Respiratory and metabolic acidosis correction with the ADVanced Organ Support system

Abstract

Background

The lung, the kidney, and the liver are major regulators of acid-base balance. Acidosis due to the dysfunction of one or more organs can increase mortality, especially in critically ill patients. Supporting compensation by increasing ventilation or infusing bicarbonate is often ineffective. Therefore, direct removal of acid may represent a novel therapeutic approach. This can be achieved with the ADVanced Organ Support (ADVOS) system, an enhanced renal support therapy based on albumin dialysis. Here, we demonstrate proof of concept for this technology.

Methods

An ex vivo model of either hypercapnic (i.e., continuous CO ₂ supply) or lactic acidosis (i.e., lactic acid infusion) using porcine blood was subjected to hemodialysis with ADVOS. A variety of operational parameters including blood and dialysate flows, different dialysate pH settings, and acid and base concentrate compositions were tested. Comparisons with standard continuous veno-venous hemofiltration (CVVH) using high bicarbonate substitution fluid and continuous veno-venous hemodialysis (CVVHD) were also performed.

Results

Sixty-one milliliters per minute (2.7 mmol/min) of CO ₂ was removed using a blood flow of 400 ml/min and a dialysate pH of 10 without altering blood pCO ₂ and HCO ₃ ⁻ (36 mmHg and 20 mmol/l, respectively). Up to 142 ml/min (6.3 mmol/min) of CO ₂ was eliminated if elevated pCO ₂ (117 mmHg) and HCO ₃ ⁻ (63 mmol/l) were allowed. During continuous lactic acid infusion, an acid load of up to 3 mmol/min was compensated. When acidosis was triggered, ADVOS multi normalized pH and bicarbonate levels within 1 h, while neither CVVH nor CVVHD could. The major determinants to correct blood pH were blood flow, dialysate composition, and initial acid-base status.

Conclusions

In conclusion, ADVOS was able to remove more than 50% of the amount of CO ₂ typically produced by an adult human. Blood pH was maintained stable within the physiological range through compensation of a metabolic acid load by albumin dialysate. These in vitro results will require confirmation in patients.