CEREBROSPINAL-FLUID AND PLASMA NITRITE AND NITRATE CONCENTRATIONS AFTER HEAD-INJURY IN HUMANS

Objectives: To measure cerebrospinal fluid and plasma nitrite and nitr ate concentrations as indicators of nitric oxide production in adults after severe closed head injury. To determine if there is an associati on between cerebrospinal fluid and plasma nitrite and nitrate concentr ations, and cerebral blood flow, arterio-jugular oxygen content differ ence, injury severity, and outcome after severe closed head injury. De sign: A prospective, clinical study. Setting: Multidisciplinary intens ive care unit. Patients: Fifteen comatose (Glasgow Coma Scale score of less than or equal to 7) adult patients with severe closed-head injur y were studied during the prospective, randomized evaluation of the ef fect of moderate hypothermia (32 degrees C for 24 hrs) on neurologic o utcome after closed-head injury. Seven patients were in the hypothermi c group and eight patients were in the normothermic treatment group. I nterventions: None. Measurements and Main Results: Patients were exami ned sequentially, every 12 hrs for 2 days. Intraventricular cerebrospi nal fluid was assayed for nitrite and nitrate concentrations. Cerebral blood flow was measured by the (133)xenon intravenous method. Simulta neous blood samples were obtained for measurements of arterio-jugular oxygen content difference and plasma nitrite and nitrate concentration s. Cerebral metabolic rate for oxygen was calculated. Cerebrospinal fl uid 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 t o 18 hrs (p < .05). At 30 to 42 hrs, cerebrospinal fluid nitrite and n itrate concentrations were 80% higher in patients who died vs. survivo rs (36.4 +/- 3.2 vs. 20.2 +/- 3.6, p < .05). Using a generalized, mult ivariate, linear regression model, both plasma nitrite and nitrate con centrations and Injury Severity Score independently predicted cerebros pinal fluid nitrite and nitrate concentrations (p < .00001 and p = .00 53, respectively). Cerebral blood flow and arterio-jugular oxygen cont ent difference were not associated with cerebrospinal fluid or plasma nitrite and nitrate concentrations using this model. Cerebrospinal flu id nitrite and nitrate concentrations were in creased over time in hyp othermic vs. normothermic patients. But, where this difference occurre d could not be determined by multiple comparisons (p = .03). The hypot hermic patients had lower admission Glasgow Coma Scale scores than nor mothermic patients (p = .04) and tended to have higher Injury Severity Scores (p = .09). Conclusions: Increases in cerebrospinal fluid nitri te and nitrate concentrations peaked at 30 to 42 hrs after severe clos ed-head injury. This increase in cerebrospinal fluid nitrite and nitra te concentrations was greater in nonsurvivors. Also, cerebrospinal flu id and plasma nitrite and nitrate concentrations were associated with Injury Severity Score, suggesting that increased nitric oxide producti on in the brain is associated with injury severity and death. Hypother mia did not prevent the increase in cerebrospinal fluid nitrite and ni trate concentrations. Further study is required to determine the sourc e of this increase in cerebrospinal fluid nitrite and nitrate concentr ations and to further define the relationship to outcome and the effec t of hypothermia on this process.