26 ANAESTHETICS, SEDATION & ANALGESIA

# 27 ANAESTHETICS, SEDATION & ANALGESIA

👩‍⚕️ Anaesthetics is predictable territory in MRCS Part A. Examiners return to the same cluster: LA dose calculations, the WHO ladder, ketamine in shock, opioid reversal, malignant hyperthermia, and suxamethonium contraindications. Recite the antidotes cold and calculate a lidocaine maximum in under thirty seconds — easy marks.

The three phases of general anaesthesia

GA rests on the triad: hypnosis + analgesia + muscle relaxation. No single drug delivers all three safely.

➡ Induction — IV agent renders the patient unconscious in ~30 s (one arm-brain circulation).

➡ Maintenance — volatile agent ± nitrous oxide ± opioid; alternatively TIVA with propofol infusion.

➡ Emergence — agents stopped, neuromuscular block reversed, reflexes return.

👩‍⚕️ Post-induction hypotension is the rule: all IV induction agents (except ketamine) venodilate, dropping preload. Propofol and thiopentone add direct myocardial depression.

IV induction agents

Agent	Mechanism	Strengths	Watch out for
Propofol	GABA-A	Rapid on/off, antiemetic, smooth recovery	Hypotension, pain on injection, propofol infusion syndrome
Thiopentone	Barbiturate (GABA-A)	Rapid, anticonvulsant	Contraindicated in porphyria, hypotension, tissue necrosis if extravasated
Ketamine	NMDA antagonist	Maintains airway, raises BP/HR, bronchodilator, analgesic	Emergence delirium, raises ICP/IOP, secretions
Etomidate	GABA-A	Most cardiovascularly stable	Adrenal suppression (11β-hydroxylase) — single dose only

👩‍⚕️ Ketamine vs etomidate is a classic discrimination. Both suit the unstable patient: ketamine raises BP (sympathomimetic — trauma, shock, asthma); etomidate is BP-neutral (cardiac patients). Stem says "stable" → etomidate. Stem says "shock/trauma/pre-hospital" → ketamine.

Inhalational agents

- Sevoflurane — sweet, non-pungent → agent of choice for gas induction (paediatrics).

- Isoflurane — cheap, stable maintenance agent.

- Desflurane — lowest blood-gas solubility → fastest onset/offset. Pungent (no induction).

- Nitrous oxide — analgesic, MAC-sparing. Diffuses into air-filled spaces → avoid in pneumothorax, bowel obstruction, middle-ear surgery. Inhibits methionine synthase → megaloblastic anaemia with prolonged use.

All volatiles trigger malignant hyperthermia.

Muscle relaxants

Both classes act at the nicotinic ACh receptor of the motor endplate.

Depolarising — suxamethonium

The only depolariser in use. Mimics ACh → sustained depolarisation → fasciculations → flaccid paralysis. Metabolised by plasma cholinesterase: onset 30–60 s, duration 5–10 min. Drug of choice for rapid sequence intubation.

Side effects:

- Hyperkalaemia — dangerous in burns (>24 h), denervation, spinal cord injury, crush.

- Malignant hyperthermia trigger.

- Bradycardia (esp. second dose, paediatrics) — pretreat with atropine.

- Raised IOP and intragastric pressure.

- Suxamethonium apnoea — prolonged paralysis in pseudocholinesterase deficiency.

👩‍⚕️ "Sux sucks potassium out of cells." Avoid in burns, crush, hyperkalaemia.

Non-depolarising — the "-curoniums"

Competitive nicotinic antagonists: rocuronium (fast onset — RSI alternative), vecuronium, atracurium (Hofmann elimination → safe in renal/hepatic failure), pancuronium. Reversed by:

- Neostigmine + glycopyrrolate — neostigmine raises synaptic ACh to outcompete the blocker; glycopyrrolate prevents muscarinic side effects.

- Sugammadex — cyclodextrin that encapsulates rocuronium/vecuronium; works at any depth of block.

Local anaesthetics

LAs are weak bases that block voltage-gated Na⁺ channels from the inner axon membrane, preventing depolarisation. Acidic environments (infected tissue) keep them ionised and impair penetration — hence the difficulty anaesthetising an abscess.

