Topic Overview

GENERAL ANAESTHETICS

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🔸 Basic Concepts

Definition of General Anaesthesia

• Reversible loss of consciousness with analgesia + amnesia + immobility + attenuation of autonomic responses

• Allows painless surgical procedures with patient safety

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Components of General Anaesthesia

• Hypnosis → loss of consciousness (propofol, thiopentone)

• Analgesia → pain relief (opioids, N₂O)

• Amnesia → loss of memory (benzodiazepines)

• Immobility → skeletal muscle relaxation (inhalational agents, NM blockers)

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Balanced Anaesthesia (VERY HIGH-YIELD)

• Use of multiple drugs in combination to achieve all components with minimal toxicity

• Advantages:

  • ↓ Dose of individual drugs

  • ↓ Side effects

  • Better hemodynamic stability

Example:

• Induction → propofol

• Analgesia → fentanyl

• Muscle relaxation → vecuronium

• Maintenance → sevoflurane

---

Minimum Alveolar Concentration (MAC)

• Defined as:
  → Alveolar concentration of anaesthetic that prevents movement in 50% of patients to surgical stimulus

Key Points

• Inverse relation with potency

• Lower MAC = more potent drug

• Additive for multiple agents

Factors affecting MAC

• ↓ MAC: age ↑, hypothermia, opioids

• ↑ MAC: chronic alcohol use, hyperthermia

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Blood : Gas Partition Coefficient

• Indicates solubility of anaesthetic in blood

Clinical Correlation

• Low coefficient → rapid induction & recovery (desflurane, sevoflurane)

• High coefficient → slow induction (halothane)

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Oil : Gas Partition Coefficient (VERY IMPORTANT)

• Reflects lipid solubility → potency

• Follows Meyer–Overton rule

Key Concept

• Higher oil:gas ratio → ↑ potency → ↓ MAC

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📊 TABLE — PHYSICOCHEMICAL PROPERTIES (HIGH-YIELD)

Parameter	Clinical Meaning	Example
MAC ↓	High potency	Halothane
Blood:gas ↓	Fast induction	Desflurane
Oil:gas ↑	High potency	Isoflurane

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🧠 DIAGRAM — MAC CONCEPT

• Surgical stimulus → patient response

• 50% no movement → defines MAC

• Graph: concentration vs response curve

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🔸 Preanaesthetic Medication (VERY HIGH-YIELD)

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Goals of Preanaesthetic Medication

• Anxiolysis → reduce fear

• Sedation → calm patient

• Analgesia → reduce pain perception

• Antisialagogue → ↓ secretions

• Prevent aspiration → ↓ gastric acidity & volume

• Reduce reflex responses

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Sedatives (Benzodiazepines)

• Drugs: midazolam, diazepam

• Actions:

  • Anxiolysis

  • Amnesia

  • Sedation

• Mechanism:

  • GABA-A receptor potentiation

---

Opioids

• Drugs: fentanyl, morphine

• Actions:

  • Strong analgesia

  • ↓ anaesthetic requirement

• Adverse:

  • Respiratory depression

---

Anticholinergics

• Drugs: atropine, glycopyrrolate

• Actions:

  • ↓ salivary & bronchial secretions

  • Prevent vagal bradycardia

---

Antiemetics

• Drugs:

  • ondansetron (5-HT3 blocker)

  • metoclopramide (D2 blocker)

• Use:

  • Prevent postoperative nausea & vomiting

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H2 Blockers / Proton Pump Inhibitors

• Drugs:

  • ranitidine (H2 blocker)

  • omeprazole (PPI)

• Actions:

  • ↓ gastric acid secretion

  • ↓ risk of aspiration pneumonitis

---

📊 TABLE — PREANAESTHETIC DRUGS

Class	Drug	Purpose
Benzodiazepine	Midazolam	Anxiolysis + amnesia
Opioid	Fentanyl	Analgesia
Anticholinergic	Glycopyrrolate	↓ secretions
Antiemetic	Ondansetron	Prevent vomiting
H2 blocker	Ranitidine	↓ acid

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🧠 FLOWCHART — PREANAESTHETIC STRATEGY

Patient anxiety → Sedative
↓
Pain risk → Opioid
↓
Secretions ↑ → Anticholinergic
↓
Aspiration risk → H2 blocker/PPI
↓
PONV risk → Antiemetic

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🔬 SLIDES (EXAM FAVORITE)

GABA-A Receptor Mechanism (Benzodiazepines Action)

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Anaesthesia Machine & Vapourizer

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MAC Dose–Response Curve

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✅ EXAM PEARLS

• MAC ↓ = potency ↑

• Low blood:gas → fastest induction (desflurane)

• Balanced anaesthesia = safest approach

• Midazolam → amnesia (very common viva)

• Glycopyrrolate preferred over atropine → less CNS effect

• Ondansetron → best for PONV prevention

 

 

GENERAL ANAESTHETICS

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🔸 Stages & Planes of Anaesthesia (Guedel’s Classification)

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Stage I – Analgesia

• From start of anaesthesia → loss of consciousness

• Features:

  • Analgesia present

  • Patient conscious initially

  • Memory gradually lost

• Clinical:

  • Useful for minor procedures

---

Stage II – Excitement / Delirium

• From loss of consciousness → onset of regular respiration

• Features:

  • Delirium, agitation

  • Irregular breathing

  • Vomiting, risk of aspiration

  • Increased reflexes

• Clinical significance:

  • Dangerous stage → must be passed rapidly

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Stage III – Surgical Anaesthesia (VERY IMPORTANT)

