EXAMINATION REPORT PRIMARY FELLOWSHIP EXAMINATION JULY/SEPTEMBER 2006

Australian and New Zealand College of Anaesthetists
ABN 82 055 042 852


EXAMINATION REPORT PRIMARY FELLOWSHIP EXAMINATION JULY/SEPTEMBER 2006
Please note that this report is prepared to provide candidates and their teachers and supervisors
of training with information about the way in which the performance of candidates in the recent examination was assessed by the examiners, 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.



PHARMACOLOGY – WRITTEN SECTION

MULTIPLE CHOICE QUESTIONS:

81 % of candidates achieved a pass in this section of the Pharmacology Examination.

SHORT ANSWER QUESTIONS:

QUESTION 1 Describe the use of different sympathomimetics to treat hypotension occurring as a result of subarachnoid block. Outline the advantages and disadvantages of these agents.

73 % of candidates passed this question.

Given the clinical scenario, a brief summary of pertinent issues resulted in less subsequent repetition.

The hypotension results from a change in tone of resistance vessels (reduced systemic vascular resistance). This is accompanied by a decrease in venous return to the heart and a lowering of cardiac output. There may be a lowering of direct sympathetic tone to the heart, leading to a reduction in heart rate and possibly force of contraction.

Answers should have included discussion of ephedrine and adrenaline (epinephrine). Credit was also given for discussion of metaraminol, phenylephrine, methoxamine, noradrenaline, dopamine, dobutamine and vasopressin, even if disadvantages outweighed the advantages of the drug. No marks were given for naming a drug without other information.


Common features of these agents include:
• Pharmaceutical presentation - all require dilution before use.
• Agents with strong vasoconstricting effects have a risk of tissue necrosis if extravasation occurs (including metaraminol).
• All the drugs have a risk of causing hypertension.
• Many drugs can cause tachycardia via direct effects or reflex bradycardia.

Better answers included a list of relevant patient problems that contribute to the advantages/disadvantages of the drugs including:
• Age/intercurrent illness, particularly cardiovascular disease and antihypertensive medications.
• Pregnancy and childbirth (allowance was made for the differences in prescribed texts regarding ephedrine and phenylephrine).
• Drug interactions - monoamine oxidase inhibitors.

QUESTION 2 Compare and contrast the clinically significant respiratory, cardiovascular and central nervous system effects of desflurane and isoflurane.

70 % of candidates passed this question.

Cardiovascular effects were well answered with most correctly describing the effects on heart rate, systemic vascular resistance, contractility and cardiac output; though there were some incorrect statements such as, hypotension at one MAC is primarily due to impaired contractility.

Better answers discussed the theoretical risk of coronary steal with isoflurane and the practical risk of increases in catecholamine levels with sudden increased desflurane concentration, however there was no mention of the secondary effect on the renin angiotensin system.

Common errors in respiratory effects included unqualified comments that both agents could be used for gaseous induction. Some candidates confused the respiratory effects of these agents with opioids where tidal volume is maintained or increased and respiratory rate is reduced.

CNS effects were well answered, though only a minority mentioned the faster return to consciousness with a comparable depth of anaesthesia with desflurane. Some said that these agents usually decrease cerebral blood flow.

Presentation was of a good standard with most information for the least effort being conveyed with tables. There were some good answers, though in plain text. Significantly there were no blank answer papers.

QUESTION 3 Describe the factors which contribute to the inter-individual variability in drug response seen with intravenous anaesthetic induction agents.

42 % of candidates passed this question.

Better answers classified the factors contributing to variability rather than providing a random list. Factors could be broadly classified as pharmacokinetic and pharmacodynamic in nature. Then within each class further division into physiological, pathological and pharmacological, including drug interaction and pharmacogenomic factors. Other schemes that encompassed these key areas were acceptable. Some indication of the relative importance of these factors in determining variability of intravenous anaesthetic agents was important.


