A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

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.

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.

Catatonia and Delirium: Assessment of Comorbidity, Prevalence, and Therapeutic Response in Medically Ill Inpatients From a University Hospital.

BACKGROUND: Catatonia is a cluster of motor features present in multiple psychiatric and clinical diseases. It may be confused with delirium because both entities are classified according to the type and degree of psychomotor activity. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for catatonia secondary to medical conditions exclude comorbid catatonia and delirium; besides, there have been increasing reports about a comorbid presentation. This study aimed to describe the prevalence of comorbid catatonia and delirium, the therapeutic response to lorazepam, and the clinical characteristics of patients with an earlier diagnosis of delirium. METHODS: A total of 120 consecutive patients at a university hospital with an earlier diagnosis of delirium were evaluated using the Delirium Scale (confusion assessment method for the intensive care unit) and the Bush-Francis Catatonia Rating Scale for catatonia. In cases of a positive diagnosis of catatonia or catatonia/delirium, a therapeutic trial with intramuscular lorazepam was performed. FINDINGS: Thirty-one patients (26%) were positive for both catatonia and delirium, and 8 patients (7%) had catatonia. Sixty-six patients (55%) were positive only for delirium, and 5 patients (4%) were negative for delirium and catatonia. Lorazepam tests were applied on 22 patients. One in 9 patients with catatonia/delirium responded positively to lorazepam. Patients with catatonia had a 60% positive response rate. CONCLUSIONS: This is the first study on lorazepam use in catatonia-delirium patients; however, further studies are needed to determine the safety and efficacy of lorazepam in these patients. Catatonia and catatonia/delirium are underdiagnosed in inpatient wards and should be routinely assessed in patients with an altered mental status.

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.

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.

Pharmacologic predictors of benzodiazepine response trajectory in anxiety disorders: a Bayesian hierarchical modeling meta-analysis.

BACKGROUND: Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown. METHODS: We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in anxiety was evaluated as a function of medication, disorder, time, potency, lipophilicity, and standardized dose and compared among benzodiazepines. RESULTS: Data from 65 trials (73 arms, 7 medications, 7110 patients) were included. In the logarithmic model of response, treatment effects emerged within 1 week of beginning treatment (standardized benzodiazepine-placebo difference = -0.235 ± 0.024, CrI: -0.283 to -0.186, P < .001) and placebo response plateaued at week 4. Doses <6 mg per day (lorazepam equivalents) produced faster and larger improvement than higher doses (P = .039 for low vs medium dose and P = .005 for high vs medium dose) and less lipophilic benzodiazepines (beta = 0.028 ± 0.013, P = .030) produced a greater response over time. Relative to the reference benzodiazepine (lorazepam), clonazepam (beta = -0.217 ± 0.95, P = .021) had a greater trajectory/magnitude of response (other specific benzodiazepines did not statistically differ from lorazepam). CONCLUSIONS: In adults with anxiety disorders, benzodiazepine-related improvement emerges early, and the trajectory and magnitude of improvement is related to dose and lipophilicity. Lower doses and less lipophilic benzodiazepines produce greater improvement.

Statewide Emergency Medical Services Protocols for Status Epilepticus Management.

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.

Prospective study of haloperidol plus lorazepam versus droperidol plus midazolam for the treatment of acute agitation in the emergency department.

STUDY OBJECTIVES: The objective of this study was to compare the combination of intramuscular (IM) droperidol/midazolam to haloperidol/lorazepam regarding time to sedation in patients with acute undifferentiated agitation in the emergency department (ED). METHODS: This was a prospective, unblinded observational study in the ED of a university teaching hospital. Subjects with acute undifferentiated agitation refractory to verbal de-escalation were assigned to receive a combination of either haloperidol 5 mg/lorazepam 2 mg or droperidol 5 mg/midazolam 5 mg IM. The primary outcome was the proportion of patients adequately sedated at 10 min defined as ED Sedation Assessment Tool (SAT) score of 0 or less. Secondary outcomes included change in ED SAT score at 5, 15, 30, and 60 min, the need for oxygen supplementation, and the need for airway intervention. RESULTS: A total of 86 patients were enrolled in the study, with 43 patients receiving droperidol/midazolam and 43 patients receiving haloperidol/lorazepam. Ten minutes after receiving medication, 51.2% of patients in the droperidol/midazolam group were adequately sedated compared to 7% of patients in the haloperidol/lorazepam group (OR: 14; 95% CI: 3.7, 52.1). Median time to adequate sedation was 10 min for the droperidol/midazolam group and 30 min for the haloperidol/lorazepam group. Eleven patients (25.6%) in the droperidol/midazolam group received oxygen supplementation compared to four patients (9.3%) in the haloperidol/lorazepam group. No study patients experienced extrapyramidal symptoms or required endotracheal intubation. CONCLUSION: Intramuscular droperidol/midazolam was superior to intramuscular haloperidol/lorazepam in achieving adequate sedation at 10 min. Patients in the droperidol/midazolam arm may be more likely to receive oxygen supplementation than those in the haloperidol/lorazepam arm.

