Postgraduate-level comprehensive notes covering general and regional anaesthesia, perioperative medicine, pain management, critical care, and the applied physiology and pharmacology of anaesthetic agents.
General anaesthesia is a reversible drug-induced state of unconsciousness, amnesia, analgesia, and immobility. The key molecular targets are GABA-A receptors, glycine receptors, NMDA receptors, and two-pore domain potassium channels. MAC is the clinical yardstick of potency for volatile agents.
GABA-A receptor subtypes and their anaesthetic sensitivity
IV induction agent selection by clinical scenario
Most common trap:
MAC is additive for volatile agents but NOT for IV agents. MAC-BAR (1.5-1.7 MAC) is rarely needed clinically — opioids and regional blocks blunt the autonomic response more effectively than deepening volatile anaesthesia alone.
Mechanisms of Action
General anaesthesia is a reversible, drug-induced state characterized by loss of consciousness, amnesia, analgesia, and immobility.
Think of general anaesthesia as a carefully orchestrated pharmacological coma — you are hitting specific molecular targets to make the patient unconscious, pain-free, amnestic, and immobile. The workhorses here are GABA-A receptors, glycine receptors, NMDA receptors, and two-pore domain potassium channels.
The molecular targets include GABA-A receptors (most important), glycine receptors, NMDA receptors, and two-pore domain potassium channels.
Most volatile anaesthetics (sevoflurane, isoflurane, desflurane) and IV agents (propofol, etomidate, barbiturates) are positive allosteric modulators of GABA-A receptors.
GABA-A receptor: pentameric ligand-gated ion channel (2 alpha, 2 beta, 1 gamma subunits). Beta subunit contains GABA binding site; anaesthetics bind to sites on alpha subunit and at alpha-beta interface.
The Meyer-Overton Correlation
The Meyer-Overton correlation established that anaesthetic potency is directly proportional to lipid solubility.
Current understanding: volatile anaesthetics act on multiple targets — potentiation of GABA-A and glycine receptors (inhibitory), inhibition of NMDA receptors (excitatory), and activation of K2P channels (TREK-1, TASK).
The minimum alveolar concentration (MAC) is the standard measure of potency for volatile anaesthetics — the concentration at which 50% of patients do not move in response to surgical incision.
MAC-awake: approximately 0.3-0.5 MAC (loss of consciousness). MAC-BAR: approximately 1.5-1.7 MAC (blunting of autonomic response to incision). MAC values are additive: 0.5 MAC sevoflurane + 0.5 MAC N2O
MAC Decreasers: COLD HIPS — Children (neonates have lower MAC), Old age, Low temperature, Drugs (opioids, sedatives, alpha-2 agonists, lithium), Hypotension, Hypothyroidism, IV agents (propofol), Pregnancy, Sepsis, Severe hypoxia, Sodium low (hyponatremia).
Common Trap: MAC is additive for volatile agents but NOT for IV agents. You cannot calculate MAC equivalents for propofol — use processed EEG (BIS) instead. MAC-BAR (1.5-1.7 MAC) is rarely needed clinically — analgesia (opioids, regional blocks) blunts autonomic response more effectively than deepening volatile anaesthesia alone. MAC changes with circadian rhythm — slightly HIGHER in the morning (~6-8%).
GABA-A Receptor Subtypes and Anaesthetic Pharmacology
Receptor Subtype
Subunit Composition
Anaesthetic Sensitivity
Physiological Role
alpha-1 beta-2/3 gamma-2
Synaptic
Benzodiazepines (sedation, amnesia)
Phasic inhibition, anterograde amnesia
alpha-5 beta-3 gamma-2
Extrasynaptic
Volatile agents, propofol, etomidate
Tonic inhibition, hippocampal LTP
beta-3 containing
Spinal cord
Volatile agents (immobility)
Immobilization to surgical stimulus
beta-2 containing
Forebrain
Etomidate (sedation)
Sedative/hypnotic action
delta subunit
Extrasynaptic (thalamus)
Neurosteroids, propofol
Tonic inhibition, thalamocortical oscillations
Non-GABAergic Anaesthetic Mechanisms
NMDA receptor antagonism: ketamine, nitrous oxide, xenon — noncompetitive antagonists at the phencyclidine binding site within the NMDA receptor pore. Produces dissociative anaesthesia with analgesia, sympathomimetic effects, and preserved airway reflexes.
