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Physiological Changes in Pregnancy - Anaesthesia Perspective

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1. RESPIRATORY SYSTEM

Airway

• Mucosal engorgement, oedema, friability (due to oestrogen) - increases Mallampati score
• Capillary engorgement - risk of bleeding with airway instrumentation
• Failed intubation 8x more common than in non-pregnant patients

Lung Volumes (by term)

Key exam point: FRC decreases while CC remains unchanged - FRC may fall below CC in supine/Trendelenburg position, causing airway closure, V/Q mismatch, and rapid desaturation.

Gas Exchange

• PaO2: 100-106 mmHg (increases)
• PaCO2: 28-32 mmHg (decreases due to hyperventilation)
• pH: 7.42-7.44 (mild respiratory alkalosis)
• HCO3: 18-21 mEq/L (renal compensation - metabolic acidosis)
• Compensated respiratory alkalosis

Clinical Anaesthesia Implications

• Rapid desaturation on induction (FRC reduced, O2 consumption increased)
• Pre-oxygenation mandatory and critical (3 min tidal breathing or 4 vital capacity breaths)
• Apnoeic threshold lower (hypocapnia - any hypoventilation triggers apnoea)
• MAC reduced by ~40% (progesterone, endorphins)
• Faster uptake of inhalational agents (increased alveolar ventilation, reduced FRC)

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2. CARDIOVASCULAR SYSTEM

Haemodynamic Changes

Dilutional (Physiological) Anaemia

• Plasma volume increases more than RBC mass
• Hb falls to ~11-12 g/dL (considered normal in pregnancy)
• Hypercoagulable state (increases in fibrinogen, factors VII, VIII, IX, X, XII, vWF)

Aortocaval Compression

• After 20 weeks gestation, supine position causes uterus to compress IVC and aorta
• IVC compression: reduces venous return, CO falls up to 30% → maternal hypotension, fetal hypoxia
• Aortic compression: may mask IVC compression (Poseiro effect) while fetal perfusion falls
• Management: Left uterine displacement (15-30° tilt) mandatory from 20 weeks onward

ECG Changes in Normal Pregnancy

• Left axis deviation (15° leftward shift)
• Flattened/inverted T-waves in III, aVF, V1-V3
• Q waves in III and aVF
• Occasional atrial/ventricular ectopics

Timing of CO Changes

• Rises from 1st trimester
• Peaks at 28-32 weeks
• Slight fall near term
• Labour: CO increases further: 10-15% in latent phase, 25-30% in active phase, 50% with contractions
• Postpartum: Immediate rise in CO (autotransfusion from uterus), returns to normal by 2-6 weeks

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3. HAEMATOLOGICAL SYSTEM

Key: Pregnancy is a hypercoagulable, hyperfibrinolytic state - risk of VTE increased 5x. However, D-dimer rises in normal pregnancy and is not useful as a screening test.

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4. GASTROINTESTINAL SYSTEM

• Progesterone causes decreased lower oesophageal sphincter (LOS) tone
• Gastrin (from placenta) increases gastric acid secretion
• Delayed gastric emptying (debated - mainly during labour due to pain, anxiety, opioids)
• Mechanical upward displacement of stomach by uterus
• Increased risk of aspiration (Mendelson's syndrome)

Mendelson's Syndrome

• Chemical pneumonitis from aspiration of acidic gastric contents
• Risk factors: pH < 2.5, volume > 25 mL
• All pregnant patients >18 weeks are considered to have full stomach

RSI (Rapid Sequence Induction) is mandatory in obstetric anaesthesia

• Pre-oxygenation + cricoid pressure + thiopentone/propofol + suxamethonium + early intubation

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5. RENAL SYSTEM

Exam point: Normal creatinine in pregnancy is 0.5-0.7 mg/dL. A value of 1.0 mg/dL (normal in non-pregnant women) represents significant renal impairment in pregnancy.

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6. HEPATIC SYSTEM

• Hepatic blood flow: unchanged
• Serum albumin: decreases (→ increased free fraction of protein-bound drugs)
• Pseudocholinesterase: decreases by ~25% (prolonged suxamethonium effect)
• Alkaline phosphatase: increases (placental isoenzyme - not indicative of liver disease)
• ALT, AST: normal or slightly decreased
• Serum bilirubin: slightly decreased
• Gallbladder: hypotonic (increased gallstone risk)
• Prothrombin time, aPTT: normal or slightly decreased (hypercoagulable)

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7. NERVOUS SYSTEM

Central

• Progesterone has sedative/anaesthetic properties
• MAC reduced by ~40% for all volatile agents
• Increased sensitivity to opioids and sedatives

Peripheral Nervous System

• Enhanced sensitivity to local anaesthetics
• Reduced requirement for spinal/epidural LA (30-40% less dose needed)
• Mechanisms: enlarged epidural veins → reduced epidural space, progesterone increases nerve sensitivity, slightly alkalotic CSF

Intracranial

• Cerebral blood flow unchanged
• ICP unchanged (unless pre-eclampsia/eclampsia)

