1. (a) F (b) T (c) F (d) F (e) F

The ASRA (American society of regional anesthesia) suggests that 12 hours should have elapsed before an epidural is sited following prophylactic LMWH. 24 hours should have elapsed before an epidural is sited after a therapeutic dose of LMWH. There is no evidence that a regional block is contraindicated in HIV patients for this indication alone. Many units use a platelet count between 70 and 80 as a cut off for regional anaesthesia if the patient has no other coagulation problems. This is not really evidence based and a bleeding time in this instance does not help with clinical decision making.

2. (a) T (b) F (c) T (d) F (e) T

A general anaesthetic is usually considered the safest option if given slowly. A spinal anaesthetic especially given as a standard dose of local anaesthetic will cause peripheral vasodilation and reduce the systemic vascular resistance (SVR). A patient with severe aortic stenosis will try to compensate by increasing heart rate. This can potentially be lethal since myocardial ischaemia will occur. An epidural anaesthetic using slow boluses of local anaesthetic may potentially provide a more stable anaesthetic from a cardiovascular point of view since any changes in SVR are likely to be more gradual. Care should be given when giving oxytocic drugs (and be avoided if possible) since they can also drop the SVR dramatically.

3. (a) F (b) T (c) T (d) F (e) T

Recent developments in genomic research have opened vast opportunities to expand and improve our understanding of how genetic variability may not only affect the efficacy in response to medication we administer on a daily basis, but may also allow us to improve patient safety in helping predict risks of adverse outcomes. The ultimate goal of pharmacogenetics research is to offer ‘tailored personalized medicine’.

4. (a) F (b) F (c) F (d) T (e) F

In a large prospective cohort study in patients receiving β-blockers after an acute coronary event, four common β ₁ and β ₂ AR SNPs were examined. Increases in mortality rates were found with possession of certain variants in the β ₂ AR, rising to 20% mortality at 3 years according to the haplotype combination of Arg16Gly and Gln27Gly. It appears from this study that patients with variants impairing β ₂ AR downregulation (Gly16/Glu27), where receptor function does not undergo desensitization, benefit from β-blocker therapy. Conversely, those with genotypes enhancing downregulation (Arg16/Gln27) do not benefit from β-blockers, most likely because less receptor is present at the cell surface, which mimics βAR antagonist activity. In fact, the administration of β-blockers to such patients appears to unmask negative effects. Also of interest, the authors report no association of the β ₁ AR variants with mortality regardless of β-blocker therapy. Pending replication, this study provides compelling evidence that genetic variability of the β ₂ AR has direct clinical relevance.

5. (a) T (b) T (c) T (d) T (e) F

Only ACE inhibitors have no evidence to show variations in response due to the genetic variability of β ₂ -adrenergic receptors.

6. (a) T (b) T (c) T (d) T (e) F

All of the first four are true but identifying SNPs for all drugs is unnecessary, just for specific drugs and conditions

7. (a) T (b) T (c) T (d) T (e) F

Respiratory depression has been extensively documented and is at its worst if pethidine is given repeatedly and three hours or more before delivery, least if given only within the last hour of labour. These effects include respiratory depression and a reduction in umbilical artery pH and base excess. The prolonged effects of pethidine on the baby may largely be attributed to the presence of its long-acting active metabolite norpethidine.

8. (a) F (b) F (c) T (d) T (e) F

Oxytocin should be discontinued during epidural insertion. Meta-analysis demonstrates that Apgar score is better after epidural than systemic opioid analgesia, while neonatal acid-base balance is improved by epidural compared to systemic analgesia and even compared to no analgesia. Bonding is dependent on early contact between mother and infant and not the use of epidural analgesia.

9. (a) T (b) T (c) T (d) T (e) T

Maternal hyperventilation in response to pain has long been known to have adverse fetal effects. It leads to: respiratory alkalosis and a left shift in the oxygen dissociation curve (potentially disadvantageous to placental transfer of oxygen); a compensatory metabolic acidosis, which becomes progressively more severe as labour advances and is also conveyed to the fetus; episodes of hypoventilation, hence haemoglobin desaturation, between contractions and uterine vasoconstriction.

10. (a) T (b) T (c) T (d) T (e) T

Entonox (a 50-50 mixture with oxygen/nitrous oxide) remains the most popular analgesic for labour in the UK. Although nitrous oxide passes readily across the placenta, it is rapidly excreted by the newborn lungs, and though maternal hypoxaemic episodes occur after hyperventilation during contractions, these are offset by the increased FiO ₂ in Entonox and have little apparent effect on Apgar score, neurologic and adaptive capacity scores or acid-base balance.

