AUSTRALIAN AND New Zealand COLLEGE OF ANAESTHETISTS ABN 82 055 042 852 EXAMINATION REPORT PRIMARY FELLOWSHIP EXAMINATION

FEBRUARY /APRIL 2013 Please note that this report is prepared to provide candidates and their teachers and supervisors of training with information about the performance of candidates in the recent examination, so that candidates and teachers may prepare appropriately for future examinations. The individual reports are not intended to represent model answers nor imply that all points mentioned are necessary in order to achieve a pass. All trainees are urged to read the questions carefully and answer the question asked. All teachers and supervisors of training are encouraged to discuss this report in detail with candidates they are preparing for future examinations.

WRITTEN SECTION ___________________________________________________________________________________ MULTIPLE CHOICE QUESTIONS: 77% of candidates achieved a pass in this section of the Pharmacology Examination.

SHORT ANSWER QUESTIONS: 1. What are the major classes of oral hypoglycaemic agents? Outline their mechanisms of action and possible side effects. 11% of candidates achieved a pass in this question The main focus for this question was on the mechanism of action and side effects of biguanide and sulphonylurea drugs. However, marks were also given for mentioning newer oral hypoglycaemic agents. Marks were not awarded for insulin or glucagon-like polypeptide-1 receptor agonists which are given subcutaneously. Knowledge of the receptor mechanism for sulphonylureas and enzyme activation for biguanides was expected. Misconceptions occurred regarding the action of sulphonylureas: they do not displace insulin from cells. Also, biguanides do more than just increase tissue sensitivity. Marks were awarded for clinically important side effects and for naming factors (many of which occur perioperatively) that increase the risk of side effects. Extra marks were awarded for: an understanding of whether or not a functioning pancreas is required for drug action, lipid effects of oral hypoglycaemic drugs and for an understanding of the major differences in the side effects between biguanides and sulphonylureas and why these occur. 2. What are the advantages and disadvantages of xenon as an anaesthetic agent? 36% of candidates achieved a pass in this question

Most candidates were able to recite the physicochemical properties of xenon gas. However, few could indicate the clinical relevance of these features. For instance, most candidates correctly pointed out that xenon is a non-pungent and odorless gas, but few could identify this as an advantage for inhalational induction. Other important advantages of xenon include that it is not metabolized and xenon is insoluble. Wash-in and wash-out of the gas can therefore be achieved quickly. Xenon anesthesia also does not suppress the myocardium. However, many candidates missed out the analgesic properties of xenon. It should be noted that xenon does not trigger malignant hyperthermia, and has been regarded as safe for MHS patients. Important disadvantages of xenon are that it is very expensive to use, and that the high MAC value (71%) limits the delivery of higher inspiratory concentration of oxygen. A number of candidates listed the features of an ideal inhalational anesthetic agent, which was not asked for in the question. 3. Classify isomers. Briefly write an account of their significance in drugs used in anaesthesia. 49% of candidates achieved a pass in this question The main points expected for a pass included a classification of isomers pertaining to drugs used in anaesthesia, and include a brief description of how these isomers may be used optimise pharmaceutics, pharmacokinetics and efficacy, and minimise side / toxic effects. The classification of isomers was handled well generally. However, descriptions of significance for optimising anaesthesia drug therapy were less universal. The second question needed to be addressed to pass. There were some excellent answers that included all these main points with detailed descriptions of how isomerism of local anaesthetics, neuromuscular blockers, volatile agents, midazolam, thiopentone, tramadol and methadone affects their pharmaceutics, pharmacokinetics and pharmacodynamics. 4. Describe how suxamethonium and non-depolarising neuromuscular blocking agents produce their adverse cardiovascular effects. 23% of candidates achieved a pass in this question In general, candidates did not provide complete answers covering the multiple mechanisms by which neuromuscular blocking agents produce adverse cardiovascular effects. Points were awarded for: a discussion of immune and non immune histamine release with an outline of histamine induced adverse effects on the cardiovascular system, a description of muscarinic cholinergic blockade and agonism, nicotinic agonism and blockade at autonomic ganglia, and noradrenergic effects. Additional points were given for identifying hyperkalaemic dysrhythmia, MH, reflex responses to suxamethonium induced compartmental pressure changes, and autonomic activation due to neuromuscular block in the non anaesthetised patient. Common errors included describing in great detail the mechanisms of action in producing paralysis, lengthy descriptions of the effects of reversal of residual paralysis with anticholinesterases and anticholinergic agents, confusion over terms - pre and post ganglionic, vagolytic and vagotonic, nicotinic and muscarinic, and attempts to compare depolarising and non depolarising agents in table form.