Divided into 4 planes

Plane 1

• Regular respiration begins

• Loss of eyelash reflex

• Suitable for minor surgery

Plane 2

• Loss of corneal reflex

• Relaxation of muscles

• Regular respiration

• Suitable for most surgeries

Plane 3

• Intercostal muscle paralysis begins

• Shallow respiration

• Pupillary dilation begins

Plane 4

• Diaphragmatic breathing only

• Severe CNS depression

• Approaching overdose

---

Stage IV – Medullary Paralysis (OVERDOSE)

• Respiratory failure

• Cardiovascular collapse

• Fatal if untreated

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📊 TABLE — STAGES OF ANAESTHESIA (HIGH-YIELD)

Stage	Features	Clinical Significance
I	Analgesia, conscious	Minor procedures
II	Excitement, delirium	Dangerous
III	Surgical anaesthesia	Ideal stage
IV	Medullary paralysis	Fatal

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🧠 FLOWCHART — ANAESTHESIA DEPTH

Induction
↓
Stage I (Analgesia)
↓
Stage II (Excitement) ⚠️
↓
Stage III (Surgical) ✅
↓
Stage IV (Overdose) ❌

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🔬 SLIDES (EXAM FAVORITE)

Clinical Signs in Guedel’s Stages

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🔸 Classification of General Anaesthetics

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1. Inhalational Anaesthetics

Gases

• Nitrous oxide (N₂O)

  • Weak anaesthetic

  • Strong analgesic

• Xenon (conceptual)

  • NMDA antagonist

  • Very expensive

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Volatile Liquids

• Halothane

• Isoflurane

• Sevoflurane

• Desflurane

Key Points

• Used for maintenance of anaesthesia

• Differ in:

  • Potency (MAC)

  • Induction speed

  • Toxicity profile

---

2. Intravenous Anaesthetics

---

Induction Agents

• Propofol

• Thiopentone

• Etomidate

Features

• Rapid onset

• Used for induction

---

Dissociative Anaesthetic

• Ketamine

  • Produces dissociative anaesthesia

  • Analgesia + amnesia

  • ↑ BP, ↑ HR (unique)

---

Benzodiazepines

• Midazolam

  • Sedation + amnesia

  • Used in premedication & procedures

---

Opioids

• Fentanyl

  • Potent analgesic

  • Used in balanced anaesthesia

---

📊 TABLE — CLASSIFICATION SUMMARY (VERY HIGH-YIELD)

Class	Drugs	Key Feature
Inhalational gas	Nitrous oxide	Analgesic
Volatile liquid	Sevoflurane	Rapid induction
IV induction	Propofol	Smooth recovery
Dissociative	Ketamine	↑ BP, analgesia
Benzodiazepine	Midazolam	Amnesia
Opioid	Fentanyl	Strong analgesia

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🧠 DIAGRAM — CLASSIFICATION OVERVIEW

General Anaesthetics
→ Inhalational
  → Gases
  → Volatile liquids
→ Intravenous
  → Induction agents
  → Dissociative
  → Benzodiazepines
  → Opioids

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🔬 SLIDES (EXAM FAVORITE)

Volatile Anaesthetic Agents Comparison (Clinical Representation)

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✅ EXAM PEARLS

• Stage II = dangerous → rapid induction required

• Stage III plane 2 = ideal for surgery

• Stage IV = overdose (medullary failure)

• Propofol = most commonly used induction agent

• Ketamine = only anaesthetic that ↑ BP & HR

• Nitrous oxide = good analgesic but weak anaesthetic

 

GENERAL ANAESTHETICS

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🔸 Mechanism of Action (VERY HIGH-YIELD)

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1. GABA-A Receptor Potentiation

• Most general anaesthetics (propofol, thiopentone, volatile agents)

• Mechanism:

  • ↑ GABA-mediated Cl⁻ influx

  • → Hyperpolarization of neurons

  • → CNS depression

• Result:

  • Sedation

  • Hypnosis

  • Amnesia

---

2. NMDA Receptor Inhibition

• Drugs: ketamine, nitrous oxide

• Mechanism:

  • Block glutamate (excitatory neurotransmitter)

  • ↓ excitatory transmission

• Result:

  • Analgesia

  • Dissociative anaesthesia

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3. Glycine Receptor Activation

• Especially in spinal cord

• Enhances inhibitory neurotransmission

• Leads to:

  • Immobility

  • Muscle relaxation

---

4. Two-Pore K⁺ Channel Activation

• Opens K⁺ channels → K⁺ efflux

• Causes:

  • Hyperpolarization

  • Reduced neuronal excitability

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5. Lipid Theory vs Protein Theory

Lipid Theory (Meyer–Overton Rule)

• Anaesthetic potency ∝ lipid solubility

• Acts by altering cell membrane fluidity

Protein Theory (MODERN ACCEPTED)

• Direct interaction with:

  • Ion channels

  • Receptors (GABA, NMDA)

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📊 TABLE — MECHANISM SUMMARY

Mechanism	Drugs	Effect
GABA ↑	Propofol, thiopentone	Sedation
NMDA ↓	Ketamine, N₂O	Analgesia
Glycine ↑	Volatile agents	Immobility
K⁺ channels ↑	Volatile agents	CNS depression

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🧠 FLOWCHART — ANAESTHETIC MECHANISM

Anaesthetic drug
↓
GABA ↑ / NMDA ↓
↓
Neuronal inhibition
↓
Loss of consciousness + analgesia + immobility

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🔬 SLIDES (EXAM FAVORITE)

GABA vs NMDA Pathway

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🔸 Pharmacokinetics

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Uptake & Distribution of Inhalational Anaesthetics