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8. ENDOCRINE SYSTEM

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9. MUSCULOSKELETAL

• Relaxin causes ligamentous laxity (sacroiliac joint, symphysis pubis)
• Weight gain 10-15 kg
• Exaggerated lumbar lordosis
• Difficulty with patient positioning

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10. PHARMACOLOGICAL IMPLICATIONS - Summary Table

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HIGH-YIELD EXAM POINTS - Quick Recap

1. FRC falls 20%, O2 consumption rises 20% - dual reason for rapid desaturation
2. Dilutional anaemia: Hb ~11 g/dL is physiologically normal
3. Cardiac output peaks at 28-32 weeks, rises further in labour, spikes 80% postpartum before return to normal
4. All patients ≥18 weeks = full stomach (RSI mandatory for GA)
5. Left lateral tilt from 20 weeks to avoid aortocaval compression
6. MAC reduced 40%, spinal/epidural dose reduced 30-40%
7. PaCO2 normal in pregnancy = 28-32 mmHg (not 40 mmHg)
8. Creatinine >0.7 mg/dL in pregnancy indicates renal impairment
9. Fibrinogen markedly elevated - if normal (200-400 mg/dL) in obstetric emergency, suspect consumptive coagulopathy (abruption, AFE)
10. Pseudocholinesterase reduced - monitor for prolonged succinylcholine paralysis

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Neuromuscular Monitoring

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WHY MONITOR NEUROMUSCULAR FUNCTION?

• Upper airway obstruction
• Aspiration
• Hypoxaemia
• Prolonged PACU stay
• Increased morbidity/mortality

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BASIC PHYSIOLOGY

• Fade (TOF ratio < 1.0) begins at ~70-75% receptor occupancy
• Clinical weakness (inability to sustain head lift) at ~70-80% occupancy
• Complete paralysis at ~95% occupancy

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NERVE STIMULATOR PRINCIPLES

Stimulus Parameters

Electrode Placement (most common)

• Ulnar nerve at wrist - monitor adductor pollicis (thumb adduction)
  • Negative electrode: 1 cm proximal to wrist crease on ulnar side
  • Positive electrode: 3-5 cm proximal to negative
• Facial nerve - monitor corrugator supercilii (eyebrow) or orbicularis oculi
  • More resistant to NMBA than adductor pollicis
  • Recovers faster - may overestimate recovery
• Posterior tibial nerve - monitor flexor hallucis
• Peroneal nerve - monitor dorsiflexion of big toe

Key exam point: Adductor pollicis via ulnar nerve stimulation is the gold standard. Facial nerve stimulation OVERESTIMATES recovery - do not use to confirm adequate reversal.

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PATTERNS OF NERVE STIMULATION

1. Single Twitch (ST)

• Single supramaximal stimulus at 0.1-1 Hz
• Compares to baseline control twitch
• Limitation: Requires baseline measurement; insensitive (requires >75% receptor occupancy to show changes)
• Use: Rarely used alone; used to establish baseline

2. Train-of-Four (TOF) - Most Important

• 4 stimuli at 2 Hz (every 0.5 seconds, total 2 seconds)
• No baseline needed
• Response expressed as TOF ratio (T4/T1)
• TOF count (TOFC): number of twitches visible/palpable (0-4)

TOF Count and Receptor Occupancy

TOF Ratio and Clinical Correlation

Critical exam point: A TOF ratio ≥ 0.9 is required for safe extubation. Clinical tests (5-second head lift, tongue depressor test) do not reliably detect TOF ratios < 0.9.

3. Tetanic Stimulation

• 50 Hz for 5 seconds (standard), or 100 Hz
• Sustained tetanus = adequate recovery
• Post-tetanic facilitation (PTF): increased acetylcholine mobilisation after tetanus
• Post-tetanic count (PTC) uses this principle for intense block

Post-Tetanic Count (PTC)

• Used when TOFC = 0 (profound/intense block)
• Protocol: 50 Hz tetanus for 5 sec → 3 sec pause → single twitches at 1 Hz
• Count number of post-tetanic twitches
• PTC 1-2: TOF count will return in ~20-30 min (vecuronium)
• PTC ≥ 15: Recovery to TOFC 1 expected very soon
• PTC 0: Very intense block - spontaneous recovery will take >40-60 min

4. Double Burst Stimulation (DBS)

• Two short bursts of 50 Hz tetanus (3 stimuli each) separated by 750 ms
• DBS 3,3 - most common
• Detects residual block more sensitively than TOF by palpation
• DBS ratio = D2/D1; fade detectable when ratio < 0.9
• Clinically: can detect fade (DBS ratio ~0.6) that may be missed by TOF palpation
• Advantage: Better subjective detection of residual block compared to TOF when using clinical assessment

5. 50 Hz Tetanus

• For routine assessment (not PTC)
• 5-second sustained tetanus
• Fade during tetanus = inadequate recovery

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TYPES OF MONITORING DEVICES

1. Mechanomyography (MMG)

• Gold standard (research standard)
• Measures isometric force of thumb adduction
• Requires immobilised thumb, preload
• Most accurate TOF ratio measurement
• Not practical for routine clinical use

