Anesthesia

Indications: anticipated haemodynamic instability (major vascular surgery, cardiac surgery, severe haemorrhage risk); need for frequent ABG sampling; patients requiring vasopressor/inotrope titration; severe hypertension; difficult-to-measure NIBP (obesity, arrhythmias); phaeochromocytoma; deliberate hypotension

Technique — radial artery (most common): Allen's test (optional — confirm dual circulation); 20G cannula; Seldinger or direct technique; sterile preparation; connect to non-compliant pressure tubing + transducer (compliant tubing distorts the waveform — "damping"); transducer levelled at the phlebostatic axis (4th

ICS, mid-axillary line) and zeroed to atmospheric pressure

Waveform components: upstroke = systole (rate reflects LV contractility); peak = systolic BP; dicrotic notch = aortic valve closure (separates systole from diastole); downslope = diastolic runoff; trough = diastolic BP; area under the curve = MAP; pulse pressure variation during IPPV indicates fluid responsiveness

Complications: haematoma; arterial occlusion (more likely with smaller arteries, prolonged cannulation, haematoma); distal ischaemia; infection; accidental intra-arterial drug injection (catastrophic — label all arterial lines prominently)

CVP measures right atrial pressure (normally 0–8 mmHg); the waveform contains: a wave (atrial contraction); c wave (tricuspid valve closure); x descent (atrial relaxation); v wave (venous filling with closed tricuspid valve); y descent (tricuspid valve opens → passive ventricular filling)

Limitations as a fluid responsiveness marker: CVP does NOT reliably predict fluid responsiveness in clinical practice; Marik (Chest 2008; systematic review of 24 studies): CVP was not correlated with blood volume and could not predict haemodynamic response to a fluid challenge; patients with low CVP may or may not respond to fluid; patients with high CVP may respond; CVP is influenced by venous tone, intrathoracic pressure, RV compliance, and many other factors independent of volume status

Current role: CVP provides information about right heart function and filling; useful for comparison over time; useful for CVP waveform analysis (cannon a waves in complete heart block, blunt y descent in tamponade); still useful to guide vasopressor vs fluid therapy in certain scenarios; SHOULD NOT be the sole guide for fluid resuscitation

Parameter Normal Value Clinical Interpretation PAWP (pulmonary artery 6–12 mmHg Left atrial filling pressure; PAWP >18 mmHg → cardiogenic pulmonary oedema; PAWP <8 with hypotension → wedge pressure) hypovolaemia or vasodilatory shock Cardiac Output 4–8 L/min Low CO → cardiogenic or obstructive shock; high CO + low SVR → septic, anaphylactic, hepatic failure (thermodilution) SVR (systemic vascular 800–1200 Low SVR = vasodilatory shock (sepsis); high SVR = cardiogenic shock (reflexive vasoconstriction) resistance) dynes·sec/cm⁵ Mixed venous O₂ sat (SvO₂) 65–75% Low SvO₂ (<65%) → inadequate O₂ delivery or ↑ O₂ extraction (anaemia, high output demand); high SvO₂ (>80%) → distributive shock (O₂ not extracted — shunting) The PAC's clinical utility has been questioned by multiple randomised trials (PACMAN, ESCAPE) showing no mortality benefit and possible harm from its complications; it retains specific roles in: complex cardiac surgery (post-cardiopulmonary bypass haemodynamic management), severe pulmonary hypertension assessment, refractory shock characterisation when less invasive measures are insufficient

Oesophageal Doppler Monitor (ODM): a small Doppler probe placed in the oesophagus (at 35–40 cm from the incisors) and positioned adjacent to the descending aorta; measures aortic blood flow velocity using a 4 MHz Doppler signal; allows continuous, real-time assessment of: stroke volume (SV), cardiac output (CO), corrected flow time (FTc — a surrogate for preload), and peak velocity (a surrogate for LV contractility); non-invasive and minimally invasive alternative to PAC for CO measurement

Goal-Directed Therapy (GDT) using ODM: algorithm-based fluid and vasopressor management targeting specific physiological endpoints: fluid challenges of 200–250 mL crystalloid/colloid → assess if SV increases >10% (fluid responsive → give more fluid) or <10% (non-responsive → stop fluid, consider vasopressor or inotrope); targets: FTc 0.35–0.40 seconds; SV index >35 mL/m²; CO optimisation OPTIMISE trial (Pearse RM, BMJ 2014; n=734 high-risk major GI surgery patients): ODM-guided GDT (stroke volume optimisation using colloid challenges) vs standard care; result: ODM-GDT significantly reduced the rate of postoperative complications (36.6% vs 43.4%) without increasing hospital mortality; meta-analysis including OPTIMISE confirms GDT reduces postoperative complications and hospital length of stay in high-risk surgical patients

Dynamic fluid responsiveness markers: SVV (stroke volume variation during IPPV >13% = fluid responsive); PPV (pulse pressure variation >13% = fluid responsive); PLR test (raise legs → ↑ CO ≥10% = fluid responsive) — these are superior to CVP/PAWP for predicting fluid responsiveness

PiCCO (Pulse Index Continuous Cardiac Output) uses transpulmonary thermodilution (cold saline injected via CVC; measured via a thermistor in the femoral artery) for intermittent CO measurement calibrating a continuous pulse contour analysis algorithm; provides: CO (continuous); GEDVI (global end-diastolic volume index — a volumetric preload marker superior to CVP); EVLWI (extravascular lung water index — measures pulmonary oedema quantitatively; EVLWI >10 mL/kg = pulmonary oedema; >14 mL/kg = severe oedema); SVV (continuous fluid responsiveness marker) Particularly useful in ARDS management (EVLWI allows quantification and monitoring of pulmonary oedema), post-cardiac surgery, and complex septic shock where distinguishing between fluid overload and under-resuscitation is difficult

