Anaesthetics and muscle relaxants

Potency and speed of inhaled agents

• MAC (minimum alveolar concentration): the alveolar concentration at 1 atmosphere that prevents movement in 50% of patients in response to skin incision. Lower MAC means higher potency. MACs are roughly additive: 0.5 MAC of nitrous oxide plus 0.5 MAC of sevoflurane gives about 1 MAC.
• MAC falls with age, pregnancy, hypothermia, opioids, benzodiazepines and acute alcohol intake; it rises in infants, hyperthermia, hyperthyroidism and chronic alcohol use.
• Blood:gas partition coefficient decides speed. A poorly soluble agent saturates blood quickly, so its alveolar and brain partial pressure rises fast: low coefficient means fast induction and recovery.
• Oil:gas coefficient tracks potency (Meyer–Overton): the more lipid-soluble, the lower the MAC.

Problems with specific inhaled agents

• Nitrous oxide is 30 times more soluble than nitrogen, so it diffuses into closed air spaces faster than nitrogen leaves: avoid in pneumothorax, bowel obstruction, air embolism, middle ear and retinal gas surgery. Prolonged exposure oxidises the cobalt of vitamin B12, inactivating methionine synthase: megaloblastic anaemia and subacute combined degeneration. Give 100% oxygen at the end to prevent diffusion hypoxia.
• Halothane hepatitis: oxidative metabolism produces trifluoroacetylated liver proteins that act as neoantigens; an immune reaction causes fulminant hepatitis, most likely after repeat exposure within weeks, in obese middle-aged women. Mild transaminase rises are a separate, direct toxic effect.
• Volatile agents depress breathing, lower blood pressure, relax the uterus and raise cerebral blood flow (halothane most, which also raises ICP).

Malignant hyperthermia

• Autosomal dominant defect, usually in the ryanodine receptor (RYR1) of skeletal muscle sarcoplasmic reticulum. Volatile agents and suxamethonium trigger uncontrolled calcium release, sustained contraction and hypermetabolism.
• Signs: unexplained rise in end-tidal CO2 (earliest), tachycardia, masseter or generalised rigidity, then hyperthermia, hyperkalaemia, metabolic acidosis, myoglobinuria.
• Treatment: stop the trigger, hyperventilate with 100% oxygen, dantrolene, which blocks calcium release through the ryanodine receptor, plus cooling and treatment of hyperkalaemia.

Exam trap Fever is a late sign of malignant hyperthermia; a rising end-tidal CO2 comes first.

Intravenous anaesthetics

• A single dose of thiopental or propofol wears off within minutes because of redistribution from brain to muscle and then fat, not because of metabolism. Repeated doses saturate these stores and recovery becomes prolonged.

Local anaesthetics

• They block voltage-gated Na+ channels from inside the axon. The un-ionised base crosses the membrane; the ionised form binds the channel. In infected, acidic tissue more drug is ionised outside the nerve, so less penetrates and the block fails.
• Order of block: small myelinated B (autonomic) fibres first, then Aδ and C (pain, temperature), then touch and pressure, and motor (Aα) last.
• Amides (lidocaine, bupivacaine, ropivacaine, prilocaine) are metabolised in the liver; allergy is rare. Esters (procaine, tetracaine, benzocaine, cocaine) are hydrolysed by plasma esterases to para-aminobenzoic acid (PABA), which is allergenic.
• Dose arithmetic: a 1% solution contains 10 mg/mL, so 10 mL of 2% lidocaine contains 200 mg.

• Methaemoglobinaemia: blue lips and chocolate-brown blood with near-normal PaO2. Treat with IV methylene blue, which reduces methaemoglobin via NADPH-methaemoglobin reductase. It can cause haemolysis in G6PD deficiency.
• Toxicity: perioral tingling, tinnitus, metallic taste, lightheadedness, slurred speech, then seizures, coma, arrhythmias and arrest. Treat with airway, benzodiazepines and 20% lipid emulsion; prolonged CPR.

Exam trap Most reported "lidocaine allergies" are vasovagal or adrenaline reactions; true allergy is mainly to esters.

Spinal and epidural anaesthesia

• Spinal: intrathecal below L1–L2; rapid dense block; hypotension from sympathetic block; post-dural puncture headache.
• Epidural: larger volume, slower onset, catheter infusion (labour).
• The main contraindication is uncorrected coagulopathy or anticoagulation (risk of epidural haematoma), plus patient refusal, local infection, raised ICP and uncorrected hypovolaemia. Wait 12 hours after prophylactic LMWH (24 hours after a treatment dose) before needle insertion.

Neuromuscular blockers

• Suxamethonium works fastest because it does not need to compete: one opening of the receptor is enough to depolarise the end-plate. It is broken down by plasma cholinesterase.
• Suxamethonium adverse effects: hyperkalaemia (burns, crush, denervation, spinal cord injury after 24–48 hours), myalgia, bradycardia with repeat doses (especially children), raised intraocular, intragastric and intracranial pressure, malignant hyperthermia, prolonged apnoea in pseudocholinesterase deficiency.
• Atracurium and cisatracurium undergo Hofmann elimination: spontaneous breakdown in plasma at body pH and temperature, independent of liver and kidney, so they suit patients with renal and hepatic failure. Atracurium releases more histamine; laudanosine is the metabolite.
• Sugammadex encapsulates rocuronium and vecuronium for rapid reversal of even deep block; neostigmine with glycopyrrolate reverses residual block.
• Potentiation: aminoglycosides (gentamicin) and magnesium reduce presynaptic ACh release by blocking calcium entry; hypothermia, acidosis, myasthenia. Neostigmine may fail; check calcium and ventilate until recovery.

Premedication and perioperative problems

• Rapid sequence induction with cricoid pressure in bowel obstruction or a full stomach prevents aspiration of gastric contents; acid aspiration causes chemical pneumonitis (Mendelson syndrome). Fasting: 6 hours solids, 2 hours clear fluids.
• Hyoscine premedication crosses the BBB and can cause postoperative confusion and agitation in the elderly; glycopyrrolate does not.
• Bleomycin lung: high inspired oxygen can precipitate pulmonary fibrosis years after treatment, so keep FiO2 as low as safe and avoid fluid overload.
• Intraoperative hypertension with adequate depth: IV labetalol usually; in a patient with asthma and angina, IV glyceryl trinitrate avoids β-blockade. Esmolol is valued for its ultra-short half-life (about 9 minutes), so its effect is easily titrated.

Remember Low blood:gas solubility means fast; low MAC means strong.

How FCPS asks about this

• Why thiopental wears off quickly: redistribution to muscle and fat.
• Halothane hepatitis mechanism: immune reaction to trifluoroacetylated proteins after repeated exposure.
• Blue lips, chocolate blood after Bier's block: prilocaine methaemoglobinaemia; IV methylene blue.
• Malignant hyperthermia treatment: dantrolene blocks ryanodine receptor calcium release.
• Relaxant for renal and hepatic failure: atracurium or cisatracurium (Hofmann elimination).
• Ester allergy and fibre order: PABA metabolite; small autonomic and pain fibres blocked first, motor last.
• 10 mL of 2% lidocaine: 200 mg; maximum 3 mg/kg plain, 7 mg/kg with adrenaline.