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Muscle Relaxants (Neuromuscular Blocking Drugs) — MD Anaesthesia Long Question

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1. ANATOMY OF THE NEUROMUSCULAR JUNCTION (NMJ)

Presynaptic Terminal

• Motor nerve terminal synthesizes acetylcholine (ACh) from choline + acetyl-CoA (choline acetyltransferase)
• ACh stored in quanta (~10,000 molecules each) within synaptic vesicles
• Action potential → voltage-gated Ca²⁺ influx → exocytosis of ACh quanta into the 50–70 nm synaptic cleft

Postsynaptic Membrane (Motor End Plate)

• Nicotinic ACh receptors (nAChR) concentrated at crests of junctional folds
• Mature (adult) receptor: α₂βδε — shorter opening time, larger central pore, high ion conductance (Na⁺ in, K⁺ out, Ca²⁺)
• Immature (fetal/extrajunctional) receptor: α₂βδγ — 10× longer opening time, smaller pore, spread throughout muscle membrane
• Binding of ACh to both α subunits required for channel opening → endplate potential (EPP) → action potential → muscle contraction
• Spontaneous small releases → miniature end-plate potentials (MEPPs)

Acetylcholinesterase

• Located within the synaptic cleft
• Rapidly hydrolyzes ACh → choline + acetic acid
• Choline recycled into presynaptic terminal

Presynaptic Nicotinic Receptors

• Pentameric α₃β₂ subunit composition
• Positive feedback — facilitate further ACh release during high-frequency stimulation
• Nondepolarizing NMBDs block these → cause "fade" with repetitive stimulation (TOF, tetanus)

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2. CLASSIFICATION OF NEUROMUSCULAR BLOCKING DRUGS

By Mechanism

By Chemical Structure

By Duration of Action (at ED₉₅ doses)

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3. PHARMACOLOGY OF INDIVIDUAL DRUGS

A. SUCCINYLCHOLINE (Suxamethonium)

• Structure: Two ACh molecules joined end-to-end
• Mechanism: Depolarizing — binds both α subunits, opens channel → sustained depolarization → Phase I block → ion channel inactivation prevents re-firing
• Phase I block: Fasciculations → flaccid paralysis; augmented by anticholinesterases; decreased by prior nondepolarizing (pretreatment)
• Phase II block (tachyphylaxis): With repeated large doses → resembles nondepolarizing block (fade on TOF, post-tetanic facilitation) — can be reversed with neostigmine cautiously
• Dose: 1–1.5 mg/kg IV (intubating); 3–4 mg/kg IM
• Onset: <60 seconds (fastest of all NMBDs)
• Duration: 5–10 minutes
• Metabolism: Rapid hydrolysis by butyrylcholinesterase (pseudocholinesterase) in plasma
  • NOT by acetylcholinesterase
  • Dibucaine number measures qualitative enzyme activity (normal ≥70; heterozygous atypical ~50–60; homozygous atypical ~20)
  • Homozygous atypical → prolonged block (2–3+ hours)

Adverse Effects of Succinylcholine (HIGH-YIELD)

Contraindications to Succinylcholine

1. Known MH susceptibility
2. Hyperkalemia or conditions predisposing to it (burns >24h, denervation, crush injury)
3. Personal/family history of MH
4. Myopathies (Duchenne's — rhabdomyolysis + hyperkalemia)
5. Penetrating eye injury (relative)

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B. NONDEPOLARIZING NMBDs

Mechanism of Action

• Competitive antagonism at both α subunits of postsynaptic nAChR
• Block presynaptic α₃β₂ receptors → impair ACh mobilization → fade on TOF and tetanus
• Reversed by increasing ACh at NMJ (anticholinesterases) or by encapsulation (sugammadex)

Onset-Potency Relationship

• Speed of onset is inversely proportional to potency (molar potency)
• Rocuronium = ~13% potency of vecuronium → faster onset
• Cisatracurium = high potency → slower onset
• To achieve rapid onset with a high-potency drug → must use large multiples of ED₉₅ (e.g., "priming" principle)

Muscle Sensitivity Ranking (Most → Least Sensitive to NMBDs)

• Diaphragm, laryngeal adductors, masseter → more resistant (higher EC₅₀), faster blood flow → faster onset and faster recovery
• Adductor pollicis → most sensitive, slower blood flow → used as clinical monitoring site

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C. INDIVIDUAL NONDEPOLARIZING DRUGS

Rocuronium

• Aminosteroidal; intermediate duration
• Dose: 0.6 mg/kg (intubating, 3 min); 1.2 mg/kg (RSI, ~60 sec — comparable to succinylcholine)
• Primarily hepatic elimination (biliary excretion ~70%); renal ~10%
• Reversal: Sugammadex encapsulates it completely
• Advantage over succinylcholine for RSI: No hyperkalemia, no MH trigger, can be fully reversed with sugammadex 16 mg/kg