Receptor Location Effect When Stimulated α₁ adrenergic Peripheral vascular smooth muscle; skin, splanchnic, Vasoconstriction → ↑ SVR → ↑ MAP; pupil dilation; urethral sphincter contraction renal vessels α₂ adrenergic Presynaptic nerve terminals (central + peripheral); Central: sedation, analgesia, ↓ sympathetic outflow; peripheral: vasoconstriction (lower vascular smooth muscle potency than α₁) β₁ adrenergic Cardiac sinoatrial node, AV node, myocardium ↑ Heart rate (chronotropy), ↑ contractility (inotropy), ↑ AV conduction, ↑ myocardial O₂ demand β₂ adrenergic Vascular smooth muscle; bronchial smooth muscle; Vasodilation → ↓ SVR; bronchodilation; uterine relaxation; mast cell stabilisation; ↑ insulin uterus; mast cells release DA₁ Renal and splanchnic vasculature Vasodilation → ↑ renal/splanchnic blood flow; historically thought to provide "renal (dopamine) protection" — now disproven V₁ Vascular smooth muscle Vasoconstriction independent of catecholamine pathway; particularly useful in (vasopressin) catecholamine-resistant vasodilatory shock

Drug Receptor Profile Haemodynamic Effect Primary Indication Key Safety Point Noradrenaline α₁ >> β₁; minimal β₂ ↑ SVR (↑ MAP); modest ↑ HR; no FIRST LINE for septic shock (SSC 2021); Peripheral ischaemia with (norepinephrine) significant vasodilation; maintains first line for most vasodilatory shock; extravasation (use central line); CO via afterload-mediated LV maintains MAP ≥65 mmHg; preferred over reflex bradycardia at high doses; optimization dopamine (De Backer NEJM 2010) splanchnic vasoconstriction at very high doses Adrenaline β₁ + β₂ at low doses; Low dose: ↑ CO, ↑ HR, ↓ SVR (β₂ Cardiac arrest (1 mg IV every 3–5 min); Tachyarrhythmias (high dose); (epinephrine) α₁ added at high dominant); High dose: ↑↑ SVR, anaphylaxis (0.5 mg IM or 50–100 mcg IV); metabolic acidosis (lactic acid from doses ↑↑ HR, ↑↑ MAP; universal potent severe refractory shock; low cardiac output β₂ glycogenolysis and impaired effect with hypotension tissue perfusion at high doses); myocardial ischaemia; hyperglycaemia Vasopressin V₁ receptor: vascular Vasoconstriction via V₁ Vasodilatory shock refractory to Coronary and mesenteric (ADH) smooth muscle (independent of adrenergic noradrenaline alone (adds V₁ vasoconstriction at high doses — vasoconstriction; V₂ receptors); ↑ SVR; ↑ MAP; no vasoconstriction via a different receptor ischaemia risk; hyponatraemia (V₂ receptor: renal water direct chronotropy or inotropy; pathway); vasodilatory shock post-CPB effect — SIADH-like); skin necrosis reabsorption reduces noradrenaline (vasopressin deficiency after bypass); with high doses and extravasation; requirements (catecholamine- relative vasopressin deficiency of septic typical ICU dose: 0.03–0.04 sparing) shock (vasopressin levels paradoxically low units/min (do not increase above in septic shock) this) Phenylephrine Pure α₁ agonist; no β ↑ SVR; ↑ MAP; reflex bradycardia Perioperative hypotension from vasodilation Reflex bradycardia; if used in activity (baroreceptor response to ↑ BP); (regional anaesthesia, volatile agents) — cardiogenic shock → worsens NO increase in HR or contractility first-line vasopressor for this; obstetric spinal cardiac output (↑ afterload on failing hypotension (preferred — no tachycardia, heart without ↑ inotropy); avoid in maintains uteroplacental blood flow); heart failure or low CO states preserves HR (useful if baseline tachycardia) Dopamine DA₁ (low dose <5 Low dose: ↑ renal/splanchnic Not recommended as first-line vasopressor Significantly more arrhythmias than mcg/kg/min); β₁ blood flow (historically "renal (De Backer NEJM 2010: dopamine → more noradrenaline; "low-dose dopamine" (medium dose 5–10); protection" — NOT proven); arrhythmias than noradrenaline + more for renal protection is NOT evidenceα₁ (high dose >10 Medium: ↑ CO; High: deaths in cardiogenic shock subgroup); only based and should be abandoned mcg/kg/min) vasoconstriction alternative if noradrenaline unavailable Dobutamine β₁ >> β₂; minimal α ↑ Contractility (↑ CO, ↑ SV); ↑ Cardiogenic shock (↑ CO in failing heart); Tachycardia and arrhythmias; Dobutamine β₁ >> β₂; minimal α ↑ Contractility (↑ CO, ↑ SV); ↑ Cardiogenic shock (↑ CO in failing heart); Tachycardia and arrhythmias; HR; ↓ SVR (β₂ vasodilation); net: acute decompensated heart failure (reduced worsens myocardial ischaemia (↑ O₂ ↑ CO, may ↓ BP if SVR falls more EF <35% + hypoperfusion); post-cardiac demand); tachyphylaxis with than CO rises surgery low output syndrome; often prolonged use; NOT for vasodilatory combined with noradrenaline (dobutamine ↑ shock (will ↓ SVR further) CO, noradrenaline maintains SVR) Milrinone PDE-III inhibitor ↑ Contractility + ↓ SVR + ↓ PVR; Acute decompensated heart failure Hypotension (significant vasodilation (phosphodiesterase the "inodilator" — lowers both (particularly in patients with β-blocker- — often requires concomitant type 3 inhibition → ↑ SVR and PVR while increasing induced receptor downregulation where vasopressor support); arrhythmias; cAMP in cardiac CO; does NOT act via adrenergic dobutamine is less effective); post-cardiac long t½ (2–3 hours) makes titration muscle → inotropy; ↑ receptors → useful when surgery LCOS (low cardiac output slow; renal excretion → accumulates cAMP in vascular downregulation of β-receptors syndrome); pulmonary hypertension (↓ PVR); in renal failure smooth muscle → has occurred (chronic HF) right heart failure vasodilation)

