Hypnotic Agent Research Articles

Pharmacogenotyping disproves genetic cause of drug-related problems in family history: a case report

BackgroundIn clinical practice, family medication history is not routinely assessed as part of a patient’s family health history (FHH). The information is self-reported and can depend on the individual’s subjective perception. To illustrate how pharmacogenetic (PGx) testing results could be used to validate self-reported family medication history on drug-related problems (DRP), as well as to inform medication-related decisions, we herein present a case involving ten members of the same family.Case PresentationPrior to a planned surgery, a preemptive PGx panel test was performed for a nine-year-old girl due to self-reported family medication history. The PGx panel test was also performed for her three siblings, parents, and grandparents. The focus was directed to the paternal grandmother, as she reported DRP from the hypnotic agent propofol, and to the maternal grandmother, as she described DRP after the administration of codeine and tramadol. A commercial PGx panel test of 100 variations in 30 different genes was conducted and analyzed focusing on genetic variants in cytochrome P450 enzyme 2B6 (CYP2B6), and CYP2D6 as they are involved in the biotransformation of propofol and the bioactivation of codeine and tramadol, respectively. The girl was identified as (1) CYP2B6 intermediate metabolizer (IM) with reduced enzyme activity and (2) CYP2D6 poor metabolizer (PM) with no enzyme activity. Regarding the planned surgery, it was recommended (1) to carefully titrate propofol dosage with increased monitoring of potential DRP and (2) to avoid opioids whose activation is mediated by CYP2D6 (e.g. codeine and tramadol). Further PGx testing revealed (1) the paternal grandmother as CYP2B6 normal metabolizer (NM) and (2) the maternal grandmother as CYP2D6 NM.ConclusionThe original trigger for PGx testing was the self-reported, conspicuous family medication history of DRP reported by the grandmothers. However, the girl’s genotype predicted phenotypes of CYP2B6 IM and CYP2D6 PM, differed from the grandmothers’. With this exemplary case, we propose that hereditary concerns based on self-reported information on DRP should be verified by a PGx panel test, when the respective drug exhibits a PGx association. Also, the girl’s PGx testing results provided important medication recommendations, which were considered perioperatively by the anesthetist suggesting to use PGx testing results preemptively to inform medication-related decisions.

Hypnotic use and the risk of cardiovascular diseases in insomnia patients

Abstract Background Insomnia, commonly treated with hypnotic agents, is an independent risk factor of cardiovascular diseases. Previous research demonstrated the detrimental effect of hypnotics on the prognosis of cardiovascular patients. Purpose We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. Methods In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting and competing risk models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of hypnotics-related genes and cardiovascular disease association. The genome-wide association data of CHD, HF, and stroke were there large-scale genome-wide association analyses. Tissue-specified expression quantitative trait loci (eQTL) data was derived from BrainSeq phase II. Results During a median follow-up of 14.3 years, the matched cohort documented a total of 1,019 CHD cases, 406 HF cases, 285 stroke cases, and 197 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality (Figure 1). The inverse probability of treatment weighting and competing risk models didn’t alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. However, GABRG1—a drug target for benzodiazepines—was associated with heightened risks for heart failure, and ischemic stroke (Figure 2). Conclusions Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Z-meds are safe regarding the risk of cardiovascular outcomes in the UKB population with insomnia.Figure 1Figure 2

Lavender improves sleep through olfactory perception and GABAergic neurons of the central amygdala

Ethnopharmacological relevanceThe use of lavender as sleep aid or hypnotic agent can be traced back as early as ancient Romans and Greeks. Yet, objective experimental data on whether and how lavender enhances sleep duration or/and sleep quality remain lacking. Aim of the studyWe aimed to characterize the sleep-wake regulating effects of lavender in the mouse and to demonstrate the brain targets and neural circuits involved. Materials and methodsA self-made precise odor delivery system combined with chronic polysomnographic recordings was employed to assess the sleep-wake effects of inhalation with lavender essential oil (LEO, extracted from lavender) and its different constituents during the light and dark phases in free-moving C57BL/6J mice. Neuroviral labeling, in situ hybridization and pharmacogenetics were combined to identify the neural circuits and targets involved. Finally, an insomniac model of DL-4-Chlorophenylalanine (PCPA)-treated mice was established to examine the sleep-inducing potential of LEO. ResultsWe found that inhalation of LEO with a concentration at 25.0% during the light (inactive) phase significantly shortened the latency to non-rapid eye movement (NREM) sleep, increased the total amount of NREM sleep at the expense of wakefulness (W), and enhanced cortical EEG slow wave activities, notably delta power spectra density. We further identified linalool, d-limonene, 1,8-cineole, linalyl acetate and terpinene-4-ol as the major effective sleep-promoting monomer components. Importantly, we found that LEO no longer produced any of the above sleep-promoting effect following either nasal injection of zinc sulfate which interrupts the olfactory pathway, or pharmacogenetics silencing of central amygdala GABAergic neurons. Finally, LEO reestablished NREM sleep with short latency in PCPA-treated insomniac mice, effects comparable with those induced by a potent sedative diazepam. ConclusionsWe have characterized the quantitative and qualitative sleep-promoting effects of LEO and its effective components via the olfactory pathway and central amygdala GABA neuronal targets. The hypnotic property of LEO is reinforced by its ability to restore sleep in insomnia. Our study thus establishes a neurobiological basis for aromatherapy of sleep disorders using lavender.