• Transfer pathway:

  • Alveoli → Blood → Brain → Other tissues

• Goal:

  • Rapid attainment of equilibrium between alveoli and brain

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Factors Affecting Induction & Recovery

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1. Blood Solubility (VERY IMPORTANT)

• Measured by blood:gas partition coefficient

Clinical Correlation:

• Low solubility → rapid induction & recovery

  • Example: desflurane, sevoflurane

• High solubility → slow induction

  • Example: halothane

---

2. Alveolar Ventilation

• ↑ ventilation → ↑ anaesthetic delivery

• → Faster induction

---

3. Cardiac Output

• ↑ cardiac output:

  • Slows induction (more uptake into blood)

• ↓ cardiac output:

  • Faster induction

---

Concentration Effect (VERY HIGH-YIELD)

• High inspired concentration → faster rise in alveolar concentration

• Leads to:

  • Faster induction

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Second Gas Effect (VERY HIGH-YIELD)

• Occurs when nitrous oxide is given with another anaesthetic

Mechanism:

• Rapid uptake of N₂O → ↓ alveolar volume

• → ↑ concentration of second gas

Result:

• Faster induction of second agent

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Diffusion Hypoxia (N₂O)

Mechanism:

• Rapid diffusion of N₂O from blood → alveoli

• Dilutes oxygen in alveoli

Result:

• Hypoxia during recovery

Prevention:

• Give 100% O₂ after stopping N₂O

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Redistribution (IV Anaesthetics)

• After IV administration:

  • Drug moves from brain → muscle → fat

Clinical Significance:

• Short duration of action (thiopentone, propofol)

• Recovery due to redistribution, not metabolism

---

Metabolism

---

Hepatic Metabolism

• Propofol, thiopentone

• Halothane (significant metabolism)

---

Minimal Metabolism

• Desflurane, sevoflurane

• Nitrous oxide

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📊 TABLE — PHARMACOKINETIC SUMMARY

Factor	Effect on Induction
Blood solubility ↓	Faster
Ventilation ↑	Faster
Cardiac output ↑	Slower
Concentration ↑	Faster

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🧠 FLOWCHART — INDUCTION DYNAMICS

Inspired concentration ↑
↓
Alveolar concentration ↑
↓
Blood concentration ↑
↓
Brain concentration ↑
↓
Anaesthesia

---

🔬 SLIDES (EXAM FAVORITE)

Uptake & Distribution Pathway

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✅ EXAM PEARLS

• GABA potentiation = most important mechanism

• Ketamine = NMDA blocker → dissociative anaesthesia

• Low blood:gas = fastest induction (desflurane)

• Second gas effect = N₂O phenomenon

• Diffusion hypoxia → prevented by 100% O₂

• IV agents act short due to redistribution, not metabolism

 

GENERAL ANAESTHETICS

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🔸 Depth of Anaesthesia Monitoring

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1. Clinical Signs (CLASSICAL – VERY IMPORTANT)

Eye Signs

• Eyelash reflex → lost early (Stage III)

• Corneal reflex → lost in deeper anaesthesia

• Pupils:

  • Constricted → adequate anaesthesia

  • Dilated → light anaesthesia or hypoxia

---

Respiratory Pattern

• Regular breathing → adequate depth

• Irregular respiration → Stage II (dangerous)

• Shallow/slow respiration → deep anaesthesia

---

Muscle Tone

• Progressive relaxation with depth

• Complete relaxation in surgical anaesthesia

---

Cardiovascular Signs

• Tachycardia, hypertension → light anaesthesia

• Hypotension → deep anaesthesia

---

2. Bispectral Index (BIS Monitoring)

• Based on processed EEG signals

• Provides numerical value (0–100)

Interpretation:

• 100 → fully awake

• 40–60 → ideal surgical anaesthesia

• <40 → deep anaesthesia

Advantages:

• Prevents awareness during surgery

• Helps titrate anaesthetic dose

---

3. EEG Monitoring

• Measures electrical activity of brain

Changes with depth:

• Awake → high frequency, low amplitude

• Anaesthesia → low frequency, high amplitude

• Deep anaesthesia → burst suppression

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🔬 SLIDES (EXAM FAVORITE)

EEG Changes During Anaesthesia

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🔸 Effects on Organ Systems

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CNS Effects

↓ CMRO₂ (Cerebral Metabolic Rate)

• Most anaesthetics ↓ brain metabolism

• Neuroprotective effect

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Effect on ICP (Intracranial Pressure)

• Volatile agents → ↑ ICP

• Propofol, thiopentone → ↓ ICP

---

Cerebral Blood Flow (CBF)

• Volatile anaesthetics → vasodilation → ↑ CBF

• IV agents → ↓ CBF

---

Seizure Threshold

• Enflurane → ↓ threshold → may cause seizures

• Others generally anticonvulsant

---

CVS Effects

• Most agents:

  • ↓ myocardial contractility

  • ↓ blood pressure

• Exception:

  • Ketamine

    • ↑ sympathetic tone

    • ↑ BP, ↑ HR

---

Respiratory Effects

• Dose-dependent respiratory depression

• ↓ tidal volume

• ↓ respiratory rate

• Loss of airway reflexes

---

Renal Effects

• ↓ renal blood flow (secondary to hypotension)

• ↓ GFR

---

Hepatic Effects

• ↓ hepatic blood flow

• Halothane:

  • Risk of hepatotoxicity

---

Uterine Effects

• Relaxation of uterine smooth muscle

• May lead to:

