title: Safety of rapid intravenous loading of valproate.
abstract: BACKGROUND
  The introduction of IV valproic acid (VPA) has facilitated its use in situations where oral administration is not feasible. The present study was designed to evaluate the safety of administration of undiluted VPA (20 or 30 mg/kg/min) administered intravenously at rates of 6 or 10 mg/kg/min.
  
  
  METHODS
  Forty patients received a VPA loading dose (20 or 30 mg/kg) at 6 or 10 mg/kg/min. Heart rate (HR), mean arterial pressure (MAP), oxygen saturation, respiratory rate, and three lead ECG measurements were taken at baseline. Following dose administration the measurements were repeated at 2.5-min intervals for the first 20 min, then at 30, 45, 60 min, and 4 h. Local tolerance was defined as absence of irritation or phlebitis at the site of injection. Systemic tolerability was defined as absence of significant changes in vital signs and level of consciousness (LOC). Changes in vital signs and local intolerance scores were compared across time using repeated measures analysis of variance.
  
  
  RESULTS
  Rapid administration was well tolerated with no significant changes in HR (p=0.9) or MAP (p=0.7). Complaints of local irritation were transient, lasting less than 3 min in all patients with no indication of redness, irritation, or phlebitis. No patient exhibited a decline in the LOC.
  
  
  CONCLUSIONS
  Rapid administration of undiluted valproate is safe and well tolerated at infusion rate up to 10 mg/kg/min and doses of up to 30 mg/kg. The lack of serious cardiovascular, neurological, hepatic, or local adverse effects supports the use of VPA in emergent situations.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Epilepsy Center, Birmingham, AL 35294-0021, USA. nlimdi@uab.edu
authors.forename: Nita A
authors.initials: NA
authors.lastname: Limdi
authors.forename: Robert K
authors.initials: RK
authors.lastname: Knowlton
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cofield
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Ver Hoef
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Paige
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
authors.forename: Edward
authors.initials: E
authors.lastname: Faught
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid