Ulinastatin May Significantly Improve Postoperative Cognitive Function of Elderly Patients Undergoing Spinal Surgery by Reducing the Translocation of Lipopolysaccharide and Systemic Inflammation

Abstract

Background: Studies have shown that perioperative inflammatory response is one of the important factors that caused postoperative cognitive dysfunction (POCD). Ulinastatin is a broad-spectrum protease inhibitor that inhibits inflammatory. We investigated the effects of ulinastatin on inflammatory response and early postoperative cognitive function in elderly patients undergoing spinal surgery. Methods: This clinical trial was approved by the Xuanwu Hospital Ethical Committee (Registration number: ChiCTR-IPR-16008931). Sixty elderly patients undergoing elective spinal surgery with American Society of Anesthesiologists (ASA) status of I-II were randomized into ulinastatin and control groups; total intravenous anesthesia was performed. The elderly patients in ulinastatin group underwent intravenous infusion of ulinastatin 10,000 units/kg following anesthesia induction and before surgical incision, and 5000 units/kg on post-operative days 1 and 2. Cognitive function was determined with Montreal Cognitive Assessment (MOCA) test preoperatively and on post-operative day 7 by a neurologist. Serum lipopolysaccharide (LPS), interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloprotease-9 (MMP-9) concentration levels were measured at baseline, the end of surgery, and on post-operative days 1 and 3. Results: All elderly patients completed the study. Ulinastatin infusion significantly reduced the incidence of POCD in elderly patients undergoing spine surgery (ulinastatin group 16% vs. control group 43%, χ ² = 5.079, P = 0.024, P < 0.05). The elderly patients in ulinastatin group exhibited lower serum LPS, IL-6, CRP, and MMP-9 concentrations, as well as a shortened peak value duration, compared with those in the control group following surgery (P < 0.05). Conclusion: Systemic inflammation and translocation of LPS were inhibited by the infusion of ulinastatin in elderly patients undergoing spinal surgery. The anti-inflammation intervention with ulinastatin can significantly improve the elderly patients' postoperative cognitive function.

Keywords: POCD; elderly patients; lipopolysaccharide; spine surgery; systemic inflammation; ulinastatin.

FIGURE 1

The patient recruitment flow chat.

FIGURE 2

IL-6 concentrations over time. IL-6, interleukin-6; Group C, the control group; Group U, the ulinastatin group. ^∗P < 0.05 from T0 in group C and group U (statistically significant), #P < 0.05 from group U (statistically significant). T0, = before skin incision, T1 = the end of operation, and T2 and T3 = 24 and 72 h postoperative.

FIGURE 3

CRP concentrations over time. CRP, C-reactive protein; Group C, the control group; Group U, the ulinastatin group. ^∗P < 0.05 from T0 in group C and group U (statistically significant), #P < 0.05 from group U (statistically significant). T0 = before skin incision, T1 = the end of operation, and T2 and T3 = 24 and 72 h postoperative.

FIGURE 4

MMP-9 concentrations over time. MMP-9, matrix metalloprotease-9; Group C, the control group; Group U, the ulinastatin group. ^∗P < 0.05 from T0 in group C and group U (statistically significant), #P < 0.05 from group U (statistically significant). T0 = before skin incision, T1 = the end of operation, and T2 and T3 = 24 and 72 h postoperative.

FIGURE 5

LPS concentrations over time. LPS, lipopolysaccharide; Group C, the control group; Group U, the ulinastatin group. ^∗P < 0.05 from T0 in group C and group U (statistically significant), #P < 0.05 from group U (statistically significant). T0 = before skin incision, T1 = the end of operation, and T2 and T3 = 24 and 72 h postoperative.