Case on Drug of Choice in Status Epilepticus

Title of the article: Case on Drug of Choice In Status Epilepticus.

Type of the article: Case study

Author’s Name: Burani Nadia Shulamite.

Affiliation of Author: Pharm. D final year (Doctor of pharmacy).

Institute Name: CMR College of Pharmacy, (Attached with Gandhi Medical College & Hospital), Medical, Hyderabad, 501401, Telangana State, India.

Correspondence Name, email Address: Burani Nadia Shulamite, nadia.shulamite@gmail.com
Article ID: TPE/20200720/01
Submission: 11 July 2020
Acceptance: 16 July 2020
Publication: 20 July 2020

ABSTRACT

It is defined as a seizure with five minutes or more of continuous clinical and/or electrographic seizure activity, or recurrent seizure activity without recovery between seizures. There are multiple aetiologies for status epilepticus they are Central nervous system (CNS) infections like meningitis, encephalitis, and intracranial abscess. Metabolic abnormalities hypoglycaemia, hyponatremia, hypocalcaemia, hepatic encephalopathy, and inborn errors of metabolism in children, Cerebrovascular accidents, Head trauma, Drug toxicity like benzodiazepines and barbiturates and Alcohol withdrawal syndrome. The diagnosis of convulsive status epilepticus is made clinically but requires emergent neuroimaging and laboratory studies to identify a potential aetiology. A head computed tomography (CT) scan is appropriate in most situations and most easily obtained. Benzodiazepams are the first-line drugs, Second-line drugs are anti-epileptic drugs fosphenytoin is the drug of choice, Phenytoin sodium should be used only when fosphenytoin is not available. This is a prospective study the case details is collected and documented in a documentation form, the case was followed up regularly. A 48 years old male patient was admitted with chief complaints of having recurrent seizures episodes since the morning of GTCS (general tonic-clonic seizure) type, Shortness of breathe, loss of consciousness, tongue bite. Patient is a known case of epilepsy, is on irregular medication of anti-convulsant drug (T.Phenytoin 500mg TID). The patient is a chronic alcoholic and smoker. I have Obtained Drug information Query regarding drug of choice in status epilepticus whether it is phenytoin or Fosphenytoin for status epilepticus by post-graduate. My response to it was According to few resources fosphenytoin is a better choice of a drug over phenytoin for status epilepsy. Fosphenytoin can be given at a faster rate than phenytoin i.e 150ml/min fosphenytoin can be infused while phenytoin only 50ml/min can be infused. High Local intolerance, Tissue necrosis is seen when phenytoin is infused, while fosphenytoin has a very high tolerance. The importance of medication adherence is explained to the patient as this is the clear case of non-adherence to the anti-epileptic drugs. Patients are advised to take iron folic acid, B12 supplements along with anti-epileptic drugs as Aplastic anaemia is observed in patients using anti-epileptic drugs.

Keywords: Drug of choice, Fosphenytoin, Status epilepticus, Medication non-adherence

INTRODUCTION

Status epilepticus is a neurological emergency requiring immediate evaluation and management to prevent significant morbidity or mortality. It is defined as a seizure with five minutes or more of continuous clinical and/or electrographic seizure activity, or recurrent seizure activity without recovery between seizures^[1].

Status epilepticus may be convulsive, non-convulsive, focal motor, myoclonic and any of these can become refractory. Convulsive status epilepticus consists of generalized tonic-clonic movements and mental status impairment. Non-convulsive status epilepticus is defined as seizure activity identified on an electroencephalogram (EEG) with no accompanying tonic-clonic movements. Focal motor status epilepticus involves the refractory motor activity of a limb or a group of muscles on one side of the body with or without loss of consciousness. Myoclonic status epilepticus Refractory status epilepticus refers to continuing seizures (convulsive or non-convulsive) despite the administration of appropriate anti-epileptic drugs.

The diagnosis of convulsive status epilepticus is made clinically but requires emergent neuroimaging and laboratory studies to identify a potential aetiology. A head computed tomography (CT) scan is appropriate in most situations and most easily obtained. Magnetic resonance imaging (MRI) of the brain is more sensitive for identifying malformations in paediatric patients, but may be difficult to obtain and may require sedation. Laboratory studies should include bedside blood glucose level, serum electrolytes (sodium, potassium, calcium, and magnesium), BUN, creatinine, serum bicarbonate, a complete blood count, and a lumbar puncture with cerebrospinal fluid (CSF) evaluation. If the patient has a known seizure disorder, anti-epileptic drug levels should be obtained^[^2].

There are multiple aetiologies for status epilepticus they are Central nervous system (CNS) infections like meningitis, encephalitis, and intracranial abscess. Metabolic abnormalities hypoglycemia, hyponatremia, hypocalcaemia, hepatic encephalopathy, and inborn errors of metabolism in children, Cerebrovascular accidents, Head trauma, Drug toxicity like benzodiazepines and barbiturates and Alcohol withdrawal syndrome^[3].