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

Background Despite 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. METHODS: Retrospective, 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. RESULTS: Twenty 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. CONCLUSION: Pharmacist 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.

Resolution of status epilepticus after ketamine administration.

BACKGROUND: Status Epilepticus is the most common non-traumatic neurologic emergency in childhood. Current algorithms prioritize the use of benzodiazepines as first line treatment followed by Levetiracetam or Valproic Acid, possibly Fosphenytoin and eventually high dose Propofol and intubation. CASE REPORT: A 9-month old girl was brought to the emergency department with a continuous seizure involving the right upper and lower extremity for 45 min prior to arrival. Patient received a dose of rectal Diazepam, intramuscular Midazolam, 2 doses of Lorazepam, Levetiracetam, Fosphenytoin and 2 additional doses of Lorazepam. The seizure remained refractory and generalized. In anticipation of intubation, and because of its action on the NMDA receptor, Ketamine (1 mg/kg IV) was administered. The clonic movements and eye deviations stopped. Patient was intubated for airway protection, sedated with Propofol, then admitted to the PICU. EEG showed no evidence of a seizure pattern. Labs (CBC, CMP, COVID) were unremarkable except for WBC 24.5, blood glucose of 346 and CO2 of 17 with normal anion gap. Urinalysis showed a urinary tract infection. Patient was at her baseline on 1 week post-discharge re-evaluation. Ketamine theoretically may abort seizures through blockade of NMDA receptors which are unregulated in status epilepticus. To date, no randomized controlled trials have been reported. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ketamine may have a role in treating status epilepticus. It may be considered for induction for rapid sequence intubation and possibly as a third or fourth line agent in refractory cases.

Efficacy of Combination Haloperidol, Lorazepam, and Diphenhydramine vs. Combination Haloperidol and Lorazepam in the Treatment of Acute Agitation: A Multicenter Retrospective Cohort Study.

BACKGROUND: Antipsychotic and sedative combinations are commonly used for treating agitation in the emergency department despite limited evidence regarding their comparative safety and efficacy. OBJECTIVES: To compare the efficacy and safety of combination haloperidol, lorazepam, and diphenhydramine (B52) to combination haloperidol and lorazepam (52) in treating acute agitation. METHODS: This multicenter, retrospective cohort study included adult patients ≥ 18 years of age who received either B52 or 52 at a Banner Health facility between August 2017 and September 2020. Patients were excluded if they had a pre-existing movement disorder or were withdrawing from alcohol. The primary outcome was administration of additional agitation medication(s) within 2 h of B52 or 52. Secondary outcomes included incidence of extrapyramidal symptoms, length of stay, and additional safety measures. RESULTS: There was no difference in administration frequency of additional agitation medication(s) (B52: n = 28 [14%] vs. 52: n = 40 [20%]; p = 0.11). Patients who received 52 were more likely to require an antimuscarinic medication within 2 days (15 vs. 6 patients, p = 0.04). Of the patients who received an antimuscarinic medication, none had documented extrapyramidal symptoms. The 52 group had shorter length of stay (13.8 vs. 17 h; p = 0.03), lower incidence of hypotension (7 vs. 32 patients; p < 0.001), and oxygen desaturation (0 vs. 6 patients; p = 0.01), and fewer physical restraints (53 vs. 86 patients; p = 0.001) compared with the B52 group. CONCLUSIONS: Both the B52 and 52 combinations infrequently required repeat agitation medication; however, the B52 combination resulted in more oxygen desaturation, hypotension, physical restraint use, and longer length of stay.

Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial.

OBJECTIVE: This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second-line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline-recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second-line agent. RESULTS: Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second-line medications in these benzodiazepine-refractory seizures. SIGNIFICANCE: Benzodiazepines as first-line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.).

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study.

