Obstetrics

Question 1

Describe the cardiovascular changes of pregnancy including parturition

Past question

Answer 1

DURING PREGNANCY

Changes to cardiac output & its distribution:
	- CO increases by 40-45% by 12-28wks, peaks at 50% 32-36wks, then reaches 47% at term
	- Heart rate: HR increases by 17% at end of first trimester,(increases to 25% at middle of third trimester); 
	- Stroke volume increases by 20-30% (predom in 1st trim)
		○ Afterload (reduced) --> TPR decreases by 30% by wk 12& 35% (by week 20th wk, then remains at 30% below non-pregnant values)
			§ Vasodilation mediated by progesterone, prostaglandins & downregulation of alpha-receptors
			§ SBP + DBP - decrease (~10%) & reach nadir at 20wks
			§ Vascular system as whole becomes more refractory to vasoconstrictors
			§ Note re: RV afterload
				□ CVP + PCWP - remain stable throughout pregnancy. PCWP balance by decreased PVR
		○ Preload (increased) --> By term, maternal blood volume increased by 35-40% (approx 1-1.5L)
			§ Plasma volume increases by 45% - Na + H2O retention by oestrogen stimulation of RAAS
			§ RBC volume increases by 20% due to renal erythropoietin synthesis
			§ Disproportionate rise in plasma volume vs red cell mass accounts for fall of haematocrit to 33% ("anaemia of pregnancy")
	- Distribution (regional flow changes)
		○ Renal blood flow - increases by 80% in first trimester (may fall slightly towards term)
		○ Large proportion of blood flow is directed to uteroplacental circulation, that increases its blood flow 10-fold to 750mL/min at term
		○ Increased blood flow to breasts, GIT, skin

Physical/mechanical changes:
	- LV mass increases by 40g by 3rd trimester
	- Heart is more rotated to left
		○ May see Q waves + TWI in inferior leads
	- Colloid oncotic pressure falls by 14% - may predispose to oedema
	- Aortocaval compression syndrome
		○ Seen as early as wk 20
		○ Compression of IVC by gravid uterus - decreases venous return & reduced CO
			§ Blood returns to heart via paravertebral epidural veins draining into azygous
			§ Uterine perfusion diminished secondary to increased uterine venous pressure
		○ Compression of aorta may be present & associated with uterine arterial hypotension + reduced uteroplacental perfusion
		○ Can be relieved by positioning mother to left side
	
PARTUITION + Post delivery:

	- Pressure:
		○ Maternal SBP + DBP increase 10-20mmHg during uterine contraction
	- Volume:
		○ Each uterine contraction squeezes ~300mL blood from uterus into central maternal circulation
	- Cardiac output:
		○ CO increases by ~15% during latent phase of labour, by 30% during the active phase & 45% during the expulsive stage
		○ Immediately after delivery, CO ~60-80% above pre-labour values as a consequence of autotransfusion & increase venous return associated with uterine involution
	- CO & SBP/DBP return to non-pregnant values by 2 wks post delivery

Question 2

Outline the changes to drug pharmacokinetics and pharmacodynamics that occur at term in pregnancy

Past question

Answer 2

Pharmacokinetics:

Absorption:
	- Oral absorption: 
		○ May decrease due to:
			§ Nausea +/- vomiting
			§ Higher gastric pH with delayed gastric emptying
		○ May increase due to:
			§ Slower gut transit
			§ Increased GIT blood flow
	- IM/SC/transdermal absorption:
		○ May increase due to:
			§ Increased CO, decreased SVR
	- IV absorption - increased rate of onset 
	- Inhalational absorption:
		○ Increases due to:
			§ Increased progesterone mediated increase in MV
			§ Increased pulmonary blood flow
		○ Eg. Volatile anaesthetics have decreased time for onset
	- Neuraxial absorption:
		○ Increased due to venodilation
		○ Less volume required
		○ Decreased epidural space

