Anesthesia

Mechanism: NMDA receptor antagonism (the primary mechanism for analgesia and sedation); inhibits nicotinic ACh receptors; modulates opioid receptors (μreceptor agonist — contributes to analgesia and some physical dependence); activates TREK-1 two-pore potassium channels (contributes to sedation)

Properties: colourless gas; sweet smell; no hepatic metabolism; excreted unchanged by the lungs; blood-gas partition coefficient = 0.47 (low — rapid onset and offset); MAC = 105% (requires hyperbaric conditions for surgical anaesthesia as sole agent; clinically used at 50–65% to provide MAC-equivalent of approximately 0.6 MAC)

Analgesia: significant analgesic effect at 30–50% concentrations — equivalent to moderate-dose opioids for procedural pain; the mechanism: endogenous opioid release + NMDA antagonism; Entonox (50% N₂O/50% O₂) provides effective labour analgesia, dental analgesia, and procedure analgesia

Cardiovascular: mild myocardial depression (direct) but sympathomimetic (↑ catecholamines) → net: relatively stable BP and HR; less vasodilatory than volatile agents; suitable for cardiac surgery supplementation

Controversy Mechanism Clinical Evidence Expansion of N₂O is 34× more blood-soluble than N₂; diffuses into gas-filled spaces faster than Strong evidence; absolute contraindication in known gas-filled N₂ leaves → expanding gas volumes (pneumothorax, bowel obstruction, middle pneumothorax, bowel obstruction, middle ear surgery (Jobsonspaces ear, pneumocephalus, intraocular gas bubbles post-vitreoretinal surgery) Horne tympanoplasty), intraocular gas (>3 months after vitreoretinal surgery with gas tamponade), pneumocephalus, and air embolism; N₂O triples/quadruples trapped gas volume PONV N₂O activates opioid receptors in the gut → ↑ PONV; also activates vomiting ENIGMA trial (Myles PS, Lancet 2007; n=2050): N₂O-free increase centre directly; meta-analyses confirm N₂O increases PONV incidence by anaesthesia significantly reduced severe PONV; eliminating N₂O approximately 20–30% relative to N₂O-free anaesthesia from routine practice is one of the most effective PONV prevention strategies Vitamin B12 / N₂O irreversibly oxidises cobalt (Co²⁺→Co³⁺) in the active site of vitamin B12 Clinically relevant in: prolonged exposures (>6 hours); patients Methionine (cobalamin) → inactivation of methionine synthase → impaired methionine with pre-existing B12 deficiency (vegans, elderly, pernicious synthase synthesis → impaired DNA synthesis (folate-methyl trap); single anaesthetic anaemia, malabsorption); ICU patients on prolonged N₂O; patients inhibition exposure → 50% reduction in methionine synthase activity within 2–6 hours; bone on antifolate drugs (methotrexate); subacute combined marrow depression with megaloblastic changes within 24 hours after prolonged degeneration of the cord reported in N₂O abuse and chronic exposure occupational exposure Environmental GWP = 265; atmospheric lifetime 114 years; also depletes stratospheric ozone Multiple hospitals have eliminated N₂O from routine use without impact (similar mechanism to CFCs); N₂O pipeline systems leak 10–30% of delivered patient outcome impact; the ENIGMA trial in fact showed improved gas into building; healthcare N₂O accounts for approximately 5% of all healthcare outcomes in the N₂O-free arm; environmental + PONV evidence greenhouse gas emissions globally together strongly support N₂O elimination from routine anaesthesia

Primary: non-competitive antagonist of the NMDA (N-methyl-D-aspartate) glutamate receptor — binds within the ion channel pore (open channel block) → prevents Ca²⁺ influx → inhibits glutamate-mediated excitatory neurotransmission; NMDA receptors mediate pain transmission in the dorsal horn, memory formation in the hippocampus, and consciousness in the thalamo-cortical circuits

Secondary: sigma receptor agonist (contributes to dissociative hallucinations); mu-opioid receptor agonist (weak analgesic contribution); muscarinic receptor antagonist (bronchodilation, tachycardia); voltage-gated sodium channel blockade (local anaesthetic-like effect at high concentrations)

Dissociation: ketamine produces EEG dissociation between the thalamus and limbic system — the thalamus (which normally relays sensory information to the cortex) is blocked while the limbic system (emotion and memory) continues activity; this produces the unique "dissociative" state: the patient appears conscious (open eyes, preserved nystagmus, intact airway reflexes) but is profoundly analgesic and amnestic and does not respond purposefully to stimuli

Highly lipid-soluble → rapid CNS penetration (peak brain concentration within 1 minute of IV administration); Vd = 3 L/kg (large — widely distributed); protein binding = 27% (low)

Hepatic metabolism: CYP3A4 → norketamine (an active metabolite — 20–30% of parent potency; contributes to prolonged clinical effect); norketamine → hydroxynorketamine metabolites (water-soluble, renally excreted) t½ = 2–3 hours; clinical duration of single bolus induction dose: 10–15 minutes (recovery from redistribution, not elimination); sub-anaesthetic infusion duration variable

Routes: IV (1–2 mg/kg induction; 0.5–1 mg/kg for procedural sedation); IM (4–6 mg/kg — useful when IV access unavailable; onset 5–15 minutes); oral, nasal, rectal (subanesthetic analgesic doses in paediatrics and chronic pain)

