Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

Development of a predictive model for hypoxia due to sedatives in gastrointestinal endoscopy: a prospective clinical study in Korea.

Background/Aims: Sedation has become a standard practice for patients undergoing gastrointestinal (GI) endoscopy. However, considering the serious cardiopulmonary adverse events associated with sedatives, it is important to identify patients at high risk. Machine learning can generate reasonable prediction for a wide range of medical conditions. This study aimed to evaluate the risk factors associated with sedation during GI endoscopy and develop a predictive model for hypoxia during endoscopy under sedation. Methods: This prospective observational study enrolled 446 patients who underwent sedative endoscopy at the Korea University Ansan Hospital. Clinical data were used as predictor variables to construct predictive models using the random forest method that is a machine learning algorithm. Results: Seventy-two of the 446 patients (16.1%) experienced life-threatening hypoxia requiring immediate medical intervention. Patients who developed hypoxia had higher body weight, body mass index (BMI), neck circumference, and Mallampati scores. Propofol alone and higher initial and total dose of propofol were significantly associated with hypoxia during sedative endoscopy. Among these variables, high BMI, neck circumference, and Mallampati score were independent risk factors for hypoxia. The area under the receiver operating characteristic curve for the random forest-based predictive model for hypoxia during sedative endoscopy was 0.82 (95% confidence interval, 0.79-0.86) and displayed a moderate discriminatory power. Conclusions: High BMI, neck circumference, and Mallampati score were independently associated with hypoxia during sedative endoscopy. We constructed a model with acceptable performance for predicting hypoxia during sedative endoscopy.

Current Practices and Safety of Medication Use During Pediatric Rapid Sequence Intubation.

OBJECTIVES: This study aimed to characterize medication-related practices during and immediately -following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. METHODS: This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. RESULTS: A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. CONCLUSIONS: Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.

Morbidity among Adolescent Hypnotic Drug Users in Norway: An Observational Population-Based Study.

We have previously shown that the use of hypnotic drugs increased among young Scandinavians during 2012-2018. This study aimed to explore psychiatric and somatic morbidity among adolescent hypnotic drug users in a cohort study of 13-17-year-old individuals during 2008-2018 in Norway. Data sources were (i) prescription data from the Norwegian Prescription Database linked to specialist health care diagnoses from the Norwegian Patient Registry and (ii) sleep disorder diagnoses from the Primary Health Care Database. Hypnotic drugs were defined as the sedative antihistamine alimemazine and the ATC group "Hypnotics and Sedatives" (N05C), excluding midazolam. In 2017, 2519 girls (16.5/1000) and 1718 boys (10.7/1000) were incident (new) users of hypnotic drugs. Most of these new users (82% of girls, 77% of boys) were referred to secondary health care, where the most frequent diagnoses were mental and behavioral disorders (51.8% of girls, 46.2% of boys), while only 3.2% received a specific sleep disorder diagnosis. The most common mental and behavioral disorders were "Neurotic stress-related disorders" among girls (27.4%) and "Behavioral and emotional disorders" among boys (23.6%). In conclusion, the trend of increasing hypnotic drug use among adolescents reflects the initiation of hypnotic drugs in a subgroup of the population with a higher disease burden, mainly due to psychiatric disorders, than the general population.

Effective remimazolam loading dose for adequate sedation in regional anesthesia.

PURPOSE: Remimazolam is a novel ultrashort-acting sedative considered appropriate for continuous infusion during surgical procedures. Nevertheless, information regarding its loading dose for sedation during surgery is limited. We aimed to determine the 90% effective dose (ED90) of the remimazolam loading dose for sedation in patients undergoing limb surgery under regional anesthesia. METHODS: We included 50 patients aged 19-80 yr undergoing limb surgery under regional anesthesia. After regional anesthesia, remimazolam besylate was administered at the assigned dose. For ten minutes after the initiation of loading, the level of sedation was evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The primary outcome was the ED90 based on whether patients reached a MOAA/S score of ≤ 3 points (loss of response to verbal command) within ten minutes. The secondary outcomes were the ED50 and the estimated effect site and plasma concentration at the time of achieving successful sedation. RESULTS: In total, 49 patients were included in the final analysis, and adequate sedation with the assigned loading dose was successful in 42 patients. The log-logistic function showed that the ED90 and ED50 were 0.617 mg·kg-1·hr-1 (95% confidence interval [CI], 0.511 to 0.722; 98% CI, 0.492 to 0.741) and 0.438 mg·kg-1·hr-1 (95% CI, 0.335 to 0.541; 98% CI, 0.315 to 0.560), respectively. CONCLUSION: The ED90 of the remimazolam loading dose to achieve adequate sedation in patients undergoing limb surgery under regional anesthesia was 0.617 mg·kg-1·hr-1 (95% CI, 0.511 to 0.722; 98% CI, 0.492 to 0.741). STUDY REGISTRATION: ClinicalTrials.gov (NCT05340335); first posted 22 April 2022.