  • Postpartum hemorrhage

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📊 TABLE — ORGAN SYSTEM EFFECTS (VERY HIGH-YIELD)

System	Effect
CNS	↓ CMRO₂, ↑/↓ ICP
CVS	↓ BP (except ketamine ↑)
Respiratory	Depression
Renal	↓ GFR
Hepatic	↓ blood flow
Uterus	Relaxation

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🔸 Neuromuscular Junction Interaction

---

1. Potentiation of Muscle Relaxants

• Inhalational anaesthetics:

  • Enhance action of non-depolarizing NM blockers

• Mechanism:

  • ↓ sensitivity of post-synaptic membrane

  • ↓ ACh release

---

2. Effect on Neuromuscular Transmission

• Direct depression of:

  • Neuromuscular transmission

  • Skeletal muscle tone

---

Clinical Significance

• Lower dose of muscle relaxants required

• Risk of:

  • Prolonged paralysis

  • Respiratory depression

---

🧠 FLOWCHART — NMJ EFFECT

Anaesthetic agent
↓
↓ ACh release + ↓ receptor sensitivity
↓
Enhanced muscle relaxation
↓
↓ skeletal muscle tone

---

🔬 SLIDES (EXAM FAVORITE)

Neuromuscular Junction Interaction

---

✅ EXAM PEARLS

• BIS 40–60 = ideal anaesthesia

• Ketamine = only agent increasing BP & HR

• Propofol ↓ ICP → DOC in neurosurgery

• Volatile agents ↑ CBF → ↑ ICP

• Respiratory depression = dose dependent

• Anaesthetics potentiate muscle relaxants → dose reduction needed

 

 

 

GENERAL ANAESTHETICS

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🔸 Individual Drug Profiles (VERY HIGH-YIELD)

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PROPOFOL

Mechanism

• Potentiates GABA-A receptor

Pharmacological Actions

• Rapid induction (within seconds)

• Smooth recovery

• Antiemetic effect

Uses

• Induction agent (DOC)

• Maintenance (TIVA)

• ICU sedation

Adverse Effects

• Hypotension

• Respiratory depression

• Pain on injection

Key Point

• Fastest recovery → day-care surgery drug of choice

---

THIOPENTONE (Thiopental)

Mechanism

• GABA-A receptor activation

Features

• Ultra-short acting (due to redistribution)

• Rapid induction

Uses

• Induction

• Control of seizures

Adverse Effects

• Respiratory depression

• Hypotension

Key Point

• Accumulation on repeated use

---

KETAMINE

Mechanism

• NMDA receptor antagonist

Unique Features

• Dissociative anaesthesia

• Strong analgesia

• Bronchodilation

CVS Effects

• ↑ BP, ↑ HR (sympathomimetic)

Uses

• Trauma patients

• Asthma

• Short painful procedures

Adverse Effects

• Emergence delirium

• Hallucinations

Key Point

• Only anaesthetic that increases BP

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ETOMIDATE

Mechanism

• GABA-A receptor potentiation

Features

• Minimal cardiovascular depression

• Hemodynamically stable

Uses

• Induction in cardiac patients

Adverse Effects

• Adrenal suppression

• Myoclonus

Key Point

• Drug of choice in shock / unstable patients

---

HALOTHANE

Type

• Volatile inhalational anaesthetic

Features

• Potent anaesthetic

• Smooth induction

Adverse Effects

• Halothane hepatitis

• Arrhythmias

• Myocardial depression

Key Point

• Rarely used now due to hepatotoxicity

---

ISOFLURANE

Features

• Moderate potency

• Stable cardiac profile

Effects

• Vasodilation → ↓ BP

• Preserves cardiac output

Key Point

• Widely used for maintenance

---

SEVOFLURANE

Features

• Low blood:gas coefficient

• Rapid induction & recovery

Advantages

• Non-irritant

• Pleasant odor

Uses

• Paediatric induction (DOC)

Key Point

• Smooth and fast acting

---

DESFLURANE

Features

• Very low blood solubility

• Fastest induction & recovery

Adverse Effects

• Airway irritation

• Cough, laryngospasm

Key Point

• Best for day-care surgeries

---

NITROUS OXIDE (N₂O)

Type

• Inhalational gas

Features

• Weak anaesthetic

• Strong analgesic

Advantages

• Rapid onset

• Minimal metabolism

Adverse Effects

• Diffusion hypoxia

• Megaloblastic anemia (B12 inhibition)

Key Point

• Used as adjunct in balanced anaesthesia

---

📊 TABLE — DRUG COMPARISON (VERY HIGH-YIELD)

Drug	Key Feature	Major Advantage	Important Adverse Effect
Propofol	Rapid onset	Smooth recovery	Hypotension
Thiopentone	Ultra-short acting	Rapid induction	Accumulation
Ketamine	NMDA blocker	↑ BP, bronchodilation	Hallucinations
Etomidate	Hemodynamic stability	Safe in shock	Adrenal suppression
Halothane	Potent	Smooth induction	Hepatitis
Isoflurane	Stable CVS	Maintenance	Hypotension
Sevoflurane	Fast induction	Pediatric use	Minimal toxicity
Desflurane	Fastest recovery	Day-care surgery	Airway irritation
Nitrous oxide	Analgesic	Rapid action	Diffusion hypoxia

---

🧠 FLOWCHART — DRUG SELECTION

Hemodynamically unstable → Etomidate
↓
Asthma / trauma → Ketamine
↓
Routine induction → Propofol
↓
Pediatric → Sevoflurane
↓
Day-care surgery → Desflurane

---

🔬 SLIDES (EXAM FAVORITE)

