Clark R S, Kochanek P M, Obrist W D, Wong H R, Billiar T R, Wisniewski S R, Marion D W
Department of Anesthesiology, Safar Center for Resuscitation Research, University of Pittsburgh, PA 15260, USA.
Crit Care Med. 1996 Jul;24(7):1243-51. doi: 10.1097/00003246-199607000-00030.
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.
A prospective, clinical study.
Multidisciplinary intensive care unit.
Fifteen comatose (Glasgow Coma Scale score of < or = 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.
None.
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 133xenon 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 microM, 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 increased 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).
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.
测量严重闭合性颅脑损伤成年患者脑脊液和血浆中亚硝酸盐和硝酸盐的浓度，作为一氧化氮生成的指标。确定脑脊液和血浆中亚硝酸盐和硝酸盐浓度与脑血流量、动静脉氧含量差、损伤严重程度及严重闭合性颅脑损伤后预后之间是否存在关联。
一项前瞻性临床研究。
多学科重症监护病房。
在对中度低温（32℃，持续24小时）对闭合性颅脑损伤后神经功能预后影响的前瞻性随机评估中，研究了15例昏迷（格拉斯哥昏迷量表评分≤7分）的严重闭合性颅脑损伤成年患者。7例患者在低温组，8例患者在常温治疗组。
无。
对患者进行连续检查，为期2天，每12小时检查一次。检测脑室内脑脊液中亚硝酸盐和硝酸盐的浓度。采用133氙静脉注射法测量脑血流量。同时采集血样，测量动静脉氧含量差以及血浆中亚硝酸盐和硝酸盐的浓度。计算脑氧代谢率。脑脊液中亚硝酸盐和硝酸盐浓度在30至42小时时最高，与6至18小时、18至30小时以及42至54小时相比（分别为26.4±3.3 vs. 17.3±2.1、20.0±2.2和18.8±2.4μM，p<0.05）。血浆中亚硝酸盐和硝酸盐浓度随时间无差异。与6至18小时相比，在18至30小时、30至42小时以及42至54小时时脑血流量增加，动静脉氧含量差降低（p<0.05）。在30至42小时时，死亡患者脑脊液中亚硝酸盐和硝酸盐浓度比存活患者高80%（36.4±3.2 vs. 20.2±3.6，p<0.05）。使用广义多元线性回归模型，血浆中亚硝酸盐和硝酸盐浓度以及损伤严重程度评分均独立预测脑脊液中亚硝酸盐和硝酸盐浓度（分别为p<0.00001和p = 0.0053）。使用该模型，脑血流量和动静脉氧含量差与脑脊液或血浆中亚硝酸盐和硝酸盐浓度无关。与常温患者相比，低温患者脑脊液中亚硝酸盐和硝酸盐浓度随时间升高。但是，这种差异出现的时间点无法通过多重比较确定（p = 0.03）。低温患者入院时格拉斯哥昏迷量表评分低于常温患者（p = 0.04），且损伤严重程度评分有更高的趋势（p = 0.09）。
严重闭合性颅脑损伤后，脑脊液中亚硝酸盐和硝酸盐浓度在30至42小时达到峰值。非存活者脑脊液中亚硝酸盐和硝酸盐浓度的升高幅度更大。此外，脑脊液和血浆中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及死亡相关。低温并不能阻止脑脊液中亚硝酸盐和硝酸盐浓度的升高。需要进一步研究以确定脑脊液中亚硝酸盐和硝酸盐浓度升高的来源，并进一步明确其与预后的关系以及低温对此过程的影响。