RéSUMé: OBJECTIF: Le remimazolam est un nouveau sédatif à action ultracourte considéré comme approprié pour la perfusion continue pendant les interventions chirurgicales. Néanmoins, les informations concernant sa dose de charge pour la sédation pendant la chirurgie sont limitées. Notre objectif était de déterminer la dose efficace à 90 % (DE90) de la dose de charge de remimazolam pour la sédation chez la patientèle bénéficiant d'une chirurgie d'un membre sous anesthésie régionale. MéTHODE: Cinquante personnes âgées de 19 à 80 ans bénéficiant d'une chirurgie des membres sous anesthésie régionale ont été incluses. Après l'anesthésie régionale, du bésylate de remimazolam a été administré à la dose assignée. Pendant dix minutes après le début de la charge, le niveau de sédation a été évalué à l'aide de l'échelle modifiée d'évaluation de la vigilance/sédation par l'observateur (MOAA/S). Le critère d'évaluation principal était la DE90 selon que les patient·es ont atteint un score MOAA/S de ≤ 3 points (perte de réponse à la commande verbale) dans les dix minutes. Les critères d'évaluation secondaires étaient la DE50 et l'estimation du site d'effet et de la concentration plasmatique au moment de l'obtention d'une sédation réussie. RéSULTATS: Au total, 49 personnes ont été incluses dans l'analyse finale, et une sédation adéquate avec la dose de charge assignée a été couronnée de succès chez 42 d'entre elles. La fonction log-logistique a montré que les DE90 et DE50 étaient de 0,617 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741) et 0,438 mg·kg−1·h−1 (IC 95 %, 0,335 à 0,541; IC 98 %, 0,315 à 0,560), respectivement. CONCLUSION: La DE90 de la dose de charge de remimazolam pour obtenir une sédation adéquate chez les personnes bénéficiant d'une chirurgie des membres sous anesthésie régionale était de 0,617 mg·kg−1·h−1 (IC 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741). ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05340335); première publication le 22 avril 2022.

[Safe discontinuation of psychotropic drugs in older people? : New evidence and practical approach]. / Sicheres Absetzen von Psychopharmaka bei älteren Menschen? : Neue Evidenz und praktisches Vorgehen.

BACKGROUND: Many older patients are permanently prescribed one or more psychotropic drugs for treatment of symptoms, such as behavioral and psychological symptoms in dementia, depressive symptoms, anxiety, and insomnia. They therefore contribute to the risk of polypharmacy. Recently, deprescribing studies have been published in order to clarify if inadequate medications can be safely discontinued. This mini-review summarizes the study results and derives practical recommendations for routine use. METHOD: A literature search was carried out in PubMed for clinical studies on deprescribing in association with psychotropic substances. RESULTS: After removal of duplications, 12 heterogeneous clinical studies were identified and reduction of psychotropic substances could be successfully achieved in 8 studies. In four of these studies psychological, behavioral and functional endpoints were reported. Criteria for successful deprescribing of sedatives were in particular motivation, information and sufficient cooperation of the patients and for antipsychotic drugs in people with dementia, the sustainable establishment of nonpharmaceutical treatment strategies. Deprescribing was not attempted in cases of a history of severe chronic mental illness and in cases of severe behavioral symptoms in dementia. Evidence for antidepressants was not sufficient to extract practical recommendations. CONCLUSION: Safe deprescribing of antipsychotic drugs in patients with dementia is justified if non-pharmacological treatment options are sustainably implemented, and for sedative drugs in well-informed, highly motivated and cooperative patients.

Exposure to Sedation and Analgesia Medications: Short-term Cognitive Outcomes in Pediatric Critical Care Survivors With Acquired Brain Injury.

