Obstetrics Flashcards
Describe the cardiovascular changes of pregnancy including parturition
Past question
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
Outline the changes to drug pharmacokinetics and pharmacodynamics that occur at term in pregnancy
Past question
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
Describe the respiratory changes during pregnancy
Past question
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
Effect of pregnancy on drug absorption
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