Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Pediatr Crit Care Med. 2012 May;13(3):328-37. doi: 10.1097/PCC.0b013e31822f18f9.
Infants are potentially more susceptible to cell death mediated via glutamate excitotoxicity attributed to cardiopulmonary bypass. We hypothesized that ketamine, via N-methyl D-aspartate receptor blockade and anti-inflammatory effects, would reduce central nervous system injury during cardiopulmonary bypass.
We randomized 24 infants, without chromosomal abnormalities, to receive ketamine (2 mg/kg, n = 13) or placebo (saline, n = 11) before cardiopulmonary bypass for repair of ventricular septal defects. Plasma markers of inflammation and central nervous system injury were compared at the end of surgery, and 6, 24, and 48 hrs after surgery. Magnetic resonance imaging and spectroscopy before cardiopulmonary bypass and at the time of hospital discharge were performed in a subset of cases and controls (n = 5 in each group). Cerebral hemodynamics were monitored postoperatively using near-infrared spectroscopy, and neurodevelopmental outcomes were assessed using Bayley Scales of Infant Development-II before and 2-3 wks after surgery.
Statistically significant differences were noted in preoperative inspired oxygen levels, intraoperative cooling and postoperative temperature, respiratory rate, platelet count, and bicarbonate levels. The peak concentration of C-reactive protein was lower in cases compared to controls at 24 hrs (p = .048) and 48 hrs (p = .001). No significant differences were noted in the expression of various cytokines, chemokines, S100, and neuron-specific enolase between the cases and controls. Magnetic resonance imaging with spectroscopy studies showed that ketamine administration led to a significant decrease in choline and glutamate plus glutamine/creatine in frontal white matter. No statistically significant differences occurred between pre- and postoperative Bayley Scales of Infant Development-II scores.
We did not find any evidence for neuroprotection or neurotoxicity in our pilot study. A large, adequately powered randomized control trial is needed to discern the central nervous system effect of ketamine on the developing brain. brain.
The trial is registered at www.ClinicalTrials.gov, NCT00556361.
由于体外循环，婴儿可能更容易受到谷氨酸兴奋毒性介导的细胞死亡的影响。我们假设氯胺酮通过 NMDA 受体阻断和抗炎作用，将减少体外循环期间中枢神经系统损伤。
我们将 24 名无染色体异常的婴儿随机分为氯胺酮（2mg/kg，n=13）或安慰剂（生理盐水，n=11）组，在体外循环修复室间隔缺损前接受治疗。在手术结束时、手术后 6、24 和 48 小时比较两组血浆炎症和中枢神经系统损伤标志物。对部分病例和对照组（每组 5 例）进行了体外循环前和出院时的磁共振成像和光谱检查。术后使用近红外光谱监测脑血流动力学，术后使用贝利婴幼儿发育量表-II 评估神经发育结局。
术前吸入氧水平、术中降温与术后体温、呼吸频率、血小板计数和碳酸氢盐水平存在统计学差异。与对照组相比，病例组在术后 24 小时（p=0.048）和 48 小时（p=0.001）时 C 反应蛋白的峰值浓度较低。病例组与对照组之间各种细胞因子、趋化因子、S100 和神经元特异性烯醇化酶的表达无显著差异。磁共振成像和光谱研究显示，氯胺酮给药导致额叶白质中胆碱和谷氨酸+谷氨酰胺/肌酐显著减少。术后贝利婴幼儿发育量表-II 评分与术前无统计学差异。
在我们的初步研究中，我们没有发现任何神经保护或神经毒性的证据。需要一项大型、充分的随机对照试验来确定氯胺酮对发育中大脑的中枢神经系统效应。
该试验在 www.ClinicalTrials.gov 注册，NCT00556361。
