Physical incompatibility of phenytoin with Isolyte P.

To the Editor: A 7-year-old female child presented with repeated episodes of vomiting for 1 month and was having signs of raised intracranial pressure. Computed tomographic scan revealed a homogeneous contrast enhancing lesion in the posterior fossa along with supratentorial hydrocephalus and was diagnosed as a case of cerebellar medulloblastoma with obstructive hydrocephalus. Suboccipital craniotomy and removal of the tumor was planned under general anesthesia. Injectable phenytoin 50-mg IV, thrice a day was started as prophylaxis for seizure after ventriculoperitoneal shunt surgery done before the definitive surgery. During the suboccipital craniectomy infusion of pediatric maintenance solution with 5% dextrose named as Isolyte P [Parenteral drugs (India) Ltd, Indore, India] was started. Patient was induced with IV thiopentone sodium and fentanyl and tracheal intubation was facilitated by muscle relaxant. Injection phenytoin sodium 100mg was added into 100mL of Isolyte P for infusion as a top up dose. A white colored precipitate was formed and, therefore, the preparation was discarded and IV set was replaced. This was an accidental observation. Literature search performed later reveled that stable solution of phenytoin sodium can be prepared which are safe for IV infusion provided the injection is diluted in a small volume of 0.9% sodium chloride or Ringer’s lactate solution and administered freshly prepared. However, there was no mention of the fact phenytoin should not be diluted in Isolyte P. Phenytoin sodium is a hydantoin derivative anticonvulsant. The chemical name is sodium 5, 5-diphenyl-2, 4 imidazolidinedione (C15H11N2 NaO2). Each milliliter of the solution contains phenytoin sodium 50mg, propylene glycol 0.4mL, ethanol 0.1mL in water for injection, adjusted to a pH of 12 with either sodium hydroxide or hydrochloric acid (Sun pharmaceutical India, Ltd, Gujarat, India). Injection phenytoin is a clear, colorless solution, free from visible particulates. The solution is suitable for use as long as it remains free of haziness and precipitate. Injection phenytoin is diluted with infusion fluids before administration. Being highly alkaline it remains stable in nonacidic solutions. The solubility of phenytoin in intravenous admixtures depends on the pH and the volume of the infusion fluid. Formation of rod-shaped crystals primarily reflects the failure to maintain the pH of the admixture above 9.5 to 10. Isolyte P [Parenteral drugs (India) Ltd, Indore, India] is a wellaccepted intravenous maintenance fluid for pediatric patients and contains 5% dextrose along with potassium chloride, dibasic potassium phosphate, sodium acetate, magnesium chloride, and sodium metabisulfite. It has a pH of approximately 6.0 and an osmolarity of 369mosmol/L. The solubility of phenytoin in IV admixtures depends on the pKa of phenytoin along with the pH and the volume of the of the IV solution. To explore the likelihood of phenytoin precipitation in different volumes of Isolyte P; we diluted phenytoin sodium (100mg) in 50, 20, 10, 5, and 2mL of Isolyte P. A white colored precipitate was formed in all the above-mentioned dilutions. We therefore suggest that literature should clearly state that Isolyte P should not be used as a vehicle for administration of phenytoin.