Doses Of Lorazepam Research Articles

Impact of gamma-aminobutyric acid receptors modulators on renal and liver functional, molecular and histological characteristics in white male mice

The gamma-aminobutyric acid (GABA) receptors are considered the main receptors that inhibit neurotransmitters in the mammalian brain, and they have been proven to exist in non-neuronal cells. The study's purpose is to determine the impact of GABA modulation on renal and liver functions and molecular and histological characteristics using different doses of lorazepam. Lorazepam, one of the benzodiazepine drugs known for its modulatory effect on GABA receptors, has been used as a modulator to determine the impact of GABA modulation on renal and liver functions and molecular and histological characteristics in 30 albino male mice, out of which 21 were divided into 3 groups. Each group were treated with different dose of lorazepam (1 mg/kg, 2 mg/kg and 3 mg/kg body weight respectively). The rest 9 of animals were considered as a control group. Histological and functional parameters were studied in kidney and liver functional states to evaluate the impact of GAPA modulation using lorazepam. Total genomic DNA was extracted from liver, brain, kidney and blood and random amplification polymorphic DNA (RAPD) technique were used to detect the molecular impact of GABA modulation on the genomic DNA. The data were analyzed using SPSS Version 20.0 (SPSS Inc.), with means and standard deviations (SD) calculated for quantitative variables, and ANOVA applied for comparing group means. Functional parameters (blood urea, creatinine, GOT, GPT, GGT) and histopathological examination showed a significant change in treated groups compared to the control group. In both the liver and kidneys of mice, with increasing doses of lorazepam, there was an increase in the severity of congestive phenomena in blood vessels with the appearance of hemorrhages, signs of inflammation, and cell degeneration and necrosis. The molecular investigation indicated substantial changes in RAPD profiles of treated groups, with normal bands disappearing and novel bands appearing in contrast to the control group. The RAPD profiles of the treated and control samples revealed 432 bands, with 109 as control bands, 167 (loss of normal bands and emergence of novel bands) as polymorphic bands, and 156 as homomorphic bands. It is concluded that GABA modulation by lorazepam increases the functional and histopathological alterations, producing variations in the genomic DNA.

Delayed drug-induced catatonia in an adolescent girl—clinical implications: a case report

BackgroundCatatonia is a potentially life-threatening condition that is characterized by psychiatric and motor disturbances, such as negativism, hypomotility, bradykinesia, and unusual movements. The diagnosis is based on clinical examination and occurs in both pediatric and adult patients and is associated with an increased mortality. Catatonia is associated with psychiatric illnesses such as schizophrenia, major depression, encephalitis, and bipolar disorder. The physiopathology of catatonia is complex and not fully understood. There is an ongoing debate in the medical community whether catatonia is an independent syndrome, or secondary to other mental illnesses. This case presentation is unique, as there are few reports describing cases of isolated catatonic syndrome in the absence of any other psychiatric or medical condition with a delayed onset caused by recreational drug abuse.Case presentationWe present the case of a 17-year-old Caucasian athletic girl with no previous contact with child and adolescent psychiatry, nor any previous drug abuse. After recreational intake of drugs, there was a delay of approximately 7 days, before the patient searched care with symptoms that were at a later stage recognized as catatonia. Treatment with a high dose of lorazepam in combination with memantine and lithium resulted in a regression of the symptoms. After 6 weeks the patient could be discharged from the hospital almost fully recovered.ConclusionsAn acute onset of psychomotor symptoms without any previous history of mental illnesses must be addressed early as a potential catatonic syndrome. Delayed onset of catatonic symptoms after intake of drugs should not be overlooked, and we here suggest that mephedrone might be capable of inducing delayed catatonia. It is feasible to use memantine as an adjuvant to the treatment of catatonia in adolescents.

Recurrent catatonia in a patient with bipolar disorder and polycythemia: A case report

We report the diagnostic and management challenges encountered in a case of a 57-year-old male patient with bipolar I disorder and comorbid polycythemia secondary to obstructive sleep apnea, who was treated in our inpatient psychiatric unit for suicidal ideation and recurrent catatonia. He was found to have catatonia with a Bush–Francis Catatonia Rating Scale score of 18. He subsequently exhibited a positive response to the lorazepam challenge test. Before discharge, his daily lorazepam dose was titrated to 6 mg, which led to resolution of catatonic symptoms, and was tapered to discontinuation. During the second hospitalization, the patient’s catatonia returned, but due to lorazepam-induced bradycardia, he refrained from taking more than 1 mg of the medication. Divalproex sodium and memantine were initiated as off-label catatonic treatment plus lurasidone for bipolar depression. The patient was also found to have a positive antinuclear antibody titer (1:160). The hemato-immunological abnormalities present in our patient complicated his catatonic condition, underscoring the need to explore medical and neuropsychiatric catatonic factors for accurate diagnosis of this neuropsychiatric syndrome.

