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What This Long Case Covers

1. Case Presentation - Demographics, diagnosis, co-morbidity, ASA grade
2. History - Fibromyoma + hyperthyroid symptoms, drug history, obstetric history
3. Clinical Examination - Including thyroid, CVS, airway assessment, proptosis note
4. Investigations - Routine + thyroid-specific + gynaecological; expected findings explained
5. Preoperative Optimization - The single most critical point: render euthyroid; 6-8 week prep with PTU/methimazole + Lugol's iodine (after antithyroid drugs) + beta-blockers + glucocorticoids
6. Pre-anaesthetic Visit - NPO, premedication, risk consent
7. Anaesthetic Management - Monitoring, induction (propofol preferred, ketamine avoided), NMB cautions (myasthenia gravis risk), airway management for goiter, maintenance goals
8. Lithotomy Position Management - Physiological changes (FRC decrease, cardiovascular shifts), technique (2-person rule, padding), full nerve injury table, compartment syndrome risk, mandatory BP check on leg lowering
9. Thyroid Storm Management - Full drug protocol table; distinction from malignant hyperthermia (critical viva question)
10. Regional Anaesthesia - Options and precautions (no epinephrine)
11. Postoperative Management - ICU criteria, monitoring, analgesia, complications
12. Viva Summary Table + Anticipated Examiner Questions

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LONG CASE PRESENTATION

MD Anaesthesiology Examination

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CASE: HYPERTHYROIDISM WITH FIBROMYOMA UTERUS FOR TOTAL ABDOMINAL HYSTERECTOMY

Anaesthesia Technique: Combined Spinal-Epidural (CSE)

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SECTION 1: PATIENT BIODATA

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SECTION 2: CHIEF COMPLAINTS

1. Heavy, prolonged, irregular menstrual bleeding for 3 years
2. Lower abdominal heaviness and pelvic pressure for 2 years
3. Increased urinary frequency for 6 months
4. Palpitations, heat intolerance, and tremors for 2 years
5. Loss of weight (approximately 7 kg over 18 months)

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SECTION 3: HISTORY OF PRESENT ILLNESS

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SECTION 4: PAST HISTORY

• Medical: Hyperthyroidism (Graves' disease) - 2 years; on treatment
• Surgical: Lower segment caesarean section (LSCS) x2 (1994, 1997) - relevant for potential intraabdominal adhesions
• Anaesthetic: Two prior spinal anaesthetics for LSCS - uneventful; no post-dural puncture headache (PDPH)
• Psychiatric: Nil
• Allergies: No known drug allergies (NKDA)

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SECTION 5: DRUG HISTORY

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SECTION 6: FAMILY AND PERSONAL HISTORY

• Family history: No known thyroid disease; no family history of bleeding disorders
• Menstrual history: Menarche at 13; cycles previously regular 28/4-5 days; now irregular 21-35 days cycle, 7-10 days duration, heavy with clots (soaking 6-8 pads/day)
• Obstetric history: G3P3+0 (LSCS x2, normal vaginal delivery x1); LMP: 18th May 2026 (heavy)
• Occupation: Homemaker; sedentary activity
• Appetite: Increased despite weight loss
• Bowel/Bladder: Frequency of stools (3-4/day); urinary frequency (9-10 times/day)
• Sleep: Disturbed; difficulty falling asleep
• Habits: Non-smoker, no alcohol, no tobacco

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SECTION 7: GENERAL PHYSICAL EXAMINATION

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SECTION 8: VITAL SIGNS

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SECTION 9: SYSTEMIC EXAMINATION

9.1 Cardiovascular System

• Hyperdynamic precordium
• Apex beat: 5th intercostal space, midclavicular line
• Heart sounds: S1, S2 heard, no murmurs; possible soft S3 (high-output state)
• No signs of cardiac failure; no raised JVP; no peripheral oedema

9.2 Respiratory System

• Equal bilateral air entry
• No added sounds; no wheeze
• Trachea: Central - no deviation from goiter compression

9.3 Thyroid Gland

• Diffusely enlarged, Grade II goiter
• Soft, non-tender, moves on swallowing
• Thyroid bruit present on auscultation
• Pemberton's sign: Negative
• No tracheal deviation

9.4 Per Abdomen

• Uterus palpable: hard, irregular; fundal height equivalent to 18 weeks gestation
• No ascites; no other palpable organomegaly
• Bowel sounds: Normal

