In physiology, as in all other sciences, no discovery is useless … we may be certain that every advance achieved in the quest of pure knowledge will sooner or later play its part in the service of man.
— Dr Ernest Henry Starling,
The Linacre Lecture on the Law of the Heart (1915)
Modern sepsis treatment owes a conceptual debt to British physiologist Dr. Ernest Starling. Starling’s experiments suggested that increasing ventricular end-diastolic volume can increase cardiac output, and this is one of the goals in mind when septic patients are given intravenous crystalloid. In a separate line of work, Starling also described the hydrostatic and oncotic forces that ultimately cause much of this intravenous crystalloid to leak into the interstitium, resulting in pulmonary and peripheral edema that can seriously complicate a septic patient’s ICU course.
In this week’s NEJM, Dr. Pietro Caironi (Universita degli Studi di Milano, Italy) and colleagues report on the therapeutic potential of improving intravascular oncotic pressure in septic patients. The multicenter, open-label ALBIOS trial randomized 1,818 adult patients with severe sepsis to an albumin group or to a control group. Both groups received intravenous crystalloid whenever clinically indicated. The albumin group additionally received daily infusions of intravenous 20% albumin from randomization until ICU discharge or day 28 (whichever came first).
Did daily albumin infusions improve outcomes? Unfortunately not. The 28-day mortality was about 32% in both groups (p = 0.94). There was also no difference on secondary outcomes such as mortality at 90 days, severity of organ dysfunction, or ICU length of stay.
“Sepsis carries a high mortality,” says cardiologist and NEJM Executive Editor Dr. Gregory D Curfman, “Rigorously conducted trials allow clinicians to confidently determine which interventions are effective in a particular patient group and which offer little to no benefit.”
Although albumin infusions didn’t confer any survival advantage to ALBIOS study subjects, some hope remains that they might be beneficial in a more select group of patients. Participants in the albumin group had higher mean arterial pressures and lower net fluid balances during the first 7 days, and a post-hoc analysis suggested daily albumin infusions might improve 90-day mortality in the subset of patients with shock. Will albumin play a part in the service of the septic patient? Perhaps the next trial will tell.