System Effect Mechanism Clinical Application Cardiovascular ↑ MAP, ↑ HR, ↑ CO Inhibition of noradrenaline reuptake → ↑ circulating Ideal induction agent for haemodynamically (sympathomimetic); catecholamines + direct sympathetic stimulation → ↑ SVR + ↑ compromised patients (trauma, cardiac tamponade, myocardial depression HR + ↑ CO; in catecholamine-depleted states (severe tension pneumothorax, septic shock when directly (but masked by haemorrhagic shock), the direct myocardial depressant effect catecholamine stores are intact); provides sympathomimetic effect in may be unmasked → hypotension paradoxically anaesthesia while maintaining or improving most patients) haemodynamics Respiratory Minimal respiratory Bronchial smooth muscle relaxation from muscarinic Bronchodilator of choice for severe depression at analgesic antagonism and catecholamine release → useful in status bronchospasm/status asthmaticus; useful for doses; preserves airway asthmaticus; airway reflexes are preserved relative to other IV sedation in spontaneously breathing patients; avoids reflexes (relatively); agents but NOT completely — aspiration can still occur; do not apnoea seen with propofol/benzodiazepines bronchodilator rely on preserved reflexes for full stomach patients

Haemodynamically unstable RSI: induction dose 1–2 mg/kg IV; maintains cardiovascular stability when other agents would cause hypotension

Procedural sedation: 0.5–1 mg/kg IV or 4 mg/kg IM; ideal for brief, painful procedures (fracture reduction, joint manipulation, wound debridement) — maintains spontaneous ventilation and airway reflexes; use with midazolam 0.05 mg/kg to reduce emergence hallucinations

Subanesthetic analgesia: 0.1–0.5 mg/kg/hr infusion; reduces opioid consumption by 30–40% in acute pain; prevents opioid-induced hyperalgesia (NMDA antagonism blocks the central sensitisation that increases pain perception with opioid use); useful in complex regional pain syndrome, burn wound care, and multimodal analgesia

Status asthmaticus: 1–2 mg/kg IV or 0.5 mg/kg/hr infusion; bronchodilation helps while providing sedation for intubated patients with severe bronchospasm

Acute depression (S-ketamine/Esketamine): intranasal esketamine (Spravato) — FDA-approved for treatment-resistant depression; administered in clinic under observation; rapid antidepressant effect within hours (unlike conventional antidepressants — weeks); mechanism via NMDA antagonism and AMPA receptor potentiation in prefrontal cortex

Emergence delirium/hallucinations: unpleasant vivid dreams, hallucinations, and psychedelic experiences during recovery; more common in adults than children (>15%); can be profoundly distressing; prevented by: benzodiazepine premedication (midazolam 0.05 mg/kg IV) markedly reduces incidence; quiet, calm environment during recovery; avoid unnecessary stimulation during emergence; propofol sub-anesthetic infusion co-administered

Contraindications: severe hypertension/pre-eclampsia (raises BP further → hypertensive crisis); raised ICP/IOP (raises both — traditionally contraindicated in head injury; however, in adequately ventilated/sedated ICU patients this is disputed — recent evidence suggests ketamine does not raise ICP when used with other drugs in the context of mechanical ventilation); history of schizophrenia or acute psychosis (NMDA antagonism can exacerbate psychotic symptoms); thyrotoxicosis (catecholamine surges dangerous)

α₂ Receptor Location Effect of Agonism Clinical Consequence Locus coeruleus (brainstem ↓ noradrenaline release → ↓ activity in the ascending arousal system → sedation The unique "co-operative sedation" — patients noradrenergic nucleus — the and hypnosis; crucially, this sedation resembles natural sleep (NREM stage 2 — can be woken easily by verbal stimulation but primary site for delta waves) rather than anaesthetic unconsciousness; the brainstem arousal return to calm sedation when stimulation stops dexmedetomidine's sedative circuits are inhibited, not the cortex directly → rousable sedation and hypnotic effects) Dorsal horn (spinal cord α₂ ↓ substance P and glutamate release from C fibre terminals → ↓ pain signal Significant analgesic effect (not as potent as receptors on presynaptic transmission → analgesia; also post-synaptically modulates dorsal horn neuron opioids but clinically meaningful); opioid-sparing nociceptive terminals) excitability (reduces morphine requirements 30–40%); reduces opioid-induced hyperalgesia Peripheral vasculature (α₂ Vasoconstriction at high doses → initially ↑ BP; at lower plasma concentrations, Bradycardia and hypotension (the most receptors on vascular smooth the presynaptic α₂ receptors on sympathetic nerve terminals are activated → ↓ common and important side effects); typically: ↑ muscle) noradrenaline release → sympatholysis → ↓ HR + ↓ BP (the predominant effect BP during loading dose followed by bradycardia at clinical infusion rates) + hypotension; atropine for severe bradycardia

Protein binding: 94%; Vd: 118 L (extensive distribution); t½: 2 hours; hepatic glucuronidation + CYP2A6 metabolism to inactive metabolites (renally excreted)

Dose: loading infusion 1 mcg/kg over 10–20 minutes (AVOID rapid loading — causes hypertension from peripheral vasoconstriction; many protocols omit loading and start at maintenance rate directly for ICU use); maintenance 0.2–1.4 mcg/kg/hr