Glycine receptors: volatile agents and propofol potentiate glycine (major inhibitory neurotransmitter in spinal cord and brainstem). Contributes to immobility and respiratory depression.
Clinical Pearl: Propofol and volatile agents produce unconsciousness primarily through GABA-A receptors containing beta-3 subunits. The spinal cord (not the brain) is the primary site for the immobilizing action of volatile anaesthetics. This is why MAC (defined by movement response) and MAC-awake (consciousness) differ.
Rapid onset (30-60 sec), smooth induction, rapid clearance. Side effects: hypotension, respiratory depression, pain on injection
Ketamine
NMDA antagonist
1-2 mg/kg IV, 4-5 mg/kg IM
Dissociative anaesthesia, preserves respiratory drive and airway reflexes, useful in haemodynamic instability. Side effects: emergence delirium, hallucinations
Etomidate
GABA-A agonist
0.2-0.3 mg/kg
Haemodynamic stability — agent of choice for haemodynamically unstable patients. Side effects: adrenal suppression (even single dose), myoclonus, nausea
Thiopental
GABA-A agonist
3-5 mg/kg
Barbiturate, rapid onset. Contraindicated in porphyria, status asthmaticus. Causes histamine release, laryngospasm
Q: Which induction agent is contraindicated in acute intermittent porphyria? A: Thiopentone (and all barbiturates) — induce ALA synthase, precipitating acute porphyric crisis. Propofol, ketamine, benzodiazepines are considered safe alternatives.
Q: A 70-year-old patient with severe aortic stenosis (AVA 0.6 cm²) requires emergency laparotomy. Which induction agent? A: Etomidate 0.2 mg/kg — maintains haemodynamic stability in fixed cardiac output states. Ketamine 1-1.5 mg/kg is an alternative. Avoid propofol and thiopentone (profound vasodilation + myocardial depression).
Clinical Pearl: Propofol causes pain on injection in 30-70% of patients. Prevention: add lidocaine 20 mg per 200 mg propofol OR pretreat with lidocaine 0.5 mg/kg IV with venous occlusion for 30-60 sec. Use large antecubital veins. Newer formulations with medium-chain triglycerides reduce pain. Pretreatment with opioids or midazolam also reduces injection pain.
ctic acidosis, rhabdomyolysis, cardiac failure with prolonged high-dose infusions (>4-5 mg/kg/hr for >48 hours) in ICU setting — more common in children and patients on catecholamines and corticosteroids.
A 35-year-old female for elective cholecystectomy. She has a history of severe anxiety about needles. Inhalation induction with sevoflurane (vital capacity breath induction, 8% sevoflurane in O2/N2O) is chosen. IV access is established after loss of consciousness. Propofol 2 mg/kg is given after IV access to deepen anaesthesia before intubation.
Total Intravenous Anaesthesia (TIVA)
TIVA is a technique of general anaesthesia using exclusively intravenous agents, most commonly propofol and remifentanil, administered via target-controlled infusion (TCI) pumps.
TCI uses pharmacokinetic models (Marsh for propofol, Minto for remifentanil) to achieve and maintain a target plasma or effect-site concentration.
Advantages of TIVA: reduced PONV, no operating room pollution, no trigger for malignant hyperthermia, better recovery quality, no environmental impact from volatile agents
TCI Model Comparison
Model
Drug
Key Parameters
Limitations
Marsh
Propofol
Weight-based only. V1=0.228 L/kg. Ke0=0.26/min
Inaccurate in obese patients (use adjusted body weight). Does not account for age. May underdose elderly
Density spectral array (DSA) display. Bilateral monitoring
Common Trap: BIS can be falsely elevated by: EMG artifact (frontal muscle activity), electrocautery interference, pacemakers, hypothermia, cerebral ischemia (paradoxical BIS increase in some cases). BIS can be falsely decreased by: ketamine (dissociative state — high BIS expected but patient anaesthetized), nitrous oxide (maintains BIS despite anaesthesia), xenon. Always interpret BIS in clinical context.
