2026 First Sitting

(a) Candidates were expected to discuss the 3 main factors that contribute to the neuronal resting membrane potential (RMP). This included: - Chemical concentration gradients - which are maintained by the active transport of ions primarily via the electrogenic Na+/K+ ATPase pump. - Selective membrane permeability to ions through protein-facilitated channels with detail on the increased membrane permeability to K+ in the resting state due to open leak channels. - Electrochemical equilibrium (diffusion potentials) which occur when the chemical driving force generated by the chemical concentration gradient is balanced against the opposing electrical force of the negatively charged intracellular anions. Importantly, discussion of the above needed to be tailored to the values and mechanisms that underpin the RMP of the neuronal cell, this was overlooked or omitted by many candidates. Better answers discussed the Nernst and Goldman- Hodgkin-Katz predictions governed by the above mechanisms. (b) For this component of the question a brief description of the Gibbs-Donnan effect was required. Good answers covered the following concepts in their description; - the unequal distribution of permeable charged ions across a semipermeable membrane that occurs in the presence of impermeable charged ions - equilibrium is achieved in the presence of electroneutrality or when the product of ions on either side of the membrane is equal. - resultant effect is an unequal distribution of ions and an osmotic gradient. It also contributes to a small electrical potential difference.

First Part Exam Report 2026.1

The question breakdown and mark allocation provided a guide to the level of detail required for each section. Well scoring answers demonstrated their understanding of the differences and similarities between the drugs rather than a list of pharmacological factors for each drug. When answering a “compare and contrast” question consider, why would you use one drug over another. These are decisions we make multiple times a shift in ICU, thus, the important details for metabolism and elimination and pharmacodynamics that may govern why one drug is chosen over the other was expected. For example: Adrenaline undergoes rapid de-activitation and metabolism via non-organ dependent mechanisms – thus high clearance, making it easy to titrate with a rapid offset, even in organ failure/critical illness. Milrinone requires renal excretion of predominantly unchanged drug – thus has a longer duration of action, slower offset, more difficult to titrate and can accumulate in renal impairment.

Information to answer this question requires assimilation of knowledge across a range of resources. a) A structured approach divided the answer into haemodialysis and haemofiltration and then described the physical principles and factors that affect solute clearance separately. Expected information included: - Haemodialysis; solute movement across a semipermeable membrane by diffusion. Dependent on: - solute characteristics (size, charge, protein binding, volume of distribution), - dialysis membrane properties (porosity, thickness, surface area) - the concentration gradient of substance in dialysate to blood, - the rate of solute delivery (blood flow vs dialysate rate). - Haemofiltration; a hydrostatic pressure gradient is generated across a semipermeable membrane to drive solute movement. A discussion of the effect of: - transmembrane pressure - blood flow - effluent/ultrafiltration rate - plasma oncotic pressure - solute concentration in plasma water - Sieving coefficient on the clearance First Part Exam Report 2026.1 b) For this section a brief outline of typical dialysis fluid was required including the rationale behind the composition and inclusion of each of the following: - major electrolytes - buffers - water - special solutions ie. Citrate, Potassium Free Information on the indications for dialysis, methods of vascular access and anticoagulation regimens was included in many answers however was not required and did not have marks allocated.

This question required a brief overview of the major neurotransmitters, their receptors and location. For example: Acteylcholine a) Nicotinic receptors (ionotropic – Na, K) - NM (neuromuscular junction) – skeletal muscle end plate - NN (autonomic ganglia) – all sympathetic and parasympathetic ganglia - in the brain both types are found, are widespread, including basal forebrain and the brainstem cholinergic nuclei Muscarinic receptors (metabotropic) - M1 – sympathetic system ganglia, CNS - M2 – heart (SA/AV node) - M3 – smooth muscle and glands (GI tract, airways, secretory glands) - M4/M5 – CNS - Muscarinic receptors act indirectly on ion channels or second messengers via G proteins at their effectors organ and can be differentiated by their response to antagonists. Candidates had overall good knowledge on ACh and NorAd but struggled to provide correct information on GABA and 5-HT. If these first two were answered in enough detail then a candidate was likely to score close to the pass mark. First Part Exam Report 2026.1

