Cerebrospinal fluid and plasma nitrite and nitrate concentrations after head injury in humans
Cerebrospinal fluid and plasma nitrite and nitrate concentrations after head injury in humans
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DOI：
10.1097/00003246-199607000-00030
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发表时间：
1996-07-01
影响因子：
8.8
通讯作者：
Marion, DW
中科院分区：
文献类型：
--
作者：
Clark, RSB;Kochanek, PM;Marion, DW
目的：测定成人严重闭合性颅脑损伤后脑脊液和血浆亚硝酸盐和硝酸盐浓度作为一氧化氮生成的指标。确定脑脊液和血浆亚硝酸盐和硝酸盐浓度与脑血流量、动脉颈动脉氧含量差异、损伤严重程度和严重闭合性颅脑损伤后预后之间是否存在关联。设计：前瞻性临床研究。环境：多学科重症监护室。患者：在前瞻性、随机评估中度低温（32℃24小时）对闭合性颅脑损伤后神经系统预后的影响时，研究了15例昏迷（格拉斯哥昏迷量表评分小于或等于7分）的严重闭合性颅脑损伤成人患者。低温治疗组7例，常温治疗组8例。干预措施:没有。测量方法及主要结果：患者按顺序进行检查，每12小时一次，连续检查2天。测定脑室内脑脊液亚硝酸盐和硝酸盐浓度。采用（133）氙气静脉注射法测定脑血流。同时取血测定动脉颈静脉氧含量差异及血浆亚硝酸盐和硝酸盐浓度。计算脑氧代谢率。脑脊液亚硝酸盐和硝酸盐浓度在30 ~ 42小时比6 ~ 18小时、18 ~ 30小时和42 ~ 54小时最高（分别为26.4 +/- 3.3比17.3 +/- 2.1、20.0 +/- 2.2和18.8 +/- 2.4 μ M, p < 0.05）。血浆亚硝酸盐和硝酸盐浓度随时间变化无差异。与6 ~ 18 h相比，18 ~ 30 h、30 ~ 42 h和42 ~ 54 h脑血流量增加，颈动脉氧含量差异减小（p < 0.05）。在30至42小时，死亡患者的脑脊液亚硝酸盐和硝酸盐浓度比幸存者高80% （36.4 +/- 3.2 vs. 20.2 +/- 3.6, p < 0.05）。采用广义多元线性回归模型，血浆亚硝酸盐和硝酸盐浓度和损伤严重程度评分独立预测脑脊液亚硝酸盐和硝酸盐浓度（分别p < 0.00001和p = 0.0053）。在该模型中，脑血流和动颈氧含量差异与脑脊液或血浆亚硝酸盐和硝酸盐浓度无关。与常温患者相比，低温患者的脑脊液亚硝酸盐和硝酸盐浓度随时间增加。但是，这种差异发生的地方不能通过多次比较来确定（p = .03）。低温患者入院时格拉斯哥昏迷评分低于常温患者（p = 0.04），损伤严重程度评分高于常温患者（p = 0.09）。结论：脑脊液亚硝酸盐和硝酸盐浓度增高在严重闭合性颅脑损伤后30 ~ 42小时达到高峰。脑脊液亚硝酸盐和硝酸盐浓度的增加在非幸存者中更大。此外，脑脊液和血浆亚硝酸盐和硝酸盐浓度与损伤严重程度评分相关，表明脑内一氧化氮生成增加与损伤严重程度和死亡有关。低温不能阻止脑脊液亚硝酸盐和硝酸盐浓度的升高。需要进一步的研究来确定脑脊液亚硝酸盐和硝酸盐浓度增加的来源，并进一步确定与结果的关系以及低温对这一过程的影响。
Objectives: To measure cerebrospinal fluid and plasma nitrite and nitrate concentrations as indicators of nitric oxide production in adults after severe closed head injury. To determine if there is an association between cerebrospinal fluid and plasma nitrite and nitrate concentrations, and cerebral blood flow, arterio-jugular oxygen content difference, injury severity, and outcome after severe closed head injury.Design: A prospective, clinical study.Setting: Multidisciplinary intensive care unit.Patients: Fifteen comatose (Glasgow Coma Scale score of less than or equal to 7) adult patients with severe closed-head injury were studied during the prospective, randomized evaluation of the effect of moderate hypothermia (32 degrees C for 24 hrs) on neurologic outcome after closed-head injury. Seven patients were in the hypothermic group and eight patients were in the normothermic treatment group.Interventions: None.Measurements and Main Results: Patients were examined sequentially, every 12 hrs for 2 days. Intraventricular cerebrospinal fluid was assayed for nitrite and nitrate concentrations. Cerebral blood flow was measured by the (133)xenon intravenous method. Simultaneous blood samples were obtained for measurements of arterio-jugular oxygen content difference and plasma nitrite and nitrate concentrations. Cerebral metabolic rate for oxygen was calculated. Cerebrospinal fluid nitrite and nitrate concentrations were highest at 30 to 42 hrs vs. 6 to 18, 18 to 30, and 42 to 54 hrs (26.4 +/- 3.3 vs. 17.3 +/- 2.1, 20.0 +/- 2.2, and 18.8 +/- 2.4 mu M, respectively, p < .05). There was no difference over time in plasma nitrite and nitrate concentrations. Cerebral blood flow was increased and arterio-jugular oxygen content difference was reduced at 18 to 30, 30 to 42, and 42 to 54 hrs vs. 6 to 18 hrs (p < .05). At 30 to 42 hrs, cerebrospinal fluid nitrite and nitrate concentrations were 80% higher in patients who died vs. survivors (36.4 +/- 3.2 vs. 20.2 +/- 3.6, p < .05). Using a generalized, multivariate, linear regression model, both plasma nitrite and nitrate concentrations and Injury Severity Score independently predicted cerebrospinal fluid nitrite and nitrate concentrations (p < .00001 and p = .0053, respectively). Cerebral blood flow and arterio-jugular oxygen content difference were not associated with cerebrospinal fluid or plasma nitrite and nitrate concentrations using this model.Cerebrospinal fluid nitrite and nitrate concentrations were in creased over time in hypothermic vs. normothermic patients. But, where this difference occurred could not be determined by multiple comparisons (p = .03). The hypothermic patients had lower admission Glasgow Coma Scale scores than normothermic patients (p = .04) and tended to have higher Injury Severity Scores (p = .09).Conclusions: Increases in cerebrospinal fluid nitrite and nitrate concentrations peaked at 30 to 42 hrs after severe closed-head injury. This increase in cerebrospinal fluid nitrite and nitrate concentrations was greater in nonsurvivors. Also, cerebrospinal fluid and plasma nitrite and nitrate concentrations were associated with Injury Severity Score, suggesting that increased nitric oxide production in the brain is associated with injury severity and death. Hypothermia did not prevent the increase in cerebrospinal fluid nitrite and nitrate concentrations. Further study is required to determine the source of this increase in cerebrospinal fluid nitrite and nitrate concentrations and to further define the relationship to outcome and the effect of hypothermia on this process.