.
Depth of Anaesthesia Monitoring
Bispectral Index (BIS): processed EEG, dimensionless number 0 (isoelectric) to 100 (awake). Target for general anaesthesia: 40-60. Reduces risk of intraoperative awareness (incidence 0.1-0.2%).
Other monitors: Entropy module (state entropy SE, response entropy RE), Narcotrend, and evoked potentials (somatosensory, motor, auditory).
GABA-A receptor structure showing binding sites for volatile and intravenous anaesthetics
Airway Management
Airway Assessment
Airway management is the most critical skill in anaesthesiology.
The Mallampati score is the most widely used single predictor of difficult intubation — Class III-IV predicts difficulty, but positive predictive value is only 30-50%.
Plan A (laryngoscopy + intubation) → Cormack-Lehane grade 3/4 → BURP + bougie → Plan B (supraglottic airway rescue: LMA) → Plan C (facemask ventilation + oropharyngeal airway) → Plan D (emergency front-of-neck access: cricothyroidotomy — scalpel-bougie technique or needle cricothyroidotomy)
Videolaryngoscopy has become the standard of care for predicted and unexpected difficult airways. Awake fibreoptic intubation (AFOI) is the gold standard for the known difficult airway.
Rapid Sequence Induction (RSI)
RSI is a technique designed to minimize the risk of pulmonary aspiration during induction of anaesthesia in patients with a full stomach.
Key principles: pre-oxygenation (3 minutes of tidal volume breathing or 8 vital capacity breaths with 100% O2), administration of a rapidly acting induction agent (propofol 2 mg/kg or ketamine 1-2 mg/kg) immediately followed by a rapidly acting NMBA (suxamethonium 1-1.5 mg/kg or rocuronium 1.2 mg/kg), cricoid pressure (Sellick's manoeuvre), and avoidance of positive pressure ventilation until the airway is secured.
Modified RSI: in patients where suxamethonium is contraindicated, rocuronium 1.2 mg/kg with sugammadex immediately available allows comparable onset with safer profile. Modified RSI may include gentle mask ventilation (low pressure, <15 cmH2O) in cases where SpO2 falls during the apnea period, such as in obese patients and the critically ill.
Cricoid pressure (Sellick's manoeuvre): application of backward pressure on the cricoid ring to occlude the oesophagus during RSI. Originally described to prevent passive regurgitation, though evidence for efficacy is limited. May worsen laryngoscopic view in up to 30%
No cuff — gel-like thermoplastic elastomer. Gastric channel
~25
Yes
LMA Fastrach
Special-purpose
Designed for intubation through SAD (rigid, anatomically curved tube)
~25
No
Clinical Pearl: If SAD rescue (Plan B) is successful and surgery is essential, you have three options: (a) Wake the patient and perform AFOI, (b) Proceed with surgery using SAD as definitive airway (only if appropriate for surgery type/duration/patient position — NEVER for full stomach, Trendelenburg, or prone), (c) Intubate through SAD using fibreoptic scope (LMA Fastrach designed for this).
RSI Quick-Revise One-Liners
The 7 Ps of RSI:
Preparation (all equipment checked), Pre-oxygenation (EtO2 >85%), Pre-treatment (optional — fentanyl 1-3 mcg/kg, lidocaine 1.5 mg/kg to attenuate pressor response), Paralysis with Induction (Propofol or Ketamine + Suxamethonium/Rocuronium), Positioning (sniffing position), Pressure (cricoid 30N after LOC), Placement with Proof (ETT + capnography)
Suxamethonium 1-1.5 mg/kg has fastest onset (30-45 sec) of any NMBA
— ideal for true RSI in patients without contraindications
Rocuronium 1.2 mg/kg (4×ED95) provides intubating conditions at 60 seconds comparable to suxamethonium
— with sugammadex 16 mg/kg available for immediate reversal if CICO
Sellick cricoid pressure:
Apply 10N while patient awake, increase to 30N (3 kg) at loss of consciousness. If laryngeal view poor, RELEASE pressure — evidence for aspiration prevention is weak
Failed RSI + cannot ventilate = CICO emergency (Plan D of DAS)
— do NOT delay front-of-neck access waiting for sugammadex or reversal agents. Scalpel-bougie technique can be performed in <40 seconds
Modified RSI:
gentle mask ventilation (peak pressure <15 cmH2O) may be used if SpO2 falls during apnea period — particularly in obese, critically ill, and paediatric patients where desaturation is rapid
if incorrectly applied.