5. Discuss the concept of volume of distribution. How may it be used in the calculation of a loading dose? What assumptions are made in this calculation? 35% of candidates achieved a pass in this question Marks were allocated for a correct definition and a basic formula for calculating Vd. Extra marks were also allocated for clear explanations about why it is called the apparent volume of distribution and how the calculated volumes can greatly exceed the physical volumes in the body. Descriptions about single versus multi-compartment modelling also scored marks. Further marks were also obtained for describing drug, physiological, and pathological factors that affected a drugs Vd. Extra marks were given for providing relevant examples of drugs. The primary assumption is that the calculation is based on a single compartment model or the Vd at steady state. Depending on the drugs distribution, this can someti mes lead to very high initial peak plasma levels with the potential for toxicity. Bonus marks were awarded for using relevant drug examples. Bonus marks were also awarded for discussion about using other variants of Vd in the calculation, e.g. Vdpe, etc., as well as discussing assumptions about bioavailability and clearance.

6. Sevoflurane and fentanyl are a common anaesthetic drug combination. Discuss pharmacological reasons why it is useful to use them together. 57% of candidates achieved a pass in this question The classifications of both sevoflurane and fentanyl were well defined. Moreover the pharmacodynamics of their actions and the side effects associated with these were also well described. Included were good explanations of the beneficial modulating effects that the two agents do have on the pharmacodynamic effects of each other e.g. analgesia, cardiovascular parameters. This was, perhaps, at times at the expense of mentioning some aspects of the pharmacokinetics pertaining to these two agents. The question does ask about the pharmacology pertaining to choosing to use the two agents together. Discussion of onset and offset relationships, lack of competition in distribution, protein binding, metabolism or elimination indicated that the two agents do have minimal kinetic interaction. Some extra marks were gained by the inclusion of a graph that related the synergism, factors which make the reduced dosages of agents influence cost and greenhouse effects. 7. Describe the pharmacology of midazolam. 60% of candidates achieved a pass in this question Better answers were set out with the headings of pharmaceutics, pharmacokinetics, and pharmacodynamics. A clear explanation of the pH dependent ring structure, main pharmacokinetic features, mechanism of action, and significant cardio-respiratory effects, were required in order to pass.

Extra marks were awarded for points such as, the offset of action of small doses due to redistribution, interactions with other medications such as opioids, effects of organ dysfunction, sensitivity in the elderly, and use of flumazenil. Common errors included providing doses without reference to weight, inappropriate doses, vague statements such as hepatically metabolised and renal eliminated, writing a long list of uses and then repeating them later under the heading of CNS effects. 8. Draw a diagram of the larynx, as it would be seen at direct laryngoscopy. Label the important anatomical structures. 80% of candidates achieved a pass in this question To gain a pass mark, candidates were expected to produce and label a reasonable drawing or schematic. Structures that were expected to be identified included the vallecula, epiglottis, laryngeal inlet (or trachea), cartilages and true vocal cords. Alternate nomenclature was acceptable. Extra marks were awarded for identifying other structures, giving anatomical orientation and mentioning that this is a Cormack and Lehane Grade 1 view. No marks were awarded for textual description of nerves, blood vessels, muscles, functions, etc, however detailed, as this was not asked for. There were many spelling errors (not penalized), but my favourite was the instruction to place my laryngoscope into the vernacular! 9. Describe the cough reflex. 32% of candidates achieved a pass in this question The cough reflex is an important protective airway mechanism, which paradoxically anaesthetists often need to suppress. Understanding this reflex and how to modify it is important to practise safe anaesthesia. An adequate answer to this question would describe the components of the reflex arc, with particular attention to the efferent limb due to its complexity. Good candidates could describe the interplay of laryngeal and respiratory muscles in stages in the generation of a cough. The question was, however, generally poorly answered. The reflex arc was frequently outlined but with insufficient detail. There were many incorrect statements, for example, a sizable minority of candidates described the diaphragm as a muscle of exhalation, responsible directly for the forceful expulsion of air from the lungs. It appeared that few candidates had considered the physiology of coughing and had difficulty integrating some relatively simple respiratory physiology in the stress of the exam. Mindful practice of novel questions is a useful study technique.