This question required a structured approach to cover the breadth of the possible reactions. A common classification and structure used in most of the recommended resources includes: - Acute immunologic reactions - acute haemolytic transfusion reaction; - Other acute non hemolytic reactions - febrile non haemolytic reactions - transfusion related lung injury (TRALI) - Acute non immunologic reactions - metabolic reactions e.g. hyperkalaemia, - infection, - coagulopathy, - fluid overload. - Delayed immunologic reaction - delayed haemolytic transfusion reactions, - graft versus host reactions - transfusion related immunomodulation. - Delayed non immunologic reactions - iron overload - infection. An ‘outline’ question requires candidates to provide some but not extensive detail of the adverse effect thus differentiating it from just a list. A lack of a structured approach often resulted in the omission of large sections of the answer scope limiting the marks available. First Part Exam Report 2026.1

This is a broad question that requires a brief overview of the changes and their causative factors. For example, a primary cardiac change is an increase in cardiac output. A good answer included a description of how the components of cardiac output change, the timing and the mechanisms for these changes. For example: Changes in cardiac output; - Increased to maximal 30-40% in second trimester this is secondary to: - initial decreased SVR - in SBP 15-20mmHg secondary to progesterone mediated vaso and venoD → compensatory increase in HR/SV BRR and + RAAS/ADH/Ald - increase in blood volume 30% – + by oestrogen, and RAAS/ADH/Ald – Na+ and H20 retention → inc. VR. Whilst many were able to list the cardiorespiratory changes throughout pregnancy – linking these changes to some of their mechanisms particularly hormonal and accurate descriptions of the timing, elevated a candidate’s answer.

This question required candidates to demonstrate their understanding of the anatomical landmarks, necessary knowledge required prior to performing a percutaneous tracheostomy. a) An at standard answer included the recognition of A as the recurrent laryngeal nerve, B & C as the superficial and pretracheal fascia, and G as the carotid sheath. Candidates who identified the additional structures scored above the expected standard. b) Inclusion of the trachea’s origin in the neck and termination in the mediastinum, a description of the structure of the trachea with mention of C- shaped anterior cartilage rings and trachealis muscle posteriorly was expected for an at standard response. Inclusion of also brief detail on blood supply and innervation was scored at above standard c) The expected standard required a brief description of a midline anterior approach between the tracheal rings 1-3. First Part Exam Report 2026.1

The question breakdown provided a guide to the level of detail required for each section. High scoring answers made a direct comparison of the similarities and key differences between the drugs which may influence the use of one over the other and the relevance to critical illness. Both drugs are commonly used in ICU and are level 1 drugs in the syllabus. A detailed knowledge of the pharmacokinetics, pharmacodynamics and adverse effects was expected. Many questions overlooked the reference to “IV administration” and “relevance to ICU” which led to the inclusion of detail not required for this question.

This is another question where the breakdown and mark allocation provided a guide to the level of detail expected. Whilst these are level 3 drugs in the syllabus, they are commonly used in ICU. It is expected that candidates have a grasp of the key differences in mechanism of action and side effect profiles of first- and second-generation antipsychotics. a) Candidates were expected to explain the contrasting mechanism of action with haloperidol having the highest affinity for D2 receptors and less so for the atypical antipsychotics (olanzapine and quetiapine) for which 5-HT2a antagonism is a key mechanism of action. b) Atypical antipsychotics have lower risks of extrapyramidal side effects related to lower D2 affinity, and candidates were expected to provide some examples of extrapyramidal side effects. c) Answers that made mention of alpha and H1 antagonism with a description of some of the resultant effects (such as sedation with H1 antagonism) were able to achieve the required standard. Additional marks were awarded for mention of muscarinic antagonism with both quetiapine and olanzapine. d) It was expected that candidates would identify that all three drugs cause QT prolongation via K+ channel blockade and that the risk is highest with haloperidol. e) Well scoring answers listed at least 3 idiosyncratic reactions including neuroleptic malignant syndrome of which the risk is highest with haloperidol. First Part Exam Report 2026.1