A 55-year-old male with BMI 42, obstructive sleep apnoea, and limited neck extension presents for emergency laparotomy. He is at high risk of difficult intubation. Plan: awake fibreoptic intubation with topical anaesthesia (lidocaine nebulization + superior laryngeal nerve block + transtracheal block). Alternative: videolaryngoscopy with backup front-of-neck access prepared.
Upper airway anatomy relevant to tracheal intubation and supraglottic airway device placement
Neuromuscular Blockade and Reversal
Neuromuscular Blocking Agents
Type
Examples
Mechanism
Depolarizing
Suxamethonium (succinylcholine)
Mimics ACh at nAChR → initial depolarization (fasciculations) → receptor desensitization → prolonged depolarization block (Phase I block)
Phase I block (depolarizing): sustained depolarization, no fade on TOF, sustained tetanus. Phase II block: occurs with prolonged/prolonged suxamethonium administration, resembles non-depolarizing block (fade on TOF, post-tetanic facilitation) — responds to neostigmine paradoxically.
Rocuronium: fastest onset among non-depolarizers (60-90 sec at 0.6-1.2 mg/kg) — used for RSI when hyperkalemia is a concern.
Elimination
Atracurium and cisatracurium undergo Hofmann elimination (spontaneous degradation at physiologic pH/temperature) and ester hydrolysis — agents of choice in hepatic and renal failure.
Monitoring and Reversal
Train-of-four (TOF) ratio (T4/T1) using peripheral nerve stimulation. TOF ratio >=0.9 indicates adequate recovery
ACh is synthesized from acetyl-CoA + choline (by choline acetyltransferase)
and stored in vesicles (~10,000 ACh molecules per vesicle)
Each nerve impulse releases 200-300 quanta (vesicles)
— each quantum produces a miniature end-plate potential (MEPP) of ~0.5 mV
Safety factor of neuromuscular transmission is ~4-5×
— meaning 75-80% of postsynaptic receptors must be blocked before transmission fails. This is why TOF ratio <0.9 is needed before clinical weakness is apparent
Eaton-Lambert syndrome:
antibodies against pre-synaptic voltage-gated Ca channels → reduced ACh release → potentiation with repetitive stimulation (opposite of myasthenia gravis). EXQUISITELY sensitive to both depolarizing and non-depolarizing NMBAs
Myasthenia gravis:
antibodies against post-synaptic nAChR → reduced receptor density → resistant to depolarizing NMBAs (fewer receptors to depolarize), hypersensitive to non-depolarizing NMBAs (fewer receptors to block)
upregulation of extrajunctional nAChR (fetal gamma-subunit type) → hypersensitive to suxamethonium (life-threatening hyperkalemia) and resistant to non-depolarizing NMBAs (more receptors to block)
Non-Depolarizing NMBA Detailed Comparison
Agent
ED95 (mg/kg)
Intubating Dose
Duration (min)
Metabolism/Elimination
Key Features
Rocuronium
0.3
0.6 mg/kg (2×ED95); 1.2 mg/kg for RSI
30-50
Hepatic (70%), Renal (30%)
Fastest onset non-depolarizer. Reversible by sugammadex. Mild vagolytic (tachycardia at high dose)
Vecuronium
0.04
0.08-0.1 mg/kg
30-45
Hepatic (80-90%), Renal (10-20%)
Cardiostable — minimal haemodynamic effects. Active metabolite accumulates in renal failure (prolonged block)
Wait until TOF=4, then neostigmine 50-70 mcg/kg OR Sugammadex 2 mg/kg
TOF count 1
Deep block
Sugammadex 4 mg/kg. NEVER attempt neostigmine reversal — will be incomplete
TOF count 0, PTC ≥2
Deep block
Sugammadex 4 mg/kg
TOF count 0, PTC 0
Profound block (immediate post-RSI)
Sugammadex 16 mg/kg if immediate reversal needed. Spontaneous recovery may take 60-120 min
TOF Block Depth: "Zero-One-Two-Three-Four" — Zero (profound, sugammadex 16), One (deep, sugammadex 4), Two (moderate, wait for 4), Three (moderate, wait for 4), Four with fade (shallow, neostigmine or sugammadex 2).
