Anesthesia

The nociceptive cascade has multiple targets: pain from surgical tissue injury involves: peripheral sensitisation (PGs, bradykinin, substance P at the wound — target: NSAIDs, local anaesthetics); ascending spinal transmission (dorsal horn — target: opioids, α₂ agonists, ketamine); central processing (thalamocortical — target: paracetamol, opioids, gabapentinoids); descending modulation (from brainstem — target: SNRIs, α₂ agonists); no single drug blocks ALL of these simultaneously

Synergy: paracetamol + NSAID produces significantly better analgesia than either alone at the same individual doses; opioid + NSAID shows opioid-sparing effect of 30–40% (less opioid needed for equivalent analgesia); combination allows adequate pain control with individually lower (and safer) doses of each drug

Opioid-sparing: reducing systemic opioid consumption reduces: PONV, sedation, respiratory depression, ileus, urinary retention, cognitive impairment, and opioid-induced hyperalgesia — all of which are major barriers to early recovery in ERAS

Level Drug / Technique Mechanism Dose/Route Key Evidence Foundation Paracetamol Inhibits prostaglandin synthesis centrally 1 g IV/oral every 6 hours; Reduces opioid consumption 20% vs placebo; (all (acetaminophen) (COX-3 in CNS); also modulates descending reduce dose in liver well tolerated; no platelet, renal, or GI effects; patients) serotonergic inhibitory pathways; DOES NOT disease and <50 kg body should be prescribed regularly for ALL inhibit peripheral COX (no anti-inflammatory weight postoperative patients unless contraindicated effect in tissues) Foundation NSAIDs (ibuprofen, COX-1 and COX-2 inhibition → ↓ Ibuprofen 400–600 mg Opioid-sparing 25–35% vs placebo; celecoxib (all diclofenac, ketorolac, prostaglandin synthesis BOTH peripherally TID oral; ketorolac 15–30 equivalent to non-selective NSAIDs for pain; patients) celecoxib) (reduces sensitisation of nociceptors at mg IV every 6 hours avoid in renal impairment (↓GFR from PG wound) AND centrally (reduces PG-mediated (max 5 days); celecoxib inhibition in kidney); avoid in active peptic ulcer; central sensitisation in dorsal horn) 200–400 mg oral avoid in coagulopathy; avoid in cardiovascular (selective COX-2 — high-risk patients (long-term COX-2 selective) better GI safety) Second Gabapentinoids Bind α₂δ subunit of voltage-gated Ca²⁺ Gabapentin 300–600 mg Reduces acute postoperative pain scores by 20– level (gabapentin, channels on presynaptic terminals in dorsal oral preoperatively + 300 30%; reduces opioid consumption 30–40%; pregabalin) horn → ↓ Ca²⁺ influx → ↓ release of mg TID for 2–3 days prevents chronic post-surgical pain development glutamate, substance P, and CGRP → post-op; pregabalin 75– (prevention of central sensitisation); sedation reduces central sensitisation and neuropathic 150 mg oral BD and dizziness at higher doses — dose reduction pain component; also supraspinal anxiolytic needed in elderly and renal impairment effects Second Ketamine (sub- NMDA antagonist → blocks central 0.1–0.5 mg/kg IV loading Cochrane meta-analysis: intraoperative ketamine level anaesthetic) sensitisation ("wind-up") at the spinal cord then 0.1–0.2 mg/kg/hr reduces 24-hour morphine consumption by level; specific efficacy against opioid- infusion for 48 hours; or approximately 8 mg (30%) and reduces resistant and neuropathic pain components; 0.5 mg/kg IV at wound postoperative pain scores at rest and on ALSO reduces opioid tolerance development closure movement; particularly beneficial for major (prevents opioid-induced hyperalgesia) surgery (thoracotomy, major orthopedic) Third level Opioids (morphine, Mu-opioid receptor agonism in brain and Morphine: 0.1 mg/kg IV; Should NOT be used as the sole agent; ERAS (for oxycodone, tramadol, spinal cord; reduces pain perception; PCA 1 mg bolus with 5- philosophy: regular paracetamol + NSAID ± moderate- codeine) sedation; respiratory depression; min lockout; oxycodone gabapentinoid as baseline; opioids as PRN severe constipation and ileus (GI opioid receptors); 5–10 mg oral 4–6 hourly; rescue for breakthrough pain only, not as the pain) tolerance with prolonged use; physical and tramadol 50–100 mg TID primary analgesic psychological dependence risk (weak opioid + SNRI effect) Regional Epidural, nerve blocks Local anaesthetic blockade of afferent nerve Site-specific techniques; Thoracic epidural analgesia = gold standard for techniques (TAP, paravertebral, conduction → complete interruption of standard blocks major abdominal surgery; reduces systemic (opioid- femoral, popliteal, etc.), nociceptive transmission from the surgical described in separate opioid requirement to near-zero; best PPCs free wound infiltration with site; the most powerful analgesic intervention questions reduction; PROSPECT guidelines provide analgesia) bupivacaine/ropivacaine available procedure-specific recommendation for which block is evidence-based for each operation

Principle and Programming

Concept: patient activates a syringe pump (by pressing a button) to self-administer a pre-set bolus dose of IV opioid; the system prevents overdose through lockout intervals; the patient "titrates" to their own analgesic requirement, accounting for interindividual pharmacokinetic variability that makes fixed-dose nurseadministered regimens suboptimal Standard Adult Parameter Setting Rationale (Morphine) Bolus dose 1–2 mg morphine Sufficient for analgesic effect in most adults; enough to "feel" the bolus working Lockout 5 minutes Allows peak effect of each bolus before next dose can be activated; prevents double-stacking; morphine Tmax ~5–10 min after IV interval dose Background NOT routinely Background infusion removes the self-limiting safety feature — if a patient falls asleep (indicating sufficient analgesia/sedation), infusion recommended for they stop pressing the button; background infusion continues regardless → respiratory depression while sedated; ONLY use opioid-naive adults background infusion in opioid-tolerant patients with careful monitoring 4-hour limit 20–30 mg/4 hours Prevents very high total opioid consumption; triggers review if frequently hit