Type of Shock Primary Agent Second Agent Septic/Distributive shock (↑ CO, Noradrenaline 0.1–1 mcg/kg/min Vasopressin 0.03 units/min if noradrenaline >0.25 mcg/kg/min; ↓ SVR) hydrocortisone 200 mg/day if vasopressor-refractory Cardiogenic shock (↓ CO, ↑ SVR) Dobutamine (↑ CO, ↓ SVR) + Noradrenaline if hypotensive Milrinone if β-receptor downregulated; levosimendan (Ca²⁺ (↑ SVR to counteract dobutamine vasodilation) sensitiser — Europe) for acute-on-chronic decompensation Anaphylactic shock (↓ CO, ↓ Adrenaline (α₁ for vasoconstriction + β₂ for bronchodilation + Vasopressin for refractory anaphylaxis (V₁ vasoconstriction SVR, bronchospasm) β₁ for ↑ CO) — the ONLY appropriate first-line agent independent of epinephrine); noradrenaline if adrenaline inadequate Perioperative vasodilatory Phenylephrine (pure α₁ — restores SVR without Noradrenaline infusion for sustained hypotension hypotension (regional/volatile tachycardia) for hypotension alone; ephedrine if bradycardic agent) Right heart failure + pulmonary Milrinone (↓ PVR + ↑ RV contractility) + Vasopressin Inhaled NO (selective pulmonary vasodilation); prostacyclin hypertension (maintains systemic BP without worsening PVR) analogues

Step Assessment Action

C — Catastrophic External haemorrhage from limb or junctional wound Tourniquet (limb haemorrhage); wound packing with haemostatic gauze haemorrhage visible BEFORE airway assessment (junctional/non-compressible); direct pressure; pelvic binder for pelvic fracture

A — Airway with C- Is airway patent? Can patient speak? Assess for Manual in-line stabilisation (MILS) of the C-spine during all airway manoeuvres; jaw spine control obstruction (blood, vomit, teeth, foreign body, soft thrust (not head tilt/chin lift); suction; nasopharyngeal airway (NPA) or OPA; RSItissue oedema, facial/laryngeal fracture) intubation if unable to maintain airway; surgical airway if CICO

B — Breathing and RR; oxygen saturation; bilateral breath sounds; High-flow O₂ via non-rebreather mask 15 L/min; needle decompression + chest drain ventilation tracheal deviation; subcutaneous emphysema for tension pneumothorax; chest drain for haemothorax; seal open chest wound with 3sided dressing

C — Circulation and HR, BP, CRT, skin colour, consciousness (surrogate Large-bore IV access (2× 14G or intraosseous); activate MTP; permissive hypotension haemorrhage control for cerebral perfusion); identify source of (SBP 80–90 mmHg until surgical haemostasis); blood products in 1:1:1 ratio; TXA haemorrhage (external/internal) within 3 hours of injury

D — Disability GCS (Eyes 4/Motor 6/Verbal 5); pupil size and Maintain CPP ≥70 mmHg in TBI (MAP ≥90 + ICP monitoring if GCS ≤8); C-spine (Neurological) reactivity; limb movements; AVPU immobilisation; anticonvulsants for TBI seizures; neurosurgical consultation for (Alert/Voice/Pain/Unresponsive) deteriorating GCS

E — Complete undressing (log-roll with spinal Active warming: warm blankets, warm IV fluids, warm theatre; prevent heat loss (wet Exposure/Environment precautions); assess posterior injuries; temperature clothing removed); temperature monitoring

Permissive hypotension: accept SBP 80–90 mmHg (MAP 50–65 mmHg) until surgical or radiological haemostasis achieved; rationale: high BP displaces blood clots from injured vessels, worsening haemorrhage; permissive hypotension maintains marginal tissue perfusion while allowing clot formation;

EXCEPTION: TBI — maintain MAP ≥80 mmHg (brain needs adequate CPP); severe thoracic aorta injury (risk of complete rupture) Haemostatic resuscitation (1:1:1): packed RBC : fresh frozen plasma : platelets in 1:1:1 ratio — PROPPR trial (JAMA 2015): 1:1:1 vs 1:1:2 → significantly better 24h and 30d survival with 1:1:1; provides volume replacement AND replaces all clotting factors AND replaces platelets simultaneously — treats the coagulopathy rather than just the volume deficit

Tranexamic acid (TXA): CRASH-2 (Lancet 2010; n=20,211): 1 g IV within 3 hours of injury → 15% relative mortality reduction; second dose 1 g IV over 8 hours if bleeding continues; TXA >3 hours after injury: NO benefit and possible harm (procoagulant effect may worsen thromboembolic complications once fibrinolysis has already resolved); give EARLY — the most time-sensitive intervention in trauma

Minimise crystalloids: large-volume crystalloids dilute clotting factors, worsen acidosis, cause hypothermia, and worsen outcomes; limit to <1.5 L during active haemorrhage resuscitation; blood products are the primary volume expanders in DCR

Calcium replacement: citrate in FFP and blood products chelates ionised calcium → hypocalcaemia impairs clotting and cardiac function; 10 mL 10% calcium gluconate IV per 4 units transfused rapidly; check ionised Ca²⁺ every 30 minutes

Challenge Management Full stomach RSI mandatory for all trauma patients regardless of fasting status; rapid loss of consciousness and NMB with immediate intubation; no mask ventilation (aspiration unless hypoxia threatened (SpO₂ <93%) risk) Potential MILS (Manual In-line Stabilisation) by assistant throughout laryngoscopy; do NOT remove cervical collar during intubation until cleared by imaging; cervical spine video laryngoscope (C-MAC, McGrath) as first-line — achieves intubation without neck extension; difficult intubation plan (bougie, fibreoptic) prepared injury in advance

Haemodynamic Induction agents: ketamine 1–2 mg/kg IV (sympathomimetic — maintains BP; bronchodilator — useful if aspiration suspected); if critically shocked (BP compromise <70 systolic): etomidate 0.2 mg/kg IV (most cardiovascularly stable) or ketamine at reduced dose (0.5–1 mg/kg); AVOID propofol in haemorrhagic shock (vasodilatory → cardiac arrest) NMB choice Succinylcholine 1.5 mg/kg IV (fastest intubating conditions; 60 seconds) — check for contraindications (burns >48h → hyperkalaemia; crush injuries with denervation); OR rocuronium 1.2 mg/kg (60-second equivalent intubating conditions; sugammadex 16 mg/kg available)

TBI Avoid: hypotension (↓ CPP → secondary brain injury); hypoxia (SpO₂ <90% even briefly); hypercapnia (↑ CBF → ↑ ICP); maintain: MAP ≥80 mmHg; management EtCO₂ 35–40 mmHg (normocapnia); consider lidocaine 1.5 mg/kg IV before laryngoscopy to blunt ICP response (evidence weak but commonly used) during RSI

The "damage control" concept — do MINIMAL surgery now to control haemorrhage and contamination; leave definitive repair for later when the patient is physiologically resuscitated from the lethal triad: abbreviated laparotomy (suture major vessels; pack the abdomen; leave the bowel stapled but not anastomosed); temporary abdominal closure (TAC — negative pressure wound dressing); transfer to ICU for resuscitation; return to theatre 24–48 hours later for definitive repair