Key pharmacokinetic factors were those that ultimately influenced the extent or duration of effect site concentration and included factors increasing the rate of drug distribution to effect site (e.g. speed of administration, arm-brain circulation time, cardiac output, distribution of cardiac output, central compartment volume, effect site equilibration time); factors influencing redistribution, offset of initial effect and body drug stores (e.g. regional blood flow, volume of distribution, body habitus, age); factors causing variability in metabolism and clearance (e.g. pharmacogenomic factors; induction, inhibition of enzymes; duration of exposure; age-related changes in metabolism; hepatic and renal function). Key pharmacodynamic factors included drug-receptor interaction, receptor numbers and regulation, acute and chronic tolerance, idiosyncratic reactions.

Higher marks were awarded for comprehensive breadth of cover of the topic including pharmacogenomic influences and where a clear understanding of the concepts mentioned was evident. Many candidates did not read the question, and did not relate answers at all to intravenous anaesthetic agents. Common errors included irrelevant emphasis on differences between drugs rather than inter-individual variability, confusion over the nomenclature and roles of the different volumes of distribution, uncertainty regarding the relative roles of redistribution and clearance in offset of drug effect and confusion over the pharmacokinetic changes in the very young and elderly patients. A clear knowledge of pharmacological principles and terminology was expected.

QUESTION 4 Describe the advantages and disadvantages of rocuronium for rapid sequence induction.

28 % of candidates passed this question.

Most candidates failed because they wrote about the pharmacology of rocuronium without addressing the advantages and disadvantages with regard to rapid sequence induction. It was noted that the better answers were more focused and usually started by stating that rapid sequence induction was a technique designed to secure the airway quickly in patients at risk of aspiration, classically using suxamethonium to cause rapid paralysis.

Rocuronium was usually compared with suxamethonium, but candidates should also have noted why rocuronium is currently preferred to alternative drugs when suxamethonium is absolutely contraindicated. Some candidates wasted pages describing all the side effects of suxamethonium that could be avoided with rocuronium. Answers should have indicated the likely doses required for rapid sequence induction because this would determine the onset and offset of neuromuscular block. There was large variation in the times given for onset and offset of block for both suxamethonium and rocuronium. Some answers did not explain why the long duration of action with rocuronium could be a disadvantage.

QUESTION 5 Briefly explain the mechanisms responsible for non-steroidal anti- inflammatory drug (NSAID) – induced side effects. Outline the advantages and disadvantages of selective cyclooxygenase (COX 2) inhibitors.

62 % of candidates passed this question.

This question is in two parts. The first part involves a brief explanation of mechanisms behind NSAID induced side effects. Candidates listing and briefly explaining the most commonly discussed effects of peptic ulceration, renal impairment, tendency to bleeding from platelet inhibition and bronchospasm were able to score most marks allocated from this section. The mention of specific subtypes of prostaglandins involved attracted marks. Absence of such information did not stop an answer from scoring well, as long as the discussion of mechanism was adequate.


The second half of the question called for a brief discussion of advantages and disadvantages of COX 2 inhibitors. Advantages: reduced peptic ulceration rate, reduced postoperative bleeding, theoretical advantage of action in inflamed tissues, possible absence of bronchospasm etc. Disadvantages: expensive, coronary and cerebral thrombosis with chronic use with rofecoxib and possibly others, similar risk of renal impairment as with undifferentiated COX inhibitors.

Extra marks were scored by those who gave a very brief overview of COX action and the role of COX 1 and COX 2, as well as discussion of other side effects such as interstitial nephritis, hypertension, fluid retention, ductus arteriosus closure and sulphur allergy.

QUESTION 6 A new clinical test called the “intubation score” has a reported 90% sensitivity and 70% specificity when used to predict difficult intubation. Describe how the accuracy, predictive value and clinical utility of this test can be evaluated. How will the incidence of difficult intubation affect the performance of this test?

34 % of candidates passed this question.

To quote from the syllabus (Section C -Statistics [e]), candidates are expected to: "Describe the features of a diagnostic test, including the concepts of sensitivity, specificity, positive and negative predictive value and how these are affected by the prevalence of the disease in question.".

Drawing a 2 x 2 table and defining the terms mentioned in the question obtained a pass mark. Unfortunately less than half the candidates accomplished this.

