Pregnancy

Question 1

What are the recommendations regarding anaesthesia during first trimester?

Answer 1

No conclusive evidence re: anaesthesia & foetal teratogenesis however 2nd trimester is preferred for non-elective surgery
Avoid prolonged hypo/hyperthermia, hypoxaemia, hypercarbia, hypotension

Question 2

Why is second trimester preferred for non-elective surgery during pregnancy?

Answer 2

Pts @ lowest risk for preterm delivery, abdo surgery exposure enhanced as uterus lower in abdomen, major embryogenic development complete by 8th week
regional favoured since LT impact of GA on foetus unknown but GA agents not considered teratogenic or have adverse effects on human brin development

Question 3

What are some particular concerns for 3rd trimester?

Answer 3

Risk preterm birth- discuss corticosteroids (foetal lung maturity) w obstetrician.
Avoid NSAIDs after 32/40 (premature closure PDA)

Question 4

When should FHR monitoring be conducted? What is the benefit of it?

Answer 4

Document presence of FHR before & after all non-obstetric surgery, regardless of gestational age. Consider continuous intra-op FHR monitoring for all viable foetuses if technically possible, depending on gestational age, resources- may be useful to optimise maternal positioning or interventions (oxygenation, bp) but hasn’t been shown conclusively to improve foetal outcomes. Can be difficult to interpret as there’s reduction in normal beat-to-beat variability under GA, with opioids & maternal cooling.

Question 5

What are particular airway considerations in pregnancy?

Answer 5

Increased mucosal friability & oedema
Avoid nasal intubation in any trimester (epistaxis risk)
Have a downsized tracheal tube & videolaryngoscope

Question 6

What are particular breathing considerations during pregnancy?

Answer 6

Compensated resp alkalosis due to incr MV mainly due to incr TV- pH nears 7.44, PaCO2 can be 30-32mmHg
FRC decreases by 20%, can have rapid desaturation during apnoea, pre-O2 vital

Question 7

What’s the increase in maternal CO by the end of T2?

Answer 7

50% (30% incr SV, 25% incr HR)

Question 8

By how much do GFR & RBF increase during pregnancy? What happens to serum Cr?

Answer 8

by 75 & 65% above baseline. Cr decreases by the end of T1.

Question 9

What are some GI considerations for pregnancy?

Answer 9

LOS tone reduces due to progesterone- nadir 36 wks
Gravid uterus, nausea & vomiting & GORD all increase the risk aspiration
Gestational age for aspiration prophylaxis & RSI w tube unclear but safest to do so from T2

Question 10

How does pregnancy impact MAC requirements?

Answer 10

Decreases it

Question 11

What are some considerations for positioning during pregnancy?

Answer 11

Aortocaval compression has been reported as early as 13 weeks gestation. Applying L) uterine displacement helps avoid aortocaval compression which impedes venous return to the heart. Use from 16 weeks (earlier if obese or multiple gestation).
Ramp or reverse trendelenberg may help with airway mechanics.

Question 12

What are some considerations with laparoscopy during pregnancy?

Answer 12

-Hypercarbia, hypoxaemia & hypotension may all cause vasoconstriction & impair uteroplacental perfusion which may –> foetal distress
-Watch CO2 w insufflation- maintain maternal baseline PaCO2
-Ensure insufflation pressures no >15mmHg
-Ensure baseline arterial BP maintained

Question 13

Should sugammadex be used during pregnancy?

Answer 13

No- not unless CICO situation, as while there is insufficient literature re: the safety of sugammadex in pregnancy there are concerns about sugammadex binding & encapsulating progesterone (4mg/kg reduces unbound progesterone levels by 34%), which is critical for pregnancy maintenance (supports endometrial growth) so it should be avoided in T1. Insufficient literature regarding effect on organogenesis. Effects of sugammadex on establishment of breastfeeding & on lactation are unknown so avoid its use for emergency LSCS & caution pts w established lactation.

Question 14

What should women of childbearing age who receive sugammadex be advised?

Answer 14

Same as a missed pill
To use non-hormonal contraception for 7 days

Question 15

Dose of sugammadex for CICO?
What are other situations during pregnancy where the benefits of sugammadex may outweigh risks?