Application Dose Advantage Over Alternatives ICU sedation 0.2–1.0 mcg/kg/hr infusion; no SEDCOM trial (Riker RR, JAMA 2009): dexmedetomidine vs midazolam ICU sedation — dexmedetomidine reduced (non-intubated loading dose recommended in delirium duration by 22% and time on ventilator; less respiratory depression → earlier extubation; PADIS 2018 and intubated ICU; titrate to RASS target 0 guidelines: dexmedetomidine preferred over benzodiazepines for ICU sedation patients) to −2 Awake 1 mcg/kg loading over 10 The ideal sedation for awake procedures — patient is cooperative on verbal command (can perform motor tasks for craniotomy / minutes then 0.5–0.7 awake cortical mapping; can follow commands for awake intubation), analgesic (reduces topical LA requirement), awake mcg/kg/hr maintenance and anti-anxiety; no respiratory depression (unlike benzodiazepines/propofol); dissipates rapidly when infusion fiberoptic stopped intubation (AFOI) MAC (Monitored 0.5–1 mcg/kg loading then Suitable for procedures under regional anaesthesia (prevents patient movement while maintaining cooperation when Anaesthesia 0.2–0.7 mcg/kg/hr needed); reduces supplement GA required for regional block procedure anxiety Care) sedation Attenuation of Added to propofol-remifentanil Reduces haemodynamic response to laryngoscopy, intubation, and extubation; reduces emergence agitation in sympathetic TIVA or as premedication paediatrics (reduces tachycardia and hypertension on emergence) responses Paediatric 0.5–1 mcg/kg loading over 10 Children sedated with dexmedetomidine are arousable → able to follow instructions for MRI positioning; minimal sedation min + infusion for MRI respiratory depression → safer than propofol in children without an anaesthesiologist for non-procedural imaging sedation

PRIS: a syndrome of new-onset metabolic acidosis (lactate acidosis — unexplained metabolic acidosis in an ICU patient on propofol infusion), rhabdomyolysis, renal failure, and cardiac failure (specifically brady-arrhythmia progressing to right bundle branch block → complete heart block → cardiovascular collapse) occurring in patients receiving high-dose propofol infusions

Incidence: approximately 1.1% of ICU patients on propofol infusions; mortality: 33–85% once the full syndrome is established; more common than recognised because early features are attributed to other causes

Propofol (particularly at high doses and prolonged infusions) → inhibition of mitochondrial Complex I (NADH-ubiquinone oxidoreductase) AND Complex II (succinateubiquinone oxidoreductase) of the electron transport chain → impaired oxidative phosphorylation → cells cannot use oxygen for ATP synthesis despite adequate O₂ delivery → cells switch to anaerobic metabolism → lactic acidosis. Simultaneously: propofol phenol ring → impairs mitochondrial β-oxidation of free fatty acids (the primary fuel source for cardiac muscle and skeletal muscle in critically ill patients who are frequently on carbohydrate-restricted or lipid-heavy nutrition) → free fatty acids and their acylcarnitine intermediates accumulate → directly toxic to the mitochondrial and cell membranes → rhabdomyolysis of cardiac and skeletal muscle → acute cardiac failure + skeletal myolysis → myoglobinaemia → AKI Risk Factors Risk Factor Mechanism Dose >4–5 mg/kg/hr for >48 hours Exceeds the mitochondrial capacity to process propofol metabolites; accumulation of toxic phenol metabolites High catecholamine state (severe illness, Catecholamines switch cellular metabolism toward fat oxidation → cells become MORE dependent on β-oxidation catecholamine infusions) pathways that propofol specifically impairs High-fat/low-carbohydrate intake Further increases reliance on fat oxidation; propofol vehicle (Intralipid — 1.1 kcal/mL) itself adds significant lipid load Mitochondrial disease Pre-existing mitochondrial impairment → much lower propofol dose required to tip into PRIS Paediatric patients Originally described in children; PRIS was first recognised as a distinct entity in paediatric critical care after reports of unexplained cardiac arrest in children on propofol sedation Concomitant steroids + catecholamines Steroids impair mitochondrial function; catecholamines increase fat metabolism; combination with propofol = perfect storm

Feature Clinical/Laboratory Finding Metabolic lactic Unexplained metabolic acidosis (↑ lactate >4 mmol/L, ↓ pH); FIRST and most consistent early feature; check lactate every 4–6 hours in patients on acidosis propofol >4 mg/kg/hr Rhabdomyolysis Rising CK (often dramatic >10,000 IU/L); myoglobinuria (dark brown urine); muscle tenderness Cardiac New right bundle branch block (RBBB) → progressing to complete heart block → cardiovascular collapse; new-onset bradycardia refractory to dysfunction atropine; cardiomegaly on CXR; LV failure on echo Lipaemia Hyperlipidaemia (lipid load from Intralipid vehicle); visible lipaemia in plasma samples AKI Rising creatinine from rhabdomyolysis-induced renal tubular necrosis; myoglobin casts in tubules

Phaeochromocytomas arise from chromaffin cells of the adrenal medulla (90%) or extra-adrenal sympathetic ganglia (10% — paragangliomas); secrete catecholamines (adrenaline, noradrenaline, dopamine) constitutively or in paroxysms Noradrenaline-secreting tumours → predominantly hypertension from α₁ vasoconstriction; adrenaline-secreting → mixed hypertension and tachycardia + β₂ vasodilation (can cause paradoxical hypotension); dopamine-secreting → hypertension from indirect catecholamine release

Rule of 10: 10% bilateral; 10% extra-adrenal; 10% malignant; 10% familial (MEN2A, MEN2B, VHL, SDH mutations); 10% in children; 10% discovered incidentally Chronic catecholamine excess → hypertrophied cardiovascular system with REDUCED intravascular volume (chronic vasoconstriction → pressure natriuresis + relative hypovolaemia); catecholamine cardiomyopathy (catecholamine-induced cardiac toxicity); increased sensitivity to vasodilators after tumour removal