10. Write brief notes on innate and acquired immunity. 67% of candidates achieved a pass in this question Main Points expected for a pass: A summary of the innate immunity mechanisms

 An overview of acquired immunity including the roles of B-cells and T-cells Notes on the structure and function of antibodies Notes on the roles of B-cell and T-cell subtypes in acquired immunity Additional points could be gained for: Extra details regarding the above points Perspective about how the different parts work together Details about more complicated aspects of the immune system Common problems: This is a big topic and requires brief notes for it to be covered adequately Only a few candidates mentioned inammation as part of the innate system Confusion over cell lines and classication Few mentioned the structure or function of antibodies Confusion over which responses were innate and which acquired Humoral and cellular elements are present in both innate and acquired immunity Lack of an overall understanding of the immune system Only two candidates mentioned any effects of anaesthesia on immunefunction Illegible handwriting Poor layout and structure and evidence of poor time management The main reason for failing this question was insufficient core knowledge 11. Compare and contrast lung function in the neonate with that in an adult. 11% of candidates achieved a pass in this question The question required a comparison of neonatal & adult lung function to achieve full marks for any given point; this was most efficiently presented in a tabular format. The main points expected for a pass included: definition of a neonate, physiologically relevant anatomy, mechanics (compliance, lung volumes, resistance), ventilatory parameters, gas exchange & control of breathing. Marks were also awarded for demonstrating physiological relevance (e.g. obligate nasal breathers with high upper airway resistance which provides auto-PEEP). Additional marks were given for brief mention of non-respiratory functions of the lung. Common mistakes included vague statements lacking quantification or magnitude of difference (e.g. higher or lower), contradictory statements regarding compliance (e.g. lungs are stiffer so compliance is increased), & incorrect information regarding dead space difference between adult & neonate. Extensive notes on upper airway anatomy relevant to intubation & management of anaesthesia attracted no marks. Similarly, events at birth with fetal transition did not attract marks nor was HbF considered relevant to lung function unless presented in the context of the diffusion barrier.

12. Briefly explain the cardiovascular responses to central neuraxial blockade. 38% of candidates achieved a pass in this question A definition of Neuraxial block and some statement as to the important nerves blocked ( 1 and ) followed by a structured discussion of the impacts on the venous system, arterial system, cardiac output and heart rate would receive a good pass. Additional credit was awarded to answers that recognised that the level of block is important in determining the extent of the

cardiovascular responses and gave examples of the likely responses for various levels of block (Sacral, lumbar, low thoracic, high thoracic). All the better answers had an obvious structure to them that seemed to result in a more complete discussion of the question. Only one answer included a discussion of the likely magnitude of change in the SVR, heart rate and other responses. The most frequent reason for not gaining a pass mark was including only a limited subset of the likely cardiovascular responses with scant explanation of those responses. A discussion of the sympathetic nervous system and of the Renin-Angiotensin-Aldosterone system was not asked for and received no marks. Information that was repeated did not receive double credit. 13. How does a fall in temperature influence blood gas solubility and acid base values? 17% of candidates achieved a pass in this question This question sought information on how a fall in temperature influences blood gas solubility and acid base values. This required candidates to address the fundamentals of temperature (e.g. a relationship with kinetic energy) and gas solubility (which changes with altered kinetic energy). This included Henrys Law, and understanding that a change in solubility will alter the content: partial pressure ratio. The direction and causes of pH changes were required. Inclusion of discussion on alpha and pH stat gained additional marks, as did discussion of Hb dissociation curve shifts. Overall, candidates frequently scored low marks. Causes of this included: little knowledge of the area, misinterpretation of the question, and frank misunderstandings of the effects of hypothermia. It was common that candidates had hypothermia-induced partial pressure changes, and solubility changes, inverted. The cause of pH changes was not well understood. Alpha and pH stat, when included, was usually addressed well. Inclusion of areas such as an effect of hypothermia on diffusion and cardiovascular/perfusion changes, did not attract marks. 14. Briefly describe the structure of mitochondria. Outline the metabolic processes that occur in mitochondria. 37% of candidates achieved a pass in this question This question was poorly answered overall however some candidates scored very well. The question came in 2 parts. Many candidates did not address the structure of the mitochondrion and this cost around one third of the potential mark. To pass Description of mitochondrion: intracellular organelle Inner and outer membrane Central matrix Cristae (folds in inner membrane)

