Is the Delivery of Hydrogen-Peroxide With Dialysate for Oxygenation of Blood Efficient and Safe?

To the Editor: It is with surprised disbelief that I read the study regarding the delivery of hydrogen-peroxide (H2O2, 34 g/mol) for oxygenation of blood during hemodialysis.1 This is reminiscent of a recent recommendation to use bleach, another strong oxidant and disinfectant, for the treatment of coronavirus disease 2019 (COVID-19). Although the combination of both efficient hemodialysis and extracorporeal membrane oxygenation within one system is certainly desirable, the use of H2O2 in dialysate is inefficient and dangerous. A closer look at O2 mass balance reveals the limited efficiency of this mode of O2 delivery:1 the maximum H2O2 concentration of 0.34 mmol/L (=0.0116/34) which avoids profuse generation of gas bubbles delivers 0.17 mmol or about 3.8 ml (=22,414 × 0.00017) of O2 per L of dialysate. This is sufficient to increase the O2 saturation in 54 g (=0.6 × 0.3 × 300) of hemoglobin in the test blood by only 5.3% (=3.8/1.34/54), in contrast to more than twice the O2 saturation increase of 13.1% (=96.5–83.4) reported within 1 h of equilibration in the “3%” study (Table 1). The difference in oxygenation must have originated from 4.96 ml O2 (=0.031 × 160) dissolved in dialysate and probably also from O2 diffusing into the system because the experiment was conducted under ambient conditions and O2 partial pressures of 160 mm Hg. Notice that the amount of physically dissolved O2 is comparable to that provided by the decomposition of H2O2. The amount of physically dissolved O2 could, however, be significantly increased further if dialysate were equilibrated with pure O2.2 But this was not studied. The O2 flow of about 3.8 ml/min obtained from H2O2 even when delivered with very high dialysate flows in the range of 1,000 ml/min is therefore largely insufficient and covering only about 1–2% of the O2 requirements in adults. The decomposition of H2O2 in dialysate equilibrated with ambient air produces a supersaturated, unstable O2 solution which will form gas bubbles at suitable nucleation sites, most likely at or within the rough and porous dialyzer membrane. This, however, interferes with transmembrane solute transport. Moreover, gas bubbles are thrombogenic. Microbubbles cannot be prevented from entering the systemic circulation and are suspected to cause various problems in dialysis.3 H2O2 is about half the mass of urea with a close to 30% higher diffusivity than urea. H2O2 must therefore be expected to more easily diffuse across the dialyzer membrane than urea. Even if the general toxicity of H2O2 has been revisited in recent literature, the rationale for exogenous administration of H2O2 must be questioned especially in kidney disease patients exposed to considerable oxidative stress, due to both antioxidant depletion as well as to increased production of highly reactive oxygen species.4 It therefore has been suggested to reduce oxidative stress and to equilibrate dialysate with molecular hydrogen as antioxidant and anti-inflammatory agent5. The addition of a highly reactive oxygen species such as H2O2 to dialysate is therefore not only expected to augment oxidative stress known to be associated with complications such as hypertension, atherosclerosis, inflammation, and anemia, but also to affect treatment safety because of gas bubble formation, and all of that with insufficient O2 delivery.