Answer 15

16mg/kg actual body weight
Those where ceiling effect of cholinesterase inhibitors has been reached but who have risk inadequate reversal eg. residual NMB due to high-dose Mg++ or if disorders of impaired NM transmission eg. myasthenia gravis

Question 16

What’s sugammadex’s structure? How work & excreted?

Answer 16

gamma-cyclodextran, hydrophilic oligosaccharide exterior with lipophilic core.
Encapsulates free aminosteroid NDNMBD (& some hormones & hormonal contraceptives) to form water-soluble complex, gradient of higher [] @ NMJ vs plasma promotes movement of NMBD to plasma, freeing nicotinic receptors & rapidly restoring muscle function. Renally excreted. With normal renal function, elimination t1/2 2 hrs.

Question 17

Incidence of anaphylaxis to sugammadex?

Answer 17

0.03%

Question 18

By how much are plasma cholinesterase levels reduced in pregnancy & the immediate postpartum period?

Answer 18

25%

Question 19

What’s sugammadex’s pregnancy category?

Answer 19

B2- taken by a limited number of pregnant women & women of childbearing age without incr frequency of malformation or direct or indirect harmful effects on the foetus. Animal studies inadequate or lacking but available data shows no evidence of increased occurrence foetal damage.

Question 20

What characteristics of drugs promote their excretion in breastmilk? Is sugammadex therefore likely to be in breastmilk in high quantities?

Answer 20

High lipid solubility
Small molecular size
Long half-life
High protein binding
Those with pKa higher than breastmilk (7.2) more likely sequestered in breastmilk due to ion-trapping

Sugammadex is hydrophilic, large, half-life only 2 hrs, renaly excreted, pKa 2.8 so, despite no protein binding, it likely has limited excretion in breastmilk.

Question 21

What advice would I give to a patient regarding resuming breastfeeding after surgery?

Answer 21

While all anaesthetic medications transfer into the breastmilk to some degree, the vast majority are in very low [] which are considered safe for the newborn.
Exceptions= opioids genetic variations for metabolism (eg. codeine, pethidine), some ABx (tetracyclines), amiodarone & statins

Question 22

What’s CO immediately after birth? How long does it take for physiological changes to normalise?

Answer 22

Labour CO incr 10-20% 1st stage, 40% 2nd, Up to 80-150% above baseline. Returns to pre-labour values by 24hrs (so if sig cardiac lesion, 24hrs HDU post-delivery), can take 3/12 to return to pre-preg. Maternal HR stabilises within 2/52. Dilutional anaemia resolves by 3/52 postpartum. Gastric emptying, volume & pH return to pre-pregnancy levels by 18hrs postpartum.

Question 23

Is the Australian pregnancy categorisation for medications hierarchical? What does category B relate to? If there are 2 + active ingredients, how is the categorisation decided?

Answer 23

No- category B medications have inadequate or lacking human data
Subcategorisation of the B category is based on animal data
Allocation to category B does NOT imply greater safety than category C

Categorisation decided based on the active ingredient with the most restrictive pregnancy categorisation

Question 24

What’s pregnancy category A?

Answer 24

Drugs which have been taken by a large number of pregnant women & women of childbearing age with no proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus

Question 25

What’s pregnancy category B1?

Answer 25

Drugs which have been taken by only a limited number of pregnant women & women of childbearing age without increased frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed.
Studies on animals have not shown evidence of an increased occurrence of foetal damage.

Question 26

What’s pregnancy category B2?

Answer 26

Drugs which have been taken only by a limited number of pregnant women & women of childbearing age without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed.
Data on animals may be inadequate or lacking but have not shown evidence of increased occurrence of foetal damage.

Question 27

What’s pregnancy category B3?

Answer 27

Drugs which have been taken by only a limited number of pregnant women & women of childbearing age, without an increase in the frequency of malformation or other indirect or direct harmful effects on the human foetus.
Data on animals has shown evidence of increased foetal damage, the significance of which is uncertain in humans.

Question 28

What’s pregnancy category C?

Answer 28

Drugs which have, due to their pharmacological effects, caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible.

Question 29

What’s pregnancy category D?

Answer 29

Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. They may also have adverse pharmacological effects.

Question 30

What’s pregnancy category X?

Answer 30

Drugs which have such a high risk of causing permanent damage to the foetus that they should not be used in pregnancy or when there is a possibility of pregnancy.