Distribution
	- Increased volume of distribution
		○ Increased total body water + plasma volume (RAAS activation) (need increase dose of hydrophilic drugs - eg NDMB)
		○ Increase body fat % (possibly longer CSHT for lipophilic drugs)
	- Protein binding
		○ Dilution of serum proteins - increased unbound fraction (eg. LAs due to dilution of α1-glycoprotein)
			§ Decreased dose required, increased transplacental transfer of drugs
		○ Increased fatty acid levels - compete with drugs for binding sites on albumin
	- Ionisation
		○ Mild increase in pH (resp alkalosis)
		○ Increased transplacental transfer of basic drugs (increased % in unionised form)
		○ Increased ion trapping (of basic drugs) in more acidic fetal circulation

Metabolism
	- Hepatic enzyme activity
		○ Progesterone induces enzymes, Oestrogen inhibits
		○ Depends on P:O ratio
		○ Egs CYP2D6 induced in pregnancy - rapid metabolisers of codeine will have high plasma peaks of morphine --> transferred to breast milk. CYP3A induction --> increased metabolism of midaz --> decreased plasma conc
	- Placenta has functioning CYP450
	- Plasma cholinesterase (30% decrease) - although nil significant increase in DoA of sux
	- Influence of changes in CO:
		○ Increased CO will increase clearance of drugs with high HER

Elimination:
	- Increased renal clearance due to increased GFR - drugs cleared solely by filtration are most affected (eg. Cephazolin)
	- Hepatobiliary clearance reduced by cholestatic effects of estrogen
	- Increased volatile washout (increased MV)

Pharmacodynamics
	- Increased sensitivity to volatile anaesthetics (decreased MAC), IV anaesthetics, Las
Changed therapeutic indices due to concerns re: fetal damage + teratogenicity

Question 3

Describe the respiratory changes during pregnancy

Past question

Answer 3

Upper airway
	- Mucosal oedema in upper airway
		○ increased Oestrogen --> capillary engorgement --> oedema --> increases airway resistance 
			§ Difficult airway and increased risk of airway collapse with sedation (can be significantly worsened during pre-eclampsia due to change in capillary dynamics)
		
Properties of the chest wall + lung mechanics
	- Anatomical
		○ Diaphragm: 
			§ progressive upwards displacement by gravid uterus (up to 4cm). Results in:
				□ Reduced FRC (20% when standing, a further 30% when supine)
				□ Reduced capacity for pre-oxygenation, rapid desaturation
				□ Impaired ventilation/oxygenation when supine
			§ increased diaphragmatic excursion (2cm) --> increases Vt
		○ Rib cage:
			§ Oestrogen-induced increased laxity of rib ligaments  --> flaring of lower ribs (increased AP and lat dimensions of thorax)
			§ Chest cavity becomes shorter, but other dimensions increase to maintain nearly constant TLC (reduced by only ~5%)
		○ Anatomical dead space:
			§ increased Progesterone  --> Bronchodilation:
				□ increases deadspace (45% - however, VD/VT remains the same) 
	- Compliance
		○ increased adipose tissue and breast mass  --> decreased chest wall compliance (lung compliance unchanged)
	- Resistance
		○ Increases in early pregnancy - mucosal oedema
		○ Progesterone-mediated bronchodilation - decreased resistance in later pregnancy (35%)

Lung volumes + respiratory control
	- Progesterone-mediated stimulation of respiratory centre in medulla oblongata (increased sensitivity to CO2) 
	 --> increased MV (up to 20-50%), due to:
		○ increased Vt by up to 50% at term (~10mL/kg)
		○ increased RR by up to 10% (15-17)
		○ increased MV even further during labour due to pain
	- increased MV results in: chronic, completely compensated respiratory alkalosis:
		○ decreased PaCO2 (26-32mmHg) with increases renal bicarb losses (plasma bicarb ~20mmol) to compensate
			§ Slightly reduced ability to buffer a metabolic acid load 
		○ increased PaO2 (~100-104mmHg) (due to decreased CO2 (Dalton’s Law))
 
Other
	* O2 Transport: Oxygen-Haemoglobin dissociation curve shifted to right due to increased 2,3-DPG in maternal RBCs
		○ p50 remains unchanged due to respiratory alkalosis
	* O2 consumption increases (20% term, 60% during labour)
		○ increased Maternal BMR and foetal consumption
	* increased CO2 production (increased BMR)
 
After birth:
	* FRC and RV return to normal within 48h
	* Vt returns to normal within 5 days