Uso de sedación endovenosa en pacientes con COVID-19 crítico en ventilación mecánica invasiva / Use of intravenous sedation in patients with critical COVID-19 in invasive mechanical ventilation

ANTECEDENTES: El objetivo del presente informe es: Describir el proceso para la elaboración de recomendaciones por el grupo de trabajo designado por el Ministerio de Salud, en adelante denominado grupo de trabajo. Trasladar las Recomendaciones efectuadas por dicho grupo de trabajo en atención al uso de sedación endovenosa en pacientes con COVID-19 crítico en ventilación mecánica invasiva, según la pregunta PICO (P: Población, I: Intervención, C: Comparador, O: Outcome o desenlaces) priorizada por el grupo de trabajo. La metodología considerada para arribar a la recomendación fue el Marco de Evidencia a la Decisión/Recomendación (EtD) desarrollado por el Grupo de Trabajo GRADE (1,2). ANALISIS: Formulación de la pregunta: En personas con COVID-19 crítico en ventilación mecánica invasiva, ¿cuál es el medicamento que debe administrarse para la sedación endovenosa? Y ¿Cuál pauta de dosificación? Identificación de la evidencia para la pregunta PICO: Se siguieron las orientaciones establecidas en el documento interno de UNAGESP: Orientaciones para el soporte metodológico otorgado al grupo de trabajo designado por el MINSA. Se describe a continuación los resultados del proceso: Se efectuó la búsqueda de guías de práctica clínica (GPC) que incluyeran recomendaciones respecto al uso de sedación endovenosa en la población de interés, con fecha de búsqueda 22 de octubre de 2021 en las siguientes plataformas: eCOVID-19 living map of recommendations (eCovid-19 RecMap), Base internacional de Guías GRADE (BIGG) , Guidelines International Network (GIN), COVID-19 Guidelines Dashboard, National Institute for Health and Care Excellence - UK (NICE) y Trip database, identificándose 7 guías de práctica clínica (Ver Anexo 1). En base a criterios como fecha de búsqueda de la evidencia, uso de metodología GRADE para evaluar la certeza de la evidencia, disponibilidad de la tabla Perfil de evidencia o Resumen de hallazgos, disponibilidad de los criterios o Tabla EtD y tipo de recomendación. Se identificaron tres guías de la Organización Panamericana de la Salud y una de la Society of Critical Care Medicine (SCCM)(3­6), sin embargo, las guías de OPS no brindan recomendaciones especificas para responder directamente a todas las alternativas de intervenciones planteadas por SOPEMI. Por otro lado, las guías de SCCM contienen recomendaciones respecto al uso de todas las alternativas de intervenciones planteadas en pacientes no COVID. La búsqueda se realizó en MEDLINE/ vía PubMed, plataforma L·OVE de Epistemonikos (7) y en MedRxiv, con fecha 22 de octubre de 2021. Los criterios de selección de los estudios fueron: ensayos clínicos aleatorizados, cohortes o casos y control que evalúen la PICO planteada y reportaran al menos uno de los desenlaces de interés. La certeza de la evidencia fue realizada según el enfoque GRADE que toma en cuenta los siguientes criterios: diseño del estudio, riesgo de sesgo, inconsistencia en los resultados, ausencia de evidencia directa, imprecisión, sesgo de publicación, tamaño de efecto, gradiente dosis-respuesta, y efecto de los potenciales factores de confusión residual (los tres últimos aplicables en estudios observacionales) (8,9). Los resultados fueron presentados utilizando la Tablas de Resumen de Hallazgos (SOF, por sus siglas en inglés) construidas a partir del software en línea GRADEpro (https://gradepro.org/)(10) a partir de la adaptación de tablas SoF de la guía de SCCM (6) para pacientes no críticos. Metodología considerada para la elaboración de las recomendaciones: Marco de Evidencia a la Decisión/Recomendación (EtD: Evidence to decisión framework): Los marcos EtD (1,2) son una herramienta del Enfoque GRADE, que tiene como finalidad fomentar el uso de la evidencia de una manera estructurada y transparente para informar decisiones relacionadas al manejo clínico de una enfermedad, salud pública, políticas del sistema de salud o en situaciones como el contexto actual de pandemia acerca de acciones con repercusión socio-económica entre otras. Se aplicaron los principios del enfoque "GRADE-ADOLOPMENT" para identificar guías de práctica clínica orientadas a las preguntas PICO propuestas por el grupo de