The question as to the effect of the incidence of disease on the positive predictive value of a test is of critical importance. Changing the incidence of a disease does not alter sensitivity or specificity, as many stated, but as the incidence falls so does the PPV - a restatement of Bayes' Theorem. This is one of the reasons why all of the predictive tests for failed intubation, a relatively uncommon event, have such a low PPV.

Some candidates invoked p values, alpha and beta errors, power and even "t-tests" in their answers, which failed to address the question asked. There were many blank answers.

QUESTION 7 Outline the drug and non-drug treatment of ventricular fibrillation in an adult. Briefly describe their mechanisms of action. (Do not discuss basic life support, airway therapies and oxygen)

44 % of candidates passed this question.

A similar question was asked in July 2005. The pass mark has improved significantly. Hopefully knowledge and understanding of this important syllabus topic will continue to improve.

Candidates were expected to describe the current management of ventricular fibrillation with particular reference to defibrillation, epinephrine and antiarrhythmic therapy. Allowance was made for both old and new guidelines given their recent introduction. ILCOR published in 2005 (www.erc.edu/index.php/guidelines_download_2005/en/) and Australian guidelines in 2006 (www.resus.org.au/)


The important areas to be addressed were:
• Defibrillation, early intervention, effective therapy, biphasic vs. monophasic, energy settings and mechanism of action.
• Epinephrine, dose, emphasis on activation of alpha 1 receptors resulting in vasoconstriction and improved coronary and cerebral blood flow.
• Antiarrhythmic therapy, amiodarone and/or lignocaine with description of dose and mechanism of action.
• Prioritisation, a description of the sequence of these therapies and how they fit into a cohesive management plan or protocol. This could be implied in description of the individual therapies.

Extra marks were gained for a description of the possible role of vasopressin, magnesium, sodium bicarbonate and potassium.

Common problems included; no clear sequence of therapies, the importance of defibrillation and energy settings omitted, epinephrine not mentioned or dosage and mechanisms incorrect.

QUESTION 8 Describe the pathogenesis and management of paracetamol toxicity.

86 % of candidates passed this question.

Most candidates exhibited a sound knowledge of the pathogenesis and toxicity of paracetamol. Many candidates wrote at length about the general pharmacokinetics of paracetamol. This did not attract marks.

Marks were given for the following points:
• Toxic dose, expressed ideally in mg/kg or a single toxic dose for adults.
• Differentiation between a toxic dose and a fatal dose.
• Normal metabolic pathway of paracetamol.
• Overdose and relationship of minor metabolic pathway with production of toxic metabolite.
• Conditions which may exacerbate toxicity.
• Cellular mechanism of hepatic toxicity.
• Other features of toxicity e.g. contribution of paracetamol to chronic renal failure.
• General management issues of drug overdose.
• Role of N-acetyl cysteine and use of normogram.
• Monitoring and tests e.g. risk of hypoglycaemia.

It was hard to score very highly without mentioning a toxic dose. When fatal doses were mentioned, the range given was from 7 to 30g for an adult. No candidate mentioned the importance of dose/kg reflecting ideal body weight, and precautions in obese patients or children on long-term paracetamol use. Very few candidates mentioned renal toxicity.

Common errors referred to the metabolism of paracetamol to phenacetin, usefulness of dialysis and urine pH manipulation in overdose.


PHARMACOLOGY – VIVA SECTION

PHARMACOLOGY TOPICS:

General topics
• Pharmaceutics; thiopentone, local anaesthetics, benzodiazepines
• Pharmacokinetics; absorption, bioavailability; hepatic clearance; renal drug handling, pharmacokinetic modelling, clearances, volumes of distribution
• Ionisation of drugs
• Mechanism of drug action
• Pharmaco-genetics
• Anti-convulsants
• Agents that decrease gastric acidity
• Drug chirality

Inhalational agents
• Induction kinetics
• Recovery
• Washout curves
• Inhalational depth, mechanisms of action
• MAC; MAC awake
• Structure-activity relationships
• Nitrous oxide, advantages and disadvantages

Obstetric pharmacology
• Tocolytics
• Magnesium, salbutamol
• Oxytocics; adverse effects
• Placental transfer of drug

Local anaesthetics
• Structure activity
• Pharmacokinetics
• Toxicity, factors affecting toxicity, toxic doses
• Mechanisms of action