Question 31

What is necessary prior to neuraxial analgesia/anaesthesia?

Answer 31

pre-anaesthetic assessment
labs if high risk (eg. a known etiology for thrombocytopenia)
informed consent
IV access
emergency equipment (for LAST, vasopressors, fluids)
FHR monitored prior to epidural as per institutional protocol (20 mins) & then continuously after block initiation.
continuous SpO2 pulse oximetry. BP 5-minutely for 15-20 mins until block established & pt harm-dynamically stable, then @ least 30-minutely (more frequent if hypotension or grade 2 or 3 trace)
block height (sensory), motor function & pain control regularly monitored (1-2hrs).
block “time out” including checking re: coagulation status/any recent anticoagulants.

Question 32

How to do an epidural test dose? What do I do instead?

Answer 32

3mL lignocaine 1% with 5microg/mL epinephrine. Motor block in 3-5 mins suggests subarachnoid catheter, increased maternal HR 20% or greater within 1 min suggests intravascular catheter.
I aspirate for blood or CSF after insertion, and before each test dose which is with a low-concentration (0.2% ropivacaine) solution

Question 33

What levels need to be covered for labour analgesia? Cesarean?

Answer 33

T10-S2
T4 (peritoneum)

Question 34

What’s the sequence of nerve blockade

Answer 34

Smaller then larger, myelinated first for an equivalent size, outer prior to inner in a mixed bundle. In general, pain/temp then touch/proprioception then motor.

Question 35

Risks with using epinephrine-containing test dose?

Answer 35

If HTN may profound
If uteroplacental insufficiency, may decrease uteroplacental perfusion

Question 36

After inadequate epidural top-up anaesthesia for caesarean, should single-shot spinal be performed?

Answer 36

No. high block ass’d w single-shot spinal after failed epidural is one of the most common serious complications of obstetric anaesthesia & can result in respiratory arrest.

Question 37

What’s the evidence for the best strategy for neuraxial analgesia after ADP?

Answer 37

Inconclusive. Based on retrospective & observational studies.
Efficacy of intrathecal catheter hasn’t been established in randomised controlled trials, most report not benefit.

Question 38

Physiological changes pregnancy & ref ranges:

Answer 38

CNS: more sensitive to inhaled & LAs, CSF pressure incr during labour as does epidural vein engorgement

Airway: vascular engorgement, friable, oedema esp if PET or prol pushing (risk difficult I&V, bleeding w instrumentation (gentle, V-L), may need smaller ETT, short-handled laryngoscope, full range airway equip

B: incr MV 50% during T1, due to incr TV 40% & incr RR 15% (incr VO2 20% by term, S1 labour 40%, S2 75%, while MV can incr to 160% in labour due to pain (300% with pushing 2nd stage) with O2 demand of uterine contractions). Progesterone centrally stimulates hyperventilation CO2 ventilatory response curve L)-shift & steeper, improves transfer gradient for CO2 from foetus–> placenta). incr DO2 (R)-shift OHDC, incr PaO2, incr tissue blood flow)
incr MRO2 & reduced FRC 20% by term (reduced ERV & RV, diaph displacement, incr pulm blood vol), worse ++ supine (reduces 70% cf sitting), incr anatomical deadspace, reduce apnoea time & risks atelectasis/shunt/hypoxaemia (meticulous positioning for pre-O2 to optimise FRC (ramp), L) lat tilt to limit A-C compression & optimise oxygenation. lung volume changes normalise by 2-5/7 postpartum. TV incr (so IC incr) but TLC decr. Altered Tx cage mechanics (relaxin incr AP & transverse diameters, more horizontal ribs)
Fully compensated resp alcalosis (PaCO2 30mmHg, pH sl incr 7.42-7.44 due to incr renal excretion bicarb (20-21 @ term), pain labour PaCO2 can reduce down to 20mmHg
PaO2 can be 105mmHg, may normalise later in preg due to atelectasis/shunt
(resp rate/volume titrated to MAINTAIN physiologic resp alkalosis (PaCO2 30mmHg), ensure adequate FiO2 to meet etabolic demands, if mask induction, incr rate of change of alv concentration of agent (incr vAlv (MV & reduced FRC)–> more rapid wash-in & wash-out of volatiles (somewhat offset by incr CO which slows equilibration of Palv & Ppulm blood but overall resp effects dominate).
Epidural may reduce catecholamines, cortisol, lessen O2 consumption, MV & risks of maternal/foetal acidaemia during 1st stage

