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Background: Sedation is a state of sleepiness and relaxation that results from the depression of the central nervous system. The depth of sedation can be assessed by hemodynamic responses and neurological signs, such as the palpebral reflex, startle response, nystagmus, and response to stimuli. Currently, the Bispectral Index (BIS) is considered the most accurate monitor for assessing brain function during anesthesia and sedation. BIS values for deep sedation between 60-70, and mild to moderate sedation between 70-90. Values above 90 indicate that the patient is awake. This study aims to compare the sedative effects of medetomidine and dexmedetomidine by evaluating the physical examination findings that indicate the depth of sedation, alongside the BIS monitoring, which is an objective monitoring method. Materials, Methods & Results: In this study, 100 cats brought to the Istanbul University-Cerrahpasa Faculty of Veterinary Science, Department of Surgery, Otorhinolaryngology (ENT) Clinic between 2018 and 2022, and indicated for Ventral Bulla Ostectomy (VBO) following examinations, were evaluated for BIS findings and physical examination results after sedation administration. Patients with 1st and 2nd degree anesthesia risk according to the ASA, based on physical, laboratory, and radiological examinations, were included in the study. The 100 patients were randomly divided into 2 groups of 50 each. Following the pre-anesthetic examination, butorphanol (0.4 mg/kg) was administered subcutaneously in both groups preemptively. After 10 min of butorphanol administration, intravenous access through the vena cephalica or vena saphena was obtained using a 22 or 24 gauge angiocath. Medetomidine HCl IV was used for sedation in the 1st group, while Dexmedetomidine HCl (20 µg/kg) IV was used in the 2nd group. After the patients were sedated and complete relaxation was achieved, the self-adhesive sensors of the BIS probe were placed on the frontal region. Posture, jaw tone, palpebral reflex, corneal reflex, pupil size, and limb withdrawal reflex (LWR) were evaluated and recorded before sedation (T0) and at the 5 min following sedation (T1). Discussion: Alpha-2 adrenoceptor agonists can affect both postural and smooth muscles. Relaxation of postural muscles may manifest as recumbency or ataxia. This study's findings were consistent with existing literature: all patients were in lateral recumbency after 5 min following alpha-2 administration, exhibited decreased jaw tone, and allowed their mouths to be opened easily. Moderate sedation in humans is defined as a reversible state in which response to tactile and vocal stimuli is preserved. However, when considering the BIS and LWR findings, we observed that 72% of the moderately sedated patients in the 1st group lost the LWR reflex, which evaluates the response to painful stimuli. This response to painful stimuli, which is more significant than tactile stimuli, partially contradicts the literature. In addition to considering that different sedative drugs may yield different findings, it was believed that the strong muscle relaxant and analgesic properties of medetomidine could explain the results without causing loss of consciousness. In the intergroup evaluation, the mean BIS value of the 1st group was 72.82, indicating moderate sedation. In contrast, the mean BIS value of the 2nd group was 67.12, which was classified as deep sedation. Contrary to the literature, the BIS findings between the groups showed that deeper sedation occurred in the dexmedetomidine group. Based on the BIS findings, we believe that dexmedetomidine will be more effective than medetomidine in procedures requiring procedural sedation by inducing a hypnotic state close to general anesthesia. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics. Results Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4–9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact. Conclusions Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.

Aim: To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs. Methods: In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity. Results: The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased. Conclusion: In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population. [ABSTRACT FROM AUTHOR]