Monitoring (all before induction) Arterial line (radial artery — beat-to-beat BP monitoring throughout); large-bore IV access (2× 14G); central venous catheter (CVP monitoring, vasopressor access); TOE or PA catheter for high-risk patients (EF <40%, bilateral tumour); temperature monitoring

Induction

Avoid laryngoscopy-induced catecholamine surge: lidocaine 1.5 mg/kg IV + fentanyl 2–3 mcg/kg + esmolol 0.5 mg/kg immediately before laryngoscopy; or high-dose opioid induction (remifentanil 2–3 mcg/kg)

Avoid: histamine-releasing drugs (morphine, atracurium — can trigger catecholamine release from the tumour or direct histamine release); succinylcholineinduced fasciculations raise intra-abdominal pressure potentially triggering tumour catecholamine release; droperidol (triggers catecholamine release from phaeochromocytoma in rare cases) Hypertensive Crisis During Tumour Manipulation Drug Dose Mechanism Phentolamine (non- 2–5 mg IV bolus; repeat Competitive α₁ + α₂ blockade → acute vasodilation; rapid onset (2 min); duration 10–15 min; drug of choice for selective reversible every 2–3 minutes until BP intraoperative hypertensive crisis management α-blocker) controlled Sodium nitroprusside 0.5–8 mcg/kg/min infusion Nitric oxide → direct arterial + venous vasodilation; immediate onset; very titratable; risk of cyanide toxicity at high (SNP) doses or prolonged use; most powerful vasodilator available; useful as infusion for sustained hypertension during tumour handling Nicardipine (IV 5–15 mg/hr infusion Dihydropyridine CCB → arterial vasodilation; does not cause reflex tachycardia to the same degree as SNP; calcium channel increasingly used as an alternative first-line infusion blocker) Magnesium sulphate 2 g IV bolus Inhibits catecholamine release from the tumour; inhibits catecholamine receptor sensitivity; useful adjunct

Assessment of Hyperthyroidism

Symptoms and clinical assessment: weight loss, heat intolerance, tremor, palpitations, anxiety, exophthalmos (Graves' disease), goitre size; assess for signs of heart failure (AF in 10–15%); thyroid bruit

Investigations: TFTs (TSH, free T4, free T3); ECG (AF, sinus tachycardia, LVH); CXR/CT neck (tracheal deviation, retrosternal extension, compression of trachea or oesophagus); flow-volume loop if significant tracheal compression; calcium and parathyroid function (risk of hypoparathyroidism post-thyroidectomy)

Airway assessment: palpate the goitre; assess tracheal position; review CT for tracheal diameter at narrowest point; if tracheal compression >50% → awake fiberoptic intubation; tracheal softening (tracheomalacia) may occur with long-standing retrosternal goitre → risk of tracheal collapse after ETT removal Achieving Euthyroid State Drug Mechanism Duration to Euthyroid Carbimazole or Inhibit thyroid peroxidase → ↓ T3 and T4 synthesis; PTU also inhibits peripheral 4–6 weeks for biochemical euthyroid state; continue up to Propylthiouracil conversion of T4→T3 day of surgery (PTU) Lugol's iodine Wolff-Chaikoff effect: excess iodide transiently inhibits thyroid hormone synthesis and Used for 10–14 days pre-operatively after anti-thyroid (KI 65%) release; also reduces vascularity of the thyroid gland (reduces intraoperative bleeding) drugs started; reduces vascularity and bleeding — an additional surgical benefit intraoperatively Beta-blockers Blocks peripheral sympathetic effects of excess T3/T4 (HR, tremor, anxiety); propranolol Immediate symptom control; continue until surgery; must (propranolol) also inhibits peripheral T4→T3 conversion (PTU-like effect) be used alongside anti-thyroid drugs (treats symptoms, not the thyroid excess)

Tracheal deviation and compression: large goitres may displace or compress the trachea; CT neck identifies the minimum tracheal diameter; if compressed <50% diameter → standard intubation with smaller ETT (6.0–6.5 mm); if >50% → consider awake fiberoptic intubation (maintains airway tone and spontaneous ventilation throughout — safest approach)

Reinforced (armoured) ETT: used for thyroid surgery to prevent ETT kinking in the extended neck position; allows surgeon access to the anterior neck without ETT obstruction

Recurrent Laryngeal Nerve (RLN) monitoring: the RLN runs in the tracheo-oesophageal groove adjacent to the thyroid; inadvertent RLN injury → immediate hoarseness or voice change (unilateral) → bilateral injury → aphonia + stridor + airway emergency; intraoperative neuromonitoring (IONM) uses a specialised ETT (NIM-EMG tube — electromyography electrodes embedded on the ETT surface monitor the RLN via laryngeal muscle EMG); if RLN is stimulated, the EMG records a response; loss of signal = nerve impaired; requires specific endotracheal tube and specific drug considerations

RLN monitoring — NIM ETT implications: NMBs MUST be allowed to wear off completely before placing the NIM tube (EMG response requires muscle activity — NMB prevents it); use the shortest-acting NMB (rocuronium 0.3–0.6 mg/kg initial dose + TOF monitoring); confirm T4 (all four twitches) on TOF before baseline NIM signal is obtained

Tracheomalacia: rare complication of long-standing retrosternal goitre; cartilaginous rings soften and lose support when external tumour pressure is suddenly removed → trachea collapses inward on extubation → immediate post-extubation stridor → may require re-intubation or even tracheostomy; anticipate by performing "cuff leak test" before extubation in long-standing large goitre

GCS and focal neurological deficit documentation (baseline for post-operative comparison); pupil assessment (unequal pupils → herniation → emergency);

