Hyperammonemia following intravenous valproate loading.
BACKGROUND
Valproic acid (VPA) has been associated with hyperammonemia with and without encephalopathy. We report the frequent but transient nature of hyperammonemia following intravenous (IV) administration of loading doses of VPA.


METHODS
Forty participants received a VPA loading dose (20 or 30 mg/kg) at 6 or 10mg/kg/min. All participants were monitored for signs of systemic and local intolerance. Serum VPA level, ammonia, complete blood count, bilirubin, transaminases, pancreatic enzymes, and level of consciousness were obtained at baseline, 1 and 24h after administration. Changes in ammonia levels were assessed using repeated-measures ANOVA.


RESULTS
Asymptomatic hyperammonemia occurred in 30 of 40 participants at 1h post-VPA infusion. Majority of the participants (66%) demonstrated decreasing ammonia concentrations at 24h post-infusion. Multivariable repeated-measures analysis indicates the lack of influence of VPA dose (p=0.8), VPA levels (p>0.24, all time points), infusion rate (p=0.41) and gender (0.68) on ammonia levels across time. Age (p=0.015), time since dosing (p=0.017) and co-therapy with enzyme-inducing antiepileptic drugs (p=0.035) were significant predictors of changes in ammonia levels.


CONCLUSIONS
Hyperammonemia is a frequent but transient finding following intravenous administration of loading doses of VPA. Hyperammonemia was not associated with alteration in consciousness or hepatic transaminases.
DeWolfe
Jennifer L
JL
University of Alabama at Birmingham Epilepsy Center, Department of Neurology, 1719 6th Avenue South, CIRC 312, Birmingham, AL 35294-0021, United States. jdewolfe@uab.edu
Knowlton
Robert C
RC
Beasley
Mark T
MT
Cofield
Stacey
S
Faught
Edward
E
Limdi
Nita A
NA
D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced*; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D014635:Valproic Acid / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D014635:Valproic Acid; D000641:Ammonia; D001663:Bilirubin