Health
Critical Care
Medical Research
Europe
Medical History
Cholera
Septic shock
Toxin mediated diarrhea
Cardiovascular collapse
Hermann
Jaehnichen
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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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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(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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(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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(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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(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)
6/16
(fortunebusinessinsights.com)
6/16
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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(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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(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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(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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(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)
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(10.1186/s13054-014-0696-5)
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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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➡️ 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)
14/16
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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➡️ 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)
15/16
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
Results via @TineMeyhoff & @AndersPerner
Trial via @CRIC_Int_Care
16/16
16/16
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
Results via @TineMeyhoff & @AndersPerner
Trial via @CRIC_Int_Care
16/16
16/16
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