C & haem:
CO incr by 50% by end T2 (30% incr SV, 25% incr HR)
MRO2 incr 20% @ term
reduced SVR (progesterone)–> BP reduces 20% by 20 wks (MAP reduced, DBP reduces >SBP) but then gradually incr as approach TERM, incr during labour
PVR reduces
Blood volume incr from T1, 50% by term, reduced total maternal [] plasma proteins (eg. alb, reduced oncotic pressure risks oedema) but incr fibrinogen & CRP
rbc mass incr 25%–> physiologic anaemia of pregnancy (Hct nadir T2 as rbc mass lags behind plasma); in pregnancy HB <110 is considered anaemia, DO2 not reduced due to incr CO
uterine blood flow incr to 700mL/hr (from 100mL/hr), further incr during labour; delivery of placenta with final uterine contraction provides autotransfusion 500mL (loss of vascular capacitance with loss of placenta, incr venous return, loss of LL venous pressure due to lack aortocaval compression, time of risk if cardiopulm disease esp valvular stenosis or pulm HTN

abdo aorta & IVC may be occluded by gravid uterus (from T2) supine, almost complete @ term, compensatory response of SNS + incr SVR, HR to maintain CO & MAP may be ablated with neuraxial, worsening supine hypoT (blood gen diverted via epidural & paravertebral vv into azygous–> SVC but if inadequate compensation symptoms nausea/vomit, diaphoresis, presyncope/syncope/dizziness signs pallor, hypoT, bradycardia, reduction in uteroplacental BF (not regulated), foetal distress (uterine & placental pefusion directly related to maternal CO, SVR, uterine venous pressure)
A-C compression also impairs renal blood flow, promotes epidural venous engorgement, LL venous stasis (ankle oedema, risk VTE)

Thrombocytopenia common (haemodilution, incr plt turnover)
hypercoaguable (incr fibrinogen, all clotting factors incr except 11 & antithrombin III drop, II & 5 ISQ), bleeding time reduces 10%
incr fibrinolysis too
mild leucocytosis common esp neutrophil count

–> incr bleeding time

reduced pseudocholinesterase activity from T1 until 6 wks postnatal
–> sux theoretically prolonged action but not usually clinically significant

–> incr VD anaes drugs, bleeding risk

GIT: reduced LOS tone (prog & oest, IAP impairs LOS mechanism & barrier pressure, gastrin secreted by placenta incr vol gastric acid & reduces gastric pH, if in labour reduced GI motility) need cuffed ETT & RSI, Na citrate
ALP doubles (placental production), all other markers liver function incr, reduced plasma protein [] (haemodilution)–> incr free blood levels highly PB drugs

RBF incr 75% & GFR incr 50% by T2 due to incr CO, remain elevated until 3/12 PN, incr urine protein, glucose, bicarb excretion

Musculoskeletal: relaxin lig’t relaxation

pH 7.42 (compensated resp alkalosis by renal excretion bicarb (prevents L)shift OHDC but reduces buffering capacity)
PaCO2 down to 30, bicarb down 20 (from 24), ie. bicarb down approx 2 for 10mmHg decr CO2 acute resp alkaosis, 5 for chronic
BE -2
PaO2 105mmHg
ABG changes rapidly normalise postpartum
maternal Hb nadir T2, anaemia is <110g/L, T3 generally Hb 120, Hct 35 (down from 41%)
plt down 5-20%, reduced PT & PTT
WCC raised esp neut
reduced total proteins but incr fibrinogen & CRP, incr ESR (incr plasma globulin, fibrinogen)
ALT, AST incr, ALP incr++++ (placental production, 2x ULN)

Question 39

Influence of pregnancy on Pk & Pd of anaes/analg agents, impact on foetus of drugs admin during preg, factors influencing the t/f of drugs across placenta to foetus

Answer 39

Incr wash-in & wash-out of volatiles hence more rapid induction/recovery as incr FA/Fi ratio (incr MV with incr RR & TV with reduced FRC, the incr CO somewhat offsets the rate of equilibration Palv & Ppulmonary blood) if maintain normal preg vent physiology; the resp depressant (suppress hypox & hypercap vent drive), reduced MV (incr RR but reduced TV) somewhat offsets the preg changes as anaes deepens but resp effects dominate

