A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department.

BACKGROUND: Phenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. OBJECTIVES: We compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. METHODS: This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. RESULTS: Among the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. CONCLUSIONS: Patients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

The role of benzodiazepines in common conditions: a narrative review focusing on lormetazepam.

This review aimed to examine the place of benzodiazepines, specifically lormetazepam, in the treatment of insomnia, including during pregnancy or in patients with psychodermatoses. PubMed was searched for the term "lormetazepam" in association with MeSH terms encompassing anxiety, insomnia/sleep disorders, pregnancy/gestation, and psychodermatoses/skin disorders. English-language articles up to 31 July 2022 were identified. Ad hoc searches for relevant literature were performed at later stages of review development. Multiple randomized, placebo-controlled studies have demonstrated that lormetazepam dose-dependently increases total sleep time, decreases wakefulness over a dosing range of 0.5-2.0 mg, and improves subjective assessments of sleep quality. Lormetazepam is as effective as other benzodiazepines in improving sleep duration and quality, but is better tolerated than the long-acting agents with minimal next-day effects. Benzodiazepines can be used as short-term monotherapy at the lowest effective dose during the second or third trimesters of pregnancy; lormetazepam is also a reasonable choice due to its limited transplacental passage. Insomnia associated with skin disorders or pregnancy can be managed by effective symptom control (especially itching), sleep hygiene, treatment of anxiety/depression, and a short course of hypnotics.

Thought Blocking as a Manifestation of Catatonia: A Case Report.

ABSTRACT: Catatonia is an underrecognized disorder that has been widely described as a psychomotor syndrome, with little emphasis on its thought and cognitive dimensions. The current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision describes only motor and behavioral presentations, whereas a few catatonia scales describe only one form of thought disorders, which is thought perseveration. Thought blocking, a disorder of the thought process, is characterized by regular interruptions in the thought stream. It was described by several scholars as a sign of schizophrenia, with few reports describing thought blocking in association with catatonia. In this article, we describe the course of a patient with bipolar I disorder who presented with catatonia and demonstrated thought blocking. Her catatonic symptoms and thought blocking improved with the addition of lorazepam, recurred upon lorazepam discontinuation, and improved with resumption of lorazepam, demonstrating a clear on/off phenomenon. This report highlights the importance of recognizing thought and cognitive manifestations of catatonia, as it can enhance recognition and improve treatment.

Lorazepam in catatonia - Past, present and future of a clinical success story.

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1-2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

Eliminating the benzos: A benzodiazepine-sparing approach to preventing and treating alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal syndrome (AWS) represents significant cost to the hospitalized trauma population from a clinical and financial perspective. Historically, AWS has been managed with benzodiazepines. Despite their efficacy, benzodiazepines carry a heavy adverse effect profile. Recently, benzodiazepine-sparing protocols for the prophylaxis and treatment of AWS have been used in medical patient populations. Most existing benzodiazepine-sparing protocols use phenobarbital, while ours primarily uses gabapentin and clonidine, and no such protocol has been developed and examined for safety and efficacy specifically within a trauma population. METHODS: In December of 2019, we implemented our benzodiazepine-sparing protocol for trauma patients identified at risk for alcohol withdrawal on admission. Trauma patients at risk for AWS admitted to an academic Level 1 trauma center before (conventional) and after (benzodiazepine-sparing [BS]) protocol implementation were compared. Outcomes examined include morphine milligram equivalent dosing rates and lorazepam equivalent dosing rates as well as the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scores, hospital length of stay, intensive care unit length of stay, and ventilator days. RESULTS: A total of 387 conventional and 134 benzodiazepine sparing patients were compared. Injury Severity Score (13 vs. 16, p = 0.10) and admission alcohol levels (99 vs. 149, p = 0.06) were similar. Patients in the BS pathway had a lower maximum daily CIWA-Ar (2.7 vs. 1.5, p = 0.04). While mean morphine milligram equivalent per day was not different between groups (31.5 vs. 33.6, p = 0.49), mean lorazepam equivalents per day was significantly lower in the BS group (1.1 vs. 0.2, p < 0.01). Length of stay and vent days were not different between the groups. CONCLUSION: Implementation of a benzodiazepine-sparing pathway that uses primarily clonidine and gabapentin to prevent and treat alcohol withdrawal syndrome in trauma patients is safe, reduces the daily maximum CIWA-Ar, and significantly decreases the need for benzodiazepines. Future studies will focus on outcomes affected by avoiding AWS and benzodiazepines in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Using Interdisciplinary Teams to Mitigate the Effects of Drug Shortages in Palliative Care: The Case of Lorazepam Injection.

Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection. Before the shortage, lorazepam was used an average of 95 times per month on the palliative care unit. The overall use of benzodiazepines decreased substantially following the recommendation for the therapeutic alternative, midazolam, during the shortage. Once the shortage ended, use roughly returned to pre-shortage baselines. During this time, there were no patient safety events documented on the palliative care unit. Moreover, no changes to the care experience were reported by patients, family/caregivers, providers, or staff. The collaborative effort between pharmacy and palliative care specialists resulted in alternative treatments for palliative care patients during the drug shortage. This preserved the hospital's supply of lorazepam injection for a patient population with no suitable alternatives while still allowing for management of palliative patients.

Acute Treatment of Adolescent Cannabinoid Hyperemesis Syndrome With Haloperidol, Lorazepam, and/or Capsaicin: A Single Institution Case Series.

Cannabinoid hyperemesis syndrome (CHS), an under-recognized and seemingly paradoxical condition, arises in some adolescents and adults who chronically use cannabis. It presents acutely with intractable nausea, vomiting, and abdominal pain but standard antiemetic therapy leads to improvement for only a minority of patients. Randomized controlled trial evidence in adults indicates the superiority of haloperidol over ondansetron in alleviating the acute symptoms of CHS, but safe and effective treatment for adolescents with the disorder is currently unknown. The successful use of topical capsaicin has also been reported. We report a case series of 6 adolescent patients with CHS who presented to Johns Hopkins All Children's Hospital and were treated with haloperidol, lorazepam, and/or capsaicin. Four patients given 5 mg intravenous (IV) haloperidol and 2 mg IV lorazepam and 1 patient treated with 5 mg IV haloperidol and peri-umbilical topical capsaicin (0.025%) experienced full acute symptomatic relief. One patient, treated only with topical capsaicin, reported improvement of symptoms with some persistent nausea. Haloperidol/lorazepam, haloperidol/capsaicin, and topical capsaicin alone appear safe and effective in adolescents, but larger studies are required to confirm our findings.

La catatonia. Diagnóstico y tratamiento a propósito de un caso / Catatonia. Diagnosis and treatment of a case report

El síndrome catatónico es un cuadro de etiología múltiple tanto médica como psiquiátrica, con una variada sintomatología que muchas veces escapa al ojo clínico, siendo por tanto un síndrome infradiagnosticado en la actualidad. Es necesario la realización de un abordaje multidisciplinar y global de estos pacientes, debido a la amplitud de factores predisponentes de tipo farmacológico, tóxico y orgánico y a la elevada morbimortalidad de este síndrome. Es por ello que presentamos un cuadro clínico de un síndrome catatónico inhibido en una paciente de 37 años con diagnóstico de esquizofrenia hebefrénica que presenta un cuadro de estupor, mutismo y negativismo.Es de vital importancia una formación en profundidad para los clínicos y la aplicación de escalas y criterios diagnósticos actualizados, para un diagnóstico, evolución y tratamiento de estos pacientes. La utilización de benzodiacepinas y la terapia electroconvulsiva de manera precoz son los tratamientos de primera línea, siempre asociados a medidas de soporte y prevención de complicaciones. (AU)

The catatonic syndrome present multiple etiologies, both medical and psychiatric, with a variety of symptoms that often escape the clinical eye; therefore, it is currently an underdiagnosed syndrome. A multidisciplinary and global approach is necessary in these patients, due to the wide range of pharmacological, toxic and organic predisposing factors and the high morbidity and mortality of this syndrome. That is why we show a clinical case of an inhibited catatonic syndrome in a 37-year-old patient diagnosed with hebephrenic schizophrenia who presents a clinical picture of stupor, mutism and negativism.In-depth training for clinicians and the application of up-to-date diagnostic scales and criteria are of vital importance for diagnosis, evolution and treatment of these patients. The use of benzodiazepines and early electroconvulsive therapy are the first-line treatments, always associated with support measures and prevention of complications. (AU)

Sublingual lorazepam as rescue therapy for seizure emergencies in adults.