9.5 Per Speculum / Per Vaginum (documented by gynaecologist)

• Cervix: Healthy; Os closed
• Uterus: Bulky, irregular, mobile; multiple fibroid masses
• Adnexa: No tenderness; no adnexal mass

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SECTION 10: AIRWAY ASSESSMENT

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SECTION 11: INVESTIGATIONS

11.1 Haematological

11.2 Biochemistry

11.3 Thyroid Function Tests

11.4 Electrocardiogram (ECG)

• Rate: 88/min
• Rhythm: Normal sinus rhythm
• Axis: Normal
• P waves: Normal morphology
• PR interval: 0.16 sec
• QRS: 0.08 sec; no widening
• QTc: 420 ms (normal)
• ST-T changes: None
• Impression: Normal sinus rhythm; no evidence of atrial fibrillation or ischaemia

11.5 Chest X-ray (PA view)

• Trachea: Central, no deviation
• Lung fields: Clear bilaterally; no consolidation; no pleural effusion
• Heart: Normal in size (cardiothoracic ratio 0.48)
• Mediastinum: Normal width
• Bones: No abnormality

11.6 Ultrasonography Pelvis (12 April 2026)

• Multiple intramural and subserosal fibroids
• Largest fibroid: 8.4 × 7.1 cm (fundal)
• Total uterus size: 18 weeks equivalent
• Endometrial thickness: 9 mm (slightly thickened)
• Ovaries: Normal bilaterally
• No free fluid in pelvis

11.7 Echocardiography (30 April 2026)

• LV function: Preserved; EF 64%
• LV dimensions: Mild increase in LV end-diastolic diameter (52 mm) - consistent with high-output state
• No regional wall motion abnormality
• Valves: Normal; no regurgitation
• No pericardial effusion
• Impression: Mild hyperdynamic circulation consistent with partially treated hyperthyroidism; no structural cardiac disease

11.8 Blood Group and Crossmatch

• Blood group: O Positive
• Crossmatch: 2 units packed red blood cells (PRBC) crossmatched and held in blood bank

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SECTION 12: PREOPERATIVE ANAESTHETIC ASSESSMENT & OPTIMIZATION

12.1 Problem List

1. Hyperthyroidism (Graves' disease) - now biochemically euthyroid
2. Mild iron-deficiency anaemia (Hb 9.4 g/dL)
3. Mild hyperdynamic cardiac state (EF preserved; LV mildly dilated)
4. Large fibromyoma uterus (18-week size) - increased surgical complexity
5. Prior LSCS x2 - risk of intraabdominal adhesions
6. Mild bilateral proptosis - eye protection required
7. Normal airway, but goiter present - difficult airway equipment mandatory

12.2 Preoperative Optimization

• TSH: 0.38 mIU/L (low-normal, acceptable)
• Free T4 and T3: Normal
• Resting heart rate: 88/min (target <90/min)
• 18 months of antithyroid therapy completed

• Iron supplementation for 6 weeks (Hb improved from 7.8 to 9.4 g/dL)
• Cardiology and endocrinology clearance obtained
• Continue all antithyroid drugs and beta-blockers up to and including morning of surgery

12.3 Pre-anaesthetic Consent

• Hypotension with neuraxial block (managed with fluids and vasopressors)
• Post-dural puncture headache (PDPH) - low risk with pencil-point needle
• Neurological complications (rare: <0.1%)
• Thyroid storm risk (low given euthyroid state; plan in place)
• Haemorrhage requiring transfusion (2 units crossmatched)
• Conversion to general anaesthesia if regional fails
• Lithotomy position: nerve injury risk, compartment syndrome (if prolonged)
• Epidural catheter complications: infection, intravascular placement, dural puncture

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SECTION 13: PRE-ANAESTHETIC MEDICATION AND PREPARATION

13.1 Night Before Surgery

• Tab. Carbimazole 15 mg (continue as scheduled)
• Tab. Propranolol 40 mg (continue as scheduled)
• Tab. Lorazepam 1 mg orally at 10 PM (anxiolysis)
• Tab. Ranitidine 150 mg orally at 10 PM (aspiration prophylaxis)
• NPO after midnight (solids 6 hours; clear fluids 2 hours before surgery)