The Neuroprotective Action of Resveratrol Against Cognitive Impairments Induced by Lorazepam in Male Rats.

The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems. Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2-deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase. Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8- HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level (p < 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests. Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

The effectiveness of the lorazepam challenge test in pediatric catatonia: A multisite retrospective cohort study

ObjectiveCatatonia is a neuropsychiatric disorder associated with changes in behavior and affect. In adults, catatonia can respond rapidly to treatment with benzodiazepines as part of the “lorazepam challenge test.” The acute effectiveness of benzodiazepine treatment in pediatric catatonia, however, has received less study. This study reports catatonia severity as measured by the Bush Francis Catatonia Rating Scale (BFCRS) in pediatric patients before and after treatment with lorazepam. MethodsMulticenter retrospective cohort study from 1/1/2018 to 6/1/2023 of patients aged 18 and younger with a clinical diagnosis of catatonia and assessment using the BFCRS before and after treatment with lorazepam. ResultsAmong 54 patients, median age was 16, and 26 (48.1 %) were female. Neurodevelopmental disabilities were present in 24 (44.4 %) of patients. Prior to treatment, patients had a mean BFCRS score of 16.6 ± 6.1, which significantly reduced to 9.5 ± 5.3 following treatment with lorazepam (mean paired difference 7.1; t = 9.0, df = 53, p < 0.001), representing a large effect size (Hedges's g = 1.20; 95 % CI: 0.85 to 1.55). No significant association was found between lorazepam dose or route of administration and clinical response, nor were age, sex, study site, the presence of a neurodevelopmental disorder, the presence of hyperactive catatonic features, or the time between treatment and reassessment associated with post-treatment BFCRS. ConclusionsLorazepam resulted in a rapid improvement in BFCRS score in pediatric patients, with a large effect size. Further research is needed into optimal dosing and route of administration of the lorazepam challenge test in pediatric patients.

Cariprazine as adjunctive treatment of catatonia in schizoaffective disorder: a case report.

IntroductionCariprazine is one of the most recent innovations in neuropsychopharmacology, with evidence for its efficacy in affective and psychotic spectrum disorders.ObjectivesTo present a case that highlights cariprazine’s potential use outside the regulatory approved indications.MethodsCase report using CARE guidelines and a narrative review.ResultsWe present the case of a 41-year-old male readmitted to a psychiatric inpatient unit due to three months of mutism and withdrawal. At admission, the patient did not communicate verbally or in writing, but he complied with simple orders, and his consciousness remained unimpaired. He scored 11 points on the Bush-Francis Catatonia Rating Scale (BFCRS), indicating immobility, mutism, staring, withdrawal, ambitendency, and automatic obedience. We observed psychomotor retardation and indirect signs of a depressive mood, including the omega sign. His medical history included ongoing psychiatric treatment since the age of 30, with two prior admissions to an acute inpatient unit. At the time of admission, he was treated with olanzapine 20 mg/day, lorazepam 2 mg/day (recently downtitrated), venlafaxine 150 mg/day, and bupropion 150 mg/day. At the start of the current episode, the patient’s diagnosis was uncertain, with previous descriptions of psychotic, affective, and catatonic features. Due to suspicion of catatonia, we administered a high dose of lorazepam (8 mg/day), resulting in a partial response with a 4-point reduction in the BFCRS. We discontinued bupropion, increased venlafaxine to 225 mg, and switched from olanzapine to cariprazine using a taper, washout, and switch strategy. Psychotic symptoms briefly appeared when the patient was not taking a dopamine D2-receptor modulatory drug. We identified mild possible adverse drug reactions, including akathisia, transient insomnia, and daytime sleepiness. At a dose of 6 mg/day of cariprazine, we observed complete remission of catatonia (BFCRS=0) and significant improvement in affective and psychotic symptoms. The patient was discharged home with diagnoses of catatonia and schizoaffective disorder, prescribed 6mg/day of cariprazine, 225mg/day of venlafaxine, and 2,5mg/day of lorazepam. At the 6-month follow-up, the patient continues to exhibit clinical stability.Conclusions This case emphasizes the safety and potential effectiveness of cariprazine in treating catatonia within the context of schizoaffective disorder. We consider that the partial agonist properties of cariprazine could theoretically reduce the risk of exacerbating catatonia, a risk typically associated with full D2-receptor antagonists. Other mechanisms of action, such as D3 partial agonism, may also contribute to the improvement or at least the non-aggravation of catatonic symptoms. Cariprazine’s mood-stabilizing properties make it a promising off-label choice for treating schizoaffective disorder, especially when catatonic features are present.Disclosure of InterestNone Declared