Is an acute overdose of zolpidem fatal?

Zolpidem, widely prescribed for short-term management of insomnia, is a non-benzodiazepine hypnotic agent. It carries a high potential for abuse and an elevated risk of suicide. Overdose generally results in mild central nervous system depression, though severe outcomes are possible when co-ingested with other CNS depressants. Standard treatments include gastric lavage, flumazenil administration, and intravenous fluids. This case report describes a 66-year-old female admitted after an apparent suicidal ingestion of approximately 200 mg of zolpidem. Upon admission, she was unconscious, with bradypnea and hypotension, scoring 5 on the Glasgow Coma Scale. Gastric lavage and N-acetylcysteine were administered due to elevated liver enzymes suggesting concomitant paracetamol poisoning, which was confirmed by urine tests. Flumazenil temporarily improved her condition, and she was subsequently transferred to the Intensive Care Unit for mechanical ventilation. Her clinical status stabilized, leading to extubation on the second day and transfer to the Psychiatry Unit. This case highlights the critical need for timely intervention and continuous monitoring in zolpidem overdose scenarios, particularly when polypharmacy is involved. In instances of respiratory failure following zolpidem overdose, it is imperative to investigate the potential co-ingestion of additional substances.

Intense Noxious Stimulus during an Adequate Depth of General Anesthesia Produces a Transient Burst Suppression Pattern in a Density Spectral Array

AbstractThere has been renewed interest in utilizing electroencephalogram (EEG)/processed EEG to assess the response to noxious stimuli under general anesthesia (GA). We are submitting multiple observations that explore the intriguing phenomenon of the transient burst suppression pattern (BSP) in the density spectral array (DSA) of the SedLine Masimo during intense noxious stimulation under GA. Three patients underwent spine surgery under sevoflurane/total intravenous anesthesia with adequate depth. Sudden transient BSP was noted on the DSA during an intense noxious stimulus. Traditionally, BSP on the processed EEG/DSA under GA in a hemodynamically stable patient indicates excessive hypnosis. It is usually treated by reducing the dose of a hypnotic agent. Decreasing the depth of anesthesia (DOA) in the presence of intense pain can have adverse consequences, especially in high-risk patients. Awareness of processed EEG/DSA changes associated with intense noxious stimuli, helps the anesthesiologist to titrate analgesia without altering DOA.

Hypnotic Use and the Risk of Cardiovascular Diseases in Insomnia Patients.

We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting, competing risk models, and shared frailty models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of the association between therapeutic targets of hypnotics and cardiovascular diseases. During a median follow-up of 14.3 years, the matched cohort documented a total of 929 CHD cases, 360 HF cases, 262 stroke cases, and 180 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality. The inverse probability of treatment weighting, competing risk models, and shared frailty models didn't alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Both observational and genetic evidence raised safety concerns regarding the cardiovascular impact of benzodiazepines. No cardiovascular hazard of Z-meds was discovered in the UKB population with insomnia.

Remimazolam for anesthesia and sedation in pediatric patients: a scoping review.