2. Electromyography (EMG)

• Records compound muscle action potential (CMAP)
• TOF-Watch SX is the most validated device
• Requires careful electrode placement and calibration
• TOF ratio measured electronically - closer to gold standard than acceleromyography

3. Acceleromyography (AMG)

• Most common in clinical practice
• Piezoelectric sensor measures acceleration of thumb movement (Newton's 2nd law: F = ma)
• TOF-Watch (Organon/MSD) - classic device
• AMG TOFR at extubation should be ≥ 1.0 (not 0.9) because AMG overestimates actual MMG values by ~10%
• Calibration (CAL2 or CAL3) required before use for accurate readings

4. Kinemyography (KMG)

• Strain gauge measures angular displacement
• Less validated than AMG/EMG
• Used in NMT module of some anaesthesia monitors (GE Datex Ohmeda)

5. Phonomyography

• Microphone detects low-frequency sounds generated by muscle contraction
• Experimental/research

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BLOCK CHARACTERISTICS

Non-Depolarising Block (e.g. vecuronium, rocuronium, atracurium)

• Fade on TOF and tetanus (competitive antagonism - high-frequency stimulation depletes ACh at presynaptic level)
• Post-tetanic facilitation present
• Reversed by anticholinesterases (neostigmine) or sugammadex

Depolarising Block (Phase 1 - Suxamethonium)

• No fade on TOF - all 4 twitches equally diminished
• No post-tetanic facilitation
• Not reversible with neostigmine (worsens it)
• Augmented by anticholinesterases

Phase 2 (Dual) Block (Suxamethonium - prolonged high dose)

• Occurs with large or repeated doses of suxamethonium (>3-5 mg/kg cumulative)
• Characteristics change to resemble non-depolarising block:
  • Fade appears on TOF
  • Post-tetanic facilitation appears
  • May be partially reversed by neostigmine

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CLINICAL MONITORING SEQUENCE

Induction Phase

• Calibrate monitor before administration of NMBA
• Establish baseline TOFC = 4, TOF ratio = 1.0
• Onset monitoring: time from injection to TOFC = 0

Maintenance Phase

• Deep block: PTC 1-5 (laparoscopic surgery, ENT, ophthalmology)
• Moderate block: TOFC 1-3
• Light block: TOFC 4 with fade

Reversal Decision (Critical Exam Topic)

Neostigmine Limitations

• Ceiling effect: cannot reverse TOF ratio < 0.2 (TOFC < 4) reliably
• Must have TOFC = 4 before giving neostigmine for reliable reversal
• Adequate reversal with neostigmine cannot be confirmed clinically - quantitative monitoring mandatory

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SUGAMMADEX vs. NEOSTIGMINE

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CLINICAL TESTS vs. QUANTITATIVE MONITORING

Major exam point: Clinical tests CANNOT reliably exclude residual block. The 5-second head lift is possible at TOF ratio 0.6, which is well below the safe threshold of 0.9. Quantitative monitoring is mandatory per current guidelines (EAA 2023, ACOG, ESA).

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FACTORS AFFECTING NMBA ACTION & MONITORING

Potentiate NMBAs (prolonged block)

• Volatile agents (especially isoflurane > sevoflurane > desflurane)
• Hypothermia
• Respiratory acidosis, metabolic alkalosis
• Hypomagnesaemia
• Antibiotics (aminoglycosides, polymyxin)
• Local anaesthetics
• Calcium channel blockers
• Dantrolene
• Hepatic/renal failure (depending on agent)

Antagonise NMBAs (shorter block)

• Metabolic acidosis
• Hypercalcaemia
• Chronic phenytoin/carbamazepine use (upregulation of AChRs)

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CURRENT GUIDELINES - HIGH-YIELD SUMMARY

• European Society of Anaesthesiology (ESA 2023): Quantitative neuromuscular monitoring recommended for every patient receiving NMBAs
• Extubation criterion: TOFR ≥ 0.9 on quantitative monitor (AMG: ≥ 1.0)
• Sugammadex is preferred over neostigmine when rocuronium/vecuronium used
• PTC should be checked before attempting reversal when TOFC = 0

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HIGH-YIELD EXAM SUMMARY

1. TOF = 4 supramaximal stimuli at 2 Hz; ratio T4/T1 ≥ 0.9 = safe extubation
2. PTC = used only when TOFC = 0 (profound block)
3. DBS = more sensitive than TOF for detecting residual block by clinical palpation
4. Non-depolarising block: fade + post-tetanic facilitation
5. Depolarising (Phase 1): no fade, no post-tetanic facilitation
6. Phase 2 block: suxamethonium mimics non-depolarising (fade present)
7. Adductor pollicis/ulnar nerve = gold standard site
8. Facial nerve OVERESTIMATES recovery - do not use for extubation decision
9. Neostigmine ceiling = only reliable with TOFC = 4
10. AMG threshold for extubation = TOFR ≥ 1.0 (not 0.9, due to overestimation bias)
11. Sugammadex 16 mg/kg = immediate reversal of rocuronium 1.2 mg/kg

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