Intraoperative considerations during damage control: permissive hypothermia acceptance (warming is a secondary concern to surgical haemostasis); goal is to terminate the surgical bleeding source as fast as possible; ICU bed should be booked before entering theatre

Burn wound: Zone of coagulation (central — irreversible cell death); Zone of stasis (middle — potentially salvageable with optimal resuscitation — inadequate fluid → extends the irreversible injury); Zone of hyperaemia (peripheral — minimal injury, will recover)

Systemic inflammatory response: massive cytokine release → capillary leak → interstitial oedema (not just locally at the burn wound — generalised); distributive shock from vasodilation; bacterial translocation from gut (mucosal barrier disruption from shock); hypermetabolism persists for months (catecholamines, glucagon → ↑ resting metabolic rate 150–200% of predicted — the most severe hypermetabolic state of any disease)

Cardiovascular phases: Early (0–24h): ↓ CO, ↑ SVR (shock), myocardial depression (from burn toxins and inflammatory mediators); Late (24–72h onward): hyperdynamic — ↑ CO, ↓ SVR, ↑ HR (from hypermetabolism and sepsis)

Type Mechanism Clinical Features Management Carbon CO binds Hb with 200× affinity of O₂ → COHb → left- Headache, confusion, seizures, coma; 100% O₂ (reduces CO t½ from 5 hours to 60 min); Monoxide shifted O₂ dissociation curve → impaired O₂ delivery cherry-red colour (unreliable); SpO₂ hyperbaric O₂ (35–90 min at 2.5 atm → t½ 20–30 min) (CO) despite normal PaO₂; inhibits mitochondrial FALSELY NORMAL (co-oximetry on for: COHb >25%; neurological symptoms; cardiac poisoning cytochrome oxidase ABG required); carboxyHb >20% → compromise; pregnancy neurological damage; >60% → fatal Upper Direct heat injury to supraglottic structures (larynx, Singed nasal hairs, facial burns, eyebrow EARLY intubation is critical — delay allows airway pharynx); steam and hot gases cause oedema which burns, hoarseness, stridor; initial airway progressive oedema to make intubation impossible; thermal can completely obstruct the upper airway within hours may appear adequate but oedema is once hoarse or stridorous → intubate IMMEDIATELY injury progressive with the largest possible ETT; awake FOI if cooperative; surgical airway if intubation fails Lower Products of combustion (aldehydes, acids, HCN, CO) Productive cough, wheezing, Humidified O₂; nebulised N-acetylcysteine (mucolytic); airway damage the tracheobronchial mucosa and alveoli → bronchospasm; late: bronchopneumonia, bronchoscopy and lavage for cast removal; ventilator chemical mucosal necrosis, cast formation, bronchospasm, ARDS; bronchoalveolar lavage showing support with lung-protective settings; prophylactic injury impaired mucociliary clearance → pneumonia; true carbonaceous particles confirms lower antibiotics controversial (selective digestive acid burns to the lower airway airway injury decontamination evidence weak)

Change Early Phase (0–48h) Late/Hypermetabolic Phase Succinylcholine SAFE in the first 24–48 hours post-burn CONTRAINDICATED after 48 hours until 2 years post-burn: upregulated extrajunctional AChRs from denervation of burned skin → K⁺ efflux 5–10 mEq/L → cardiac arrest; use rocuronium instead Non- Reduced protein binding (↓ albumin) → RESISTANCE to NDMR develops (upregulated AChRs bind more drug without equivalent effect); need depolarising enhanced effect; reduced Vd in early 2–3× higher doses; use TOF monitoring to titrate NMBs shock Opioids Normal initially; reduced binding with ↓ ↑ Clearance from hypermetabolism + ↑ Vd (oedema); patients may need very high doses for adequate protein analgesia Propofol Normal ↑ Volume of distribution; ↑ clearance; increased dose requirements; AVOID prolonged high-dose propofol (PRIS risk, especially in paediatric burns)

Temperature regulation: burns patients are profoundly hypothermic-prone (loss of skin barrier → massive heat and water evaporation); theatre temperature must be raised to 28–30°C; all fluids warmed to 40°C; forced-air warming; minimise exposed body surface area; temperature monitoring mandatory

Blood loss: burns excision and grafting can cause massive haemorrhage (1 mL/cm² burn area excised); blood products must be available; large-bore IV access; cell salvage; topical thrombin or adrenaline-soaked dressings (reduce surgical blood loss); tourniquets for limb excisions

IV access difficulty: extensive burns may make peripheral IV access impossible; central venous access through burned skin (sterility maintained) or through non-burned areas

Repeated anaesthetics: burns patients often require 10–20 or more anaesthetics over months; opioid tolerance and opioid-induced hyperalgesia develop rapidly; multimodal analgesia (ketamine, gabapentinoids, regional techniques) essential; ketamine specifically useful in burns — procedural sedation and analgesia during dressing changes (0.5–1 mg/kg IV or 2–4 mg/kg IM in paediatric burns)

Posterior fossa surgery (posterior cranial fossa tumours, cerebellar tumours, acoustic neuromas) — sitting position provides gravity-assisted tumour exposure and reduces venous bleeding into the surgical field (the surgical site is above heart level) Cervical spine surgery (laminectomy, foraminotomy) — gravity helps keep the surgical field dry; reduces mediastinal weight on the spinal cord in the prone position Alternative positions (prone, lateral decubitus) are increasingly preferred in many centres because of the VAE risk — the sitting position is now used only when the surgical advantages clearly outweigh the anaesthetic risks

↓ Venous return (venous pooling in the lower limbs → reduced preload → ↓ CO → ↓ MAP); magnitude: MAP may fall 15–25% from supine to full upright sitting position; patients with impaired cardiac reserve tolerate this poorly ↑ Cerebrovascular risk: the surgical site is 15–30 cm above heart level; the cerebral perfusion pressure must account for the hydrostatic gradient (MAP measured at heart level is higher than MAP at brain level by approximately 0.77 mmHg per cm elevation); Correct for hydrostatic gradient: CPP = MAP (at heart) − ICP − (height of brain above heart × 0.77 mmHg/cm); a patient with MAP 80 mmHg at heart level with the brain 20 cm higher has effective cerebral MAP = 80 − (20 × 0.77) = 80 − 15.4 = 64.6 mmHg; this must be maintained well above the lower limit of cerebral autoregulation