OBJECTIVE: We aimed to examine the impact of resumption of home antiseizure drugs alone (ASD-) compared with adjunct administration of scheduled intravenous (IV) lorazepam 2 mg every 6 h (ASD+) following ictal single-photon emission computed tomography (SPECT) injection on the localization value of SPECT studies and treatment-emergent adverse events (TEAEs). METHODS: We conducted a prospective study at Mayo Clinic inpatient epilepsy monitoring unit (EMU) between January 2018 and May 2020 in Jacksonville, Florida. The ASD- and ASD+ groups were compared for concordance of SPECT studies with the epilepsy surgical conference (ESC) consensus or intracranial electroencephalography (icEEG) findings as reference. Treatment-emergent adverse events, obtained from surveys at 24 h and one week postictal SPECT injection, were also compared between both groups. RESULTS: Twenty-two consecutive patients with temporal (eight patients, 36%) and extratemporal (14 patients, 64%) epilepsy were included: 12 ASD+ and 10 ASD-. The two groups were well matched with regard to clinical and ictal SPECT injection characteristics including the occurrence of seizure between ictal and interictal SPECT injections. The localization value of SPECT studies was similar in the two groups. Patients in the ASD+ group reported higher rates of dizziness and excessive sedation at 24 h (p-value = 0.008). Fourteen patients (64%) underwent icEEG monitoring. For the entire cohort, the localization concordance of SPECT analysis by statistical parametric mapping (SPM) was superior to raw ictal SPECT (p-value = 0.003) and subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM; p-value = 0.021). Eventually, seven patients (31.8%) underwent resective brain surgery of whom four (57.1%) became seizure-free (median follow-up = 22 months). CONCLUSIONS: Our findings suggest that resuming home ASDs without the addition of scheduled IV lorazepam following inpatient ictal SPECT injection is equally efficacious for seizure onset zone (SOZ) localization on SPECT studies, especially SPM. This approach is also associated with fewer transient TEAEs and lower financial cost with no difference in preventing seizure between ictal and interictal SPECT injections.

Concomitant lorazepam use and antidepressive efficacy of repetitive transcranial magnetic stimulation in a naturalistic setting.

BACKGROUND/OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective therapeutic intervention for the treatment of depression. Preliminary data suggest that the efficacy of rTMS is reduced in patients taking benzodiazepines (BZD). Here, we use real-world data from a large sample to investigate the influence of lorazepam on the effectiveness of rTMS. METHODS: From a retrospective cohort of clinically depressed patients that were treated with rTMS, we compared 176 patients not taking any BZD with 73 patients taking lorazepam with respect to changes in the Hamilton Depression Rating Scale (HRDS). RESULTS: Both groups improved during rTMS according to HRDS scores, but the amelioration of symptoms was significantly less pronounced in patients taking lorazepam (18% vs. 38% responders in the non-lorazepam group). We could not see any association of intake regimen of lorazepam with response in rTMS. CONCLUSION: Our observational study suggests that intake of lorazepam impedes the response to rTMS. The impact of lorazepam and other BZD on rTMS should receive more attention and be further investigated in prospective, hypothesis-based treatment studies to determine causal relationships between medication treatments and outcome. This could lead to specific recommendations for pharmacological treatment for depressed patients undergoing rTMS.

Association among rescue neuroleptic use, agitation, and perceived comfort: secondary analysis of a randomized clinical trial on agitated delirium.

BACKGROUND: Few studies have examined how the use of rescue medications could be used to inform on the efficacy of interventions in delirium clinical trials. The objective of this study was to determine the association among rescue medication use, Richmond Agitation-Sedation Scale (RASS), and perceived comfort by the nurses and caregivers. METHODS: This was a pre-planned secondary analysis of a double-blind, randomized clinical trial comparing the use of a single dose of lorazepam plus haloperidol versus placebo plus haloperidol in patients with agitated delirium. Rescue medications were considered the gold standard for this analysis. The optimal cutoff for RASS analysis was calculated by using general linear regression models and determining the area of the curve and using the top left approach. We used 2 × 2 tables to examine the association between rescue medication use and perceived comfort. RESULTS: Fifty-eight patients received the study medications and 52 (89%) completed the 8-h observation period. There were 26 (50%) patients in each arm. The lorazepam/haloperidol arm required fewer rescue doses (4/26 (15%)) vs. 16/26 (62%), p = 0.004). Patients with a greater initial RASS reduction required fewer rescue doses. The cutoff value for RASS improvement was 4 points, area under the curve (AUC) 0.64 (95% CI 0.49-0.79) for those who required no rescue doses, and 3 points, AUC 0.74 (95% CI 0.52-0.96) for those who required more than one rescue dose. CONCLUSIONS: Rescue medication use was responsive to change and associated with both RASS scores and perceived patient comfort by the nurse and caregiver.

Front-loaded diazepam versus lorazepam for treatment of alcohol withdrawal agitated delirium.

