GABAergic Stimulation by Benzodiazepines at Stroke Onset May Ameliorate Functional Outcome in Cardioembolic Stroke Patients

Lodder, J.; Raak, L. Heuts-van; Kessels, Fons

doi:10.1159/000108009

Cited by 8 publications

(4 citation statements)

References 3 publications

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“…It decreases infarct volume in a focal ischemia model when administered after infarct induction, probably by neuronal nitric monoxide inhibition, and may attenuate anoxic CNS white matter dysfunction [8][9][10] . Other animal experiments and a retrospective clinical study support the idea of a neuroprotective effect of benzodiazepines [11][12][13] . Any eventual neuroprotective effect would be likely to be stronger in cardioembolic (CE) stroke because of spontaneous emboli fragmentation and subsequent refl ow in embolic stroke [11,14] .…”

mentioning

confidence: 68%

“…Other animal experiments and a retrospective clinical study support the idea of a neuroprotective effect of benzodiazepines [11][12][13] . Any eventual neuroprotective effect would be likely to be stronger in cardioembolic (CE) stroke because of spontaneous emboli fragmentation and subsequent refl ow in embolic stroke [11,14] . Without refl ow a drug is unlikely to arrive at the target tissue, and we emphasized such a possible effect a priori.…”

mentioning

confidence: 68%

“…Initially we had planned to conduct the trial only in CE stroke patients, because in our retrospective analysis a potential neuroprotective effect of benzodiazepines was most convincing in the CE stroke patients [11] . We tentatively related such an effect to spontaneous reperfusion, which may occur sooner or later in many CE stroke patients, and which seems a biologically plausible condition for a neuroprotective drug to be effective [14] .…”

Section: Discussionmentioning

confidence: 99%

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Diazepam to Improve Acute Stroke Outcome: Results of the Early GABA-Ergic Activation Study In Stroke Trial

Lodder¹,

Raak²,

Hilton³

et al. 2006

Cerebrovasc Dis

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Background: We tested whether diazepam, a GABA-ergic drug that also inhibits brain nitric monoxide formation, improves acute stroke prognosis. Methods: 880 patients, randomized within 12 h of acute stroke, received diazepam 10 mg or placebo by rectiole, as soon as possible, followed by 10-mg tablets twice daily for 3 days. Primary outcome was independence (Rankin score <3) at 3 months; secondary outcome was complete recovery (Barthel index ≧95 or Rankin score ≤1). Results: Intention-to-treat analyses on all 849 patients with full follow-up (50.4% on diazepam): odds ratio (OR) 1.14, 95% CI 0.87–1.49 for primary endpoint, and an OR of 1.26 (0.90–1.76) for complete recovery, both favoring diazepam. Adjusted analyses for all stroke patients (843): OR 1.20 (0.87–1.65), and 1.25 (0.89–1.74), respectively, and for all infarct patients (748): OR 1.31 (0.93–1.85), and 1.46 (1.02–2.09; p = 0.037), respectively. Analyses restricted to cardioembolic infarct patients (200) showed treatment benefit for the primary outcome: OR 2.26, 95% CI 1.07–4.76, p = 0.032, and complete recovery: OR 2.65, 95% CI 1.06–6.59, p = 0.037. About one third of ischemic stroke patients had ‘any adverse event’, without any difference between treatment groups. In 95 intracerebral hemorrhage patients, frequency of pneumonia and death were higher in the diazepam group than in the placebo group: 35 and 10%, 22 and 12%, respectively. Conclusions: Although point estimates favored diazepam treatment in various analyses, our data did not confirm our primary hypothesis. Diazepam treatment seems beneficial in cardioembolic infarct patients, is safe in acute ischemic stroke, but may better be avoided in intracerebral hemorrhage.

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confidence: 68%

mentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Diazepam to Improve Acute Stroke Outcome: Results of the Early GABA-Ergic Activation Study In Stroke Trial

Lodder¹,

Raak²,

Hilton³

et al. 2006

Cerebrovasc Dis

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“…The relation between BZD use and subsequent risk of stroke remains controversial. Some studies have indicated that BZD use may improve acute stroke outcomes through GABAergic stimulation, whereas other studies have indicated that there are greater risks of stroke in BZD users because of possible GABA A ‐mediated neurochemical mechanisms . Because BZD are so commonly prescribed, even a small risk accompanying their use could have important clinical implications and also spark the interest of the public.…”

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confidence: 99%

Benzodiazepine use and risk of stroke: A retrospective population‐based cohort study

Huang

Muo²,

Chang³

et al. 2013

Psychiatry Clin Neurosci

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Aim:The aim of this study was to investigate the possible association between benzodiazepine (BZD) use and risk of incident stroke by utilizing data from 2000 to 2003 from the National Health Insurance system of Taiwan.Methods: Study subjects consisted of 38 671 patients with new BZD use and 38 663 people without BZD use who were frequency-matched for age, sex and baseline comorbidity with BZD users. All subjects had no history of stroke. Each study patient's case was followed until a new diagnosis of stroke was made or until the patient was censored by loss to follow up, death, or termination of insurance. The study lasted until the end of 2009. A Cox proportional hazards regression model was used to estimate the incidences and hazard ratios (HR) of stroke.Results: The HR of hemorrhagic stroke was significantly lower in the BZD group when compared with the non-BZD group. For patients aged 20-39 years, the HR of ischemic stroke was significantly higher in the BZD group when compared with the non-BZD group. Compared to the non-BZD group, patients with a lower annual dosage (<1 g) or duration (<30 days) of BZD use had a lower risk of stroke in the elder group (P < 0.0001) and patients with a higher annual dosage (≥ 4 g) or duration (≥ 95 days) of BZD use had a higher risk of stroke in all age groups (P < 0.0001). Conclusions:Our findings may suggest neuroprotection under lower-dosage BZD use and neurotoxicity under higher-dosage BZD use.

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Diazepam reduces brain lesion size in a photothrombotic model of focal ischemia in rats

Aerden

Kessels

Rutten

et al. 2004

Neuroscience Letters

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GABAergic Stimulation by Benzodiazepines at Stroke Onset May Ameliorate Functional Outcome in Cardioembolic Stroke Patients

Cited by 8 publications

References 3 publications

Diazepam to Improve Acute Stroke Outcome: Results of the Early GABA-Ergic Activation Study In Stroke Trial

Diazepam to Improve Acute Stroke Outcome: Results of the Early GABA-Ergic Activation Study In Stroke Trial

Benzodiazepine use and risk of stroke: A retrospective population‐based cohort study

Diazepam reduces brain lesion size in a photothrombotic model of focal ischemia in rats

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