The Challenge of Lorazepam Failure: Malignant Catatonia Treated Successfully with Valproate

IntroductionDespite the unclear nature of catatonia, the treatment response of catatonia to benzodiazepines is widely known for its typical, dramatic recovery. The neurobiological correlates of this phenomenon regarding specific receptors and neurotransmitters are unclear, as are the potential treatment options. This is important to consider when the most commonly recommended treatments of catatonia with Lorazepam or Electroconvulsive Therapy (ECT) are unavailable or unsuccessful. In this report, we describe a case of severe, malignant catatonia and psychosis mostly unresponsive to Lorazepam during two different hospitalizations, but with eventual return to baseline after successful treatment with Valproate.Objectives-To describe a unique case of malignant catatonia that was unresponsive to Lorazepam-To illustrate the potential utility of Valproate as an alternative treatment strategy for catatonia MethodsThis is a case report.ResultsA 19-year-old Hispanic male presented to our hospital initially with family reports of severe and sudden depression with bizarre behavior. Prior to this admission, the patient had been discharged recently from another tertiary hospital following a 2-week admission for severe catatonia. Chart review from that admission scored the patient’s Bush-Francis Catatonia Rating Scale (BFCRS) at 16, which remained mostly unchanged after numerous additional intramuscular doses and standing oral doses of Lorazepam, with a reduction of BFCRS the next day of only 2. During the patient’s admission at our hospital, the patient endorsed bizarre, guilt-related delusions, and his catatonia was more severe and malignant with a BFCRS of 19, with tachycardia and diaphoresis. The patient was initially given a total of seven doses of a mix of intramuscular and oral Lorazepam (total 18mg), with a minimal 2-point reduction in BFCRS. As ECT was unavailable, Lorazepam was discontinued in favor of a trial of oral Valproate 500mg twice daily, and after his catatonia subsided (with a serum level of 60.8), he was started on oral Risperidone 0.5mg once at night, titrated up to 3mg twice daily, and eventually returned to baseline as confirmed by his family members.ConclusionsThe treatment of catatonia with Lorazepam is usually reliable and has been found to be up to 80% effective, but when the recommended use of benzodiazepines and ECT fail or are unavailable, there are few studies exploring the viability of alternative treatment options. With the use of Valproate, previous studies have shown it can treat even severe catatonia (KrÜger, J Neuropsychiatry 2001; 13:303-304), or can actually be its cause (Lauterbach, Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 1998 Jul;11(3):157-163). As such, this case report highlights the importance of exploring alternative treatments for catatonia, including Valproate, in order to better tailor the management of this unique syndrome.Disclosure of InterestNone Declared

&lt;b&gt;Enhanced inhibitory effects of GABA on renal and hepatic function, molecular profiles, and histological changes in male albino mice&lt;/b&gt;

