Outpatient acute seizure management at the level of the general practitioner clinic: a proposed treatment algorithm

Outpatient acute seizure management at the level of the general practitioner clinic: a proposed treatment algorithm


Prahlad K Sethi, MD1 Dhrumil Shah, MD1 Anuradha Batra, MD 1 Nitin K Sethi, MD2


1 Department Neurology, Sir Ganga Ram Hospital, New Delhi, India

2 Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY (U.S.A.)



Seizures beget seizures has been a point of contention over the years. There is some scientific evidence to suggest that each seizure increases the risk for future seizures and that failure to control seizures in a timely fashion can lead to status epilepticus (SE). Status epilepticus is a life threatening neurological emergency which can present as an exacerbation of a pre-existing seizure disorder such as in an epilepsy patient who is non-compliant with his anti-epileptic drug (AED) regimen or as the initial manifestation of a seizure disorder (epilepsy) or as the manifestation of other systemic and cerebral insults. Prolonged seizures are also associated with worse neurological outcomes. With the aim to reduce the time to treatment gap, outpatient treatment of seizures is now been explored. We discuss this approach in relation to the health care system of India.


General practitioners (GPs) also referred to as primary care physicians (PCPs) form the backbone of the Indian health care delivery system. Usually, they are in solo practice working in small clinics (offices) which are ill-equipped to handle medical and surgical emergencies such as seizures and SE.

As awareness about coronary artery disease has increased, GPs now feel comfortable administering aspirin and nitrates before transferring the patient to the hospital. With respect to emergency management of seizures, their knowledge and experience is more limited. If the seizure has stopped, the patient is usually referred to a neurologist. If the patient is actively seizing, the patient is referred to the nearest hospital. The time to treatment gap results in increased morbidity and mortality especially for patients presenting with SE. Unlike developed countries, India lacks a well-organized and responsive 911 type medical emergency system manned by well trained and certified emergency medical technicians (EMTs) and paramedics who can administer life-saving 1st line and 2nd line antiseizure medications such as benzodiazepines (lorazepam, diazepam) and phenytoin or fosphenytoin parenterally en-route to the hospital.


Status epilepticus is a neurological emergency. Early effective treatment of SE results in termination of seizure activity and thereby reduction in cerebral hypoxia and damage. Hence every effort should be made to treat SE at the earliest. In India this goal would be best achieved by initiation of treatment of SE at the GP level. Till recently only intravenous benzodiazepine (diazepam or lorazepam) or rectal diazepam was available for the emergent management of seizures and SE. Now drugs which can be rapidly administered via the intranasal or intramuscular routes are also available such as intranasal midazolam and intramuscular fosphenytoin. Neurocritical Care Society guidelines recommend the administration of benzodiazepines via rectal, intramuscular, intranasal or buccal routes if intravenous or oral administration is not feasible. 1Administration via the above routes has been determined to be quick, easy, safe and to achieve high and consistent blood levels of the active compound. 2


We feel that antiseizure drugs in these formulations can be easily administered by a GP at the clinic without any special expertise or formal training.


















Intranasal midazolam: Currently in Indian market 2 midazolam formulations are available, one is MIDACIP (Cipla Pharmaceuticals) and other is MIDASPRAY (Intas Pharmaceuticals). They are both metered spray preparations. Two strengths of MIDACIP are commercially available: (1.25mg and 0.5mg)


Method of administration of MIDACIP nasal spray (Figure 1):



  1. Shake the bottle gently.
  2. Remove the dust cap.
  3. Hold the bottle with your forefinger and middle finger on either side of the nozzle and your thumb underneath the bottle
  4. If using first time, spray it six times in the air with the nozzle pointing away from the patient until the consistent mist of the drug is delivered, this is called priming, which ensures that correct dose is delivered.
  5. If the patient is in supine position, head is slightly lifted upwards and the device should be placed near the patient’s nose.
  6. Insert the nozzle into patient’s nostril, depress the pump with a firm even stroke. (Patient need not inhale)
  7. Tilt the patient head backward while spraying, this will avoid swallowing of the solution.
  8. Administer one spray at a time in each nostril to continue prescribed dose
  9. Reprime the device for subsequent use if the bottle is not used for more than a day. To reprime spray it two to three times in the air until a fine mist appears. For reusing the device nozzle and dust cap must be washed before storage.





Figure 1. Method of administration of intranasal midazolam.


Each nasal spray delivers either 1.25mg or 0.5mg of midazolam. Dose is titrated according to individual patient weight and full effective dose should be administered. For adults, dose is 5 mg if weight <50 kg and 10 mg if weight>50 kg. The dose should be equally divided and administered into each nostril. For children the recommended dose of MIDACIP nasal spray is 0.2 mg/kg body weight. The dose should be equally divided and administered into each nostril. Placing half the medication in each nostril reduces the volume while doubling the available surface area for absorption.



Table 1. Dosing Guidelines of MIDACIP Nasal Spray in children


Age (years) Weight (kg) Dose (mg) Metered Doses in Each Nostril
½ – 1 <10 1.25 – 2 1 – 2
1 – 4 10 – 16 2.5 2 – 3
4 – 10 16 – 32 5 4 – 6
>10 > 32 10 10









Intramuscular midazolam and fosphenytoin: GPs by virtue of their training can administer intramuscular injections with ease. In India intramuscular midazolam (MIDAZ, Abbott Healthcare or FULSED, Ranbaxy Laboratories) injections are widely available and cost effective. Midazolam is given intramuscularly at the dose of 10mg once or 0.2mg/kg once but not exceeding 10mg. Intramuscular fosphenytoin formulations are also available (Fosolin, Zydus Cadila Healthcare or Fosphen, Intas Pharmaceuticals) but more expensive. These preparations are available as ampoules of 150mg (75mg/ml, 2ml). It is our recommendation that the GP administer 2 ampoules of fosphenytoin stat in the clinic prior to transporting the patient to the hospital. Doing so may abort the seizure and possibly terminate the SE.



