensory/autonomic block including brainstem → apnoea, cardiovascular collapse, loss of consciousness. Management: immediate airway control + ventilation + cardiovascular support (essentially converting to GA).
| System | Effects | Mechanism |
|---|---|---|
| Respiratory | Respiratory depression, ↓cough reflex, ↓lung volumes, ↑V/Q mismatch, bronchospasm, retained secretions → post-op pneumonia | Central respiratory centre depression; loss of airway reflexes; diaphragm displacement; atelectasis [3] |
| Cardiovascular | ↓CO, vasodilation, hypotension, arrhythmias, myocardial depression | Direct drug effects (propofol, volatile agents); loss of sympathetic tone |
| Hepatic | ↓Drug metabolism, ↓albumin production, impaired clotting | Reduced hepatic blood flow; direct drug effects |
| Renal | ↓GFR, ↓urine output, electrolyte disturbance | ↓Renal blood flow from ↓CO and ↓MAP |
| Endocrine | Stress response (↑cortisol, catecholamines, glucose), worsened diabetic control | Surgical stress + anaesthetic effects |
Surgery plus general anaesthesia equals gross disturbances in physiological homeostasis. Effects extend well into the post-operative period. Patient assessment and optimization. Notify your anaesthetic colleagues early. [1]
High Yield Summary
Key exam facts from GC 001:
- Types of anaesthesia: GA, RA, MAC, combinations — know definitions and when each is used
- Five objectives of GA: Hypnosis, Amnesia, Analgesia, Areflexia, ± Muscle Relaxation
- Fasting rules: 2h clear fluids, 4h breast milk, 6h solids/formula — EVEN FOR RA (may need conversion to GA)
- IV induction agents: Propofol (most common), Thiopentone, Etomidate (haemodynamic stability), Ketamine (doesn't drop BP, analgesia, bronchodilation)
- Volatile maintenance agents: Sevoflurane, Desflurane, Isoflurane ± N₂O; TIVA with propofol as alternative
- NMBs: Non-depolarising (rocuronium, atracurium) vs Depolarising (suxamethonium — fastest onset but dangerous side effects including hyperkalaemia and malignant hyperthermia)
- Reversal: Neostigmine + atropine/glycopyrrolate for non-depolarising NMBs; Sugammadex for rocuronium/vecuronium ONLY
- Analgesics: Paracetamol, NSAIDs, opioids (fentanyl, morphine, oxycodone, pethidine), tramadol, gabapentinoids, ketamine, regional techniques. Remifentanil provides NO postoperative analgesia.
- Regional anaesthesia: Spinal vs Epidural; local infiltration; nerve/plexus blocks. LA toxicity spectrum: CNS → CVS. Treat with lipid emulsion.
- Complications of RA: LA toxicity, haemodynamic disturbances (sympathectomy), excessive/total spinal, block failure
- Always prepare for GA even when RA is planned — fasting, monitoring, drugs ready
Likely Exam Questions
-
Which IV induction agent is MOST appropriate for a trauma patient with haemodynamic instability? → Ketamine — sympathomimetic, maintains BP and HR, provides analgesia. Etomidate is also acceptable but lacks analgesia.
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A patient undergoing spinal anaesthesia develops hypotension and bradycardia. What is the MOST LIKELY mechanism? → Sympathetic blockade → vasodilation (↓SVR) + venodilation (↓preload) ± blockade of cardiac accelerator fibres (T1–T4) → bradycardia.
-
Which drug given intraoperatively would NOT be useful for reducing pain AFTER surgery? (2025 MCQ [2]) → Remifentanil — ultra-short half-life (~3 min), completely metabolized before emergence.
-
A patient develops perioral numbness, tinnitus, and then seizures after a nerve block. What is the MOST LIKELY diagnosis and immediate treatment? → Local anaesthetic systemic toxicity (LAST). Treat: stop injection, manage airway, IV benzodiazepine for seizures, 20% intralipid for cardiovascular collapse.
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Which NMB is appropriate for rapid sequence induction in a patient with burns > 48h old? → Rocuronium (high dose 1.2 mg/kg) — suxamethonium contraindicated due to risk of lethal hyperkalaemia from upregulated receptors.
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List the five objectives of general anaesthesia and name one drug class that achieves each. → Hypnosis (propofol/volatile agents), Amnesia (midazolam/volatile agents), Analgesia (opioids/NSAIDs), Areflexia (opioids/deeper anaesthesia), Muscle relaxation (NMBs).
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Why must neostigmine be co-administered with atropine or glycopyrrolate? → Neostigmine inhibits acetylcholinesterase → ↑ACh at both nicotinic (NMJ, desired effect) AND muscarinic (heart, glands — undesired) receptors. Atropine blocks muscarinic side effects (bradycardia, excessive secretions, bronchoconstriction) while allowing NMJ reversal.
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A confused patient (GCS E2V1M5) with pinpoint pupils, RR 8, SpO₂ 90%. Which drug would BEST improve mental status? (2023 MCQ [7]) → Naloxone — clinical picture consistent with opioid overdose (pinpoint pupils, respiratory depression, ↓GCS, track marks/contracted scars in groin).
Active Recall - Lecture Notes
[1] Lecture slides: GC 001 - How would you anaesthetise me - Pharmacology of anaesthetic drugs.pdf (all pages) [2] Past papers: 2025 Fourth Summative MCQ.pdf (Question 59) [3] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (p1, p5) [4] Senior notes: Maksim Surgery Notes.pdf (p291, p305) [5] Lecture slides: Preoperative Assessment.pdf (p19) [6] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p109); Maksim Surgery Notes.pdf (p295); Crisis Management.pdf (p9) [7] Past papers: 2023 Fourth Summative MCQ.pdf (Question 74)
Molecular Pathology Seminar 8: Molecular Genetic Testing In Breast Cancer With Case Study
Molecular genetic testing in breast cancer involves analyzing tumor biomarkers such as HER2 amplification, estrogen/progesterone receptor status, and gene expression profiles (e.g., Oncotype DX, MammaPrint) to guide prognosis, predict therapeutic response, and personalize treatment decisions.
GC002 Is He Fit For Surgery - Pre-operative Assessment
Pre-operative assessment is a systematic evaluation of a patient's medical history, physical status, and risk factors to determine their fitness for surgery and optimize outcomes.