Management: leg compression stockings (reduce venous pooling); adequate IV fluid loading before positioning; vasopressors (phenylephrine infusion) to maintain MAP; arterial line for beat-to-beat monitoring; correct MAP target must be adjusted for height of the brain above the heart

Patent foramen ovale (PFO) is present in 25–30% of the population; in the sitting position, VAE causes right atrial pressure to rise → may reverse the atrial pressure gradient → air crosses the PFO from right to left → arterial system → paradoxical air embolism → stroke, MI, sudden death Pre-operative transoesophageal echocardiography (TOE) or transthoracic bubble study (agitated saline injected IV with TOE or TTE monitoring) is used to screen for significant PFO before sitting-position neurosurgery; a large PFO is a relative or absolute contraindication to the sitting position (some centres use it as an absolute contraindication)

If a PFO is found: consider alternative surgical position (prone); if sitting is essential, ensure the right atrial catheter is perfectly positioned for aspiration; plan for immediate Durant's manoeuvre if VAE occurs

Monitoring setup (all placed before positioning):

Precordial Doppler: probe placed over the right precordium (right sternal border, 2nd–4th ICS); calibrate with agitated saline (IV injection should produce Doppler signal change confirming correct placement and sensitivity); this is the STANDARD monitoring for VAE in sitting-position neurosurgery Right atrial catheter (CVC with tip at the cavoatrial junction or within the right atrium): the Bunegin-Albin multi-orifice catheter is purpose-designed for air aspiration from the right atrium; position confirmed by right atrial ECG waveform (p-wave morphology changes when CVC tip is in the right atrium) or by fluoroscopy; central venous catheter positioned to allow emergency air aspiration

TOE (where available): most sensitive monitor; used when the precordial Doppler is insufficient (obese patients) or when PFO is known

ETCO₂: routine monitoring; ↓ ETCO₂ confirms significant VAE (as CO₂ delivery to lungs falls)

Preventive positioning: avoid excessive head elevation (minimise hydrostatic gradient); neck should be in neutral position; avoid venous obstruction from excessive neck flexion (internal jugular compression → ↑ venous pressure at surgical site → provides some protection against VAE)

PEEP: PEEP 5 cmH₂O is sometimes used to raise CVP and reduce the negative pressure gradient driving air entrainment; however, PEEP can paradoxically worsen paradoxical air embolism risk (by raising right atrial pressure → promotes right-to-left flow through PFO if present) — benefit vs risk must be considered individually

VAE management: see Q100 for detailed stepwise protocol; key summary: flood field → stop N₂O → compress jugulars → aspirate via RA catheter → Durant's manoeuvre → vasopressors → CPR if arrest

TIVA preferred (propofol-remifentanil): avoids volatile agents at concentrations that cause cerebral vasodilation; allows more precise CO₂ control; lower PONV (critical in post-craniotomy patients — PONV raises ICP)

N₂O must be AVOIDED in sitting-position neurosurgery: N₂O will expand any VAE dramatically (25× more soluble than N₂ → diffuses into the embolism); use air-O₂ mixture instead; FiO₂ 0.35–0.5 (to minimise absorption atelectasis risk)

Arm position: both arms padded and placed on the thighs or alongside the body; avoid shoulder abduction (brachial plexus injury risk from arm falling during prolonged surgery)

Eye protection: tape eyes closed; confirm eyes not compressed by the headrest frame; orbital compression → central retinal artery occlusion → permanent blindness

Metabolism: de-esterification by non-specific blood and tissue esterases (NOT plasma pseudocholinesterase — patients with pseudocholinesterase deficiency have normal remifentanil metabolism); produces remifentanil acid — essentially inactive (1/300th to 1/1000th potency of parent); excreted renally as the inactive acid

Context-sensitive half-time (CSHT): remains constant at approximately 3 minutes regardless of infusion duration — this is the defining pharmacokinetic property; even after an 8-hour infusion, the plasma concentration falls to 50% within 3 minutes of stopping; contrast with fentanyl (CSHT rises steeply with infusion duration) and alfentanil (CSHT rises moderately)

TCI (Target-Controlled Infusion): remifentanil TCI uses the Minto model (accounts for age, weight, and gender); target plasma or effect-site concentration typically 1–8 ng/mL for surgical anaesthesia; combined with propofol TCI (Marsh or Schnider model) for TIVA

Clinical implications of ultrashort action: precise intraoperative titration; no cumulative sedation from the opioid component; fastest emergence of any opioid-based TIVA; BUT immediate pain on cessation → post-operative pain management must be planned and implemented BEFORE stopping the infusion

Definition: OIH is a state of nociceptive sensitisation caused by exposure to opioids, in which the patient becomes MORE sensitive to painful stimuli — paradoxically, opioid therapy increases rather than decreases pain; this is distinct from opioid tolerance (which is reduced analgesic effect from the same dose) although both occur with chronic opioid exposure Mechanism: Activation of spinal NMDA receptors by dynorphin (an endogenous opioid released by the same pathways activated by exogenous opioids); NMDA receptor activation → enhanced glutamate-mediated central sensitisation → wind-up → lower pain thresholds and expanded pain areas Upregulation of spinal prostaglandin E₂ pathways by mu-opioid receptor activation → ↑ spinal pain signalling Descending facilitation (opioids inhibit the descending inhibitory pathways → remove tonic pain inhibition → NET INCREASE in pain transmission) PKC (protein kinase C) phosphorylation of NMDA receptors → receptor sensitisation → allodynia and hyperalgesia

Clinical manifestation of post-remifentanil OIH: after prolonged high-dose remifentanil infusion (typically >2–4 ng/mL for >2 hours), patients often report: immediate severe pain on emergence that is disproportionate to the surgery performed; pain that does not respond as expected to rescue opioids; in some cases, allodynia (pain from normally non-painful stimuli — touch, pressure at the wound site is exquisitely painful); overall higher post-operative opioid consumption despite apparently adequate plasma morphine concentrations