Use of the above formulations in the clinic setting by the GP along with established seizure first aid guidelines (Figure 2) has the potential to save many lives and reduce the morbidity from seizures and SE in our country.











Figure 2. Seizure first-aid guidelines (Source: Epilepsy Foundation Eastern Pennsylvania, www.epepa.org)





  1. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3–23.


  1. Agarwal SK, Cloyd JC. Development of benzodiazepines for out-of-hospital management of seizure emergencies. Neurol Clin Pract. 2015; 5:80-85.




Sudden Unexpected Death In Epilepsy

Sudden Unexpected Death In Epilepsy

Nitin K Sethi, MD

Assistant Professor of Neurology

New York-Presbyterian Hospital

Weill Cornell Medical Center

New York, NY 10021

I recently read about the tragic death of John Travolta’s son from a reported seizure while on a family vacation. The news got extensive coverage on prime time television networks but unfortunately none of the news segments provided any credible information about death from a seizure or epilepsy in general.  While I respect medical journalists and the work they do, I feel they owe a bigger moral obligation not just in getting news across to the public but also going a step forward in researching the topic and utilizing the news story  to spread awareness about a disease. The tragic death of Mr. Travolta’s son limelights epilepsy and its at times unexpected tragic consequences.

When people think of a seizure or epilepsy, death as a possible consequence does not come to mind as conjured by other illnesses like cancer. Seizures usually are discreet episodes, guaranteed they are frightening to witness (if you happen to be a family member or a bystander). The patient falls down (if standing at the time of seizure onset), shakes and jerks violently, eyes roll up, drools and may bite his or her tongue. After a minute or two (which for the caregiver or bystander may seem like an eternity), the person stops shaking and may infact appear to fall asleep and breathe loudly. Emergency medical staff are there by then and take the person to the hospital.


Well yes and no. As I tell most of my patients and their concerned family members, most seizures end on their own and do not need any “active intervention” (meaning giving them some drug to stop the seizure). By the time EMS arrive, the seizure is already over and the patient is confused and disoriented (we call this the post-ictal stage meaning the stage after the ictus/seizure is over). There are a few patients in whom the seizure may not stop or in whom one seizure is followed in rapid succession by another seizure without regaining consciousness in between. These patients are said to be in “status epilepticus” and need urgent medical attention to abort the onoing seizures. These are the patients who the EMS give intravenous medications to stop the seizure (you can read about this more on my website http://braindiseases.info), once these patients reach the ER, intravenous medications to abort the seizure are administered.

But coming back to where I started most seizures do abort on their own. That is what I tell my patients and their caregivers. As a physician the seizure itself does not worry me so much, it is the circumstances surrounding the seizure which can prove to be fatal. When a person is having a seizure, his or her brain is malfunctioning (think of it as a massive short circuit in the neural pathways), he is thus unable to fend for himself.  Seizures are usually associated with a loss of body tone, a standing patient thus may fall and injure himself. A hard fall on the head may result in a fatal head injury due to intracranial hemorrhage. A person standing next to a subway line in New York City may fall onto the tracks after a seizure episode and get hit by an oncoming train, he or she may suffer a fatal car crash if the seizure happens to occur while they are driving (this of course poses a risk to other motorists and pedestrians who share the road. There are rules with respect to driving with epilepsy and these vary from state to state). Deaths have occurred due to submersion and drowning if the patient has a seizure while swimming or while taking a bath in a tub.

So what I tell my patients is this


There is a further entity called “Sudden Unexplained Death in Epilepsy” also called SUDEP. SUDEP refers to patients with epilepsy/ seizure disorder who are found dead due to no “apparent reason”.  These usually are epilepsy patients who on the surface seem to be fine and one day are found dead. At times they may go to bed okay but are found in bed dead the next morning. A lot of research and studies have looked into SUDEP to try to determine its etiology and thus help in better identification of those epilepsy patients who are more prone to SUDEP. While we still do not know what causes SUDEP, we now do know certain facts.

There is neural control of heart rate (meaning parts in the brain control our heart rate). Hence seizures which arise from certain areas in the brain such as the insular cortex may at times be accompanied with bradycardia (that is the heart slows down and in extreme cases may even stop for a few seconds to minutes). Thus ictal bradycardia or ictal asystole may be one of the mechanism underlying SUDEP.  In other documented cases of SUDEP, patient was found to have severe laryngeal muscle spasm  thus impairing respiratory effort.

So who are the patients who are at high risk for SUDEP? These are usually patients who have poorly controlled epilepsy (seizure control is inadequate on current therapy). Patients who have seizures associated with ictal bradycardia and/or laryngeal spasm remain at exceptionally high risk.

Epilepsy is a relatively common neurological disorder. It imposes a high price in terms of socio-economic costs and quality of life issues. Every attempt should be made to attain good seizure control (thankfully we now have many options both medical therapy ( anti-seizure medications) as well as surgical, you can read about them on my website http://braindiseases.info).

The battle is still to be won but together we can!!!