Vecuronium

• Aminosteroidal; intermediate duration (2-desmethyl derivative of pancuronium)
• More lipid soluble than pancuronium (no quaternizing methyl group at 2-position)
• Metabolism: Hepatic deacetylation → principal metabolite 3-desacetylvecuronium (80% potency of parent)
  • 3-desacetylvecuronium accumulates in renal failure → prolonged block in ICU patients
• Elimination: 30–40% biliary (unchanged), up to 25% renal
• Dose: 0.1 mg/kg; clinical duration 25–40 min
• Minimal cardiovascular effects (no vagolysis, no histamine release)

Pancuronium

• Aminosteroidal; long-acting
• Causes tachycardia and hypertension (vagolytic — blocks muscarinic receptors; also sympathomimetic via NE release)
• Primarily renal elimination (80%); avoid in renal failure
• Reversal: Neostigmine (or edrophonium)

Atracurium

• Benzylisoquinolinium; intermediate duration
• Hofmann elimination (spontaneous non-enzymatic degradation at physiological pH and temperature) + ester hydrolysis → organ-independent elimination → safe in hepatic/renal failure
• Metabolite: Laudanosine — CNS stimulant; accumulates with infusion/renal failure → theoretical seizure risk at very high levels
• Histamine release (dose-dependent) → hypotension, bronchospasm; administer slowly
• Dose: 0.5 mg/kg

Cisatracurium

• Benzylisoquinolinium; one of 10 stereoisomers of atracurium (the R-cis R'-cis isomer)
• Hofmann elimination only (no ester hydrolysis)
• 3–5× more potent than atracurium → less laudanosine generated → preferred for ICU infusions
• Minimal histamine release (major advantage over atracurium)
• Dose: 0.15–0.2 mg/kg; slower onset than atracurium
• Safe in hepatic/renal failure

Mivacurium

• Benzylisoquinolinium; short-acting
• Hydrolyzed by butyrylcholinesterase (like succinylcholine) — same vulnerability to atypical cholinesterase
• NOT eliminated by Hofmann; hydrolysis >95% of clearance
• Dose: 0.15–0.2 mg/kg; clinical duration 15–20 min
• Histamine release with rapid bolus
• Can be antagonized with neostigmine (once some spontaneous recovery is evident)

d-Tubocurarine (Historical)

• First NMB used clinically (1942)
• Long-acting benzylisoquinolinium
• Causes significant histamine release and ganglionic blockade → hypotension
• Now replaced by newer agents

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4. MONITORING NEUROMUSCULAR BLOCK

Peripheral Nerve Stimulator Patterns

TOF Interpretation

• TOF ratio ≥ 0.9 = adequate recovery (full neuromuscular function)
• TOF ratio 0.7–0.9 = subclinical residual paralysis (impaired upper airway, swallowing)
• TOF ratio < 0.4 = unable to sustain head lift >5 sec
• Fade in nondepolarizing block = presynaptic receptor blockade
• No fade (equal depression of all 4 twitches) = depolarizing (Phase I) block

Residual Paralysis Consequences

• Decreased upper esophageal tone and coordination
• Impaired hypoxic ventilatory drive
• Upper airway obstruction, aspiration risk
• Increased ICU stay, length of hospital stay, morbidity, and mortality
• (Miller's Anesthesia, 10e, p. 3220)

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5. FACTORS AFFECTING NEUROMUSCULAR BLOCK

Physiological Factors

Drug Interactions

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6. REVERSAL OF NEUROMUSCULAR BLOCK

A. Anticholinesterases (Cholinesterase Inhibitors)

Limitations of Neostigmine

• Ceiling effect: If >2 twitches on TOF are absent, neostigmine may be inadequate
• Paradoxical block: At high doses, excess ACh can cause depolarizing block
• Must be combined with anticholinergic (atropine or glycopyrrolate) to prevent:
  • Bradycardia, salivation, bronchospasm, gut hypermotility
  • Glycopyrrolate preferred (does not cross BBB, slower heart rate response matches neostigmine)
• Contraindicated for reversal of Phase I succinylcholine block (deepens it)

Prerequisites for Neostigmine Reversal

• At least 2–4 TOF twitches should be present
• TOF ratio should approach 0.4 before reversal attempted
• Do not use in the absence of any TOF twitches without PTC guidance

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B. Sugammadex (REVOLUTIONARY — HIGH-YIELD)

• Pulls drug away from NMJ → free drug gradient reverses block
• Does NOT affect muscarinic receptors → no need for anticholinergic

• Works at any depth of block
• Complete reversal (TOF ratio → 1.0 rapidly)
• No anticholinergic needed
• Can reverse immediately after intubating dose of rocuronium ("can't intubate, can't oxygenate" rescue)
• Faster reversal of deep block

• Does NOT reverse benzylisoquinolinium drugs (atracurium, cisatracurium, mivacurium)
• Does NOT reverse succinylcholine
• Hormonal contraceptives (OCP): sugammadex binds progestins → advise backup contraception for 7 days
• May cause bradycardia (rare)
• Recurrence of block if insufficient dose or aminoglycoside interaction
• Cost