Extra marks : stating matrix site of Krebs cycle and ETC on inner membrane with H ions abundant in intermembrane space. increased number in metabolically active tissue. Some cells lack mitochondria e.g. RBC DNA (smaller genome, maternal inheritance) T RNA Ribosomes present Second part Main function is oxidative phoshphorylation Needed to explain Krebs cycle (where it occurs, substrate, products:NADH and FADH2,) Extra marks for stating C02 produced from this cycle, NADH creates 3 ATP FADH2 creates 2 ATP. Also needed to explain electron transport chain: where, substrates, how it works, purpose and product. Extra marks for correct stoichiometry, naming the cytochrome enzymes, appreciating 3 of the 5 complexes pump H+ out of the matrix into the inter membrane space against a concentration gradient, describing the H+ ion passing down an electochem gradient via ATP synthase to facilitate ADPATP, stating O2 is final electron acceptor, metabolic water produced and overall 36 ATP for 1 mol glucose Other functions: Drug biotransformation Apoptosis (programmed cell death) Ca sequestration

15. Explain how oxygen supply of organs is maintained during isovolaemic haemodilution. 33% of candidates achieved a pass in this question A good answer included normal values for haemoglobin and oxygen content for arterial and venous blood, with a discussion on oxygen flux, the flux equation, the reserve of most tissues with low extraction ratios and demonstrated those that had a high extraction ratio had less tolerance for anaemia, e.g. the heart in exercise. The answer required an explanation of viscosity of blood and flow dynamics through blood vessels recognizing that decreased viscosity decreased resistance and encouraged flow through vessels and back to the heart, increasing venous return will increase cardiac output to aid oxygen flux. Good answers included local autoregulation responses (vasodilation, shift of oxygen dissociation curve to encourage offloading of oxygen) and systemic responses, activation of the sympathetic nervous system at critical levels of anaemia. Only one or two candidates mentioned some form of time frame for responses. The question specifically stated isovolaemia so that no points were scored for explanations of responses to hypovolaemic shock. A discussion of predilution of blood for surgery was not required in this question, and similarly scored no marks.

ORAL SECTION ________________________________________________________________________________ OPENING QUESTIONS: 1. Describe the role of platelets in haemostasis 2. Respiratory function tests are part of the patients assessments prior to anaesthetic. What respiratory function tests are readily available? 3. What is normal body temperature? 4. What are the respiratory effects of volatile agents? 5. What is meant by the term oxygen extraction? 6. What hormones are secreted by the posterior pituitary? 7. With respect to the heart, what is meant by the term afterload? 8. What physiological parameters do we usually monitor during an anaesthetic? 9. Describe the anatomy of the sensory pathways related to pain sensation 10. What hormones are secreted from the adrenal gland? 11. What is LaPlaces Law ? 12. List some physical properties of sevoflurane 13. What are the physiological functions of calcium? 14. When considering the use of neuromuscular blocking drugs, what does the term train-of-four stimulation refer to? 15. What is the normal plasma sodium concentration? 16. What are the main neurotransmitters of the autonomic nervous system? 17. Draw me a wash-out curve for sevoflurane. 18. Why do people vomit after anaesthesia? 19. What factors affect resistance? 20. What is anaphylaxis? 21. What is an electroencephalogram (EEG)? 22. We wish to assess the lung function of a patient preoperatively. What tests can you order? 23. What are the functions of the placenta? 24. How is nitrous oxide stored? 25. With a nerve stimulator, what is a single twitch? 26. What is pain? 27. What is the thermonentral zone? 28. Draw a Lead II ECG Trace 29. Describe the role of platelets in haemostasis 30. What are the patient factors affecting the speed of onset of Propofol? 31. What are the principle processes of pharmacokinetics? 32. What is normal pulmonary artery pressure? 33. Why do we produce carbon dioxide? 34. General anaesthesia invariably interferes with control of ventilation. How is ventilation controlled? 35. What physiological parameters do we normally monitor during anaesthesia? 36. Why do we produce carbon dioxide? 37. Can you draw me a washin curve for desflurane 38. What is the definition of half-life in Pharmacology? 39. What anatomical structures do you pass through in a midline approach to the epidural space? 40. What changes are there in the respiratory system during pregnancy? 41. What class of drugs can be useful in inducing a diuresis?

42. A patient has a strong history of post-operative nausea & vomiting. What are the physiological mechanisms involved in the act of vomiting? 43. Which artery would you cannulate for arterial pressure monitoring? 44. What is heat? 45. How do you define pain? 46. After you have intubated a patient, how can you tell it is in the trachea? 47. What anatomical layers are crossed by a spinal needle when performing a subarachnoid block? 48. What is MAC? 49. What is the oxygen cascade? 50. What are the main determinants of resistance in a tube?

Dr Andrew Gardner Chair, Primary Examination Sub-Committee