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Effects of induced relative hypoxia during the postoperative period of abdominal oncologic surgery, on hemoglobin and reticulocyte levels: a prospective, randomized controlled clinical trial


Anemia is a frequent complication in oncologic patients. Erythropoietin (EPO) stimulating agents are known as alternatives to transfusion. However, they expose patients to thrombosis and are expensive. Recently, a new phenomenon, the normobaric oxygen paradox (NOP), has been described. In brief, transient hyperoxia followed by a prolonged return to normoxia acts as an effective trigger for EPO production. The mechanism depends on free oxygen radicals and on reduced glutathione (GSH) availabilities. Also, N-acetylcystein (NAC) is known to regenerate the stock of GSH. Very few clinical trials have investigated this phenomenon [1]. The goal of this study was to test the NOP theory on the evolution of hemoglobin and reticulocytes in patients receiving intermittent oxygen with or without NAC compared to a control group.


This prospective, randomized study included 78 patients (three groups). The first group (G1; n = 26) received 60% FiO2 for 2 consecutive hours on the first, third, and fifth days postoperatively. The second group (G2; n = 26) in addition to oxygen received NAC 200 mg/day for 5 days. The third group (G3; n = 26) was the control group which did not receive any oxygen variation. On postoperative day 6, hemoglobin, hematocrit and reticulocytes were measured and compared to the baseline values. A total of five patients (three in G1 and two in G2) were excluded for discontinuing oxygen and/or early discharge from hospital.


The reticulocyte count in G1 showed statistically different values compared to G2 and G3. These findings correlate with other clinical trials [2]. The fact that no statistical difference of hemoglobin level was recorded could be attributed to the lack of follow-up after patient discharge (postoperative day 6). See Figure 1.



Induced relative hypoxia seems to be an effective stimulus for reticulocyte synthesis. However, further investigations are needed to confirm these findings and their impact on hemoglobin.


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Correspondence to M Khalife.

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Khalife, M., Wiams, K., Ben Aziz, M. et al. Effects of induced relative hypoxia during the postoperative period of abdominal oncologic surgery, on hemoglobin and reticulocyte levels: a prospective, randomized controlled clinical trial. Crit Care 16, P262 (2012).

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  • Erythropoietin
  • Reduce Glutathione
  • Free Oxygen Radical
  • Oncologic Patient
  • Free Oxygen