The Effect of Keppra Prophylaxis on the Incidence of Early Onset, Post-traumatic Brain Injury Seizures

Hazama, Ali; Ziechmann, Robert; Arul, Manu; Krishnamurthy, Satish; Galgano, Michael A.; Chin, Lawrence S.

doi:10.7759/cureus.2674

Cited by 12 publications

(23 citation statements)

References 16 publications

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“… 20 , 30 Other retrospective cohort study subgroup analysis has mentioned that patients with more severe TBI suffer a higher incidence of PTE, but these studies have failed to adjust the severity of TBI on odds ratio analyses. 31 In a population-based study with Taiwanese TBI patients from the National Health Insurance Research (NHIR) database, the author observed that PTE patients who were prescribed more AEDs were associated with a higher mortality risk than those who had been administered none or only one AED. 32 However, this study was not able to obtain the severity levels of TBI for this to be adjudicated.…”

Section: Discussionmentioning

confidence: 99%

Preventing epilepsy after traumatic brain injury: A propensity score analysis

Liou

Chang

Lee

et al. 2020

Journal of the Chinese Medical Association

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Background: Due to the potential consequences of post-traumatic epilepsy (PTE) exacerbating secondary injury following traumatic brain injury (TBI), the use of antiepileptic drugs (AEDs) is an accepted option for seizure prophylaxis. However, there is only a paucity of data that can be found regarding outcomes surrounding the use of AEDs. The purpose of this retrospective study is to evaluate whether the prophylactic administration of AEDs significantly decreased the incidence of PTE, when considering the severity of TBI. Methods: All trauma patients who had been newly diagnosed with TBI from January 1, 2010 to December 31, 2017 were retrospectively analyzed. Statistical comparisons were made using the chi-square test, Mann-Whitney U test, and Cox regression modeling. After excluding any exposed subjects with no appropriate match, patients who had received AED prophylaxis were matched by propensity score with those who did not receive AEDs. All of the TBI populations were followed up until June 30, 2018. Results: We identified 1316 patients who met the inclusion and exclusion criteria in our matched cohort through their propensity scores, where 138 patients had been receiving prophylactic AEDs and 138 patients had not. Baseline characteristics were similar in gender, age, Glasgow Coma Scale (GCS) scores, and risk factors of PTE including skull fracture, chronic alcoholism, subdural hematoma, epidural hematoma, and intracerebral hematoma. After adjusting for those risk factors, the relative incidence of seizure was not statistically significant in either of the groups ( p = 0.566). Conclusion: In our cohort analysis, AED prophylaxis was ineffective in preventing seizures, as the rate of seizures was similar whether patients had been receiving the drugs or not. We therefore concluded that the benefits of routine prophylactic anticonvulsant therapy in patients with TBI need to be re-evaluated.

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Section: Discussionmentioning

confidence: 99%

Preventing epilepsy after traumatic brain injury: A propensity score analysis

Liou

Chang

Lee

et al. 2020

Journal of the Chinese Medical Association

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“…Although several therapeutic targets have been ascribed for levetiracetam, it is clear that it modulates the synaptic vesicle glycoprotein 2A, with consequent reduction of the release of synaptic excitatory neurotransmitters, restoring the balance between inhibitory and excitatory synaptic activities [ 3 , 4 , 5 , 6 , 7 ]. This unique mechanism of action may be linked with the usefulness of levetiracetam for the management of status epilepticus in pediatric and adult patients [ 8 , 9 , 10 , 11 , 12 ], prophylaxis of seizures from post-traumatic brain injury [ 13 , 14 , 15 , 16 , 17 ], neuropathic pain [ 18 ], and some psychiatric pathologies [ 19 ]. Moreover, its safety profile and linear pharmacokinetics, together with its low ability to cross the placental barrier, make levetiracetam a first-line option in pregnant women with epilepsy [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Monitoring of Levetiracetam in Portuguese Refractory Epileptic Patients: Effect of Gender, Weight and Concomitant Therapy