Abstract Background Although vasopressor and sedative agents are commonly used within the intensive care unit to mediate systemic and cerebral physiology, the full impact such agents have on cerebrovascular reactivity remains unclear. Using a prospectively maintained database of high-resolution critical care and physiology, the time-series relationship between vasopressor/sedative administration, and cerebrovascular reactivity was interrogated. Cerebrovascular reactivity was assessed through intracranial pressure and near infrared spectroscopy measures. Using these derived measures, the relationship between hourly dose of medication and hourly index values could be evaluated. The individual medication dose change and their corresponding physiological response was compared. Given the high number of doses of propofol and norepinephrine, a latent profile analysis was used to identify any underlying demographic or variable relationships. Finally, using time-series methodologies of Granger causality and vector impulse response functions, the relationships between the cerebrovascular reactivity derived variables were compared. Results From this retrospective observational study of 103 TBI patients, the evaluation between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies was completed. The assessment of the physiology pre/post infusion agent change resulted in similar overall values (Wilcoxon signed-ranked p value > 0.05). Time series methodologies demonstrated that the basic physiological relationships were identical before and after an infusion agent was changed (Granger causality demonstrated the same directional impact in over 95% of the moments, with response function being graphically identical). Conclusions This study suggests that overall, there was a limited association between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies including that of cerebrovascular reactivity. Thus, current regimens of administered sedative and vasopressor agents appear to have little to no impact on cerebrovascular reactivity in TBI.

Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics. Results: Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4–9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact. Conclusions: Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required. [ABSTRACT FROM AUTHOR]

There has been a substantial increase in the use of extracorporeal membrane oxygenation (ECMO) support in critically ill adults. Understanding the complex changes that could affect drugs' pharmacokinetics (PK) and pharmacodynamics (PD) is of suitable need. Therefore, critically ill patients on ECMO represent a challenging clinical situation to manage pharmacotherapy. Thus, clinicians' ability to predict PK and PD alterations within this complex clinical context is fundamental to ensure further optimal and, sometimes, individualized therapeutic plans that balance clinical outcomes with the minimum drug adverse events. Although ECMO remains an irreplaceable extracorporeal technology, and despite the resurgence in its use for respiratory and cardiac failures, especially in the era of the COVID-19 pandemic, scarce data exist on both its effect on the most commonly used drugs and their relative management to achieve the best therapeutic outcomes. The goal of this review is to provide key information about some evidence-based PK alterations of the drugs used in an ECMO setting and their monitoring. [ABSTRACT FROM AUTHOR]

Background: Although vasopressor and sedative agents are commonly used within the intensive care unit to mediate systemic and cerebral physiology, the full impact such agents have on cerebrovascular reactivity remains unclear. Using a prospectively maintained database of high-resolution critical care and physiology, the time-series relationship between vasopressor/sedative administration, and cerebrovascular reactivity was interrogated. Cerebrovascular reactivity was assessed through intracranial pressure and near infrared spectroscopy measures. Using these derived measures, the relationship between hourly dose of medication and hourly index values could be evaluated. The individual medication dose change and their corresponding physiological response was compared. Given the high number of doses of propofol and norepinephrine, a latent profile analysis was used to identify any underlying demographic or variable relationships. Finally, using time-series methodologies of Granger causality and vector impulse response functions, the relationships between the cerebrovascular reactivity derived variables were compared. Results: From this retrospective observational study of 103 TBI patients, the evaluation between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies was completed. The assessment of the physiology pre/post infusion agent change resulted in similar overall values (Wilcoxon signed-ranked p value > 0.05). Time series methodologies demonstrated that the basic physiological relationships were identical before and after an infusion agent was changed (Granger causality demonstrated the same directional impact in over 95% of the moments, with response function being graphically identical). Conclusions: This study suggests that overall, there was a limited association between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies including that of cerebrovascular reactivity. Thus, current regimens of administered sedative and vasopressor agents appear to have little to no impact on cerebrovascular reactivity in TBI. [ABSTRACT FROM AUTHOR]

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The impact of vasopressor and sedative drugs on cerebrovascular reactivity in traumatic brain injury (TBI) remains unclear. The aim of this study was to evaluate the impact of changes of doses of commonly administered sedation (i.e., propofol, fentanyl, and ketamine) and vasopressor agents (i.e., norepinephrine [NE], phenylephrine [PE], and vasopressin[VSP]) on cerebrovascular reactivity and compensatory reserve in patients with moderate/severe TBI. Using the Winnipeg Acute TBI Database, we identified 38 patients with more than 1000 distinct changes of infusion rates and more than 500?h of paired drug infusion/physiology data. Cerebrovascular reactivity was assessed using pressure reactivity index (PRx) and cerebral compensatory reserve was assessed using RAP (the correlation [R] between pulse amplitude of intracranial pressure [ICP; A] and ICP [P]). We evaluated the data in two phases. First, we assessed the relationship between mean hourly dose of medication and its relation to both mean hourly index values, and time spent above a given index threshold. Second, we evaluated time-series data for each individual dose change per medication, assessing for a statistically significant change in PRx and RAP metrics. The results of the analysis confirmed that, overall, the mean hourly dose of sedative (propofol, fentanyl, and ketamine) and vasopressor (NE, PE, and VSP) agents does not impact hourly cerebrovascular reactivity or compensatory reserve measures. Similarly, incremental dose changes in these medications in general do not lead to significant changes in cerebrovascular reactivity or compensatory reserve. For propofol with incremental dose increases, in situations where PRx is intact (i.e., PRx