Propofol & Ketamine Clinical Representation

---

Volatile Anaesthetics Delivery System

---

✅ EXAM PEARLS

• Propofol = most commonly used induction agent

• Ketamine = dissociative anaesthesia + ↑ BP

• Etomidate = DOC in shock

• Sevoflurane = DOC in pediatrics

• Desflurane = fastest recovery

• Nitrous oxide = strong analgesic, weak anaesthetic

• Halothane = hepatotoxic → obsolete

 

 

 

GENERAL ANAESTHETICS

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🔸 Adverse Effects & Toxicity

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Respiratory Depression (VERY IMPORTANT)

• Dose-dependent ↓ in:

  • Respiratory rate

  • Tidal volume

• Mechanism:

  • Depression of medullary respiratory center

Clinical Risks

• Hypoventilation

• Hypercapnia

• Apnea (high doses)

---

Hypotension

• Due to:

  • ↓ myocardial contractility

  • Peripheral vasodilation

Drugs commonly causing:

• Propofol

• Volatile anaesthetics

---

Arrhythmias

• Especially with halothane

• Mechanism:

  • Sensitization of myocardium to catecholamines

Clinical importance

• Ventricular arrhythmias possible

---

Emergence Delirium (Ketamine)

• Features:

  • Hallucinations

  • Agitation

  • Vivid dreams

Prevention:

• Benzodiazepines (midazolam)

---

📊 TABLE — COMMON ADVERSE EFFECTS

Effect	Mechanism	Drug Example
Respiratory depression	CNS depression	Propofol
Hypotension	Vasodilation	Isoflurane
Arrhythmias	Catecholamine sensitivity	Halothane
Delirium	NMDA block	Ketamine

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🔸 Specific Toxicities (EXPANDED – VERY HIGH-YIELD)

---

Malignant Hyperthermia (EMERGENCY)

Cause

• Genetic mutation in ryanodine receptor (RYR1)

• Triggered by:

  • Volatile anaesthetics

  • Succinylcholine

---

Pathophysiology

• ↑ Ca²⁺ release from sarcoplasmic reticulum
  → Sustained muscle contraction
  → ↑ heat production

---

Clinical Features

• Hyperthermia

• Muscle rigidity

• Tachycardia

• Hypercapnia

---

Treatment

• Dantrolene (drug of choice)

• Cooling measures

• Oxygen support

---

🧠 FLOWCHART — MALIGNANT HYPERTHERMIA

Trigger (anaesthetic)
↓
RYR mutation → ↑ Ca²⁺
↓
Muscle rigidity + heat production
↓
Hyperthermia + acidosis
↓
Dantrolene treatment

---

🔬 SLIDES (EXAM FAVORITE)

Malignant Hyperthermia Clinical Features

---

Halothane Hepatitis

Types

• Type I (mild) → transient liver enzyme rise

• Type II (severe) → immune-mediated hepatic necrosis

---

Risk Factors

• Repeated exposure

• Obesity

• Female sex

---

Mechanism

• Formation of trifluoroacetylated proteins
  → Immune-mediated injury

---

Fluoride Nephrotoxicity

Cause

• Metabolism of certain volatile agents

• ↑ serum fluoride ions

Effect

• Renal tubular damage

---

Compound A Toxicity (Sevoflurane)

Cause

• Reaction with soda lime → formation of Compound A

Effect

• Nephrotoxicity (experimental relevance)

---

Desflurane Airway Irritation

Features

• Pungent odor

• Causes:

  • Cough

  • Laryngospasm

Clinical Use

• Not preferred for induction

---

Nitrous Oxide Toxicity

Mechanism

• Inactivates vitamin B12
  → Impairs DNA synthesis

---

Effects

• Megaloblastic anemia

• Neuropathy

---

📊 TABLE — SPECIFIC TOXICITIES (VERY HIGH-YIELD)

Drug	Toxicity	Mechanism
Halothane	Hepatitis	Immune-mediated
Sevoflurane	Compound A toxicity	Soda lime reaction
Desflurane	Airway irritation	Direct irritation
N₂O	Megaloblastic anemia	B12 inhibition
Volatile agents	Malignant hyperthermia	Ca²⁺ dysregulation

---

✅ EXAM PEARLS

• Malignant hyperthermia → treat with dantrolene

• Halothane → hepatitis (classic viva)

• Sevoflurane → Compound A (nephrotoxicity concept)

• Desflurane → airway irritation → not for induction

• Nitrous oxide → B12 inhibition → anemia

• Propofol → hypotension + respiratory depression

 

 

GENERAL ANAESTHETICS

---

🔸 Malignant Hyperthermia (VERY IMPORTANT)

---

Etiology

• Autosomal dominant disorder

• Mutation in ryanodine receptor (RYR1) → skeletal muscle Ca²⁺ channel

---

Triggering Agents

• Volatile anaesthetics:

  • Halothane, isoflurane, sevoflurane, desflurane

• Depolarizing muscle relaxant:

  • Succinylcholine

---

Pathophysiology

• Abnormal ↑ Ca²⁺ release from sarcoplasmic reticulum
  → Sustained muscle contraction
  → ↑ ATP consumption
  → Heat production + metabolic acidosis

---

Clinical Features

• Early signs

  • Hypercapnia (↑ CO₂ – earliest sign)

  • Tachycardia

• Late signs

  • Muscle rigidity

  • Hyperthermia

  • Acidosis

  • Rhabdomyolysis

---

Treatment (EMERGENCY MANAGEMENT)

• Dantrolene (Drug of choice)