Background: The gamma-aminobutyric acid GABA receptors are considered the main inhibitory neurotransmitter receptors in mammalian brain and they have been proved to be existing in non-neuronal cells. Aim: Lorazepam which is one of the benzodiazepines, drugs known for their effect of GABA receptors, has been used in this study as an enhancer to determine the impact of GABA activity enhancement on renal and liver functions, molecular and histological characteristics in male albino mice. Methods: Male albino mice were divided in to 3 groups (each has 7 animals) each group was treated with a different dose of lorazepam and 9 animals served as a control group. The molecular parameters included the usage of raped -PCR to detect any universal variations. The histological changes were detected using hematoxylin and eosin histopathological examination. Liver and kidney function test were utilized to detect any functional changes. Results: The results of the functional parameters (serum urea, creatinine, glutamate-oxaloacetic transaminase (GOT), glutamate-pyruvic transaminase (GPT), gamma glutamyl enzyme (GGT)) and histopathological examination demonstrated that there was a significant change in treated groups compared to the control group. As for the molecular study, seven primers out of ten gave a single and polymorphic bands using random amplification of polymorphic DNA (RAPD) technique. The results revealed great changes in RAPD profiles of treated groups as normal bands lost and new bands appeared in comparison with the control group. The RAPD profiles of the treated and control samples gave 432 bands, 109 as control bands, 167 (loss of normal bands and appearance of new bands) as polymorphic bands and other 156 as a homomorphic band. Conclusion: The marked changes in various biochemical, histopathological and RAPD-PCR profiles indicate that lorazepam-mediated GABA modulation brings about widespread alterations in peripheral organ systems. Taken together, these data suggest caution in the use of lorazepam clinically and potentially represents an unmet need for safer therapeutic alternatives or strategies to limit benzodiazepine-induced organ toxicity.

Effect of Lorazepam on the Development of the Hairy Maggot Blow Fly, Chrysomya rufifacies (Macquart): Implication for Forensic Entomology.

Entomotoxicology is based on using insect evidence recovered from a dead body to find out the cause and time of the death. Drugs can accumulate in fly larvae when they ingest the flesh of deceased persons and alter the normal development of the fly causing implications in calculating postmortem intervals. Lorazepam is an antidepressant generally used to treat anxiety. Larvae of Chrysomya rufifacies were fed on the beef liver mixed with lorazepam to study the effect of lorazepam on the developmental rate of larvae and to count delay in postmortem interval. Larvae grown on the beef liver with different doses of lorazepam showed delayed development as compared to normal larvae. The life cycle durations in experimental cultures with different concentrations of lorazepam completed in 1 ppm (272.56 hrs), 2 ppm (289.23 hrs), 3 ppm (324.10 hrs), and 4 ppm (350.72 hrs), while in the control culture life cycle completed in 257.26 hrs. The length, weight, and width of the larvae treated with lorazepam were smaller than the untreated culture. Length, weight, and width decreased with increased concentration of lorazepam. This delay in development ultimately affects the postmortem interval. That is why prior knowledge of the life cycle of flies with respect to various drugs needs to be studied, and these baseline data can be used to calculate postmortem interval and cause of death.

Lorazepam use during clinical trials of adults with bipolar mania episodes

BackgroundLorazepam has commonly been prescribed to reduce agitation during bipolar 1 mania trials. Its use has varied considerably by trial methodology and in clinical practice. MethodsThe extent and amount of lorazepam treatment was recorded and analyzed from available brief, controlled trials of acute bipolar mania and in clinical reports in adults. ResultsIn 3-week, placebo-controlled clinical trials (n = 19), most manic subjects (79%) were treated with lorazepam to reduce agitation. This treatment was most prominent during the antimanic drug wash-out phase that preceded placebo-controlled trials. Doses of lorazepam administered during the first 7–10 days of the pre-trial and the early trial phases averaged 2.2 mg/day. These doses were one-third the lorazepam/clonazepam doses administered during placebo-controlled, non-washout trials. Far higher benzodiazepine doses for manic agitation were noted in emergency department reports. Intake enrollment was strikingly restricted only in placebo-controlled trials that used pretrial drug wash-out. ConclusionsMedication treatment conclusions from placebo-controlled, drug washout trials are not representative of clinical treatment for acute bipolar mania.

Adolescents and Young Adults With Anti-N-methyl-D-aspartate Receptor Encephalitis With Excited Catatonia: Literature Review and 2Illustrative Cases.

Catatonia is a complex neuropsychiatric syndrome that can be associated with several underlying etiologies including primary psychiatric and autoimmune disorders. Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune disorder typically characterized by seizures, movement abnormalities, and behavioral changes. Anti-N-methyl-D-aspartate can present with complex neuropsychiatric symptoms including catatonia which can be challenging for clinicians to identify as excited catatonia can mimic delirium and psychiatric disorders such as psychosis and mania. To identify and present cases of anti-N-methyl-D-aspartate receptor encephalitis where excited catatonia is the presenting symptom. We present 2 case studies of agitation and disinhibition in an adolescent and young adult that were ultimately found to be secondary to autoimmune receptor encephalitis, in both cases, confirmed by cerebrospinal fluid analysis to be due to anti-N-methyl-D-aspartate receptor antibodies. Excited catatonia was suspected and initially treated with immunological therapy and high doses of lorazepam. As the severity of catatonia progressed with limited improvement with lorazepam, both cases were ultimately effectively treated with electroconvulsive therapy. Excited catatonia should be considered with presentations of bizarre behavior, agitation, disinhibition, and other psychotic symptoms in patients with no prior psychiatric history. Although the primary treatment for catatonia associated with anti-N-methyl-D-aspartate receptor encephalitis is immunomodulatory therapy paired with benzodiazepines, electroconvulsive therapy has been shown to be an effective and safe adjuvant treatment that is especially useful for management of excited catatonia.