Background and Aims: The aim of the study was to enumerate the sedative drugs used, assess the efficacy of sedative drugs, and determine the incidence of adverse events. Material and Methods: A prospective audit of children sedated for computerized tomography (CT) by anesthesiology team was conducted for a period of 4 months. The data included patient demographic variables, fasting period, medications administered, adequacy of sedation, imaging characteristics, adverse events, and requirement for escalated care. Results: A total of 331 children were enrolled for sedation by the anesthesia team. The drugs used for sedation were propofol, ketamine, and midazolam. Twenty-two percent children received one sedative drug, 60% children were administered two drugs, and 5% children required a combination of all three drugs for successful sedation. Sedation was effective for successful conduct of CT scan in 95.8% patients without the requirement of a repeat scan. Twelve (5%) children experienced adverse events during the study period. However, none of the adverse events necessitated prolonged postprocedural hospitalization or resulted in permanent neurologic injury or death. Conclusions: The current practice of sedation with propofol, ketamine, and midazolam, either single or in combination was efficacious in a high percentage of patients. The incidence of adverse events during the study period was low.

Aims: To analyze the hospital emergency department (HED) consultations for schizophrenia-spectrum disorders in nine Italian hospitals during the 2020 lockdown and postlockdown periods, compared to the equivalent periods in 2019. Methods: Characteristics of consultations, patients, and drug prescriptions were analyzed. Joinpoint models were used to identify changes in the weekly trend of consultations. Results: During the 2020 lockdown the overall number of HED consultations for schizophrenia decreased by 40.7% and after the lockdown by 12.2% compared with 2019. No difference was found in the proportion of consultations that led to GHPU admissions or compulsory admissions. Suicidality rates did not differ across the two years, with the exception of ideations and plans (+5.9%) during the postlockdown period. We found an increase in benzodiazepine prescriptions in 2020 during the lockdown and postlockdown periods (+10.6% and +20.8%, respectively), and a decrease of prescriptions for short-acting sedative agents in the postlockdown period (-7.9%). An increase in the weekly trend of consultations occurred from March 11 to 17 (week 11) till June 26 to 30 (week 26). As a result, the initial gap in the number of consultations between the 2 years canceled out at the end of June. Conclusions: HED consultation rate for schizophrenia-spectrum disorders declined consistent with that of other psychiatric disorders. In the postlockdown period, the growth of suicidal ideation/planning and increase in the prescriptions of anxiolytic-sedating drugs may foreshadow that for some schizophrenia patients the exit from the lockdown period is not liberating, but rather a source of agitation or perturbation. [ABSTRACT FROM AUTHOR]