a) This section was generally well answered. Candidates were expected to outline the principles that apply to this method of measurement, describing its relationship to the Beer-Lambert Law and the options of either in-line or side stream sampling of exhaled gases and their implications. b) This component of the question required candidates to describe the four phases of the capnogram, describe or demonstrate on a diagram where the end tidal CO2 value is derived and indicate the alpha and beta angles and what they represent. This part of the question could have been achieved by providing a rough but accurate drawing of the carbon dioxide vs time graph with axes, key features labelled and a few explanatory points or providing a more detailed description of the shape and phases of the graph including the features outlined above. Many drawings did not help the candidates due to their inaccuracies in labelling or incorrect shape/axis, many went on to also describe what they had already drawn not taking advantage of the time saved in providing an accurate drawing encompassing all relevant points. c) This section examined the translation of measurement methods into clinical application. Many candidates provided a good structure dividing the derived information into perfusion and ventilation. The information provided under these headings tended to lack depth and explanation to score well. For example; a candidate may list – cardiac output – however not link it to the reason it can be inferred from the capnograph. Expected information for a good answer included the following key points with an example of each: - Perfusion: PETCO2 approximates PaCO2 and changes in PETCO2 reflect changes in pulmonary perfusion and thus cardiac output. - Ventilation: PETCO2 is an indicator of endotracheal tube placement, respiratory rate, and adequacy of alveolar ventilation. The slope of phase three provides an indication of the heterogeneity of alveolar time constants throughout the lung. First Part Exam Report 2026.1

a) Many answers discussed factors that contribute to pulmonary vascular resistance. Whilst pulmonary vasocontriction is a component of this, discussing PVR would lead to including other details on a broader range of concepts detracting from the level of detail needed when just focusing on pulmonary vascular tone. This question required a discussion of the effect of O2, CO2, pH, and neurohormonal mediators on pulmonary vascular tone. O2 is the major determinant of the pulmonary vascular tone, and a more detailed discussion of the mechanism of hypoxic pulmonary vasoconstriction was expected. CO2 and pH have a lesser effect. A description of a range of neurohormonal mediators such as catecholamines and their contribution to pulmonary vasoconstriction also attracted marks. b) This section sought knowledge of these commonly used pulmonary vasodilators and was generally well answered. Given the verb “describe” for mechanism of action, the cellular mechanisms by which these drugs cause pulmonary vascular dilation was expected. Adverse effects required a list of common or serious adverse effects AND a brief outline of the mechanism by which they occur. Commonly candidates provided a list of adverse effects however many answers didn’t link the mechanism to the side effect or omitted common OR serious adverse effects.

Venous return is the volume of blood returning to the heart per unit time and is determined by the pressure gradient [mean systemic filling pressure (MSFP]) – right atrial pressure (RAP)] divided by the resistance to venous return. High scoring answers structured their discussion around this definition and were able to link other physiological factors like intrathoracic pressure, skeletal muscle pump activity, venous valves, and posture to changes in venous return. Pressure gradient is the major determinant of venous return and therefore a more detailed discussion of the effect of blood volume and venous tone on MSFP as well as the determinants of RAP was expected and was more heavily weighted in its scoring. Normal values when provided also attracted marks. A common pitfall was to provide a detailed discussion of the determinants of cardiac output at the expense of other important factors mentioned above – thus limiting the available marks that could be awarded. First Part Exam Report 2026.1

The question breakdown provided a clear structure to approach this question. a) This section required a factual recall of information and was generally well answered. b) Good answers included a comprehensive overview of parathyroid hormone (PTH), Vitamin D and calcitonin, (the three hormones involved in calcium regulation). A good structure included sensor and effector mechanisms. c) This section explored the understanding of factors that affect plasma calcium levels such as protein binding; acid-base status and its effect of ionisation of calcium; and other hormones e.g. glucocorticoids which lower plasma calcium levels. A simple list of some of these factors particularly albumin and plasma proteins, with a brief explanation as to their effect on plasma calcium and why, was enough to score well.

