Use of Sedatives and Neuromuscular-Blocking Agents in Mechanically Ventilated Patients with COVID-19 ARDS

Objectives: To assess differences in the use of analgesics, sedatives and neuromuscular-blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19 or other conditions. Methods: Retrospective observational cohort study, single-center tertiary Intensive Care Unit. COVID-19 patients with ARDS (March–May 2020) and non-COVID ARDS patients (2017–2020) on mechanical ventilation and receiving sedation for at least 48 h. Results: A total of 39 patients met the inclusion criteria in each group, with similar demographics at baseline. COVID-19 patients had a longer duration of MV (median 22 (IQRs 16–29) vs. 9 (6–18) days; p < 0.01), of sedatives administration (18 (11–22) vs. 5 (4–9) days; p < 0.01) and NMBA therapy (12 (9–16) vs. 3 (2–7) days; p < 0.01). During the first 7 days of sedation, compared to non-COVID patients, COVID patients received more frequently a combination of multiple sedative drugs (76.9% vs. 28.2%; p < 0.01) and a higher NMBA regimen (cisatracurium: 3.0 (2.1–3.7) vs. 1.3 (0.9–1.9) mg/kg/day; p < 0.01). Conclusions: The duration and consumption of sedatives and NMBA was significantly increased in patients with COVID-19 related ARDS than in non-COVID ARDS. Different sedation strategies and protocols might be needed in COVID-19 patients with ARDS, with potential implications on long-term complications and drugs availability.

Structure and nature of hypertensive intracerebral hemorrhages of supratentorial localization

Objective ‒ to analyze data of patients with hypertensive supratentorial hemorrhages who were hospitalized in Kyiv Emergency Hospital in 2019‒2020.Materials and methods. We analyzed data of 232 patients who were treated for hypertensive intracerebral hemorrhage at the Kyiv Emergency Hospital in 2019‒2020. Patients were included regardless of admission status and chosen treatment tactics (surgical, medical). The study did not include patients with subtentorial hemorrhage, patients with tumor hemorrhage, arteriovenous malformations, aneurysms, angiomas, ischemic and mixed strokes.Results. Among patients males are predominated (149 (64 %)). The average age of patients was 60 years (group of men ‒ 56 years, group of women ‒ 69 years). 77 (33 %) patients were delivered in a comatose state (GCS ≤8 points), 36 (16 %) were in a coma (GCS 9‒12 points), 81 patients were in a state of stupor (GCS 13‒14 points), in a clear mind ‒ 31 (13 %). In 7 (3 %) cases it is impossible to determine the level of consciousness (in patients with seizures or after the introduction of sedative drugs before admission to hospital). 85 patients were operated (surgical activity ‒37 %), who underwent 97 surgical interventions. The overall mortality was 42 %, postoperative mortality ‒ 43 %. Patients who had a compression-dislocation syndrome were operated on. Mortality in the group of patients admitted in a coma mortality was 85 % regardless of the method of treatment.Conclusions. Hemorrhagic strokes predominate in men, due to lifestyle and uncontrolled hypertension in patients. The results of treatment of patients with hypertensive intracerebral hemorrhage indicate the need for early hospitalization, early CT, differentiated approache to surgical removal of hematomas (lobar, lateral with dislocation syndrome), intensive care in patients in a comatose state, even with massive hemorrhages. The results of hypertensive intracerebral hemorrhage depend on the location of the hemorrhage, the severity of the patient’s condition, the timing of hospitalization in specialized stroke departments, the dynamics of cerebrovascular disorders (completed stroke and stroke in development).