Background/Objective: Pediatric intensive care unit (PICU) survivors risk significant cognitive morbidity, particularly those with acquired brain injury (ABI) diagnoses. Studies show sedative and analgesic medication may potentiate neurologic injury, but few studies evaluate impact on survivor outcomes. This study aimed to evaluate whether exposures to analgesic and sedative medications are associated with worse neurocognitive outcome. Methods: A retrospective cohort study was conducted of 91 patients aged 8 to 18 years, undergoing clinical neurocognitive evaluation approximately 1 to 3 months after PICU discharge. Electronic health data was queried for sedative and analgesic medication exposures, including opioids, benzodiazepines, propofol, ketamine, and dexmedetomidine. Doses were converted to class equivalents, evaluated by any exposure and cumulative dose exposure per patient weight. Cognitive outcome was derived from 8 objective cognitive assessments with an emphasis on executive function skills using Principal Components Analysis. Then, linear regression was used to control for baseline cognitive function estimates to calculate a standardized residualized neurocognitive index (rNCI) z-score. Multivariable linear regression evaluated the association between rNCI and medication exposure controlling for covariates. Significance was defined as P < .05. Results: Most (n = 80; 88%) patients received 1 or more study medications. Any exposure and higher cumulative doses of benzodiazepine and ketamine were significantly associated with worse rNCI in bivariate analyses. When controlling for Medicaid, preadmission comorbid conditions, length of stay, delirium, and receipt of other medication classes, receipt of benzodiazepine was associated with significantly worse rNCI (ß-coefficient = -0.48, 95% confidence interval = -0.88, -0.08). Conclusions: Exposure to benzodiazepines was independently associated with worse acute phase cognitive outcome using objective assessments focused on executive function skills when controlling for demographic and illness characteristics. Clinician decisions regarding medication regimens in the PICU may serve as a modifiable factor to improve outcomes. Additional inquiry into associations with long-term cognitive outcome and optimal medication regimens is needed.

Effects of sedatives on radiologic enema reduction in children with ileocolic intussusception: A systematic review and meta-analysis.

BACKGROUND: In children with ileocolic intussusception, sedatives such as midazolam, ketamine and propofol may facilitate radiologic enema reduction, but studies on their separate and joint effects remain controversial. OBJECTIVES: We aimed to systematically analyze studies for the effects of sedatives on the radiologic reduction of ileocolic intussusception in children. METHODS: We searched PubMed, EMBASE, CINAHL, Scopus and Web of Science from database inception through March 2023 for articles that enrolled children with ileocolic intussusception who underwent non-operative pneumatic or hydrostatic enema reduction under ultrasound or fluoroscopic guidance with or without the use of sedatives. The primary and secondary outcomes were success rate in radiologic reduction of ileocolic intussusception and risk of perforation, respectively. Effect estimates from the individual studies were extracted and combined using the Hartung-Knapp-Sidik-Jonkman log-odds random-effects model. Heterogeneity between studies was checked using Cochran's Q test and the I2 statistic. RESULTS: A total of 17 studies with 2094 participants were included in the final review, of which 15 were included in the meta-analysis. Nine studies reported on the success rate of radiologic reduction performed under sedation in all participants, while six studies compared the success rate in two patient groups undergoing the procedure with or without sedation. The pooled success rate of non-operative reduction under sedation was 87 % (95 % CI: 80-95 %), P = 0.000 with considerable heterogeneity (I2 = 85 %). A higher success rate of 94 % (95 % CI: 88-99 %) and homogeneity (I2 = 12 %) were found in studies with pneumatic enema reduction. Among comparative studies, the odds of success of non-operative reduction were increased when the procedure was performed under sedation, with a pooled odds ratio of 2.41 (95 % CI: 1.27-4.57), P = 0.010 and moderate heterogeneity (I2 = 60 %). In a sensitivity analysis, homogeneity was found between analyzed studies when two outliers were excluded (I2 = 0.73 %). The risk of perforation was not significantly different (OR 1.52, 95 % CI: 0.09-23.34), P = 0.764 indicating small study effects. No publication, bias was detected on visual inspection of the funnel plots or the Begg's and Egger's bias tests. Most studies were categorized as having a low risk of bias using Joanna Briggs Institute checklists. CONCLUSIONS: In selected patient groups, sedation can increase the success rate of radiologic enema reduction in children with ileocolic intussusception without evidence of increased risk of perforation. Systematic review protocol registration: PROSPERO CRD42023404887.

Melatonin versus chloral hydrate on sleep induction for recording electroencephalography in children: a randomized clinical trial.