Anesthetic management of pediatric patients poses several challenges and the optimal anesthetic agent for use in this population is still a matter of debate. We systematically searched PubMed/MEDLINE and Google Scholar from their inception for studies that investigated the role and potential applications of remimazolam, a novel ultra-short-acting benzodiazepine, in pediatric patients. Furthermore, in March 2024, an update of the literature search along with an additional post-hoc search on the EMBASE database were performed. A total of fourteen pertinent studies which spanned the 2021-2023 period explored remimazolam as either the primary or adjuvant hypnotic agent for inducing and/or maintaining general anesthesia or sedation. Preliminary evidence derived from these studies highlighted that remimazolam is a safe and effective option for both sedation and general anesthesia in pediatric patients, particularly those with concurrent mitochondrial disorders, myopathic diseases, or at risk for malignant hyperthermia. Moreover, the current evidence suggested that remimazolam may contribute to reducing preoperative anxiety and postoperative delirium in children. Its favorable pharmacodynamic and pharmacokinetic profile demonstrated potential safety, effectiveness, and ease-of-use in various perioperative pediatric contexts, making it suitable for integration into specific protocols, such as intraoperative monitoring of evoked potentials and management of difficult intubation. Notwithstanding these promising findings, further research is essential to determine optimal dosages, establish conclusive evidence of its superiority over other benzodiazepines, and elucidate the impact of genetic factors on drug metabolism.

HIF1A overexpression caused by etomidate activates PGK1-induced oxidative stress in postoperative cognitive dysfunction

Etomidate (ETO), a hypnotic agent used for anesthesia induction, has been shown to induce long-lasting cognitive deficits. In the present study, we investigated whether ETO could activate the HIF1A/PGK1 pathway to antagonize oxidative damage in mice with postoperative cognitive dysfunction (POCD). A mouse model of ETO-mediated POCD was established, and pathological changes, apoptosis, and inflammatory factors in mouse hippocampal tissues were analyzed by HE staining, TUNEL assay, and ELISA. ETO was revealed to cause cognitive dysfunction in mice. Integrated database mining was conducted to screen out transcription factors that are both related to ETO and POCD. Hypoxia-inducible factor 1-alpha (HIF1A) was overexpressed in mice with POCD, and downregulation of HIF1A alleviated cognitive dysfunction in mice. HIF1A downregulation inhibited the transcription of phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 abated the alleviating effects of HIF1A knockdown on oxidative stress in mice with POCD. In addition, HIF1A activation of PGK1 induced oxidative stress and apoptosis in HT-22 cells while inhibiting cell viability. Taken together, we demonstrated that HIF1A activation of PGK1 induced oxidative stress in ETO-mediated POCD.

Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

Toxicological and Sedative Effects of Chipilin (Crotalaria longirostrata) Leaf Extracts Obtained by Maceration and Supercritical Fluid Extraction.

Chipilin (Crotalaria longirostrata) is consumed as a vegetable in the preparation of traditional dishes. As a folk medicine, Chipilin extracts are used as a hypnotic and sedative agent; however, there are few reports that support these uses. This study aimed to characterize the compounds present in Chipilin leaf extracts and to investigate their sedative effect using zebrafish as an in vivo model. Extracts were obtained by maceration with water (H2O), ethanol (EtOH), and EtOH-H2O, while oleoresin was obtained by supercritical fluid extraction (SFE). Total phenolic and flavonoid contents were quantified by colorimetric methods. Phytochemical constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The chronic and acute toxicities of Chipilin extracts were tested in zebrafish embryos and larvae, respectively. Chipilin sedative effect was tested by the larvae response to dark-light-dark transitions. EtOH-H2O extracts had the highest value of total phenolics (5345 ± 5.1 μg GAE/g), followed by water and oleoresin (1815 ± 5.1 and 394 ± 5.1 μg GAE/g, respectively). In water extracts were identified the alkaloid trachelanthamidine, 1,2β-epoxy- and the alkyl ketone 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, while oleamide, α-monostearin, and erucamide were detected in all samples except in water extracts. Oleoresin extract had the lowest embryotoxicity (LC50 = 4.99 μg/mL) and the highest sedative effects. SFE is a green alternative to obtain Chipilin extracts rich in erucamide, an endocannabinoid analogue, which plays an important role in the development of the central nervous system and in modulating neurotransmitter release.

The clinical role of remimazolam: Protocol for a scoping review.

Remimazolam, a novel benzodiazepine, shows promise as an alternative to traditional sedatives and hypnotic agents in procedural sedation and general anaesthesia. While preliminary research indicates potential advantages over conventional agents, such as faster onset, predictable duration, and improved safety profile, the extent and quality of existing evidence remain unclear. This scoping review aims to investigate the current clinical role of remimazolam and provide a broad and comprehensive overview. The proposed review will adhere to the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews. A comprehensive search will be conducted across major peer-reviewed databases and grey literature will be sought. All studies involving individuals undergoing procedural sedation or general anaesthesia with remimazolam will be eligible. Data extraction will encompass trial and participant characteristics, intervention details, reported outcomes, comparative efficacy versus midazolam and propofol, patient and operator experience and economic costs. We will provide a descriptive summary supplemented by statistics, figures and tables where applicable. The outlined scoping review aims to assess the clinical use of remimazolam in procedural sedation and as the hypnotic component of general anaesthesia. The review will map the current body of evidence of remimazolam and identify knowledge gaps, contributing to understanding its clinical implications and guiding future research efforts in procedural sedation and general anaesthesia.

