Abstract
Dear Editor,
I write to raise some concerns about the protocol of the ABC-Sepsis Study. 1 Firstly I would challenge the assertion that human albumin solutions (HAS) hold ‘physiological promise’ that defies the failure of many decades of clinical trials to prove a therapeutic benefit. I have previously ex- plained why biophysical infusion therapy to raise the plasma oncotic pressure will have much less effect on plasma volume and on tissue oedema than the traditional filtration–absorption balance interpretation of the Starling forces had once led us to expect. 2 As I concluded at the time, “The hope that biophysical intravascular colloid therapy with albumin or plasma substitutes can deliver plasma volume support without causing oedema is in vain.” The big question in resuscitation today is not colloid versus crystalloid, but fluid bolus versus continuous infusion re- suscitation, 3 a question this protocol misses. Professor Maitland published preliminary results of her FEAST trial after 150 patients were enrolled in 2005, suggesting sur- vival superiority of HAS bolus therapy with high statistical confidence. The trial was terminated after 3141 patients were enrolled and finally published in 2011. There was absolutely no difference between HAS bolus or saline bolus therapy, and the best survival was reported in the “no-bolus” control group.
Boluses of any fluid to patients with arteriolar vasoplegia will cause a peak of capillary pressure and hyperfiltration of solvent from plasma to the interstitium; volume for volume, a HAS bolus is expected to be more oedema-causing than a crystalloid bolus. The Michel-Weinbaum model explains why hyperfiltration is not matched by absorption of fluid back to the plasma. 4 Then there is the unavoidable accu- mulation within a few hours of most of the infused albumin within the tissues, where it is believed that every Gram of albumin holds 18 mL water as oedema fluid. Colloids cause more haemodilution than crystalloids when used for re- suscitation, leading to more blood transfusion prescriptions and reduced oxygen delivery to the tissues. The best pro- tection against raised capillary pressure and hyperfiltration is the early reversal of vasoplegia by titrated vasopressor therapy. The trial protocol should not restrict clinicians from using vasopressors at the earliest opportunity.
The non-necessity of plasma albumin for good health and a long life is starkly demonstrated by people with the rare autosomal recessive disorder that causes analbumi- naemia. 5 If in spite of the above the EMERGE researchers continue to believe that albumin holds physiological promise, I would strongly urge them at least to include a no- bolus control group as described by Professor Maitland. Failure to include a true Control group is considered unethical.
