Membership of the Royal College of Paediatrics and Child Health (MRCPCH) Foundation of Practice: Core Science, Pharmacology and Acute Care Syllabus

Differentiate a competitive antagonist from a non-competitive antagonist on a dose-response curve.

A competitive antagonist shifts the agonist dose-response curve to the right (higher $EC_{50}$) but $E_{max}$ is unchanged and surmountable by more agonist. A non-competitive antagonist reduces $E_{max}$ (insurmountable) and the curve cannot be fully restored by adding agonist.

What is the formula for calculating body surface area (BSA) using the Mosteller method?

$$BSA\ (m^{2}) = \sqrt{\frac{\text{height (cm)} \times \text{weight (kg)}}{3600}}$$ BSA is used for dosing drugs such as chemotherapy where weight-based dosing is less accurate.

Why is body-surface-area-based dosing preferred over weight-based dosing for certain drugs in children?

BSA correlates better with physiological parameters such as cardiac output, glomerular filtration rate and metabolic rate than weight alone. It avoids overdosing in small/obese children for narrow-therapeutic-index drugs like cytotoxics, though weight-based mg/kg dosing is standard for most paediatric prescribing.

Classify adverse drug reactions using the A-to-E (or Type A vs Type B) system.

Type A (Augmented): dose-related, predictable from pharmacology, common (e.g. bleeding on warfarin). Type B (Bizarre): idiosyncratic, not dose-related, unpredictable (e.g. anaphylaxis). Extended: C chronic, D delayed, E end-of-treatment (withdrawal).

Explain the mechanism by which enzyme inducers and inhibitors cause drug interactions, with an example of each.

Enzyme inducers (e.g. rifampicin, carbamazepine, phenytoin) increase cytochrome P450 activity, lowering plasma levels of co-administered drugs. Enzyme inhibitors (e.g. erythromycin/clarithromycin, ketoconazole) reduce P450 activity, raising plasma levels and toxicity risk.

Which drugs commonly require therapeutic drug monitoring in children, and why?

Drugs with a narrow therapeutic index: gentamicin/vancomycin (nephro/ototoxicity), phenytoin and carbamazepine (anticonvulsants), digoxin, theophylline, and ciclosporin/tacrolimus. TDM ensures efficacy while avoiding toxicity.

For TDM of a drug, what is the difference between a trough and a peak level, and which guides gentamicin dosing?

Trough is the lowest concentration, taken immediately before the next dose, reflecting clearance/accumulation (toxicity risk). Peak is the maximum after distribution, reflecting efficacy. For once-daily gentamicin, the trough (pre-dose) level is the key marker of safe clearance.

What are the core aims and key strategies of antimicrobial stewardship in children?

Aim: optimise outcomes while minimising resistance, toxicity and cost. Strategies: use narrowest effective spectrum, correct dose/duration, IV-to-oral switch when stable, de-escalation guided by cultures, 'Start Smart then Focus', and review at 48-72 hours.

Give the standard Holliday-Segar formula for daily maintenance fluid volume in children.

Per 24 hours: $100\ mL/kg$ for the first $10\ kg$, $+50\ mL/kg$ for the next $10\ kg$ ($10$-$20\ kg$), $+20\ mL/kg$ for each kg above $20\ kg$. Example: a $25\ kg$ child needs $1000 + 500 + 100 = 1600\ mL/day$.

State the '4-2-1' rule for hourly maintenance fluids.

$4\ mL/kg/hr$ for the first $10\ kg$, $2\ mL/kg/hr$ for the next $10\ kg$, and $1\ mL/kg/hr$ for each kg above $20\ kg$. It is the hourly equivalent of the Holliday-Segar formula.

Why does current UK (NICE) guidance recommend isotonic rather than hypotonic maintenance fluids in children?

Hypotonic fluids (e.g. 0.18% saline) increase the risk of iatrogenic hyponatraemia and cerebral oedema, especially with raised ADH. NICE recommends isotonic fluids such as 0.9% sodium chloride with 5% glucose (with potassium as needed).

How is the percentage of dehydration estimated from acute weight loss, and what fluid deficit does it represent?

$$\%\ \text{dehydration} = \frac{\text{weight loss (kg)}}{\text{pre-illness weight (kg)}} \times 100$$ Fluid deficit (mL) $= \%\ \text{dehydration} \times \text{weight (kg)} \times 10$. For example 5% dehydration in a 10 kg child = $5 \times 10 \times 10 = 500\ mL$ deficit.

