Naloxone lowers cerebrospinal fluid levels of excitatory amino acids after thoracoabdominal aortic surgery.
OBJECTIVE
Although naloxone has been used to prevent ischemic spinal cord injury (SCI), its effect on excitatory amino acids (EAAs) has not been understood. We investigated the clinical significance of naloxone by measuring EAAs in the cerebrospinal fluid (CSF) in patients undergoing thoracoabdominal aortic surgery.


METHODS
Twenty-seven patients (15 men and 12 women; mean age, 66 +/- 12 years) undergoing prosthetic replacement of the thoracoabdominal aorta (n = 19) or the descending thoracic aorta (n = 8) from April 1997 to June 2003 under distal perfusion and mild hypothermia were enrolled in this cohort study with historical controls. Their etiology was 7 dissections and 20 nondissections. In 16 patients (naloxone group), intravenous infusion of naloxone (1 microg/kg/h) was continued until the patients became alert. In the remaining 11 patients (control group) naloxone was not given. CSF drainage was used in all patients. CSF levels of EAAs, glutamate, aspartate, and glycine were measured at 6 points in time until 72 hours postoperatively, using a high-performance liquid chromatography method.


RESULTS
In 5 patients with SCI (2 patients in control group, 3 in naloxone group), CSF levels of glutamate and glycine continued to increase even at 72 hours postoperatively, and were significantly more elevated than those in patients without SCI ( P < .0001, glutamate; P = .0006, glycine). Postoperative maximum levels of CSF glutamate and glycine were also significantly higher in patients with postoperative SCI than in patients without SCI (glutamate: 215.3% +/- 158.6% vs 32.9% +/- 37.3% increase from baseline, P < .0001; glycine: 309.1% +/- 218.2% vs 89.2% +/- 103.1% increase from baseline, P = .0036). CSF levels of glutamate and aspartate in naloxone group were significantly lower than those in control group ( P = .0161, glutamate; P < .0001, aspartate). Postoperative maximum level of CSF aspartate was also significantly lower in the naloxone group than in the control group (8.3% +/- 75.5% vs 119.7% +/- 120.6% increase from baseline, P = .0077). In multivariate logistic regression analysis, postoperative maximum CSF glutamate >100% from baseline ( P < .001) and postoperative maximum level of CSF glycine ( P = .005)were identified as the independent risk factors for SCI. Both SCI ( P < .001) and postoperative maximum level of CSF glycine ( P = .005) were the independent predictors for postoperative maximum level of CSF glutamate >100% from baseline.


CONCLUSIONS
CSF levels of EAAs are elevated in patients with SCI. CSF glutamate is the strongest independent predictor of SCI. Naloxone is effective in lowering CSF levels of EAAs.
Department of Cardiovascular Surgery, Hokkaido University Hospital, Sapporo, Japan. kunihara@med.hokudai.ac.jp
Takashi
T
Kunihara
Kenji
K
Matsuzaki
Norihiko
N
Shiiya
Yasuaki
Y
Saijo
Keishu
K
Yasuda
D000328:Adult; D000368:Aged; D000784:Aortic Dissection / Q000601:surgery; D001012:Aorta, Abdominal / Q000601:surgery; D001013:Aorta, Thoracic / Q000601:surgery; D001014:Aortic Aneurysm / Q000601:surgery*; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects*; D015331:Cohort Studies; D018846:Excitatory Amino Acids / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
D018846:Excitatory Amino Acids; D009292:Narcotic Antagonists; D009270:Naloxone