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Pharmacological Management of Status Epilepticus

Abstract

Status epilepticus (SE) is a serious neurological condition that requires immediate diagnosis and treatment. Among the available benzodiazepines, nurses should choose the best drug to use for SE. The purpose of this paper is to assess the pharmacological treatment of SE using benzodiazepines and determine nursing implications.

Introduction

Status epilepticus (SE) is a serious neurological condition that requires immediate diagnosis and treatment because delays in treatments have been associated with adverse outcomes related to reduced responses to administered drugs (Arif & Hirsch, 2008). In some instances, patients may not have immediate access to intravenous and, therefore, alternatives such as nasal, buccal midazolam, or rectal diazepam should be administered. In addition, these alternatives have also been administered as out-of-hospital interventions to treat or avert status epilepticus. The purpose of this drug study paper is to explore pharmacological management of status epilepticus using benzodiazepines.

Treatment Overview

Generally, rapid treatment is necessary for status epilepticus. In fact, it is observed that most first-line medications work well among 80 percent of patients when administered in less than 30 minutes after the onset of the condition. The efficacy declines to 40 percent when administered after two hours of the onset. Thus, interventions are more effective when they are administered earlier because efficiency declines vitally with delays during a seizure (Arif & Hirsch, 2008). It is therefore recommended that treatment should be initiated within five minutes after the seizure.

On this note, the most effective treatment involves the use of benzodiazepines.

Pharmacological management of status epilepticus with benzodiazepines

Earlier studies had shown that benzodiazepines were the most favored initial treatment for status epilepticus (Treiman, 1990). While recommendations may differ, physicians have often prescribed IV lorazepam as the initial therapy. It is also observed that patients who demonstrate positive outcomes with the initial treatment are most likely to use maintenance medications. During patient management, it is necessary to offer further treatment immediately when the patient’s condition is sustained to prevent possible refractory status epilepticus associated with the persistent seizure.

The potent nature of these drugs has led to observable actions in “presynaptic, postsynaptic, and nonsynaptic” (Treiman, 1990, p. 32) after administration. Thus, the drugs can be effective for acute cases of seizures. They work through antiepileptic reactions to inhibit the increase of seizures instead of curbing the condition itself (Lockey, 2001). The fast action of these drugs has been attributed to a relatively higher rate of lipid solubility and their abilities to move fast to the brain. It has however been observed that benzodiazepines with a booster of gamma-aminobutyric acid (GABA) can inhibit the seizure and work by reducing possible recurring firing that may take place due to the concentration of uninhibited drugs. Conversely, other drugs block nonexistence seizures or prevent clinical status epilepticus (Treiman, 1990). Hence, these activities may be largely responsible for the effectiveness of benzodiazepines because of their anti-status epilepticus and antiepileptic properties. From experiments, an expected string of progressive electroencephalographic (EEG) alteration has been observed during the process of generalized convulsive status epilepticus. The similarity observed in the series of EEG activities in patients can be effective for assessing the treatment of status epilepticus. Hence, benzodiazepines can be effectively used to inhibit status epilepticus. However, it is always necessary for nurses to monitor patients’ responses to treatment.

Initially, there were no findings to support the efficacy of all benzodiazepines. Hence, these drugs were generally reported as highly effective (Treiman, 1990). By then, nurses relied on drug accessibility and pharmacokinetic variations to make their choices. However, Treiman (1990) demonstrated that lorazepam had a lesser rate of distribution of its unbound components, and it was, therefore, noted that it had prolonged impacts on treating status epilepticus relative to diazepam. Diazepam is believed to be quickly transported for storage in the body after the treatment. Based on this finding, nurses have opted for lorazepam as the first-line drug for patients with SE.

An overview is provided to understand individual drugs for treating SE.

Diazepam / Valium

For several decades, diazepam has been the drug of choice for immediate treatment of patients with status epilepticus. The drug has been favored until recently when other drugs have been introduced (Lockey, 2001). Diazepam works by changing generalized convulsive status epilepticus (GCSE) in nearly 80 percent of patients just within a few minutes after administration. The drug is however known to cause venous thrombosis as a side effect.