OBJECTIVE: Limited acute home treatments are available for patients with prolonged (>5 minutes) or repetitive (≥2 in 24 hours) seizures. While this early seizure treatment may reduce the need for emergency care, intermittent intranasal benzodiazepine formulations are expensive and rectal diazepam administration is often socially unacceptable. We determined whether caregivers could use sublingual lorazepam oral concentrate solution effectively as acute treatment for adults with prolonged and repetitive seizures. METHODS: Patients prescribed sublingual lorazepam solution at the Johns Hopkins Epilepsy Center for acute seizure treatment during a 5-year period (2012-2017) were screened. We determined clinical history of seizure patterns and number of antiseizure medications (ASMs) through patient and caregiver surveys, and we verified this history in patients' medical records and charts. During a 2-year span (2017-2018), patients and caregivers were surveyed on responses to their most recent use of sublingual lorazepam solution, including seizure cessation (prolonged seizure stopping <5 minutes or ≤1 repetitive seizure), presence of sedation and adverse events within 24 hours of administration, and whether refrigeration limited use. RESULTS: In total, 52 patients used sublingual lorazepam for treatment of acute seizures during the study period (median dose 1 mg, range 0.5 to 2 mg). Of them, 48 patients participated in treatment survey interviews. Family caregivers usually administered lorazepam (88%); 3 self-administered. Patients were surveyed on responses to their most recent use of sublingual lorazepam treatment: 66% (23/35) of patients with repetitive seizures reported no further seizure activity after administering treatment; 70% (7/10) with prolonged seizures reported seizure activity ceased within 5 minutes of treatment. Three patients treated auras and had no seizures. There were no serious adverse events during most recent use: 31% of patients developed moderate/severe sedation. Of note, 98% refrigerated lorazepam, often with coolers; 44%, however, said this limited treatment access. There was high treatment satisfaction; 79% reported that having the emergency treatment available made them feel safer. SIGNIFICANCE: This patient survey and retrospective chart review demonstrates that home treatment with sublingual lorazepam solution may be effective for interrupting prolonged and repetitive seizures. No patients had sedation complications with home doses of 0.5 to 2 mg, and patients report high satisfaction with the treatment.

Utilization of Antiseizure Medications in Women of Childbearing Age With Epilepsy and Nonepilepsy Indications: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Antiseizure medications (ASMs) are among the most commonly prescribed teratogenic drugs in women of childbearing age. Limited data exist on utilization patterns across different indications for therapy and for the newer-generation ASMs in this population. Thus, we assessed the pattern of ASM use in women of childbearing age with epilepsy and nonepilepsy indications (pain and psychiatric disorders). METHODS: We conducted a retrospective analysis of deidentified administrative data submitted to the Optum Clinformatics database. Eligible participants included women aged 12-50 years who filled ASMs between year 2011 and 2017. Participants were followed from date of index prescription filled to study end or insurance disenrollment, whichever came first. For the overall cohort and potential therapy indications, we assessed the type and frequency of ASMs filled; proportion of participants on monotherapy, polytherapy, or treatment switching; and duration of continuous use. Trends were characterized using annual percent change from study start to study end. RESULTS: Our analysis included 465,131 participants who filled 603,916 distinct ASM prescriptions. At baseline, most of the participants had chronic pain (51.0%) and psychiatric disorders (32.7%), with epilepsy the least common (0.9%). The most frequently dispensed were diazepam (24.3%), lorazepam (20.1%), gabapentin (17.4%), clonazepam (12.7%), topiramate (11.3%), and lamotrigine (4.6%). Significant linear increase in trends were observed with gabapentin (annual percent change [95% CI]: 8.4 [7.3-9.4]; p < 0.001) and levetiracetam (3.4 [0.7-6.2]; p = 0.022) and decreasing trends for diazepam (-3.5 [-2.4 to 4.5]; p < 0.001) and clonazepam (-3.4 [-2.3 to 4.5]; p = 0.001). No significant change in trend was observed with valproate (-0.4 [-2.7 to 1.9]; p = 0.651), while nonlinear changes in trends were observed with lorazepam, topiramate, lamotrigine, and pregabalin. DISCUSSION: Decreasing trends were observed with older ASMs in the overall cohort and across the potential indications for therapy. Conversely, increasing trends were seen with the newer ASMs. Considering the risk of teratogenicity associated with the newer medications largely unknown, counseling and education in addition to a careful consideration of the benefits vs potential risks should remain pivotal when prescribing ASMs for women of childbearing age.

Cannabis-Induced Catatonia in a 15-Year-Old Male: A Case Report.