11. (a) F (b) T (c) T (d) F (e) F

Although there is usually only minimal change in systolic arterial pressure, there is a substantial reduction in systemic vascular resistance leading to increased cardiac output, stroke volume and sustained cardiac filling. This generally results in increased tissue perfusion. The common perception that the maintained systolic arterial pressure is indicative of insignificant haemodynamic alteration is incorrect. The calcium antagonistic effect of magnesium on the heart results in improved cardiac relaxation, which, in concert with maintained cardiac filling, results in enhanced cardiac output and stroke volume. This leads to improved tissue perfusion but may be of benefit in the pre-eclamptic patient, particularly through enhancement of uterine cerebral perfusion. The reduction in systemic arterial tone produced by magnesium does increase the hypotension seen during epidural analgesia, but this does not appear to be hazardous, provided that animal data can be transferred to the human situation. The combination of uterine arteriolar vasodilatation produced by magnesium put together with the lowered blood pressure produced by the epidural, results in well maintained uterine arterial flow and an absence of adverse fetal consequences. Magnesium is a potent alpha-adrenergic antagonist and appears to inhibit the vasopressor effects of phenylephrine to a greater extent than those of ephedrine, which has mixed alpha and beta activity. Rather than using larger doses of phenylephrine, fluid loading and ephedrine is preferable in a patient treated with magnesium. Magnesium has almost no cardiac toxic effects demonstrable in intact animal or human models. While older texts do suggest that cardiac arrest may occur in the vicinity of 7 mmol/litre, these comments are based on older animal work.

The best available data suggests that cardiac arrest may occur at 12.5 mmol/litre, but not at levels below this.

12. (a) T (b) F (c) F (d) F (e) T

Elevated plasma magnesium concentrations act at the pre-synaptic nerve terminal at the motor endplate, competing for calcium entry and inhibiting the release of acetylcholine. This pre-synaptic inhibition of acetylcholine release increases the sensitivity to non-depolarising neuromuscular blocking drugs, but not suxamethonium. It may also mask pre-existing neurological deficits, particularly those associated with impaired acetylcholine release and sensitivity such as myasthenia gravis and the Eaton Lambert syndrome. Magnesium has no effect on respiratory drive. The only respiratory depressant consequences of magnesium infusions are the result of the neuromuscular blockade detailed above. Magnesium is a cerebral arteriolar vasodilator, and there is no clear description of its effects on intracranial pressure. As a cerebral vasodilator, it may be expected to increase intracranial pressure, but current research suggests that magnesium may reduce the risk of intracranial hypertension by lowering cerebral perfusion pressure. Although the calcium non-competitive nature of magnesium ions would suggest an anticoagulant effect, no clinically relevant inhibition of coagulation has been described and there is no suggestion that magnesium therapy leads to increased risk of bleeding either during normal delivery or during surgery. Magnesium is a highly effective alpha adrenergic antagonist and inhibits the release of catecholamines from the adrenal gland and at noradrenergic terminals. These actions, together with its calcium-antagonist vasodilatation make it an ideal agent for the management of hypertensive emergencies, particularly in obstetrics.

13. (a) T (b) F (c) F (d) T (e) F

The evidence that magnesium is superior to the other anticonvulsants for the prevention of eclamptic convulsions is established, both in pre-eclampsia, where it reduces the likelihood of convulsions occurring, and in eclamptic patients for the control of recurrent convulsions. At the plasma magnesium concentrations required to reduce the risk of convulsions, the effects at the motor end plate are minimal and insufficient to mask a central convulsion through peripheral neuromuscular blockade. Perhaps surprisingly, there is no evidence that magnesium impairs uterine contraction or contributes to prolonged labour. However, there is a possible association with an increased rate of caesarean section associated with the use of magnesium. For reasons that are not clear, magnesium does interfere with fetal heart rate variability, possibly through its ability to inhibit the release of acetylcholine and noradrenaline. However, there is no evidence that this indicates that the fetus is at risk. Hypotonia has been associated with fetal magnesium exposure in utero, but is not linked to adverse neonatal outcome. Magnesium is an exceptionally safe drug with a very high cardiac therapeutic index. The biggest risk of magnesium infusion is that of neuromuscular paralysis.