Background: Electroencephalography (EEG) plays an essential role in the diagnosis of seizures. EEG recording in children is done with partial sleep deprivation and sedative drugs. To compare the effectiveness of melatonin and chloral hydrate on sleep induction and EEG recording in children. Materials and methods: In a parallel blinded randomized clinical trial study, 78 patients (6 months-5 years) were included to record EEG. Patients were randomly divided into two groups to receive melatonin (0.4 mg/kg) or chloral hydrate (0.5 ml/kg). After receiving the sedative drug, the start and duration of sedation, recovery time, side effects, and epileptiform waves in the EEG were recorded. The data was analyzed using SPSS version 16, and the significance level was determined to be less than 0.05. Results: A total of 78 children, including 34 girls (43.6%) and 44 boys (56.4%) (average age of 27.15±17.15 months), were examined. Success in the induction of sedation was reported by melatonin in 36 patients (92%) and chloral hydrate in 37 patients (95%), which was similar between the two drugs (P=0.5). The start time (P=0.134) and the duration of sedation (P=0.408) were alike between the two drugs. However, compared to the chloral hydrate, the recovery time in the melatonin group was significantly shorter (P<0.001). Side effects were not seen in melatonin, while six children (15%) using chloral hydrate had mild side effects (P=0.013). Epileptiform waves in EEGs were reported to be similar and positive for melatonin in 18 children (50%) and chloral hydrate in 16 children (43%) (P=0.410). Conclusion: The findings show that using melatonin in the dose prescribed in this study had similar effects to success in inducing sedation with the minimum quantity of chloral hydrate. Regardless of the start time and duration of sedation, the shorter recovery time and the absence of side effects are the advantages of using melatonin.

An Unusual Case of Delayed Midazolam Anaphylaxis and a Review of the Current Literature.

Midazolam is a commonly used, well-tolerated, anxiolytic, sedative, anesthesia induction agent, and an adjunct for procedural sedation that is used widely in the emergency department. The ability to administer midazolam via multiple routes, including intranasal, makes it a particularly common choice for use in children. Intranasal administration is safe, easy, and well tolerated and has been shown to be an effective method of obtaining anxiolysis and/or sedation. Adverse drug reactions, including allergic reactions, can occur with any medication. However, anaphylaxis is an uncommon phenomenon from midazolam. Despite being one of the most common medications used in the emergency department and operating room, there are only a handful of unequivocal cases of anaphylaxis secondary to midazolam. The rarity of this presentation may lead to delays in care and potential adverse outcomes as a result. We present one such case of a 10-year-old patient who experienced anaphylaxis after administration of intranasal midazolam to facilitate a computed tomography scan.

Expert-approved best practice recommendations on the use of sedative drugs and intentional sedation in specialist palliative care (SedPall).

BACKGROUND: The use of sedative drugs and intentional sedation in end-of-life care is associated with clinical, ethical and legal challenges. In view of these and of the issue's great importance to patients undergoing intolerable suffering, we conducted a project titled SedPall ("From anxiolysis to deep continuous sedation - Development of recommendations for sedation in palliative care") with the purpose of developing best practice recommendations on the use of sedative drugs and intentional sedation in specialist palliative care and obtaining feedback and approval from experts in this area. DESIGN: Our stepwise approach entailed drafting the recommendations, obtaining expert feedback, conducting a single-round Delphi study, and convening a consensus conference. As an interdisciplinary group, we created a set of best practice recommendations based on previously published guidance and empirical and normative analysis, and drawing on feedback from experts, including patient representatives and of public involvement participants. We set the required agreement rate for approval at the single-round Delphi and the consensus conference at ≥80%. RESULTS: Ten experts commented on the recommendations' first draft. The Delphi panel comprised 50 experts and patient and public involvement participants, while 46 participants attended the consensus conference. In total, the participants in these stages of the process approved 66 recommendations, covering the topics "indications", "intent/purpose [of sedation]", "decision-making", "information and consent", "medication and type of sedation", "monitoring", "management of fluids and nutrition", "continuing other measures", "support for relatives", and "team support". The recommendations include suggestions on terminology and comments on legal issues. CONCLUSION: Further research will be required for evaluating the feasibility of the recommendations' implementation and their effectiveness. The recommendations and the suggested terminology may serve as a resource for healthcare professionals in Germany on the use of sedative drugs and intentional sedation in specialist palliative care and may contribute to discussion on the topic at an international level. TRIAL REGISTRATION: DRKS00015047 (German Clinical Trials Register).

