Treatment of hyperammonemia using in-line renal replacement and hyperosmolar therapies within an extracorporeal membrane oxygenation circuit.

After orthotopic lung transplantation, hyperammonemia can be a rare complication secondary to infection by organisms that produce urease or inhibit the urea cycle. This can cause neurotoxicity, cerebral edema, and seizures. Ammonia is unique in that it has a large volume of distribution. However, it is also readily dialyzable given its small molecular weight. As such, removal of ammonia requires renal replacement modalities that can both rapidly remove ammonia from the plasma space and allow for continuous removal to prevent rebound accumulation from intracellular stores. Prevention of iatrogenic osmotic lowering in this setting is required to prevent worsening of cerebral edema. Herein, we describe use of sequential in-line renal replacement therapy using both intermittent hemodialysis and continuous venovenous hemofiltration within an extracorporeal membrane oxygenation circuit in conjunction with higher sodium dialysate and 7.5% hypertonic saline to achieve these treatment goals.

High-efficiency, high-flux in-line hemofiltration using a high blood flow extracorporeal circuit.

The ability of current renal replacement therapy modalities to achieve rapid solute removal is limited by membrane surface area and blood flow rate. Extracorporeal membrane oxygenation offers high blood flow and hemodynamic support that may be harnessed to overcome limitations in traditional renal replacement therapy. Using an extracorporeal membrane oxygenation circuit, we describe a high blood flow, high-efficiency hemofiltration technique using in-line hemofilters (hemoconcentrators) and standard replacement fluid to enhance solute clearance. Using this approach and a total of 5 L of replacement volume per treatment, creatinine (Cr) clearances of 8.3 L/hour and 11.2 L/hour using one and two hemoconcentrators, respectively, were achieved. With use of a high blood flow rate of up to 5 L/min, this hemofiltration technique can potentially offer clearance of 30 times that of continuous renal replacement therapy and of 6 times that of hemodialysis which may expand the ability to remove substances traditionally not considered removable via existing extracorporeal therapies.

Using Electrolyte Free Water Balance to Rationalize and Treat Dysnatremias.

Dysnatremias or abnormalities in plasma [Na+] are often termed disorders of water balance, an unclear physiologic concept often confused with changes in total fluid balance. However, most clinicians clearly recognize that hypertonic or hypotonic gains or losses alter plasma [Na+], while isotonic changes do not modify plasma [Na+]. This concept can be conceptualized as the electrolyte free water balance (EFWB), which defines the non-isotonic components of inputs and outputs to determine their effect on plasma [Na+]. EFWB is mathematically proportional to the rate of change in plasma [Na+] (dPNa/dt) and, therefore, is actively regulated to zero so that plasma [Na+] remains stable at its homeostatic set point. Dysnatremias are, therefore, disorders of EFWB and the relationship between EFWB and dPNa/dt provides a rationale for therapeutic strategies incorporating mass and volume balance. Herein, we leverage dPNa/dt as a desired rate of correction of plasma [Na+] to define a stepwise approach for the treatment of dysnatremias.