Induction agents
• Factors affecting induction dose and maintenance infusion rate
• Propofol pharmaceutics
• Propofol pharmacokinetics
• Cardiovascular effects
• Principles of TIVA
• Ketamine
Benzodiazepines
• Mechanism of action
• Pharmacokinetics
• Adverse effects
• Midazolam
• Flumazenil

Neuromuscular blocking agents
• Factors affecting clinical choice and dose
• Recovery from neuromuscular blockade
• Neuromuscular monitoring
• Inter-individual variability
• Potency
• Suxamethonium; dose response curve, side effects
• Malignant hyperthermia and dantrolene

Opioid agonists and antagonists
• Mechanism of action
• Structure activity relationship
• Pharmacokinetics
• Pharmacodynamics
• Adverse effects
• Morphine, remifentanil
• Oxycodone, buprenorphine
• Tramadol
• Neuraxial opioids

Anticholinesterase and anticholinergics
• Classification
• Mechanisms of action
• Muscarinic receptors
• Adverse effects
• Toxicology

Cardiovascular drugs
• Antiarrhythmics; classification, beta blockers, digoxin, amiodarone
• Drug therapy of myocardial ischemia
• Anti-hypertensives
• Calcium antagonists
• Vasodilators; GTN and SNP
• Inotropes


Drugs and coagulation
• Unfractionated heparin, low molecular weight heparin
• Warfarin
• Antiplatelet drugs
• Protamine

Pain
• Oral analgesics
• Mechanisms of action
• Bio-availability

Statistics
• Clinical trial design
• Evidence based medicine
• Levels of evidence
• Meta-analysis
• Selection of appropriate statistical tests
• Randomised controlled trials
• Confidence intervals
• Drug testing
Endocrine
• Oral hypoglycaemic agents
• Insulin

Histamine and antihistamines
• Histamine receptors
• Anaphylaxis, mechanisms, drug treatment

Antiemetics
• Classification
• Mechanisms of action
• Adverse effects






PHYSIOLOGY – WRITTEN SECTION

MULTIPLE CHOICE QUESTIONS:

76 % of candidates achieved a pass in this section of the Physiology Examination.

SHORT ANSWER QUESTIONS:

QUESTION 9 Describe the factors that oppose left ventricular ejection.

14 % of candidates passed this question.

A large proportion of candidates misinterpreted this question to be about determinants of left ventricular ejection fraction and wasted a lot of time on describing pre-load, contractility and heart rate for which no marks were awarded.

This is essentially a question about determinants of afterload which is the sum of all forces that oppose left ventricular ejection.

Important points looked for were:
• Recognition that the sum of factors which oppose LV ejection is afterload.
• Afterload can also be described as ventricular wall tension.


Factors that determine afterload:
• Systemic Vascular Resistance. Recognition that this is a major contributor to afterload.
Definition, role of SVR in determining afterload and factors which alter SVR attracted extra marks.
• Left ventricular outflow tract resistance and examples of conditions that change this e.g. aortic stenosis.
• Effect of aortic compliance on afterload.
• Ventricular wall factors such as radius and thickness. The relevance of Laplace’s law in relating ventricular wall radius and thickness to wall tension.
• Effect of blood viscosity.
• Effect of arterial impedance.
• Effect of changes in intrathoracic pressure as a result of IPPV or other states. The fact that IPPV actually reduces afterload by reducing transmural pressure was rarely stated.

QUESTION 10 Describe the determinants of work of breathing in an adult human at rest.
62 % of candidates passed this question. The main points expected were:
• Work is the product of pressure x volume and the SI unit is the Joule.
• Inspiratory work has to overcome elastic and resistance forces.
• Elastic work consists of deforming elastic tissues and overcoming surface tension.
• Resistance work must overcome airway resistance and viscous forces.
• Potential energy is acquired during inspiration and stored elastically to provide energy for passive expiration.
• The components of work of breathing are best illustrated on a pressure-volume diagram.

Additional points:
• The percentage contributions of the components to work of breathing.
• The oxygen cost and efficiency of work of breathing.