13.2 Morning of Surgery (06:00 AM)

• Tab. Carbimazole 15 mg with a sip of water at 6 AM
• Tab. Propranolol 40 mg with a sip of water at 6 AM
• Tab. Ranitidine 150 mg orally at 6 AM
• Tab. Metoclopramide 10 mg orally at 6 AM
• IV access secured: 18G IV cannula in right dorsal hand vein
• Co-loading: Ringer's Lactate 500 mL commenced 30 min before block

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SECTION 14: ANAESTHETIC MANAGEMENT

14.1 Choice of Anaesthesia: COMBINED SPINAL-EPIDURAL (CSE)

• Platelets >1,00,000 (2,18,000) - safe
• INR 1.0 (normal) - safe
• No systemic sepsis / skin infection at site
• No patient refusal
• No raised intracranial pressure

14.2 Monitoring Setup (Before Block)

• Right hand: 18G cannula (for drugs, fluids)
• Left antecubital fossa: 16G cannula (for rapid fluid/blood transfusion if needed)

• Inj. Phenylephrine 100 mcg/mL (first-line vasopressor for neuraxial hypotension; preferred direct-acting agent in hyperthyroid patient) (Miller's Anaesthesia 10e)
• Inj. Mephenteramine 6 mg/mL (alternate vasopressor)
• Inj. Atropine 0.6 mg/mL (avoid unless truly needed; watch bradycardia from spinal)
• Inj. Esmolol 10 mg/mL ready (for tachycardia or impending thyroid storm)
• Inj. Ephedrine 6 mg/mL (as backup only - use cautiously given hyperthyroid state)
• Inj. Succinylcholine 100 mg (for failed CSE or emergency GA conversion)

14.3 Pre-loading

• Inj. Ringer's Lactate 500 mL co-loading commenced 30 minutes before spinal injection
• Rationale: Reduces incidence and severity of spinal-induced hypotension

14.4 CSE Technique

• Skin cleaning with 10% povidone-iodine; sterile draping
• Subcutaneous infiltration: Inj. Lignocaine 2% - 2 mL at L3-L4
• 16G Tuohy needle inserted at L3-L4 using midline approach
• Loss of resistance (LOR) to saline technique used
• Epidural space identified at 5.5 cm from skin
• (Air avoided in LOR syringe to allow clear differentiation of CSF from air when spinal needle inserted)

• 25G Whitacre pencil-point spinal needle inserted through Tuohy needle (needle-through-needle technique)
• Subtle "pop" felt as dura pierced; stylet withdrawn
• Free flow of clear CSF confirmed in upright position
• Spinal needle hub and Tuohy hub stabilised by pinching between thumb and index finger (Barash 9e)
• Intrathecal injection:
  • Inj. Bupivacaine 0.5% heavy (hyperbaric) - 2.2 mL (11 mg)
  • Inj. Fentanyl 25 mcg (0.5 mL) - intrathecal adjuvant (enhances quality and duration of block, reduces bupivacaine requirement)
  • Inj. Morphine 0.1 mg (intrathecal, for postoperative analgesia)
  • Total intrathecal volume: 2.7 mL
• Injection over 20 seconds; barbotage avoided

• After spinal injection, spinal needle withdrawn
• 18G epidural catheter threaded through Tuohy needle - 4 cm in the epidural space (total 9.5 cm from skin)
• Tuohy needle withdrawn; catheter aspirated (no blood, no CSF)
• Test dose: Inj. Lignocaine 2% with adrenaline 1:200,000 - 3 mL via epidural catheter
  • Monitor for 5 minutes: no tachycardia (caution in hyperthyroid patient - baseline HR 88/min), no sensory change in upper limbs (intrathecal)
  • Test dose NEGATIVE - catheter in epidural space
  • Note for hyperthyroid patients: The tachycardia criterion for positive intravascular test dose may be unreliable due to baseline tachycardia and beta-blockade; rely on blood pressure and CNS symptoms
• Catheter secured and labelled "EPIDURAL"

14.5 Assessment of Block

• Motor block (Bromage scale): Grade 3 bilaterally at 15 minutes (unable to move legs)
• Haemodynamics at 15 minutes: BP 118/68 mmHg, HR 80/min
• Mild hypotension managed (see below)
• Patient comfort: Comfortable; no pain; pressure sensation at lower abdomen (acceptable and expected)

