Doses Of Benzodiazepines Research Articles

A multifaceted quality improvement intervention to improve management of alcohol withdrawal on a general medicine ward: impact on benzodiazepine use

Objective: To measure the effects of a quality improvement intervention on length of stay and benzodiazepine use among patients admitted for alcohol use disorder. Methods: This retrospective cohort study was performed at the Salt Lake City Veterans Affairs Medical Center. Patients 18 years and older admitted to a general medical ward with a diagnosis of alcohol related disorders who were treated for alcohol withdrawal were included. The baseline cohort included patients admitted over 12 months. The post-intervention cohort included patients admitted over 12 months. Primary outcomes were total benzodiazepine dose and length of stay. Secondary outcomes included episodes of delirium tremens and seizures. Results: Total benzodiazepine dose decreased significantly over the intervention period. Length of stay also decreased. No episodes of delirium tremens or seizures were observed. Conclusions: A quality improvement intervention directed at general medicine inpatients admitted for alcohol withdrawal was associated with reductions in total benzodiazepine administration and length of stay.

Prediction of Postictal Delirium Following Status Epilepticus in the ICU: First Insights of an Observational Cohort Study.

To identify early predictors of postictal delirium in adult patients after termination of status epilepticus. Retrospective study. ICUs at a Swiss tertiary academic medical center. Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018. None. Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation). Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1-3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53-7.33). Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2-3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.

Convulsive Status Epilepticus in a Cohort of Patients from a Peruvian Academic Hospital.

Background and PurposeStatus epilepticus is a neurologic emergency whose epidemiology, etiology and management are scarcely known in developing countries. Our objective was to describe the demographic and clinical features as well as the management of generalized convulsive status epilepticus (GCSE) in adult patients admitted to the emergency department of an academic hospital in Peru, between March 2019 and March 2020.MethodsObservational study of a prospective cohort in which patients were assessed by the emergency and neurology department on the first day of hospitalization, at discharge and at 30 days post-discharge in a follow-up visit. Relevant demographics and clinical data were collected. After being encoded and sorted, univariate statistical analysis was carried out.ResultsOf the sample of 59 patients, 62.7% were males, 57.6% were unemployed, 89.8% did not finish high school, and 55.9% had intermittent GCSE with no seizure at arrival. The total calculated median times were: 60 minutes from GCSE onset to hospital arrival, 110 minutes from GCSE onset to 1st line therapy, and 7 minutes from hospital arrival to 1st line therapy. The most frequently used antiepileptic drugs were one dose of benzodiazepine (41.7%), phenytoin (76.9%), and additional doses of benzodiazepines (60%) for 1st, 2nd, and 3rd line therapies, respectively. The most frequent etiologies were antiepileptic drug suspension (27.1%), undetermined (25.4%) and acute stroke (11.8%). 62.71% had 0–2 modified Rankin score at discharge.ConclusionsIn this cohort of patients, GCSE was mainly intermittent. Management times differed from the guidelines’ recommendations.

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Modern H1- antihistamines in the treatment of allergic rhinitis: focus on bilastine

The second generation of H1-antihistamines is approved for the stepwise treatment of seasonal and perennial allergic rhinitis in adults and children by international and national guidelines. They reduce the severity of nasal and ocular symptoms of rhinitis and improve the quality of life of patients.
 Bilastine, a piperidine derivative, is a novel H1-antihistamine. It has a potent and selective effect on H1- receptors and a rapid onset and long duration of action and substantially reduces nasal and ocular symptoms of seasonal and perennial allergic rhinitis. Bilastine has no clinically substantial hepatic metabolism and has a high safety profile: it has no sedative effect, does not affect cognitive functions, has no cardiotoxic effects, and does not interact with alcohol and benzodiazepines in normal and high doses. Tachyphylaxis does not develop despite long-term (up to 1 year) use.
 Bilastine is registered for clinical use in adults and children aged 12 years. The results of clinical and experimental studies have demonstrated that bilastine has many of the features of modern H1-antihistamines recommended by international guidelines.

