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.

Comparison of Sleep Disturbances Among Women with and without a History of COVID-19 Infection

Objective: This study was conducted to compare sleep disturbances between women with and without a history of Coronavirus disease-2019 (COVID-19) infection. Materials and Methods: In this descriptive study, the "Pittsburgh Sleep Quality Index" was used to evaluate sleep problems. The research sample was calculated as 120: 1. group 60 (with a history of COVID-19) and 2. group 60 (without a history of COVID-19) using the G*Power 3.1 method. A total of 141 women were interviewed in case of data loss. Due to the ongoing pandemic, the forms were filled in via google form in the social media environment. The data were analyzed with Statistical Package for Social Sciences for the Windows 22.0 program. Results: The mean age of the women involved in the study was 22.241±6.593 (min: 18, max: 58). Women with a history of COVID-19 experience occasional sleep problems several times a week and have difficulty falling asleep. Statistically significant differences were found between the sleep quality of women with and without a history of COVID-19. Subjective sleep quality, sleep latency, habitual sleep efficiency, use of sleeping medication, daytime dysfunction, and total sleep quality scores were found to be higher in women with a history of COVID-19. Conclusion: Sleep quality is lower in women with a history of COVID-19. During the COVID-19 pandemic, sleep quality should be evaluated, and sleep problems should be identified and treated within a short period. It is recommended to develop methods of coping with anxiety and stress experienced, especially during the COVID-19 pandemic and to raise awareness on this issue among people with a COVID-19 history. Amaç: Bu araştırmanın amacı Koronavirüs hastalığı-2019 (COVID-19) geçiren ve geçirmeyen kadınlar arasındaki uyku bozukluklarının karşılaştırılmasıdır. Gereç ve Yöntem: Tanımlayıcı olarak planlanan bu çalışmada uyku problemlerinin değerlendirilmesi için "Pittsburgh Uyku Kalitesi Índeksi" kullanılmıştır. Araştırma örneklemi G*Power 3.1 yöntemiyle birinci grup 60 (COVID-19 geçiren), ikinci grup 60 (COVID-19 geçirmeyen) olmak üzere 120 olarak belirlenmiştir. Kayıplar göz önüne alınarak toplamda 141 kadın ile görüşülmüştür. Pandeminin devam etmesi sebebi ile formlar sosyal medya ortamında Google form ile doldurulmuştur. Araştırma verileri Statistical Package for Social Sciences for Windows 22.0 programı ile analiz edilmiştir. Bulgular: Çalışmaya katılan kadınların yaş ortalaması 22,241±6,593 (min: 18, maks: 58) idi. COVID-19 geçiren grup arasında uyku problemlerini haftada birkaç kez sıklıkla ve ara sıra görüldüğü, kadınların uykuya dalmada zorluk yaşadıkları tespit edildi. COVID-19 geçiren ve geçirmeyen kadınlar arasında uyku kalitesinin değerlendirilmesi sonucunda gruplar arasında istatistiksel olarak anlamlı farklar tespit edildi. COVID-19 geçiren kadınlar arasında öznel uyku kalitesi, uyku latansı, alışılmış uyku etkinliği, uyku ilacı kullanımı, gündüz uyku işlev bozukluğu ve toplam uyku kalitesi puanlarının daha yüksek olduğu tespit edildi. Sonuç: COVID-19 geçiren kadınlar arasında uyku kalitesi daha düşüktür. COVID-19 sürecinde uyku kalitesinin değerlendirilmesi ve uyku problemlerinin kısa sürede belirlenerek tedavi edilmesi önemlidir. Özellikle COVID-19 sürecinde yaşanılan kaygı ve stresle baş etme yöntemlerinin geliştirilmesi ve tanı alan kişilerin bu konuda da farkındalıklarının sağlanması önerilmektedir.

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.

Aerosol generation during paediatric procedural sedation with continuous-flow nitrous oxide suggests a low risk of airborne viral transmission to health-care workers.

AIM: Inhaled nitrous oxide is a common form of procedural sedation in paediatric care. During the COVID-19 pandemic, concerns about potential aerosol generation and associated viral transmission to health-care workers have led to controversy regarding its use. We aimed to measure the degree of aerosol generation during continuous flow nitrous oxide sedation to inform future guidelines. METHODS: Aerosol numbers in the respirable range were measured using a particle counter during 30 procedures undertaken in children under nitrous oxide sedation in the Emergency Department. RESULTS: Changes from baseline measurements were greatest in particles in the 0.3 µm range. The mean increase from baseline in 0.3 µm particles per cubic metre was 18 022 (95% confidence interval (CI) 5949-30 096) after the child entered the room, and 2931 (95% CI -4407 to 10 269) during nitrous oxide administration. CONCLUSION: Variation of respirable particle numbers from baseline levels was no greater during nitrous oxide administration than for breathing and talking asymptomatic children. These results suggest the additional risk of airborne viral transmission to staff during inhaled nitrous oxide sedation is low.

Electroencephalogram-Based Evaluation of Impaired Sedation in Patients with Moderate to Severe COVID-19 ARDS.

