Albumin on the Cutting Edge

DESPITE AN EXCELLENT emergency care system, ischemic stroke remains a leading cause of death in the U.S. More than one in five survivors faces serious long-term disability. Many would-be neuroprotective drugs have been tested in clinical trials with the hope of limiting the damage to brain tissue. None has worked.

Then there is severe sepsis, an even more efficient killer that will claim the lives of roughly one-third of its 750,000 victims this year. This complex infectioninduced syndrome has managed to outflank a long list of conceptually appealing experimental agents: antioxidants, antibodies targeting endotoxin and cytokines, vasoregulators, anti-inflammatory agents. All of them have fallen short.

So it may surprise many that, after all the years and billions of research dollars spent on failed drug candidates, doctors could soon have a single, effective new treatment to reduce the terrible toll of both stroke and sepsis. Interestingly, however, this potentially transformative new product isn’t really new: It’s human albumin.

Albumin Through History

Albumin was developed in the laboratory of a Harvard chemist named Edwin J. Cohn on the eve of the U.S. entry into World War II. The first inventory of 50 bottles of purified albumin was airlifted to Honolulu to treat the severely burned and wounded just days after the December 1941 bombing of Pearl Harbor. Since then, albumin has been within reach of military surgeons in every U.S. armed conflict, including Iraq and Afghanistan. It is credited with saving thousands of lives.

Over the last six decades, albumin has been administered to millions of hospitalized patients to restore blood volume, boost blood pressure and combat dangerous edema. Yet prior to a landmark 1999 trial in which its use cut mortality and renal impairment by roughly threefold in patients with cirrhosis and bacterial peritonitis, it had never been evaluated in a large-scale clinical trial.

Now — a mere 68 years since it emerged from Cohn’s lab in Cambridge — this simple plasma protein finds itself back on the center stage of critical care medicine.

Albumin as a Neuroprotective Agent After Stroke

In a 2001 study, human albumin proved remarkably effective in protecting the brains of rats given experimental strokes. Against a saline comparison group, high-dose 25 percent albumin reduced infarct size by two-thirds. Instead of 11 percent brain swelling, the albumininfused animals had zero. Neurological function was significantly improved.

Then, a 2006 pilot human safety trial suggested a strong neuroprotective benefit in stroke patients who received the highest albumin doses, especially those who also got thrombolytic therapy.

Based on these findings, more than 80 study sites are now actively enrolling 1,100 stroke patients in the pivotal National Institutes of Health-sponsored ALIAS (Albumin in Acute Stroke) trial. Similar to thrombolytic dosing within three hours, subjects must get their high-dose albumin or saline placebo infusion within five hours of the onset of stroke symptoms.

Will some mix of albumin’s well-known hemodilution, antioxidant, anti-adhesion and anti-inflammatory properties reduce disability or even save lives of stroke victims? When the ALIAS trial finishes in a couple of years, we’ll have our answer.

Albumin Takes on Severe Sepsis and Septic Shock

Albumin has been used for decades to temporarily restore blood pressure in patients with established septic shock. But now, a network of 27 French hospitals is going a big step further.

Starting within hours of the onset of shock, 800 patients will receive three daily infusions of either saline or concentrated albumin. By late next year, we should learn whether albumin supplementation translates into fewer deaths, fewer days on ventilator and dialysis, fewer hospital days and fewer nosocomial infections.

An Italian research team is casting a wider net. A total of 1,350 patients with severe sepsis or septic shock will be given either a salt solution or concentrated albumin. But in this case, albumin will be dosed on a daily basis to maintain its serum concentration above a minimum threshold — for as long as the patient remains in the ICU.

Could simple sustained albumin therapy reduce hospital stays or actually save the lives of severe sepsis patients? While suggestive evidence from older studies abounds, these larger trials may settle the question.

Albumin and the Future of Healthcare

Albumin has patiently waited its turn while more exotic therapeutic candidates were pushed to the front of the research pipeline. Now the most versatile blood protein that nature could create has returned to do battle.