Status epilepticus: Practice variation and adherence to treatment guideline in a large community hospital

PurposeTo evaluate the treatment of status epilepticus (SE) and adherence to treatment guideline in a large Finnish community hospital. Materials and methodsA consecutive series of 137 patients treated in the emergency department of Kuopio University Hospital. Enrollment took place between March 23 and December 31, 2015. Pediatric patients and postanoxic seizures were excluded. The Finnish Status Epilepticus Current Care Guideline was used as the evaluation benchmark. ResultsSeventeen patients recovered spontaneously. First-line treatment was given to 108 patients with 35.2% efficacy. Second-line treatment was given to 81 patients with 87.7% efficacy. Six patients with refractory SE received successful third-line treatment and four were excluded from intensive care because of futility. The starting dose of a first-line drug was lower than the lowest therapeutic dose in 37.0% of the patients. The escalation from first- to second-line treatment took longer than 60 min in 55.1% of the 70 patients who received both treatments. The first loading dose of a second-line drug was markedly low (<80% of the recommended dose) in 26.2% of the 81 patients treated with second-line drugs. ConclusionsPrompt and effective pharmacotherapy is the cornerstone of good SE treatment. Subtherapeutic doses of first-line benzodiazepines should be avoided. Benzodiazepine-resistant SE must be recognized early to facilitate rapid treatment escalation. The quality of second-line treatment suffers from excessive delays and inadequate weight-based dosing of antiseizure medications.

Integrating pharmacists into aged care facilities to improve the quality use of medicine (PiRACF Study): protocol for a cluster randomised controlled trial

BackgroundMedication management in residential aged care facilities is an ongoing concern. Numerous studies have reported high rates of inappropriate prescribing and medication use in aged care facilities, which contribute to residents’ adverse health outcomes. There is a need for new models of care that enhance inter-disciplinary collaboration between residential aged care facility staff and healthcare professionals, to improve medication management. Pilot research has demonstrated the feasibility and benefits of integrating a pharmacist into the aged care facility team to improve the quality use of medicines. This protocol describes the design and methods for a cluster randomised controlled trial to evaluate the outcomes and conduct economic evaluation of a service model where on-site pharmacists are integrated into residential aged care facility healthcare teams to improve medication management.MethodsIntervention aged care facilities will employ on-site pharmacists to work as part of their healthcare teams 2 to 2.5 days per week for 12 months. On-site pharmacists, in collaboration with facility nurses, prescribers, community pharmacists, residents and families will conduct medication management activities to improve the quality use of medicines. Aged care facilities in the control group will continue usual care. The target sample size is 1188 residents from a minimum of 13 aged care facilities. The primary outcome is the appropriateness of prescribing, measured by the proportion of residents who are prescribed at least one potentially inappropriate medicine according to the 2019 Beers Criteria. Secondary outcomes include hospital and emergency department presentations, fall rates, prevalence and dose of antipsychotics and benzodiazepines, Anticholinergic Cognitive Burden Score, staff influenza vaccination rate, time spent on medication rounds, appropriateness of dose form modification and completeness of resident’s allergy and adverse drug reaction documentation. A cost-consequence and cost-effectiveness analysis will be embedded in the trial.DiscussionThe results of this study will provide information on clinical and economic outcomes of a model that integrates on-site pharmacists into Australian residential aged care facilities. The results will provide policymakers with recommendations relevant to further implementation of this model.Trial registrationACTRN12620000430932. Registered on 1 April 2020 with ANZCTR

Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A Multicenter Study.

Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements. The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS. This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation. There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality. Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.

Different Attitudes of Patients and Psychiatrists Toward Benzodiazepine Treatment.