Strategy Drug Mechanism Evidence NMDA Ketamine sub-anaesthetic Directly blocks NMDA receptors → prevents OIH sensitisation; Multiple RCTs confirm ketamine reduces postantagonist 0.1–0.5 mg/kg IV at the most effective anti-OIH intervention; reduces post- remifentanil pain and opioid requirements; most pre-treatment induction then 0.1–0.2 remifentanil pain scores and opioid consumption effective prevention available mg/kg/hr infusion throughout Gabapentinoid Pregabalin 75–150 mg oral Blocks α₂δ Ca²⁺ channels → reduces presynaptic glutamate Gabapentinoids reduce post-remifentanil pre-loading 1 hour before surgery; or release in dorsal horn → reduces central sensitisation hyperalgesia in multiple RCTs; also effective for gabapentin 600–1200 mg preventing chronic post-surgical pain Magnesium MgSO₄ 50 mg/kg loading Mg²⁺ is the endogenous NMDA channel blocker (voltage- Meta-analyses support Mg infusion for opioid-sparing sulphate then 8 mg/kg/hr infusion dependent block of the Mg²⁺ pore plug); IV magnesium and OIH reduction reduces OIH and post-operative opioid requirements Regional Epidural, nerve blocks, Blocks the afferent nociceptive input to the spinal cord → Strong evidence that regional anaesthesia reduces anaesthesia wound infiltration reduces the central sensitisation trigger; if nociceptive signals OIH and prevents chronic post-surgical pain never reach the dorsal horn, NMDA activation does not occur Start long- Morphine 0.1–0.15 mg/kg The 3-minute remifentanil CSHT means pain begins Standard clinical practice based on remifentanil acting opioid IV 20–30 min before end of immediately on stopping; a long-acting opioid given before pharmacokinetics; failure to pre-load long-acting BEFORE surgery; or oxycodone 0.1 stopping allows it to reach peak effect at approximately the analgesia before stopping remifentanil is a common stopping mg/kg; or hydromorphone time of waking; prevents the "pain tsunami" on emergence clinical error causing severe emergence pain remifentanil

The "remifentanil gap": the time between stopping remifentanil (and immediate loss of its analgesic effect at 3–5 min) and the onset of the long-acting opioid (typically 30–60 min for IV morphine to achieve peak analgesia) — this gap must be managed; give the long-acting opioid 20–30 min before stopping remifentanil to close the gap

Multimodal analgesia initiated intraoperatively: paracetamol 1 g IV + ketorolac 15–30 mg IV + regional technique (wound infiltration, nerve block, epidural) + ketamine infusion; all started before stopping remifentanil so they are active by emergence PCA morphine should be available in the recovery room for breakthrough pain; nurse-administered morphine 1–2 mg IV titrated in recovery if VAS >6

Feature Clonidine Dexmedetomidine α₂:α₁ selectivity 200:1 (less selective) 1600:1 (highly selective — 8× more α₂-selective than clonidine; ratio fewer α₁-mediated peripheral effects) Potency Standard reference 8× more potent than clonidine at α₂ receptors t½ (elimination) 8–12 hours (longer — less titratable) 2 hours (shorter — more titratable for IV infusion) Routes of Oral, transdermal (patch), IV, epidural, intrathecal IV infusion only (approved); intranasal in some paediatric administration protocols ICU sedation Not suitable (too long t½; oral only; imprecise titration) Standard ICU sedative (SEDCOM trial); 0.2–1.4 mcg/kg/hr infusion; less delirium, less ventilator time vs benzodiazepines Oral 100–300 mcg oral 60–90 min pre-op; reduces anxiety, reduces MAC (25–40%), Not available orally; no role as oral premedication premedication blunts haemodynamic stress response; inexpensive; widely available Awake intubation / Less suitable (longer duration, less titratable) Preferred; rousable co-operative sedation; no respiratory procedural depression; ideal for AFOI, awake craniotomy, procedural sedation sedation Neuraxial adjuvant 15–30 mcg intrathecal (prolongs spinal block 3–4h); 1 mcg/kg caudal (extends Limited data intrathecally; not standard neuraxial practice caudal block duration in children); 150 mcg epidural (prolongs epidural block) Paediatric Oral or IV; widely used as premedication 0.5–1 mcg/kg IV loading + infusion; rousable sedation allows sedation (MRI) MRI positioning instructions Haemodynamic Bradycardia and hypotension; initial BP may rise transiently from peripheral α₂ Similar; biphasic BP (initial ↑ from peripheral α₂ then ↓ from effects vasoconstriction before central sympatholysis predominates central sympatholysis); bradycardia; avoid rapid loading dose Cost Inexpensive; generic widely available Expensive; limits routine ICU use in resource-limited settings

Choose clonidine for: oral premedication (anxiety reduction, MAC reduction, stress response blunting); neuraxial adjuvant (spinal, epidural, caudal block prolongation); when cost is a significant constraint; when oral or transdermal route is needed

Choose dexmedetomidine for: ICU sedation (especially PADIS guideline recommendation — preferred over benzodiazepines); awake procedures (AFOI, awake craniotomy) requiring rousable cooperative sedation; procedural sedation without respiratory depression; paediatric MRI sedation; situations where precise IV titration of sedation depth is needed

A TCI pump uses a three-compartment pharmacokinetic model (central compartment V1 → rapidly equilibrating peripheral V2 → slowly equilibrating peripheral V3) pre-programmed with population-derived PK parameters (volume and clearance estimates); the pump calculates the infusion rate required to achieve and maintain the clinician's target plasma concentration (Cp) or effect-site concentration (Ce) in real-time The pump continuously updates the infusion rate calculation as drug distributes between compartments; to achieve a step-change to a new target, the pump initially runs at a very high rate (saturating V1) then rapidly reduces to the maintenance rate

Plasma targeting (Cp): targets the plasma concentration — requires time for effect-site (brain) equilibration (the ke0 constant); the displayed Cp does not equal brain concentration until equilibrium

Effect-site targeting (Ce): accounts for the plasma-to-brain equilibration delay using the ke0 constant; displays the estimated brain concentration directly; more clinically intuitive — the displayed target corresponds more closely to the observed clinical effect; preferred for clinical use