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7. RAPID SEQUENCE INDUCTION (RSI) AND MUSCLE RELAXANTS

Classic RSI Protocol

1. Preoxygenation (3 min tidal volume or 4 vital capacity breaths)
2. Cricoid pressure (Sellick's maneuver) — controversial
3. Thiopental 4–5 mg/kg or propofol 1.5–2 mg/kg or ketamine 1.5 mg/kg
4. Succinylcholine 1.5 mg/kg — gold standard (onset <60 sec)
5. No mask ventilation → intubate at 60 sec

RSI with Rocuronium ("Modified RSI")

• Rocuronium 1.2 mg/kg (3× ED₉₅) → comparable onset to succinylcholine
• Evidence (2015 Cochrane review): at appropriate dose (1.2 mg/kg), no significant difference in intubating conditions vs succinylcholine
• Reversal with sugammadex 16 mg/kg if intubation fails → rescue strategy
• Preferred when succinylcholine is contraindicated

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8. SPECIAL SITUATIONS

Renal Failure

• Avoid: Pancuronium (80% renal), Vecuronium (risk of 3-desacetylvecuronium accumulation in ICU)
• Safe: Atracurium, Cisatracurium (Hofmann elimination), Mivacurium (plasma esterase)
• Rocuronium — use with caution (prolonged block); reversal with sugammadex reliable

Hepatic Failure

• Avoid: Vecuronium, Rocuronium (hepatic elimination prolonged)
• Safe: Atracurium, Cisatracurium
• Succinylcholine — butyrylcholinesterase reduced in severe liver failure → prolonged block

Burns / Denervation / Immobilization

• Contraindication to succinylcholine (after first 24h) — upregulation of extrajunctional immature nAChR → lethal hyperkalemia
• Resistance to nondepolarizing NMBDs (upregulated receptors; larger doses needed)

Myasthenia Gravis

• Extremely sensitive to nondepolarizing NMBDs (reduced functional nAChR reserve)
• Resistant to succinylcholine (Phase I block requires high doses)
• Anticholinesterase treatment reduces pseudocholinesterase → also prolonged succinylcholine effect
• Use reduced doses of NDNMBs with careful TOF monitoring

Eaton-Lambert Syndrome (Myasthenic Syndrome)

• Sensitive to both depolarizing and nondepolarizing NMBDs
• Presynaptic Ca²⁺ channel antibodies → impaired ACh release

Malignant Hyperthermia (MH)

• Triggering agents: Succinylcholine + volatile agents (halothane, isoflurane, sevoflurane, desflurane)
• Nondepolarizing NMBDs are safe in MH-susceptible patients
• Treatment: Dantrolene (blocks RyR1 receptor), cooling, hyperventilation, bicarbonate

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9. NMBDs IN THE ICU

• Avoid NMBDs by maximizing analgesics/sedatives and manipulating ventilator modes
• Minimize dose; use peripheral nerve stimulator (quantitative preferred)
• Do NOT administer for more than 2 days continuously
• Prefer bolus over infusion
• Allow periodic recovery ("drug vacation" periods)
• Consider alternatives

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10. SUMMARY TABLE — KEY PHARMACOKINETICS

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11. EXAM-FOCUSED VIVA POINTS

1. Why does rocuronium have faster onset than vecuronium despite being less potent? Low molar potency → more molecules delivered to NMJ per dose → faster receptor saturation. (Miller's 10e, p. 3220)
2. Why is fade seen with nondepolarizing but not depolarizing block? Fade = presynaptic nAChR blockade → impaired ACh mobilization during high-frequency stimulation. Phase I depolarizing block does not block presynaptic receptors.
3. What is the "ceiling effect" of neostigmine? Above a dose of ~0.07 mg/kg, further neostigmine does not increase reversal; excess ACh can accumulate causing depolarizing block. Most effective when at least 2 TOF twitches are present.
4. How does sugammadex reverse block in "can't intubate, can't oxygenate"? 16 mg/kg sugammadex given immediately after 1.2 mg/kg rocuronium — encapsulates free + NMJ-bound rocuronium → full reversal within 3 minutes.
5. Why is cisatracurium preferred over atracurium in ICU? 5× more potent → less drug given → less laudanosine generated; no histamine release; pure Hofmann elimination.
6. Dibucaine number: Normal ≥70 (>95% inhibition of pseudocholinesterase by dibucaine); heterozygous atypical 50–60; homozygous atypical ~20 → prolonged succinylcholine block.
7. Immature vs mature nAChR: Immature (γ subunit) in burns/denervation → sensitive to succinylcholine → hyperkalemia; resistant to nondepolarizers.
8. Volatile anesthetics potentiate NMBDs in this order: Isoflurane > enflurane > halothane > desflurane ≈ sevoflurane > N₂O/opioid technique.