Common errors included mislabelling axes and writing detailed descriptions of compliance, airway resistance and patho-physiological conditions.

QUESTION 11 List the hormones that regulate tubular reabsorption and describe their action and site of action.

81 % of candidates passed this question.

The five principal hormones of relevance to tubular re-absorption are; Angiotensin II, Aldosterone, ADH, ANP and Parathyroid Hormone. These are hormones affecting the absorption or excretion of Na+, H2O, Ca ++ and K+. In addition to listing these hormones, marks were awarded for clearly stating the action and precisely stating the site and mechanism of action. Many direct effects were relevant but indirect effects were also rewarded where they played a major part in these hormones’ actions on tubular re-absorption.

The style of the question suited a highly structured answer. The candidates who used lists, headings, subheadings, space and columns were able to get many marks with relatively little writing. This style of answer was easy to understand.


Many candidates wrote a lot about the processes involved in the release of these hormones which was not asked for and received no marks. Extra-renal effects were not rewarded e.g. effects of Angiotension II and ADH on systems vasculature. Likewise effects on non-tubular parts of the nephron e.g. renal bloodflow and glomerular filtration were often not relevant. Some candidates forgot Parathyroid Hormone and calcium re-absorption.

Overall though, most candidates had a thorough knowledge of the topic, were able to communicate effectively and many good marks were awarded.

QUESTION 12 Explain the difference between viscosity and density. Outline the effects of changes in viscosity and density on the flow of gases and liquids.

47 % of candidates passed this question.

Many more candidates were able to adequately define density than viscosity. Few candidates noted that these are separate properties of gases and liquids and extra marks were awarded for noting that gases of similar viscosity may have differing densities e.g. helium and oxygen. Extra marks were also awarded for describing the effects of temperature on the density and viscosity of gases and liquids.

The second part of this question should have included discussion on how both viscosity and density effect laminar and turbulent flow. The effects of viscosity on laminar flow, the Hagen- Poiseuille equation and the Reynold’s number were well described by most candidates. Common omissions were; comment on the effect of density on laminar flow, and comment on the effect of changing viscosity on turbulent flow. A common mistake was to state that turbulent flow was directly (rather than inversely) related to density. Many candidates gave detailed descriptions of the characteristics of laminar and turbulent flow that did not pertain to either viscosity or density and therefore did not attract any marks.

QUESTION 13 Briefly describe the structure of a mammalian skeletal muscle fibre and explain how its structure is related to its contractile function. DO NOT describe excitation-contraction coupling.

35 % of candidates passed this question.

There were few high scoring answers. In order to pass this question, a simple outline of the structural components of the skeletal muscle fibre and their related functions as related to contraction would suffice. Additional marks were obtained for a more detailed description of the components of the muscle fibre and for disorders of the fibre structures.

Many candidates confused the muscle fibre with myofibril or myofilaments, and as such were not able to obtain sufficient marks to pass. Many candidates failed to appreciate that the skeletal muscle fibre was a cell, and therefore did not mention basic cellular components, especially those modified to have a specific function in skeletal muscle fibres.


QUESTION 14 Compare and contrast the physiological effects of a six hour fast of fluids and food with a twenty four hour fast in a healthy adult.

33 % of candidates passed this question.

To pass this question, candidates were expected to appreciate that a six hour fast occurs daily and is thus well tolerated whilst a twenty four hour fast involves a significant mobilisation of reserves. In doing this, a comparison of the likely water and caloric requirements for each period, with some mention as to the origin of these calories, was required. An appreciation of the total fuel reserves available in a healthy adult, along with recognition of the thirst, hunger, lethargy and other physiological consequences of a twenty four hour fast would round out an acceptable answer.

Additional marks were awarded to those candidates who were able to more fully quantify the use of reserves during a short and a longer fast and were able to briefly indicate the pathways the body utilises for glucose and ketone production.

Few candidates appreciated that the liver is central in the adaptive process whereby the blood sugar level is maintained by the conversion of fat and amino acids to glucose.

The most frequent reasons for not obtaining a pass mark were; the absence of enough information to indicate that the key principals were understood, and failing to mention the actual reserves of energy in the body. Very few candidates mentioned that a twenty four hour fast would render the patient hungry, thirsty and lethargic. Many candidates incorrectly used the words glucagon and glycogen interchangeably.