Remimazolam Protects Against LPS-Induced Endotoxicity Improving Survival of Endotoxemia Mice

Remimazolam is a new benzodiazepine of sedative drugs with an ultra-short-acting anesthetic effect, commonly used for critically ill patients (especially septic patients) in intensive care units (ICUs). Although some anesthetics have been reported to show certain anti-inflammatory effects, the role of remimazolam in inflammation is still remained unknown. Here, we studied the effects of remimazolam on macrophage in response to LPS both in vivo and in vitro. Interestingly, compared with LPS treatment group, remimazolam remarkably improved survival rate of endotoxemia mice and decreased the release of LPS-induced inflammatory mediators (such as TNF-α, IL-6, and IL-1β). We further found that remimazolam not only inhibited the activation of MAPK signal pathway at 15 min after LPS treatment but also disturbed Rab5a related TLR4 expression at cell surface in response to LPS at a later time. Such evidence suggests that remimazolam might be beneficial to septic patients who are suffering from uncontrolled inflammatory responses.

Deprescribing to reduce polypharmacy: study protocol for a randomised controlled trial assessing deprescribing of anticholinergic and sedative drugs in a cohort of frail older people living in the community

Background Targeted deprescribing of anticholinergic and sedative medications in older people may improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community. Methods and analysis The standard protocol items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomized controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients. Study population Community-dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly. Intervention New Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend anticholinergic and sedative medications that could be deprescribed to the participant’s general practitioner. The total use of anticholinergic and sedative medications will be quantified using the Drug Burden Index (DBI). Outcomes The primary outcome will be the change in total DBI between baseline and 6-month follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalization, and death. Data collection points Data will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3). Ethics and dissemination Ethical approval has been obtained from the Human, Disability and Ethics Committee: ethical number (17CEN265). Trial registration ClinicalTrials.gov ACTRN12618000729224. Registered on May 2, 2018, with the Australian New Zealand Clinical Trials Registry

Comparative Evaluation of Hemodynamic Stability and Recovery during Conscious Sedation by Dexmedetomidine-Fentanyl Versus Ketamine- Fentanyl in procedures outside the operating room

Background Conscious sedation is a technique of providing analgesia, sedation and anxiolysis while ensuring rapid recovery without side effects. Conscious sedation is administered with the dual goals of rapidly and safely establishing satisfactory procedural condition for the performance of therapeutic or diagnostic procedures while ensuring rapid, Email: predictable recovery with minimal post-operative sequels. Aim of the Work to study the effect of dexemdetomidine with fentanyl versus ketamine with fentanyl on hemodynamic stability and recovery during conscious sedation in dilatation and curettage procedure. Patients and Methods In our study, 50 patients were randomly divided into 2 equal groups. group DF received dexmedtomidine loading dose 1 μg/kg over 10 min and followed by 0.5 μg/kg/hr infusion till completion of surgery. And group KF received ketamine 0.5 mg/kg slow intravenous Bolus. Results Our study showed that dexmedetomidine is a safe drug with good hemodynamic and recovery time, also exerts sedative and analgesic effects without respiratory depression, unlike most analgesic/sedative drugs, such as ketamine, opioids, benzodiazepines, and propofol. Conclusion dexmedetomidine in combination with fentanyl is useful to provide conscious sedation for non operating room procedures in adults and it may be a valuable alternative to ketamine.

Why Do People Want to Die? The Meaning of Life from the Perspective of Euthanasia

One way to examine the enigmatic meaningfulness of human life is to ask under which conditions persons ask in earnest for assistance to die, either through euthanasia or physician assisted suicide. The counterpart of intolerable suffering must consist in some form of, however minimal, flourishing that makes people want to go on with their lives, disregarding other reasons to reject assisted dying that have more to do with religious prohibitions. To learn more about why persons want to hasten death during the last days, weeks or months of their lives, what kinds of suffering they fear and what they hold to be the main reasons to carry on or not carry on living, the paper offers some examples from a book written by the physician Uwe-Christian Arnold. He has helped hundreds of persons in Germany to die with the aid of sedative drugs the last 25 years, despite the professional societies and codes in Germany that prohibit such actions. The paper discusses various examples from Arnold's book and makes use of them to better understand not only why people sometimes want to die but what made their lives meaningful before they reached this final decision.