Therapy used in status epilepsy is Lorazepam 4 mg (0.1 mg/kg in children) injected i.v. at the rate of 2 mg/min, repeated once after 10 min if required, is the first choice drug now. It is effective in 75–90% cases and produces a more sustained anticonvulsant effect (lasting 6–12 hours) than diazepam, because of lower lipid solubility and slower redistribution. Moreover, thrombophlebitis of the injected vein is less likely with lorazepam. Diazepam 10 mg (0.2–0.3 mg/kg) injected i.v. at 2 mg/min, repeated once after 10 min if required, has been the standard therapy till recently. However, its anticonvulsant effect starts fading after 20 min, and many supplemental doses may be required. It is also more damaging to the injected vein.

Fosphenytoin 100–150 mg/min i.v. infusion to a maximum of 1000 mg (15–20 mg/kg) under continuous ECG monitoring is a slower acting drug that should be given if the seizures recur or fail to respond 20 min after onset, despite lorazepam/diazepam. It may also be employed to continue anticonvulsant cover after the seizures have been controlled by the BZD. Phenytoin sodium should be used only when fosphenytoin is not available, because it can be injected only at the rate of 25–50 mg/min and causes more marked local vascular complications

Phenobarbitone sod. 50–100 mg/min i.v. injection to a maximum of 10 mg/kg is another slower acting drug that can be used as an alternative to fosphenytoin. It is also employed to maintain a seizure-free state over the short term before definitive oral therapy is instituted. Refractory cases who fail to respond to lorazepam and fosphenytoin within 40 min of seizure onset may be treated with i.v. midazolam/propofol/thiopentone anaesthesia, with or without curarization (Induction of muscular relaxation or paralysis by the administration of curare or related compounds that have the ability to block nerve impulse transmission at the myoneural junction) and full intensive care [4].

Methods

This prospective case study was conducted on Jan 29 - Feb 06, 2020, in the Department of General Medicine, Gandhi Hospital, Hyderabad. The Case was collected, followed up, and documented in a structured data form from the in-patient department of General Medicine till discharge. The outcome was framed after interpreting the data gathered in a case documentation form according to various categories and parameters. Further results were discussed thoroughly with doctors, post-graduates in a regular manner to accomplish the outcome.

CASE PRESENTATION

A 48 years old male patient was admitted with chief complaints of having recurrent seizures episodes since the morning of GTCS (general tonic-clonic seizure) type, Shortness of breathe, loss of consciousness, tongue bite. Patient is a known case of epilepsy, is on irregular medication of anti-convulsant drug (T.Phenytoin 500mg TID). The patient is a chronic alcoholic and smoker. The patient was in a postical state, with an oxygen saturation of 92% (>96%), Afebrile, blood pressure of 180/80 mmHg (120/80), Pulse rate of 140/mt (70-100), Respiratory system examination both lungs were conducting sounds (+) crepts (+) CNS examination patient was stupor [ Glasgow scale-E1V1M5 ] moving all limbs. Radiology CT-Scan findings were patient was having atrophic changes. Laboratory findings, On Complete blood picture T. RBC-7.8 mill cells/cumm (4.7-6.1), Hb- 19.4 gm/dl, MCV- 98.7 mic (78-90),TLC-12.04 (4.5-11) , HCT- 83% (45-52), Serum Electrolytes - S. Sodium: 134 mEq/L (135-145), S. Potassium: 3.8 (3.5-5) mEq/L , S. Chlorides: 96mEq/L (97-106) .

Based on Recurrent seizure episodes, tongue bite, H/O of seizures it was provisionally diagnosed as Status epilepticus secondary to Alcohol withdrawal (Chronic Alcoholic) with Aspiration pneumonia. Supportive therapy like Oxygen Inhalation was given, drugs on admission given were under anti-convulsant Hydantoins Injection Phenytoin 7amp in 1pint NS {1amp = 250mg} OD was given. Under benzodiazepines Injection Midaz (Midazolam) 2 cc {1amp= 5mg} in 1 pint NS QID and Injection Levipil (Levetiracetam) 1cc {1amp=100mg} in 1 pint NS OD were given. Under antibiotics Injection, Monocef (Ceftriaxone) 1gm IV BD, Injection Metrogyl (Metronidazole) 500mg TID were given. And Injection Optineuron 100mg in 1 pint NS.

On day 2 Vitals were as follows patient was conscious, Temperature subsided to normal blood pressure was 130/80 mmHg, pulse rate was 100/mt , Respiratory system conducting sounds were heard. Oxygen was 92% CNS examination [Glasgow scale E3V1M5]. The same treatment was continued. On day 3 the Vitals were as follows patient was conscious, blood pressure was 120/80 mmHg, CVS-S1S2+ , Pulse rate 100/mt , Respiratory system conducting sounds were still heard. Oxygen saturation was 98%, CNS - [Glasgow scale E4V1M5] moving all limbs. Medications prescribed were the same treatment was continued in addition to Tab.librium (Chlordiazepoxide) 10 mg TID was given.

