Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs

Restricted access

Object

Prophylactic use of antiepileptic drugs (AEDs) in patients admitted with aneurysmal subarachnoid hemorrhage (SAH) is common practice; however, the impact of this treatment strategy on in-hospital complications and outcome has not been systematically studied. The goal in this study was twofold: first, to describe the prescribing pattern for AEDs in an international study population; and second, to delineate the impact of AEDs on in-hospital complications and outcome in patients with SAH.

Methods

The authors examined data collected in 3552 patients with SAH who were entered into four prospective, randomized, double-blind, placebo-controlled trials conducted in 162 neurosurgical centers and 21 countries between 1991 and 1997. The prevalence of AED use was assessed by study country and center. The impact of AEDs on in-hospital complications and outcome was evaluated using conditional logistic regressions comparing treated and untreated patients within the same study center.

Results

Antiepileptic drugs were used in 65.1% of patients and the prescribing pattern was mainly dependent on the treating physicians: the prevalence of AED use varied dramatically across study country and center (intraclass correlation coefficients 0.22 and 0.66, respectively [p < 0.001]). Other predictors included younger age, worse neurological grade, and lower systolic blood pressure on admission. After adjustment, patients treated with AEDs had odds ratios of 1.56 (95% confidence interval [CI] 1.16–2.10; p = 0.003) for worse outcome based on the Glasgow Outcome Scale; 1.87 (95% CI 1.43–2.44; p < 0.001) for cerebral vasospasm; 1.61 (95% CI 1.25–2.06; p < 0.001) for neurological deterioration; 1.33 (95% CI 1.01–1.74; p = 0.04) for cerebral infarction; and 1.36 (95% CI 1.03–1.80; p = 0.03) for elevated temperature during hospitalization.

Conclusions

Prophylactic AED treatment in patients with aneurysmal SAH is common, follows an arbitrary prescribing pattern, and is associated with increased in-hospital complications and worse outcome.

Abbreviations used in this paper:AED = antiepileptic drug; BP = blood pressure; CI = confidence interval; CT = computed tomography; GCS = Glasgow Coma Scale; GOS = Glasgow Outcome Scale; OR = odds ratio; SAH = subarachnoid hemorrhage; SD = standard deviation; WFNS = World Federation of Neurosurgical Societies.
Article Information

Contributor Notes

Address reprint requests to: Axel J. Rosengart, M.D., Ph.D., Neu-rocritical Care and Acute Stroke Program, The University of Chicago, 5841 South Maryland Avenue, MC 2030, Chicago, Illinois 60637. email: arosenga@neurology.bsd.uchicago.edu.
Headings
References
  • 1

    Anonymous: Behavioral and cognitive effects of anticonvulsant therapy. American Academy of Pediatrics Committee on Drugs. Pediatrics 96:5385401995

    • Search Google Scholar
    • Export Citation
  • 2

    Baker CJPestigiacomo CJSolomon RA: Short-term perioperative anticonvulsant prophylaxis for the surgical treatment of low-risk patients with intracranial aneurysms. Neurosurgery 37:8638711995

    • Search Google Scholar
    • Export Citation
  • 3

    Bidziński JMarchel ASherif A: Risk of epilepsy after aneurysm operations. Acta Neurochir (Wien) 119:49521992

  • 4

    Butzkueven HEvans AHPitman ALeopold CJolley DJKaye AH: Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology 55:131513202000

    • Search Google Scholar
    • Export Citation
  • 5

    Cabral RJKing TTScott DF: Epilepsy after two different neurosurgical approaches to the treatment of ruptured intracranial aneurysm. J Neurol Neurosurg Psychiatry 39:105210561976

    • Search Google Scholar
    • Export Citation
  • 6

    Goldstein LB: Common drugs may influence motor recovery after stroke. The Sygen In Acute Stroke Study Investigators. Neurology 45:8658711995

    • Search Google Scholar
    • Export Citation
  • 7

    Goldstein LB: Prescribing potentially harmful drugs to patients admitted to hospital after head injury. J Neurol Neurosurg Psychiatry 58:7537551995

    • Search Google Scholar
    • Export Citation
  • 8

    Haley EC JrKassell NFApperson-Hansen CMaile MHAlves WM: A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America. J Neurosurg 86:4674741997

    • Search Google Scholar
    • Export Citation
  • 9

    Haley EC JrKassell NFTorner JC: A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg 78:5375471993

    • Search Google Scholar
    • Export Citation
  • 10

    Hart RGByer JASlaughter JRHewett JEEaston JD: Occurrence and implications of seizures in subarachnoid hemorrhage due to ruptured intracranial aneurysms. Neurosurgery 8:4174211981

    • Search Google Scholar
    • Export Citation
  • 11

    Huff JSPerron AD: Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology 56:142314242001

  • 12

    Kassell NFHaley EC JrApperson-Hansen CAlves WM: Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg 84:2212281996

    • Search Google Scholar
    • Export Citation
  • 13

    Kreiter KTCommichau CKowalski RGOstapkovich NHuddleston DFitzsimmons BF: Fever burden and cognitive out-come after subarachnoid hemorrhage. Neurology 60:A2302003. (Abstract)