Safety Features

Lockout interval (primary safety): prevents re-dosing within the lockout period even if button pressed repeatedly 4-hour limit: nurse reviews if maximum 4-hour dose is reached; may indicate inadequate analgesia requiring reassessment of the regimen

Anti-siphon valve: prevents gravity-assisted free-flow of opioid from the syringe if the pump is placed below patient level

Tamper-evident syringe: prevents drug diversion

One-way valve on the dedicated IV line: prevents bolus of opioid being pushed backward into a concurrent running IV line (avoiding inadvertent bolusing) Monitoring Requirements for PCA Continuous SpO₂ monitoring throughout PCA use (standard of care — most guidelines); hourly sedation score; hourly RR; 4-hourly pain score; only the patient must press the PCA button — family or staff pressing the button on behalf of the patient ("PCA by proxy") bypasses the self-limiting safety feature and causes respiratory arrest

Anatomy: the lateral abdominal wall has three muscle layers: external oblique (most superficial), internal oblique (middle), and transversus abdominis (deepest, just above the peritoneum); the intercostal nerves T10–L1 (supplying the anterior abdominal wall from the umbilicus to the groin) travel within the fascial plane between the internal oblique and transversus abdominis — the TAP (Transversus Abdominis Plane); injection of LA into this plane bathes the nerve trunks as they fan out across the abdominal wall Approaches:

Lateral TAP (midaxillary approach): probe in the mid-axillary line between the iliac crest and costal margin; image the three muscle layers; inject 20 mL 0.25% bupivacaine (or 0.2% ropivacaine) into the TAP layer (between IO and TA); covers T10–L1 (lower abdomen and groin); best for lower abdominal surgery (appendicectomy, hernia repair, Pfannenstiel incision)

Subcostal TAP: probe obliquely from the xiphoid toward the ASIS; targets T6–T9 nerves in the TAP layer below the costal margin; covers upper abdomen; for laparoscopic port sites below the costal margin

Bilateral TAP: bilateral injection for midline laparotomies or bilateral laparoscopic port sites; 20 mL each side = 40 mL total (stay within LA maximum dose)

Sonoanatomy: high-frequency (12–15 MHz) linear probe; identify three muscle layers (EO = thin superficial layer; IO = middle, usually thickest; TA = deepest, most echogenic with deep fascia); the TAP lies between IO and TA; visualise the fascial plane as a bright line; inject LA to see hypoechoic spread in the plane (if "dome" appears in TA → too deep, peritoneum injected; if injection raises IO → too superficial)

QL Type Needle Target Coverage Indication QL1 (anterior) Anterior to the QL muscle, T10–L1 (lateral cutaneous branches); similar to lateral TAP Lower abdominal surgery, hip lateral to the transversalis surgery fascia QL2 Posterior to the QL muscle, T7–L1; better posterior cutaneous coverage than QL1; may provide Laparotomy, colectomy, renal (lateral/posterior) in the thoracolumbar fascia some visceral analgesia via epidural-like spread in the thoracolumbar surgery fascia QL3 Between the QL and psoas T5–L1; most extensive coverage; may reach the paravertebral space; Major abdominal surgery, (transmuscular) major muscles (anterior QL) provides both somatic and visceral analgesia components hysterectomy, colectomy as epidural alternative Intramuscular Within the belly of the QL Variable; less commonly used Selected cases QL muscle QL technique (lateral decubitus approach — most common): patient lateral decubitus; low-frequency curved array probe (3–5 MHz) placed on the posterior flank, lateral to the spine; identify the "shamrock sign" — the three muscles (psoas major, QL, erector spinae) meeting at the L4 transverse process like a three-leaf shamrock; place the needle tip at the correct fascial plane relative to the QL (depending on QL1, QL2, or QL3 target); inject 20–30 mL 0.375% ropivacaine or 0.25% bupivacaine; bilateral for midline surgery

Feature TAP Block QL Block Coverage T10–L1 (lateral TAP); T6–T9 (subcostal); cannot reliably T5–L1 (QL3); broader coverage including posterior abdominal wall and potentially level cover upper abdomen from a single approach visceral component via thoracolumbar fascia spread

Visceral None — purely somatic abdominal wall Some visceral analgesia from QL2/QL3 (thoracolumbar fascia spread toward analgesia paravertebral space)

Ultrasound Easier — superficial, familiar anatomy; suitable for trainees More difficult — requires identification of the shamrock sign; deeper target; more difficulty variable anatomy Duration 8–12 hours (plain bupivacaine); 24–36 hours with continuous Similar; some studies show longer duration with QL (15–16 hours) due to the fascial catheter or liposomal bupivacaine depot providing slower diffusion

Evidence Moderate — effective for port-site analgesia in laparoscopic Growing — QL3 provides superior analgesia to TAP for open colectomy in multiple for surgery; less effective than epidural for open laparotomy RCTs; increasingly used as epidural alternative when epidural is contraindicated laparotomy

PROSPECT recommendation 2022: bilateral TAP blocks (subcostal + lateral) recommended for laparoscopic colectomy (Grade A evidence); QL2 or QL3 block for open colectomy as alternative to epidural; single-shot TAP for Pfannenstiel CS incision analgesia (combined with intrathecal morphine)

Liposomal bupivacaine TAP: 266 mg liposomal bupivacaine (Exparel) diluted to 60 mL for bilateral TAP → provides 72-hour analgesia from a single injection; FDA-approved indication for TAP block; allows ambulatory colectomy/hysterectomy without epidural catheter management

Maximum LA dose: bilateral blocks consume twice the dose; for bilateral TAP or bilateral QL: use 0.2–0.25% ropivacaine (lower concentration × larger volume) to maintain total dose <3 mg/kg; avoid bilateral blocks with high-concentration solutions in obese patients where the total dose may approach toxic levels

Criterion Specification Timing Within 1 week of a known clinical insult OR new/worsening respiratory symptoms Chest imaging Bilateral opacities on CXR or CT — not fully explained by effusions, lobar/lung collapse, or nodules Origin of oedema Not fully explained by cardiac failure or fluid overload; echocardiography if no risk factor for ARDS Oxygenation (on PEEP ≥5 cmH₂O) Mild: PaO₂/FiO₂ 200–300 mmHg; Moderate: PaO₂/FiO₂ 100–200 mmHg; Severe: PaO₂/FiO₂ <100 mmHg

Global Definition 2023 (Matthay et al.): expands Berlin to include patients on high-flow nasal O₂ ≥30 L/min with SpO₂/FiO₂ ≤315 (mild), and patients in resource-limited settings without PEEP-capable ventilators; acknowledges ARDS can be diagnosed without intubation

Trigger (direct: pneumonia, aspiration, COVID-19; indirect: sepsis, trauma, pancreatitis, transfusion) → inflammatory cascade (neutrophil activation, macrophage cytokine storm: IL-1β, IL-6, IL-8, TNF-α) → alveolar-capillary membrane disruption → protein-rich fluid floods alveoli → hyaline membrane formation → Type II pneumocyte damage → impaired surfactant production → alveolar collapse → severe V/Q mismatch → refractory hypoxaemia. Simultaneously: fibroblast activation → fibrin deposition → fibrosing alveolitis in survivors (fibrotic phase after 5–7 days)

Phase Timing Pathology Clinical

Exudative Days 1– DAD, hyaline membranes, neutrophil infiltration, oedema, Refractory hypoxaemia, bilateral infiltrates, poor compliance (acute) 7 protein exudate

Proliferative Days 7– Type II pneumocyte proliferation, early fibroblast activation, Some improvement in oxygenation; risk of ventilator-induced lung injury 14 beginning repair Fibrotic >2 Collagen deposition, lung fibrosis, emphysema-like bullae Prolonged ventilator dependence; barotrauma risk; survivors: long-term weeks reduced DLCO

Therapy Evidence When to Use

Neuromuscular ACURASYS trial (2010): early NMBA improved 90-day mortality by 9% vs placebo in moderate-severe ARDS; Severe ARDS (P/F <150) + failure blockade ROSE trial (2019): NMBA not superior to light sedation target (contradictory); current: NMBA for severe of sedation alone to prevent (cisatracurium dyssynchrony, refractory hypoxaemia, or prone positioning dyssynchrony; facilitate prone 48h) Recruitment Sustained inflation (40 cmH₂O × 40 sec) or PEEP incremental staircase; improves oxygenation acutely; ART After ETT suctioning, accidental manoeuvres trial showed no mortality benefit and possible harm in moderate ARDS; not routinely recommended; use disconnection, or circuit change selectively in severe ARDS after derecruitment events Inhaled nitric Selective pulmonary vasodilator → improves V/Q matching → ↑PaO₂; does not improve mortality; use as Refractory hypoxaemia as bridge oxide (iNO) bridge to lung transplant or ECMO decision therapy

ECMO (VV- EOLIA trial (Combes A, NEJM 2018): VV-ECMO for severe ARDS (P/F <50–80 despite optimal ventilation); Severe ARDS (P/F <80) at ECMOECMO) significant reduction in 60-day mortality (35% vs 46%); rescue therapy when conventional management fails capable centre; bridge to recovery or transplant

Conservative FACTT trial: conservative fluid management (target CVP <4 cmH₂O vs liberal CVP <10) reduced ventilator- Haemodynamically stable ARDS — fluid strategy free days and ICU days without worsening renal outcomes; reduce fluid once haemodynamically stable switch from resuscitative to conservative fluid balance

Domain Criteria for Readiness Cause of The primary reason for ventilatory support is improved or resolved (pneumonia improved, pulmonary oedema resolved, post-operative recovery respiratory adequate) failure Oxygenation PaO₂/FiO₂ ≥150–200 mmHg on FiO₂ ≤0.4–0.5 with PEEP ≤5–8 cmH₂O; SpO₂ ≥90% on these settings Ventilation Stable spontaneous respiratory effort; pH ≥7.25; PaCO₂ at or near baseline; RR ≤35 breaths/min spontaneously

Haemodynamics Stable — MAP ≥65 mmHg without escalating vasopressor requirements; no active ischaemia; HR ≤120 bpm Neurological Patient awake and following commands (GCS ≥8 if no sedation); capable of protecting the airway (cough and gag reflex present); secretion management — can clear secretions (not requiring suctioning more than every 2 hours) Sedation SAT (Spontaneous Awakening Trial) has been performed — sedation stopped or weaned to allow patient to demonstrate neurological readiness; Ely

EW (NEJM 2008): SAT + SBT combined strategy reduces ventilator days by 3 days and 1-year mortality by 14% vs SBT alone

Mode: T-piece (patient breathes entirely spontaneously through the ETT circuit with no ventilator support) OR low-level pressure support (PS 5 cmH₂O +

PEEP 5 cmH₂O — overcomes ETT resistance while minimising support); duration: 30–120 minutes

Success criteria (pass SBT): all of the following maintained throughout: SpO₂ ≥90% (or PaO₂ ≥60 mmHg on ≤40% O₂) RR ≤35 breaths/min No accessory muscle use or paradoxical breathing HR 50–140 bpm; MAP ≥65 mmHg; no new arrhythmia

No agitation, diaphoresis, or distress

Failure criteria (abort SBT): any of the above reversed — reinstate full ventilatory support; do NOT retry SBT for at least 24 hours (patient needs rest); identify and treat the cause of SBT failure

