Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy

Abstract

According to clinical investigations, early postoperative cognitive dysfunction is the most common adverse event in pediatric patients after tonsillectomy. A previous study has indicated that dexmedetomidine (DEX) is an efficient drug for the treatment of postoperative cognitive dysfunction. However, the efficacy of DEX in alleviating early postoperative cognitive dysfunction in pediatric patients following tonsillectomy has remained elusive, which was therefore assessed in the present study. A total of 186 children presenting with cognitive dysfunction subsequent to tonsillectomy were recruited to analyze the efficacy of DEX. Patients were randomly divided into two groups and received intravenous treatment with DEX (n=112) or placebo (n=74). Duration of treatment, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of DEX were evaluated in a preliminary experiment. The improvement of postoperative cognitive function in children with tonsillectomy was analyzed with a Mini-Mental State Examination (MMSE) following treatment with DEX. A 40-item quality of life (MONEX-40) questionnaire was used to assess the efficacy of DEX. The plasma levels of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), neuron-specific enolase (NSE), C-reactive protein (CRP), cortisol and melatonin were also analyzed. The preliminary experiment determined that the DLT was 10 mg/kg and the MTD was 15 mg/kg. In the major clinical trial, it was revealed that MMSE scores in the DEX treatment group were markedly improved, indicating that DEX had a beneficial effect in pediatric patients with early postoperative cognitive dysfunction after tonsillectomy. In addition, IL-1and TNF-α were downregulated, while IL-6 and SOD were upregulated in patients with cognitive dysfunction after treatment with DEX compared with those in the placebo group. Furthermore, DEX treatment markedly decreased the serum levels of CRP, NSE cortisol and melatonin, which are associated with the occurrence of postoperative cognitive dysfunction in pediatric patients following tonsillectomy. In conclusion, intravenous administration of DEX at a dose of 10 mg/kg improves postoperative cognitive function in pediatric patients with tonsillectomy by decreasing the serum levels of inflammatory factors and stress-associated signaling molecules. Trial registration no. QLSDHOS0200810102C (Qilu Hospital of Shandong University, Jinan, China).

Keywords: dexmedetomidine; inflammation; postoperative cognitive dysfunction; tonsillectomy.

Figure 1.

Evaluation the effects of DEX on cognitive dysfunction using MMSE scores. **P<0.01 vs. control. MMSE, Mini Mental State Examination; DEX, dexmedetomidine; ns, not significant.

Figure 2.

Analysis of efficacy of DEX on improvement of postoperative complications in children with tonsillectomy. **P<0.01 vs. control. DEX, dexmedetomidine; ns, not significant.

Figure 3.

Analysis of efficacy of DEX on NSE plasma concentration after an 8-week treatment period. **P<0.01 vs. control. DEX, dexmedetomidine; NSE, neuron-specific enolase; ns, not significant.

Figure 4.

Detection of CRP plasma concentration levels between DEX and placebo groups. **P<0.01 vs. control. DEX, dexmedetomidine; CRP, C-reactive protein; ns, not significant.

Figure 5.

Changes of melatonin serum levels in pediatric patients with post-operative cognitive dysfunction after DEX treatment. **P<0.01 vs. control. DEX, dexmedetomidine; ns, not significant.

Figure 6.

Analysis of efficacy of DEX in regulating the cortisol plasma concentration. **P<0.01 vs. control. DEX, dexmedetomidine; ns, not significant.

Figure 7.

Clinical analysis of IL-6 plasma levels after DEX treatment. **P<0.01 vs. control. DEX, dexmedetomidine; IL, interleukin; ns, not significant.

Figure 8.

Clinical analysis of IL-1 plasma levels after DEX treatment. **P<0.01 vs. control. DEX, dexmedetomidine; IL, interleukin; ns, not significant.

Figure 9.

Analysis of the effect of DEX on the plasma concentration of TNF-α. **P<0.01 vs. control. DEX, dexmedetomidine; TNF, tumor necrosis factor; ns, not significant.

Figure 10.

Analysis of the effect of DEX on the plasma concentration of SOD. **P<0.01 vs. control. DEX, dexmedetomidine; SOD, superoxide dismutase; ns, not significant.