Diazepam is extremely soluble in lipid and up to 99 percent is lipid-bound. These properties make the drug be highly distributed in large volumes. In addition, diazepam can work for 30 hours, which is the longest eradication half-life relative to other alternative benzodiazepines. Diazepam is quickly reallocated from the brain to closer fat stores regardless of its rapid absorption into the brain. The redistribution and rapid uptake explain the shorter time of action (usually between 15 and 30 minutes) associated with the drug. On this note, it is noted that other injections of diazepam for recurring seizures may therefore result in large volumes of an accumulated drug in the body. Given the longer half-life for the elimination of diazepam in the body, patients are most likely to experience several side effects related to the drug, including unexpected hypotension, circulatory and respiratory issues. Further, it has also been observed that desmethyldiazepam, which is the product released after metabolism, has a longer half-life and, therefore, the advanced outcomes of side effects could be prolonged.

Patients with the condition can receive the drug through intravenous and rectal administration. It is noted that a high-level of concentration between 5 and 30 minutes can be achieved through rectal administration. Overall, diazepam has been the first choice for out-of-hospital treatment of status epilepticus, particularly with cases where it could be difficult to get intravenous administration of other drugs.

Lorazepam

Since 1977, Lorazepam has been used as an anxiolytic agent in the US. The drug is hydroxylated benzodiazepine. Relative to diazepam, lorazepam has a low distribution rate. As a result, the drug may have increased benefits because it stays for longer in the brain. For this reason, lorazepam can last for more than 24 hours in the brain as noted in its anticonvulsant impacts. The higher percentage of free drugs is responsible for the large difference in time between lorazepam and diazepam. Through a study investigating variations in elimination half-life and distributed volumes of the two drugs, it was established that diazepam had significantly higher volumes and half-life (ten times more) than lorazepam (Lockey, 2001). Another study also established that lorazepam had the ability to end seizures within ten minutes after administration (Lockey, 2001). In addition, the drug also lacks vigorous metabolites.

Rectal administration is not the best for lorazepam because the drug is slowly absorbed and its bioavailability varies significantly. Hence, it may not be as effective as diazepam when administered. In addition, lorazepam is not a suitable option for prehospital management of status epilepticus because the intravenous drug must be kept at low temperatures. It also lacks a consistent rectal preparation method. Cases of respiratory interference and hypotension have also been noted due to the administration of lorazepam. It is imperative to note that patients become unconscious after the use of any benzodiazepines and, thus, the succeeding neurological assessments could be complicated. Lorazepam has limited cases of venous thrombosis after intravenous administration.

Clonazepam

Status epilepticus has also been managed by clonazepam in the early stages. In addition, the drug has been evaluated on performance against lorazepam and diazepam. The drug can be administered through intravenous injection. Based on a comparison with lorazepam, it was established that EEG activities were faster with lorazepam. However, clinical side effects associated with the use of clonazepam were not long-lasting.

Midazolam

The drug is water-soluble. This type of benzodiazepine has an elimination half-life of about two hours (Lockey, 2001). Midazolam displays the same effects as diazepam. The drug is popular for small operative procedures due to its amnesic and anxiolytic qualities. Midazolam is extremely lipophilic at a normal body pH and fast flows into the brain within a few seconds. This benzodiazepine has the shortest period of action relative to other drugs and, therefore, allows for earlier effective neurological evaluation of the patient. Midazolam can also be administered as an intravenous mixture. Relative to other high-dose drugs, midazolam can be safe and effective, particularly when normal treatment has yielded poor outcomes.