BackgroundConcern regarding the benefit/risk ratio of the long-term use of benzodiazepines (BDZs) and Z-drugs is increasing. To prevent the risk of dependence in BDZ long-term use, it is essential to understand the attitudes of patients and psychiatrists toward BDZ treatment. The aims of this investigation were to 1) obtain information on patients’ attitudes with long-term BDZ use and their referring psychiatrists’ attitudes toward BDZ treatment, including their perception of the difficulty of reducing the dose of BDZs, and 2) identify discrepancies between patients’ and psychiatrists’ perceptions.MethodsA brief questionnaire was constructed to investigate the attitudes of patients receiving BDZ treatment and their referring psychiatrists. Our sample comprised 155 patients who received BDZ treatment for more than one year and their referring eight psychiatrists. Both the patients and their psychiatrists completed our questionnaire between August 2017 and December 2017.ResultsOf the patients, 13% felt that it was more difficult to reduce the dose of BDZs than their referring psychiatrists (type A discrepancy), while 25% felt that it was less difficult (type B discrepancy). In the multivariate logistic regression analysis, the female sex and both the patients’ (“psychotherapy plus BDZs was necessary” and “it was necessary to increase the dose of BDZs”) and psychiatrists’ beliefs (“short-term prescription was justified”) were associated with type A discrepancies. Type B discrepancies were associated with psychiatrists’ beliefs that the patient’s wishes justified the use of BDZs and that the cessation of treatment with BDZs would lead to the deterioration of their rapport with their patients.ConclusionTo overcome the discrepancies in the attitudes of patients and psychiatrists toward the cessation of BDZ treatment, it is necessary to promote patient-centered care involving patient psychoeducation and practice guidelines for the decision-making process. Further studies investigating the promotion of patient-centered care to reduce BDZ use are needed.

An audit of the use of psychotropic medications over the course of admission to a specialist dementia ward

AimsThe aim of this audit project was to establish the practices in prescribing and de-prescribing of psychotropic medications for patients on a specialist dementia ward.BackgroundThere is a great deal of evidence demonstration high rates of polypharmacy, defined as ≥5 drugs, in older adults in general and in those with dementia more specifically. NICE guidelines recommend a structured assessment of a patient with dementia to exclude other potential causes, e.g. pain or delirium. Psychosocial interventions are recommended as first line. Antipsychotics should only be offered second line who present a risk to themselves or others. These should only be used for the shortest time possible and reassessed at least every 6 weeks.MethodData were collected for patients (n = 20) discharged from a specialist dementia ward between September 2018 and March 2019. The unit has 14 beds caring for patients with predominantly severe behavioural and psychological symptoms associated with dementia (BPSD). The team is comprised of doctors, nurses, a clinical psychologist, occupational therapists, physiotherapists and pharmacists who meet twice a week to review patients. Data were coded by drug class and counts of medication on admission, at the midpoint and at discharge were conducted. Antipsychotic and benzodiazepine dosages were converted into haloperidol and diazepam equivalence.ResultOf the 20 patients, 70% were male and 30% female. 95% of the patient (n = 19) were admitted under the Mental Health Act (1983). 20% were managed on 1 to 1 observations and 80% were on 15 min observations. In general, the results show little change in the overall rate of psychotropic prescribing. The mean number of psychotropic medications prescribed per patient on admission was 2.30, at the mid-point of admission it was 2.30 and at discharge it was 2.05. Mean benzodiazepine dosage in diazepam equivalence reduced between admission and discharge from 3.20 mg to 2.10 mg. Mean haloperidol equivalent dosages increased at the midpoint of admission from 1.11 mg to 2.27 mg before reducing to 0.78 mg at discharge.ConclusionThe results demonstrate minimal change in the overall average number and composition of drugs prescribed. There are differences in the use of regular antipsychotics and benzodiazepines between admission and discharge which are consistent with NICE guidelines. Patients had a structured assessment with regular medicines reconciliation supervised by the team pharmacist. Therefore, the ward environment did allow for detailed discussions about de-prescribing which may not be the case elsewhere.