QUESTION 15 Explain how a metabolic acidosis develops in hypovolaemic shock.
Describe the consequences of this metabolic acidosis for the body.

53 % of candidates passed this question.

Candidates who scored well answered the question in a structured fashion, with definitions of the issues at hand and answered both sections. Although an understanding of how metabolic acidosis develops in hypovolaemic shock was essential, extra credit was earned for understanding the factors that exacerbate the metabolic acidosis in this situation and for demonstrated knowledge of the metabolic pathways involved. Some candidates demonstrated an excellent understanding of these and how they relate to one another.

A common error among candidates was to detail physiological consequences of hypovolaemic shock at the expense of addressing the physiological consequences of metabolic acidosis. There was limited information on the cardiovascular effects of a metabolic acidosis. Many candidates were able to state that a metabolic acidosis results in myocardial depression. Few were able to outline how a metabolic acidosis effects the response of the cardiovascular system to sympathetic outflow, or at what pH these effects may occur. Respiratory and renal compensatory mechanisms, when addressed, were generally well described.


QUESTION 16 Describe the physiological consequences of acute hypoglycaemia.

57 % of candidates passed this question.

This was an applied question asking about hypoglycaemia. The physiological response has two broad components. The first is neurologic because of the brains’ reliance on glucose. These symptoms become increasingly serious as the hypoglycaemia worsens and range from confusion to coma, fitting and death. An early component is significant hunger. Associated with the neurologic response is the sympathetic response that is responsible for several of the signs of a “hypo”. This includes agitation, sweating and pallor. The other component is the endocrine response. The “aim” of this is to increase the blood sugar. This response includes decreased insulin production (if any is usually produced), and increased glucagon, cortisol, and growth hormone.

Two errors were to include details of diabetic ketoacidosis and focussing on changes in plasma osmolality based on the equation that includes glucose. A minor point is that the Australian and New Zealand unit for glucose is mmol/l not mg/dl.



PHYSIOLOGY - VIVA SECTION

PHYSIOLOGY TOPICS:

Cardiovascular
• Determinants of cardiac output
• Measurement of cardiac output
• ECG
• Arterial waveforms, radial and aortic root
• Pulmonary circulation
• Pulmonary artery trace and capillary wedge pressure
• Frank-Starling relationship
• Contractility
• CVP waveform
• Pressure-volume loops for ventricles
• Myocardial oxygen balance
• Blood pressure
• Capillary exchange
• Effects of IPPV, PEEP

Renal and acid/base
• Renal blood flow, regional variations
• Glomerular filtration
• Clearance
• Renal production of concentrated urine
• Renal handling of water
• Response to hypovolaemia
• Kidney and acid base balance
• Respiratory acidosis
• Metabolic alkalosis
Respiratory
• Lung volumes
• Dead space
• Regional lung differences
• Alveolar gas equation, universal gas equation
• Oxygen cascade
• Respiratory changes at altitude
• Spirometry
• V/Q mismatch
• Mixed venous oxygen tension
• Closing capacity, FRC
• Respiratory effects of anaesthesia, positioning
• CO2 carriage
• Forced expiratory flow loop
• Physiological response to hypercapnia, hypocapnia

CNS/Pain
• Blood brain barrier
• CSF, composition, production, absorption
• Cerebral blood flow
• Sleep
• Response to acute pain
• Resting membrane potential


Measurement
• Errors in pulse oximetry
• Pressure measurement
• Arterial pressure monitoring
• Damping
• Principles of Doppler Ultrasound
• Measurement of humidity
• Temperature
• Capnography
• Pneumotachograph
Other


• Thermoregulation
• Oxygen delivery to the foetus
• Principles of parenteral nutrition
• Lipid metabolism
• CHO metabolism
• Amino acid metabolism
• The red blood cell
• I.V fluids
• Functions of the liver
• Immune function
• Thyroid function
• Anaemia, physiological effects
• Diffusion, Fick’s law
• Gastric contents, emptying
• Lower oesophegeal function













Dr. N Roberts
Chairman, Primary Examination Committee