Amides vs esters

	Amides (two "i"s)	Esters (one "i")
Examples	Lidocaine, bupivacaine, prilocaine, ropivacaine	Cocaine, procaine, tetracaine, benzocaine
Metabolism	Hepatic (CYP450)	Plasma cholinesterase
Allergy	Very rare	More common (PABA metabolite)

Maximum doses (must memorise)

Drug	Plain	With adrenaline
Lidocaine	3 mg/kg	7 mg/kg
Bupivacaine	2 mg/kg	2 mg/kg (adrenaline doesn't raise the max)
Prilocaine	6 mg/kg	9 mg/kg

1% = 10 mg/mL. Worked example: 70 kg, 1% lidocaine + adrenaline → 70 × 7 = 490 mg → 49 mL max.

👩‍⚕️ "Lidocaine 3 alone, 7 with adr-E-naline."

Why add adrenaline?

Vasoconstriction (1) reduces systemic absorption → raises max safe dose, (2) prolongs block, (3) provides haemostasis (scalp, face).

Never in end-artery territories: fingers, toes, nose, ears, penis. Never in Bier's block — catastrophic if the tourniquet fails.

LA toxicity

Progressive CNS then cardiac signs as plasma levels rise:

➡ Perioral tingling, tinnitus, visual disturbance → seizures → coma → cardiovascular collapse.

👩‍⚕️ "Lips Tingle, Ears Ring, Eyes Blur, Brain Seizes, Heart Stops."

Bupivacaine is the most cardiotoxic LA — "fast in, slow out" at Na⁺ channels → refractory arrhythmias. Severe toxicity → 20% Intralipid (lipid sink sequestering the lipophilic drug) plus ALS.

Prilocaine is the least toxic — agent of choice in Bier's block. Risk: methaemoglobinaemia (treat with methylene blue).

Spinal vs epidural anaesthesia

	Spinal	Epidural
Space	Subarachnoid (CSF)	Epidural (outside dura)
Level	Below L2	Any level
Onset	Rapid (5 min)	Slow (15–30 min)
Duration	Fixed (single shot)	Indefinite (catheter)
Use	C-section, TURP, lower limb	Labour analgesia, post-op

Both risk hypotension (sympathetic block), urinary retention, total spinal and epidural haematoma (anticoagulated patients). Dural puncture → post-dural puncture headache (treat with fluids, caffeine, blood patch).

👩‍⚕️ "Spinal = Single shot, Subarachnoid. Epidural = Extradural, cathEter."

Sedation tiers

Sedation is a continuum; the operator must be able to rescue from one level deeper.

Tier	Response	Airway
Minimal (anxiolysis)	Normal to verbal	Unaffected
Moderate (conscious)	Purposeful to verbal/touch	Maintained
Deep	Only to painful stimulus	May need support
GA	Unrousable	Often needs intervention

- Midazolam — benzodiazepine; conscious sedation for endoscopy. Reversed by flumazenil.

- Propofol — deep sedation; no reversal agent.

- Ketamine — preserves airway reflexes; useful for paediatric procedural sedation.

Analgesia — the WHO ladder

➡ Step 1 — non-opioid (paracetamol, NSAIDs) ± adjuvant.

➡ Step 2 — weak opioid (codeine, tramadol) + non-opioid ± adjuvant.

➡ Step 3 — strong opioid (morphine, oxycodone, fentanyl) + non-opioid ± adjuvant.

Adjuvants: gabapentin/amitriptyline (neuropathic); dexamethasone (cerebral oedema, nerve compression); bisphosphonates/radiotherapy (bone mets).

Opioids

All act at μ, κ, δ opioid receptors — Gi-coupled GPCRs that hyperpolarise neurons. Morphine is a full μ agonist: brainstem μ receptors mediate analgesia, euphoria, respiratory depression, miosis, reduced GI motility.

- Morphine — gold standard; active metabolite M6G accumulates in renal failure.

- Fentanyl — 100× more potent, lipophilic, rapid onset; intra-op and transdermal.

- Oxycodone — preferred in renal impairment.

- Tramadol — weak μ agonist + SNRI activity. Lowers seizure threshold; serotonin syndrome with SSRIs.

Opioid toxicity triad: pinpoint pupils + respiratory depression + reduced GCS → naloxone (competitive μ antagonist). Short half-life (~30–60 min) → re-narcotisation; redose or infuse.

NSAIDs

Inhibit COX-1 and COX-2 → reduced prostaglandins. Side effects mirror lost physiological PGs:

- GI: ulceration, bleeding (PGE₂ protects mucosa).

- Renal: AKI (PGs maintain afferent arteriolar dilatation).

- CV: hypertension, fluid retention, MI risk (COX-2).

- Bronchospasm in aspirin-sensitive asthma.

- Bleeding (platelet COX-1; aspirin irreversible).

Avoid in renal impairment, active GI bleeding, severe HF, and the triple whammy (NSAID + ACEi + diuretic).