Relationship between benzodiazepine prescription, aggressive behavior, and behavioral disinhibition: a retrospective study in a Swiss prison

BackgroundBenzodiazepines are commonly prescribed in prisons amidst the controversies surrounding their potential role in causing behavioral disinhibition and aggressive behavior and their association with use and trafficking of illicit and addictive substances. The present study aimed to (1) ascertain the relationship between benzodiazepine prescription (including their dosage and duration of use) and aggressive behavior and behavioral disinhibition in prison and (2) investigate whether there was an association between benzodiazepine prescription, (including their dosage and duration of use) and using and trafficking illicit and addictive substances during imprisonment.MethodsData were extracted from the electronic database of an “open” Swiss prison (n = 1206, 1379 measures) over a 5-year period (2010–2015). Measures included benzodiazepine prescription, duration of benzodiazepine use and mean dosage, and punishable behaviors (physical and verbal aggression, disinhibited but not directly aggressive behaviors, property damage or theft, substance-related offenses, and rule transgression). We assessed the relationship between benzodiazepine prescription and punishable behaviors after propensity score matching. Logistic regressions were also used to test the relationship of benzodiazepine use duration and dosage with punishable behaviors among participants who received benzodiazepines.ResultsAfter propensity score matching, benzodiazepine prescription was not significantly associated with any punishable behavior. Among detained persons who took benzodiazepines, there was no significant association of dosage and duration of use with offenses involving illicit or addictive substance use or trafficking.ConclusionsOur study did not empirically support the occurrence of increased aggressive or disinhibited behaviors or increased risk of substance abuse in detained persons who received benzodiazepines in prison. This suggests a need to reconsider restrictions in prescribing benzodiazepines in the prison setting.

744 Correlates to improvement in sleep in acute mania

Abstract Introduction Sleep disruption and reduced sleep duration are potential triggers and also core symptoms of a manic episode. Our understanding of how sleep duration changes during the course of a manic episode and its potential association with symptom improvement is limited. We examined the natural course of sleep duration and its association with time to discharge and other clinical and demographic factors in patients with mania. Methods This was a retrospective study conducted in patients admitted to an acute care psychiatric unit with a manic episode. Sleep duration was determined based on observer report as logged by nursing staff. Sleep duration at admission and discharge were determined by averaging the total sleep time on day 2/3 of hospitalization and day 3/2 preceding discharge date. We obtained data on possible confounders including antipsychotic (chlorpromazine equivalents), benzodiazepine (diazepam equivalents) and other hypnotic medication doses administered at admission and discharge. We examined the associations between the change in sleep duration from admission to discharge with length of hospitalization and other clinical and demographic characteristics. Results The sample consisted of 35 patients (54.3% male) aged 32 ± 9.96 years with an average length of hospitalization of 20.63 ± 18.62 days. The mean sleep duration on admission was 6.23 ± 1.77 hours and was 7.45 ± 1.49 hours on discharge, with a mean change of 1.23 ± 1.93 hours. The change in sleep duration was positively correlated with length of hospitalization (r=0.42; p=0.01). Other clinical factors including benzodiazepine or antipsychotic dose on admission, age, sex, and use of mood stabilizers were not correlated with the change in sleep duration. Conclusion There was a substantial improvement in the total sleep duration in patients with mania over the course of hospitalization. Overall, the change in sleep duration was only correlated to the length of stay and did not appear to be impacted by other clinical and demographic characteristics. Support (if any):

Effect of medication on risk of traumatic brain injury in patients with bipolar disorder: A nationwide population-based cohort study.