Neostigmine vs Sugammadex — Head-to-Head
Feature
Neostigmine
Sugammadex
Mechanism
Indirect — increases ACh in synaptic cleft (AChE inhibitor)
Direct encapsulation of NMBA molecule
(modified gamma-cyclodextrin)
Anticholinergic needed
Yes — glycopyrrolate 10 mcg/kg or atropine 15 mcg/kg
No anticholinergic needed
Block depth reversible
Only shallow/moderate block (TOF count ≥2)
ANY depth of rocuronium/vecuronium block
Onset to TOF ≥0.9
5-15 min (slower)
2-3 min (faster)
PONV risk
Increased (muscarinic effect)
Decreased (no muscarinic effect)
Recurarization risk
Present — if neostigmine wears off before NMBA
Very low
— but possible in renal failure (complex dissociation)
Cost
Low (~$2-5)
High (~$80-120)
Special considerations
Ceiling effect — cannot overcome deep block
Interferes with hormonal contraception (7 days). May increase aPTT/INR (transient, not clinically significant). Rare hypersensitivity (0.04%)
Q: A patient received rocuronium 0.6 mg/kg for intubation. At the end of a 2-hour surgery, TOF count is 1. Which reversal strategy is appropriate? A: Sugammadex 4 mg/kg — neostigmine CANNOT reverse deep block (TOF count <2). If sugammadex is unavailable, wait for spontaneous recovery until TOF count ≥4 before administering neostigmine.
Q: What is the dibucaine number? A: Measures percentage inhibition of plasma cholinesterase (pseudocholinesterase) activity by dibucaine. Normal homozygous: 70-80 (normal enzyme). Heterozygous atypical: 40-60 (moderately prolonged suxamethonium block — 30-60 min). Homozygous atypical: <20 (severely prolonged block — 2-8 hours). Used to diagnose prolonged suxamethonium paralysis.
Neuromuscular Blockade Quick-Revise One-Liners
TOF ratio for safe extubation is ≥0.9
— even at 0.7, pharyngeal dysfunction, impaired swallowing, aspiration risk, and hypoxic ventilatory drive depression occur. Clinical tests (head lift, grip strength) are unreliable for detecting residual block
Sugammadex-rocunium complex is renally excreted
— in severe renal failure (CrCl <30), complex may dissociate over days causing recurarization. Use neostigmine (after spontaneous recovery) or cisatracurium in renal failure
PTC (Post-Tetanic Count) is used when TOF count = 0
— applies tetanic stimulation (50 Hz for 5 sec), then counts responses to single twitches. PTC 10-15 = moderate deep block; PTC 0 = profound block
Double burst stimulation (DBS)
is more sensitive than TOF for detecting residual block clinically — two short tetanic bursts, fade is easier for clinicians to detect by feel/touch
Monitoring site matters:
diaphragm and laryngeal adductors recover faster than adductor pollicis (ulnar nerve). TOF ratio 0.9 at adductor pollicis ensures full diaphragmatic recovery. Corrugator supercilii (facial nerve) recovers similarly to diaphragm
Magnesium potentiates non-depolarizing NMBAs
— pre-synaptic inhibition of ACh release. Reduce NMBA dose by 25-50% in pre-eclamptic patients on MgSO4
Antibiotics potentiating NMBA:
aminoglycosides (pre-synaptic Ca channel block), clindamycin, polymyxins, tetracyclines — all reduce ACh release or decrease post-synaptic sensitivity
.
