Show the model answerAttempt it first — that is what makes it stick
What earns the marks10 marks
| (a) Resembles natural NREM sleep | 1 mark. The distinguishing clinical feature, not the mechanism — some answered the wrong question here |
|---|---|
| (b) Selective α2 agonist at the locus coeruleus | 2 marks. Acting centrally in the brainstem to modulate noradrenaline release |
| (b) Agonist, not antagonist | A small number said antagonist. Excessive cellular detail was beyond the expected scope |
| (c) Biphasic, not just hypotension and bradycardia | 2 marks. Most named the two but omitted the initial transient hypertensive phase |
| (c) The mechanism of each phase | The underlying biphasic haemodynamic mechanism was specifically wanted |
| (d) Link each advantage to the ICU | 5 marks, and the part the question turned on |
| (d) Do not repeat (a), (b) and (c) | Several candidates did, rather than expanding |
| (d) Advantages only | Some included disadvantages, which was off the question |
1 mark
The characteristics of dexmedetomidine-induced sedation
Commonly lost: Some candidates focused on the mechanism of action rather than the distinguishing clinical features, and occasionally conflated them with the effects of other sedative agents. The mechanism is worth two marks in the very next part; spending it here earns nothing twice.
2 marks
The mechanism of action
The pathway, at the level two marks asks for
Commonly lost: A small number of candidates incorrectly identified dexmedetomidine as an antagonist. Several included excessive cellular-level explanation beyond the expected scope, and others gave physicochemical and pharmacokinetic detail that was not asked for. Two marks buys three sentences.
2 marks
The cardiovascular effects
| Phase | Effect | Mechanism | Where |
|---|---|---|---|
| Early, transient | Hypertension — mean arterial pressure rises about 12% at higher concentrations, seen particularly after a rapid loading dose | Stimulation of post-synaptic α2 receptors on vascular smooth muscle causes vasoconstriction. It appears first because the drug reaches the peripheral receptors before the central effect is established | Peripheral — the vessel wall |
| Later, sustained | Hypotension and bradycardia — mean arterial pressure falls about 13% at low concentrations, heart rate falls by up to 29% and cardiac output by up to 35% | Centrally mediated sympatholysis, with presynaptic α2 inhibition of noradrenaline release and a vagomimetic component. It eventually overwhelms the peripheral vasoconstriction | Central — the brainstem |
Reported incidences in a phase III trial of 401 patients were hypotension 30%, hypertension 12% and bradycardia 9%. All three are common.
Commonly lost: A substantial proportion of candidates named hypotension and bradycardia without elaborating on the initial transient hypertensive phase or the underlying biphasic mechanism. Several also repeated similar points in varied phrasing, which added length without depth. Two marks: two phases, two mechanisms, two places.
5 marks — half the question
Pharmacodynamic advantages in the intensive care unit
| Property | What it buys in the intensive care unit |
|---|---|
| Minimal respiratory depression | The respiratory centre is not a step in the sedative pathway. Sedation can be continued through extubation and during weaning without depressing the drive being tested, and non-intubated patients can be sedated for procedures. This is the single largest advantage |
| Rousable, cooperative sedation resembling NREM sleep | Daily sedation-hold and neurological assessment can be performed safely and without stopping the infusion — and daily wake-up testing shortens ventilated days and length of stay |
| Reduced incidence of delirium | More days alive without delirium or coma than with lorazepam, and better patient ability to communicate pain than with midazolam or propofol. Delirium is an independent predictor of longer stay and higher mortality, which is what makes this a survival argument rather than a comfort one |
| Analgesia and opioid sparing | Opioid requirement falls by more than 50%, which reduces opioid-associated ileus, tolerance and respiratory depression, and reduces the sedative load needed alongside |
| Sympatholysis and haemodynamic stability during weaning | Blunts the stress response of weaning and extubation, giving more stable haemodynamics in patients at high risk of myocardial ischaemia |
| No active metabolites | Complete biotransformation with no active metabolite, so no accumulation of an active moiety over days — the specific failing of midazolam, whose 1-hydroxymidazolam accumulates in renal impairment |
| No tolerance of the kind midazolam shows | Avoids the escalating dose requirement, and the withdrawal and paradoxical agitation that follow prolonged benzodiazepine sedation |
| Antisialagogue effect and preserved airway | Reduced salivation and preserved airway tone make it usable for awake fibreoptic intubation and for airway procedures on the unit |
Commonly lost: Many responses gave general descriptions of pharmacodynamic effects without effectively linking them to the intensive care context. Several repeated the content of parts (a), (b) and (c) rather than expanding. Some included disadvantages, which was off the question. And time management was apparent: brief, superficial responses to the part carrying half the marks.
The teaching behind this answer — dexmedetomidine and the locus coeruleus