After passing SBT: assess for extubation readiness (additional criteria beyond ventilation ability)

RSBI = f/VT where f = respiratory rate (breaths/min) and VT = tidal volume (litres) measured during 1 minute of spontaneous breathing (T-piece or minimal PS)

Normal: RSBI <105 breaths/min/L (the original Yang & Tobin 1991 threshold); values below this predict successful extubation with sensitivity 97%, specificity 64%

Practical interpretation: patient breathing at 25 breaths/min with TV 0.35 L → RSBI = 25/0.35 = 71 → favourable for extubation; patient breathing at 35/min with TV 0.20 L → RSBI = 175 → very high risk of extubation failure

Limitations: alone insufficient — high sensitivity but lower specificity; must be combined with clinical assessment; not validated in chronically ventilated patients or COPD; some guidelines now use RSBI <80 as a stricter threshold for high-confidence extubation

Additional extubation criteria beyond passing SBT: adequate cough force (peak cough flow >60 L/min); secretion burden manageable (<2-hourly suctioning); upper airway intact — cuff leak test positive (if failed cuff leak → laryngeal oedema → consider IV dexamethasone 8 mg, delay extubation 24 hours, consider airway exchange catheter before extubation); no recent high aspiration risk episode

High-risk extubation: patients with >2 risk factors for re-intubation (age >65, underlying cardiac/respiratory disease, ≥2 comorbidities, BMI >30, weak cough, excessive secretions, prolonged ventilation >7 days) should receive preventive NIV (BiPAP) immediately post-extubation for at least 24 hours — reduces reintubation rate by 20–30%

High-flow nasal O₂ (HFNO) post-extubation: alternative to NIV; delivers heated-humidified O₂ at 30–60 L/min; reduces work of breathing from washout of dead space; evidence (FLORALI trial): HFNO equivalent to NIV for post-extubation respiratory failure in non-hypercapnic patients; now widely used as default post-extubation support

Reintubation: 15–20% of extubated patients require reintubation within 48–72 hours; associated with significantly higher mortality; early reintubation (within 6 hours of extubation failure signs) is associated with better outcomes than delayed reintubation after prolonged failed rescue NIV

Domain SSC 2021 2024 Updates/Evolving Evidence Fluid type Balanced crystalloids preferred PLUS trial (NEJM 2022; n=5037): Plasmalyte-148 vs 0.9% NaCl in ICU — NO significant difference in 90-day over 0.9% NaCl (SMART trial — mortality or AKI; raises questions about the magnitude of benefit of balanced vs saline; current consensus: balanced ↓ AKI); weak balanced crystalloids remain preferred but the benefit is modest recommendation Fluid volume 30 mL/kg crystalloid bolus in CLASSIC trial (NEJM 2022; n=1554): restrictive vs standard fluid in septic shock — restrictive (boluses only if Hour-1 for hypotension/lactate severe hypoperfusion; target CVP ≤5) vs standard: NO significant difference in 90-day mortality; confirms that the ≥4; reassess after each 500 mL traditional 30 mL/kg "mandate" is not evidence-based beyond the initial resuscitation; current emphasis: titrate fluid to dynamic fluid responsiveness markers (SVV, PLR), not a fixed volume Vasopressor Noradrenaline first-line (strong); VANCS trial: vasopressin vs noradrenaline in septic shock — vasopressin first-line non-inferior, fewer arrhythmias; choice vasopressin second (weak); ongoing debate; noradrenaline remains standard first-line; vasopressin as second agent to reduce noradrenaline consider terlipressin dose (catecholamine-sparing) Corticosteroids IV hydrocortisone 200 mg/day if CAPE-COVID, APROCCHSS trials: hydrocortisone + fludrocortisone in septic shock → significant 90-day mortality noradrenaline ≥0.25 mcg/kg/min reduction; growing evidence that corticosteroids benefit a broader population than previously defined; threshold for for ≥4 hours (weak initiation may be lower than noradrenaline 0.25 mcg/kg/min recommendation; ADRENAL trial basis) Lactate-guided Measure lactate; if >2 mmol/L → LACTATES trial: lactate-guided vs usual care in septic shock — lactate-guided resuscitation did not improve resuscitation reassess every 2 hours; lactate outcomes; questions whether lactate normalisation is the appropriate endpoint; tissue oxygenation markers and clearance ≥10% per 2 hours is a organ function (creatinine, bilirubin, mental status) may be equally or more relevant endpoints target

The SSC 2021 Hour-1 bundle (measure lactate, blood cultures before antibiotics, broad-spectrum antibiotics within 1 hour, 30 mL/kg crystalloid if hypotensive, vasopressor if MAP <65) has been validated in multiple observational studies showing that compliance with all 5 elements is associated with reduced mortality

Controversy: the 1-hour antibiotic target for all sepsis (not just septic shock) — some evidence that for less severe sepsis without shock, the 1-hour target may lead to unnecessary broad-spectrum antibiotic use and antibiotic resistance, without clearly improving outcomes; the 2024 updates may refine the antibiotic timing based on clinical severity

Antibiotic de-escalation: increasingly emphasised in 2024 updates — broad-spectrum antibiotics started in Hour-1 must be de-escalated as soon as culture results and clinical response allow (typically at 48–72 hours); de-escalation reduces resistance, side effects (C. difficile, nephrotoxicity), and costs

Agent Role in 2024 Guidelines Specific Advantage

Noradrenaline FIRST LINE — strong recommendation; start early Best evidence base; predictable dose-response; less tachyarrhythmia than dopamine (De (norepinephrine) (before completing 30 mL/kg if MAP <65) Backer trial)