trabajo de MINSA, además que tener disponibles los perfiles de evidencia GRADE o Tablas de resumen de hallazgos y los marcos EtD. Dependiendo de la evaluación, estas pueden ser consideradas para la adaptación con contextualización o para la adopción (11). Los siguientes criterios del marco EtD fueron seleccionados para la discusión y juicio por el grupo de trabajo: Efectos deseables, Efectos indeseables, Certeza de la evidencia, Valores y preferencias de los pacientes, Balance de efectos, Recursos necesarios, Equidad, Aceptabilidad y Factibilidad. En caso de no haber consenso en la valoración del juicio, se efectuó una votación, determinándose la valoración por mayoría simple. La perspectiva fue del sistema de salud. Elaboración de las Recomendaciones: La metodología EtD considera determinar la fuerza y dirección de una recomendación (12). Ambas, como resultado del juicio acerca del balance beneficio-riesgo, calidad global de la evidencia, confianza en los valores y preferencias de los pacientes, uso de recursos, equidad en salud, aceptabilidad, y factibilidad. En este sentido, existirán recomendaciones "a favor de la intervención" o "en contra de la intervención" (a favor de la alternativa u opción). Asimismo, las recomendaciones fueron determinadas como fuertes o condicionales. Una recomendación será fuerte si existe una clara diferencia entre los efectos deseables e indeseables de la intervención, la certeza global de la evidencia alta o moderada, todos o casi todos los pacientes informados toman la misma decisión, el costo de la intervención está plenamente justificado, existe un impacto favorable en la equidad en salud, la intervención es aceptable para los usuarios interesados (pacientes y personal de salud) y la implementación de dicha intervención es viable. Una recomendación será condicional si alguna de las consideraciones siguientes está presente: Exista poca diferencia entre los efectos deseables e indeseables de la intervención, la calidad de la evidencia es baja o muy baja, existe variabilidad o incertidumbre respecto de lo que decidirán los pacientes informados o el costo de la intervención pudiera no estar justificado en algunas circunstancias. Diálogo Deliberativo para la valoración de los criterios del Marco EtD y elaboración de las recomendaciones: El Diálogo deliberativo se llevó a cabo el día 27 de octubre de 2021, reunión virtual a través de la herramienta Zoom, con la participación de: 1. Profesionales del Grupo de trabajo designado por el Ministerio de Salud: integrantes de la Sociedad Peruana de Medicina Intensiva y Representantes del Ministerio de Salud, en su calidad de panel de expertos, habilitados para emitir los juicios para cada criterio, votar en caso de ser necesario y elaborar la recomendación. 2. Representantes de la Unidad de Análisis y Generación de Evidencias en Salud Pública (UNAGESP) del INS, quienes efectuaron la identificación de la evidencia presentada ante los expertos, en calidad de facilitadores y conductores de los aspectos metodológicos de la reunión. RECOMENDACIÓN: Se sugiere el uso de Propofol sobre benzodiazepinas para la sedación en pacientes con COVID 19 críticos en ventilación mecánica invasiva. Recomendación condicional, basada en evidencia de muy baja calidad: Consideraciones adicionales: La sedación en pacientes COVID 19 críticos en ventilación mecánica invasiva debe ser precedida por una adecuada analgesia. En los pacientes COVID 19 críticos en ventilación mecánica invasiva que no se alcance el objetivo de sedación con las dosis adecuadas de Propofol, o se tenga efectos colaterales, se podría considerar el uso de otro sedante. No se ha establecido la seguridad de Propofol en el embarazo, porque atraviesa la barrera placentaria y puede causar depresión neonatal. Se sugiere usar dexmedetomidina sobre benzodiazepinas para la sedación en pacientes COVID 19 críticos en ventilación mecánica durante la fase de destete. Recomendación condicional, calidad de la evidencia muy baja: Consideraciones adicionales: Tener precaución sobre los efectos adversos como bradicardia e hipotensión. Evitar su uso en pacientes inestables hemodinámicamente. No se recomienda dar dosis de carga de dexmedetomidina. Se sugiere el uso de dexmedetomidina sobre Propofol para la sedación en pacientes COVID 19 críticos en ventilación mecánica durante la fase de destete.