14.6 Management of Haemodynamics During Block

14.7 Epidural Catheter Management Intraoperatively

• Inj. Bupivacaine 0.5% isobaric - 8 mL via epidural catheter (fractionated: 3 mL + 5 mL with 2-minute interval)
• Sensory level restored to T4 within 15 minutes
• No adverse event from top-up

• Inj. Bupivacaine 0.1% + Fentanyl 2 mcg/mL infusion at 8 mL/hour via epidural catheter (postoperative analgesia)

14.8 Sedation / Anxiolysis During Surgery

• Patient awake but comfortable; mild anxiety noted at start
• Inj. Midazolam 1 mg IV given slowly (avoid excessive sedation; titrate cautiously in hyperthyroid state due to heightened CNS sensitivity)
• Supplemental oxygen: 3L/min via nasal prongs (SpO2 maintained 99-100%)

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SECTION 15: MANAGEMENT OF LITHOTOMY POSITION (INTRAOPERATIVE)

15.1 Physiological Changes and Management

• FRC decreases in lithotomy position - predisposes to atelectasis and hypoxia (Morgan & Mikhail 7e)
• Supplemental O2 via nasal prongs maintained at 4L/min
• SpO2 monitored continuously; maintained at 99-100%

• Elevation of legs acutely autotransfuses ~300-500 mL blood into central circulation - cardiac output and MAP may transiently increase (Morgan & Mikhail 7e)
• In this hyperthyroid patient (already hyperdynamic, EF 64%), this caused brief increase in BP to 128/78 mmHg at leg elevation; HR 86/min
• Esmolol 10 mg IV given as a slow bolus to manage the rise; HR settled to 80/min

• Lowering legs from lithotomy acutely reduces venous return, causing SUDDEN HYPOTENSION (Morgan & Mikhail 7e)
• Blood pressure MEASURED IMMEDIATELY after legs lowered - mandatory (Morgan & Mikhail 7e)
• Both legs lowered simultaneously and slowly by two theatre staff members
• BP at 1 minute post-lowering: 112/64 mmHg - mild hypotension - treated with Inj. Phenylephrine 50 mcg IV; BP normalised to 122/70 mmHg within 90 seconds

15.2 Positioning Technique Used

15.3 Nerve Injury Prevention

15.4 Compartment Syndrome Precautions

• Total lithotomy time: 55 minutes - low risk
• No tight straps or circumferential compression applied
• Calves checked for tense compartments at end of surgery - soft bilaterally
• Plan: CK level at 6 hours postoperatively (protocol for lithotomy >30 minutes)

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SECTION 16: INTRAOPERATIVE VIGILANCE FOR THYROID STORM

16.1 Triggering factors in this case

• Surgical stress (intraabdominal surgery, peritoneal handling)
• Prior anxiety (mitigated by anxiolysis)
• Blood loss

16.2 Intraoperative Course (Thyroid Storm - Not Occurred)

• Temperature monitored every 30 minutes throughout surgery
• Highest temperature recorded: 37.4°C (no fever; no storm)
• HR range: 78-88/min throughout
• No tachyarrhythmia; no ST changes on ECG

16.3 Thyroid Storm Protocol - STANDING ORDERS IN OR

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SECTION 17: INTRAOPERATIVE SUMMARY

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SECTION 18: POSTOPERATIVE MANAGEMENT

18.1 Immediate Recovery (PACU)

• ECG: Continuous
• NIBP: Every 5 minutes for 30 minutes, then every 15 minutes
• SpO2: Continuous
• Temperature: Every 30 minutes
• Urine output: Hourly via Foley catheter
• Neurological status: Every 15 minutes

• BP: 124/72 mmHg
• HR: 82/min
• SpO2: 99%
• Temperature: 37.2°C
• Pain score (NRS): 1/10 (epidural working well)
• Sensory level: T8 (receding appropriately)

18.2 Postoperative Analgesia

• Epidural infusion (commenced intraop): Inj. Bupivacaine 0.1% + Fentanyl 2 mcg/mL at 8 mL/hr (PCEA mode with 3 mL bolus, 30-min lockout)
• Inj. Paracetamol 1 g IV q6h (non-opioid adjunct; safe in hyperthyroid patient)
• Tab. Ibuprofen 400 mg q8h (from Day 2 if Hb adequate and renal function normal)
• Epidural catheter to be removed at 48 hours (standard post-surgical protocol)