The retrospective and observational study of catatonia - Diagnosis, course of illness, and the response to lorazepam - in a tertiary health-care center.

In patients with catatonia, it has been discovered that benzodiazepines (BZD) have a remarkable impact. However, there is not much evidence reflecting the long-term treatment with only BZDs before considering electroconvulsive therapy. One-year retrospective data of patients obtained from the health management information system (HMIS) portal and records of the department of psychiatry with the diagnosis of catatonia. This data was then analyzed for adequate history, presenting complaints, treatment taken, substance use, and was organized into five groups depending on the primary diagnosis as per the Diagnostic and Statistical Manual of Mental. The scores of Bush-Francis Catatonia Rating Scales of day 1 and subsequent follow-ups were secured. Categorical variables were analyzed with the Chi-squared test. The response overtime for all the groups and its correlation with the number of visits was compared using repeated measures analysis of variance. We found that the lorazepam challenge test versus improvement after 1 week of oral lorazepam had Pearson's correlation of 0.604, this correlation decreased in the following weeks. In the 3 week, the correlation was 0.373, which was statistically significant. This shows that the highest correlation was seen in the 1st week. Hence, our study suggested that lorazepam challenge test is a good predictor of response in the 1st week alone. We observe negative correlation which is significant in the 3rd week (P = 0.048) and not in the 1st and 2nd week. Our study analyzed the patients with catatonia in psychiatric diagnostic categories, history, and the outcome after treating them with lorazepam at every visit over 3 weeks. The correlation in the level of improvement of symptoms at subsequent visits was noteworthy and had a strong association with the lorazepam challenge test. When dose of lorazepam was tapered, on an average dose was reduced in the 2nd week. Suggesting that at least 3 week treatment would be ideal.

Acute Hyperactive Delirium followed by Excited Catatonia: A case study

Acute Hyperactive Delirium followed by Excited Catatonia: A case studyOluwole A Babatunde, MD, Frank Clark, MD, Jessica Hill, DO, Belynda Veser, MD, Anu Nagar, MDDepartment of Psychiatry, Prisma Health,109 Physicians Drive, Greer, SC 29650.Ms. A. is an 84-year-old Hispanic female with a past psychiatric history of Mild Neurocognitive Disorder due to Frontotemporal lobar degeneration, major depressive disorder (MDD), and one episode of catatonia about six years prior to current presentation. She first presented to the emergency department (ED) for a motor vehicle collision that led to bruising and generalized tenderness. She had four ED visits over the next four weeks. At the fifth visit, she was hospitalized because of concerns of altered mental status (AMS), agitation, and hallucinations. She was noted to have a urinary tract infection (UTI) and bacteremia with positive blood cultures for Escherichia Coli. She was subsequently admitted to the inpatient medical service and the working diagnosis was delirium secondary to UTI/bacteremia, exacerbated by sleep deprivation. Imaging was performed to rule out intracranial abnormalities (e.g., subdural hematoma) following MVC.Psychiatry was consulted for the recent onset of altered mental status (AMS), increasing confusion, and hallucinations. Patient was assessed by consult liaison psychiatry service on day one of admission. Mental status exam was remarkable for the following pertinent positives: oriented to self only, tangential with loose associations, perseveration on her deceased husband, religiously preoccupied and responding to internal stimuli. She was able to recall 0 out of 3 objects in both immediate and delayed recall and having auditory and visual hallucinations. Patient consistently denied suicidal ideation and homicidal ideation. CT scan and MRI were negative and helped rule out acute intracranial abnormalities (e.g., subdural hematoma).Working diagnosis of acute hyperactive delirium secondary to UTI/bacteremia was managed with quetiapine, improving gradually over the subsequent eight days. Medical team managed UTI/bacteremia with 10 days of antibiotics as recommended by the Infectious Disease team and there was clinical evidence of resolved bacteremia and UTI. Quetiapine was titrated to maximum dosage of 100mg QAM, 100mg QPM and 200mg QHS with ongoing gradual improvement. However, she decompensated on day eight with new symptoms of catatonic-like stereotypical hand movements, repetition of words, and general sustained hyperactivity. The Bush Francis score (BFS) was 12. It was at this point that the daughter (a nurse) provided additional collateral history that there was a history of a similar episode of catatonia six years ago. A trial dosage of lorazepam 2mg IV was administered with subsequent improvement of BFS to 6. Over the next four days, lorazepam 1 mg IV was administered daily, and patient continued to improve. During this time, the dosage of Quetiapine was reduced, considering that delirium had improved, and Quetiapine could have been exacerbating the catatonia. However, titrating down of Quetiapine was done slowly to avoid abrupt discontinuation which could cause delirium to re-emerge. After receiving second dose of lorazepam, Montreal Cognitive Assessment (MoCA) score also dramatically improved from 6/30 to 22/30. She was subsequently discharged on day 13 to a nursing home where she was managed for 20 days and discharged home.Two learning objectives.• There is need to ask about history of catatonia in elderly patients as this may help heighten clinical suspicion especially in patients with delirium.• It is possible for a patient who presented with hyperactive delirium with clinical improvement and resolution of delirium to develop excited catatonia in a short time, so clinicians need to have a high index of suspicion especially among patients who have a history of catatonia. Given that hyperactive delirium alone responds excellent to antipsychotics while excited catatonia responds excellent to lorazepam IV, early diagnosis is of utmost important to adjust medications at the earliest time of noticing symptoms of excited catatonia.