Malignant hyperthermia

Autosomal dominant RyR1 mutation in skeletal muscle. Triggers — all volatiles and suxamethonium — cause uncontrolled Ca²⁺ release → sustained contraction → hypermetabolic crisis.

Presentation: rising end-tidal CO₂ (earliest), masseter spasm, tachycardia, rigidity, late hyperthermia, rhabdomyolysis, hyperkalaemia, acidosis.

Management: stop trigger, 100% O₂, dantrolene 2.5 mg/kg IV (inhibits RyR1), cool, treat K⁺ and acidosis.

👩‍⚕️ Antidote table — memorise cold:

Effect	Antidote
Opioid	Naloxone
Benzodiazepine	Flumazenil
Non-depolarising block	Neostigmine + glycopyrrolate
Rocuronium/vecuronium	Sugammadex
LA toxicity	20% Intralipid
Malignant hyperthermia	Dantrolene
Paracetamol	N-acetylcysteine
Heparin	Protamine
Warfarin	Vitamin K / PCC

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Test yourself

A patient develops hypotension immediately after induction of GA. What is the most likely mechanism?

• ((Decreased preload due to venodilation::☑️ Almost all IV induction agents venodilate — the dominant mechanism.))
• ((Direct myocardial depression::Contributes (propofol/thiopentone) but secondary to venodilation.))
• ((Anaphylaxis::Possible but rare; expect rash and bronchospasm.))
• ((Increased vagal tone::Seen with airway instrumentation, not the main driver.))
• ((Tension pneumothorax::Needs trauma or PPV.))

👩‍⚕️ Ketamine is the only IV induction agent that does not drop BP.

A lady suffers a Colles fracture. She has CKD and IHD. Which anaesthesia should be given?

• ((Bier's block (IV regional anaesthesia)::☑️ Avoids GA — ideal forearm technique in cardiac/renal comorbidity.))
• ((General anaesthesia::Cardiovascular depression and altered drug clearance.))
• ((Axillary nerve block::Overkill for a distal radius reduction.))
• ((Haematoma block::Less reliable surgical anaesthesia.))
• ((Local infiltration only::Cannot reliably anaesthetise the fracture for manipulation.))

A 72-year-old female suffers a distal radial fracture. Which anaesthesia is most suitable for manipulation and reduction?

• ((Bier's block::☑️ Avoids GA risk in elderly; bloodless field for short forearm work.))
• ((General anaesthesia::Higher cardiovascular and cognitive risk in this age group.))
• ((Haematoma block::Less reliable for manipulation.))
• ((Axillary brachial plexus block::Slower onset and technically demanding.))
• ((Sedation with morphine only::Inadequate for reduction.))

In a Bier's block, which local anaesthetic is most commonly used?

• ((0.5% Prilocaine::☑️ Lowest systemic toxicity — the margin you need if the tourniquet fails.))
• ((0.5% Bupivacaine::Contraindicated — refractory cardiotoxicity on tourniquet failure.))
• ((2% Lidocaine::Higher toxicity than prilocaine.))
• ((0.75% Ropivacaine::Not standard in IVRA.))
• ((1% Lidocaine with adrenaline::Adrenaline is forbidden in Bier's block.))

👩‍⚕️ Bier's: prilocaine yes, bupivacaine never, adrenaline never.

A patient dislocates his thumb. Lidocaine ring block is given. What is the main side effect?

• ((Cardiotoxicity::☑️ Na⁺-channel block depresses myocardial conduction at toxic plasma levels.))
• ((Methaemoglobinaemia::A prilocaine problem.))
• ((Anaphylaxis::Extremely rare with amides.))
• ((Seizures::Occur in toxicity but cardiotoxicity is the lethal endpoint.))
• ((Digital ischaemia::Caused by adrenaline, not lidocaine.))

A patient injured the tip of their index finger. What is the best anaesthetic for a ring block?

• ((Lidocaine (plain)::☑️ End-artery territory — adrenaline risks digital necrosis.))
• ((Lidocaine with adrenaline::Contraindicated in fingers, toes, nose, ears, penis.))
• ((Bupivacaine::More cardiotoxic; lidocaine is standard for ring blocks.))
• ((Prilocaine::Usable but lidocaine is first-line.))
• ((Topical EMLA cream::Insufficient depth.))

👩‍⚕️ No adrenaline in "Fingers, Toes, Nose, Ears, and the Hose."

Which is the best anaesthesia type for a pilar (trichilemmal) cyst removal in the scalp?