Deep Sedation in Traumatic Brain Injury Patients.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability in adults. In cases of severe TBI, preventing secondary brain injury by managing intracranial hypertension during the acute phase is a critical treatment challenge. Among surgical and medical interventions to control intracranial pressure (ICP), deep sedation can provide comfort to patients and directly control ICP by regulating cerebral metabolism. However, insufficient sedation does not achieve the intended treatment goals, and excessive sedation can lead to fatal sedative-related complications. Therefore, it is important to continuously monitor and titrate sedatives by measuring the appropriate depth of sedation. In this review, we discuss the effectiveness of deep sedation, techniques to monitor the depth of sedation, and the clinical use of recommended sedatives, barbiturates, and propofol in TBI.

Assessment of high-risk opioid use metrics among individuals with spinal cord injury: A brief report.

OBJECTIVE: To examine high-risk opioid prescription metrics among individuals with chronic spinal cord injury (SCI) living in South Carolina. DESIGN: Cohort Study. SETTING: Two statewide population-based databases, an SCI Surveillance Registry and state prescription drug monitoring program (PDMP). PARTICIPANTS: Linked data was obtained for 503 individuals with chronic (>1year-post injury) SCI who were injured in 2013 or 2014 and who survived at least 3 years post-injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Opioid prescription metrics were obtained from the PDMP. Fill data during the period between January 1, 2014 and December 31, 2017 were analyzed to assess high-risk opioid use. Outcomes included: percentage of individuals prescribed chronic opioids, high-dose chronic opioid therapy (daily morphine milligram equivalents (MME) ≥50 and ≥90), and chronic concurrent opioids and benzodiazepines, sedatives, or hypnotics (BSH). RESULTS: Over half (53%) of the individuals filled an opioid in years 2-3 after injury. Of those, 38% had a concurrent BSH fill during the study period, 76% of which were for benzodiazepines. In any given quarter over the two-year timeframe, over half of the opioid prescriptions were for 60 days or more (chronic opioid prescriptions). Of those, roughly 40% of the individuals had high-dose chronic opioid prescriptions ≥50 MME/d and 25% were ≥90 MME/d. Over 33% had a concurrent BSH prescription for ≥60 days. CONCLUSIONS: While the number of individuals receiving high-risk opioid prescriptions may not be large, it is a concerning number of prescriptions. The findings suggest a need for more cautious opioid prescribing and monitoring of high-risk use in adults with chronic SCI.

Enteral Sedation in Patients Requiring Mechanical Ventilation During an Intravenous Analgesic and Sedative Shortage.

Background: There is a paucity of data evaluating the use of enteral sedation in mechanical ventilation. A sedative shortage resulted in the use of this approach. Purpose: To evaluate the feasibility of using enteral sedatives to decrease intravenous (IV) analgesia and sedative requirements. Materials/Methods: This single-center, retrospective, observational study compared two groups of patients admitted to the ICU who were mechanically ventilated. One group received a combination of enteral and IV sedatives and the second group received IV monotherapy. Linear mixed model (LMM) analyses were performed to assess the impact of enteral sedatives on IV fentanyl equivalents, IV midazolam equivalents, and propofol. Mann-Whitney U tests were performed on percent of days at goal for Richmond Agitation and Sedation Scale (RASS) and critical care pain observation tool (CPOT) scores. Results: One hundred and four patients were included. The average cohort age was 62 years and 58.7% were male. The median length of mechanical ventilation was 7.1 days and the median length of stay was 11.9 days. The LMM estimated that enteral sedatives reduced IV fentanyl equivalents received per patient by an average of 305.6 mcg/day (P = .04), although did not significantly decrease midazolam equivalents or propofol. There was no statistically significant difference in CPOT scores (P = .57 and P = .46 respectively), however RASS scores in the enteral sedation group were more often at goal (P = .03); oversedation occurred more in the non-enteral sedation group (P = .018). Conclusion: Enteral sedation may be a possible way to decrease IV analgesia requirements during periods of shortage.

Prescribing Trends in Psychotropic Medications Among Outpatients of a Latin American Healthcare Setting: A Five-Year Retrospective Study.