  • Blocks Ca²⁺ release from SR

• 100% oxygen

• Active cooling

• Correction of acidosis (NaHCO₃)

---

📊 TABLE — MALIGNANT HYPERTHERMIA SUMMARY

Feature	Description
Cause	RYR1 mutation
Trigger	Volatile agents, succinylcholine
Early sign	Hypercapnia
Key drug	Dantrolene

---

🧠 FLOWCHART — MALIGNANT HYPERTHERMIA

Trigger drug
↓
RYR mutation → ↑ Ca²⁺
↓
Muscle contraction
↓
↑ Heat + acidosis
↓
Dantrolene + supportive care

---

🔬 SLIDES (EXAM FAVORITE)

Ryanodine Receptor & Ca²⁺ Release

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🔸 Drug Interactions

---

1. With Muscle Relaxants

• Inhalational anaesthetics:

  • Potentiate non-depolarizing NM blockers

Mechanism

• ↓ ACh release

• ↓ sensitivity of post-synaptic receptors

Clinical Significance

• Lower dose of muscle relaxant required

• Risk of prolonged paralysis

---

2. With Opioids and Sedatives

• Additive CNS depression

Effects

• ↑ sedation

• ↑ respiratory depression

• ↑ hypotension

---

3. Potentiation Effects

• Combined use leads to:

  • Enhanced anaesthetic depth

  • Reduced dose requirement

  • Increased risk of overdose

---

📊 TABLE — DRUG INTERACTIONS

Combination	Effect
Anaesthetic + NM blocker	↑ muscle relaxation
Anaesthetic + opioid	↑ analgesia + respiratory depression
Anaesthetic + benzodiazepine	↑ sedation

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🔸 Clinical Uses

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Induction vs Maintenance

Induction

• Rapid-acting IV agents:

  • Propofol (most common)

  • Thiopentone

  • Etomidate

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Maintenance

• Inhalational agents:

  • Isoflurane

  • Sevoflurane

  • Desflurane

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Day-Care Surgery

• Requirements:

  • Rapid onset

  • Rapid recovery

Drugs:

• Propofol

• Desflurane

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Obstetrics

• Requirements:

  • Minimal fetal depression

  • Rapid recovery

Drugs:

• Nitrous oxide

• Low-dose volatile agents

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Neurosurgery

• Requirements:

  • ↓ intracranial pressure (ICP)

Drugs:

• Propofol

• Thiopentone

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📊 TABLE — CLINICAL USES

Situation	Drug of Choice
Induction	Propofol
Maintenance	Isoflurane
Day-care surgery	Desflurane
Shock	Etomidate
Asthma	Ketamine
Neurosurgery	Propofol

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🔸 Obstetric Anaesthesia (EXPANDED)

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Physiological Effects

• Volatile anaesthetics:

  • Cause uterine relaxation

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Clinical Consequence

• ↓ uterine tone
  → Postpartum hemorrhage risk

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Drug Considerations

Preferred

• Nitrous oxide (analgesia)

• Low-dose inhalational agents

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Avoid / Use with caution

• High-dose volatile anaesthetics → excessive uterine relaxation

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🧠 FLOWCHART — OBSTETRIC ANAESTHESIA

Anaesthetic drug
↓
Uterine relaxation
↓
↓ uterine tone
↓
Risk of hemorrhage

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🔬 SLIDES (EXAM FAVORITE)

Uterine Relaxation Mechanism

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✅ EXAM PEARLS

• Malignant hyperthermia → earliest sign = hypercapnia

• Dantrolene = life-saving drug

• Volatile agents potentiate muscle relaxants

• Propofol = DOC for induction & neurosurgery

• Desflurane = best for day-care surgery

• Ketamine = preferred in asthma & shock

• Volatile agents → uterine relaxation → PPH risk

 

GENERAL ANAESTHETICS

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🔸 Contraindications / Precautions

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Raised Intracranial Pressure (ICP)

Problem

• Many volatile anaesthetics → cerebral vasodilation → ↑ cerebral blood flow (CBF)

• → ↑ ICP

Clinical Risk

• Worsening of:

  • Brain edema

  • Intracranial hypertension

  • Herniation risk

Preferred Drugs

• Propofol

• Thiopentone
  → ↓ CBF and ↓ ICP

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Shock (Hemodynamic Instability)

Problem

• Most anaesthetics:

  • ↓ myocardial contractility

  • ↓ blood pressure

Clinical Risk

• Severe hypotension

• Organ hypoperfusion

Preferred Drug

• Etomidate

  • Minimal cardiovascular depression

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Cardiac Instability

Problem

• Anaesthetics may cause:

  • Arrhythmias

  • Myocardial depression

Examples

• Halothane → sensitizes myocardium to catecholamines → arrhythmias

Precaution

• Avoid arrhythmogenic agents

• Careful monitoring required

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📊 TABLE — CONTRAINDICATIONS & DRUG CHOICE

Condition	Risk	Preferred Drug
Raised ICP	↑ ICP	Propofol
Shock	Hypotension	Etomidate
Cardiac instability	Arrhythmia	Isoflurane (relatively safe)

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🧠 FLOWCHART — DRUG SELECTION IN SPECIAL CONDITIONS

Raised ICP → Propofol
↓
Shock → Etomidate
↓
Cardiac instability → Avoid halothane

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🔸 Environmental & Occupational Aspects

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Operating Room Pollution

Sources

• Leakage of anaesthetic gases:

  • Nitrous oxide

  • Volatile anaesthetics

Causes

• Faulty equipment

• Poor scavenging systems

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Chronic Exposure Risks

In Healthcare Workers

• Headache

• Fatigue

• Reduced alertness

Long-Term Risks

• Reproductive issues (infertility, miscarriage)