Residual neuromuscular blockade (TOF ratio <0.9) occurs in 40-60%
Peripheral Nerve Stimulator Sites and Interpretation
Nerve
Muscle
Block Sensitivity
Clinical Use
Ulnar nerve
Adductor pollicis
Most sensitive to NMBA (recovers LAST)
Standard monitoring site. TOF ratio ≥0.9 here = safe extubation
Facial nerve
Corrugator supercilii
Similar to diaphragm (recovers EARLY)
Use when TOF is 0 at adductor pollicis but need to assess deeper block recovery
Posterior tibial nerve
Flexor hallucis brevis
Intermediate
Alternative when upper limbs not accessible
Common peroneal nerve
Tibialis anterior
Similar to adductor pollicis
Alternative lower limb site
Diaphragm/Laryngeal recovery is EARLIER than thumb: \Laryngeal Adductors Open Earlier\ (and Diaphragm) vs Thumb
Quantitative vs Qualitative NM Block Monitoring
Qualitative (subjective) TOF assessment by clinicians is unreliable — residual block (TOF ratio <0.9) cannot be reliably detected by feel/visual assessment when TOF ratio is 0.4-0.9. QUANTITATIVE monitoring (AMG, EMG, KMG) is the gold standard. DBS (double burst stimulation) is better than TOF for qualitative assessment but still imperfect.
of patients in the recovery room — major risk factor for postoperative pulmonary complications.
Reversal Agent
Mechanism
Dose
Neostigmine
Acetylcholinesterase inhibitor (given with glycopyrrolate to prevent muscarinic side effects)
40-70 mcg/kg
Sugammadex
Modified gamma-cyclodextrin — selectively encapsulates rocuronium and vecuronium
Sugammadex does not require anticholinergics and is superior to neostigmine for rapid reversal.
Can increase INR in patients on warfarin and may interfere with hormonal contraception.
Q: A patient with burns >48 hours requires emergency surgery. Which NMBA is contraindicated? A: Suxamethonium — risk of life-threatening hyperkalemia from upregulation of extrajunctional acetylcholine receptors. Use rocuronium 1.2 mg/kg for RSI instead.
Neuromuscular junction transmission showing the site of action of depolarizing and non-depolarizing NMBAs
Nicotinic acetylcholine receptor at the neuromuscular junction with drug-binding sites
Inhalational Anaesthetics
Volatile Anaesthetic Agents
Volatile agents: isoflurane, sevoflurane, desflurane, and halothane (now rarely used).
Agent
Blood:Gas Coefficient
MAC (%)
Key Feature
Sevoflurane
0.65
2.0
Lowest blood:gas among volatile agents — most rapid onset/offset, agent of choice for inhalation induction
Desflurane
0.42
6.0
Rapid emergence, highest global warming potential, requires specialized heated vaporizer
Isoflurane
1.4
1.15
Slower onset and offset, coronary vasodilation (coronary steal phenomenon debated)
Halothane
2.3
0.75
Sensitizes myocardium to catecholamines (arrhythmias), hepatitis risk (1:35,000), rarely used
Pharmacokinetics and Uptake
The rate of rise of alveolar concentration (FA/Fi) depends on: blood:gas solubility coefficient (inversely), cardiac output (inversely), alveolar ventilation (directly), and partial pressure gradient.
Nitrous Oxide
Nitrous oxide (N2O) is an inorganic gas with a MAC of 104% — cannot be used as a sole anaesthetic.
Risks: expansion of air-filled spaces (pneumothorax, bowel obstruction, intraocular gas), diffusion hypoxia on emergence (prevent by administering 100% O2 for first 5-10 min), megaloblastic anemia (inhibition of methionine synthase affecting B12 — with prolonged use), increased PONV.
Second Gas Effect and Fink Effect
Second gas effect: when N2O is administered in high concentration, it is rapidly taken up from alveoli, increasing concentration of co-administered volatile agents in alveoli (concentration effect) — accelerates onset.
Environmental Impact
Desflurane has the highest global warming potential (GWP 2540 over 100 years vs 130 for isoflurane and 20 for sevoflurane). Low-flow and minimal-flow anaesthesia reduce environmental impact.
Soda lime can interact with sevoflurane to produce Compound A (nephrotoxic in rats — not clinically significant in humans at low flows). Desflurane can produce carbon monoxide in dry soda lime.