INTRODUCTION: Catatonia is a syndrome of primarily psychomotor disturbances most common in psychiatric mood disorders but that also rarely has been described in association with cannabis use. CASE PRESENTATION: A 15-year-old White male presented with left leg weakness, altered mental status, and chest pain, which then progressed to global weakness, minimal speech, and a fixed gaze. After ruling out organic causes of his symptoms, cannabis-induced catatonia was suspected, and the patient responded immediately and completely to lorazepam administration. DISCUSSION: Cannabis-induced catatonia has been described in several case reports worldwide, with a wide range and duration of symptoms reported. There is little known about the risk factors, treatment, and prognosis of cannabis-induced catatonia. CONCLUSIONS: This report emphasizes the importance of clinicians maintaining a high index of suspicion to accurately diagnose and treat cannabis-induced neuropsychiatric conditions, which is especially important as the use of high-potency cannabis products in young people increases.

Resistant Catatonia in a 10-year-old Child: A Case Report.

Catatonia is a psycho-motor disorder associated with various psychiatric, neurological, and medical illnesses. It is due to alteration in GABAergic circuits and basal ganglia. Management includes identifying the underlying cause and handling complications with supportive treatment. It can cause life-threatening complications like dehydration and cardiac arrest. The risks are more in children and adolescent populations. Benzodiazepines and electro-convulsive therapy are treatment modalities. In this case report we discuss about a child who was resistant to both lorazepam and electroconvulsive therapy. Resistance to both first-line management is a rare phenomenon. We were able to manage with a combination of antipsychotics and antidepressants. Catatonia in children may respond late to treatment. Symptomatic treatment, ruling out organic causes, and judicious use of pharmacotherapy can be beneficial in resistant cases. Keywords: benzodiazepines; case reports; catatonia; electroconvulsive therapy.

Another Option for Aggression and Self-Injury, Alternative Benzodiazepines for Catatonia in Profound Autism.

Introduction: Individuals with profound autism often present for inpatient care due to aggression. Diagnostic and treatment options are limited. Agitated catatonia is a treatable comorbidity in autism, which should be considered in cases of aggression. Preliminary data report high clinical response rates of catatonia in autism when treated with electroconvulsive therapy (ECT), with poor response to lorazepam. However, access to ECT is often limited, especially in pediatric populations. Methods: We conducted a retrospective chart review to identify cases of hyperactive catatonia with partial response to lorazepam in profoundly autistic children presenting to the pediatric medical hospital. Five cases were identified, all of whom were followed by the child and adolescent psychiatry consult-liaison service during admission and treated without the use of ECT. Data from the medical record were obtained after institutional review board (IRB) approval including the following: (1) treatment course, (2) Bush-Francis Catatonia Rating Scale (BFCRS) scores, and (3) Kanner Catatonia Rating Scale (KCRS) severity scores. The Clinical Global Impressions-Improvement (CGI-I) Scale was applied retrospectively to each case. Results: All five patients demonstrated clinically significant improvements. The average CGI-I score was 1.2. The average percentage reduction in the BFCRS and KCRS severity scores was 63% and 59%, respectively. Two of five patients were first stabilized with infusions midazolam and dexmedetomidine due to the symptom severity and then transitioned to long-acting oral benzodiazepines. Overall, four of five patients were stabilized with oral clonazepam and one of five with oral diazepam. Notably, four of five patients experienced an acute worsening of aggression, self-injury, and other catatonic symptoms with escalating dosages of antipsychotic treatment, which occurred before inpatient admission. All patients experienced resolution of physical aggression toward self and/or others, experienced improvement in their communicative abilities, and were able to return home or enter residential level of care upon discharge. Conclusions: Given the limited availability of ECT and the unclear utility of lorazepam for hyperactive catatonia in autism, the use of long-acting benzodiazepines and/or midazolam infusion may offer a safe and readily available treatment alternative.

COVID-19 and catatonia: Prevalence, challenges, pathophysiology, and treatment.

