BACKGROUND: 

Haptoglobin may reduce hemolysis-induced kidney injury in patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Haptoglobin may be given empirically when hemolytic urine is observed, or pre-emptively when detected by elevated free hemoglobin concentrations. In the present study, we investigated whether pre-emptive haptoglobin therapy guided by serum-free hemoglobin concentrations could prevent postoperative renal dysfunction in patients who underwent major cardiovascular surgery using CPB.

METHODS: 

This study was a single-center, open-label, randomized controlled trial. Adult patients who underwent major cardiovascular surgery using CPB were included. Serum-free hemoglobin concentrations were measured in all patients who consented for this study. Patients with free hemoglobin concentrations that reached 0.05 g/dL were randomized to either (i) pre-emptive haptoglobin therapy group or (ii) standard of care group. Patients in the pre-emptive haptoglobin therapy group were administered 4000 U of haptoglobin when serum-free hemoglobin concentration reached 0.05 g/dL within 2 hours after the start of CPB. In the standard of care group, 4000 U of haptoglobin was administered when hemolytic urine was confirmed after the start of CPB. The primary outcome was the difference between the preoperative creatinine concentration and the maximum creatinine concentration within 48 hours after surgery (ΔCr).

RESULTS: 

The study was terminated with the results of interim analysis due to patients’ safety concerns. Finally, 34 patients in the pre-emptive haptoglobin therapy group and 33 in the standard of care group were included in the analysis. Median (interquartile range) ΔCr values were 0.20 (0.05–0.44) in the pre-emptive haptoglobin therapy group and 0.14 (0.04–0.19) in the standard of care group (P = .05). Multiple linear regression analysis with ΔCr as objective variable and preoperative estimated glomerular filtration rate (eGFR), age, and randomize group as explanatory variables revealed that pre-emptive administration of haptoglobin significantly increased ΔCr (P = .03).

CONCLUSIONS: 

The interim study results demonstrated that in patients undergoing major cardiovascular surgery using CPB, pre-emptive haptoglobin administration worsened Cr values and independently associated with increased ΔCr.