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Anaesthesia for Laparoscopic Surgery — MD Anaesthesia Long Question

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1. INTRODUCTION

1. The physiology of pneumoperitoneum
2. The effects of patient positioning
3. Anaesthetic technique and monitoring
4. Intra- and postoperative complications

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2. SURGICAL APPROACH

Establishing the Pneumoperitoneum

• Veress needle technique: spring-loaded blunt needle inserted through a subumbilical incision; CO₂ delivered via automated insufflator
• Hasson open technique (cut-down): direct trocar placement under vision — safer in adhesions
• Maximal IAP: Should NOT exceed 15 mmHg to minimize cardiopulmonary instability
• Trocars inserted under direct visualization after pneumoperitoneum established

Choice of Insufflation Gas

Patient Positioning

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3. PHYSIOLOGY OF PNEUMOPERITONEUM (HIGH-YIELD)

A. CARDIOVASCULAR EFFECTS

Effect of Intra-Abdominal Pressure (IAP)

• Reflex bradycardia (vasovagal) may occur with rapid peritoneal insufflation — treat with atropine + deflation
• Hypercarbia from absorbed CO₂ → sympathetic stimulation → ↑ HR, ↑ BP, dysrhythmias
• Cardiac output has been observed to decrease with insufflation in most studies
• Severe hypotension during pneumoperitoneum → treat with desufflation ± conversion to open procedure (Barash/Stoelting, Key Point 12)

Positioning Effects on Cardiovascular System

• Trendelenburg (head-down): ↑ preload, but MAP and CO usually unchanged or ↓ due to baroreceptor-mediated reflex vasodilatation
• Reverse Trendelenburg (head-up): ↓ preload, ↓ CO, ↓ MAP
• High IAP + hypovolaemia = severely impaired venous return (Barash/Stoelting, Key Point 7)

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B. RESPIRATORY EFFECTS

Mechanical Effects of Pneumoperitoneum

• Diaphragm displaced cephalad → ↑ peak airway pressure, ↓ pulmonary compliance
• ↓ FRC, ↑ atelectasis, V/Q mismatch, pulmonary shunting → ↓ PaO₂
• ETT may migrate into right main bronchus during Trendelenburg + insufflation (diaphragm pushes up → ETT descends) (Barash/Stoelting, Key Point 8)

CO₂ Absorption

• CO₂ absorbed through peritoneum → hypercarbia develops within 15–30 minutes
• Consequences of hypercarbia:
  • Sympathetic stimulation → tachycardia, hypertension, dysrhythmias
  • Vasodilation at high levels → ↓ inotropy
  • Respiratory acidosis
  • ↑ ICP (dangerous in neurosurgical patients)
• Managed by increasing minute ventilation (↑ RR preferred over ↑ TV)
• ETCO₂ is a reliable guide in healthy patients; gradient between PaCO₂ and ETCO₂ increases if cardiac output falls or dead space increases

Postoperative Respiratory Dysfunction

• FEV₁, FVC, and forced expiratory flow reduced by ~25% after laparoscopic cholecystectomy (vs ~50% after open) — persist for at least 24 hours (Morgan, p. 1014)

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C. RENAL EFFECTS

• ↓ Renal blood flow, ↓ GFR, ↓ urine output during pneumoperitoneum (Barash/Stoelting, Key Point 9)
• Mechanism: ↑ renal vascular resistance → direct renal parenchymal compression → renin–angiotensin–ADH activation
• Intraoperative oliguria expected → does not necessarily indicate hypovolaemia
• Usually followed by postoperative diuresis

D. NEUROENDOCRINE/STRESS RESPONSE

• ↑ Catecholamines, cortisol, ACTH, ADH, renin, angiotensin — but less so than open surgery
• CO₂ directly stimulates hypothalamo-pituitary axis

E. HEPATIC/SPLANCHNIC EFFECTS

• ↑ IAP → ↓ portal blood flow, ↓ hepatic arterial flow → transient hepatic ischaemia possible
• Splanchnic vasoconstriction

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4. PRE-OPERATIVE ASSESSMENT

Standard Assessment

• Cardiovascular: exercise tolerance, history of IHD, valvular disease, arrhythmias
• Respiratory: COPD, asthma, obesity, OSA — all aggravate pneumoperitoneum effects
• Gastro-oesophageal reflux disease (GERD): increased aspiration risk

High-Risk Groups Requiring Special Attention

Absolute Contraindications to Laparoscopy

• Uncorrected coagulopathy
• Haemodynamic instability / hypovolaemic shock
• Bowel obstruction (relative — risk of bowel injury, aspiration)

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5. ANAESTHETIC TECHNIQUE

Choice of Technique

General Anaesthesia (PREFERRED)

• Standard of care for laparoscopic procedures
• Mandatory in:
  • Prolonged procedures
  • Steep Trendelenburg position
  • Obese patients
  • High aspiration risk
  • Need for muscle relaxation
  • Need for controlled ventilation to manage hypercarbia