The buccal route has been used as an alternative channel for the administration of the drug. In fact, this mode of administration is more effective in children and teenagers with about 75 percent of cases terminated within the initial ten minutes after treatment (Lockey, 2001). In terms of effectiveness, midazolam has been ranked with rectal diazepam and is, therefore, an alternative for out-of-hospital treatment for acute cases of ES. The intramuscular path is also an alternative route for the administration of the drug because of the water solubility property. Recent studies have established that intranasal midazolam is effective and safe just like intravenous diazepam, particularly in children (Wietholter, 2013). However, there is no available evidence to support the use of midazolam as an alternative drug for adults with SE.

Overall, a comparison of all benzodiazepines based on the management of status epilepticus revealed that seizure cessation took place in 59.1 percent of patients who received lorazepam (2 -4 mg) while 42.6 percent in patients who received diazepam (5-10 mg) (Wietholter, 2013). In addition, another study established no variations in adverse effects between lorazepam and diazepam while the rates of seizure cessation were 89 percent and 76 percent respectively when one or two doses were administered (the variation was not statistically significant) (Wietholter, 2013). An assessment of IV lorazepam against IM midazolam based on adverse effect profiles and recurrent seizure rates established the same outcomes (Wietholter, 2013). A significant improvement in the rate of seizure cessation (from 63.4% to 73.4%) was noted with IM midazolam drugs when patients arrived at the emergency department, as well as in patients admitted in ICUs. The available information, therefore, shows that the safety and efficacy of IM midazolam can be compared with IV lorazepam when used for prehospital status epilepticus.

Nursing Implications

It is established that various drugs classified under benzodiazepines are available for the management of status epilepticus. However, further studies are required to provide advanced treatments that go beyond cessation and suppression of SE. This implies that the goal of treating status epilepticus using benzodiazepines should be identified from suppression or cessation of seizure. While IM midazolam and IV lorazepam are important for prehospital treatment, subsequent usages have not been established. In addition, IM midazolam is quite effective for children as a prehospital drug, but its safety and efficacy in adults should be investigated. Nurses should consider benzodiazepines that offer fast treatment and eliminate delays associated with a diagnosis. This would reduce cases of refractory status epilepticus and enhance patient outcomes. Thus, all these benzodiazepines alongside clinical trials will provide the best, more authoritative evidence-based treatments and management of SE to improve patient management. Finally, patient education about their conditions and the use of benzodiazepines is greatly relevant. Specifically, nurses should not delay diagnosis to avoid poor prognosis associated with such actions.

Conclusion

Status epilepticus is considered a neurological critical condition that requires immediate treatment. In this case, fast diagnosis and treatment should be considered first before choices are made among benzodiazepines. At the same time, prehospital drugs are now available for immediate interventions for suppression or cessation, and they should be used. The reduced cases of refractory SE have been attributed to the increased use of benzodiazepines by paramedics and caregivers. Despite this achievement in the pharmacological management of SE, further studies are necessary to determine the best treatment that goes beyond suppression and cessation to enhance outcomes in patients with SE. In addition, nurses should adopt evidence-based practices for more effectual pharmacological treatment and enhanced patient outcomes (Arif & Hirsch, 2008).

References

Arif, H., & Hirsch, L. J. (2008). Treatment of Status Epilepticus. Seminars in Neurology, 28(3), 342-354.

Lockey, A. S. (2001). Emergency department drug therapy for status epilepticus in adults. Emergency Medicine Journal, 19(2), 96-100. Web.

Treiman, D. M. (1990). The role of benzodiazepines in the management of status epilepticus. Neurology, 40(5 Suppl 2), 32-42.

Wietholter, J. P. (2013). Generalized Convulsive Status Epilepticus in Adults: Initial Pharmacologic Management. US Pharmacist, 38(1), HS-12-HS-16.

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OctoStudy. "Pharmacological Management of Status Epilepticus." April 17, 2022. https://octostudy.com/pharmacological-management-of-status-epilepticus/.

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OctoStudy. 2022. "Pharmacological Management of Status Epilepticus." April 17, 2022. https://octostudy.com/pharmacological-management-of-status-epilepticus/.

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