BACKGROUND: Front-loaded diazepam is used to rapidly control agitation in patients with severe alcohol withdrawal syndrome (AWS). Our institution began using front-loaded lorazepam in August 2017 secondary to a nation-wide shortage of intravenous (IV) diazepam. Currently, there are no studies comparing lorazepam to diazepam for frontloading in severe AWS. METHOD: Retrospective cohort study of all adults presenting to the emergency department with a diagnosis of AWS and prescribed the institution's alcohol withdrawal agitated delirium protocol 8 months pre and post shortage of IV diazepam were eligible inclusion for the study. Of these, 106 patients were front-loaded with diazepam and 70 patients were front-loaded with lorazepam. RESULTS: There was no difference in the mean change in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised scores 24 h pre and post front-loading in the two groups (-13.9 ± -8.08 vs. -13.1 ± -8.91, p = 0.534). Patients who received front-loaded lorazepam had an increased incidence of ICU-delirium (positive for the Confusion Assessment Method in the ICU: 75% with lorazepam vs. 52.6% with diazepam, p = 0.009) and a higher risk of over-sedation, but this did not reach statistical significance (Richmond Agitation-Sedation Scale score < -1: 32.1% with lorazepam vs. 18.2% with diazepam, p = 0.063). CONCLUSION: Front-loaded lorazepam was similar to front-loaded diazepam in controlling AWS symptoms. Lorazepam's delayed onset of action should be considered when determining how quickly repeat doses are administered to avoid the potential for adverse drug events.

Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study.

BACKGROUND: Clinicians often encounter agitated patients, and current treatment options include benzodiazepines and antipsychotics. Ketamine rapidly induces dissociation, maintains cardiovascular stability, spontaneous respirations, and airway reflexes. There are no prospective, randomized studies comparing ketamine to other agents in the initial management of acute agitation in the Emergency Department (ED). OBJECTIVE: Determine the efficacy and safety of ketamine compared to parenteral haloperidol plus lorazepam for initial control of acute agitation. METHODS: This study was a prospective, single-institution, randomized, open-label, real world, standard of care pilot study. Adult patients with combative agitation were randomized to ketamine (4 mg/kg IM or 1 mg/kg IV) or haloperidol/lorazepam (haloperidol 5-10 mg IM or IV + lorazepam 1-2 mg IM or IV). The primary outcome was sedation within 5 min, and secondary outcomes included sedation within 15 min, time to sedation, and safety. RESULTS: Ninety three patients were enrolled from January 15, 2018 to October 10, 2018. Significantly more patients who received ketamine compared to haloperidol/lorazepam were sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p < 0.001). The median time to sedation in patients who received ketamine compared to haloperidol/lorazepam was 15 vs 36 min respectively (p < 0.001). Patients who received ketamine experienced a significant, but transient tachycardia (p = 0.01) and hypertension (p = 0.01). CONCLUSION: In patients with combative agitation, ketamine was significantly more effective than haloperidol/lorazepam for initial control of acute agitation, and was not associated with any significant adverse effects.

Lorazepam Versus Diazepam in the Management of Emergency Department Patients With Alcohol Withdrawal.

STUDY OBJECTIVE: Alcohol withdrawal is a common emergency department (ED) presentation. Although benzodiazepines reduce symptoms of withdrawal, there is little ED-based evidence to assist clinicians in selecting appropriate pharmacotherapy. We compare lorazepam with diazepam for the management of alcohol withdrawal to assess 1-week ED and hospital-related outcomes. METHODS: From January 1, 2015, to December 31, 2018, at 3 urban EDs in Vancouver, Canada, we studied patients with a discharge diagnosis of alcohol withdrawal. We excluded individuals presenting with a seizure or an acute concurrent illness. We performed a structured chart review to ascertain demographics, ED treatments, and outcomes. Patients were stratified according to initial management with lorazepam versus diazepam. The primary outcome was hospital admission, and secondary outcomes included in-ED seizures and 1-week return visits for discharged patients. RESULTS: Of 1,055 patients who presented with acute alcohol withdrawal, 898 were treated with benzodiazepines. Median age was 47 years (interquartile range 37 to 56 years) and 73% were men. Baseline characteristics were similar in the 2 groups. Overall, 69 of 394 patients (17.5%) receiving lorazepam were admitted to the hospital compared with 94 of 504 patients receiving diazepam (18.7%), a difference of 1.2% (95% confidence interval -4.2% to 6.3%). Seven patients (0.7%; 95% confidence interval 0.3% to 1.4%) had an in-ED seizure, but all seizures occurred before receipt of benzodiazepines. Among patients discharged home, 1-week return visits occurred for 78 of 325 (24.0%) who received lorazepam and 94 of 410 (23.2%) who received diazepam, a difference of 0.8% (95% confidence interval -5.3% to 7.1%). CONCLUSION: In our sample of ED patients with acute alcohol withdrawal, patients receiving lorazepam had an admission rate similar to that of those receiving diazepam. The few in-ED seizures occurred before medication administration. For discharged patients, the 1-week ED return visit rate of nearly 25% could warrant enhanced follow-up and community support.

Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. OBJECTIVE: In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.