Feature Marsh Model Schnider Model Published Marsh B et al. — 1991 (originally derived from 1 to 16 years Schnider TW et al. — Anesthesiology 1998/1999 (adult volunteers) paediatric data, adapted for adults) Variables used Total Body Weight (TBW) only; does not adjust for age, gender, Age, weight, height, gender → calculates LBW (Lean Body Weight) from these; height uses LBW for Vd calculations; V1 adjusted by LBW; clearance depends on weight and age Volume of Large V1 (scales directly with TBW) → higher initial bolus Smaller V1 (0.228 L/kg LBW) → smaller initial bolus → more conservative distribution (V1) predicted → may overshoot induction induction; may be more appropriate for elderly and obese

Age adjustment None — gives the same PK parameters for a 20-year-old and Yes — clearance decreases with age; elderly patients receive lower infusion rates an 80-year-old of the same weight for same target concentration; more physiologically appropriate for age-related pharmacokinetic changes Performance in Total body weight → overestimates volume and clearance in LBW-based → more appropriate for obese; avoid using TBW in obese patients obese patients obese → may underdose during maintenance if TBW is used with the Schnider model (LBW is automatically calculated from height, weight, for a very obese patient age, gender) Effect-site ke0 ke0 = 0.26 min⁻¹ (equilibration constant) ke0 = 0.456 min⁻¹ (faster equilibration assumed → Ce rises more rapidly) Clinical Acceptable for routine use; simpler (TBW only); slight tendency Preferred for elderly patients (age adjustment); more conservative initial bolus; the recommendation to deeper initial induction with effect-site targeting model most commonly used in European anaesthesia practice

The combination of propofol and remifentanil produces pharmacodynamic SYNERGY — each drug enhances the other's effect beyond simple additivity; at a given propofol Ce (e.g., 2 mcg/mL), the addition of remifentanil at 2–4 ng/mL dramatically reduces the probability of movement to stimulus and improves haemodynamic stability; conversely, remifentanil reduces the propofol concentration required for loss of consciousness and maintenance of surgical anaesthesia by 30–50% The interaction is mathematically described by a response surface model; at the typical TIVA targets (propofol 2–4 mcg/mL + remifentanil 2–6 ng/mL Ce), the combination is within the steep part of the synergistic surface — both drugs contribute meaningfully and neither should be reduced to zero without compensating with the other

Clinical implication: when remifentanil is stopped at end of surgery, propofol may need to be continued (or switched to a lower maintenance concentration) until analgesic alternatives (morphine, NSAIDs) have reached adequate effect — to prevent emergence from a sedated state that is inadequately analgesic and poorly tolerated

Indication Why TIVA is Superior One-lung ventilation Propofol does NOT inhibit HPV (preserves diversion of blood from the collapsed lung); multiple RCTs show 15–25 mmHg higher PaO₂ during (thoracic surgery) OLV with TIVA vs volatile; volatile agents inhibit HPV dose-dependently MH-susceptible All volatile halogenated agents are MH triggers; TIVA with propofol + non-depolarising NMB is the mandatory technique for MH-susceptible patients patients Intracranial Propofol reduces CMRO₂ and ICP; volatile agents at >0.5 MAC cause cerebral vasodilation → ↑ ICP; TIVA preferred for raised ICP hypertension Day surgery / Propofol's antiemetic properties reduce PONV (25–30% less than volatile); faster return to street fitness; no volatile greenhouse gas contribution ambulatory anaesthesia Environmental Volatile anaesthetic gases are greenhouse gases (desflurane GWP 2540; sevoflurane GWP 130); TIVA produces zero volatile emissions; in a sustainability movement toward net-zero healthcare, TIVA is the most environmentally responsible technique

TIVA Safety Requirements

Anti-free-flow IV line: prevents gravity siphoning of propofol if the pump is positioned below patient level

Pressure-sensing IV line / anti-disconnect alarm: detects line disconnection; TIVA awareness typically results from line disconnection which has no ETCO₂ equivalent warning; most TIVA awareness events (NAP5) occurred when the line became disconnected or kinked without detection

BIS monitoring: the primary processed EEG awareness monitor for TIVA (no ETAC to rely on); target BIS 40–60

Dedicated IV lumen: TIVA should run through a dedicated IV line — not a port shared with crystalloids or blood (dilution) or through a long extension that creates a reservoir of propofol that may not be cleared when the pump is stopped (the extension tube may contain 30–60 minutes of propofol at a low flow rate)

Ignition source (CO₂ or Nd:YAG laser — directed at laryngeal/tracheal lesions; laser beams reflect off surgical instruments) + Oxidiser (O₂ in inspired gas; N₂O also supports combustion) + Fuel (the ETT — particularly PVC ETTs burn rapidly and intensely; also surgical drapes, pharyngeal packs, adhesive dressings, pledgets)

The airway is the most dangerous location for a surgical fire because: the fire is enclosed within the airway (cannot be simply smothered); burning products are inhaled directly; immediate airway destruction; the patient is anaesthetised and cannot respond

Risk increases dramatically with: FiO₂ >0.30 (oxygen-enriched atmosphere ignites more easily); N₂O in the gas mixture (N₂O supports combustion equally to

O₂ — must be AVOIDED during laser airway surgery); use of PVC ETTs (PVC ignites readily at laser energies used clinically; when PVC burns, it produces hydrogen chloride gas — severely toxic to the airway); high laser powers, multiple laser pulses, or misdirected beams

ETT Type Design Laser Safety Limitations Laser- Standard polymer tube wrapped with High laser resistance; saline-filled Stiff and less flexible than standard ETTs; limited sizes; more resistant aluminium/stainless steel foil; cuff filled with cuff reduces ignition risk even if laser expensive; still not completely laser-proof at very high laser metal- saline (saline absorbs laser energy and self- strikes the cuff energies wrapped seals if cuff is punctured) ETT (LaserFlex, LaserShield II) Xomed Silicone tube wrapped with aluminium and Laser-resistant; double saline cuffs Larger diameter for equivalent internal diameter (reduced working Laser- then Teflon tape; double cuff (proximal provide redundant protection space for surgeon); complex cuff inflation Shield saline, distal saline) (silkwrapped)

Jet No ETT in the trachea — a thin catheter or The safest option for ignition risk No formal airway protection (aspiration risk); high-pressure jet ventilation needle jet ventilator injects O₂/air under high — no combustible tube in the can cause barotrauma; CO₂ accumulation risk; requires specific (high- pressure directly into the trachea or surgical field; the surgeon has technique and training; anaesthesiologist must constantly monitor frequency subglottic larynx; the patient's airway and completely unobstructed laryngeal for adequate oxygenation and ventilation; not suitable if the or manual) elastic recoil serve as the expiratory pathway access; cannot ignite a tube that is airway is too obstructed for jet ventilation to work not there Laser- Silicone tubes with red rubber for improved Silicone has higher ignition threshold Not truly "laser-proof"; should be combined with saline-filled cuff; resistant heat resistance than PVC; but still combustible at FiO₂ minimisation still required silicone very high laser energies tubes