On Day 4 vitals were as follows patient was conscious, blood pressure was 120/60 mmHg,CVS-S1S2+, Respiratory system No conducting sounds were heard. Oxygen saturation was 98%, On CNS - [Glasgow E4V1M5] moving all limbs. I have Obtained Drug information Query regarding drug of choice in status epilepticus whether it is phenytoin or Fosphenytoin for status epilepticus by post-graduate. My response to it was According to few resources fosphenytoin is a better choice of a drug over phenytoin for status epilepsy^[4]. Treatment for the anti-convulsant choice was replaced with fosphenytoin from phenytoin. Medications prescribed on day 4 was Injection Neofost (Fosphenytoin) 75mg in 5% Dextrose BD. Injection Thiamine 100 mg IV OD Injection Midaz Drip 2cc {1amp-5mg} per 1 pint NS QID.

On Day 5 vitals were as follows patient was Conscious, blood pressure was 110/70 mmHg, CVS-S1S2+ , Respiratory system No conducting sounds were heard. Oxygen saturation was 98%.CNS - [E4V2M5] moving all limbs. The same treatment was continued along with Tab. IFA (Iron folic acid) 5mg OD. On day 6 vitals were as follows patient was conscious, blood pressure was 120/80 mmHg, pulse rate was 86/mt, CVS-S1S2+ , Temp- N, Respiratory system no conducting sounds were heard. Oxygen saturation was 98% CNS - [Glasgow scale E5V3M5] moving all limbs. The same treatment was continued.

On day 7 patient was discharged. Drugs on Discharge given were Tab. Eptoin (Phenytoin) 500mg TID, Tab. IFA 5mg OD, Tab. B. Complex OD. The advice given was to Abstain from alcohol, Review OP after 15 days with CBP, and other reports.

Patient counselling on Medication Adherence was given because this is a known case of status epilepsy case due to non-adherence to the medication the condition arises, Hence patient was counselled to take medications on time, And to Eat Green leafy vegetables, beans, Meat, Eggs. And should avoid alcohol consumption and smoking.

DISCUSSION

This is a known case of epilepsy, and the patient was non-adherent to anti-convulsants hence there was the recurrence of the condition occurred. The patient was a chronic alcoholic, due to alcohol withdrawal symptoms the conditional exaggerated. It was diagnosed as Status epilepticus secondary to alcohol withdrawal, One of cause for status epilepsy is alcohol withdrawal symptoms. The main aetiology behind this case was History of epilepsy with non-adherence to the medication and alcohol withdrawal symptoms. On query why is fosphenytoin a better choice of a drug over phenytoin in status epilepsy is because fosphenytoin can be given at faster rate than phenytoin i.e 150ml/min fosphenytoin can be infused while phenytoin only 50ml/min can be infused. High Local intolerance, Tissue necrosis is seen when phenytoin is infused, while fosphenytoin has very high tolerance, Phenytoin should never be given through IM route, while fosphenytoin can be given through IM route, One of the major causes of status epilepticus is hypoglycaemic, so it is favourable that the drug is infused with 5% Dextrose rather Normal saline. But phenytoin shouldn’t be given with 5% Dextrose because it gets precipitated. While fosphenytoin can be infused with 5% Dextrose ^[5][6][7]. So, hence fosphenytoin is a standard drug of choice for status epilepticus over phenytoin when given intravenously in status epilepticus patient which can be seen in Table 1.

The importance of medication adherence is explained to the patient as this is a clear case of non-adherence to the anti-epileptic drugs. There can be many reasons for non-adherence it can be a financial crisis, forgetfulness, age factor, depression, intentionally not taking medication due to non-compliance with the drug or other factors.

Fosphenytoin Vs Phenytoin
Fosphenytoin (Pro-drug of phenytoin)	Phenytoin (Active drug)
Can be given at a faster rate than phenytoin i.e 20 PE/kg IV at 150mg/min.	It is administered at 15-20 mg/kg IV at 50mg/min
pH 8.6 extravasation is well tolerated	pH 12 extravasation causes severe tissue injury
The onset of action is 5-10 min	The onset of action is 10-30 min
Less cardiac complications as it is water-soluble	Can cause hypotension, dysrhythmia
It can be given in 5% Dextrose, NS doesn't precipitate.	It can't be given through 5% Dextrose because it gets precipitated.
It can be given through IM	Cannot be given through IM, It causes tissue necrosis

Table 1: Showing Comparative study of fosphenytoin and phenytoin.

Patients are advised to take iron folic acid, B12 supplements along with anti-epileptic drugs as Aplastic anaemia is a common adverse effect using anti-epileptic drugs ^[8]. A healthy lifestyle is required to maintain by a cessation of consumption of alcohol, smoking. Intake green leafy vegetables like spinach, lentils are to be taken. Exercise regularly.

CONCLUSION

In status epilepticus condition, the choice of drug for anti-convulsant is fosphenytoin over phenytoin. Phenytoin should be only given when fosphenytoin is unavailable. Patients with a history of epilepsy should adhere to the anti-epileptic drugs, as non-adherence to prescription, can lead to a recurrence of the condition. Iron folic acid supplements are to be taken along with anti-epileptic drugs to avoid anaemia.

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