Sevoflurane preconditioning in living liver donation is associated with better initial graft function after pediatric transplantation: a retrospective study

IntroductionInitial allograft function determines the patient’s immediate prognosis in pediatric liver transplantation. Ischemia-reperfusion injuries play a role in initial poor graft function (IPGF). In animal studies, preconditioning with inhaled anesthetic agents has demonstrated a protective effect on the liver. In humans, the few available studies are conflicting. This study assesses the association between the hypnotic agent used to maintain anesthesia during hepatectomy in living donors and the occurrence of IPGF after pediatric transplantation.MethodsWe conducted a single-center retrospective analysis of children who received a living donor liver transplant (LDLT) between 2010 and 2019. We analyzed the incidence of EAD according to the hypnotic agent used to maintain general anesthesia during donor hepatectomy.ResultsWe included 183 pairs of patients (living donors-recipients). The anesthetics used in the donor were propofol (n = 85), sevoflurane (n = 69), or propofol with sevoflurane started 30 min before clamping (n = 29). Forty-two children (23%) developed IPGF. After multivariate logistic regression analysis, factors significantly associated with the occurrence of IPGF were the anesthesia maintenance agent used in the donor (p = 0.004), age of the donor (p = 0.03), duration of transplant surgery (p = 0.009), preoperative receiver neutrophil to lymphocyte ratio (p = 0.02), and albumin (p = 0.05).ConclusionSignificantly fewer children who received a graft from a donor in whom only sevoflurane was used to maintain anesthesia developed IPGF. Although additional research is needed, this preconditioning strategy may provide an option to prevent IPGF after living liver donation.

Electroencephalographic Features of Elderly Patients during Anesthesia Induction with Remimazolam: A Substudy of a Randomized Controlled Trial.

Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram characteristics of remimazolam are not well known. The purpose of this study was to identify the electroencephalographic features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol. Remimazolam (n = 26) or propofol (n = 26) were randomly administered for anesthesia induction in surgical patients. The hypnotic agent was blinded only to the patients. During the induction of anesthesia, remimazolam was administered at a rate of 6 mg · kg-1 · h-1, and propofol was administered at a target effect-site concentration of 3.5 μg/ml. The electroencephalogram signals from eight channels (Fp1, Fp2, Fz, F3, F4, Pz, P3, and P4, referenced to A2, using the 10 to 20 system) were acquired during the induction of anesthesia and in the postoperative care unit. Power spectrum analysis was performed, and directed functional connectivity between frontal and parietal regions was evaluated using normalized symbolic transfer entropy. Functional connectivity in unconscious processes induced by remimazolam or propofol was compared with baseline. To compare each power of frequency over time of the two hypnotic agents, a permutation test with t statistic was conducted. Compared to the baseline in the alpha band, the feedback connectivity decreased by averages of 46% and 43%, respectively, after the loss of consciousness induced by remimazolam and propofol (95% CI for the mean difference: -0.073 to -0.044 for remimazolam [P < 0.001] and -0.068 to -0.042 for propofol [P < 0.001]). Asymmetry in the feedback and feedforward connectivity in the alpha band was suppressed after the loss of consciousness induced by remimazolam and propofol. There were no significant differences in the power of each frequency over time between the two hypnotic agents (minimum q value = 0.4235). Both regimens showed a greater decrease in feedback connectivity compared to a decrease in feedforward connectivity after loss of consciousness, leading to a disruption of asymmetry between the frontoparietal connectivity.