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

IntroductionStatus 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. MethodsThis 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. ResultsOne 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). DiscussionThe 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.

Enteral lorazepam is a promising weaning strategy for midazolam-responsive febrile infection-related epilepsy syndrome (FIRES): a case series

Prolonged and repetitive cycles of pharmacological coma, with midazolam or other general anaesthetics, is often the mainstay for seizure control in febrile infection-related epilepsy syndrome (FIRES). Here we present our experience of enteral lorazepam as an effective weaning substitute in midazolam-dependent patients. This was a retrospective study based on a review of medical records of all FIRES patients who had received enteral lorazepam as a weaning substitute for midazolam, between January 2020 and July 2021. The patients were divided into an early group (lorazepam initiated after one failed attempt to wean off midazolam) and late group (lorazepam initiated after two or more failed attempts). The conversion from intravenous midazolam to enteral lorazepam was also calculated, and epilepsy outcome at follow-up was also assessed. Seven patients (five males) were eligible. The median age at onset of FIRES was seven years (range: 4-14). A median of six (range: 6-8) anti-seizure medications (ASMs) had failed (including clobazam in two and clonazepam in one) to control seizures. The early and late lorazepam groups were comparable regarding the maximum midazolam dose for seizure control, total ASMs tried and days to wean off midazolam. The median (range) duration of hospital stay was 27 days (22-46) in the early group, compared to 51 days (40-78) in the late group. The early group patients were also on fewer ASMs (median: 3;range: 3-5) compared to the late group (median: 5; range: 4-6) at discharge. Five patients were sedated with initial lorazepam dose, but this side effect resolved on dosage reduction. On follow-up, all seven patients had seizure recurrence. In four, seizures recurred on reducing lorazepam, however, in three of these patients, this was resolved by escalating the dose. Enteral lorazepam can be an effective weaning substitute for midazolam-dependent children with FIRES. Early introduction of enteral lorazepam was associated with reduced duration of hospital stay.

Pharmacist involvement with antiepileptic therapy for status epilepticus in the emergency department

