Physiological Changes in Pregnancy

Summary Table of Key Changes

1. Central Nervous System

• MAC decreases progressively during pregnancy — by up to 40% at term for all general anesthetic agents. It returns to normal by the third day postpartum.
• Progesterone rises up to 20× normal at term and, being inherently sedating, is largely responsible for the reduced MAC.
• A surge in β-endorphin levels during labor also contributes.
• Pregnant patients show enhanced sensitivity to local anesthetics during regional anaesthesia; neural blockade occurs at reduced drug concentrations. This may relate to progesterone-induced sensitization of nerve membranes and the dilutional effect of epidural venous engorgement (reducing epidural/subarachnoid space volume).

2. Respiratory System

Anatomical Changes

• Progesterone causes capillary engorgement of the respiratory mucosa → mucosal swelling, friability, and increased secretions throughout the nose, oropharynx, larynx, and trachea.
• The growing uterus elevates the diaphragm by ~4 cm, reducing FRC. Rib cage flaring partially compensates.

Lung Volume Changes

• The closing volume may exceed FRC in the supine position, causing atelectasis, V/Q mismatch, and shunting — especially relevant during induction of anaesthesia.

Ventilation Changes

• Minute ventilation ↑ 50%: primarily driven by ↑ tidal volume (40%), with a smaller ↑ in respiratory rate (15%).
• Progesterone is the main stimulus, increasing sensitivity of the respiratory centre to CO₂.
• Result: chronic respiratory alkalosis — PaCO₂ falls to ~28–32 mmHg; renal compensation lowers HCO₃⁻ to ~20 mEq/L, maintaining pH near normal (7.44).
• PaO₂ rises to ~103–107 mmHg (due to hyperventilation).
• Oxygen consumption ↑ 20–50% (fetal/placental metabolism + increased cardiac/respiratory work).
• Apnoeic desaturation is rapid in pregnant patients because of the combination of ↓ FRC and ↑ O₂ consumption — critical consideration during airway management.

3. Cardiovascular System

Cardiac Output

• CO ↑ 40% by the end of the first trimester and stays elevated through term.
• Driven by ↑ stroke volume (30%) and ↑ heart rate (20%).
• In labour, CO increases further (15–50%) with each uterine contraction (autotransfusion of ~300–500 mL blood from the uterus).
• Immediately postpartum, CO rises sharply as the uterus involutes, then gradually falls over 2 weeks.

Blood Pressure

• Systolic BP ↓ ~5%, diastolic BP ↓ ~15% despite the raised CO — due to reduced peripheral vascular resistance from progesterone-mediated vasodilation and arteriovenous shunting through the placenta.

Blood Volume

• Plasma volume ↑ 55%, red cell mass ↑ ~20–30% → dilutional (physiological) anaemia (Hb falls ~20%).
• Provides a buffer against haemorrhage at delivery.

Aortocaval Compression

• After ~20 weeks, the gravid uterus compresses the inferior vena cava and the aorta in the supine position.
• IVC compression reduces venous return → ↓ CO and hypotension ("supine hypotensive syndrome"); the aorta compression reduces uteroplacental flow.
• Left lateral tilt (15°) relieves this.

Other Cardiac Changes

• ECG findings: left axis deviation (diaphragm elevation), sinus tachycardia, ST-T changes, and increased ectopic beats — all normal.
• Heart sounds: S1 louder; S3 audible; soft systolic ejection murmur common due to ↑ flow.

4. Haematological System

Blood and Coagulation

• Plasma volume ↑ more than red cell mass → dilutional anaemia (physiological Hb ~11 g/dL at term).
• Clotting factors I (fibrinogen), VII, VIII, IX, X, XII ↑ 30–250% → hypercoagulable state.
• Protein S ↓, resistance to activated protein C → further prothrombotic tendency (risk of DVT/PE ↑ 5×).
• Platelets ↓ ~10% (dilutional); gestational thrombocytopaenia common but usually benign.
• Fibrinolysis is reduced.

5. Renal System

• Renal blood flow and GFR ↑ ~50% by the end of the first trimester.
• Serum creatinine and urea fall (values normal in non-pregnant women may represent renal impairment in pregnancy).
• Glycosuria is common (GFR exceeds tubular reabsorption threshold) — does not indicate diabetes alone.
• Progesterone-induced smooth muscle relaxation causes ureteral dilation and urinary stasis → ↑ risk of urinary tract infection and pyelonephritis.
• Mild proteinuria (up to 300 mg/day) is normal.