Acute COVID-19 Infection Associated With Necrotizing Disseminated Acute Leukoencephalopathy and Brain Microhemorrhages in a Pediatric Patient.

We present a case of a 14-year-old, previously healthy female, admitted with acute coronavirus disease 2019 infection and new-onset seizures secondary to virus-associated necrotizing disseminated acute leukoencephalopathy. Her symptoms resolved completely with intravenous immunoglobulin and steroids. Pathophysiology and prognosis of neurologic manifestations of coronavirus disease 2019 remain unclear.

Neurochemical and behavioral effects of lorazepam: A dose related study.

Present study was designed to monitor the dose dependent effects of lorazepam; a benzodiazepine (CNS depressant). It is the primary drug of choice for treatment of anxiety and to produce calming effects. However, repeated administration of this lorazepam causes dependence and this might be caused by increased dopaminergic neurotransmission. Besides dopamine, 5-hydroxy tryptamine (5-HT) has also been reported to have pivotal role in the pathophysiology as well as treatment of anxiety and addiction. Repeated administration of lorazepam might involve altered 5-HT metabolism as well. Present study was therefore designed to monitor dose-dependent effects of lorazepam and to select its optimum dose for further experiments and pharmacological interventions. Effects of lorazepam were monitored on food intake, growth rate, activities in familiar and novel environments, light dark box activity, forced swim test and metabolism of dopamine and 5-HT. oral administration of lorazepam was done at the doses of 0mg/kg, 2mg/kg, 4mg/kg and 6mg/kg. Behaviors parameters were monitored following single administration of lorazepam. Rats were decapitated and whole brain samples were collected and stored at -70°C until neurochemical analysis by HPLC-EC. Findings from the present study could be implicated to increased therapeutic utility of lorazepam and related benzodiazepines.

Effects of benzodiazepine and orexin receptor antagonist on cognitive function revealed by auditory event-related potentials.

BACKGROUND: Cognitive decline after oral administration of sedatives, such as benzodiazepines, is a serious side effect. Suvorexant, an orexin receptor antagonist, has a favorable tolerability and a limited side-effect profile. AIM: The purpose of this study was to estimate the cognitive decline 1 day after oral medication with lormetazepam, a benzodiazepine, and suvorexant by comparing mismatch negativity (MMN) and P300 reflecting auditory discrimination function. METHODS: Sixty healthy subjects (42 males) were randomly assigned to three groups receiving suvorexant 20 mg, lormetazepam 2 mg, or placebo in this double-blind, randomized control study. Event-related potential recordings during an auditory oddball task and a digit symbol substitution test (DSST) were performed 1 day after oral administration. RESULTS: MMN, on the day after oral administration, was significantly attenuated in the lormetazepam group compared with the other two groups, but there was no difference between the suvorexant and placebo groups. No significant difference was found in P300 amplitudes and DSST scores among the three groups. CONCLUSION: These findings suggest that suvorexant, unlike benzodiazepine, is not associated with cognitive deficits, as revealed by MMN but not P300. This study shows a neurophysiological difference in the effects of suvorexant and benzodiazepine on cognitive function.

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.).

Effects of Oral Administration of Alprazolam and Lorazepam as Hypnotics on Cardiovascular Parameters in Hypertensive Patients.