    • Search Google Scholar
    • Export Citation
  • 14

    Lanzino GKassell NF: Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part II. A cooperative study in North America. J Neurosurg 90:101810241999

    • Search Google Scholar
    • Export Citation
  • 15

    Lanzino GKassell NFDorsch NWPasqualin ABrandt LSchmiedek P: Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I. A cooperative study in Europe, Australia, New Zealand, and South Africa. J Neurosurg 90:101110171999

    • Search Google Scholar
    • Export Citation
  • 16

    Lin CLDumont ASLieu ASYen CPHwang SLKwan AL: Characterization of perioperative seizures and epilepsy following aneurysmal subarachnoid hemorrhage. J Neurosurg 99:9789852003

    • Search Google Scholar
    • Export Citation
  • 17

    Loring DWMeador KJ: Cognitive side effects of antiepiletic drugs in children. Neurology 62:8728772004

  • 18

    Macdonald RLKelly KM: Antiepiletic drug mechanisms of action. Epilepsia 36:Suppl 2S2S121995

  • 19

    Macdonald RLWeir BKRunzer TDGrace MGFindlay JMSaito K: Etiology of cerebral vasospasm in primates. J Neurosurg 75:4154241991

    • Search Google Scholar
    • Export Citation
  • 20

    Mattson RHCramer JACollins JFSmith DBDelgado-Escueta AVBrowne TR: Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 313:1451511985

    • Search Google Scholar
    • Export Citation
  • 21

    Meador KJ: Cognitive side effects of medications. Neurol Clin 16:1411551998

  • 22

    Meador KJ: Neurodevelopmental effects of antiepileptic drugs. Current Neurol Neurosci Rep 4:3733782002

  • 23

    Meador KJLoring DWAbney OLAllen MEMoore EEZamrini EY: Effects of carbamazepine and phenytoin on EEG and memory in healthy adults. Epilepsia 34:1531571993

    • Search Google Scholar
    • Export Citation
  • 24

    Meador KJLoring DWAllen MEZamrini EYMoore EEAbney OL: Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. Neurology 41:153715401991

    • Search Google Scholar
    • Export Citation
  • 25

    Murakami AFurui T: Effects of conventional anticonvulsants, phenytoin, carbamazepine, and valproic acid, on sodium-potassium-adenosine triphosphatase in acute ischemic brain. Neurosurgery 34:104710511994

    • Search Google Scholar
    • Export Citation
  • 26

    North JBPenhall RKHanieh AFrewin DBTaylor WB: Phenytoin and postoperative epilepsy. A double-blind study. J Neurosurg 58:6726771983

    • Search Google Scholar
    • Export Citation
  • 27

    Olney JWWozniak DFJevtovic-Todorovic VFarber NBBittigau PIkonomidou C: Drug-induced apoptotic neurodegeneration in the developing brain. Brain Pathol 12:4884982002

    • Search Google Scholar
    • Export Citation
  • 28

    Pinto ANCanhao PFerro JM: Seizures at the onset of subarachnoid haemorrhage. J Neurol 243:1611641996

  • 29

    Reinisch JMSanders SAMortensen ELRubin DB: In utero exposure to phenobarbital and intelligence deficits in adult men. JAMA 274:151815251995

    • Search Google Scholar
    • Export Citation
  • 30

    Scolnik DNulman IRovet JGladstone DCzuchta DGardner HA: Neurodevelopment of children exposed in utero to phenytoin and carbamazepine monotherapy. JAMA 271:7677701994

    • Search Google Scholar
    • Export Citation
  • 31

    Shaw MD: Post-operative epilepsy and the efficacy of anticonvulsant therapy. Acta Neurochir Suppl (Wien) 50:55571990

  • 32

    Smith DB: Cognitive effects of antiepileptic drugs. Adv Neurol 55:1972121991

  • 33

    Vanoverloop DSchnell RRHarvey EAHolmes LB: The effects of prenatal exposure to phenytoin and other anticonvulsants on intellectual function at 4 to 8 years of age. Neurotoxicol Teratol 14:3293351992

    • Search Google Scholar
    • Export Citation
  • 34

    Vining EPGMellitis EDDorsen MMCataldo MFQuaskey SASpielberg SP: Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 80:1651741987

    • Search Google Scholar
    • Export Citation
  • 35

    Walton JN: The electroencephalographic sequelae of spontaneous subarachnoid haemorrhage. Electroencephalogr Clin Neurophysiol Suppl 5:41521953

    • Search Google Scholar
    • Export Citation
  • 36

    Watson GBLanthorn TH: Phenytoin delays ischemic depolarization, but cannot block its long-term consequences, in the rat hippocampal slice. Neuropharmacology 34:5535581995

    • Search Google Scholar
    • Export Citation
  • 37

    Young BRapp RPNorton JAHaack DTibbs PABean JR: Failure of prophylactically administered phenytoin to prevent early posttraumatic seizures. J Neurosurg 58:2312351983

    • Search Google Scholar
    • Export Citation
  • 38

    Zubkov AYTibbs REAoki KZhang JH: Morphological changes of cerebral penetrating arteries in a canine double hemorrhage model. Surg Neurol 54:2122202000

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 655 609 60
Full Text Views 292 117 4
PDF Downloads 180 76 2
EPUB Downloads 0 0 0
PubMed
Google Scholar