Increased traumatic brain injury (TBI) risk was found in patients with bipolar disorder (BPD). Whether the medications for BPD and dosage moderate the risk of TBI is not clear. This study aimed to determine whether an association exists between BPD and TBI and whether the prescription of psychotropics moderates TBI risk. A total of 5606 individuals who had received diagnoses of BPD between January 1, 1997 and December 31, 2013 and 56,060 matched controls without BPD were identified from Taiwan's National Health Insurance Research Database. Cases and controls were followed until the date of TBI diagnosis. BPD was associated with a high risk of TBI (adjusted hazard ratio (aHR): 1.85; 95% CI: 1.62-2.11). Patients with BPD, with or without a history of psychiatric hospitalization, had increased risks of TBI (aHR: 1.94, 95% CI: 1.57-2.4 and aHR: 1.82, 95% CI: 1.55-2.1, respectively). The prescription of typical antipsychotics (0 < defined daily dose (DDD) < 28: hazard ratio (HR) = 1.52, 95% CI: 1.19-1.94; ⩾28 DDD: HR = 1.54, 95% CI: 1.15-2.06) and tricyclic antidepressants (TCAs) (0 < DDD < 28: HR = 1.73, 95% CI: 1.26-2.39; ⩾28 DDD: HR = 1.52, 95% CI: 1.02-2.25) was associated with higher TBI risk. Patients receiving higher doses of benzodiazepines (BZDs) (cumulative dose ⩾28 DDD) had a higher TBI risk (HR = 1.53, 95% CI: 1.13-2.06). Patients with BPD have a higher risk of TBI. The use of typical antipsychotics, TCAs, or high-dose BZDs increases the risk of TBI in BPD.

Association Between Benzodiazepine and Opioid Prescription and Mortality Among Patients in a Large Healthcare System.

Coprescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ coprescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system. Using data from the California state Prescription Drug Monitoring Program during 2010 to 2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5202 patients (1978 with OUD, 3224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality. About 10.5% of the sample died on or before December 31, 2014. About 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]=1.34, 95%CI: 1.15-1.55 per 10 mg/d increment) and opioids (OR = 1.04, 95%CI: 1.02-1.05 per 10 mg/d increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) = 3.83, 95%CI: 1.78-8.21). Study findings highlight significant mortality associated with the coprescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are co-prescribed opioids and BDZ.

Older adults’ perceptions of deprescribing chronic benzodiazepines

ObjectiveThe primary objective of our study was to explore older adults’ willingness to stop or lower the dose or frequency their chronic benzodiazepine with the long-term goal of developing a patient-centered intervention to support older adults during the deprescribing process. MethodsWe conducted semistructured interviews with adults aged 60 years and older who reported taking a benzodiazepine for at least 3 months. We recruited participants using our institutional research recruitment website between September and November 2019. Eligible participants completed an interview which was audio-recorded and subsequently transcribed. We identified themes related to older adults’ willingness to consider deprescribing their benzodiazepine, if recommended by their prescriber in a hypothetical scenario. Secondary outcomes focused on their use and perceptions of taking a benzodiazepine as well as their experiences attempting to stop the medication. ResultsAmong the 21 participants, most were female (n = 14, 66.7%), white (n = 20, 95.2%), and reported good or fair health (n = 17, 81.0%). More than three-fourths of participants who reported data (n = 14 of 18, 77.8%) had taken a benzodiazepine for 6 or more years. Participants generally reported that the medication was very effective (n = 16, 76.2%) and adverse effects were infrequent (n = 5, 23.8%). Participants varied widely in their attitudes toward the hypothetical questions about changing their current benzodiazepine. A total of 7 people were open to stopping the medication, 4 were willing to potentially consider it, and 10 were resistant. However, most of the participants were open to the idea of de-escalation (n = 17, 81.0%). ConclusionMany older adults were willing to consider deprescribing a long-term benzodiazepine if it were recommended by their prescriber. Older adults were more open to consider lowering the dose or frequency of the chronic benzodiazepine than stopping the medication. Further research is needed to design a patient-centered intervention tool to support prescribers and older adults in deprescribing conversations about benzodiazepines.