• ((Lidocaine with adrenaline::☑️ Vasoconstriction gives haemostasis in the vascular scalp and prolongs the block.))
• ((Lidocaine plain::Anaesthetises but leaves a bloody field.))
• ((General anaesthesia::Overkill for a minor excision.))
• ((Bupivacaine with adrenaline::Unnecessarily long and more cardiotoxic.))
• ((Topical anaesthesia::Inadequate for excision.))

A 50 kg patient requires 1% lidocaine + adrenaline for a scalp wound. What is the maximum dose?

• ((35 mL::☑️ 7 × 50 = 350 mg; 1% = 10 mg/mL → 35 mL.))
• ((15 mL::Plain lidocaine max (3 mg/kg).))
• ((50 mL::Exceeds safe maximum.))
• ((25 mL::Arithmetic error.))
• ((70 mL::Twice the safe dose.))

👩‍⚕️ Volume (mL) = (weight × mg/kg) ÷ concentration (mg/mL).

Which drug is best for induction in a shocked patient?

• ((Ketamine::☑️ Sympathomimetic — raises BP and HR; preserves airway reflexes.))
• ((Bupivacaine::A local anaesthetic.))
• ((Sodium thiopentone::Vasodilator and myocardial depressant.))
• ((Suxamethonium::A muscle relaxant.))
• ((Propofol::Profound vasodilation — avoid in shock.))

Which induction agent to intubate a hypotensive patient being transported by helicopter?

• ((Ketamine::☑️ Pre-hospital drug of choice — supports BP, gives analgesia.))
• ((Propofol::Drops BP.))
• ((Vecuronium::A muscle relaxant.))
• ((Sodium thiopentone::Drops BP.))
• ((Midazolam::Sedative; hypotensive as sole induction.))

👩‍⚕️ Ketamine is the only induction agent that raises BP.

What general anaesthetic is cardiovascularly stable in hypotensive patients?

• ((Etomidate::☑️ Haemodynamically neutral — minimal effect on BP or HR.))
• ((Ketamine::Raises BP rather than being "stable".))
• ((Sodium thiopentone::Significant hypotension.))
• ((Propofol::Moderate hypotension.))
• ((Sevoflurane::Dose-dependent vasodilation.))

👩‍⚕️ "Stable" → etomidate. "Raises BP" → ketamine. The stem keyword decides.

Which of the following is a depolarising neuromuscular blocker?

• ((Suxamethonium::☑️ Only depolariser in use; rapid onset, ultra-short duration.))
• ((Vecuronium::Non-depolarising.))
• ((Atracurium::Non-depolarising; Hofmann elimination.))
• ((Rocuronium::Non-depolarising; sugammadex reverses.))
• ((Pancuronium::Non-depolarising.))

👩‍⚕️ All "-curoniums" are non-depolarising.

Post-colonoscopy a patient is unresponsive with slow respiratory rate and pinpoint pupils. Which drug reverses the sedation?

• ((Naloxone::☑️ Classic opioid triad — miosis, bradypnoea, depressed consciousness.))
• ((Flumazenil::Reverses benzodiazepines.))
• ((Neostigmine::Reverses non-depolarising block.))
• ((Atropine::Anticholinergic for bradycardia.))
• ((N-acetylcysteine::Paracetamol antidote.))

What is the mechanism of action of naloxone?

• ((Competitive antagonism at μ-opioid receptors::☑️ Displaces opioids; reversible binding.))
• ((Non-competitive antagonism::Same site as opioids — competitive.))
• ((Inverse agonism::Naloxone is a pure antagonist.))
• ((Irreversible receptor blockade::Reversible — hence re-narcotisation risk.))
• ((Enzyme inhibition::Wrong site of action.))

👩‍⚕️ Naloxone t½ ~30–60 min is shorter than most opioids — anticipate re-narcotisation.

Which drug reverses non-depolarising neuromuscular blockade?

• ((Neostigmine::☑️ AChE inhibitor; raises synaptic ACh to outcompete the blocker. Give with glycopyrrolate.))
• ((Dantrolene::For malignant hyperthermia.))
• ((Naloxone::Opioid antagonist.))
• ((Intralipid::For LA toxicity.))
• ((Sugammadex::Specific to roc/vec; neostigmine is the classic exam answer for any non-depolariser.))

Morphine is a full agonist on which receptors?

• ((μ opioid receptors::☑️ Mediate analgesia, euphoria, respiratory depression, miosis, ↓GI motility.))
• ((κ opioid receptors::Minor activity.))
• ((δ opioid receptors::Minor role.))
• ((α adrenergic receptors::Sympathetic system.))
• ((GABA receptors::Benzodiazepine/barbiturate target.))