Regional Anaesthesia (Spinal/Epidural) — Rarely Used

• Disadvantages (Morgan, p. 1012):
  • Dyspnoea and discomfort from diaphragmatic irritation by CO₂
  • High neuraxial block required (T2–T4) for adequate muscle relaxation
  • Cannot control ventilation → hypercarbia in spontaneous breathing
  • Referred shoulder pain from phrenic nerve irritation
  • Not suitable for obese patients or those with respiratory disease
• Occasionally used for very brief, simple diagnostic laparoscopies

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Airway Management

Tracheal Intubation (Preferred)

1. ↑ IAP → risk of regurgitation and aspiration
2. Controlled ventilation required to prevent hypercarbia
3. High peak airway pressures with poor compliance
4. Need for NMB (adequate muscle relaxation → lower IAP needed → less CO₂ absorption)
5. Nasogastric tube for gastric decompression
6. Prevent ETT migration — can be checked and secured

Supraglottic Airway Devices (Second-Generation LMA)

• Increasingly used for selected low-risk patients with brief procedures
• Requirements: low aspiration risk, normal BMI, non-Trendelenburg position, short surgery
• Advantages: reduced airway trauma, lower incidence of sore throat, faster recovery
• Second-generation devices (ProSeal/Supreme LMA) allow gastric decompression

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Induction

• Adequate preoxygenation mandatory (denitrogenation)
• Rapid sequence induction if:
  • GERD / full stomach
  • Hiatus hernia
  • Obesity
  • Emergency surgery
• Standard induction: propofol + opioid + succinylcholine or rocuronium
• Ensure deep NMB for creation of pneumoperitoneum → lower IAP needed (10–12 mmHg) → reduced cardiopulmonary effects

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Maintenance

Inhalational vs. TIVA

• Nitrous oxide: generally avoided (↑ PONV, risk of bowel distension, flammable with bowel gas, worsens gas embolism)
• Sevoflurane or desflurane most commonly used volatile agents

Muscle Relaxation

• Deep neuromuscular block improves surgical conditions, allows lower insufflation pressures (10–12 vs 15 mmHg) → less cardiopulmonary compromise
• Monitor NMB: TOF or PTC (monitoring can be challenging during surgery) (Barash/Stoelting, Key Point 10)
• Sugammadex preferred for reversal (deep block reversal possible; no risk of inadequate reversal)

Mechanical Ventilation Strategy

• Volume-controlled or pressure-controlled ventilation
• ↑ RR (preferred over ↑ TV) to manage hypercarbia → avoids high peak airway pressures
• PEEP 5 cmH₂O: improves oxygenation and prevents atelectasis, especially in Trendelenburg
• Avoid excessive TV (causes diaphragm movement → impairs surgical field)
• Target: ETCO₂ 35–40 mmHg (but note widened A-a gradient in patients with ↓ CO)
• In Trendelenburg: watch for ETT migration → reconfirm position after positioning

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Monitoring

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Fluid Management

• Avoid aggressive fluid loading — ↑ IAP reduces effectiveness and may worsen outcomes
• Goal-directed fluid therapy where available
• Intraoperative oliguria expected → do not over-treat
• Postoperative diuresis will usually follow

Temperature Management

• Cold, dry CO₂ gas → hypothermia
• Use: forced-air warming blanket, warmed IV fluids, heated humidified CO₂ insufflation (Barash/Stoelting, Key Point — Body Temperature)

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6. COMPLICATIONS (HIGH-YIELD)

A. INTRAOPERATIVE COMPLICATIONS

1. Cardiovascular

2. CO₂ Gas Embolism (SERIOUS — MUST KNOW)

• Mechanism: Inadvertent CO₂ insufflation into an open vein
• Signs: Sudden ↑ ETCO₂ followed by rapid ↓, mill-wheel murmur, ↓ SpO₂, cardiovascular collapse, pulmonary hypertension, "lock" of right heart → obstructive shock
• Treatment (Morgan, p. 1013):
  1. Immediately desufflate the abdomen
  2. Discontinue N₂O (N₂O expands gas bubble)
  3. Place in left lateral decubitus + head-down (Durant's position) — keeps gas in right heart, away from pulmonary outflow tract
  4. Insert central venous catheter → aspirate gas
  5. 100% O₂, hyperventilate
  6. Cardiovascular support

3. Respiratory

4. Surgical

• Major vascular injury: Trocar / Veress needle into aorta, IVC → immediate laparotomy; rare but highest mortality (Barash/Stoelting, Key Point 11)
• Visceral perforation: Bowel / bladder injury during trocar placement
• Haemorrhage: May be underestimated laparoscopically

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B. POSITIONING-RELATED COMPLICATIONS (Barash/Stoelting)

Airway oedema management: Before extubating after prolonged steep Trendelenburg, perform cuff-leak test; consider keeping intubated until oedema resolves.