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness. Of 478 patients, 117 (24.5%) were intubated within 120 minutes. Among high-enrolling sites, intubation rates ranged from 4% to 32% at pediatric sites and 19% to 39% at adult sites. Baseline characteristics, including seizure precipitant, benzodiazepine dosing, and admission vital signs, provided limited discrimination for predicting intubation (area under the curve [AUC] 0.63). However, treatment at sites with an intubation rate in the highest (vs lowest) quartile strongly predicted endotracheal intubation independently of other treatment variables (adjusted odds ratio [aOR] 8.12, 95% confidence interval [CI] 3.08-21.4, model AUC 0.70). Site-specific variation was the factor most strongly associated with endotracheal intubation after adjustment for 20-minute (aOR 23.4, 95% CI 6.99-78.3, model AUC 0.88) and 60-minute (aOR 14.7, 95% CI 3.20-67.5, model AUC 0.98) neurologic recovery. Endotracheal intubation after established status epilepticus is strongly associated with site-specific practice pattern variation, independently of baseline characteristics, and early neurologic recovery and should not alone serve as a clinical trial endpoint in established status epilepticus. ClinicalTrials.gov Identifier: NCT01960075.

S2k-Leitlinie: Status Epilepticus im Erwachsenenalter

Diese S2k-Leitlinie (LL) zum Status epilepticus (SE) im Erwachsenenalter schreibt die letzte DGN-LL zum SE von 2012 fort. Neue Definitionen und Evidenz wurden bei der Erstellung der LL und des Clinical Pathway berücksichtigt. Jeder epileptische Anfall, der länger als 5 Minuten anhält (oder ≥ 2 Anfälle über einen Zeitraum von mehr als 5 Minuten ohne Wiedererlangen des neurologischen Ausgangsstatus), soll als SE behandelt werden.In der Diagnostik sollte initial eine CCT oder, wenn möglich, eine MRT erfolgen. Das EEG spielt bei der Diagnosestellung und beim Therapiemonitoring von non-konvulsiven SE und zum Ausschluss bzw. Nachweis psychogener nichtepileptischer Anfälle eine wesentliche Rolle. Der prognostische Einfluss von insbesondere entzündlichen Begleiterkrankungen (z. B. Pneumonie) wurde besser belegt, weshalb entsprechende Laborparameter auch im Verlauf kontrolliert werden sollten und ggf. frühzeitig eine antibiotische Therapie initiiert werden sollte.Die Therapie erfolgt in 4 Stufen: 1. Initialer SE: Gabe eines ausreichend hoch dosierten Benzodiazepins i. m., i. v. oder i. n.; 2. Benzodiazepin-refraktärer SE: 1. Wahl ist die i.v. Gabe von Levetiracetam oder Valproat; 3. Refraktärer SE (RSE) und 4. Superrefraktärer SE (SRSE): I.v. Propofol oder Midazolam alleine oder in Kombination oder Thiopental in anästhetischen Dosen. Beim fokalen non-konvulsiven RSE kann unter Umständen auf die Einleitung eines therapeutischen Komas verzichtet werden. Bei SRSE sollte die ketogene Diät zum Einsatz kommen. I.v. Ketamin oder inhalatives Isofluran kann erwogen werden. In Einzelfällen kann die elektrokonvulsive Therapie und, bei resektabler epileptogener Zone, ein Epilepsie chirurgischer Eingriff erwogen werden. I.v. Allopregnanolon oder die Hyperthermie sollen nicht eingesetzt werden.

Factors associated with the severity of delirium.

Various factors affecting the development of delirium have been identified. However, the associations between the severity of delirium and potentially related factors have not been adequately investigated. The aim of the present study was to explore factors associated with the severity of delirium and to identify the reversible contributing factors. A total of 577 patients with delirium referred to the Department of Psychiatry during the 5 years from May 2015 to April 2020 at a general hospital were included. The Delirium Rating Scale-revised-98 (DRS-R-98) was used to measure the severity of delirium. Multiple regression analysis was used to determine whether individual factors were associated with the severity of delirium. Intensive care unit admission (p=0.003), use of benzodiazepines (p=0.01), dementia (p=0.02), and older age (p=0.045) were all positively associated the severity of delirium, while use of β-blockers (p=0.001) was negatively associated with the severity of delirium. Reversible contributing factors, that is use of benzodiazepines, should be avoided as much as possible, especially in elderly patients or patients with dementia or patients who need critical care in ICU. Reducing the dose of benzodiazepines or switching them to other drugs should be a priority.