6. Gastrointestinal System

• Gastric emptying is delayed in labour (pain, opioids, anxiety).
• Progesterone reduces lower oesophageal sphincter (LES) tone and increases intragastric pressure (from the enlarged uterus) → high risk of gastro-oesophageal reflux and pulmonary aspiration (Mendelson's syndrome).
• These changes begin as early as the first trimester and are most pronounced after 20 weeks.
• Hepatic function is broadly maintained, though plasma alkaline phosphatase rises (placental isoenzyme).

7. Musculoskeletal System

• Progesterone and relaxin loosen ligaments → instability of sacroiliac, sacrococcygeal, and symphysis pubis joints.
• The lumbar lordosis increases as the uterus enlarges, shifting the centre of gravity → common low back pain.

8. Uteroplacental Circulation

• At term, uterine blood flow = 600–700 mL/min (~10% of CO), compared with 50 mL/min in the non-pregnant state. About 80% supplies the placenta.
• Uterine vasculature is maximally dilated (no autoregulation) but remains sensitive to α-adrenergic agonists.

1. Systemic hypotension (aortocaval compression, haemorrhage, sympathetic block)
2. Uterine vasoconstriction (catecholamines, α-agonists)
3. Uterine contractions (↑ venous pressure, arterial compression)

Uteroplacental circulation — Morgan & Mikhail's Clinical Anesthesiology

Clinical Implications Summary

APACHE Score in Critical Care

What is APACHE?

Purpose & Utility

• Predicting population-level mortality (not reliably individual outcomes)
• Stratifying patients for clinical trials and epidemiologic research
• Guiding hospital administrative decisions — resource allocation, nursing ratios
• Benchmarking ICU quality over time
• Defining disease severity (e.g., acute pancreatitis, sepsis, ARDS)

Scoring system validations are based on the premise that age, chronic medical illness, and derangements from normal physiology are associated with increased mortality. — Harrison's Principles of Internal Medicine, 22e

APACHE II — Components

A. Acute Physiology Score (APS) — 12 Variables

B. Age Score

C. Chronic Health Score

• +5 points if non-operative or emergency postoperative admission
• +2 points if elective postoperative admission

• Liver: cirrhosis with portal hypertension, encephalopathy, or variceal bleeding
• Cardiovascular: NYHA Class IV heart failure
• Respiratory: chronic hypoxia, hypercapnia, polycythaemia, severe pulmonary hypertension, or ventilator dependence
• Renal: chronic dialysis
• Immunocompromise: receiving immunosuppressive therapy, chemotherapy, steroids, or having haematologic malignancy/AIDS

APACHE II Total Score

Score Interpretation & Mortality

Disease-Specific Thresholds

• APACHE II ≥ 8 at 24 hours → associated with ICU need, pancreatic necrosis, secondary infection, and increased mortality. — Swanson's Family Medicine Review

• Rising scores over time correlate with worsening prognosis
• Used alongside other systems (SOFA, Ranson, BISAP depending on context)

APACHE Versions

APACHE vs. Other ICU Scoring Systems

Limitations

1. Not validated for individual prediction — a high score does not mandate withdrawal of care
2. Requires 24 hours of data — not useful for immediate triage
3. Does not capture trajectory of illness (unlike SOFA)
4. Worst-value rule may over-penalise transient derangements
5. Chronic health scoring is subjective in borderline cases
6. Originally validated on 1980s patient populations — may not reflect modern ICU outcomes

Key Clinical Takeaway

Management of ARDS in a Pancreatitis Patient

Background: ARDS as a Complication of Pancreatitis

Pathogenesis of Lung Injury in Pancreatitis

Diagnosis: Berlin Criteria for ARDS

Management: General Principles

"Treatment of pancreatitis-associated ARDS is supportive and does not differ from that for other forms of ARDS. Key measures include cardiovascular support and lung-protective ventilation." — Murray & Nadel's Textbook of Respiratory Medicine

1. Lung-Protective Ventilation (Standard of Care)

Targets:

• The landmark ARMA trial (ARDSNet) showed 6 mL/kg PBW versus 12 mL/kg PBW reduced mortality significantly — establishing low tidal volume ventilation as standard of care.
• Volutrauma and barotrauma from overdistension drive ventilator-induced lung injury (VILI) and amplify the systemic inflammatory response.

Permissive Hypercapnia

• Deliberate hypoventilation to keep Pplat < 30 cm H₂O causes hypercapnia and respiratory acidosis.
• Managed medically with sodium bicarbonate or tromethamine (THAM).
• Use with caution if raised intracranial pressure is a concern.

2. PEEP Titration

• Optimal PEEP may be individualised using transpulmonary pressure (measured by oesophageal balloon manometry) or driving pressure titration.
• Both under-distension and over-distension worsen VILI.