The influence of drugs used for sedation during mechanical ventilation on respiratory pattern during unassisted breathing and assisted mechanical ventilation: a physiological systematic review and meta-analysis

Sedation management has a major impact on outcomes in mechanically ventilated patients, but sedation strategies do not generally consider the differential effects of different sedatives on respiration and respiratory pattern. A systematic review was undertaken to quantitatively summarize the known effects of different classes of drugs used for sedation on respiratory pattern during both spontaneous breathing and assisted mechanical ventilation. This was a systematic review and meta-analysis conducted using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials up to June 2020 to retrieve studies that measured respiratory parameters before and after the administration of opioids, benzodiazepines, intravenous and inhaled anaesthetic agents, and other hypnotic agents (PROSPERO #CRD42020190017). A random-effects meta-analytic model was employed to estimate the mean percentage change in each of the respiratory indices according to medication exposure with and without mechanical ventilation. Risk of bias was assessed using the Cochrane risk of bias assessment tools. Fifty-one studies were included in the analysis. Risk of bias was generally deemed to be low for most studies. Respiratory rate decreased with the administration of opioids in both non-ventilated patients (18% decrease, 95% CI 12-24%) and ventilated patients (26% decrease, 95% CI 15-37%) and increased with inhaled anaesthetics in non-ventilated patients (83% increase, 95% CI 49-118%) and ventilated patients (50% increase, 28-72%). In non-ventilated patients, tidal volume decreased following administration of inhaled aesthetics (55% decrease, 95% CI 25-86%), propofol (36% decrease, 95% CI 20-52%), and benzodiazepines (28% decrease, 95% CI 17-40%); in patients receiving assisted mechanical ventilation, tidal volume was not significantly affected by sedation. Administration of other hypnotic agents was not associated with changes in respiratory rate or tidal volume. Different classes of drugs used for sedation exert differential effects on respiratory pattern, and this may influence weaning and outcomes in mechanically ventilated patients. This study did not receive any funding support.

Study of Total Intravenous Anaesthesia in laparoscopic Surgery

Background: Total intravenous anaesthesia in laparoscopic surgery is safer than open laparotomy operationsbecause propofol, a sedative hypnotic agent with excellent recovery drug and having anti-emetic properties, andnew synthetic opioids (fentanyl congeners) provide excellent analgesia; hence, TIVA has become more popular inlaparoscopic surgery.Method: 45 adult patients aged between 18 to 65 undergoing laparoscopic surgery were studied. A solutionof propofol containing different concentrations of sufentanil (1 μgm per ml and 2 μgmper ml) was infused.Patient’s HR, SBP, DBP, MAP, and peripheral O2 saturation from the anaesthesia monitor was taken as a baselinemeasurement. All the hemodynamic parameters were recorded intra-operatively at different intervals of duration.Results: The changes in mean values of hemodynamic values were insignificant, and only significant parameterswere noted. 158.12 (± 80.9) mean value time to rescue analgesia (in minutes) Post-surgical complications are 3(6.6%) Nausea and vomitingConclusion: Propofol, containing different concentrations of sufentanil, provides hemodynamic stability withthe least post-surgical complications; hence, total intravenous anaesthesia is an ideal substitute for inhalationanaesthesia in laparoscopic surgery because inhalation anaesthesia has a higher risk of hemodynamic instability.

Identification of post-mortem product of zolpidem degradation by hemoglobin via the Fenton reaction.

Zolpidem, N,N-dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide, is a hypnotic agent widely used in clinical practice but is detected in many clinical cases of fatal intoxication and suicide. In forensic toxicology, the precise determination of zolpidem concentration in blood is a must to provide concrete evidence of death by zolpidem poisoning. However, the concentrations of zolpidem in blood at autopsy often differ from those at the estimated time of death. In the present study, we found that zolpidem was degraded by hemoglobin (Hb) via the Fenton reaction at various temperatures. The mechanism underlying zolpidem degradation involved the oxidation of its linker moiety. The MS and MS/MS spectra obtained by liquid chromatography quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap-MS) showed the formation of 2-hydroxy-N,N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl)acetamide (2-OH ZOL) in Hb/H2O2 solution incubated with zolpidem and in the blood of several individuals who died from ingestion of zolpidem. These results suggest that 2-OH ZOL is the post-mortem product of zolpidem degradation by Hb via the Fenton reaction.