P0046 / #639: THE IMPACT OF BENZODIAZEPINES AND OPIOIDS ON NEUROCOGNITIVE DEVELOPMENT IN CHILDREN

Aims & Objectives: General anesthetics and sedatives are widely used for critically ill children admitted to the Pediatric Intensive Care Unit (PICU). Animal studies have indicated that exposure of the immature brain to these agents may cause neurodegeneration. In human adults, studies have shown an inverse association between cumulative doses of benzodiazepines and neurocognitive functioning. Literature on this association in children is scarce. This study aims to explore the impact of benzodiazepines and opioids on neurocognitive development in children. Methods: Children aged 6-12 years admitted to our PICU (age ≤10 months) for respiratory insufficiency due to severe viral lower respiratory tract infections were included. All children required mechanical ventilation for which they also received midazolam and morphine. Healthy peers, matched with patients on age, sex and socio-economic status, acted as controls. We assessed full-scale IQ (FSIQ) and computerized tests of attention, learning and memory, executive functioning and sensory and motor functioning. Results: Included were 41 patients (24 males) and 41 controls (17 males). Mean (SD) age of patients and controls was 8.6 (0.8) and 8.9 (1.0) years, respectively. Preliminary results indicate that, compared to healthy peers, children in the exposure group have a significantly lower FSIQ (d=-0.56, p = 0.02); and a significantly poorer verbal memory, including both short (d=-0.47, p = 0.04) and long-term memory (d=-0.50, p = 0.03). Other results await analyses. Conclusions: Preliminary results suggest that children with a history of mechanical ventilation and exposure to midazolam and morphine are at risk of decreased neurocognitive functioning.

P0455 / #1198: CARING FOR ACTIVELY DYING CHILDREN AND THEIR PARENTS IN THE PEDIATRIC ICU: A MIXED METHODS STUDY – PRELIMINARY QUANTITATIVE FINDINGS

Aims & Objectives: End-of-life (EOL) care is steeped in tradition, locally bound, and historically has not been informed by parent perspectives. This study uses a mixed methods design (QUAN → qual) to explain and contextualize quantitative clinical data with parent interviews about their child’s EOL care. Here, we present QUAN data describing a cohort of children with acute respiratory failure who died following withdrawal of support. Methods: Secondary analysis of the RESTORE dataset including demographics, baseline characteristics and care trajectories for up to 5 days prior to death. Results: Data reflect 67 patients from 24 U.S. PICUs. Nonsurvivors were primarily white (79%), non-Hispanic (78%) with PCPC/POPC ≤2 (69%). Diagnoses were acute (33%), complex-chronic disease (33%), or cancer (34%). Primary cause of death included respiratory (40%) or multisystem organ failure (27%). Prior to death, daily pain scores were 0 (modal), SBS were -1/-2 (modal). Opioid and benzodiazepine doses ranged from 6.0-4.4 mg/kg and 4.8-3.8 mg/kg, repectively. The nursing manpower use score (NEMS) increased from 33 to 36. On the day of death, 12% were supported on ECMO, 76% on vasopressors, 29% on dialysis and patients had a median of 5 medical devices in place. Eleven (16%) patients were extubated prior to death. Conclusions: Parents’grief following their critically ill child’s death is shaped by their memories around EOL care in the PICU. As patients approach EOL, nursing care requirements increased and many patients died with invasive devices/interventions, but with little to no pain. Qualitative and mixed-methods findings are forthcoming.