Introduction Mental health problems affect millions worldwide, and the prescription of psychotropic drugs is increasing globally. The World Health Organization (WHO) has emphasized the need for proper monitoring of psychotropic drug prescriptions. This study aims to characterize and find trends in the prescription of psychotropics in a Latin American General Hospital. Methods The study analyzed the dispensation of psychotropic prescriptions to outpatients at three pharmacies in the central headquarters of Hospital Clínica Bíblica in San José, Costa Rica, from 2017 to 2021. Psychotropic drugs were classified by the Anatomical Therapeutic Chemical (ATC) code, and the amount of each medication dispensed was standardized using the defined daily dose per 10,000 population per day metric. Patients' ages were categorized into four groups: under 18 years, 18 to 39 years, 40 to 64 years, and 65 years and above. The prescriptions were categorized according to medical specialty. Regression analyses were performed to determine the significance of trends observed in the data Results A total of 5793 psychotropic prescriptions were recorded. The average age of the patients was 58 years. The total consumption of psychotropics decreased by 33.94% from 2017 to 2021, with the most significant decline until 2020. However, there was an increase in consumption in 2021. Clonazepam was the most consumed medication, followed by bromazepam and alprazolam, which was the sole drug to exhibit an escalation in usage between 2017 and 2021. Regression analysis showed that only alprazolam and zopiclone had statistically significant trends. The highest number of prescriptions was dispensed to patients aged between 40 and 64 years, followed by those aged over 65 years. Anxiolytics were also the most commonly prescribed group of drugs. General medicine (20.22%), psychiatry (19.95%), and internal medicine (12.73%) were the primary specialties that prescribed psychotropic; 38.6% of prescriptions were associated with the 10th decile of patients, and 44.9% of prescriptions were issued by the 10th decile of physicians.  Conclusion The consumption of psychotropic drugs decreased from 2017 to 2020 but increased in 2021, with alprazolam being the only drug that showed an increase in consumption throughout the entire period. General practitioners and psychiatrists were found to be the specialties that most commonly prescribe these medications. The study found significant trends only for the consumption of alprazolam and zopiclone and for prescription patterns among psychiatrists and internal medicine physicians.

"At the time I only wanted to relieve stress": Exploring motivation for behaviour change in long-term hypnotic users.

Background: Motivating patients to discontinue long-term benzodiazepine receptor agonist (BZRA) use for insomnia remains an important challenge in primary care because of the medication's unfavourable risk-benefit profile. Previous studies have shown that understanding the complexity of patients' motivation is crucial to the primary care physician for providing effective interventions efficiently. Theoretical frameworks about behaviour change show that motivation is a multi-layered concept that interacts with other concepts, which aligns with a holistic perspective or implementation of the biopsychosocial model. Aim: Exploring primary care patients' views and ideas on what factors helped or hindered them in discontinuing long-term BZRA use, in relation to motivation as conceptualised in the Behaviour Change Wheel, and associated domains of the Theoretical Domains Framework. Design and setting: A qualitative study with semi-structured interviews in primary care in Belgium between September 2020 and March 2021. Method: Eighteen interviews with long-term hypnotic users were audio recorded, transcribed and thematically analyzed, using the Framework Method. Results: The success of discontinuation interventions does not solely rely on patients' spontaneous sense of striving for improvement. Reinforcement and identity were found to be important domains for motivation. Beliefs about personal capabilities, and about consequences of both BZRA intake and discontinuation, differed between previous and current users. Conclusion: Motivation is a multi-layered concept which is not fixed in time. Patient empowerment and goal setting could help long-term BZRA users to lower their intake. As well as public health interventions that might change social attitudes towards the use of hypnotic medication.

[Prescribing Trends of Benzodiazepine and other Sedatives in the Lisbon and Tagus Valley Regional Health Administration between 2013 and 2020: A Retrospective Study]. / Prescrição de Benzodiazepinas e outros Sedativos na Administração Regional de Saúde de Lisboa e Vale do Tejo de 2013 a 2020: Um Estudo Retrospetivo.