NIHSS if focal deficits present

CT/MRI: tumour location and size; degree of midline shift; presence of hydrocephalus; oedema extent (vasogenic vs cytotoxic); vascular supply (hypervascularity → blood loss risk)

Medication review: dexamethasone (started by neurology — reduces vasogenic oedema; must continue perioperatively; stress dose not routinely needed for steroids already prescribed); anti-epileptic drugs (continue perioperatively); anticoagulation history Clinical Cushing's triad: hypertension + bradycardia + abnormal breathing = impending herniation → urgent CT + possible emergency ventricular drainage before anaesthesia

Goal Target How Achieved Maintain CPP CPP = MAP − ICP ≥ 60 mmHg Arterial line for continuous BP; vasopressors (phenylephrine) for MAP; ICP reduction strategies Reduce ICP / brain ICP <20 mmHg; slack brain at craniotomy Mannitol; moderate hyperventilation; head-up 15–30°; TIVA; steroids pre-operatively; relaxation CSF drainage Control CMRO₂ Reduce metabolic demand; prevent secondary injury Adequate depth; normothermia; normoglycaemia (6–10 mmol/L); normocapnia Rapid, smooth Awake, oriented, able to follow commands within 15– TIVA with propofol + remifentanil; short-acting agents; no residual NMB emergence 20 min of surgery end (sugammadex); avoid hypothermia (delays emergence) Avoid secondary PaO₂ >80 mmHg; PaCO₂ 35–40 mmHg; MAP ≥65 Mandatory monitoring; active warming; arterial blood gas monitoring every 60 min injury factors mmHg; Temperature 36–37°C

Agent Choice

TIVA preferred for craniotomy: propofol reduces CMRO₂ and ICP, maintains cerebral autoregulation; remifentanil provides precise analgesic control and allows rapid emergence (context-sensitive half-time 3 min); no effect on ETCO₂ monitoring interpretation

Volatile agents: acceptable at ≤0.5 MAC (low doses preserve cerebral autoregulation); above 0.5 MAC → cerebral vasodilation → ↑ CBV → ↑ ICP; desflurane causes cerebral vasodilation and sympathetic activation → avoid; sevoflurane preferred if volatile is used

N₂O: avoid in craniotomy — increases CMRO₂ and CBF; expands any pneumocephalus; may worsen PONV Avoid ketamine (↑ CMRO₂ and ICP; cerebral vasodilation) Brain Relaxation ("Slack Brain") Strategies Strategy Drug/Intervention Mechanism Osmotherapy Mannitol 0.5–1 g/kg IV over 15–20 min; 7.5% hypertonic Osmotic gradient draws water from brain interstitium into plasma → reduces cerebral water saline 3–5 mL/kg IV alternatively → reduces ICP; effect begins at 15 min, peaks at 30–60 min, lasts 3–4 hours; monitor serum osmolality (<320 mOsm/L); avoid repeat doses if hypernatraemic Head 15–30° head-up; neutral neck Improves jugular venous drainage → reduces cerebral venous volume → reduces ICP position Controlled Normocapnia (PaCO₂ 35–40 mmHg) for routine Hypocapnia → cerebral vasoconstriction → ↓ CBV → ↓ ICP; effect immediate but tolerance ventilation maintenance; moderate hyperventilation (PaCO₂ 30–35 develops within 4–6 hours; ischaemia risk with prolonged hyperventilation; use ONLY as mmHg) if brain tight at opening — TEMPORARY only bridge to surgical decompression Position at Local anaesthetic at pin sites + remifentanil bolus before Pin insertion through the scalp into the outer table of the skull is extremely painful; Mayfield pins pin insertion inadequate analgesia → massive sympathetic surge → hypertension + ↑ ICP (skull clamp) Surgical CSF Surgeon opens cisterna magna or places intraventricular CSF removal directly reduces ICP and brain volume → provides surgical access without drainage drain excessive brain retraction

Smooth emergence critical: coughing, straining, bucking on ETT during emergence → ↑ ICP → brain herniation through the craniotomy defect → catastrophic; ensure adequate analgesic level before emergence; use remifentanil to bridge until patient can follow commands without response to ETT; lidocaine 1.5 mg/kg IV 3–5 minutes before extubation reduces cough response to ETT

Immediate neurological assessment: is there a new deficit? Is the patient at the same GCS as pre-operatively? Can they squeeze both hands, follow commands bilaterally, speak? Any new deficits → urgent CT to exclude haematoma/oedema/ischaemia; haematoma within hours of craniotomy → reexploration

When NOT to extubate: prolonged surgery (>8 hours); significant brain swelling requiring dural closure under tension; haemodynamic instability; GCS baseline was low pre-operatively; posterior fossa surgery (risk of respiratory centre compression); brainstem surgery; plan for ICU intubated

PONV prevention mandatory: even mild vomiting → ↑ ICP → dangerous; full multimodal PONV prophylaxis (ondansetron + dexamethasone + droperidol); TIVA reduces PONV substantially vs volatile