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7. POSTOPERATIVE MANAGEMENT

PONV (MAJOR CONCERN — HIGH-YIELD)

• Laparoscopic surgery is a high-risk factor for PONV
• Mechanisms: peritoneal CO₂, bowel stretching, opioids, visceral pain
• Multimodal prophylaxis (Barash/Stoelting, Key Point 15):
  • TIVA with propofol (most effective single intervention)
  • Dexamethasone 4–8 mg IV at induction
  • Ondansetron (5HT₃ antagonist) at end of surgery
  • Avoid N₂O, minimize opioids (multimodal analgesia)
  • PONV score (Apfel score): ≥2 risk factors → prophylaxis mandatory

Pain Management

• Multimodal analgesia:
  • Port-site local anaesthetic infiltration (bupivacaine/ropivacaine) — reduces somatic pain
  • Intraperitoneal local anaesthetic (IPLA) — instillation into peritoneal cavity for visceral/shoulder tip pain
  • NSAIDs/COX-2 inhibitors
  • Paracetamol (acetaminophen)
  • Low-dose opioids as rescue
  • Regional blocks where applicable (TAP block for port-site pain)
• Shoulder tip pain: Referred pain from diaphragmatic irritation by residual CO₂ → encouraged ambulation, Trendelenburg to drain CO₂

Respiratory

• FEV₁/FVC reduced ~25% post-laparoscopic cholecystectomy (recovers in 24–48h)
• Incentive spirometry, early ambulation
• Monitor for delayed subcutaneous emphysema or capnothorax

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8. SPECIAL SITUATIONS

Robotic-Assisted Laparoscopic Surgery (RALS)

• Prolonged steep Trendelenburg (often 5–6 hours) → severe physiological effects
• Limited patient access once robot docked — cannot reposition or do CPR easily (Barash/Stoelting, Key Point 6)
• Increased risk of:
  • Subcutaneous emphysema (especially with retroperitoneal access — CO₂ tracks widely)
  • Airway oedema: consider leaving intubated post-procedure
  • Intraoperative oliguria followed by postoperative diuresis
  • Compartment syndrome (legs in lithotomy for hours)
• Risk factors for SCE: BMI <25 kg/m², ETCO₂ ≥46 mmHg, operative time >200 min
• Have emergency plan for robot undocking if cardiovascular/airway emergency

Laparoscopy in Pregnancy

• Increased aspiration risk → RSI mandatory
• Risk of aortocaval compression → left lateral tilt
• Fetal monitoring
• IAP should be kept ≤12 mmHg
• CO₂ absorption → fetal hypercarbia/acidosis → maintain maternal normocarbia
• Best performed in 2nd trimester (organogenesis complete, uterus not yet very large)

Laparoscopy in Morbid Obesity

• BMI >40 + obesity-related comorbidities → significantly more perioperative complications (Barash/Stoelting, Key Point 3)
• Difficult airway: ramped positioning, video laryngoscope
• Rapid desaturation: preoxygenation in 20° head-up position, CPAP during preoxygenation
• Compliance severely reduced in Trendelenburg + pneumoperitoneum
• Higher PONV risk
• VTE prophylaxis mandatory

Paediatric Laparoscopy

• Lower IAP (8–10 mmHg) used
• More vulnerable to CO₂ absorption (body surface area/weight ratio)
• Strict temperature management

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9. CONTRAINDICATIONS TO LAPAROSCOPY

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10. SUMMARY OF KEY EXAM POINTS

1. CO₂ preferred insufflation gas — highly soluble, nonflammable, safe with electrocautery; complications from its absorption are managed by hyperventilation.
2. IAP >15 mmHg should be avoided — causes IVC compression → ↓ CO; deep NMB allows surgery at lower pressures (10–12 mmHg).
3. ETT migration into right bronchus: recheck auscultation after positioning AND after insufflation. (Barash/Stoelting, Key Point 8)
4. CO₂ embolism — ETCO₂ rises then suddenly falls; treat with immediate desufflation, Durant's position, D/C N₂O, CVC aspiration.
5. Tension capnothorax — life-threatening; high airway pressure + haemodynamic collapse → immediate needle decompression.
6. Oliguria during laparoscopy is expected — renal compression by IAP; do not over-treat with fluids.
7. PONV: laparoscopic surgery is high risk; use Apfel score + multimodal prophylaxis (TIVA, dexamethasone, 5HT₃ antagonist).
8. Shoulder tip pain = referred pain from residual intraperitoneal CO₂ irritating the diaphragm → drain CO₂ at end of surgery, Trendelenburg, IPLA instillation.
9. Airway oedema after prolonged steep Trendelenburg — do cuff-leak test before extubation; have reintubation plan ready.
10. N₂O: generally avoided — PONV, gas embolism worsening, bowel distension, flammable.