BACKGROUND: Emerging literature supports the association between acute COVID-19 infection and neuropsychiatric complications. This article reviews the evidence for catatonia as a potential neuropsychiatric sequela of COVID-19 infection. METHODS: PubMed was searched using the terms catatonia, severe acute respiratory syndrome coronavirus 2, and COVID-19. Articles were limited to those published in the English language between 2020 and 2022. Forty-five articles that specifically studied catatonia associated with acute COVID-19 infection were screened. RESULTS: Overall, 30% of patients with severe COVID-19 infection developed psychiatric symptoms. We found 41 cases of COVID-19 and catatonia, with clinical presentations that varied in onset, duration, and severity. One death was reported in a case of catatonia. Cases were reported in patients with and without a known psychiatric history. Lorazepam was successfully used, along with electroconvulsive therapy, antipsychotics, and other treatments. CONCLUSIONS: Greater recognition and treatment of catatonia in individuals with COVID-19 infection is warranted. Clinicians should be familiar with recognizing catatonia as a potential outcome of COVID-19 infection. Early detection and appropriate treatment are likely to lead to better outcomes.

Pharmacological Relief of Acute Urinary Retention in a Remote Environment.

BACKGROUND: In spaceflight, acute urinary retention (AUR) could develop as a sequela of medication use, urinary tract infection, urolithiasis, or intentional urine holding. While AUR is generally treated with bladder decompression, urinary catheterization could be difficult operationally in terms of training and proficiency, supplies, and lack of space or privacy. This report discusses a case in which tamsulosin and lorazepam were used successfully on an offshore ship while awaiting medical evacuation, a situation that could arise in remote locations where aerospace operations are conducted.CASE REPORT: A 52-yr-old man with hypertension and obstructive sleep apnea but no formal diagnosis of benign prostatic hyperplasia was unable to urinate for over 16 h while on a deep-sea fishing vessel approximately 200 nmi offshore. By phone, the physician providing remote medical direction diagnosed AUR in the setting of possible infection and prescribed acetaminophen, ciprofloxacin, and a trial of tamsulosin as the ship did not have any medical personnel trained to perform urinary catheterization and there were no catheter supplies available. Lorazepam was later added for anxiolysis and potential smooth muscle relaxation. Within 1 h of initial medication administration, the patient successfully voided a large quantity of urine, which tested positive for infection by urine dipstick. The patient was continued on antibiotics and evacuated to a medical facility onshore for further management.DISCUSSION: Pharmacological treatment could be considered as a temporizing measure where operational constraints limit the ability to perform urinary catheterization to relieve acute urinary retention.Law J, Cardy V. Pharmacological relief of acute urinary retention in a remote environment. Aerosp Med Hum Perform. 2023; 94(2):90-93.

Evaluation of intravenous lorazepam dosing strategies and the incidence of refractory status epilepticus.

INTRODUCTION: Status epilepticus (SE) is a neurological emergency associated with high mortality if not identified and treated promptly. For the emergent treatment of SE, the recommended intravenous (IV) lorazepam dose is 0.1 mg/kg/dose, up to a maximum of 4 mg. It has been shown that lorazepam is commonly under dosed in SE, but there is conflicting data on whether this has a negative impact on patient outcomes. This study assessed any dose less than 4 mg to help identify the effects of under dosing lorazepam in SE. METHODS: This was a retrospective cohort study of patients admitted to a quaternary health system between October 1, 2017 and September 30, 2019 that experienced SE and were initially treated with IV lorazepam. Patients were divided into two cohorts, less than 4 mg or 4 mg, based on the initial one-time dose of lorazepam received. The primary outcome was the proportion of patients that progressed to refractory status epilepticus (RSE) that received an initial IV lorazepam dose of 4 mg compared to less than 4 mg for the treatment of SE. Secondary outcomes evaluated include length of stay, mortality, time in SE, number of seizures, cumulative lorazepam dose prior to urgent therapy, number of lorazepam doses prior to urgent therapy, time to urgent therapy, appropriately dosed urgent therapy, and number of antiepileptic drugs given in SE. RESULTS: One hundred twenty patients were included in this study (107 patients received less than 4 mg and 13 patients received 4 mg). All patients included in the study were greater than 40 kg. The primary outcome of progression to RSE was observed in a significantly greater proportion of patients in the less than 4 mg group compared to the 4 mg group (93 [87%] vs. 8 [62%], p = 0.03). There was no difference in hospital or intensive care unit length of stay. However, there was an increased rate of in-hospital mortality in patients who received 4 mg compared to less than 4 mg (5 [39%] vs. 12[11%], p = 0.02). DISCUSSION: The majority of patients in the study received less than the recommended dose of IV lorazepam for SE. Patients who received less than 4 mg experienced an increased progression to RSE, which supports current guideline recommended dosing. While there was an increased rate of mortality in patients who received 4 mg compared to less than 4 mg, time in SE was prolonged in the patient population and severity of illness was only available for a limited number of patients included.