Vasopressin SECOND LINE — add when noradrenaline dose V1 receptor vasoconstriction — no catecholamine effects; may preserve renal blood flow; ≥0.25 mcg/kg/min; reduces noradrenaline reduces relative vasopressin deficiency of septic shock requirement Hydrocortisone Add when noradrenaline ≥0.25 mcg/kg/min (2021 Not a vasopressor per se but restores catecholamine receptor sensitivity (corticosteroidthreshold; 2024 may lower this) deficient state → reduced receptor responsiveness to noradrenaline; hydrocortisone restores this) Dopamine NOT recommended as first-line; alternative only if De Backer NEJM 2010: dopamine → more arrhythmias + higher mortality in cardiogenic shock noradrenaline unavailable subgroup vs noradrenaline Angiotensin II Rescue therapy for refractory shock on high-dose AT1 receptor agonist → vasoconstriction independent of catecholamine pathway; ATHOS-3 (Giapreza) noradrenaline + vasopressin trial: improved MAP in refractory vasodilatory shock; expensive, limited availability

Haemorrhage → hypothermia (heat loss from haemorrhage, exposure, resuscitation with cold fluids) + acidosis (tissue hypoperfusion → lactic acidosis) + coagulopathy (dilution by crystalloids + consumption of clotting factors + direct hypothermia/acidosis impairment of coagulation enzyme activity) → these three form a positive feedback loop: hypothermia impairs coagulation enzymes → worse coagulopathy → more bleeding → more acidosis → more cooling → death Component Mechanism Consequence Hypothermia Blood and tissue heat loss; cold IV fluids; OR exposure; factor activity falls 10% for Progressive coagulopathy despite "normal" laboratory (<35°C) every 1°C below 37°C; platelet function impaired at <33°C; fibrinogen activity coagulation tests (which are performed at 37°C — not impaired at <30°C reflecting the patient's actual temperature) Acidosis (pH Tissue hypoperfusion → lactate accumulation → metabolic acidosis; pH <7.2 reduces Even normal factor levels fail to generate adequate thrombin at <7.2) coagulation enzyme activity by 50%; inhibits thrombin generation low pH — coagulopathy despite normal PT/APTT Coagulopathy Factor dilution by crystalloids; factor consumption; hyperfibrinolysis (plasmin Fibrinogen is consumed first (critical threshold <1.5 g/L in activation); hypothermia/acidosis-induced enzyme failure; early trauma-induced trauma); then factor V, VIII, XI; then platelet dysfunction coagulopathy (TIC — before any resuscitation)

TEG/ROTEM: whole blood point-of-care coagulation tests; provide results within 10–20 minutes vs 60+ minutes for standard laboratory coagulation tests; guide targeted blood product replacement: TEG R time prolonged → FFP; MA reduced → platelets; LY30 elevated → tranexamic acid; fibrinogen reduced (Alpha angle low) → cryoprecipitate/fibrinogen concentrate

Standard lab tests during MTP: FBC (Hb, Plt), PT/APTT/fibrinogen, ABG (pH, lactate, calcium, glucose, temperature), TEG if available — all repeated every 30–60 minutes during active haemorrhage

Rotational thromboelastometry (ROTEM): equivalent to TEG but uses different parameter names (CT = R time; MCF = MA; LI30 = LY30); EXTEM/FIBTEM/INTEM/APTEM channels provide comprehensive haemostatic profile in <30 minutes

MTP termination criteria: haemorrhage surgically or radiologically controlled; haemodynamic stability with reducing vasopressor requirements; normal coagulation parameters (TEG normalised; pH >7.25; temperature >35°C)

Post-haemostasis care: switch from DCR (permissive hypotension, haemostatic resuscitation) to damage control surgery phase: repair injuries in planned stages; prevent abdominal compartment syndrome; reverse hypothermia aggressively; correct remaining acidosis; ICU monitoring for multi-organ failure in the subsequent days

Thromboprophylaxis after MTP: VTE risk is extremely high post-trauma; start LMWH as soon as haemostasis is secure and surgical team agrees (usually 12–24 hours after haemostasis); mechanical compression devices from admission

Definition (World Allergy Organisation 2011): anaphylaxis is a severe, life-threatening, generalised hypersensitivity reaction; clinical diagnosis: "highly likely when ONE of the following 3 criteria is fulfilled": Acute onset with skin/mucosal involvement + either respiratory compromise OR reduced BP/end-organ dysfunction

Two or more of: skin/mucosal involvement, respiratory compromise, reduced BP, GI symptoms — occurring after EXPOSURE to a LIKELY ALLERGEN Reduced BP after exposure to a KNOWN allergen Immunological (IgE-mediated — Type I hypersensitivity): previous sensitisation → IgE antibodies bound to mast cells and basophils; re-exposure → allergen cross-links IgE → mast cell degranulation → histamine, tryptase, leukotrienes, prostaglandins, PAF → vasodilation + vascular permeability ↑ + bronchospasm + GI effects Non-immunological (anaphylactoid — no prior sensitisation needed): direct mast cell degranulation without IgE; drugs that cause this: opioids (morphine, codeine — direct mast cell degranulation; NOT IgE-mediated), hyperosmolar solutions, contrast media, aspirin (via COX pathway → ↑ leukotrienes), dextrans, protamine (complement activation)

Key mediators: histamine (H1 → bronchospasm, vasodilation; H2 → ↑ gastric acid); tryptase (the most specific mast cell marker — peaks at 60–90 min postanaphylaxis; used for diagnostic confirmation); leukotrienes C4 and D4 (potent bronchoconstrictors); prostaglandins; platelet activating factor (PAF)

Finding Detail Most common NMBAs 50% (suxamethonium 26%, rocuronium 14%); antibiotics 15% (teicoplanin, co-amoxiclav, cefuroxime); chlorhexidine 9%; patent blue dye 6%; triggers latex 2%; all others 18% Incidence 1 in 10,000 general anaesthetics (estimated); true incidence uncertain due to under-reporting; approximately 266 cases identified in a 12-month period across UK Mortality 9 deaths in the audit period; estimated UK mortality from perioperative anaphylaxis: 3–9 per million GAs