14. (a) T (b) F (c) T (d) T (e) F

A recent meta-analysis of all tocolytics showed that all agents were more effective than placebo at delaying labour at 48 hours and at 7 days, but there were no other significant differences. However, magnesium was less effective in delaying labour than prostaglandin inhibitors although the differences were not significant. The combination of magnesium and calcium antagonists has been feared on a theoretical basis but there is little evidence of a dangerous interaction, either in terms of haemodynamic function or in terms of neuromuscular blockade. The greatest difficulty in assessing the effectiveness of magnesium as a tocolytic is the variety of dosages that have been employed. Although there is no absolute concensus on the most appropriate dosage, there is some evidence that higher doses are more likely to be effective. The effect of magnesium on cerebral palsy remains controversial, but two recent meta-analyses strongly suggest that there is a reduction in the incidence of severe cerebral palsy in children who, as premature neonates, were exposed to magnesium in utero. Magnesium and nifedipine remain the two most widely used tocolytic agents in the USA according to a recent survey.

15. (a) F (b) T (c) F (d) T (e) T

Asthma is a common condition that varies widely in severity, and is present in 3–8% of pregnancies. There is little evidence of an association between asthma in pregnancy and increased maternal mortality, although there is a significantly higher risk of maternal and neonatal morbidity. Pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by the cardiovascular changes associated with pregnancy. Pulmonary hypertension markedly increases mortality during pregnancy, and death rates can be as high as 30–50%. Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is relatively common condition that has a prevalence of 2-3% in the population. It is generally a benign condition and is not associated with a significantly increased risk of death in pregnant mothers who have the condition. Mothers with SCD have high rates of spontaneous miscarriage, and increased maternal and fetal mortality. Cerebral vein thrombosis, pyelonephritis, pneumonia, deep venous thrombosis, peripartum infection and sepsis are much more common among women with SCD, who are also more likely to experience pregnancy-related complications (such as gestational hypertension/pre-eclampsia, abruption, eclampsia, preterm labour and fetal growth restriction), undergo cesarean delivery, and to have cardiomyopathy or pulmonary hypertension at the time of delivery. Psychiatric illnesses have been highlighted as being among the group of conditions that are responsible for the most maternal and mortality. In recent UK reports, suicide has been a major cause of death overall.

16. (a) F (b) T (c) F (d) F (e) T

Epidural anaesthesia causes sympathetic blockade and vasodilatation below the level of block, and this causes a drop in systemic vascular resistance. The concern in women with conditions such as aortic stenosis is that they cannot compensate for the epidural related drop in SVR by increasing their cardiac output and hence they may become severely hypotensive. In the past this has led to the avoidance of regional anaesthetic techniques in such patients. However, there is now extensive experience suggesting that low dose epidural techniques can be used safely in fixed cardiac output conditions, if used appropriately – that is, with due care and attention including avoidance of large bolus doses and concentrated local anaesthetic conditions, use of invasive monitoring and vasoconstrictors. Most anaesthetists would consider the presence of untreated sepsis a relative, if not absolute, contraindication to the use of regional anaesthesia, especially if also complicated by hypotension (septic shock). The concerns are the increased risk of spinal/epidural abscess formation and iatrogenic worsening of pathological hypotension. Although mothers with a lesion above T10 may not experience labour pain, the absence of central inhibition of the sympathetic neurons in the spinal cord can result in the syndrome of autonomic hyper-reflexia. Noxious stimuli such as uterine contractions can precipitate massive release of catecholamines from the sympathetic chain which can result in extreme hypertension, and even maternal death. Therefore the use of regional anaesthesia – usually epidural – is advised during labour for any patient with an injury at T7 or higher. Concerns about an increased relapse rate in parturients with multiple sclerosis following regional anaesthesia have not been borne out by large prospective series. Lack of maternal consent to epidural analgesia is an absolute contraindication to its use. If a patient has capacity, and this may still be the case if she has a mental illness, she has the right to accept or refuse any treatment.

