Some treatments save lives. Others teach medicine how to stop. For centuries, bloodletting was medicine’s answer to illness: plausible, authoritative, visible, and wrong. It survived because it made sense — until clinicians began to count. The Last Drop follows that old lesson into the COVID-19 pandemic, where ivermectin travelled from in-vitro signal to public certainty, influencer promotion, widespread use, and clinical demand before robust evidence caught up. REMAP-CAP’s ivermectin trial did not produce a miracle. It produced something more uncomfortable, and perhaps just as important: evidence of non-benefit. This is a story about bloodletting, ivermectin, REMAP-CAP, and why de-implementing an ineffective treatment can be as important as discovering a effective one.

Added May 13th

ANDROMEDA-SHOCK-2 asks a deceptively simple question: can the fingertip guide septic-shock resuscitation better than the laboratory? From Rivers’ EGDT to CLASSIC and CLOVERS, the field has swung between protocol and restraint, searching for the right physiological compass. AS-2 returns to the bedside — capillary refill time, pulse pressure, diastolic pressure — and builds a personalised algorithm around repeated reassessment rather than fixed dogma. In 1,467 patients across 19 countries, the strategy shortened vasopressor, ventilation and renal-support durations, yet left mortality unchanged. Was this precision physiology, subconscious bias in an open-label trial, or both? This piece follows the science from Galileo’s telescope to modern haemodynamic resuscitation, exploring whether AS-2 marks the dawn of precision septic-shock care — or another star briefly mistaken for the centre of the universe.

Added November 7th

Vitamin C in critical illness has always hinted at more than scurvy’s salvation. From Lind’s lemons to Linus Pauling’s promise to an ICU cocktail that briefly looked like a cure, the arc swings between elegant biology and stubborn clinical reality. We track the enzymes and endothelium, the catecholamines and carnitine, and the redox alchemy that can both shield and scorch. Then we meet the trials—VITAMINS neutral, LOVIT unnerving—and ask why sepsis would not yield while burns, post-arrest care, and megadose strategies still tempt inquiry. This piece follows the CCR thread through Belfast to Melbourne, where VITaCCA may yet decide whether our romance with ascorbate is requited or finally unmasked.

Added October 16th

Induction for rapid sequence intubation (RSI) in the critically ill often feels like the swing of a pendulum. Toward etomidate—haemodynamic poise, clean hypnosis, and familiar dosing. Back toward ketamine—sympathomimetic support, bronchodilation, and neuro-myths in slow retreat. The science, at times, looks just as mercurial. This review examines the terrain with a steady eye: what goes wrong when we intubate the critically ill; why physiology, not just anatomy, governs risk; what etomidate and ketamine truly offer; what the best comparative trials show; and where ongoing research is taking the field.

Added September 4th

We review the RE-ENERGIZE trial, investigating glutamine for patient's with severe burns, and seek to understand why the trial failed to identify benefit. Was it a methodological failure, a flawed execution, or a correct identification of a non-beneficial intervention?

Added December 20th, 2023

The Fragility Index is the minimum number of subjects whose status would have to change from a non-event to an event to convert a statistically significant result of the trial into a non-significant result. It is an expression of the study characteristics, and not of validity.

Guest post by Dr Ed Palmer

Added August 21st, 2022

Why did the REST trial¹ fail to clearly demonstrate benefit with the addition of an ECCO₂R  device in invasively mechanically ventilated patients with acute hypoxaemic respiratory failure?

Added October 4th, 2021