MAC reduces 40% (progesterone sedating effect, B-endorphins analgesia)

Response to induction/maintenance IV drugs unpredictable; incr VD & elimination but incr sensitivity to agents; induction based on actual body weight & titrate to effect

more sensitive to NMDAs, use quantitative NMT

lack of pseudocholinesterase from T1 to 6/52 PN likely not clinically significant, VD increases, use 1.5mg/kg sux, fasciculations tend to be less prominent as does postop myalgia

base NDMBAs on ideal body weight then use quantitative NMT

Neuraxial: 25% reduce LA dose (incr neuraxial spread due to EDV distension (smaller size epidural space & vol of CSF), incr sensitivity of n fibres to LA, incr diffusion of LA to receptor sites). incr risk bloody tap due to EDV distension esp w contractions

volatiles uterine relaxation

agents reducing CO & SVR risk impaired uterine & placental flow (UBF not autoregulated), if incr uterine artery resistance (catecholamines or vasopressors, extreme hypocapnia) also risk impaired uteroplacental flow; phenylephrine= vasopressor of choice for mat hypoT during labour & delivery, effective for hypoT but less foetal acidosis & base deficit)

incr free levels of highly PB drugs as reduced plasma proteins

systemic opioids cross placenta & may reduce FHR variability but no evidence that this is detrimental to the foetus, if baby born soon after exposure to systemic opioids may need reversal w naloxone +/- resp support

NSAIDs incr risk miscarriage & foetal malformation if used early preg, incr risk PDA & oligohydramnios if used >30wks gestation

Paracetamol considered safe

GENERALLY: drugs that don’t cross the BBB don’t cross placenta to any appreciable degree.

Rate of diffusion & peak foetal levels (drugs MW <1000Da) depends on: maternal blood [] & mat/foetal gradient, maternal PB, drug MW, lipid solubility & degree of ionisation
Fick’s: rate diffn= (SA x concn grad x solubility) / (root MW x thickness). substances >6kDa impermeable. some substances (glucose) by facilitated transport (protein carrier). some by active transport against [] gradient (eg. Fe++, Ca++) using ATP. larger lipid insoluble (eg. IgG) in vesicles (endocytosis).

NDMRs (high MW, poor lipid sol) & sux (low MW but highly ionised) minimal t/f
heparin & glyco minimal as highly charged
volatiles/BZD/opioids/LAs transfer facilitated by low MWs, neutral charge, lipophilicity

GAs all cross placenta, foetal CO sensitive to depression by GA drugs, no evidence specific toxicity but animal studies suggest prolonged exposure may–> neuronal apoptosis & Bx abnormalities; critical period of rapid synaptic development= prenatal to 2yrs. no particular GA agent shown to be safer.

foetal blood more acidic than maternal so weakly basic may diffuse across unionised then become ionised & trapped in acidic foetal blood (“ion trapping”), if foetal distress (& lower pH foetal circulation), there may be higher [] weakly basic drugs (eg. LAs) which may reduce foetal NM tone, if extremely high [], brady/arrhythmias

Approx 40% of umbi venous blood passes through foetal liver so sig first pass metabolism before drug reaches foetal heart & brain & any blood entering foetal IVC from DV is diluted by blood from LLs & pelvic viscera so foetal drug [] < maternal
while enzyme activity less developed, most drugs crossing placenta can be metabolised

Question 40

lung volume changes (normalise by 2-5/7 postpartum)

Answer 40

TLC reduces 4200-4000mL
IC incr 2500-2650mL
IRV ISQ (2050)
TV incr 450-600mL
ERV decr 700-550mL
RV decr 1000-800mL
FVC decr 1700-1350mL

Question 41

factors relevant to neuraxial block in obs

Answer 41

reduced size of epidural space (with edv engorgement) so lower dose needed
also this incr systemic absorption, augmented by incr plasma [] highly PB drugs, incr risk toxicity (eg. CC:CNS ratio of bupiv decr to 2.7 vs 3.7)
also incr neuronal sensitivity to LAs during pregnancy

epidural vein engorgement via pressure transmitted from gravid uterus, incr with labour & risk inadvertent vein EDV cannulation

incr systemic absorption neuraxial drugs due to incr CO however if from intrathecal it’s negligible