INTRODUCTION: Among the Organization for Economic Co-operation and Development members, Portugal has the highest reported consumption of anxiolytics, hypnotics, and sedatives, of which a large proportion are benzodiazepines or related drugs. These are known to cause tolerance and dependence. Other drugs with hypnotic effect, such as antidepressants, antihistamines, antipsychotics, or anticonvulsants have been identified by some reports as alternatives to benzodiazepines for the treatment of insomnia. In this regard, the aim of this study was to characterize the consumption of benzodiazepines, non-benzodiazepine anxiolytic, hypnotic or sedative effect drugs and other drugs with the potential to be used off-label to treat insomnia, and the results concerning benzodiazepine consumption related indicators in the primary health care setting in the Lisbon and Tagus Valley region. MATERIAL AND METHODS: From 2013 to 2020, a census, descriptive and retrospective study was conducted. The evolution of the variables total defined daily doses, defined daily doses per 1000 inhabitants per day (DHD) and relevant indicators were characterized. Data were extracted from the SIARS platform used in the Lisbon and Tagus Valley regional Health Administration. RESULTS: There was a decrease in the consumption of benzodiazepines (from 57.44 to 63.11 DHD) and an increase of non-benzodiazepines and of drugs with potential off-label use (from 6.56 to 8.56 DHD and from 14.70 to 25.95 DHD, respectively). Among non-benzodiazepines, zolpidem was the most consumed drug, also showing an increasing trend (from 4.86 to 6.96 DHD). For the group of drugs with off-label use potential, there was an increased consumption of trazodone (from 3.81 to 7.92 DHD), mirtazapine (from 3.52 to 6.48 DHD), pregabalin (from 3.15 to 4.87 DHD), quetiapine (from 2.68 to 4.59 DHD) and gabapentin (from 1.32 to 1.90 DHD), which was only the case (or, at least, more significantly) for the lower dose formulations. The median of results of the Primary Health Care setting indicator "proportion of elderly patients without prescription of sedatives, anxiolytics, and hypnotics", was 81.0 in 2015 and increased to 84.9 in 2020. For the indicator "proportion of patients without prolonged prescription of sedatives, anxiolytics, and hypnotics", the median was 93.6 in 2019 and 94.3 in 2020. CONCLUSION: There was, overall, a decreasing trend in the dispensing of benzodiazepines in the Lisbon and Tagus Valley Region. Even though this data suggests a change in the therapeutic pattern for insomnia, more robust studies are needed to confirm this observation.

Introdução: Portugal é o país da Organização para a Cooperação e Desenvolvimento Económico com maior consumo de ansiolíticos, hipnóticos e sedativos, sendo uma proporção significativa constituída por benzodiazepinas ou análogos, associados a efeitos de tolerância e dependência. Por este motivo, em alternativa às benzodiazepinas para tratamento da insónia, algumas publicações identificam outros fármacos com efeito hipnótico, como antidepressivos, anti-histamínicos, antipsicóticos ou anticonvulsivantes. Assim, torna-se necessário compreender a evolução do consumo destes medicamentos, pelo que foi objetivo deste estudo avaliar a evolução da dispensa de benzodiazepinas, outros fármacos ansiolíticos, hipnóticos ou sedativos não benzodiazepínicos, fármacos com potencial uso off-label na insónia e os resultados de indicadores dos Cuidados de Saúde Primários neste âmbito na região de Lisboa e Vale do Tejo. Material e Métodos: Realizou-se um estudo em base de dados, censitário e retrospetivo, no período de 2013 até 2020, avaliando-se a evolução das variáveis total de doses diárias definidas, doses diárias definidas por 1000 habitantes por dia (DHD) e dos indicadores relevantes. Os dados foram extraídos da plataforma SIARS da Administração Regional de Saúde de Lisboa e Vale do Tejo. Resultados: Verificou-se uma diminuição da dispensa de benzodiazepinas (de 57,44 para 51,77 DHD) mas o aumento da dispensa de não benzodiazepinas e de fármacos com potencial uso off-label (de 6,56 para 8,56 DHD e de 14,70 para 25,92 DHD, respetivamente). O zolpidem foi o mais dispensado entre os fármacos não benzodiazepínicos, acompanhando a tendência crescente de dispensa (de 4,86 para 6,96 DHD). Do conjunto de fármacos com potencial para uso off-label verificaram-se aumentos da dispensa para a trazodona (de 3,81 para 7,92 DHD), mirtazapina (de 3,52 para 6,48 DHD), pregabalina (de 3,15 para 4,87 DHD), quetiapina (de 2,68 para 4,59 DHD) e gabapentina (de 1,32 para 1,90 DHD), mas mais significativo ou apenas verificado nas formulações com dosagem mais baixa. A mediana dos resultados do indicador "proporção de idosos sem prescrição de sedativos, ansiolíticos e hipnóticos" em 2015 foi de 81,0, tendo em 2020 aumentado para 84,9. A mediana do indicador "proporção de utentes sem prescrição prolongada de ansiolíticos, sedativos e hipnóticos" em 2019 foi de 93,6 e aumentou para 94,3 em 2020. Conclusão: Globalmente, verificou-se uma redução da dispensa de benzodiazepinas prescritas na Região de Lisboa e Vale do Tejo. Parece existir uma alteração do padrão de prescrição no tratamento da insónia. São necessários estudos mais robustos para confirmar esta observação.