BackgroundDespite there being an estimated 50,000–150,000 emergency department (ED) visits per year related to status epilepticus, there are limited data regarding pharmacist involvement in patient care. The purpose of this study was to evaluate differences in time to antiepileptic drug (AED) administration and appropriate AED use and dose when a pharmacist was present or not. MethodsRetrospective, single-center, observational study of adult status epilepticus patients presenting to the ED between January 2018 through July 2020. The primary outcome was time to AED administration. Secondary outcomes included occurrence of appropriate AED selection and dose, escalation of care, length of stay (LOS), and 30-day mortality. Wilcoxon rank-sum was used for continuous variables and nominal data was analyzed by Chi-square or Fisher's Exact test, as appropriate. ResultsTwenty patients were included; 13 in the pharmacist-present and seven patients in the no-pharmacist-present groups. Median time to first and second AED was 26 min (IQR 17–177) versus 37 min (IQR 21–206), p = 0.58, and 51 min (IQR 30–221) versus 171 min (IQR 99–433), p = 0.07, in the pharmacist-present and no-pharmacist-present groups, respectively. Although there was no difference between groups for appropriate AED selection, those in the pharmacist-present group received a higher median dose of lorazepam equivalents (2.5 mg [IQR 2–4] vs 2 mg [IQR 2–2]; p = 0.04) and were more likely to receive at least 4 mg of lorazepam equivalents (38% vs 0%; p = 0.11). There were no differences in hospital LOS or 30-day mortality. ConclusionPharmacist presence during status epilepticus patient management was associated with a clinically significant reduction in time to administration of AEDs. Medication doses were more guideline adherent and more patients received a lorazepam dose of at least 4 mg compared to when a pharmacist was not present.

Pots syndrome: the importance of organic screening in anxiety patients. Case report

Introduction16-year-old female who starts psychiatric follow-up due to episodes of anxiety crises with dizziness and tremors.Objectives To expose a case in which it is essential to rule out organic pathology in cases where there is anxiety and physical symptoms.MethodsCase report and literature reviewResultsThe patient explains that she was in a situation of conflict with her ex-partner, commenting that he did not accept the breakup. Sertraline was prescribed in ascending doses up to 100 mg per day with complete remission of anxiety. 8 months later, she went to the emergency room for loss of consciousness and tremor of the lower limbs. She was diagnosed with conversive disorder and was prescribed lorazepam up to 3 mg per day. Since then, there has been a worsening in the frequency of syncope occurring up to 10 times a day, limiting her academic and social life. She was evaluated by a cardiologist who diagnosed Pots Syndrome (postural orthostatic tachycardia syndrome) and started treatment with ivabradine and mineralocorticoids. With this treatment, the episodes were drastically reduced and spaced out to 1-2 per week. The dose of lorazepam is decreased until its withdrawal without worsening of the anxious symptomatology.ConclusionsThis disorder consists of an involvement of the autonomic nervous system in which there is a sudden drop in blood pressure together with an abrupt increase in heart rate. Its treatment is based on increasing blood volume with drugs such as corticosteroids as well as postural measures with adequate water intake.DisclosureNo significant relationships.

Catatonia as the Initial Presentation of Depression in an Older Adult

<h3>Introduction</h3> Background: Catatonia is a neuropsychiatric syndrome characterized by a variety of motor, behavioral, emotional, and autonomic abnormalities. It can be caused by general medical, neurological, or psychiatric disorders, as well as by medications and drugs of abuse . Although there is a high prevalence of catatonia in the geriatric population, there is less data available when compared to other age group. . Among psychiatric disorders, depression is commonly associated with catatonia. And in most instances, there is a known history of depression reported in these catatonic patients. We are presenting a unique case in which an older adult presented with catatonia as the initial presentation of depression. We will then present a review of the literature of catatonia in older adults. Case: Mr. B is a 75 year old man with a history of alcohol use disorder in sustained remission for five years, no other psychiatric history, who was admitted to neurology for encephalopathy developed after a hernia repair surgery. His neurological work up including MRI brain, CSF analysis, Vit B12, TSH, video EEG, all of which were normal. The neurology team considered treating the patient with steroids for possible autoimmune encephalitis. They consulted psychiatry as he demonstrated posturing and echolalia. Upon psychiatric evaluation, his presentation was notable for stupor, mutism and negativism. He showed modest response to an initial lorazepam challenge with improved speech. Upon receiving a second dose of lorazepam, the response was significant, marked by improvement in his speech, thought process, and the ability to verbalize his subjective experience . As his catatonia improved, his depression was unmasked. He demonstrated depressed mood, feelings of guilt, helplessness, hopelessness, ruminations about past alcohol use, paranoia against the hospital staff, auditory hallucinations and referential thinking. His condition did not improve with aripiprazole or olanzapine, so team decided to administer electroconvulsive treatment in addition to escitalopram. Over the course of 7 index sessions, the patient showed minimal improvement. With a switch to bilateral ECT (index sessions #8-15), the patient ultimately showed significant improvement, including complete resolution of catatonia, and remission of depressive and psychotic symptoms. This was evidenced by improved mood, sleep, and consistent denial of AH and paranoia. He was discharged on maintenance ECT, escitalopram, and quetiapine. <h3>Methods</h3> Electronic searches of the standard bibliographic databases PubMed, MEDLINE, EMBASE, and PsycINFO will be performed for papers focusing on catatonia, first episode of depression and older adults. <h3>Results</h3> The literature on catatonia in older adults will be reviewed. The prevalence, complexities in diagnosis, and prognosis will be described, as available in the literature. <h3>Conclusions</h3> In the geriatric population, its crucial to identify and treat the catatonia in early stages to limit overall morbidity and preserve functioning. In some instances, the underlying etiology becomes evident after the treatment of catatonia. <h3>This research was funded by</h3> None

