Thread by @CritCareReviews

One of the most outstanding questions in critical care is whether patients benefit from IV fluid resuscitation in septic shock.
A thread...
(image shutterstock)
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In the 1800s, cholera was the scourge of Europe, killing over a million people through its toxin mediated diarrhoea and subsequent cardiovascular collapse
(image shutterstock)
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In 1830, Hermann suggested treating the haemoconcentration seen in cholera patients with intravenous water. His colleague Jaehnichen injected 6 oz of water to a patient, with an apparent clinical improvement, but the patient died 2 hours later
(10.1016/j.clnu.2008.01.008)
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Based on animal work by William O’Shaughnessy, the first saline-like solution was administered to humans with cholera in 1832 by Thomas Latta. This IV fluid had an electrolyte composition closer to blood than water.
(Image - O’Shaughnessy - Wikipedia)
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Latta's description was memorable: "Shortly after the commencement of the injection the pulse, which was not perceptible, gradually returns; the eyes, which were sunk & turned upwards, are suddenly brought forward, & the patient looks round as if in health..."
(ref - wiki)
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IV fluids have since become commonplace in medicine. Hundreds of millions of litres of saline are used annually, creating a global market worth almost $3 billion in 2019, which is expected to rise to almost $4 billion by 2026
(fortunebusinessinsights.com)
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Although IV fluids have become ubiquitous, evidence examining their benefit versus no fluid therapy in non-fluid losing pathologies is largely absent, with fluid trials focusing on comparisons between different fluid types instead
(Image - Shutterstock)
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In 1994, in a small study comparing immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries, those receiving delayed therapy had superior outcomes (in hospital mortality 70% vs 62%)
(10.1056/NEJM199410273311701)
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In 2011, the landmark FEAST trial reported a reduction in mortality in African children with febrile illness and impaired perfusion managed without a fluid bolus, in comparison with those treated with either a saline or albumin bolus.
(10.1056/NEJMoa1101549)
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The mechanism may have been fluid bolus induced cardiogenic shock, leading to cardiovascular collapse and death
(10.1186/1741-7015-11-68)
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The physiological effects from fluid bolus therapy are largely transient, with short lived effects on heart rate, blood pressure, cardiac output and intra-vascular volume.
(10.1186/s13054-014-0696-5)
11/16

A triumvirate of trials investigating a goal-directed approach to septic shock, based on the administration of IV fluids and cardiovascular monitoring with optimisation (ProCESS, ProMISE, ARISE) failed to demonstrate benefit & reported increased resource use.
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With no clear difference in outcomes between giving fluids at a fast or slow rate (10.1001/jama.2021.11444) or different types of fluid (10.1056/EVIDoa2100010), should focus rather be on the question of fluids versus no fluids?
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Enter the CLASSIC trial!
➡️ Investigator-initiated, international, randomised, stratified, and analyst-blinded
➡️ 1554 ICU patients with septic shock randomised to IV fluid restriction or standard care
(10.1111/aas.13434)
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The pilot trial demonstrated feasibility in separating fluid doses
➡️ unpowered, but intriguing, effects on ischaemic events (3/75 vs 9/76) & 90 day mortality (25/75 vs 31/76), favouring fluid restriction
(10.1007/s00134-016-4500-7)
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What will CLASSIC show?

Will a restrictive approach to fluid therapy in septic shock become a new standard?

Join us in June at #CCR22 to find out !
criticalcarereviews.com/meetings/ccr22

Results via @TineMeyhoff & @AndersPerner
Trial via @CRIC_Int_Care
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