Compare the clinical features of no/mild, clinical, and shock (severe) dehydration in children.

No clinical dehydration (<5%): no signs. Clinical dehydration (5-10%): dry mucous membranes, reduced urine, sunken eyes, reduced skin turgor, tachycardia, irritability. Clinical shock (>10%): cold peripheries, prolonged capillary refill, weak pulses, hypotension (late), decreased consciousness.

How are rehydration fluids calculated for a dehydrated but not shocked child over 24 hours?

Total = maintenance + deficit, replaced over 24 hours (slower over 48h if hypernatraemic). Deficit (mL) = % dehydration $\times$ weight (kg) $\times 10$. Use isotonic fluid; reassess electrolytes and clinical status regularly.

What are the ECG features and emergency management of severe hyperkalaemia in a child?

ECG: tall tented T waves, flattened/absent P waves, widened QRS, sine wave, then arrest. Management: IV calcium gluconate (cardioprotection), then salbutamol nebs and insulin-dextrose to shift $\ce{K+}$ into cells, plus measures to remove $\ce{K+}$ (e.g. resonium, dialysis).

What is the main danger of correcting chronic hyponatraemia too rapidly, and what is the safe rate?

Overly rapid correction risks osmotic demyelination (central pontine myelinolysis). Serum sodium should generally rise by no more than ~$8$-$10\ mmol/L$ per 24 hours in chronic hyponatraemia.

Distinguish enteral from parenteral nutrition and state the guiding principle for choosing between them.

Enteral nutrition delivers feed into a functioning gut (oral, NG, NJ or gastrostomy); parenteral nutrition (PN) delivers nutrients intravenously, bypassing the gut. Principle: 'if the gut works, use it' — enteral is preferred as it is safer, cheaper and maintains gut integrity.

List two serious complications associated with parenteral nutrition in children.

Central line sepsis/CLABSI, PN-associated liver disease (cholestasis/IFALD), electrolyte and metabolic disturbances (including refeeding syndrome), hyperglycaemia, and thrombosis. Refeeding syndrome features falling phosphate, potassium and magnesium.

Define faltering growth (failure to thrive) and the recommended weight-centile criteria used by NICE.

Faltering growth is a slower rate of weight gain than expected for age/sex. NICE thresholds: a sustained drop across 1 centile space if birthweight was below the 9th centile; 2 spaces if between 9th-91st; 3 spaces if above the 91st; or current weight below the 2nd centile.

What initial nutritional assessment tools and measurements are used in a child with faltering growth?

Plot serial weight, length/height and head circumference on growth charts; calculate weight-for-age, height-for-age and BMI/weight-for-height. Assess feeding history, dietary intake, and screen for organic causes. Mid-upper arm circumference can assess acute malnutrition.

List the components of the structured ABCDE assessment for an acutely unwell child.

A - Airway (with cervical spine control if trauma); B - Breathing; C - Circulation; D - Disability (AVPU/GCS, pupils, glucose); E - Exposure (full examination, temperature, while preventing heat loss). Reassess after each intervention.

In paediatric Basic Life Support, what is the compression-to-ventilation ratio and initial step for a non-breathing child?

Give 5 initial rescue breaths first (respiratory causes predominate in children), then for a lone rescuer use 30:2 and for healthcare teams 15:2 compressions to ventilations. Compress the lower sternum to one-third of chest depth at $100$-$120$/min.

In paediatric Advanced Life Support (APLS/EPALS), which rhythms are shockable and what are the key drug doses?

Shockable: VF/pulseless VT — defibrillate at $4\ J/kg$. Non-shockable: PEA/asystole. Adrenaline $10\ \mu g/kg$ ($0.1\ mL/kg$ of 1:10000) IV/IO every 3-5 minutes (immediately in non-shockable; after 3rd shock in shockable). Amiodarone $5\ mg/kg$ after the 3rd and 5th shocks.

What is the definition of shock, and what is the recognised difference between compensated and decompensated shock in children?

Shock is inadequate tissue perfusion/oxygen delivery to meet metabolic demands. Compensated: normal blood pressure maintained by tachycardia and vasoconstriction. Decompensated: hypotension develops — a late, pre-terminal sign in children because they compensate well until collapse.

State the initial fluid bolus for a child in shock (non-DKA, non-cardiac) and how it is titrated.

