To Study Perioperative Changes in Plasma Phenytoin Levels in Patients with Brain Tumor Undergoing Craniotomy and Its Correlation with Postoperative Seizures

Abstract

Introduction

Phenytoin, although commonly used for postoperative seizure prophylaxis, exhibits variable results in mitigating seizure frequency following craniotomy. These discrepancies may be linked to a reduction in plasma phenytoin levels subsequent to the surgical intervention.

Aims

This prospective study aims to characterize changes in plasma phenytoin levels after craniotomy and their relationship with intraoperative blood loss.

Methods

Fifty consecutive patients were enrolled in this study after obtaining written informed consent. These patients had either been on oral phenytoin for at least 7 days or had received an intravenous loading dose before undergoing craniotomy. Serum phenytoin levels were measured 24 hours preoperatively, immediately before craniotomy (prior to skin incision), postcraniotomy (after skin closure), and 24 hours postcraniotomy. Additionally, intraoperative blood loss was calculated using a modified Gross formula.

Results

Immediately following craniotomy, there was a statistically significant mean decline of 28.16% in serum phenytoin levels. Furthermore, the analysis revealed a robust positive correlation between the decrease in phenytoin concentration level and several factors, including blood loss during surgery, the duration of the surgical procedure, intravenous fluids administered during surgery, and the occurrence of postoperative seizures.

Conclusion

This study underscores the potential utility of routinely measuring perioperative serum phenytoin levels in high-risk patients to prevent postcraniotomy seizures. Moreover, it suggests that patients with substantial intraoperative blood loss may benefit from an additional bolus dose of phenytoin toward the end of the surgical procedure.