FiO₂ minimisation: use the minimum FiO₂ compatible with SpO₂ ≥95%; target FiO₂ 0.25–0.30 where possible; oxygen-enriched atmosphere (>30% O₂) dramatically reduces the energy needed to ignite the ETT

Eliminate N₂O: N₂O supports combustion equally to O₂ — must be COMPLETELY EXCLUDED from the gas mixture during laser airway surgery

Saline-filled cuff: saline in the ETT cuff acts as a heat sink and thermal damper — if the laser strikes the cuff, the saline absorbs energy and the cuff may selfseal; add methylene blue to the saline (blue colour leak immediately indicates cuff breach → surgeon can stop laser immediately)

Moist pledgets/packs: wet surgical pledgets packed around the ETT cuff in the subglottis protect the cuff from direct laser beam exposure; must be kept moist (dry pledgets become fuel)

Communication: surgeon and anaesthesiologist must communicate clearly: "Laser on" / "Laser off" signals; reduce FiO₂ before each laser burst; allow 2–3 minute washout after FiO₂ increase before resuming laser use

Minimum laser energy: use the minimum power, pulse duration, and number of pulses needed for the surgical task; misdirected beam awareness (always know where the beam is aimed)

Class Features

I — Ocular only Only ocular muscles (ptosis, diplopia); no systemic involvement

IIa — Mild generalised Mild limb/axial weakness; no respiratory involvement; responds well to treatment

IIb — Moderate generalised (this patient) More severe limb weakness; oropharyngeal involvement (dysphagia, dysarthria); no respiratory crisis; reduced daily function

III — Acute fulminant Rapid-onset severe generalised weakness; respiratory involvement; may require ventilation

IV — Late severe Severe with respiratory crisis; develops >2 years from onset

V — Muscle atrophy Wasting in addition to weakness

Respiratory assessment: spirometry (FVC, FEV1, peak cough flow); if FVC <2 L or <50% predicted → high risk of post-operative ventilatory failure; ICU bed booked; plan for post-operative ventilation; if FVC >2.5 L → likely to avoid post-op ventilation if optimised

Acetylcholinesterase inhibitor (AChEI) management: pyridostigmine (Mestinon) is continued up to the morning of surgery (sip of water); do NOT stop abruptly (withdrawal can precipitate myasthenic crisis) Optimisation before surgery:

Plasmapheresis (PLEX): exchange of IgG antibodies (anti-AChR antibodies) over 3–5 sessions in the 2 weeks pre-operatively → temporarily reduces antibody titers → improves neuromuscular function → best clinical state for surgery; effect lasts 4–8 weeks

Intravenous immunoglobulin (IVIg): 2 g/kg over 2–5 days; modulates immune response; alternative to plasmapheresis; similar clinical improvement; effect lasts 4–8 weeks

Corticosteroids: if not on long-term steroids — prednisolone; if on chronic steroids → continue + stress dose hydrocortisone 100 mg TDS perioperatively

NMB Strategy — The Core Decision

NMB MG-Specific Behaviour Recommendation

Succinylcholine RESISTANCE: reduced AChR number → depolarising stimulus AVOID if possible; if needed for RSI → use 2 mg/kg; monitor TOF; expect spread across fewer receptors → higher dose needed (2–3× variable response normal) for equivalent block; Phase II block develops faster; unpredictable duration

Non- HYPERSENSITIVITY: fewer functional AChRs → same drug Use minimum necessary dose (10–30% of normal intubating dose if NMB depolarising dose produces more complete block AND more prolonged block essential); TOF monitoring mandatory; cisatracurium preferred (organNMBs (50–70% dose reduction needed vs normal); spontaneous independent); prefer avoiding NMB entirely (use deep volatile or TCI propofol + (vecuronium, recovery markedly delayed remifentanil for intubation conditions without NMB) rocuronium, atracurium) No NMB Intubation conditions achieved with deep anaesthesia Recommended approach where surgical access permits; LA infiltration of the (preferred) (sevoflurane >2 MAC or propofol-remifentanil TCI high dose) surgical site as supplementary analgesia; TIVA with propofol-remifentanil TCI without any NMB → no NMB reversal concerns; post-operative allows precise depth control recovery not complicated by residual NMB

If NMB unavoidable: use 10–20% of the normal intubating dose (e.g., atracurium 0.05 mg/kg instead of 0.5 mg/kg); TOF monitoring from the start; allow full recovery (TOF ratio ≥0.9 confirmed by acceleromyography) before considering extubation; sugammadex preferred for reversal (rocuronium 0.3 mg/kg → sugammadex 2 mg/kg for reversal)

Anticholinesterase timing: resume pyridostigmine when patient is fully awake and can swallow; do NOT give IV neostigmine intraoperatively for NMB reversal if the patient is on pyridostigmine (potential for cholinergic crisis from combined anticholinesterase effect)

Crisis Type Trigger Features Diagnosis Management Myasthenic Inadequate anticholinesterase Progressive weakness (including respiratory muscles Tensilon test: 2 mg IV IPPV support; increase Crisis (missed dose, increased → respiratory failure); dry skin/secretions; tachycardia; edrophonium → clinical pyridostigmine dose; disease severity); infection; improved with edrophonium (Tensilon test) improvement confirms plasmapheresis; IVIg; ICU surgery stress; myasthenic crisis aminoglycosides; betablockers; magnesium Cholinergic Excessive anticholinesterase Progressive weakness (paradoxically — ACh excess Tensilon test: no STOP all anticholinesterases; Crisis (pyridostigmine overdose) → depolarising block of NMJ + muscarinic improvement (or atropine 1–2 mg IV for muscarinic overactivity); wet (SLUDGE): Salivation, Lacrimation, worsening) with effects; IPPV support; allow Urination, Defaecation, GI distress, Emesis; miosis; edrophonium confirms spontaneous recovery when ACh bradycardia; WORSENED by more pyridostigmine cholinergic crisis; excess clears (hours); ICU clinical SLUDGE monitoring features