Cardiovascular In perioperative anaphylaxis: cardiovascular collapse is the predominant feature (73%) in contrast to community anaphylaxis where skin and predominance respiratory symptoms predominate; skin features may be absent due to vasoconstriction/surgical drapes masking urticaria Under- Only 60% of confirmed cases were referred for formal allergy investigation; many patients discharged without follow-up testing — leaving them at risk investigation of recurrence without knowing their triggers Key practice Initial adrenaline dosing often inadequate or delayed; 25% received adrenaline >10 minutes after first symptoms; some received non-adrenaline concerns vasopressors first (noradrenaline — inadequate in anaphylaxis which requires both alpha + beta effects)

ACUTE TRYPTASE SAMPLES — MANDATORY after every suspected anaphylaxis:

Sample 1: as soon as possible after reaction (within 30 minutes of onset)

Sample 2: 1–2 hours after reaction (peak tryptase — typically 60–90 minutes)

Sample 3: 24 hours (baseline tryptase — to exclude mastocytosis as an underlying cause) Serum tryptase >20 mcg/L (or >2× baseline + 2) confirms mast cell degranulation → supports anaphylaxis diagnosis Refer to allergy clinic at 4–6 weeks: this is the mandatory post-event investigation window; earlier testing is unreliable (residual drug/antibodies may interfere) Skin testing (SPT — skin prick test + ID — intradermal): gold standard for identifying the causative agent; each drug used during the anaesthetic is tested individually at non-irritating concentrations; a positive SPT (wheal ≥3 mm) confirms IgE sensitisation to that drug; helps identify the trigger and guide future safe anaesthesia

RAST/ImmunoCAP (specific IgE ELISA): blood test for specific IgE antibodies against drugs/allergens; less sensitive than skin testing for NMBAs but useful for penicillin allergy, latex, and chlorhexidine; complements skin testing

Future anaesthesia document: after full investigation, a written report must be provided to the patient specifying the identified trigger, safe alternative agents, and a detailed future anaesthesia plan; this document should be worn as a medical alert bracelet or kept with the patient's records

Grade Features Management Mild Wheeze on auscultation; ↑ peak airway pressure 20–30%; SpO₂ maintained; ETCO₂ Deepen anaesthesia; salbutamol MDI via ETT adapter; upsloping plateau; patient comfortable under adequate anaesthesia continue monitoring Moderate Audible wheeze; peak airway pressure ↑30–50%; SpO₂ 90–94%; clear shark-fin ETCO₂; Salbutamol 5 mg nebulised via circuit; increase volatile agent increased work of breathing if spontaneously ventilating concentration; IV magnesium 2 g; reduce RR to lengthen expiratory time Severe Severe wheeze or silent chest (no air entry — life-threatening); peak airway pressure Emergency protocol (see below); IV adrenaline; ketamine; IV ↑>50% or cannot ventilate; SpO₂ <90%; potential auto-PEEP development and aminophylline; consider whether this is anaphylaxis cardiovascular compromise

Common triggers: intubation/laryngoscopy in light anaesthesia; aspiration of gastric contents or secretions; airway irritation (ETT irritation, suctioning); histamine-releasing drugs (atracurium, morphine, thiopentone at high doses); anaphylaxis; irritant volatile agents (desflurane — most pungent; isoflurane); cold dry gas; GORD; active smoking; uncontrolled asthma

Cause Distinguishing Features Action ETT obstruction Unilateral or no breath sounds; passes suction catheter easily (if secretion plug) or does not pass (if Suction ETT; reposition; replace ETT if (kink, secretion, kinked); pass suction catheter immediately — rules out/confirms most ETT obstruction causes kinked bite) Endobronchial Unilateral breath sounds only; ↑ airway pressure; hypoxia; SpO₂ falls; confirm with fibreoptic or pull Withdraw ETT 1–2 cm; confirm bilateral intubation back ETT slowly until bilateral sounds return breath sounds Pneumothorax Absent unilateral breath sounds; hypotension; tracheal deviation; JVP raised; cardiovascular collapse if Emergency needle decompression 2nd (tension) tension; immediate clinical diagnosis; confirm with CXR or POCUS ICS MCL if tension; formal chest drain True BILATERAL wheeze; shark-fin ETCO₂; bilateral reduced air entry; responsive to bronchodilators; no Bronchodilators; deepen anaesthesia; bronchospasm sudden cardiovascular collapse (unless anaphylaxis) ventilation adjustment Anaphylaxis Bronchospasm + cardiovascular collapse + urticaria/flush (may be masked by drapes); tryptase Adrenaline IM/IV; IV fluids; full elevated; multiple drug exposures anaphylaxis protocol

1. FiO₂ 1.0 immediately — maximum oxygenation while managing airway 2. Deepen anaesthesia: increase volatile agent to 1.5–2 MAC (sevoflurane/isoflurane — inherent bronchodilators); propofol bolus 1–2 mg/kg IV (bronchodilator properties); avoid desflurane (airway irritant) 3. Salbutamol (albuterol): 5–10 puffs MDI via ETT adapter (actuate MDI into the circuit during inspiration); or 5 mg nebulised via the inspiratory limb; the fastest and most effective initial bronchodilator; mechanism: β₂ agonist → airway smooth muscle relaxation → bronchodilation + mast cell stabilisation 4. Ventilation adjustments: reduce RR to 8–10 breaths/min (extend expiratory time → reduce auto-PEEP); I:E ratio 1:4; reduce TV if necessary (accept permissive hypercapnia rather than high airway pressures); if patient fighting ventilator → NMBA (rocuronium 0.6 mg/kg) to eliminate respiratory dyssynchrony 5. IV Magnesium sulphate: 2 g IV over 10–20 minutes — inhibits Ca²⁺-mediated smooth muscle contraction; modest bronchodilator; well tolerated; safe to give empirically 6. IV Ketamine: 0.5–1 mg/kg IV — bronchodilator via catecholamine release and direct smooth muscle relaxation; also provides additional depth of anaesthesia; particularly useful if patient is light under anaesthesia 7. IV Aminophylline: 5 mg/kg loading over 20 minutes (reduce to 3 mg/kg if on theophylline); phosphodiesterase inhibitor → ↑ cAMP → bronchodilation; narrow therapeutic index — requires ECG monitoring (tachyarrhythmia risk) 8. IV Adrenaline: if severe, life-threatening, or anaphylaxis suspected — 50–100 mcg IV boluses; activates β₂ receptors → most powerful bronchodilator; also reverses any anaphylaxis component 9. IV Hydrocortisone: 200 mg IV — anti-inflammatory; effect delayed 4–6 hours but appropriate for medium-term management; reduces airway inflammation perpetuating bronchospasm

