Saturday, 25 August 2012

GranuFlo and NaturaLyte Withdrawal

Granuflo and NaturaLyte are products made by Fresenius, as buffer solutions in the final dialysis solution. Buffers control the pH of the solution and blood. There is concern that incorrectly mixed dialysate could lead to problems for dialysis patients.

Both products are an acetic acid / sodium acetate mixture. Buffers are a mixture of a weak acid and its sodium salt, and the choice of acid and salt determine the pH range over which the buffer will operate.

The first problem is that the body can metabolize acetate ions to carbonate and hydrogencarbonate (bicarbonate) ions, thus raising the level of bicarbonate in the blood. And bicarbonate ions are are part of one of the body's own buffer control systems. Altering the bicarbonate levels can lead to a pH imbalance and metabolic alkalosis - the blood is too alkaline during and after dialysis.

And metabolic alkalosis is an independent risk factor for low blood pressure, low blood oxygen, high blood carbon dioxide, heart rhythm problems, and sudden cardiac death.

Now the second problem.

A leaked memo from Fresenius was made available to the FDA. In it, Fresenius warned doctors at its company-owned clinics of the risk of GranuFlo side effects when using these concentrates. It advised its doctors to check bicarbonate levels in patients before dialysis, and to adjust prescriptions as necessary. The company failed, however, to warn outside clinics of the risks associated with GranuFlo and NaturaLyte.

Eventually the FDA issued a class 1 recall on these two products.

One interesting result I found was this article, dated 2009, claiming that acetate buffers are an old-fashioned type of buffer and, on my reading of it, had been replaced. So why were Fresenius still producing these products at all? Well, neither product is dangerous in it's own right, it is the risk of errors when making up the final solutions to administer to patients that is the problem.

Other acid concentrates are primarily just acetic acid. As a PhD chemist I have to point out that the acetic acid in these concentrates will interact with any sodium in the blood to result in sodium acetate being present in solution. Thus the acetate ions are present once again and metabolism to bicarbonate will still occur. Presumably the amount of acetate ions will be so much lower in these cases that the conversion will be much less of a problem.