The sedation management of patients with severe COVID-19 is challenging. Processed electroencephalography (pEEG) has already been used for sedation management before COVID-19 in critical care, but its applicability in COVID-19 has not yet been investigated. We performed this prospective observational study to evaluate whether the patient sedation index (PSI) obtained via pEEG may adequately reflect sedation in ventilated COVID-19 patients. Statistical analysis was performed by linear regression analysis with mixed effects. We included data from 49 consecutive patients. None of the patients received neuromuscular blocking agents by the time of the measurement. The mean value of the PSI was 20 (±23). The suppression rate was determined to be 14% (±24%). A deep sedation equivalent to the Richmond Agitation and Sedation Scale of -3 to -4 (correlation expected PSI 25-50) in bedside examination was noted in 79.4% of the recordings. Linear regression analysis revealed a significant correlation between the sedative dosages of propofol, midazolam, clonidine, and sufentanil (p < 0.01) and the sedation index. Our results showed a distinct discrepancy between the RASS and the determined PSI. However, it remains unclear to what extent any discrepancy is due to the electrophysiological effects of neuroinflammation in terms of pEEG alteration, to the misinterpretation of spinal or vegetative reflexes during bedside evaluation, or to other causes.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels. METHODS: Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels. RESULTS: Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01). CONCLUSIONS: A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Diaphragm dysfunction induced by mechanical ventilation – pathophysiology and treatment options

Majority of mechanically ventilated patients in intensive care units (ICU) suffer from diaphragm dysfunction. It occurs in approximately 60 to 80 % of such patients. Early after the initiation of mechanical ventilation pathophysiological processes leading to diaphragm dysfunction are triggered. Inadequate diaphragm function significantly contributes to difficult weaning, prolonged mechanical ventilation as well as increased morbidity and mortality. Etiology of ventilation induced diaphragm dysfunction (VIDD) is complex and multifactorial. Metabolic and inflammatory changes in muscular tissue are one of the hallmarks of critical illness and together with patient-ventilator asynchrony and prolonged vasopressor support play a key role in VIDD pathophysiology. Treatment of primary cause of respiratory insufficiency is of utmost importance, but besides this, adequate titration of sedatives and muscle relaxants, monitoring of respiratory mechanics and deployment of proportional modes of ventilation are of great significance in prevention and treatment of VIDD. Proportional modes offer support to spontaneous breathing. However, unlike the conventional modes, this support is not constant, it changes with every breath, offering assistance that is proportional to activity of respiratory muscles. The aim of this article was to offer an insight into latest data from scientific literature to healthcare providers. The electronic search of Pubmed, Medline and Google Scholar was conducted by using MeSH (Medical Subject Headings) terms. Our search was limited to randomized controlled trials and review articles written in English, which were published from 2016 to 2021 and conducted on adult patients. Conclusion: During the pandemic of SARS-CoV-2, the importance of mechanical ventilation with all its aspects came into the focus of medical community. Mechanical ventilation is considered as a life saving method of treatment, but serious adverse effects such as dysfunction of diaphragm can be encountered. There are ongoing developments of new strategies and modes of mechanical ventilation aiming at protection of lungs and diaphragm. Diaphragm protective mechanical ventilation reduces the duration of mechanical ventilator support, decreases the incidence of severe complications such as multiple organ failure and consequntely mortality. © 2022 Hrvatski Lijecnicki Zbor. All rights reserved.

Associated Factors of High Sedative Requirements within Patients with Moderate to Severe COVID-19 ARDS.

The coronavirus pandemic continues to challenge global healthcare. Severely affected patients are often in need of high doses of analgesics and sedatives. The latter was studied in critically ill coronavirus disease 2019 (COVID-19) patients in this prospective monocentric analysis. COVID-19 acute respiratory distress syndrome (ARDS) patients admitted between 1 April and 1 December 2020 were enrolled in the study. A statistical analysis of impeded sedation using mixed-effect linear regression models was performed. Overall, 114 patients were enrolled, requiring unusual high levels of sedatives. During 67.9% of the observation period, a combination of sedatives was required in addition to continuous analgesia. During ARDS therapy, 85.1% (n = 97) underwent prone positioning. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) was required in 20.2% (n = 23) of all patients. vv-ECMO patients showed significantly higher sedation needs (p < 0.001). Patients with hepatic (p = 0.01) or renal (p = 0.01) dysfunction showed significantly lower sedation requirements. Except for patient age (p = 0.01), we could not find any significant influence of pre-existing conditions. Age, vv-ECMO therapy and additional organ failure could be demonstrated as factors influencing sedation needs. Young patients and those receiving vv-ECMO usually require increased sedation for intensive care therapy. However, further studies are needed to elucidate the causes and mechanisms of impeded sedation.

Ketamine infusion as a sedative-analgesic in severe ARDS (KISS).

RATIONALE: Ketamine has been used as a sedative analgesic in trauma setting, but data regarding its efficacy and safety is lacking in severe ARDS. This retrospective study aims to determine if Ketamine is safer as a sedative agent in mechanically ventilated patients. During the COVID pandemic, as there was a shortage of sedative agents, Ketamine was used. OBJECTIVES: The primary objective was to compare the safety of ketamine to other sedatives. The secondary objective was to compare the effect of ketamine to other sedatives regarding the need for vasopressor, incidence of delirium, infectious complications, acute kidney injury, hospital length of stay, and length of ventilator days. METHODS: A retrospective, observational cohort study was conducted. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-four patients (63 men and 61 women) were included. Thirty-four patients received ketamine, while 90 patients received other traditionally used sedatives such as propofol and midazolam. The patients' median age was 64 years in the ketamine group and 68 years in the non-ketamine group. Seventeen patients in the ketamine group (50%) and 65 patients (72%) in the non-ketamine group had mortality (p < 0.02). The hospital length of stay was 22.85 days (± 16.36) in the ketamine group and 15.62 days (± 14.63) in the non-ketamine group (p < 0.02). There was no statistically significant difference among the outcomes of the need for vasopressor, the incidence of delirium, infectious complications, and acute kidney injury. CONCLUSIONS: Ketamine as a sedative-analgesic agent in COVID-19 patients with severe acute respiratory distress syndrome demonstrated safety with reduced mortality. The ketamine group had a higher hospital length of stay, but a similar complication profile compared to the non-ketamine group. Further prospective randomized controlled trials are warranted to confirm these findings.