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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest No conflicts of interest to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest This study did not receive any study funding or grants, and the authors of this manuscript declare they have no relevant financial disclosures or conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Serotonin syndrome (SS) is a rare, potentially life-threatening adverse drug reaction. Selective serotonin reuptake inhibitors (SSRIs) are among a number of pharmaceuticals that all contribute to SS, but SS caused by SSRI monotherapy is rare. We present a case of probable sertraline-induced SS. A 36-year-old male presented to the emergency department four times in one week with a constellation of autonomic and neuromuscular symptoms. He had been taking sertraline at a therapeutic dose for less than three months. Moderate SS was diagnosed using the Hunter criteria during the fourth visit, when it was seen that he had hyperreflexia and inducible ankle clonus. The patient's symptoms resolved within 24 hours with lorazepam, intravenous fluids, and discontinuation of sertraline. In the emergency department it is important to have a high clinical suspicion for SS even if the patient is taking SSRI monotherapy at therapeutic doses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate the safety and efficacy of a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam for the acute management of alcohol withdrawal syndrome (AWS)., Methods: This was a retrospective chart review of adult patients who presented to the Emergency Department with moderate or severe symptoms of alcohol withdrawal. Patients were included if they received at least 4 mg of lorazepam through the hospital's Alcohol Withdrawal Order Set on hospital day one. Patients who received a single parenteral dose of phenobarbital on hospital day one were compared to those who did not., Results: Forty patients received phenobarbital and 38 patients received lorazepam only. Median daily lorazepam requirements, disposition, hospital length of stay, and median maximum daily CIWA-Ar scores were not statistically significant different between the groups. Significantly more patients in the phenobarbital group were discharged within three days in comparison to the lorazepam only group (9 patients vs. 2 patients, respectively, p < 0.05). In the lorazepam only group, two patients were intubated, one patient had delirium tremens, and no patients seized. In the phenobarbital group no adverse events were observed., Conclusions: More patients were discharged within three days if they received a single parenteral dose of phenobarbital on hospital day one, in addition to symptom-triggered lorazepam for the acute management of AWS. Emergency Medicine physicians should consider ordering one parenteral phenobarbital dose on hospital day one to patients presenting with AWS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Long-term alcohol use confers neurochemical changes in response to alcohol's exogenous inhibitory effects. Downregulation and decreased sensitivity of γ-aminobutyric acid receptors render benzodiazepines less effective at controlling psychomotor agitation. Propofol has been reported to have successfully relieved alcohol withdrawal syndrome (AWS) symptoms in part because of activation of γ-aminobutyric acid channels in combination with antagonism of excitatory amino acids such as N-methyl-D-aspartate. Successful use of propofol in refractory AWS in patients with endotracheal intubation and mechanical ventilation has been reported. We present a case of resolution of AWS symptoms in a benzodiazepine-refractory, nonintubated, non-mechanically ventilated alcohol withdrawal patient with low-dose, continuous-infusion propofol.

We conducted a prospective double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia. Patients were randomized to either oral olanzapine (10 mg per day) or oral haloperidol (10 mg per day), plus lorazepam as needed (up to 12 mg per day). Antipsychotic dosage was increased to 20 mg per day as early as day 3. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) Agitation subscale during the first 24 hours of treatment, daily for the first week, then weekly until study completion. Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy (-5.79 +/- 6.30 for olanzapine and -4.89 +/- 6.05 for haloperidol, P <.001). This study demonstrated that accelerated dose titration of oral olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia.

The purpose of the present study was to compare the use of lorazepam plus nitroglycerine (NTG) versus NTG alone in the reduction of cocaine induced chest pain in the emergency department. The secondary objective of the study was to help determine the safety of lorazepam in the treatment of cocaine- associated chest pain. The study was a prospective, randomized, single-blinded, controlled trial conducted at an university-affiliated urban emergency department (ED). All patients who presented with cocaine-associated chest pain were enrolled. Exclusion criteria included age greater than 45 years, documented coronary artery disease, chest pain of more than 72 hours duration, or pretreatment with nitroglycerin. Patients were given either sublingual nitroglycerine (SL NTG) (Group 1) or SL NTG plus 1 mg of lorazepam intravenously (Group 2) every 5 minutes for a total of 2 doses. Chest pain was recorded on an ordinal scale of 0 to 10 at baseline, and then at 5 minutes after each dose. Adverse reactions to medication were also recorded. Twenty-seven patients met the inclusion criteria and were enrolled in the study. The average age of these subjects was 34.1 years, and 67% were men. The NTG-only group consisted of 15 patients and the NTG-plus-lorazepam group consisted of 12 patients. Baseline mean chest-pain scores were 6.87 in Group 1 and 6.54 in Group 2, with no differences between groups. Five minutes after initial treatment, mean scores for the two groups were 5.2 and 3.9, respectively, with a difference in means of 1.24 (95% confidence interval [CI] -0.8-3.8). Five minutes after the second treatment, the mean scores were 4.6 and 1.5, respectively, with a difference in means of 3.1 (95% CI 1.2-5). Kruskal-Wallis testing showed a significant difference in pain relief between the two study groups (P =.003), with greater pain relief noted at 5 and 10 minutes in the NTG-plus-lorazepam group (P =.02 and P =.005, respectively). All patients in the study were admitted to the hospital, but no patient in either group had an acute myocardial infarction or cardiac complications in the ED. No adverse side effects were noted for either group. The early use of lorazepam with NTG was more efficacious than NTG alone, and appears to be safe in relieving cocaine-associated chest pain., (Copyright 2003, Elsevier Science (USA). All rights reserved.))

A 49-year-old man presented with dizziness and altered behavior associated with a nonconvulsive seizure. He had a long history of well-controlled tonic-clonic seizures and daily episodes of 10-second staring spells. Despite normal neurological and laboratory examinations, an emergent electroencephalogram showed changes consistent with nonconvulsive generalized status epilepticus.

Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation.

A 15-year-old boy presented to the emergency department with status epilepticus and a blood ethanol concentration of 757 mg/dL. Mechanical ventilation and substantial amounts of benzodiazepines were required. His hospital course was complicated by aspiration pneumonia, but he had no episodes of hypoglycemia. He received 2.8 hours of hemodialysis, which increased the rate of ethanol elimination, but there is no evidence that hemodialysis improved his clinical outcome. To our knowledge, this is the highest blood ethanol level reported in a child or adolescent who survived.