et al. 2020

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Levetiracetam is a second-generation antiepileptic drug, widely used in the treatment of focal and generalized epilepsy due to its pharmacokinetic and safety profiles. Its pharmacokinetic monitoring is ascribed as useful to personalize its dosing regimen. The aim of the present study was to describe, for the first time, the pharmacokinetics of levetiracetam in Portuguese refractory epileptic patients. Therefore, a retrospective study was carried out on 65 Portuguese refractory epileptic patients (pharmacokinetic study: 48; validation study: 17) admitted to the Refractory Epilepsy Centre of the Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. The pharmacokinetic parameters of levetiracetam were estimated by applying a one-compartment model with first-order absorption and elimination analysis. Male patients showed higher distribution volume (Vd/F) and oral clearance (CL/F) than female patients (median Vd/F: 52.40 L in males and 38.60 L in females, p = 0.011; median CL/F: 4.71 L/h in males and 3.91 L/h in females, p = 0.028). Higher values of Vd/F (p = 0.026) and CL/F (p = 0.003) were also found in overweight patients relative to normal weight and obese patients. Carbamazepine was the co-administered antiepileptic drug that mostly affected the pharmacokinetics of levetiracetam, increasing both Vd/F (61.30 L with carbamazepine and 39.10 L without carbamazepine, p = 0.007) and CL/F (6.71 L/h with carbamazepine and 3.91 L/h without carbamazepine, p < 0.001). The pharmacokinetics of levetiracetam was affected by gender, body mass index, and co-administration of carbamazepine. This study highlights the impact of several factors on the CL/ and Vd/F of levetiracetam when administered to refractory epileptic patients. The importance of its pharmacokinetic monitoring in clinical pharmacy stands out, thereby enabling the optimization of antiepileptic drug therapy.

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“…However, according to a multicenter prospective study conducted in 2013, both phenytoin and LEV had no significant differences in seizures rates, adverse drug reactions, or mortality [10]. More recently, a retrospective cohort study conducted in 2018 showed a lower incidence of seizures in those treated with LEV versus without prophylaxis, although this difference did not reach statistical significance [11]. Conservative use of LEV is recommended largely due to insufficient evidence.…”

Section: Discussionmentioning

confidence: 99%

Administration of Levetiracetam in Traumatic Brain Injury: Is it Warranted?

D'John¹,

Ibrahim²,

Patel³

et al. 2020

Cureus

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Background Antiepileptic agents are recommended to prevent early post-traumatic seizures (PTS) within seven days of injury in patients with severe traumatic brain injury (TBI). These agents are not routinely recommended for patients with mild-to-moderate TBI, defined as Glasgow Coma Scale (GCS) score > 8. At St. Joseph Mercy Oakland, levetiracetam (LEV) is commonly prescribed to prevent PTS. The objective of this study was to evaluate the appropriateness of LEV use in patients with mild, moderate, and severe TBI. Methods This retrospective cohort study evaluated the use of LEV in adult patients admitted with TBI over a five-year period. Patients who were younger than 18 years, had a history of seizures, were transferred to a tertiary center, or succumbed to their injuries were excluded. The primary outcome was appropriateness of LEV use. Secondary outcomes included duration of LEV treatment and rate of seizures. Results Of the 448 patients evaluated, 36 patients were excluded. Of the 412 included patients, 403 (97.8%) had a non-severe TBI, defined as GCS score > 8. In patients with non-severe TBI, 153 (38%) received LEV and 94 (23.3%) received LEV for more than seven days. Additionally, 105 (26.1%) patients with non-severe TBI were discharged with a prescription for LEV despite not having a seizure during hospitalization. All six patients with non-severe TBI who experienced a seizure were receiving LEV. Conclusions Inappropriate use of LEV is common in patients admitted with non-severe TBI, with many patients continuing LEV post-discharge. With careful patient selection, patients with mild and moderate TBI likely do not need seizure prophylaxis with LEV. Education on appropriate indication and duration of LEV in patients with TBI is warranted.

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The Effect of Keppra Prophylaxis on the Incidence of Early Onset, Post-traumatic Brain Injury Seizures

Cited by 12 publications

References 16 publications

Preventing epilepsy after traumatic brain injury: A propensity score analysis

Preventing epilepsy after traumatic brain injury: A propensity score analysis

Pharmacokinetic Monitoring of Levetiracetam in Portuguese Refractory Epileptic Patients: Effect of Gender, Weight and Concomitant Therapy

Administration of Levetiracetam in Traumatic Brain Injury: Is it Warranted?

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