Binding to which receptor mediates morphine's respiratory depressant effect?

• ((μ opioid receptors::☑️ Brainstem μ receptors blunt CO₂ response.))
• ((κ opioid receptors::Dysphoria and sedation, not respiratory drive.))
• ((δ opioid receptors::Minor role.))
• ((Nicotinic::Neuromuscular junction.))
• ((Muscarinic::Cholinergic — wrong family.))

When placing a chest tube, LA reaches the parietal pleura via which nerves?

• ((Intercostal nerves::☑️ Costal parietal pleura — somatic T1–T11, sharp localised pain.))
• ((Phrenic nerve::Mediastinal/diaphragmatic pleura; pain referred to shoulder (C3–C5).))
• ((Vagus nerve::Visceral pleura — no pain.))
• ((Long thoracic nerve::Motor to serratus anterior.))
• ((Sympathetic chain::Autonomic, not somatic.))

👩‍⚕️ Costal → intercostals. Diaphragmatic/mediastinal → phrenic (shoulder tip). Visceral → vagus (no pain).

A patient with bone metastases from breast cancer presents with pain. What is the management?

• ((Radiotherapy::☑️ Gold standard for painful bone metastases.))
• ((Chemotherapy::Treats disease but not first-line for focal bone pain.))
• ((Bisphosphonates alone::Adjunct only.))
• ((Surgical fixation::For actual/impending pathological fracture.))
• ((Increasing oral morphine only::Symptom control without addressing cause.))

A patient with metastatic renal cancer has a painful lesion in the left humerus. What is the management?

• ((Radiotherapy::☑️ Targeted relief for painful bone metastases.))
• ((Prophylactic intramedullary nailing::For high fracture risk (Mirels), not pain alone.))
• ((Amputation::Disproportionate.))
• ((NSAIDs alone::Inadequate.))
• ((Observation and analgesia::Radiotherapy more effective.))

A man with bronchogenic carcinoma presents with early morning headache, nausea, and visual blurring. What is the initial management?

• ((Dexamethasone::☑️ Reduces vasogenic oedema around brain metastases — fastest relief.))
• ((Urgent CT head::Needed but dexamethasone is the immediate therapeutic step.))
• ((Mannitol::For acute herniation, not subacute oedema.))
• ((Whole brain radiotherapy::Definitive but not initial.))
• ((Surgical decompression::Medical management first.))

A patient with known breast carcinoma presents with headache and vomiting. What is the initial management?

• ((Dexamethasone::☑️ Reduces cerebral oedema from brain metastases.))
• ((Antiemetics alone::Treats symptom, not cause.))
• ((Lumbar puncture::Contraindicated if raised ICP — coning risk.))
• ((Urgent neurosurgical referral::May follow; not the immediate step.))
• ((Furosemide::Not first-line for tumour oedema.))

👩‍⚕️ Cancer + early morning headache + vomiting + visual change = raised ICP from brain mets → dexamethasone. Never LP.

Revision summary

➡ Induction: propofol (↓BP), thiopentone (avoid porphyria), ketamine (↑BP — shock), etomidate (neutral — adrenal suppression).

➡ Suxamethonium — only depolariser; RSI; hyperkalaemia, MH trigger, sux apnoea.

➡ Non-depolarisers ("-curoniums") → neostigmine + glycopyrrolate; sugammadex for roc/vec.

➡ Lidocaine: 3 mg/kg plain, 7 mg/kg with adrenaline. 1% = 10 mg/mL.

➡ Bupivacaine — most cardiotoxic; never in Bier's. Prilocaine — least toxic; IVRA agent; methaemoglobinaemia risk.

➡ No adrenaline in fingers, toes, nose, ears, penis.

➡ LA toxicity: lips→ears→eyes→seizures→arrest. Treat with 20% Intralipid.

➡ Spinal = single shot, subarachnoid, below L2. Epidural = catheter, extradural; PDPH risk.

➡ WHO ladder: non-opioid → weak opioid → strong opioid ± adjuvants.

➡ Opioid triad (miosis + bradypnoea + ↓GCS) → naloxone (short t½ — re-narcotisation).

➡ NSAIDs: avoid in renal failure, GI bleeding, severe HF, aspirin-sensitive asthma.

➡ MH: RyR1; triggered by volatiles + sux; treat dantrolene.

➡ Cancer + raised ICP → dexamethasone; painful bone mets → radiotherapy.