Anticonvulsant prophylaxis for brain tumor surgery: determining the current best available evidence

Abstract

Patients who undergo craniotomy for brain tumor resection are prone to experiencing seizures, which can have debilitating medical, neurological, and psychosocial effects. A controversial issue in neurosurgery is the common practice of administering perioperative anticonvulsant prophylaxis to these patients despite a paucity of supporting data in the literature. The foreseeable benefits of this strategy must be balanced against potential adverse effects and interactions with critical medications such as chemotherapeutic agents and corticosteroids. Multiple disparate metaanalyses have been published on this topic but have not been applied into clinical practice, and, instead, personal preference frequently determines practice patterns in this area of management. Therefore, to select the current best available evidence to guide clinical decision making, the literature was evaluated to identify meta-analyses that investigated the efficacy and/or safety of anticonvulsant prophylaxis in this patient population. Six meta-analyses published between 1996 and 2011 were included in the present study. The Quality of Reporting of Meta-analyses and Oxman-Guyatt methodological quality assessment tools were used to score these meta-analyses, and the Jadad decision algorithm was applied to determine the highest-quality meta-analysis. According to this analysis, 2 metaanalyses were deemed to be the current best available evidence, both of which conclude that prophylactic treatment does not improve seizure control in these patients. Therefore, this management strategy should not be routinely used.

Analysis of the Adherence to Seizure Prophylaxis Guidelines in Neurosurgery Patients

“…Earlier studies have found that the highest incidence of seizures in the peri-operative period occurs within the first 7 days [20] . During this short timeframe, drug interactions and adverse events are less likely to occur as drug-induced hepatic enzyme induction generally requires 2 weeks of treatment [26] .Therefore, prescribing prophylactic AED for up to 1-2 weeks after surgery may be reasonable as long as patients are not maintained on AEDs in the long-term [20] .…”

“…In addition, in a 2010 single center teaching hospital in Alberta, Lwu et al found the rate of seizure prophylaxis to be 27% [15] . Deviation from the guideline recommendations may be attributed to the perceived harms of seizures on the patients' psychosocial and physical well-being, especially during the immediate post-operative period where the risk of seizures is known to be higher [6,18,20] . Our center revealed a 28% prophylaxis rate overall, which is similar to the prophylaxis rate found by Lwu and colleagues in Alberta.…”

“…During this short timeframe, drug interactions and adverse events are less likely to occur as drug-induced hepatic enzyme induction generally requires 2 weeks of treatment [26] .Therefore, prescribing prophylactic AED for up to 1-2 weeks after surgery may be reasonable as long as patients are not maintained on AEDs in the long-term [20] . Lwu et al expressed concern that most patients in their study (30 out of 44 patients) received prophylaxic AED beyond the first post-operative week and in some cases, continued for the rest of the patients' lives [15] .…”

“…Not only is there no evidence that long-term prophylactic AED administration will significantly reduce the risk of seizures, brain tumour patients are more prone to experience serious side effects, especially with older AEDs [27] . Phenytoin, for example, has many adverse effects, such as rash, nausea or vomiting, encephalopathy, myelosupression, ataxia, hepatic toxicity, and ginginval hyperplasia, which can impact patients significantly [20] . In addition, use of AEDs may interact with other important therapeutic medications needed to manage these patients' conditions.…”

“…One study looking specifically at this issue, however, demonstrated that re-analysis of data excluding patients with sub-therapeutic blood levels still showed no benefit of AED prophylaxis [10] . One reason that many brain tumour patients receive prophylactic AEDs is because they have undergone craniotomy, which is associated with higher seizure risk [20] . However, the evidence for seizure prophylaxis in neurosurgery patients is conflicting as well.…”