17. (a) T (b) F (c) F (d) F (e) F

Myotonic disorders are associated with respiratory muscle weakness, cardiomyopathy and cardiac conduction defects. General anaesthesia therefore presents a higher risk to these patients. Additionally some of the drugs used during general anaesthesia can precipitate myotonic spasms in patients with myotonic dystrophy and myotonia congenita and are best avoided. As a general rule, regional anaesthesia is a better choice for individuals with a history of chronic abuse or acute intoxication as it will reliably produce anaesthesia/analgesia even in patients highly tolerant to opioids, and it avoids the systemic drug interactions and unpredictable dose responses that can occur with general anaesthesia. Acute intoxication with cocaine makes cardiac arrhythmias more likely under general anaesthesia. Most anaesthetic agents used during a general anaesthetic have seizure depressant effects. There are issues that make epilepsy relevant to the anaesthetist such as medication and drug interactions, and the possibility of postoperative seizures, but general anaesthetics may be given if indicated. Suxamethonium is used when a rapid sequence induction is performed, but there are alternative neuromuscular blocking agents available (eg rocuronium). These alternatives do not have some of the adverse effects (malignant hyperthermia, hyperkalaemia) or contraindications (muscular dystrophy, recent spinal trauma and paralysis) as suxamethonium. Uncorrected coagulopathies are a risk factor for the development of spinal/epidural haematoma, which if not promptly identified and treated can lead to permanent paralysis. In such cases an overall risk/benefit analysis must be done on an individual patient level, but regional anaesthesia may be relatively contraindicated. In addition a general anaesthetic is a better choice if massive obstetric haemorrhage is anticipated, e.g. when a coagulopathy exists.

18. (a) T (b) T (c) T (d) T (e) F

In the morbidly obese, direct laryngoscopy may be more difficult to perform. Hypoxaemia occurs because of a decrease in functional residual capacity and increase in airway closure in the supine position. Hypertension is more common but care should be taken not to overestimate arterial pressure because an inappropriately small sphygmomanometer cuff is used. Because of the increase in intra-abdominal pressure and the weight of fat on the legs, the peripheral venous return is sluggish, pregnancy is a hypercoagulable state and the patients are more prone to thromboembolism. The risk of LSCS increases as BMI increases; over 40% of women with BMI > 40 may require caesarean section delivery

19. (a) F (b) T (c) T (d) T (e) F

Gastrointestinal activity is diminished and stomach acidity increased during pregnancy and labour. A 15 degree left lateral tilt or a wedge under the right hip have been described to treat symptomatic aorto-caval compression but manual displacement of the uterus may occasionally be necessary to treat its symptoms. The residual volume and functional residual capacity are reduced in pregnancy causing a decrease in the O2 storage capacity, Thus de-saturation occurs much faster. Mechanical displacement and reduced lower oesophageal sphincter tone increases the risk of aspiration in late pregnancy. In pregnancy, the accumulation of fluid and fat in the soft tissues, particularly that in the face with soft tissue oedema in the airway may make mask ventilation and visualization of the laryngeal opening during laryngoscopy difficult.

20. (a) F (b) T (c) T (d) T (e) F

Recent studies have shown that the use of ephedrine has been found to be less efficacious in managing post spinal anaesthesia hypotension, resulting in a higher incidence of fetal acidosis. CEMACH reports since 1979 have shown a dominance of deaths under general anaesthesia compared to regional anaesthesia. The use of single-shot spinal anaesthesia limits the ability to extend the regional block when anaesthesia is inadequate or surgery is expected to be prolonged or difficult, which may occur in obese parturients. Morbidly obese parturients are at an increased risk of operative delivery, coupled with the hazards of general anaesthesia, and so should have a functioning epidural catheter placed early in labour. This will provide adequate pain relief in labour as well as can be used to induce anaesthesia quickly in the event of an emergency caesarean section. Spinal anaesthesia is not necessarily slower than general anaesthesia. In addition, the safety benefits for mother and baby count for more than saving a small amount of time.

21. (a) T (b) F (c) T (d) T (e) T

Left lateral tilt displaces the uterus from compressing the aorta and IVC is important in ensuring adequate maternal blood pressure, and thus fetal oxygen delivery. In some circumstances e.g. placental abruption, uterine rupture, the shorter the interval would lead to an improved fetal outcome. Continuous intra-partum fetal heart rate monitoring may be able to detect changes in fetal status after placement of labour analgesia which are amenable to treatment. Giving 100% oxygen improves fetal oxygenenation. Early communication and teamwork of all caregivers of the high risk parturient may help to prevent a “crash” caesarean section, where all parties may be less prepared to manage a more complicated patient.

22. (a) F (b) F (c) F (d) T (e) F

The increase in clotting factors is maximal at the time of delivery and returns to normal around 4 weeks postpartum. Whilst most coagulation factors increase in pregnancy, not all do including factor X1. Whilst thrombocytopaenia may be common in pregnancy platelet counts rarely are less than 100 × 109·L ⁻¹ at term. Fibrinolysis is reduced in pregnancy and returns to normal at about one hour post partum. Neuraxial hematomas are very rare in obstetric anaesthesia.