18.3 Thyroid Storm Surveillance

• Temperature monitored 4-hourly for 48 hours
• Peak risk: 6-24 hours postoperatively (Morgan & Mikhail 7e)
• Continue Carbimazole 15 mg via NGT/orally as early as possible post-surgery
• Continue Propranolol 40 mg BD orally (restart once tolerating oral fluids)
• Endocrinology notified of surgery; will review on postoperative Day 1

18.4 Lower Limb Neurology Check (Lithotomy Position Protocol)

18.5 Other Postoperative Orders

• Deep breathing exercises and incentive spirometry (every 2 hours)
• Early ambulation: Sit up at 24 hours; walk with assistance at 48 hours
• TED stockings + LMWH (Inj. Enoxaparin 40 mg SC OD from 12 hours postop) - VTE prophylaxis (TAH is high-risk)
• Hb recheck at 24 hours; reassess transfusion need
• NPO until bowel sounds return (~24-36 hours)
• IV fluids continue until oral intake adequate
• Foley catheter: In situ for 48 hours (TAH; urinary tract monitoring)
• Check serum electrolytes at 24 hours

18.6 Criteria for ICU/HDU Transfer (Not Required in This Patient)

• Thyroid storm developed intraoperatively
• Haemodynamic instability not responding to treatment
• Blood loss >1500 mL requiring >3 units PRBC
• ECG evidence of AF or ischaemia

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SECTION 19: POSTOPERATIVE COMPLICATIONS - NONE IN THIS PATIENT

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SECTION 20: DISCHARGE SUMMARY (Day 5)

• Patient discharged on Day 5 in stable condition
• Continue: Tab. Carbimazole 15 mg OD + Tab. Propranolol 40 mg BD
• Follow-up with endocrinology in 4 weeks (TFT reassessment; may reduce Carbimazole dose)
• Follow-up with gynaecology in 2 weeks (wound check, histopathology review)
• Return immediately if: fever, palpitations, extreme anxiety, tremors (signs of thyroid storm)

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SECTION 21: DISCUSSION POINTS (For Oral Examination)

Q1. Why CSE was chosen over GA for this patient?

Q2. What is the level of spinal block required for TAH?

Q3. Why is phenylephrine the preferred vasopressor in this patient?

Q4. What is the mandatory BP check rule in lithotomy?

Q5. How do you distinguish thyroid storm from malignant hyperthermia intraoperatively?

Q6. What are the specific risks of lithotomy position in this patient?

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REFERENCES

1. Morgan & Mikhail's Clinical Anaesthesiology, 7th Edition - Chapter 32 (Lithotomy position, p.1298-1300); Chapter 56 (Thyroid and Parathyroid Disease)
2. Miller's Anaesthesia, 10th Edition - Thyroid Disease chapter, p.4251-4253; Combined Spinal-Epidural Anaesthesia
3. Barash, Cullen & Stoelting's Clinical Anaesthesia, 9th Edition - Chapter 47: Thyroid Disease (Table 47-3: Thyroid Storm Management, p.3992-3994); CSE Technique (p.2832-2833)
4. Goldman-Cecil Medicine, 26th Edition - Thyroid Storm/Crescendo Thyrotoxicosis
5. Bailey and Love's Short Practice of Surgery, 28th Edition - Lithotomy and Lloyd-Davies position

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Inhaled Anaesthetic Uptake and Distribution

From Miller's Anaesthesia (10th ed.) and Barash's Clinical Anaesthesia (9th ed.)

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THE FA/FI CONCEPT - THE FOUNDATION

FA = PA / Pbarometric, and PA = Pblood = PCNS

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THE MULTICOMPARTMENTAL MODEL (Miller's 10e)

1. Vaporizer → breathing circuit (fresh gas flow)
2. Circuit → alveolar airspace (ventilation)
3. Alveolar gas → pulmonary capillary blood (transcapillary diffusion)
4. Arterial blood → body tissues, including CNS (distribution)
5. Venous outflow from tissues → pulmonary artery (return)
6. Mixed venous blood → re-equilibrates with alveolar gas

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PART 1: BIOPHYSICAL PROPERTIES - PARTIAL PRESSURE AND PARTITION COEFFICIENTS