Parameter Neonate/Infant Adult Clinical Implication Heart rate CO = HR × SV; SV is FIXED in neonates (immature Can increase SV Bradycardia = cardiac arrest in neonates; ALWAYS give atropine 20 mcg/kg dependency Frank-Starling mechanism — stiff, non-compliant substantially (min 100 mcg) before laryngoscopy; normal neonatal HR 120–160 bpm; HR myocardium cannot increase SV significantly); CO (preload reserve, <100 = emergency is entirely rate-dependent Starling mechanism) Transitional Foetal shunts (PDA, foramen ovale) may reopen in No foetal shunts Maintain SpO₂ ≥94–98%; avoid hypoxia, acidosis, hypothermia — all trigger circulation hypoxia, acidosis, hypothermia, or surgical stress (all closed) ductal reopening; give O₂ carefully in prematurity (retinopathy risk with high → right-to-left shunting → cyanosis; particularly in SpO₂) first weeks of life Circulating 80–90 mL/kg (neonates); 70–80 mL/kg (infants); 65–70 mL/kg Meticulous blood loss monitoring (weigh swabs in grams — 1 g = 1 mL); blood even 5 mL blood loss can = 5–10% of total blood transfusion triggers lower (Hb <80 g/L in most neonates, <70 g/L in older volume volume in a 1 kg premature neonate children); use small (10 mL) syringes for fluid management; calculate maximum allowable blood loss preoperatively Glycogen Limited glycogen reserves → rapid hypoglycaemia Adequate hepatic Dextrose-containing maintenance IV fluids mandatory during nil-by-mouth stores with fasting; premature neonates particularly glycogen for periods in neonates and infants ≤6 months; blood glucose hourly monitoring vulnerable; high glucose consumption rate (6 moderate fasting intraoperatively; target 4–8 mmol/L mg/kg/min)

Parameter Neonate/Infant Clinical Implication O₂ 6–8 mL/kg/min (vs 3 mL/kg/min in adults) — very high Rapid desaturation during apnoea (SpO₂ falls to critical in 60–90 seconds in neonates); consumption metabolic rate preoxygenate adequately; work fast during airway management FRC relative FRC only 3× TV (vs 7× TV in adults); closing capacity may Rapid onset of hypoxia; needs higher FiO₂ baseline; PEEP 3–5 cmH₂O even during routine to TV exceed FRC → small airway closure at FRC in infants → spontaneous ventilation under anaesthesia shunting even during spontaneous ventilation Chest wall Highly compliant; ribcage collapses inward during During respiratory distress: see "see-saw" breathing (chest wall sinks in, abdomen compliance respiratory distress rather than stabilising to generate protrudes) — an emergency sign requiring immediate intervention negative pressure (paradoxical breathing) Apnoea risk Post-conceptional age <60 weeks → immature respiratory All ex-premature infants under 60 weeks PCA must have apnoea monitoring for minimum in ex- centre → risk of postoperative apnoea for up to 12–24 12 hours post-GA; regional anaesthesia preferred to GA where possible in this group; premature hours after GA caffeine 10 mg/kg IV preoperatively reduces post-op apnoea incidence infants

Neonates and infants have: very large body surface area:mass ratio (4–5× adult); thin skin with minimal subcutaneous fat; no shivering mechanism in neonates (brown adipose tissue thermogenesis — "non-shivering thermogenesis" — instead, which consumes large amounts of O₂ and generates heat from BAT oxidation); immature hypothalamic thermoregulation

Under GA: all anaesthetic agents abolish behavioural thermoregulation and impair the autonomic thermoregulatory vasoconstriction threshold → body temperature falls rapidly to ambient; at 20°C theatre temperature, a neonate can become hypothermic in minutes

Prevention mandatory: theatre temperature 26–28°C for neonates (adults find this uncomfortably hot); warm all IV fluids and blood; forced-air warming blankets; warming mattress; warm cotton blankets; humidified gases; minimise exposed skin area; temperature probe mandatory throughout

Consequences of hypothermia: impaired drug metabolism → prolonged anaesthesia; coagulopathy; cardiac arrhythmia; impaired immune function → infection; hypoglycaemia (thermogenesis depletes glucose); prolonged post-op recovery

Parameter Neonate/Infant vs Adult Clinical Implication Volume of ↑ Total body water (neonates 80% body weight vs 60% adults); drugs distributing to TBW Higher weight-based dose of NMBs, antibiotics; neonates distribution have larger Vd → need higher mg/kg doses for equivalent plasma concentration; e.g., need larger mg/kg loading doses of many drugs water-soluble drugs (NMBs, aminoglycosides) Hepatic CYP450 enzyme systems immature at birth; CYP2C9, CYP2D6, CYP3A4 all below adult Prolonged half-lives of hepatically metabolised drugs metabolism activity levels; reached adult activity at 6 months–3 years depending on the isoenzyme (morphine, propofol, midazolam) in neonates; start low and titrate carefully; risk of accumulation Renal GFR 25–30% of adult value at birth; reaches adult GFR per body surface area by 18–24 Renally cleared drugs (vancomycin, aminoglycosides, excretion months; tubular secretion also immature NMBs) have prolonged half-lives; reduce dose frequency or extend intervals; monitor drug levels Protein Lower albumin and α₁-acid glycoprotein in neonates → more free (active) drug for given Enhanced effects of protein-bound drugs (local anaesthetics binding total plasma concentration — higher LAST risk; propofol; thiopentone); reduce doses accordingly MAC MAC is highest in neonates (1–6 months), falls with increasing age; term neonates: Neonates require HIGHER volatile concentrations for (volatile sevoflurane MAC ~3.3% (vs 2.0% in adults); falls to adult value by age 10–12 years equivalent depth of anaesthesia than children or adults — agents) counter-intuitive but well-established

Glucose: neonates have limited glycogen stores and high glucose utilisation; hypoglycaemia (blood glucose <2.6 mmol/L) causes seizures and brain injury; maintain dextrose infusion throughout GA; check glucose hourly; prolonged preoperative fasting without IV dextrose is contraindicated