Mechanisms and implications in gene polymorphism mediated diverse reponses to sedatives, analgesics and muscle relaxants.

Responses to sedatives, analgesics and muscle relaxants vary among patients under general anesthesia, which could be ascribed to the disparities of clinical characteristics and genetic factors of individuals. Accumulating researches have indicated that gene polymorphisms of the receptors, transporters and metabolizing enzymes associated with anesthetics play a considerable role in their efficacy. However, a systematically summarized study on the mechanisms of gene polymorphisms on pharmacodynamics and pharmacokinetics of anesthetics is still lacking. In this paper, the recent researches on pharmacogenomics of sedatives, analgesics and muscle relaxants are comprehensively reviewed, and the contributions and mechanisms of polymorphisms to the differences of individual efficacy of these drugs are discussed, so as to provide guidance for the formulation of a rational anesthesia regimen for patients with various genotypes.

Psychotropic consumption before and during COVID-19 in Asturias, Spain.

BACKGROUND: Spain as multiple other countries has been experiencing an increasing and sustained trend in the use of psychotropic medications since the mid 90s. Recent studies show public health measures implemented to control SARS-Cov2, such as mobility restrictions and the shutdown of nonessential activities increased mental suffering, even contributing to a higher number of anxiety, depression and insomnia disorders that could lead to an increase in the consumption of psychotropics. The aims were: 1) Evaluate the temporal trend in psychotropic consumption by pharmacological subgroup, sex, and age group 2) Estimate the effect of the COVID-19 pandemic in the use of psychotropic drugs. METHODS: We conducted a retrospective observational study, retrieving all prescriptions of anxiolytics, hypnotics and sedatives, and antidepressants dispensed in pharmacies of Asturias (Northern Spain) for Primary Care patients for the period 2018-2021. We presented the data expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD). To estimate changes in DHDs by year and age group we conducted two multiple linear regressions (one for males and one for females) for every pharmacological subgroup studied. Changes were considered statistically significant when the regression coefficient was p < 0.05. We used the Software R 4.1.0. RESULTS: For the studied period, the highest DHDs are for antidepressants, although all of the subgroups experienced an increase in consumption rates. Women consumed more psychotropic drugs than men. In 2021, 372 out of every 1000 women were taking daily 1 DDD of these drugs versus 184 out of every 1000 men. Consumption rates for all psychotropic drugs progressively increases with age. Conversely, the biggest increases in consumption were among the youngest age groups (0-14 and 15-29 years) for women, while for men there is more variability. The regression models suggest an upward trend in psychotropic consumption during all the period, especially remarkable from 2020, for both genders and all age groups. CONCLUSIONS: - The consumption of psychotropic drugs has gradually increased over the last 4 years, with a significant boost starting in 2020 for both sexes, matching the start of the SARS-COV2 pandemic and the implementation of strict Public Health measures to contain it. - The increase observed on children and adolescents is a matter of concern.

[Safe discontinuation of psychotropic drugs in older people? : New evidence and practical approach]. / Sicheres Absetzen von Psychopharmaka bei älteren Menschen? : Neue Evidenz und praktisches Vorgehen.

BACKGROUND: Many older patients are permanently prescribed one or more psychotropic drugs for treatment of symptoms, such as behavioral and psychological symptoms in dementia, depressive symptoms, anxiety, and insomnia. They therefore contribute to the risk of polypharmacy. Recently, deprescribing studies have been published in order to clarify if inadequate medications can be safely discontinued. This mini-review summarizes the study results and derives practical recommendations for routine use. METHOD: A literature search was carried out in PubMed for clinical studies on deprescribing in association with psychotropic substances. RESULTS: After removal of duplications, 12 heterogeneous clinical studies were identified and reduction of psychotropic substances could be successfully achieved in 8 studies. In four of these studies psychological, behavioral and functional endpoints were reported. Criteria for successful deprescribing of sedatives were in particular motivation, information and sufficient cooperation of the patients and for antipsychotic drugs in people with dementia, the sustainable establishment of nonpharmaceutical treatment strategies. Deprescribing was not attempted in cases of a history of severe chronic mental illness and in cases of severe behavioral symptoms in dementia. Evidence for antidepressants was not sufficient to extract practical recommendations. CONCLUSION: Safe deprescribing of antipsychotic drugs in patients with dementia is justified if non-pharmacological treatment options are sustainably implemented, and for sedative drugs in well-informed, highly motivated and cooperative patients.