Partial Pressure

• Partial pressure is the portion of total pressure contributed by one gas component; it is the thermodynamic force driving gas transfer between compartments
• Anesthetics move from high to low partial pressure, regardless of other gas components
• Equilibrium is reached when partial pressure is equal across compartments
• Example: 1.5% isoflurane in air at 760 mmHg = isoflurane at 11.4 mmHg
• At high altitude, the same inhaled percentage delivers a lower absolute partial pressure and therefore a reduced pharmacologic effect (Miller's 10e, p.1922-1923)

Partition Coefficients (λ)

"The more soluble the inhaled anesthetic, the larger the capacity of the blood and tissues for that anesthetic, and the longer it takes to saturate at any given delivery rate." - Barash 9e, p.1390

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PART 2: FACTORS DETERMINING FA/FI - INDUCTION PHARMACOKINETICS

Step 1: From Vaporizer to Breathing Circuit

• Increasing FGF shortens τ and speeds rise of FI
• Overpressurization (setting vaporizer higher than target concentration) compensates for slow circuit filling - analogous to an IV bolus (Barash 9e, p.1388-1389)

Step 2: From Circuit to Alveoli - Effect of Ventilation

• Increasing MV accelerates the rise of FA toward FI
• The effect is greater for more soluble agents (e.g., halothane) because they have a larger driving gradient that ventilation can exploit
• Increased ventilation also accelerates washout during recovery

"Raising minute ventilation accelerates the rise of PA by delivering more anesthetic to the lungs. The effect is seen whether anesthetic is highly soluble in blood (e.g., halothane) or relatively insoluble (e.g., sevoflurane). However, the relative size of the ventilation effect is greater for soluble agents." - Miller's 10e, Fig. 18.4

Step 3: Alveolar Uptake into Blood - The Most Important Step

• λb/g = blood:gas partition coefficient (solubility)
• Q̇ = cardiac output
• PA = alveolar partial pressure
• PV = mixed venous partial pressure
• PB = barometric pressure

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Factor A: Solubility (Blood:Gas Partition Coefficient)

• High λb/g (halothane 2.4): blood absorbs large quantities of agent → FA rises slowly → slow induction
• Low λb/g (desflurane 0.42): blood absorbs little agent → FA rises quickly → fast induction

• Halothane (λb/g = 2.5): 71.4% transfers to blood, only 28.6% remains in alveolus → FA is low
• Desflurane (λb/g = 0.42): only 29.6% transfers to blood, 70.4% remains in alveolus → FA is high

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Factor B: Cardiac Output (Q̇)

• High cardiac output → more blood passes through the pulmonary capillaries per minute → more agent removed from alveoli → slower rise of FA → slower induction
• Low cardiac output → less blood-mediated removal → faster rise of FA → faster induction (but CNS drug delivery is also reduced, so the effect partially cancels)

• States of high CO (hyperthyroidism, pregnancy, anxiety, fever): slower alveolar rise - need higher delivered concentration
• States of low CO (shock, cardiac failure, hypovolemia): faster alveolar rise - induction may be unexpectedly rapid; overdose risk with soluble agents

"Patients with low cardiac output may absorb inhaled anesthetic faster; the alveolar partial pressure may rise more quickly... this is of particular concern with more soluble anesthetics." (Barash 9e)

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Factor C: Alveolar-Venous Partial Pressure Difference (PA - PV)

• At induction start, PV = 0 (no drug in tissues); the gradient PA - PV is maximal → uptake is highest
• As tissues absorb drug, PV rises → gradient falls → uptake decreases → FA rises faster
• This is why FA/FI curves are steep initially then flatten (the characteristic "knee" shape)

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PART 3: DISTRIBUTION INTO TISSUES

The Four Tissue Groups

Vessel-Rich Group (VRG) - Clinical Target

• Receives ~70% of cardiac output despite being only 10% of body mass
• Tissue perfusion: ~75 mL/min per 100 g of tissue (brain)
• Equilibrates within a few minutes → this is why induction is clinically rapid
• The CNS (primary target) is within the VRG; PCNS = Pblood = Palveolar at equilibration

