XV · Critical appraisal — what we still don't know Severe Falciparum Malaria15 / 18
Evidence gaps & where the field is moving.
No adult RCT in HIC ICUs
AQUAMAT/SEAQUAMAT enrolled SE Asian/African populations. Extrapolation to ventilated, RRT-supported HIC patients is implicit.
Optimal artesunate dosing
2.4 mg/kg fixed dose may under-dose obese patients and small children. Pop-PK suggests weight-banded regimens — not yet adopted.
Delayed post-artesunate haemolysis
Mechanism (pitting of once-infected RBCs) understood; predictors and prophylaxis not. No trial of prophylactic transfusion vs surveillance.
CRRT vs IHD timing
No malaria-specific data. Practice extrapolated from septic AKI trials with different physiology (haemoglobinuria, intravascular haemolysis).
Resistance surveillance
Kelch13 mutations now in East Africa (Uganda, Rwanda). Artesunate monotherapy failure rates rising — combination ACTs essential post-IV phase.
Adjunctive therapies
Statins, NO donors, sevuparin, rosiglitazone — all phase II signals, no phase III. Active area; nothing ready for the bedside.
Examiner framing"Demonstrate that you can cite the trial, name its limitation, and defend your bedside choice when the evidence is thin."
— how distinction candidates are separated from pass candidates.
Three sentences that score
- "The mortality evidence rests on AQUAMAT and SEAQUAMAT — both open-label, both outside HIC ICUs."
- "FEAST cannot be applied verbatim to a ventilated adult, but the signal of harm from reflex bolusing is real."
- "For exchange transfusion and steroids, absence of benefit in available trials outweighs mechanistic appeal."
Critical appraisal isn't a separate section of the viva — it's the texture of every good answer.
CICM Fellowship Masterclass · 2026Dr Timothy Chimunda FCICM