June 2013

Anticonvulsant prophylaxis use in supratentorial tumour surgery

Hannah Church, Consultant Neuroanaesthetist

Katie Clift, Consultant Neuroanaethetist

Postoperative Epilepsy: A double blind Trial of phenytoin after craniotomy. North et al

The Lancet, Vol 315, Issue 8165, 384-386, Feb 1980

 In a double blind trial of phenytoin for the prevention of postoperative epilepsy in craniotomy patients, epilepsy was observed in 7.9% (8/101) of patients treated with phenytoin and in 16.7% (17/102) of those receiving placebo. Therapeutic drug levels were associated with a significant reduction in frequency of seizures. Three quarters of seizures occurred within one month of cranial surgery.

This paper, although historical, gives clear indication of the very real risk of post-operative seizures, which can be disastrous. It also gives some direction to neurosurgeons on how long they need to continue post operative anticonvulsant prophylaxis.

Antiepileptic drugs as prophylaxis for post-craniotomy seizures (Review), Pulman et al

The Cochrane Collaboration, Dec 2012

 Authors concluded that there is little evidence to suggest anticonvulsant prophylaxis is either effective or not effective in preventing post-craniotomy seizures. Many studies are limited in their usefulness or applicability due to variety in tumour locations, surgical approaches and pathologies. There is suggestion within this review that prophylaxis has the potential to do harm.

This review may not be of use in producing clinical guidelines, but may be useful support in a court of law and does prompt us to reflect on the side effect profiles of anticonvulsants we may consider using.

Postoperative seizures following the resection of convexity meningiomas: are prophylactic anticonvulsants indicated?

Sughrue et al

J Neurosurg 114: 705-709, 2011

• Population- 188 patients with convexity meningiomas over 17 years with no previous history of seizures. It is essentially a review of 3 surgeons’ patients in a department.
• Intervention- patients from 2 surgeons were always given prophylaxis (phenytoin initially and levetericetam more latterly), and patients of the third surgeon never given prophylaxis.
• Outcome- 129 patients received prophylaxis, 52 did not. Only one seizure observed and came from the no-prophylaxis group. The difference is not statistically significant. There is a considerable limitation to the study-  there are essentially 2 variables: the surgeon and the use of prophylaxis.
• The seizure rate is very low in both groups and this study asks us to question whether the cost and side effects of anticonvulsant prophylactic medications is warranted.

Prophylactic antiepileptic drug therapy in patients undergoing supratentorial meningioma resection: a systematic analysis of efficacy. Komotar et al

J Neurosurg 115:483-490, 2011

• Population- patients undergoing resection of supratentorial meningiomas with no prior seizures reported since 1979.
• Intervention- use of antiseizure prophylaxis
• Comparator- no antiseizure prophylaxis given
• Outcome- 19 studies found in total, 698 patients in total of which 145 patients received no prophylaxis, 553 received a variety of prophylactic medications. There were no statistically significant differences in patient or tumour characteristics. The group who received prophylaxis had a seizure rate of 1.4% before discharge and 8.8% after discharge. The group who did not receive prophylaxis had a seizure rate of 1.4% before discharge and 9% after discharge. The difference is not statistically significant.

There is not evidence easily available from the literature to support the use of anticonvulsant prophylaxis in this group of patients.

A prospective randomised trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumours.

Wu et al

J Neurosurg 118:873-883,2013

Population- patients with intraparenchymal tumours (biopsy or compelling imaging) with no previous seizures.

Intervention- administration of phenytoin as seizure prophylaxis

Comparison- no prophylaxis

Outcome- trial was closed early after 123 patients as independent analysis demonstrated there was unlikely to be any clinically significant difference between the groups. Seizure rate was 10% in the phenytoin group and 8% in the control group. The phenytoin group experienced significantly more adverse effects.

Postoperative seizure rates are low, which raises concerns about use of a prophylactic agent with side effects. Adverse effects of phenytoin may be more significant in some patient groups.

Levetiracetam compared to phenytoin for the prevention of postoperative seizures after craniotomy for intracranial tumours in patients without epilepsy.

Kern et al

Journal of Clinical Neuroscience 19 (2012) 99-100

• Population- 235 patients with intracranial neoplasms undergoing craniotomy who were deemed to require anticonvulsant prophylaxis due to tumour location.
• Intervention-  phenytoin was standard therapy received by 154 patients
• Comparator- 81 patients had contraindications to phenytoin and were given levetericetam instead. This was a retrospective review of the two patient groups.
• Outcome- 9 patients in total had post operative seizures. There was no statistically significant difference between the groups. There were no side effects reported in either group.

Levetericetam is a valid alternative to phenytoin where there is concern about the side effect profile.