Drug-facilitated sexual assault followed by femicidal chloroform poisoning and suffocation: A case-report of criminal responsibility

IntroductionCriminal responsibility evaluation represents one of the most controversial and debated issues in forensic psychiatry. Although clear procedures have been recommended, little research exists on decision-making process by forensic psychiatrists. We present a case assessing the criminal responsibility of a murderer who committed femicide as a result of chloroform poisoning and suffocation after a drug-facilitated sexual assault. Materials and methodsA.S., a 30-year-old female, was found dead in the home of S.P., a 50-year-old male. S.P. recounted killing A.S. by forced inhalation of chloroform, when the woman had experienced sensory clouding following unintentional ingestion of Zolpidem, a hypnotic agent. A multidisciplinary approach was taken to resolve the case. Autopsy, histological, genetic, and toxicological examinations were performed by a forensic pathologist, while a digital forensic examiner analysed electronic devices. A pool of three forensic psychiatrists and two psychologists was asked to assess the mental state of S.P. at the time of the crime. Results and conclusionsThe cause of death of A.S. was identified as a lethal chloroform intoxication in altered consciousness caused by Zolpidem, while homicidal suffocation was also described. Mobile forensics demonstrated that S.P. had videotaped the crime scene, clearly revealing that A.S. had been sexually assaulted by S.P. before dying. Criminal responsibility of S.P. was evaluated through various psychological tests and seven interviews with the accused, each lasting an average of 180 min. Specialists concluded that S.P. could not be exempted from being responsible for the homicide.

Acid-base Status and Electrolyte Changes During Propofol Based General Anesthesia in Patients Undergoing Septoplasty

Propofol is a widely used hypnotic agent globally; however, it may have adverse effects on critical patient outcomes, potentially by interfering with the organ-protective properties of other interventions. Propofol anesthesia can lead to disruptions in metabolic balance. This research aims to examine alterations in acid-base and electrolyte levels during septoplasty surgery when propofol-based anesthesia is administered. In this prospective, observational cohort study, a total of 30 patients between the ages of 18 and 65 with an American Society of Anesthesia physical status I-II were included. Arterial blood samples were collected both before the administration of propofol and five minutes after propofol injection, with the purpose of evaluating the acid-base status and electrolyte parameters including sodium, chloride, calcium and potassium. No cases of acidosis or statistically significant alterations in electrolyte levels were observed in patients following the administration of propofol. Furthermore, none of the patients exhibited any adverse effects such as cardiac failure, rhabdomyolysis, severe metabolic acidosis, or renal failure attributable to propofol during the study. We suggest that the induction dose of propofol for general anesthesia does not lead to metabolic acidosis or electrolyte disturbances. Keywords: Propofol, Arterial, Metabolic acidosis, Anesthesia, Acid-base balance, Potassium, Anion gap

Tratamento da intoxicação por zolpidem com flumazenil em um gato

This report aims to describe the case of a cat intoxicated with zolpidem that was treated with flumazenil. Flumazenil is an imidazodiazepine that effectively reverses the central effects of benzodiazepines. In humans, it is used to treat zolpidem poisoning. Zolpidem is a sedative hypnotic agent, non-benzodiazepine, that is used to treat patients with insomnia. A 2-year-old Bengal cat weighing 2.5 kg showed signs of ataxia, incoordination and diarrhea after accidental ingestion of 10 mg zolpidem (Stilnox®). The cat was administered with 0.1 mg/kg of flumazenil intravenously, and after 20 minutes all clinical signs disappeared. To our knowledge, this is the first report of the use of flumazenil for the treatment of zolpidem poisoning in cats. Discussion regarding the treatment of zolpidem poisoning is necessary owing to the increased prescription of this drug in humans and, consequently, to a greater possibility of accidental poisoning in domestic animals.

Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.

Chronic insomnia affects 5% to 10% of the US population, increasing the demand for treatment options and the corresponding research to prove their validity.1 This review compares recommendations from 3 clinical guidelines and summarizes hypnotic medications, including their newly reported side effects not mentioned in the guidelines. In addition, we aim to provide an overview of what pharmacotherapies are available for prescribers and patients. A literature search was conducted for articles published prior to January 10, 2022, and case reports and clinical studies were retrieved from PubMed and Google Scholar. Definitive conclusions cannot be drawn regarding the safety and efficacy of medications reviewed; however, trends are apparent. All 3 guidelines included in this review remarked most treatment recommendations as weak except for cognitive behavioral therapy for insomnia, which is effective but not readily available. Furthermore, based on the 15 case reports and 13 clinical studies presented in this review, many of the medications used for treatment of insomnia present safety concerns. Benzodiazepines and benzodiazepine receptor agonists are commonly used hypnotic agents with the "Z-drugs" having robust data establishing their efficacy for the short-term treatment of chronic insomnia. However, significant adverse effects related to the central nervous system (CNS), including developing tolerance, addiction, CNS depression, and amnesia, remain barriers to their long-term use. In comparison, newer agents present more favorable side-effect profiles although with less established efficacy. Additionally, off-label agents, including antidepressants, antihistamines, and natural supplements, are discussed due to their prominent use.