Preoperative optimisation: ensure asthma is well-controlled (PEFR ≥80% predicted); continue all inhalers on morning of surgery; consider salbutamol nebulisation 20–30 minutes before induction; avoid elective surgery during active exacerbation

Induction: topicalise the airway (lignocaine spray) before intubation; ensure adequate depth (sevoflurane >1 MAC or propofol 2.5 mg/kg) before laryngoscopy; LMA preferred over ETT in reactive airway disease if surgically feasible (avoids subglottic stimulation); avoid histamine-releasing NMBs (atracurium → use rocuronium or cisatracurium); avoid thiopentone in high-dose (histamine release); propofol preferred induction agent

4 Hs Perioperative Context 4 Ts Perioperative Context Hypoxia ETT displacement, oesophageal intubation, airway Tension Central line insertion, barotrauma, laparoscopy CO₂ tracking, obstruction, failed oxygenation; FIRST thing to exclude Pneumothorax ARDS over-ventilation; absent breath sounds + sudden — check bilateral breath sounds, SpO₂, ETCO₂ cardiovascular collapse; immediate needle decompression Hypovolaemia Surgical haemorrhage, aortocaval compression Tamponade Cardiac surgery complication, central line perforation, chest (pregnancy), fluid deficit; PEA in context of surgery and (cardiac) trauma; PEA after cardiac surgery is tamponade until proven haemorrhage; transfuse blood products immediately otherwise; pericardiocentesis or surgical drainage Hypo/Hyperkalaemia Succinylcholine in denervated patients, renal failure, Thrombosis PE during surgery (DVT, air embolism, fat embolism, amniotic fluid transfusion; ECG changes; calcium gluconate for (pulmonary) embolism); sudden hypoxia + hypotension + reduced ETCO₂; hyperkalaemia; calcium for hypocalcaemia thrombolyse if PE confirmed in arrest Hypothermia Prolonged surgery + inadequate warming; VF refractory Toxins Drug overdose (opioids, local anaesthetics), volatile agent to defibrillation below 28°C; warm the patient before overdose, anaphylaxis, medication errors; specific antidotes: lipid declaring death; "not dead until warm and dead" emulsion (LAST), naloxone (opioids), sugammadex (CICO), adrenaline (anaphylaxis)

Airway already managed: ETT usually in situ → confirm bilateral breath sounds and ETCO₂ waveform first (excludes oesophageal intubation as arrest cause); ensure 100% O₂; ventilate manually at 10 breaths/min (not continuous ventilation — pauses for CPR compression are acceptable if ETCO₂ waveform visible)

IV access established: use existing IV/central access; if fluids are running → check for medication errors or anaphylaxis-triggering drug

Abandon the surgical field: inform the surgeon immediately; control haemorrhage if possible; non-critical surgery → close and focus on resuscitation

Team roles: anaesthesiologist leads CPR and drug management; surgeon manages surgical cause if relevant; ODP/nurse circulates drugs; second anaesthesiologist for airway relief; immediate defibrillator application

Immediate defibrillation for VF/pVT: 200J biphasic immediately; do not delay defibrillation for any other intervention in shockable rhythms

Higher quality CPR target in operating theatre: sternal compression 5–6 cm depth at 100–120/min; full chest recoil; minimal interruptions; CPR feedback device if available

Mechanism: bupivacaine "fast in, slow out" cardiac Na⁺ channel block → VF/VT refractory to standard ACLS

Management: standard CPR; 20% lipid emulsion 1.5 mL/kg IV bolus immediately; then 0.25 mL/kg/min infusion; may repeat bolus once after 5 minutes; max 12 mL/kg total; AVOID propofol as the lipid source (not adequate lipid content for LAST at clinical doses); avoid vasopressin in LAST; adrenaline doses ≤1 mcg/kg (higher doses may worsen outcomes in LAST); consider ECMO early if LAST arrests persist despite lipid emulsion

Mechanism: massive vasodilation + myocardial depression + bronchospasm → PEA or VF

Management: FULL DOSE adrenaline 1 mg IV every 3–5 minutes (standard ACLS dose — do NOT use reduced dose in anaphylaxis arrest); IV fluids 1–2 L crystalloid rapidly; lie flat, legs up; stop causative drug; chlorphenamine and hydrocortisone are secondary — do not delay CPR for these; once ROSC: vasopressor infusion (noradrenaline); tryptase samples; allergy follow-up

Mechanism: air in the pleural space under pressure → compresses the lung, mediastinum, and great veins → reduced venous return → obstructive shock →

PEA arrest

Recognition during anaesthesia: sudden ↑ airway pressure + sudden ↓ ETCO₂ + sudden ↓ BP → absent breath sounds unilaterally

Management: immediate needle decompression 2nd intercostal space, mid-clavicular line (anterior approach — 14G IV cannula; confirm by hiss of air under pressure and haemodynamic improvement); formal chest drain after needle decompression; do NOT delay for CXR in arrest; if bilateral pneumothorax suspected (both sides absent breath sounds, bilateral raised airway pressures in ARDS) → bilateral needle decompression simultaneously

Immediate check: is the correct drug drawn up? Syringe labelling error? Dose calculation correct? Weight entered correctly into TCI?

