Erythropoietin (EPO) stimulating agents are known as alternatives to transfusion. However, they expose patients to thrombosis and are expensive. A phenomenon, “the normobaric oxygen paradox” (NOP), has been described. A transient hyperoxia followed by a prolonged return to normoxia acts as an effective trigger for EPO production. The mechanism depends on free O2 radicals and on reduced gluthatione (GSH) availabilities. Also, N–acetylcystein (NAC) is known to regenerate the stock of GSH. Our study sought to determine whether a NOP regime administered alongside NAC could produce an increase in reticulocyte count via an increase of EPO production, in patients undergoing oncological abdominal surgery.Prospective, controlled trial randomized 78 patients in 3 parallel groups. The first group (NOP) received 60% oxygen for two hours on days 1,3 and 5 postoperatively via a venti–mask. The second group (NOP+NAC), in addition to the NOP oxygen regime, received 300 mg IV once a day of N–acetyl–cysteine (NAC) on the first day postoperatively and 200 mg orally once a day until the fifth day post–op. The third group received neither NOP nor NAC. On postoperative day 6, reticulocytes were measured and compared to the baseline values. The 95 percent confidence intervals of the mean percentage change from baseline revealed, that the increase in reticulocyte counts was statistically significant for the NOP Group and NOP+NAC Group, whereas it was not significant for the control group.

These data suggest that relative hypoxia by means of oxygen gradient is an effective stimulus for reticulocyte production.