3. Fluid Management — Critical Nuance in Pancreatitis

• Aggressive fluid resuscitation is standard in acute pancreatitis (to prevent organ failure and pancreatic necrosis).
• However, overzealous resuscitation increases both pulmonary and non-pulmonary complications in this setting.
• Once ARDS is established, a conservative fluid strategy is recommended:
  • Reduces duration of mechanical ventilation and ICU stay.
  • Consider diuresis if CVP > 4 with persistent hypoxaemia — but only after confirming adequate perfusion and cardiac output.

"Although aggressive fluid resuscitation remains a pillar in the management of acute pancreatitis, overzealous resuscitation may increase the rate of both pulmonary and nonpulmonary complications." — Murray & Nadel's

4. Prone Positioning (Moderate–Severe ARDS)

• Indicated for PaO₂:FiO₂ < 150 with FiO₂ ≥ 0.6, PEEP ≥ 5 cm H₂O.
• PROSEVA trial: prone ≥16 hours/day → 90-day mortality 23.6% vs. 41% in controls.
• Mechanism: recruits dependent (posterior) lung zones, improves V/Q matching.
• Must be initiated within 36 hours of moderate–severe ARDS for benefit.
• Requires careful planning to avoid: unplanned extubation, pressure injuries, inadvertent line removal.

5. Neuromuscular Blockade (NMB)

• Consider for early, severe ARDS (PaO₂:FiO₂ ≤150, within 36 hours of intubation).
• ACURASYS trial: NMB improved 90-day survival and increased ventilator-free days.
• ROSE trial (follow-up): no clear mortality benefit vs. light sedation — but NMB remains a salvage option to:
  • Eliminate ventilator dyssynchrony
  • Reduce consumptive hypoxaemia
  • Prevent patient-self-inflicted lung injury

6. Cardiovascular Support

• Maintain adequate MAP (typically ≥65 mmHg) to preserve organ perfusion.
• Vasopressors: noradrenaline first-line in vasodilatory/distributive shock pattern.
• Avoid excess fluid after initial resuscitation once ARDS is established.

7. Salvage Strategies for Refractory ARDS

Recruitment Manoeuvres (RM)

• Transiently increase transpulmonary pressure to reopen collapsed alveoli.
• Common approach: 40 cm H₂O airway pressure for 2 minutes.
• Caution: a trial using very high pressures (45 cm H₂O) showed higher 28-day mortality — routine high-pressure RMs should be avoided.

Inhaled Pulmonary Vasodilators

• Inhaled nitric oxide (iNO) and inhaled prostacyclin improve short-term oxygenation but do not reduce mortality or ventilator days.
• Reserved for life-threatening hypoxaemia despite all other measures, or as a bridge to ECMO or transfer.

Extracorporeal Membrane Oxygenation (ECMO)

• For severe refractory ARDS failing all standard + salvage therapies.
• CESAR trial: transfer to ECMO-capable centre improved outcomes.
• EOLIA trial: stopped early for futility on primary outcome, but secondary outcomes suggested benefit.
• Approximate survival ~50% in experienced centres.
• Requires veno-venous (VV) ECMO for respiratory failure.

8. Pancreatitis-Specific Adjuncts

Octreotide (Somatostatin Analogue)

• Two small studies (mid-1990s) suggest octreotide may reduce ARDS incidence and mortality in severe acute pancreatitis by inhibiting exocrine pancreatic secretions (and thus reducing systemic enzyme release).
• Evidence is preliminary — larger RCTs needed before routine recommendation.

Treatment of the Underlying Pancreatitis

• Adequate analgesia (IV opioids)
• Nil by mouth / enteral nutrition via nasojejunal tube early (within 24–48 h in severe cases)
• Treat the cause (biliary: ERCP if obstruction; alcohol: supportive)
• Antibiotics only if proven infected pancreatic necrosis

Summary Algorithm

ARDS in Pancreatitis
        │
        ├─ Intubate + Mechanical Ventilation
        │     └── VT 6 mL/kg PBW | Pplat <30 | Permissive hypercapnia
        │
        ├─ PEEP titration (FiO2/PEEP table or transpulmonary pressure)
        │
        ├─ Conservative fluid strategy (avoid excess resuscitation)
        │
        ├─ PaO2:FiO2 <150 → Prone positioning (≥16 h/day)
        │
        ├─ PaO2:FiO2 <150 → Consider NMB (cisatracurium)
        │
        ├─ Refractory → Recruitment manoeuvres ± iNO/prostacyclin
        │
        └─ Failing all → VV-ECMO at specialised centre

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