Comparison of Dexmedetomidine with Fentanyl and Pentazocine – Promethazine in patients undergoing dilation and curettage in monitored anesthesia care

Dilatation and curettage (D and C) is an essential and common minor surgery in obstetrics and gynecology. Sedation, hypnosis and analgesia are used in combination for such short procedures. These days conscious sedation is provided to patients for day care surgeries which includes analgesia, sedation and anxiolysis while rapid recovery is ensured without side effects. Dexmedetomidine is a highly selective alpha-2 agonist that provides anxiolysis and conscious sedation without respiratory depression. It was to study the effect of dexemedetomidine with fentanyl versus Pentazocine with promethazine on hemodynamic stability and recovery during sedation in dilatation and curettage procedure. The comparison included the hemodynamic data and recovery time. The effect of the drugs on hemodynamics and monitoring the occurrence of any complication were also done. In our study, 50 patients were randomly divided into 2 equal groups; group DF received dexmedetomidine loading dose 1 μg/kg over 10 min and followed by 0.5 μg/kg/hr infusion till completion of surgery and group PP received pentazocine 0.5 mg/kg (max 30mg) and Promethazine 12.5 mg slow intravenous Bolus. Dexmedetomidine is a safe drug which provides good hemodynamics and less recovery time. It also exerts sedative and analgesic effects without respiratory depression unlike most analgesic/sedative drugs, such as ketamine, pentazocine and benzodiazepines. This study demonstrates that dexmedetomidine is a safe drug with good hemodynamic and recovery profile. Dexmedetomidine administration showed better preservation of MAP and SpO2.

“We don’t want to sedate him” - A qualitative interview study on intentions when administering sedative drugs at the end of life in nursing homes and hospitals

Background Previous data indicate major differences between countries and settings regarding the intention when administering sedative drugs at the end of life and the perception, which drugs are sedating. Therefore, we aimed to explore the concept of ‘sedative drugs’ and the intentions of German healthcare professionals in general palliative care when administering sedative drugs at the end of life. Methods Semi-structured qualitative interviews with physicians and nurses (n = 49). Recruitment took place via contact persons in five hospital departments (haematology/oncology (n = 2), neurology, geriatrics, gynaecology) and five nursing homes. We thematically analysed the transcripts by the Framework approach, using MAXQDA version 2018.2. Results Most interviewees referred to benzodiazepines, opioids, and antipsychotics. Some subsumed all into sedative drugs, others differentiated between sedative drugs, anxiolytics, and analgesics. In explaining their intention, interviewees particularly emphasized what they want to avoid when administering sedative drugs. We identified three main themes regarding (excluded) intentions: (1) use of sedative drugs to relieve the patient’s suffering with reduction of consciousness as side effect, (2) use of sedative drugs to relieve the situation for the team and/or the family, (3) distinction between intention and expectation regarding hastening death. Interviewees often equated the term ‘sedation’ with inducing a state of unconsciousness, which should be avoided. Conclusion German healthcare professionals in general palliative care seem to negatively connote the term ‘sedation’. Moreover, they see themselves in a more passive role by accepting a side effect rather than performing an intentional act. Critical reflection of indications and intentions in accordance with respective guidelines is needed.

Sleep Disorders and Risk of Motor Vehicle Accident

Driving is a complicated process that demands coordination between a range of neurocognitive functions, including attention, visuo-perception, and appropriate judgment, as well as sensory and motor responses. Therefore, several factors may reduce the driving performance of an individual, such as sleepiness, distraction, overspeeding, alcohol consumption, and sedative drugs, all of which increase the hazard of motor vehicle accidents. Among them, drowsy driving is a major cause of traffic accidents, leading to more serious injuries as compared to other causes of major traffic accidents. Although sleep disorders have been highly associated among drowsy drivers, they are often untreated and unrecognized as a disease. In particular, obstructive sleep apnea and narcolepsy are some sleep disorders that are highly related to traffic accidents. Insomnia, which can cause inadequate sleep duration and promote sedative effects from sleeping pills, may also cause traffic accidents. These conditions are especially applicable to commercial bus or truck drivers, nocturnal workers, and shift workers, who are highly vulnerable to drowsy driving. Therefore, assertive screening and management of sleep disorders are necessary in general private drivers and relevant occupational drivers.