23. (a) T (b) F (c) F (d) T (e) F

There are three types of vWd: Types 1 and 3 are quantitative and Type 2 s a qualitative defect of vWf. There are subtypes in type 2 (2A, 2B, 2 M, 2 N). vWd is generally inherited in an autosomal dominant manner. Diagnosis of vWd is made on the basis of clinical history and the results of laboratory tests which involve measuring vWf,RcoA and FVIII levels. Women with vWd generally do have a good outcome and this is thought to be related to the increase in coagulation factors seen in pregnancy, especially fibrinogen, FVII, FVIII, FX and vWf. Whilst epidural and spinal anesthesia appear safe in type 1 vWd patients in whom coagulation factors are normal and FVIII levels are > 50IudL ⁻¹ , neuraxial anesthesia is generally contraindicated in type 2 and 3 vWd patients.

24. (a) T (b) F (c) F (d) T (e) T

Venous thromboembolism occurs in 10 per 100,000 women of childbearing age and affects 100 per 1000,000 pregnancies. It is 20 times more common following cesarean delivery rather then vaginal delivery. The hypercoagulation that accompanies pregnancy is maximal at the time of delivery at which time the risk of thromboembolism is greatest. LMWH is commonly used as prophylaxis in pregnancy and there are guidelines issued to advise on its use. It has a longer half life then heparin and neuraxial anaesthesia must not be give within 12 h of a prohylatic dose. Inherited thrombophilias are present in about 30-50% of women with venous thromboembolism and they increase the risk of developing thromboembolism in pregnancy

25. (a) T (b) F (c) T (d) F (e) F

Ergometrine is a well-known emetogenic agent. Misoprostol is associated with pyrexia, not ergometrine. Ergometrine causes smooth muscle contraction which includes the smooth muscle of the arterioles, resulting in hypertension. Ergometrine is therefore contraindicated in pre-eclamptics. Misoprostol can be given rectally but not ergometrine. Carboprost is associated with bronchospasm, ergometrine is not and therefore the latter can be given to asthmatics.

26. (a) F (b) F (c) T (d) T (e) T

Donor blood has poor oxygen carrying capacity because it has reduced levels of 2,3 DPG. The level of this rises after three or four days. Potassium is released from the lysed red cells after transfusion resulting in hyperkalaemia. This can contribute to arrhythmias after massive transfusion. The citrate in transfused blood binds the calcium causing hypocalcaemia. Cold blood will increase coagulopathy so all donor blood especially given quickly in massive haemorrhage when the risk of coagulopathy is already high should be warmed. A unit of blood costs £140 whereas cell salvage disposables cost less than £100 per case.

27. (a) F (b) F (c) F (d) T (e) F

Some Jehovah’s Witnesses will accept some coagulation products even though they are derived from blood: e.g. cryoprecipitate, platelets. They will universally refuse red cell concentrates. They have an increased risk of both morbidity and mortality. Jehovah’s witnesses should be delivered in a tertiary referral centre where techniques to reduce blood loss at delivery and cell salvage are available. An active third stage will reduce haemorrhage at delivery. Virtually all Jehovah’s Witness will accept cell salvage but a full discussion and written acceptance should be obtained antenatally.

28. (a) T (b) F (c) F (d) T (e) T

One of the great advantages of tamponade balloons is that they are relatively painless to insert and avoid a challenging anaesthetic in the critically ill mother. The balloons are inflated with 500–1000 mls and kept inflated for several hours. They are then deflated by removing 200 ml aliquots over several more hours. Compression sutures are done with absorbable material and there is no need to remove them. Successful pregnancies have occurred after compression sutures. The uterus is supplied by both ovarian and uterine arteries, therefore ligating the uterine arteries will reduce but not necessarily stop the bleeding. A total hysterectomy is more difficult to perform on a recently pregnant uterus and particularly in the presence of massive haemorrhage.

29. (a) F (b) T (c) F (d) F (e) F

The incidence of intrinsic obstetric palsy resulting in lower extremity peripheral nerve palsy is almost 1:100. The incidence of all other nerve injuries, including injuries directly related to neuraxial procedures is so low that it cannot be accurately assessed.

30. (a) T (b) F (c) F (d) F (e) T

Meningitis related to neuraxial procedures is most often caused by viridans type of streptococci. Strep pneumoniae, N. meningitis, and less frequently, H. influenza are more often causes of community-acquired meningitis. Staph aureus is the most common organism responsible for epidural abscesses but has been documented as a cause of meningitis.