Pathophysiology of hemodialysis-associated hypoxemia

The dialysis patient treated intermittently on a three-times-weekly schedule is exposed during the short dialysis period (4 hours) to abrupt changes in the internal milieu. During the 44 hours of the interdialytic period, H+ ions accumulate slowly, causing respiratory-compensated (hyperventilation) metabolic acidosis in the patient at the start of dialysis. The arterial bicarbonate concentration (HCO3-) is between 17 and 23 mEq/L and a relatively low arterial carbon dioxide tension (PaCO2) of 33-36 mm Hg is observed. Four hours later, after exposure to a biocompatible (polyacrylonitrile) or bioincompatible membrane (cuprophane) and a bicarbonate or acetate dialysis bath, the patient reaches metabolic alkalosis after mild to moderate hypoventilation, with or without breathing irregularities. Defined another way, the dialysis patient is an acid accumulator for 44 hours, after which a 4-hour period of efficient retitration occurs that is accompanied by a variable degree of hypoxemia. The latter phenomenon has been the subject of numerous investigations during the past 10 years. As happens with complex biologic processes, the conclusions reached by the various investigators are conflicting, depending on their viewpoint and the variables they examined. Since Sherlock in 1977 showed that patients dialyzed with an acetate-containing dialysate became hypoxemic and attributed it to hypoventilation after carbon dioxide (CO2) losses through the dialyzer, a number of other mechanisms have been proposed, defended by some and questioned by others. The purpose of this short overview is to evaluate critically the various proposed mechanisms, showing the minor role played by some and defining the respective roles of the two principal mechanisms, i.e., CO2 unloading, and the complement activation-hypoxemia cascade.