AiRDose: Developing and Validating an Augmented Reality Smartphone Application for Weight Estimation and Dosing in Children.

Inaccurate weight estimation is a contributing factor to medical error in pediatric emergencies, especially in the prehospital setting. Current American Heart Association guidelines recommend the use of length-based weight estimation tools such as the Broselow tape. We developed the AiRDose smartphone application that uses augmented reality to provide length-based weight estimates, as well as medication dosing, defibrillation energy, and equipment sizing recommendations; AiRDose was programmed to use Broselow conversions to obtain these estimates. The primary objective was to compare the length estimated by AiRDose with the actual length obtained by the standard tape measure. The secondary objectives were to compare the estimated weights and critical medication doses from AiRDose with current established methods. In this prospective validation study, lengths and estimated weights were obtained for children presenting to 2 emergency departments using AiRDose, Broselow, and a standard tape measure; actual weight was recorded from the patient chart. Using the AiRDose estimated weights, hypothetical doses of epinephrine and lorazepam were calculated and compared with doses recommended via Broselow and to actual weight-based doses. Spearman rank correlation coefficients were calculated. We defined an acceptable difference of 20% between AiRDose and standard measurements as clinically relevant. Five hundred forty-nine children (mean age, 4.8 years; standard deviation [SD], 2.9 years) were recruited. There were 99.6% of AiRDose lengths within a 20% difference of tape-measure lengths. There was a significant correlation between AiRDose and tape-measure length measurements (r = 0.989, P < 0.0001), and between AiRDose and Broselow weights (r = 0.983, P < 0.0001) and AiRDose and actual weights (r = 0.886, P < 0.0001). AiRDose lorazepam and epinephrine doses correlated significantly with Broselow lorazepam (r = 0.963, P < 0.0001) and epinephrine (r = 0.966, P < 0.0001) doses. Anthropometric estimates and medication dose recommendations provided by AiRDose strongly correlate with established techniques. Further study will establish the feasibility of using AiRDose to accurately obtain weight estimates and medication doses for pediatric patients in the prehospital setting.

Clinical pharmacology of lorazepam in infants and children

Lorazepam is a benzodiazepine has antiepileptic activity; it may be administered intravenously, intramuscularly, orally, by intranasal or buccal application and following oral dosing it is well absorbed. In infants, the initial intravenous dose of lorazepam is 100 µg/kg and in children the initial oral and intravenous dose is 50 to 100 µg/kg and the dose varies according to the child age. Lorazepam has been found efficacy and safe in infants and children but it may induce adverse-effects. Lorazepam is a racemate and the R and S enantiomers are conjugated with glucuronic acid in human liver microsomes and the respective Km and Vmax values are 29+8.9 and 36+10 µM and 7.4+1.9 and 10+3.8 pmol/min*mg. Lorazepam interacts with drugs and the interaction may affect the activity or metabolism of lorazepam. The pharmacokinetics of lorazepam have been studied in infants and children and in diseased children. In infants and children the elimination half-life is about 15 hours and it is about 24 hours and about 37 hours in children with severe malaria and convulsions following intravenous and intramuscular administration, respectively. The treatment and trials with lorazepam have been studied in infants and children. Lorazepam freely crosses the human placenta and poorly migrates into the breast-milk. The aim of this study is to review the published data on lorazepam dosing, efficacy and safety, adverse-effects, metabolism, interaction with drugs, pharmacokinetics, treatment and trials in infants and children and the lorazepam transfer across the human placenta and migration into the breast-milk.