• Possible hepatotoxicity

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Preventive Measures

• Proper ventilation

• Use of gas scavenging systems

• Regular equipment maintenance

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📊 TABLE — OCCUPATIONAL HAZARDS

Exposure	Effect
Acute	Headache, dizziness
Chronic	Reproductive risk
High exposure	Organ toxicity

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🔬 SLIDES (EXAM FAVORITE)

Anaesthetic Gas Scavenging System

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🔸 Historical Anaesthetics (Conceptual)

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Ether

Features

• First effective general anaesthetic

• Good analgesia and muscle relaxation

Disadvantages

• Highly flammable

• Slow induction and recovery

• Irritating to airway

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Chloroform

Features

• Rapid induction

• Pleasant odor

Toxicity

• Severe hepatotoxicity

• Cardiac arrhythmias

• Sudden cardiac death

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Clinical Status

• Both are obsolete due to:

  • Safer modern anaesthetics

  • Better control and fewer adverse effects

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📊 TABLE — HISTORICAL AGENTS

Drug	Advantage	Major Problem
Ether	Effective anaesthesia	Flammable
Chloroform	Rapid induction	Cardiotoxic

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🧠 FLOWCHART — EVOLUTION OF ANAESTHESIA

Ether / Chloroform
↓
Halothane
↓
Modern agents (Sevoflurane, Desflurane)

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🔬 SLIDES (EXAM FAVORITE)

Early Anaesthesia Apparatus (Historical)

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✅ EXAM PEARLS

• Raised ICP → avoid volatile agents, use propofol

• Shock → etomidate is safest

• Halothane → arrhythmogenic

• Chronic anaesthetic exposure → occupational hazard

• Ether = flammable, chloroform = cardiotoxic

• Modern anaesthesia = safer, controlled, rapid recovery

 

GENERAL ANAESTHETICS

📊 TABLES (FINAL COMPLETE)

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Inhalational vs IV Anaesthetics

Feature	Inhalational Anaesthetics	IV Anaesthetics
Route	Inhaled through lungs	Intravenous
Main use	Maintenance	Induction
Onset	Depends on blood:gas solubility	Very rapid
Recovery	Depends on ventilation, solubility, duration	Mainly by redistribution initially
Control of depth	Easy by changing inspired concentration	Less easily controlled
Examples	N₂O, sevoflurane, desflurane, isoflurane	Propofol, thiopentone, etomidate, ketamine
Common toxicity	Respiratory depression, hypotension, malignant hyperthermia	Respiratory depression, hypotension
Special point	Useful for long procedures	Useful for rapid induction

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MAC Values Comparison (VERY HIGH-YIELD)

Drug	Approximate MAC	Potency
Halothane	0.75	High
Isoflurane	1.15	Moderate-high
Sevoflurane	2	Moderate
Desflurane	6	Low
Nitrous oxide	>100	Very low

Key rule:

• Lower MAC = higher potency

• Higher MAC = lower potency

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Blood:Gas vs Oil:Gas Partition Coefficients

Coefficient	Meaning	Clinical Importance
Blood:gas coefficient	Solubility in blood	Determines speed of induction and recovery
Low blood:gas	Poorly soluble in blood	Fast induction and recovery
High blood:gas	Highly soluble in blood	Slow induction and recovery
Oil:gas coefficient	Lipid solubility	Determines potency
High oil:gas	More lipid soluble	More potent, lower MAC

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Propofol vs Thiopentone vs Etomidate vs Ketamine

Feature	Propofol	Thiopentone	Etomidate	Ketamine
Mechanism	GABA-A potentiation	GABA-A potentiation	GABA-A potentiation	NMDA blockade
Onset	Rapid	Rapid	Rapid	Rapid
Recovery	Smooth, rapid	Slower after repeated doses	Rapid	May have delirium
CVS effect	Hypotension	Hypotension	Minimal depression	↑ BP, ↑ HR
Respiration	Depression	Depression	Mild depression	Less depression
Analgesia	Poor	Poor	Poor	Good
Special use	Day-care, TIVA	Induction, seizures	Shock, cardiac instability	Trauma, asthma
Important adverse effect	Pain on injection, hypotension	Accumulation	Adrenal suppression	Emergence delirium

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Volatile Anaesthetics Comparison

Drug	Induction/Recovery	Airway Irritation	Important Toxicity	Key Use
Halothane	Slow-moderate	Non-irritant	Hepatitis, arrhythmia	Mostly obsolete
Isoflurane	Moderate	Irritant	Hypotension	Maintenance
Sevoflurane	Rapid	Non-irritant	Compound A concept	Pediatric induction
Desflurane	Fastest	Irritant	Cough, laryngospasm	Day-care surgery

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Organ System Effects Comparison

System	Main Effect
CNS	↓ CMRO₂; volatile agents may ↑ CBF and ICP
CVS	Hypotension due to myocardial depression/vasodilation; ketamine increases BP
Respiratory	Dose-dependent respiratory depression
Liver	↓ hepatic blood flow; halothane hepatitis
Kidney	↓ renal blood flow and GFR; fluoride nephrotoxicity concept
Uterus	Relaxation → postpartum hemorrhage risk
NMJ	Potentiates non-depolarizing muscle relaxants

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Stages of Anaesthesia (Guedel)