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Deep Vein Thrombosis (DVT) — MD Anaesthesia Long Question

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1. DEFINITION AND EPIDEMIOLOGY

• VTE causes >50,000 deaths per annum in the United States; ~25% occur perioperatively
• ICU patients: DVT incidence 10–30%; PE incidence 1.5–5%
• Without prophylaxis, DVT occurs after ~20% of all major surgical procedures
• Orthopedic surgery (hip/knee arthroplasty): DVT rate 40–80% without prophylaxis
• Fatal PE after elective hip/knee surgery: 1–5% without prophylaxis (Fishman's / Barash)

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2. PATHOPHYSIOLOGY — VIRCHOW'S TRIAD

Molecular Cascade

• TF:FVIIa → thrombin generation → platelet activation → polyphosphate release
• Activated neutrophils → neutrophil extracellular traps (NETs) → FXI activation → intrinsic pathway → propagation of thrombus
• Inflammation is a shared feature across all three components of Virchow's triad (Fishman's, p. 1291)

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3. RISK FACTORS FOR DVT

By Strength of Risk (Fishman's Pulmonary Diseases, Table 73-2)

Inherited (Thrombophilias) (Sabiston)

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4. ANAESTHESIA-SPECIFIC RISK FACTORS (HIGH-YIELD)

Regional vs. General Anaesthesia — Effect on DVT

1. Sympathectomy → ↑ lower extremity venous blood flow
2. Systemic anti-inflammatory effects of local anaesthetics
3. Decreased platelet reactivity
4. Attenuated post-operative ↑ in factor VIII and von Willebrand factor
5. Attenuated post-operative ↓ in antithrombin III
6. Alterations in stress hormone release

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5. CLINICAL FEATURES OF DVT

Symptoms

• Unilateral leg pain, swelling, heaviness
• Calf tenderness (Homan's sign — dorsiflexion calf pain; low sensitivity/specificity)
• Redness, warmth, distended superficial veins

Clinical Probability Score — Wells Score for DVT

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6. DIAGNOSIS

First-Line Investigation

• Good positive and negative predictive value vs. contrast venography
• Failure to compress the vein under the probe = non-compressibility = DVT
• Sensitivity ~95% for proximal DVT; lower (~70%) for calf DVT (Barash/Stoelting)

D-Dimer

• Fibrin degradation product; elevated in DVT/PE
• High sensitivity, LOW specificity — useful to rule OUT DVT (if low pre-test probability + negative D-dimer → no further testing)
• Not useful in ICU patients — nonspecifically elevated in critically ill patients (Barash/Stoelting)
• Elevated by: surgery, pregnancy, malignancy, infection, trauma, age

Contrast Venography

• Gold standard but invasive; rarely used clinically
• Reserved for: equivocal USS results, suspected calf DVT, pre-thrombectomy planning

CT Venography / MRI Venography

• Useful for iliac/inferior vena cava thrombus

Caprini VTE Risk Assessment Model (Barash/Stoelting, ICU Table 57-8)

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7. TREATMENT OF ESTABLISHED DVT

A. ANTICOAGULATION (First-Line)

Low Molecular Weight Heparin (LMWH) — Preferred

• Advantages over UFH: Predictable pharmacokinetics, no routine monitoring needed, SC administration, lower HIT risk
• Dose-adjust in renal failure (anti-Xa monitoring)
• Reversal: Protamine sulfate (partially reverses LMWH; 1 mg per 1 mg enoxaparin)

Unfractionated Heparin (UFH)

• IV infusion: 80 IU/kg bolus → 18 IU/kg/hr infusion, adjusted by aPTT (target 1.5–2.5× control)
• SC: 5000 IU 8-12 hourly (prophylaxis) or weight-based therapeutic dosing
• Advantages: Reversible with protamine; monitorable; useful in renal failure
• Reversal: Protamine 1 mg per 100 IU heparin IV (maximum 50 mg)
• Monitoring: aPTT; or anti-Xa levels for prophylaxis

Vitamin K Antagonist — Warfarin

• Inhibits vitamin K–dependent clotting factors (II, VII, IX, X) and proteins C and S
• INR target 2.0–3.0 for DVT treatment
• Loading: 5–10 mg/day; titrate to INR; overlap with heparin for at least 5 days and until INR >2 for 2 consecutive days (because initial period → anticoagulant proteins C and S fall first → early procoagulant effect)
• Reversal: Vitamin K (IV/oral), FFP, 4-factor PCC (Prothrombin Complex Concentrate), recombinant FVIIa
• Monitoring: INR

Direct Oral Anticoagulants (DOACs) — Modern Standard

• Fast onset (no bridging needed for Xa inhibitors)
• Renally excreted → caution with eGFR <30
• Reversal: Idarucizumab (dabigatran); Andexanet alfa (rivaroxaban/apixaban)
• Special consideration for regional anaesthesia: Must observe washout periods before neuraxial techniques (see Section 9)

B. DURATION OF ANTICOAGULATION

C. THROMBOLYSIS

• Systemic thrombolysis (alteplase): Indicated in massive PE with haemodynamic instability; rarely for isolated DVT
• Catheter-directed thrombolysis: For extensive proximal DVT (iliofemoral), limb-threatening ischaemia
• Contraindications: Recent surgery/trauma, active bleeding, stroke within 3 months, CNS tumour