Answers were generally well structured by following the subheadings provided. Common errors and omissions related to either limited knowledge about both drugs with some inaccurate information or whole sections not answered. Neostigmine and sugammadex are used frequently in clinical practice and the information required by this question directly relates to the knowledge required to safely administer these drugs. First Part Exam Report 2026.1

This question tests factual recall of knowledge and was generally well answered. Candidates used the provided headings and mark allocation to structure their answers. The areas with the most common omissions related to the composition and storage of bile. Candidates are encouraged to not overthink questions that appear surprisingly simple – for part c) mentioning that bile is stored in the gall bladder where is undergoes concentration was enough to meet the standard required.

a) Answers that scored well in this section were able to provide a description of fever and hyperthermia including the physiological mechanisms of each, their triggers and regulation. Then providing some explanation of the differences. Hyperthermia is due to a failure of thermoregulatory responses to deal with heat gain (from either the internal or external environment). The hypothalamic set point in hyperthermia is unaltered. Whereas fever is part of the innate immune response and involves an increase in the set-point and inappropriately triggering of the body’s heat conservation mechanisms. Candidates were largely able to list some causes of fever and hyperthermia; however, the role of pyrogens in fever was commonly omitted. b) The pharmacology of paracetamol required an overview of the mechanism of action – with focus on its anti-COX activity and a brief statement regarding its other non-COX mediated effects. Adverse effects were generally well covered, again a brief demonstration of the relative commonality of the effects or the seriousness elevated good answers. The toxicity section required a brief outline of the mechanism including depletion of glutathione leading to NAPQI accumulation, and subsequent oxidative stress injury to hepatocytes. First Part Exam Report 2026.1

This question required candidates to apply their knowledge of viscoelastic assays to describe changes in different haematological states. The key viscoelastic changes to mention under each state include: - clot firmness - rate of clot initiation - rate of clot formation to maximum thickness - rate of clot lysis a) Platelet dysfunction is associated with decreased clot firmness, and prolonged time to maximum thickness due to impaired platelet-fibrin interaction. Clot initiation is unchanged. b) Therapeutic heparin binds to antithrombin III and inactivates several serine proteases in the coagulation pathway and slows conversion of fibrinogen to fibrin. The typical changes seen on a viscoelastic assay include delayed clot initiation, decreased firmness, and reduced maximal thickness. c) Hyperfibrinolysis increases the rate of clot lysis by increasing the activity of the fibrinolytic system. Using this to describe the resultant TEG/Rotem parameters was required. Commonly candidates were able to list some of the alterations seen with each state however omitted the reasons why these changes came about. Candidates who provided a thorough overview of the changes seen and the areas of the TEG/Rotem measurements that were preserved scored highly. Details of the normal coagulation pathways and the mechanisms of TEG/Rotem including how the assays are performed were not required, though many candidates provided detailed descriptions of these at the expense of considering the above changes. First Part Exam Report 2026.1

Well scoring answers explained the concept of compartment models including the central and peripheral compartments and the observation of drug concentration over time as it distributes between compartments. Candidates were expected to discuss the different phases involved (distribution phase from central to peripheral compartments and terminal phase from peripheral to central compartment prior to elimination). The clinical relevance of these models is in predicting drug offset following single dose vs infusions depending on extent of distribution to other compartments; understanding the link between plasma concentration and clinical effect at non-plasma effect site; and guiding dosing decisions. A diagram was not required but was well utilised to explain these concepts by candidates. Good answers considered, with examples, physicochemical, pharmacokinetic and pharmacodynamic factors that apply to drugs that follow a multicompartment model.

a) Most candidates were able to classify hypersensitivity reactions correctly. Candidates are reminded to use the mark allocation as a guide to the level of detail with many providing extensive detail on each category when only a brief description was required. b) This section carried the most marks and therefore a more detailed discussion was expected. This included the 3 essential phases of the anaphylaxis response: sensitisation, activation and mediator release. High scoring answers also discussed amplification and the biphasic response. A mention of relevant mediators was expected. Candidates were familiar with histamine but omitted other mediators such serotonin and prostaglandins. c) Adrenaline is a level 1 drug in the syllabus and was generally well answered, better answers tailored their pharmacology description to information that was relevant to the management of anaphylaxis ie. Including the role in mast cell stabilisation and the mechanism of this. Pharmacokinetic information expected included IM delivery, fast onset, fast offset due to metabolism thus may need repeated doses and can be given by infusion for severe anaphylactic shock and titrated to haemodynamic parameters. First Part Exam Report 2026.1