Stage	Name	Features	Importance
Stage I	Analgesia	Analgesia, consciousness gradually lost	Minor procedures
Stage II	Excitement	Delirium, irregular respiration, vomiting risk	Dangerous stage
Stage III	Surgical anaesthesia	Regular breathing, muscle relaxation	Desired stage
Stage IV	Medullary paralysis	Respiratory failure, CVS collapse	Overdose

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Induction vs Recovery Characteristics

Drug	Induction	Recovery	Key Point
Propofol	Very rapid	Smooth and rapid	Best routine induction
Thiopentone	Rapid	Delayed with repeated doses	Redistribution initially
Etomidate	Rapid	Rapid	CVS stable
Ketamine	Rapid	Emergence reactions	Analgesic
Sevoflurane	Rapid	Rapid	Pediatric use
Desflurane	Rapid	Fastest	Day-care surgery

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Adverse Effects Comparison

Adverse Effect	Common Drug/Group
Respiratory depression	Propofol, thiopentone, volatile agents
Hypotension	Propofol, volatile agents
Arrhythmias	Halothane
Emergence delirium	Ketamine
Hepatitis	Halothane
Airway irritation	Desflurane
Diffusion hypoxia	Nitrous oxide
Megaloblastic anemia	Nitrous oxide
Adrenal suppression	Etomidate
Malignant hyperthermia	Volatile agents + succinylcholine

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Malignant Hyperthermia — Triggers vs Treatment

Feature	Details
Genetic defect	Ryanodine receptor mutation
Triggers	Halothane, isoflurane, sevoflurane, desflurane, succinylcholine
Earliest sign	Hypercarbia
Other features	Muscle rigidity, tachycardia, hyperthermia, acidosis
Treatment	Dantrolene
Supportive care	100% O₂, cooling, correction of acidosis

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Clinical Uses vs Drug of Choice

Clinical Situation	Preferred Drug
Routine induction	Propofol
Day-care surgery	Propofol / desflurane
Shock/cardiac instability	Etomidate
Asthma/bronchospasm	Ketamine
Pediatric inhalational induction	Sevoflurane
Neurosurgery/raised ICP	Propofol / thiopentone
Balanced anaesthesia analgesic adjunct	Nitrous oxide / fentanyl
Obstetric analgesia	Nitrous oxide cautiously

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Preanaesthetic Medication Drugs & Roles

Drug Class	Examples	Role
Benzodiazepines	Midazolam, diazepam	Anxiolysis, sedation, amnesia
Opioids	Fentanyl, morphine	Analgesia, ↓ anaesthetic requirement
Anticholinergics	Atropine, glycopyrrolate	↓ secretions, prevent vagal bradycardia
Antiemetics	Ondansetron, metoclopramide	Prevent nausea and vomiting
H2 blockers / PPIs	Ranitidine, omeprazole	↓ gastric acidity, aspiration prophylaxis

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🧠 DIAGRAMS / FLOWCHARTS (FINAL CORE)

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Mechanism of Anaesthesia — GABA/NMDA Pathways

Anaesthetic agents
↓
GABA-A potentiation
→ ↑ Cl⁻ influx
→ neuronal hyperpolarization
→ hypnosis, sedation, amnesia

Anaesthetic agents
↓
NMDA inhibition
→ ↓ glutamate excitatory transmission
→ analgesia, dissociative anaesthesia

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Stages of Anaesthesia Flowchart

Induction
↓
Stage I — Analgesia
↓
Stage II — Excitement
↓
Stage III — Surgical anaesthesia
↓
Stage IV — Medullary paralysis

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Uptake & Distribution of Inhalational Anaesthetics

Inspired anaesthetic
↓
Alveoli
↓
Pulmonary blood
↓
Arterial blood
↓
Brain
↓
Anaesthesia

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Factors Affecting Induction & Recovery

Blood solubility ↓
→ faster induction and recovery

Alveolar ventilation ↑
→ faster induction

Cardiac output ↑
→ slower induction

Inspired concentration ↑
→ faster induction

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MAC Concept Diagram

Anaesthetic concentration increases
↓
Movement response decreases
↓
Concentration at which 50% patients do not move
↓
MAC

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Second Gas Effect

Nitrous oxide rapidly enters blood
↓
Alveolar volume decreases
↓
Concentration of second anaesthetic gas rises
↓
Faster induction of second gas

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Diffusion Hypoxia Mechanism

Stop nitrous oxide
↓
N₂O rapidly diffuses from blood to alveoli
↓
Dilutes alveolar oxygen
↓
Hypoxia
↓
Prevent with 100% oxygen

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Malignant Hyperthermia Pathogenesis

Volatile anaesthetic / succinylcholine
↓
RYR1 mutation
↓
Excess Ca²⁺ release from sarcoplasmic reticulum
↓
Sustained muscle contraction
↓
Hypercarbia + rigidity + acidosis + hyperthermia
↓
Dantrolene

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Balanced Anaesthesia Concept

Premedication
↓
IV induction agent
↓
Opioid analgesic
↓
Muscle relaxant
↓
Inhalational maintenance
↓
Safe surgical anaesthesia with reduced toxicity

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IV Anaesthetic Redistribution

IV bolus
↓
Brain uptake
↓
Rapid anaesthesia
↓
Redistribution to muscle
↓
Redistribution to fat
↓
Recovery from single dose

 

 

GENERAL ANAESTHETICS

🔬 SLIDES (EXAM FAVORITE)

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GABA-A Receptor Diagram

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NMDA Receptor Schematic

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Guedel’s Stages Clinical Signs

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Malignant Hyperthermia Features

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Vapourizer & Anaesthesia Machine

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EEG Changes During Anaesthesia

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Muscle Rigidity in Malignant Hyperthermia