A 3-year-old child requiring MRI-guided biopsy. Inhalation induction with sevoflurane 8% in O2 via vital capacity breath technique. After IV access, anaesthesia maintained with sevoflurane 2-3% in air/O2 mixture. Spontaneous ventilation throughout. Recovery rapid and smooth.
The circle absorber breathing system for administration of volatile anaesthetics with CO2 absorption
Guedel Stages, MAC Values and Volatile Agent Pharmacology
Guedel Stages of Anaesthesia
Guedel's stages describe the progressive depth of anaesthesia originally described for diethyl ether, and are still conceptually applied today to understand the continuum from consciousness to surgical anaesthesia.
Stage
Name
Features
Stage I
Analgesia / Induction
Conscious, analgesic, amnesia begins; full recall possible; patient cooperative
Stage II
Excitement / Delirium
Loss of consciousness, uninhibited CNS activity; breath-holding, vomiting, laryngospasm, hypertension, tachycardia — most dangerous stage; AVOID airway instrumentation here
Stage III
Surgical Anaesthesia
Four planes: Plane 1 (regular respiration, eye movement ceases), Plane 2 (loss of lid reflex, surgical stimuli tolerated), Plane 3 (intercostal paralysis begins, diaphragmatic breathing), Plane 4 (complete intercostal paralysis, diaphragm only)
Modern IV induction agents (propofol, thiopentone) produce rapid transition through Stage II — fast enough that the dangers are minimized. Never allow stimulation (airway instrumentation, venepuncture) during Stage II — risk of laryngospasm, vomiting, breath-holding.
MAC (Minimum Alveolar Concentration) = the concentration of inhaled anaesthetic at 1 atmosphere that prevents movement in response to a surgical skin incision in 50% of patients. MAC is a measure of potency — lower MAC = more potent agent.
Agent
MAC (%)
Blood:Gas Coefficient
Oil:Gas Coefficient
Key Clinical Point
Halothane
0.75
2.3
224
Hepatotoxicity (halothane hepatitis — immune-mediated, 1:35,000 with repeated exposure); sensitizes myocardium to catecholamines (arrhythmias with adrenaline). Largely abandoned.
Isoflurane
1.15
1.4
98
Coronary steal syndrome (vasodilates coronary vessels — may divert blood from ischaemic myocardium); systemic vasodilation + hypotension.
Sevoflurane
2.0
0.65
47
Most popular for inhalational induction (non-pungent); Compound A formation with soda lime at low flows (not clinically significant); slight nephrotoxicity at high doses — avoid flows < 2 L/min for > 2 MAC hours.
Desflurane
6.0
0.42
18.7
Fastest onset and offset; pungent — airway irritant (bronchospasm, coughing, laryngospasm on induction); sympathetic activation with rapid increase; highest GWP (3714× CO₂); being phased out in UK/EU.
Nitrous Oxide
104
0.47
1.4
Cannot produce surgical anaesthesia alone (MAC > 100%); second gas effect; Fink effect on emergence; expands gas-filled spaces; inhibits methionine synthase (B12 depletion); PONV.
Factors DECREASING MAC: old age (MAC decreases ~6% per decade
MAC by Age — High-Yield NEET PG Table
Age Group
MAC Trend
Sevoflurane MAC
Clinical Implication
Preterm neonates (<32 weeks)
Very low
~2.0%
Use minimum volatile, monitor for hypotension
Term neonates (0-1 month)
Lower than infants
~2.5%
Immature CNS — reduced anaesthetic requirement
Infants (1-6 months)
HIGHEST MAC of any age group
~3.3%
Peak at ~6 months. Higher synaptic density and metabolic rate
Children (1-12 years)
Gradually decreasing
~2.5%
MAC decreases with age throughout childhood
Adults (40 years)
Baseline
2.0%
Standard reference MAC
Elderly (>40 years)
Decreases ~6% per decade
~1.4% at 80 years
Reduce volatile dose by ~6% per decade after 40
Guedel Stage III Planes (1-4): "Everything Regular, Lid Reflex Lost, Chest Paralysis Begins, Diaphragm Only"
Q: A 6-month-old infant requires anaesthesia. How does MAC compare to an adult? A: HIGHER — MAC peaks in infants 1-6 months of age (highest of any age group). This is due to increased CNS synaptic density, higher metabolic rate, and increased neurotransmitter turnover. Neonates (<1 month) have LOWER MAC due to immature CNS.