Calcium: neonates (especially premature) have immature calcium regulation; hypocalcaemia (ionised Ca²⁺ <1.1 mmol/L) causes cardiac depression, apnoea, and seizures; check ionised calcium before major neonatal surgery; give calcium gluconate 10% 0.5 mL/kg IV for hypocalcaemia

Acid-base: neonatal kidneys have limited bicarbonate reabsorption capacity → any acid load causes metabolic acidosis more readily than adults; standard base excess target slightly more negative acceptable in neonates (−4 to +2 mEq/L)

Drug toxicity — succinylcholine and atropine: succinylcholine causes more pronounced bradycardia in children (high vagal tone); ALWAYS give atropine 20 mcg/kg before succinylcholine in children; succinylcholine-induced hyperkalaemia and cardiac arrest from undiagnosed muscular dystrophy (Duchenne muscular dystrophy — DMD) in boys → succinylcholine increasingly avoided in paediatric elective cases

Category Definition DDI Target Anaesthetic Priority 1 — Immediate threat to life of mother or fetus; examples: severe fetal <30 minutes Fastest available safe technique; epidural top-up Immediate bradycardia, cord prolapse, placental abruption with acute fetal compromise, (ideally <15 if in situ; rapid-sequence spinal if no epidural; threat to life uterine rupture, maternal haemodynamic collapse minutes for cord RSI-GA if spinal not feasible prolapse) 2 — Not immediately life-threatening but requires urgent delivery; examples: non- <75 minutes Regional anaesthesia preferred; time allows Maternal or reassuring CTG, failure to progress with maternal compromise careful spinal or epidural top-up fetal compromise 3 — No Early delivery needed but no current compromise; examples: failed induction, Within a scheduled Standard elective spinal or epidural anaesthesia; compromise prolonged latent phase time frame no time pressure 4 — Elective Elective CS at a time convenient to patient and team Elective scheduled Full preoperative assessment; standard spinal anaesthesia

Fastest Route to Surgical Anaesthesia from a Functioning Labour Epidural Check epidural function first (10–15 seconds): ask patient if she can still feel the block; test cold/warm sensation; if dense bilateral block present → proceed to top-up; if patchy or one-sided → may need rapid-sequence spinal instead

Top-up drug: 2% lidocaine with adrenaline 1:200,000 + optional fentanyl 50–100 mcg — fastest-onset epidural solution for surgical anaesthesia; inject 15– 20 mL in 5 mL increments (2–3 mL test dose first to re-confirm not intravascular); onset of T4 sensory block in 5–10 minutes (faster than 0.5% bupivacaine which takes 15–20 minutes)

Alternative: 0.5% levobupivacaine 15–20 mL (slower onset than 2% lidocaine; onset 12–15 min) or 3% chloroprocaine (if available — fastest epidural agent, onset 3–5 minutes; suitable for true Category 1)

Simultaneous actions while topping up: left lateral tilt; IV fluid co-load 500 mL crystalloid; phenylephrine infusion running (prevent spinal hypotension); supplemental O₂ by face mask; fetal monitoring (CTG off for delivery); surgical team ready; neonatologist present

Assess level: confirm T4 level by cold/pinprick test before incision; if inadequate despite full top-up dose → proceed to RSI-GA (do not delay surgery waiting for inadequate epidural)

When appropriate: no epidural in situ; patient haemodynamically stable; no significant coagulopathy; uncomplicated expected airway; DDI is <30 minutes (achievable with spinal)

Drug choice: hyperbaric bupivacaine 0.5% 2 mL + fentanyl 15–25 mcg + morphine 100–150 mcg (intrathecal morphine provides 12–24 hours post-op analgesia — significant advantage over GA for post-CS pain); onset of surgical T4 level within 5–8 minutes

Simultaneous preparation: position patient in lateral decubitus or sitting; one hand on the patient, one drawing up drugs — no time for separate preparation; assistant preparing vasopressor; left lateral tilt immediately after injection; do not wait for full block to assess — check block level at 3 minutes (usually adequate T4 by then)

Failed spinal: if block is inadequate after 5 minutes → RSI-GA; do NOT give a second spinal (risk of total spinal from accumulated doses)

Indications for RSI-GA over Regional Patient refusal of regional; coagulopathy (HELLP, DIC, thrombocytopenia); severe haemodynamic instability (cannot tolerate sympathectomy of spinal); local anaesthetic allergy (rare); severe urgency where time for spinal is unavailable; failed spinal or epidural top-up; major placenta praevia with active major haemorrhage Modified RSI Protocol for Obstetrics Step Detail Obstetric-Specific Modification Aspiration Sodium citrate 30 mL oral + ranitidine 50 mg IV + Mandatory pre-GA in pregnancy >16 weeks; reduce gastric acid pH and volume prophylaxis metoclopramide 10 mg IV Preoxygenation 100% O₂ × 3–5 minutes (head-up 20°); ETO₂ >90% Reduced safe apnoea time in pregnancy (↓FRC + ↑O₂ consumption); mandatory full preoxygenation; HFNO 60 L/min during apnoea Induction agent Thiopentone 4–5 mg/kg IV (classic; proven fetal safety) Reduce dose 20% in pre-eclampsia (enhanced CNS sensitivity); MAC reduced 25–40% in OR propofol 2–2.5 mg/kg pregnancy NMB Succinylcholine 1.5 mg/kg IV (classic RSI); OR Both acceptable; succinylcholine provides shortest duration (10 min) if airway fails; rocuronium 1.2 mg/kg + sugammadex 16 mg/kg rocuronium provides CICO rescue option available Cricoid Applied at induction; release if impairs laryngoscopy Higher risk of regurgitation in pregnancy; cricoid pressure standard; video laryngoscope pressure (DAS 2018) first-line Intubation Confirm with ETCO₂ × 6 breaths; 6.5–7.0 mm ETT Higher failed intubation rate in obstetrics (1:224 vs 1:1800 general surgical); video (oedematous obstetric airway → smaller tube) laryngoscope as first-line for all obstetric GA; have DAS failed intubation plan ready Maintenance Volatile agent (sevoflurane 1.0–1.5 MAC) + opioid after Awareness risk until delivery (deliberately reduced anaesthetic to minimise fetal exposure); delivery; N₂O 50% optional give fentanyl after cord clamped; must increase anaesthetic depth after delivery

