Effect of recombinant human erythropoietin on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To evaluate the effect of recombinant human erythropoietin (rHuEPO) on brain injury in the patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB). Methods Forty-five patients with chronic valvular heart disease, aged 36-62 yr, weighing 42-92 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association of Ⅱ or Ⅲ, undergoing cardiac valve replacement with CPB, were randomly divided into 3 groups (n=15 each) using a random number table: control group (group C), and different doses of rHuEPO groups (EPO1 group, EPO2 group). In EPO1 and EPO2 groups, rHuEPO 40 and 80 IU/kg were injected intravenously before anesthesia induction, respectively.Before anesthesia induction (T0, baseline value), immediately after endotracheal intubation (T1), immediately after aortic cannulation (T2), immediately after cannulation of superior and inferior vena cava (T3), immediately after the beginning of CPB (T4), when each index was decreased to the minimal value during CPB (T5), after rewarming to 36.5 ℃ (T6), immediately after termination of CPB (T7), and at 1 h after termination of CPB (T8), regional cerebral oxygen saturation (rSO2), tissue hemoglobin index (THI), and changes in concentrations of oxyhemoglobin(△O2Hb), deoxyhemoglobin (△HHb) and total hemoglobin (△cHb) in bilateral frontal lobes were recorded.The patients whose minimal rSO2 ≤50% and decrease in minimal rSO2 ≥20% of the baseline value (△rSO2) were recorded.At T0, T8 and 2 h after termination of CPB (T9), venous blood samples were taken for determination of serum concentrations of S100 protein and neuron-specific enolase (NSE) by ELISA.At 1 day before surgery and 8 days after surgery, the patient's cognitive function was assessed using Mini-Mental State Examination, the Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Digit Symbol subtest of the WAIS-R, the Trailing Making Test (Part A) and the Stroop Color Word Interference Test, while depression and anxiety were assessed by Zung Self-Rating Depression Scale and Zung Self-Rating Anxiety Scale, respectively.The occurrence of postoperative cognitive dysfunction was recorded. Results There was no significant difference among the three groups in bilateral rSO2 and △cHb, incidence of bilateral rSO2 ≤50% and postoperative cognitive dysfunction, Zung Self-Rating Depression Scale score, and Zung Self-Rating anxiety Scale score at each time point (P>0.05). Compared with group C, the incidence of left △rSO2≥20% was significantly decreased, the right △O2Hb was increased at T6, 8, the serum NSE concentrations were decreased at T9, the serum S100 protein concentrations were decreased at T8, and the number of the Digit Symbol subtest of the WAIS-R completed was increased in group EPO1, and right THI was significantly decreased at T2, T3, T5, T7 and T8, right △HHb was increased at T2 and T3, and the completion time of Stroop color word interference test B was shortened at 8 days after surgery in group EPO2 (P<0.05 or 0.01). Compared with group EPO1, the incidence of left △rSO2≥20% was significantly increased, the right THI was decreased at T2-4 and T6-8, and the left △O2Hb at T6-7 and right △O2Hb at T8 were decreased in group EPO2 (P<0.05). Conclusion rHuEPO 40 IU/kg injected intravenously before induction of anesthesia can mitigate brain injury in the patients undergoing cardiac valve replacement with CPB. Key words: Erythropoietin, recombinant; Brain injuries; Cardiopulmonary bypass; Heart valve prosthesis implantation