Volatile Agent Organ System Effects — Quick-Revise One-Liners
Organ System
Effect of Volatile Agents
Clinical Relevance
Cerebral
Decrease CMRO2 (neuroprotective), but increase CBF (↑ICP). Uncoupling of flow-metabolism
Use <1 MAC + opioid in neurosurgery to minimize CBF increase. Sevoflurane has least CBF effect
Halothane hepatitis: repeated exposure within short interval, middle-aged obese females, fever + jaundice + eosinophilia
Renal
Reduce RBF and GFR. Compound A (sevoflurane) nephrotoxic in rats — not clinically significant in humans
Maintain flows ≥2 L/min with sevoflurane for >2 MAC-hours (FDA recommendation — debated)
Neuromuscular
Potentiate NMBA effect. Volatile agents alone provide some muscle relaxation
Reduce NMBA dose by 30-50% when using volatile agents. Desflurane potentiates NMBA the most
Uterine
Relax uterine smooth muscle — dose-dependent
Use <0.5 MAC for LSCS before delivery to prevent uterine atony; increase after delivery. Halothane used for retained placenta (uterine relaxation)
Inhalational Anaesthetics Quick-Revise One-Liners
Halothane sensitizes myocardium to catecholamines
— maximum safe adrenaline dose with halothane: 1 mcg/kg (vs 3-5 mcg/kg with sevoflurane/isoflurane). This is the most important reason halothane was abandoned
Desflurane has the highest global warming potential
(GWP 2540 over 100 years) — being phased out in UK/NHS. Sevoflurane has the lowest GWP among volatile agents (130)
N2O MAC = 104%
— cannot produce surgical anaesthesia alone. MAC-sparing effect: 60% N2O reduces volatile MAC by 40-50%
Fink effect (diffusion hypoxia):
on N2O discontinuation, N2O rapidly diffuses from blood into alveoli, diluting alveolar O2. Prevent with 100% O2 for first 5-10 min of emergence
Second gas effect:
rapid N2O uptake from alveoli concentrates co-administered volatile agent, accelerating onset. Clinically significant only in first 5-10 min of anaesthesia
after 40), hypothermia (↓by 5% per °C below normal), pregnancy (MAC reduces 25-40% — progesterone effect), acute alcohol intoxication, opioids, IV anaesthetic agents, lithium, alpha-2 agonists (clonidine, dexmedetomidine), hypoxia, hypotension, hypothyroidism.
Factors INCREASING MAC: hyperthermia (↑5% per °C), hyperthyroidism, chronic alcohol use, cocaine, CNS stimulants, hypernatraemia, young age (MAC peaks in infants 6 months–1 year).
Derived MAC Values
MAC-awake
(MACaw): concentration at which 50% of patients respond to verbal command — approximately 0.3-0.4 × MAC; awareness risk above this value
MAC-BAR
: concentration blocking adrenergic response (tachycardia, hypertension) to surgical incision — approximately 1.5 × MAC
MAC-intubation
: higher than MAC-incision — approximately 1.3 × MAC due to greater noxious stimulus
Additive MAC
: 70% N₂O + 0.5% isoflurane = 0.67 MAC + 0.43 MAC = 1.1 MAC (surgical anaesthesia)
Q: What is the MAC of isoflurane? A: 1.15%. Which volatile agent has the lowest blood:gas partition coefficient and why does this matter? A: Desflurane (0.42) — lower blood solubility means faster equilibration between alveolar and blood concentrations, resulting in rapid onset and offset of anaesthesia.
The oil:gas partition coefficient correlates directly with potency (Meyer-Overton rule): halothane (224) is most potent, desflurane (18.7) is least potent among modern agents. The blood:gas coefficient determines speed of onset: desflurane (0.42) has fastest onset, isoflurane (1.4) has slowest among modern agents.
Volatile anaesthetic pharmacodynamics: GABA-A potentiation and MAC values in clinical practice
Pharmacokinetics of volatile anaesthetics: alveolar uptake determined by blood:gas partition coefficient