Condition Definition Hypertension SBP ≥140 mmHg OR DBP ≥90 mmHg on at least two occasions ≥4 hours apart after 20 weeks gestation in pregnancy

Pre- New hypertension after 20 weeks PLUS one or more of: proteinuria (≥300 mg/24h or spot PCR ≥30 mg/mmol); thrombocytopenia (<150,000/μL); renal eclampsia insufficiency (creatinine >88 μmol/L); impaired liver function (↑ LFTs); pulmonary oedema; new-onset headache unresponsive to medication; visual disturbances Severe pre- Pre-eclampsia with severe hypertension (SBP ≥160 mmHg or DBP ≥110 mmHg on two occasions) OR end-organ dysfunction (neurological symptoms, eclampsia HELLP syndrome, pulmonary oedema, severe renal impairment) Eclampsia New-onset grand-mal seizures in a patient with pre-eclampsia (or other hypertensive disorder of pregnancy); seizures in the context of hypertension and proteinuria HELLP Haemolysis (LDH >600 IU/L, abnormal blood film) + Elevated Liver enzymes (AST/ALT ≥2× ULN) + Low Platelets (<100,000/μL) — a severe variant of syndrome pre-eclampsia

Abnormal placentation (failure of trophoblast invasion of spiral arteries) → inadequate placental blood flow → placental ischaemia → release of anti-angiogenic factors (sFlt-1 — soluble FMS-like tyrosine kinase 1 — antagonises VEGF and PlGF) → systemic maternal endothelial dysfunction → widespread vasospasm (hypertension) + endothelial permeability ↑ (oedema, proteinuria) + platelet activation (thrombocytopenia, DIC) + organ ischaemia (renal, hepatic, cerebral)

Haemodynamics: paradox — pre-eclamptic patients have HIGH BP (vasospasm) but LOW intravascular volume (protein leaks out of vessels into interstitial space; venous tone ↑); vasodilators reduce BP but may worsen the already-contracted intravascular volume; fluid management is a delicate balance

Cerebral: vasospasm → headache, scotomata, altered consciousness; loss of cerebral autoregulation at high BP → breakthrough cerebral oedema → eclamptic seizures → cerebral haemorrhage (leading cause of maternal death in pre-eclampsia)

Indication: severe pre-eclampsia → MgSO₄ for seizure prophylaxis (MAGPIE trial: MgSO₄ reduced eclampsia rate by 58% vs placebo in severe preeclampsia; NNT = 63); ACTIVE eclampsia → MgSO₄ is first-line treatment (superior to diazepam or phenytoin for controlling eclamptic seizures —

Collaborative Eclampsia Trial)

Dosing: loading dose 4 g IV over 5–15 minutes; maintenance 1–2 g/hr IV infusion; continue for 24 hours after delivery (or 24 hours after last fit)

Toxicity monitoring — the clinical signs of hypermagnesaemia:

Therapeutic range: 2–3.5 mmol/L (serum Mg)

Loss of patellar reflexes: first sign of toxicity — Mg 3.5–5 mmol/L; CHECK PATELLAR REFLEXES HOURLY on MgSO₄ infusion

Respiratory depression: Mg 5–6.5 mmol/L; monitor RR ≥12 breaths/min

Cardiac arrest: Mg >7.5 mmol/L

Also maintain: UO ≥25 mL/hr (Mg is renally cleared; renal failure → rapid Mg accumulation) Antidote for MgSO₄ toxicity: calcium gluconate 10% 10 mL IV over 10 minutes (competes with Mg at the receptor; reverses respiratory and cardiac effects); have at bedside of every patient on MgSO₄ infusion

Regional preferred: spinal anaesthesia is SAFE in severe pre-eclampsia (the historical concern about catastrophic hypotension is not supported by evidence — Dyer RA et al.: pre-eclamptic patients have LESS hypotension after spinal than healthy parturients, because their high baseline SVR provides a buffer against the sympathectomy-induced fall in SVR); epidural also safe and allows gradual titration

Platelet threshold: neuraxial anaesthesia safe if platelets ≥70,000/μL (most institutional guidelines 70–80,000); review trend (rapidly falling counts are more concerning than a stable 80,000); check recent result (<6 hours in rapidly deteriorating HELLP)

If GA required: oedematous obstetric airway — use 6.5 mm ETT; video laryngoscope first-line; attenuate laryngoscopy response (alfentanil 10 mcg/kg or remifentanil 1 mcg/kg or labetalol 10 mg IV 1 minute before laryngoscopy — pre-eclamptic patients have exaggerated hypertensive response to laryngoscopy → stroke risk); esmolol NOT preferred in CS (crosses placenta → neonatal bradycardia)

Postoperative: HDU monitoring minimum 24 hours; continue MgSO₄ 24 hours post-delivery; continued antihypertensive therapy; watch for late eclampsia (can occur up to 48 hours post-delivery — the most dangerous time is actually the first 24 hours postpartum)