BACKGROUND: Previous studies have suggested that evening intake of benzodiazepine affects blood pressure (BP) and/or heart rate (HR) in healthy and hypertensive subjects. The aim of this study was to compare the effect of chronic oral administration of alprazolam and lorazepam as hypnotics on ambulatory BP and HR in patients with mild hypertension. METHODS: Consecutive outpatients of both sexes with newly diagnosed, never-treated mild hypertension were randomized, after a 4-week placebo run-in period, to receive alprazolam 0.5 mg plus placebo, lorazepam 1 mg plus placebo, or placebo plus placebo for 2 weeks in 3 crossover periods, each separated by a 1-week placebo wash-out period. At the end of the initial placebo run-in and of each treatment period, 24-hour ambulatory BP and HR monitoring was performed using a noninvasive device. RESULTS: In the 32 patients, no treatment had any effect on 24-hour and daytime systolic BP (SBP), diastolic BP (DBP), and HR, which remained unchanged. During the nighttime, SBP and DBP values were unaffected by alprazolam, as compared with placebo, whereas DBP was significantly higher after treatment with lorazepam (+3.7%, P < 0.05 vs placebo). Nocturnal HR mean values were significantly increased by lorazepam (+10.1%, P < 0.01 vs placebo), whereas they did not change after alprazolam. CONCLUSIONS: In patients with mild hypertension, oral intake of alprazolam or lorazepam as hypnotics did not affect ambulatory BP or HR values. A slight increase in nighttime DBP was observed with lorazepam, whereas alprazolam showed no effect on nocturnal BP and HR, probably reflecting a stimulating effect of the drug on central α2-receptors.

Treatment of opioid and alcohol withdrawal in a cohort of emergency department patients.

BACKGROUND: The safety of combining buprenorphine with a benzodiazepine or barbiturate in the treatment of concurrent alcohol and opioid withdrawal has not been well established. In this study we examine a cohort of patients treated with buprenorphine and phenobarbital or benzodiazepines for co-occurring opioid and alcohol withdrawal. METHODS: This is a retrospective cohort study of ED patients treated for opioid and alcohol withdrawal from January through December 2018. The primary outcome was unexpected airway intervention, or the administration of naloxone for respiratory depression. RESULTS: There were 16 patients treated for opioid and alcohol withdrawal. The mean age was 44.3 (standard deviation [SD] 13.1), 12 (75.0%) were male, and 8 (50.0%) of the patients were admitted to the hospital. For opioid withdrawal, six patients received intravenous buprenorphine, with doses between 0.3 mg to 1.8 mg; 12 patients received sublingual buprenorphine, with doses between 4 mg to 32 mg. For alcohol withdrawal, 10 patients received lorazepam with doses between 1 mg and 8 mg; 10 patients received phenobarbital with doses between 260 mg to 1040 mg. There were no unexpected airway interventions related to medications used for opioid or alcohol withdrawal. One patient with severe pneumonia was an expected intubation for respiratory failure. CONCLUSIONS: We describe a cohort of patients treated for opioid and alcohol withdrawal in the ED. There were no serious adverse events related to the medications used to treat opioid or alcohol withdrawal. Further work should assess optimal use of medical therapy for opioid and alcohol withdrawal and the transition to maintenance treatment for substance use disorders.

Can oral formulation increase the risk of lormetazepam abuse?

The slowness of dripping and the presence of alcohol have been offered/suggested as possible causes for the increased risk of developing dependence to the oral formulation of lormetazepam rather than to other anxiolytic and hypnotic drugs. We hence assessed the time of dripping of the most used benzodiazepines and z-drugs oral solution products under experimental conditions and the different employed excipients through a comparative analysis of the Summaries of Product Characteristics. A wide range of the median overall dispensing time was found across the eight products included in the analysis. Among the products containing LMZ, Minias® ranked in the fourth position, while LMZ Mylan Generics® and Noctamid® in the sixth and third, respectively. Our data suggest that the pace of dripping and the presence of alcohol cannot be considered themselves the cause that triggered the abuse of lormetazepam. More precisely, the quantity of alcohol per bottle has been found negligible at therapeutic doses; however, when these are exceeded, they may have clinical implications for patients. Further studies are needed to assess them. Meanwhile, the public-health problem remains and some improvements should be carried out at different levels, to guarantee the appropriate prescription and use of lormetazepam oral solution.

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.

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.

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.

Brief psychotic disorder associated with quarantine and mild COVID-19.

A 30-year-old man with no significant previous or family psychiatric history became severely anxious about his health after a positive COVID-19 test. Physical symptoms of COVID-19 were mild, with no evidence of hypoxia or pneumonia, throughout his illness. He was admitted to a quarantine facility. He remained highly anxious, and 1 week later, he developed paranoid delusions and auditory hallucinations (his first psychotic episode). He was treated with lorazepam 1 mg four times a day, mirtazapine 30 mg nocte and risperidone 1 mg two times a day. His psychotic symptoms lasted 1 week. He stopped psychiatric medication after 4 weeks and had remained well when reviewed 3 months later. A Diagnostic and Statistical Manual of Mental Disorders fifth edition diagnosis of brief psychotic disorder with marked stressor (brief reactive psychosis) was made. Anxiety about his health and social isolation appeared the main aetiological factors but an inflammatory component cannot be excluded. The case highlights that first episode psychosis can be associated with mild COVID-19.