Give $10\ mL/kg$ of isotonic crystalloid (e.g. 0.9% saline) as a rapid bolus, reassess, and repeat as needed. Larger $20\ mL/kg$ may be used in fluid-responsive sepsis; reassess for fluid overload after each bolus and consider inotropes/escalation if refractory.

Define status epilepticus and outline the first two steps of the APLS convulsing-child algorithm.

Status epilepticus is a seizure lasting $\geq 5$ minutes or recurrent seizures without recovery of consciousness. Step 1 (5 min): ABC, oxygen, check glucose, give a benzodiazepine (IV lorazepam $0.1\ mg/kg$ or buccal midazolam). Step 2 (10 min): repeat benzodiazepine, call for senior help.

In the convulsing child algorithm, what second-line agent is given if benzodiazepines fail, and what is the final step?

After two doses of benzodiazepine, give a second-line agent such as IV levetiracetam, phenytoin ($20\ mg/kg$ over 20 min) or phenobarbital. If seizures continue, proceed to rapid sequence induction with thiopental and intubation, involving anaesthesia/PICU.

What are the key features and immediate treatment of anaphylaxis in a child?

Acute onset of Airway (swelling/stridor), Breathing (wheeze/hypoxia) and/or Circulation (hypotension) problems, usually with skin changes. Treatment: IM adrenaline to the anterolateral thigh, repeated after 5 minutes if needed; high-flow oxygen; IV fluid bolus; lay flat with legs raised.

State the age-based IM adrenaline (1:1000) doses for anaphylaxis.

$<6$ years: $150\ \mu g$ ($0.15\ mL$); $6$-$12$ years: $300\ \mu g$ ($0.3\ mL$); $>12$ years/adult: $500\ \mu g$ ($0.5\ mL$). Given IM into the anterolateral thigh and repeated after 5 minutes if no improvement.

In major paediatric trauma, what does the <C>ABCDE primary survey prioritise, and how is circulating volume estimated?

Catastrophic haemorrhage control first (<C>), then Airway with C-spine control, Breathing, Circulation, Disability, Exposure. Estimated circulating blood volume is ~$70$-$80\ mL/kg$; signs of shock appear after ~25-30% loss because of strong compensation.

In the hierarchy of evidence, rank these study designs from strongest to weakest: case-control, RCT, cohort, systematic review/meta-analysis, case series.

From strongest to weakest: systematic review/meta-analysis of RCTs > randomised controlled trial > cohort study > case-control study > case series/case report > expert opinion.

Define sensitivity and specificity, and give their formulas.

Sensitivity = proportion of true cases correctly identified by a positive test: $$\text{Sensitivity} = \frac{TP}{TP + FN}$$ Specificity = proportion of non-cases correctly identified by a negative test: $$\text{Specificity} = \frac{TN}{TN + FP}$$ A highly sensitive test is good for ruling out (SnNout).

Distinguish relative risk, absolute risk reduction and number needed to treat.

Relative risk (RR) = risk in exposed/treated divided by risk in control. Absolute risk reduction (ARR) = control event rate $-$ treatment event rate. Number needed to treat: $$NNT = \frac{1}{ARR}$$ NNT is the number treated to prevent one additional adverse outcome.

What does a p-value represent, and what does a 95% confidence interval crossing the null value indicate?

A p-value is the probability of observing the data (or more extreme) if the null hypothesis were true; $p < 0.05$ is conventionally significant. A 95% CI for a ratio crossing 1 (or 0 for a difference) indicates a non-statistically-significant result.

Describe the four stages of a PDSA (Plan-Do-Study-Act) cycle in quality improvement.

Plan: identify the change/objective and predict outcomes. Do: implement the change on a small scale and collect data. Study: analyse results against predictions. Act: adopt, adapt or abandon the change, then begin the next cycle — iterative, rapid improvement.

What is the difference between clinical audit and research?

Audit measures current practice against established standards/guidelines to improve local care (does not generate new knowledge, no randomisation, completes the loop by re-auditing). Research aims to generate new generalisable knowledge, tests a hypothesis, and usually requires ethics approval.

What is the role of NICE guidelines, and how does shared decision-making fit alongside them?

NICE produces evidence-based national guidance to standardise and optimise care and resource use; guidelines inform but do not replace clinical judgement. Shared decision-making combines the best evidence with the child's/family's values and preferences to reach individualised decisions.