Opioid-induced arrest: naloxone 400 mcg IV; propofol overdose: supportive CPR + lipid emulsion if unresponsive

Potassium bolus error (concentrated KCl given as IV push): hyperkalaemia → VF → calcium gluconate 1 g IV immediately; sodium bicarbonate 50 mEq IV; insulin-dextrose; defibrillate for VF; dialysis

Targeted Temperature Management (TTM): cool to 32–36°C for 24 hours in comatose post-cardiac arrest patients (TTM2 trial 2021: 33°C vs 37.5°C — no mortality difference; maintain normothermia at minimum; avoid hyperthermia >37.5°C); continuous EEG monitoring for seizures (post-anoxic seizures are common)

Haemodynamic optimisation: MAP ≥65–70 mmHg; avoid hypotension post-ROSC; vasopressor infusion; coronary angiography if STEMI suspected as cause

Neuroprognostication: defer formal neurological assessment until 72 hours post-arrest (and 24 hours after stopping TTM); use multimodal approach: EEG, SSEP, CT brain, MRI brain, biomarkers (NSE, S100β)

Hypothalamic thermostat: the preoptic nucleus of the anterior hypothalamus integrates thermal signals from the skin (peripheral warm/cold receptors) and the blood temperature (central core sensing); it maintains core temperature within a narrow range (36.5–37.5°C) by triggering heat gain or loss responses

Heat production mechanisms: shivering (skeletal muscle tremor — increases metabolic heat production 2–5×); non-shivering thermogenesis (brown adipose tissue in neonates and some adults — uncoupled oxidative phosphorylation); piloerection (traps insulating air — minimal in humans)

Heat loss mechanisms: vasodilation (increases skin blood flow → radiation and convection); sweating (evaporative cooling — most powerful heat loss mechanism at high ambient temperatures); radiation (60% of normal heat loss), convection (15%), evaporation (22%), conduction (3%)

Interthreshold range: the range of core temperatures at which no thermoregulatory response is triggered (approximately 0.2°C wide in awake humans); anaesthesia widens this range dramatically (2–4°C under GA and neuraxial anaesthesia) → the body tolerates a much wider temperature fluctuation without triggering a corrective response

Redistribution hypothermia (Phase 1 — first hour): the most important mechanism; GA abolishes the vasoconstrictor response that normally maintains a temperature gradient between the warm core (vital organs) and the cooler periphery (arms, legs, skin); vasodilation from anaesthetic agents → peripheral blood vessels dilate → warm core blood redistributes to the cool periphery → core temperature falls rapidly (1–1.5°C in first 30 minutes despite no net heat loss from the body — the heat has moved from core to periphery); this cannot be prevented by any warming measure alone Heat loss to the environment (Phase 2 — hours 1–3): the patient loses heat to the cool operating theatre environment (typically 18–20°C ambient) through radiation from exposed skin, convection from unwarmed gas flows, and conduction from cold fluid infusions and preparation solutions; the rate of heat loss exceeds metabolic heat production under anaesthesia New equilibrium (Phase 3 — after 3 hours): core temperature stabilises at a new (lower) equilibrium when heat loss and production balance

Contributing factors: cold operating theatre (18–20°C vs optimal 21–22°C); unwarmed IV fluids and blood products (stored at 4°C); unwarmed irrigation solutions; large exposed body cavities (abdominal, thoracic); prolonged surgery; regional anaesthesia (vasodilates below the block level); neonates and extremes of age; thin patients with low body fat

Consequence Mechanism Evidence Surgical Site Hypothermia → vasoconstriction of skin/subcutaneous tissue → ↓ O₂ delivery to the Kurz A (NEJM 1996): maintaining normothermia (36.6°C vs Infection wound → ↓ oxidative bacterial killing by neutrophils → ↑ SSI rate; also impairs 34.7°C) reduced SSI rate from 18% to 6% in colorectal (SSI) collagen deposition surgery — a 3× reduction; this landmark trial established warming as a patient safety standard Coagulopathy Each 1°C below 37°C → 10% reduction in coagulation enzyme activity; platelet Frank SM (Anesthesiology 1997): hypothermic patients (34°C) function impaired; fibrinolysis altered; coagulopathy occurs at "normal" PT/APTT required 20% more blood transfusion than normothermic (tested at 37°C in the lab, not at the patient's actual temperature) patients in hip arthroplasty Cardiac Vasoconstriction → ↑ SVR → ↑ cardiac workload; shivering → ↑ O₂ consumption; Frank SM (JAMA 1997): hypothermic patients had significantly events tachycardia → ↑ myocardial O₂ demand; hypothermia → arrhythmias (AF below 35°C, more morbid cardiac events (MI, unstable angina) in the 24 VF below 28°C) hours after major non-cardiac surgery Prolonged Hypothermia reduces hepatic and renal blood flow → ↓ drug metabolism; ↓ plasma NMB duration prolonged by 30–60% at core temperature drug action pseudocholinesterase activity → prolonged succinylcholine; ↓ cytochrome P450 34°C; extends post-operative recovery room time activity; volatile agents: MAC falls ~5% per °C below 37°C → deeper anaesthesia at lower vaporiser settings than expected Patient Post-anaesthetic shivering occurs in 20–60% of patients; increases O₂ consumption Shivering: treat with pethidine 25 mg IV (most effective) or discomfort 400–500%; increases CO₂ production → impairs wound oxygenation; profoundly ondansetron; prevent with active warming and shivering uncomfortable — frequently rated by patients as the worst part of their surgical experience (worse than pain)