Neuropsychiatric manifestations in adult-onset Still's disease.

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition characterised by a triad of fevers, arthralgias and a salmon-coloured rash. It is also strongly associated with high ferritin levels, whose role in its pathogenesis is not entirely clear. Central nervous system (CNS) manifestations are exceedingly rare in this disease, accounting for only a handful of reported cases. Herein, we describe a case of a 63-year-old woman who developed new-onset psychiatric symptoms in the months preceding her diagnosis. 2 months after her diagnosis, she experienced an exacerbation of psychiatric symptoms followed by new-onset seizures in conjunction with an acute lung infection. In addition, we discuss two other previously reported cases of AOSD patients with psychiatric symptoms as their initial presentation.

Anticipatory prescribing in community end-of-life care in the UK and Ireland during the COVID-19 pandemic: online survey.

BACKGROUND: Anticipatory prescribing (AP) of injectable medications in advance of clinical need is established practice in community end-of-life care. Changes to prescribing guidelines and practice have been reported during the COVID-19 pandemic. AIMS AND OBJECTIVES: To investigate UK and Ireland clinicians' experiences concerning changes in AP during the COVID-19 pandemic and their recommendations for change. METHODS: Online survey of participants at previous AP national workshops, members of the Association for Palliative Medicine of Great Britain and Ireland and other professional organisations, with snowball sampling. RESULTS: Two hundred and sixty-one replies were received between 9 and 19 April 2020 from clinicians in community, hospice and hospital settings across all areas of the UK and Ireland. Changes to AP local guidance and practice were reported: route of administration (47%), drugs prescribed (38%), total quantities prescribed (35%), doses and ranges (29%). Concerns over shortages of nurses and doctors to administer subcutaneous injections led 37% to consider drug administration by family or social caregivers, often by buccal, sublingual and transdermal routes. Clinical contact and patient assessment were more often remote via telephone or video (63%). Recommendations for regulatory changes to permit drug repurposing and easier community access were made. CONCLUSIONS: The challenges of the COVID-19 pandemic for UK community palliative care has stimulated rapid innovation in AP. The extent to which these are implemented and their clinical efficacy need further examination.

A clinical method of evaluating simple reaction time and reaction accuracy is sensitive to a single dose of lorazepam.

RATIONALE: Benzodiazepines are useful and commonly prescribed. Unfortunately, they are associated with subtle but functionally significant neurocognitive side effects that increase the risk of motor vehicle accidents and falls. OBJECTIVE: The objective of this study was to determine whether clinically feasible measures of simple reaction time and reaction accuracy are sensitive to a single dose of lorazepam. METHODS: Using a randomized, double-blind, crossover design, 26 healthy adults (13 women; age = 26.9 ± 8.2 yr) were given 1.0 mg lorazepam or placebo 90 minutes prior to two data collection sessions. Participants completed simple and reaction accuracy tasks using a standardized "ruler drop" testing paradigm during each session. Outcomes were mean and variability of simple reaction time and reaction accuracy, which evaluates a participant's ability to catch the device solely on the random 50% of trials that lights affixed to it illuminate on release. Reaction accuracy requires a go/no-go decision within 420 ms before the falling device strikes the floor. RESULTS: As compared with placebo, lorazepam increased simple reaction time variability (range = 43 ± 18 vs. 60 ± 23 ms, respectively; p = 0.004 and standard deviation = 14.6 ± 5.7 vs. 19.7 ± 7.3 ms, respectively; = 0.006) and decreased reaction accuracy (90 ± 7% vs. 84 ± 11%, respectively; p = 0.010). CONCLUSION: Given prior work demonstrating associations between simple reaction time and reaction accuracy and functional outcomes such as self-protection, response to perturbations, and fall risk, these clinically available measures may have a role in identifying subtle, functionally significant cognitive changes related to short-term benzodiazepine use.