Muscle Group

• Largest single compartment by mass (~40%)
• Perfusion: only 3 mL/min per 100 g - 25× less than VRG
• Muscle:blood partition coefficients ~2× higher than brain:blood
• Combined effect: equilibration takes hours
• Slow muscle uptake means it continues absorbing drug during prolonged anaesthesia

Fat Group

• Highly lipid-soluble volatile agents partition avidly into fat (fat:blood coefficients = 27-51 for most volatile agents)
• Fat represents the largest effective volume for potent volatile agents
• Despite only ~10% of cardiac output, the immense effective volume gives equilibration times of days
• Not clinically significant for induction speed
• Very significant for recovery after prolonged anaesthesia (>4 hours) - fat acts as a reservoir releasing drug back into blood

"After long anesthetic exposures (>4 hours), the high saturation of fat tissue may play a role in delaying emergence." - Barash 9e, p.1392

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PART 4: SPECIAL EFFECTS

The Concentration Effect

• 5 parts anesthetic + 45 parts other gas remain → anesthetic = 10% of remaining volume
• Compare to 1% anesthetic delivered: 0.5 parts absorbed, 0.5 parts + 99 parts other gas remain → only 0.5% of remaining volume

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The Second Gas Effect

1. Rapid uptake of N₂O into blood concentrates the second gas in the alveolus
2. Augmented inflow of fresh gas further increases second gas delivery
3. Result: FA of the volatile agent (e.g., isoflurane) rises faster than it would alone

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PART 5: FACTORS AFFECTING SPEED OF INDUCTION - SUMMARY TABLE

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PART 6: RECOVERY - WASHOUT PHARMACOKINETICS

• VRG (brain, heart, liver) begins recovery at full equilibration with alveoli (PCNS = Pblood = Palveoli)
• Muscle and fat begin recovery with variable partial pressures depending on duration of anaesthesia
• After short anaesthesia, muscle and fat have low anesthetic content → little redistribution back to blood
• After prolonged anaesthesia, fat contains large reservoir of agent; even after alveolar clearance, fat continues to release agent back into blood for hours → delayed emergence

"With the less soluble anesthetic sevoflurane, the time to orientation was independent of the anesthetic duration. In contrast, long anesthetic durations with isoflurane were associated with delayed times to orientation." - Barash 9e (citing Ebert et al., Anesthesiology 1998)

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PART 7: DIFFUSION HYPOXIA

• Diluted O₂ → alveolar hypoxia → arterial hypoxaemia
• Diluted CO₂ → alveolar hypocarbia → reduced respiratory drive → worsens hypoxaemia

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PART 8: EFFECT OF VENTILATION-PERFUSION MISMATCH

• With right-to-left (pulmonary) shunt: blood passes from pulmonary artery to pulmonary vein without gas exchange → carries no anesthetic → dilutes arterial concentration → slows induction
  • This effect is greater for insoluble agents (e.g., N₂O, desflurane) - because their arterial uptake depends almost entirely on alveolar exchange. Soluble agents (halothane) are less affected because blood can still absorb agent from other gas exchange units.
• With dead space (high V/Q): relatively minor effect on induction

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QUICK REFERENCE SUMMARY

UPTAKE = λb/g × Q̇ × (PA - PV) / PB

The three determinants of blood uptake:
  1. Solubility (λb/g)    → Most important
  2. Cardiac output (Q̇)
  3. Alveolar-venous gradient (PA - PV)

More uptake = slower rise of FA = slower induction

Four tissue groups (time to equilibrate):
  VRG (brain, liver, heart)  → minutes   ← clinical induction endpoint
  Muscle                      → hours
  Fat                         → days      ← recovery after long cases
  Vessel-poor (bone, skin)    → very slow

Special effects (N₂O only, clinically significant):
  Concentration effect → faster FA/FI rise at high [N₂O]
  Second gas effect    → speeds codelivered volatile agent
  Diffusion hypoxia    → give 100% O₂ on N₂O discontinuation

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• Miller's Anaesthesia, 10th Edition - Chapter 18: Uptake and Distribution of Inhaled Anesthetics (p.1922-1955), including multicompartmental model, biophysical properties, tissue distribution table (Table 18.2)
• Barash, Cullen & Stoelting's Clinical Anaesthesia, 9th Edition - Chapter 18: Inhaled Anesthetics - Uptake and Distribution, FA/FI curves (Fig. 18-2), concentration effect, tissue compartments (p.1386-1404)