D. INFERIOR VENA CAVA (IVC) FILTER

• Indications:
  • DVT/PE with absolute contraindication to anticoagulation (active haemorrhage, recent intracranial surgery)
  • Recurrent PE despite therapeutic anticoagulation
  • Prophylactic in high-risk patients unable to receive anticoagulation (trauma, perioperative)
• Retrievable filters preferred (can be removed once anticoagulation safe to resume)
• Reduces PE risk but does not treat DVT; may increase long-term DVT risk

E. MECHANICAL / SURGICAL

• Thrombectomy: Surgical or catheter-based; for massive iliofemoral DVT, phlegmasia cerulea dolens
• Compression stockings / bandaging: Reduce oedema; prevent post-thrombotic syndrome

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8. PROPHYLAXIS — PERIOPERATIVE DVT PREVENTION (HIGH-YIELD)

Risk Stratification (Barash/Stoelting, Table 32-5)

Mechanical Prophylaxis

IPC should be applied before sedation/induction and maintained until patient is awake and mobile (Barash/Stoelting)

Pharmacological Prophylaxis

• Without chemical prophylaxis: DVT in 40–80% of orthopaedic patients (Morgan & Mikhail)
• Rates now <1% for hip/knee arthroplasty with appropriate prophylaxis (Barash/Stoelting)

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9. NEURAXIAL ANAESTHESIA AND ANTICOAGULATION (ASRA GUIDELINES, 4th Edition) — CRITICAL FOR MD EXAM

Core Principle: Spinal Haematoma Risk

• Guidelines apply equally to deep peripheral and plexus blocks (Morgan & Mikhail)
• HIT (Heparin-Induced Thrombocytopenia): Avoid all heparin products → use argatroban or fondaparinux instead

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10. PULMONARY EMBOLISM — COMPLICATION OF DVT

Classification (Miller's Anesthesia 10e)

Diagnosis

• First-line imaging: CT Pulmonary Angiography (CTPA) — gold standard (Miller's)
• Echocardiography: NOT for initial diagnosis; useful for risk stratification and RV function assessment
• V/Q scan: if renal impairment or equivocal CTPA
• Pulmonary angiography: gold standard when: high pre-test probability + anticoagulation contraindicated → IVC filter decision

Intraoperative PE — Signs (Morgan & Mikhail)

• Sudden ↓ ETCO₂ (↑ dead space)
• ↓ SpO₂, hypotension, tachycardia
• Elevated airway pressures
• ECG: S1Q3T3 pattern, right heart strain, new RBBB

Treatment of Massive PE

1. Haemodynamic support: IV fluids cautiously, vasopressors (noradrenaline), avoid large fluid loads (worsens RV failure)
2. Systemic thrombolysis: Alteplase 100 mg IV over 2h (if no contraindications)
3. Anticoagulation: UFH IV (start after thrombolysis if used; or immediately)
4. Surgical embolectomy / catheter embolectomy: If thrombolysis contraindicated / failed
5. Mechanical circulatory support: ECMO in refractory cases

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11. POST-THROMBOTIC SYNDROME

• Long-term complication of DVT (30–50% of patients)
• Chronic venous insufficiency → leg swelling, aching, skin changes, venous ulcers
• Prevention: adequately treated DVT + compression stockings for 2 years

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12. UPPER EXTREMITY DVT — ICU CONSIDERATIONS (Barash/Stoelting)

• Increasingly common in ICU due to central venous catheters (subclavian > internal jugular)
• PE in up to one-third of upper extremity DVT cases → occasional fatalities
• Associated with: ↑ CRBSI (catheter-related bloodstream infection), postthrombotic syndrome
• Prevention: position catheter tip in superior vena cava; consider heparin-bonded catheters

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13. SUMMARY OF KEY EXAM POINTS

1. Virchow's Triad = stasis + endothelial injury + hypercoagulability — underpins all DVT pathophysiology
2. Highest-risk surgeries: Hip/knee arthroplasty, major trauma, spinal cord injury → DVT 40–80% without prophylaxis
3. Regional > General anaesthesia for DVT prevention — via sympathectomy, anti-inflammatory LA effects, preserved fibrinolysis
4. IPC must be applied before induction and maintained until ambulation
5. Compression Doppler USS = first-line diagnostic test; D-dimer useful to rule OUT in low-probability patients only
6. LMWH: 12h washout before neuraxial block (prophylactic); 24h for therapeutic dosing
7. Warfarin: Neuraxial safe only when INR ≤1.5; catheter removal only when INR ≤1.5
8. DOACs: Increasingly preferred — fast onset, no monitoring, specific reversal agents available (idarucizumab, andexanet alfa)
9. Duration: 3 months for provoked DVT; indefinite for unprovoked or recurrent
10. IVC filter: Only when anticoagulation absolutely contraindicated — does not treat DVT, reduces PE risk
11. Intraoperative PE: Sudden ↓ ETCO₂ + haemodynamic collapse → treat with heparin, vasopressors, thrombolysis if massive
12. Caprini score: Validated perioperative VTE risk tool — guides prophylaxis intensity in surgical patients

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