Keywords

phenytoin - postcraniotomy seizure - postoperative seizure

Publikationsverlauf

Artikel online veröffentlicht:
03. Mai 2024

• References

• 1 Shaw MD, Foy PM. Epilepsy after craniotomy and the place of prophylactic anticonvulsant drugs: discussion paper. J R Soc Med 1991; 84 (04) 221-223
• 2 De Santis A, Villani R, Sinisi M, Stocchetti N, Perucca E. Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study. Epilepsia 2002; 43 (02) 175-182
• 3 Yeh JS, Dhir JS, Green AL, Bodiwala D, Brydon HL. Changes in plasma phenytoin level following craniotomy. Br J Neurosurg 2006; 20 (06) 403-406
• 4 Hanish B, Gulzar G, Rakesh K, Ashwani CK, Sandeep K, Gupta V. Evaluation of changes in serum phenytoin level after craniotomy and its relation to intraoperative blood loss. Indian J Neurotrauma 2014; 11: 109-112
• 5 Greenhalgh J, Weston J, Dundar Y, Nevitt SJ, Marson AG. Antiepileptic drugs as prophylaxis for postcraniotomy seizures. Cochrane Database Syst Rev 2020; 4 (04) CD007286
• 6 Horiuchi S, Kanaya K, Horiuchi T. The occurrence and relationship of postoperative seizure and de novo epilepsy after craniotomy surgery: a retrospective single-center cohort study. Front Surg 2022; 9: 881874
• 7 Wu AS, Trinh VT, Suki D. et al. A prospective randomized trial of perioperative seizure prophylaxis in patients with intraparenchymal brain tumors. J Neurosurg 2013; 118 (04) 873-883
• 8 Joiner EF, Youngerman BE, Hudson TS. et al. Effectiveness of perioperative antiepileptic drug prophylaxis for early and late seizures following oncologic neurosurgery: a meta-analysis. J Neurosurg 2018; 130 (04) 1274-1282
• 9 Glantz MJ, Cole BF, Forsyth PA. et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000; 54 (10) 1886-1893
• 10 Kong X, Guan J, Yang Y, Li Y, Ma W, Wang R. A meta-analysis: do prophylactic antiepileptic drugs in patients with brain tumors decrease the incidence of seizures?. Clin Neurol Neurosurg 2015; 134: 98-103
• 11 Perry J, Zinman L, Chambers A, Spithoff K, Lloyd N, Laperriere N. Neuro-oncology Disease Site Group, Cancer Care Ontario's Program in Evidence-Based Care. The use of prophylactic anticonvulsants in patients with brain tumours: a systematic review. Curr Oncol 2006; 13 (06) 222-229
• 12 Tremont-Lukats IW, Ratilal BO, Armstrong T, Gilbert MR. Antiepileptic drugs for preventing seizures in people with brain tumors. Cochrane Database Syst Rev 2008; 2008 (02) CD004424
• 13 North JB, Penhall RK, Hanieh A, Frewin DB, Taylor WB. Phenytoin and postoperative epilepsy. A double-blind study. J Neurosurg 1983; 58 (05) 672-677
• 14 Foy PM, Chadwick DW, Rajgopalan N, Johnson AL, Shaw MDM. Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy?. J Neurol Neurosurg Psychiatry 1992; 55 (09) 753-757
• 15 Lee ST, Lui TN, Chang CN. et al. Prophylactic anticonvulsants for prevention of immediate and early postcraniotomy seizures. Surg Neurol 1989; 31 (05) 361-364
• 16 Franceschetti S, Binelli S, Casazza M. et al. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Acta Neurochir (Wien) 1990; 103 (1–2): 47-51
• 17 North JB, Penhall RK, Hanieh A, Hann CS, Challen RG, Frewin DB. Postoperative epilepsy: a double-blind trial of phenytoin after craniotomy. Lancet 1980; 1 (8165) 384-386
• 18 Tsolaki M, Yannacou-Peftoulidou M, Grammaticos P, Sofianos E, Foroglou G. Phenytoin plasma levels after intraoperative administration, for the prevention of post-craniotomy seizures. Acta Neurochir (Wien) 1987; 84 (1–2): 36-38
• 19 Hortin GL, Goldberger BA. Chromatography and extraction. In: Burtis CA, Ashwood ER, Bruns DE. eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th ed.. Philadelphia, PA: WB Saunders; 2012: 307-328
• 20 Gross JB. Estimating allowable blood loss: corrected for dilution. Anesthesiology 1983; 58 (03) 277-280
• 21 Freund B, Probasco JC, Ritzl EK. Seizure incidence in the acute postneurosurgical period diagnosed using continuous electroencephalography. J Neurosurg 2018; 130 (04) 1203-1209
• 22 Nanda A, Patra DP. Surgical complications in neurosurgery. In: Nanda A. ed. Complications in Neurosurgery. London: Elsevier; 2018: 17-22
• 23 Fugate JE. Complications of neurosurgery. Continuum (Minneap Minn) 2015; 21 (5, Neurocritical Care): 1425-1444
• 24 Chassoux F, Landre E. Prevention and management of postoperative seizures in neuro-oncology. Neurochirurgie 2017; 63 (03) 197-203
• 25 Manaka S, Ishijima B, Mayanagi Y. Postoperative seizures: epidemiology, pathology, and prophylaxis. Neurol Med Chir (Tokyo) 2003; 43 (12) 589-600 , discussion 600
• 26 Pruitt AA. Medical management of patients with brain tumors. Curr Treat Options Neurol 2011; 13 (04) 413-426
• 27 Phunsawat A, Tuchinda L, Somboonviboon W. Plasma phenytoin levels and incidence of seizure in patients undergoing craniotomy for supratentorial brain tumors. J Anesth Clin Res 2012; 3: 10
• 28 Radhakrishnan M, Devaraj ND, Umamaheswara Rao GS, Subhash MN. Additional phenytoin is frequently needed in patients undergoing craniotomy for supratentorial tumour. Eur J Anaesthesiol 2008; 25 (07) 601-603
• 29 Levati A, Savoia G, Zoppi F, Boselli L, Tommasino C. Peri-operative prophylaxis with phenytoin: dosage and therapeutic plasma levels. Acta Neurochir (Wien) 1996; 138 (03) 274-278 , discussion 278–279