The role of bronchoscopy during COVID-19 pandemic is still debated. The detection of SARSCoV- 2 on lower respiratory tract samples allows the diagnosis of COVID-19 in around 50% of patients with high clinical suspicion/radiologic findings but with one or more negative naso-pharyngeal swabs. When an alternative diagnosis to COVID-19 could significantly impact on the therapeutic management of the patients, bronchoscopy remains the examination of choice. Actually, the certainty of diagnosis of COVID-19 is based only on a microbiological criterion, potentially implying a broad application of bronchoscopy both in patient not invasively and invasively supported. However, the guidelines released by different scientific Societies of bronchology or infectious diseases from the beginning of the pandemic, only partially agree about the diagnostic role of bronchoscopy. The respiratory support and the sedative drugs administered during the procedure still belong to a “grey zone” of intervention, potentially conditioning the clinical course of the disease (i.e., worsening of respiratory failure) and the utilization of hospital resources. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of the study was to enumerate the sedative drugs used, assess the efficacy of sedative drugs, and determine the incidence of adverse events. Material and Methods: A prospective audit of children sedated for computerized tomography (CT) by anesthesiology team was conducted for a period of 4 months. The data included patient demographic variables, fasting period, medications administered, adequacy of sedation, imaging characteristics, adverse events, and requirement for escalated care. Results: A total of 331 children were enrolled for sedation by the anesthesia team. The drugs used for sedation were propofol, ketamine, and midazolam. Twenty-two percent children received one sedative drug, 60% children were administered two drugs, and 5% children required a combination of all three drugs for successful sedation. Sedation was effective for successful conduct of CT scan in 95.8% patients without the requirement of a repeat scan. Twelve (5%) children experienced adverse events during the study period. However, none of the adverse events necessitated prolonged postprocedural hospitalization or resulted in permanent neurologic injury or death. Conclusions: The current practice of sedation with propofol, ketamine, and midazolam, either single or in combination was efficacious in a high percentage of patients. The incidence of adverse events during the study period was low. [ABSTRACT FROM AUTHOR]

A study of electrochemical behaviour of authentic chlordiazepoxide using (DPP) technique which is the famous method using in electrochemical field, which gave atypical sharp very good reduction peak at potential range (-0.94 -1.06) volt versus reference electrode (Ag/AgCl,sat.KCl) . Also we made calibration curve was studied in aqueous solution in the presence of freshly human urine , the relation of the peak current (Ip) versus concentration was linear within the range of [(9.8×10-6)- (74.88×10-6)] molar , with a correlation coefficient of (R= 0.9984). also we made another calibration curve[(7.5×10-6)-(52.6×10-6)] molar , with a correlation coefficient of (R= 0.9974) respectively. (DPP) technique was successfully applied to determine chlordiazepoxide in ten sample of urine and tablets from the famous company using the calibration curve mentioned.The results obtained show a good similarity with concentrations (Taken and Found). Finally we compared our method with slandered method from British pharmacopeia. [ABSTRACT FROM AUTHOR]

Background: The effects of different sedative drugs on all-cause mortality rate, duration of ICU stay, and risk of delirium in mechanically ventilated ICU patients are unclear. This meta-analysis aimed to compare the effectiveness and safety of individual sedative drugs and drug combinations in mechanically ventilated ICU patients.Materials and Methods: Medline, Embase, Cochrane, EBSCOhost, and ISI Web of Science databases were searched for studies that assessed sedation in ICU mechanically ventilated patients. A Bayesian random-effects model was used to combine the direct comparisons and indirect evidence.Results: Thirty-one randomized, controlled trials were included, which consisted of 4491 patients who received one of seven sedative drugs or a combination of drugs. There were no significant differences regarding the all-cause mortality rate. Compared to propofol, inhalation anesthetics (hazard ratio [HR] 0.121; 95% credible interval [CrI] -7.58 to 7.62), alpha agonists (HR 2.2; 95% CrI 0.776 to 5.22), propofol with benzodiazepines (HR 0.306; 95% CrI -6.97 to 7.65), ketamine with benzodiazepines (HR 6.57; 95% CrI -6.05 to 19.1) and placebo (HR 2.4; 95% CrI -5.37 to 10.3), benzodiazepines (HR 3.62; 95% CrI 0.834 to 6.2) may increase the duration of ICU stay. Compared to alpha agonists, propofol (HR 2.4; 95% CrI 0.304 to 21.1) and placebo (HR 6.12; 95% CrI 0.745 to 54.6), benzodiazepines (HR 2.59; 95% CrI 1.08 to 7.4) were associated with incremental risks of delirium.Conclusion: Compared to propofol, benzodiazepines may increase the duration of ICU stay. Compared to alpha agonists, benzodiazepines were associated with an increased risk of delirium. [ABSTRACT FROM AUTHOR]

The problem of sedation in cardiosurgical intensive care units has obvious scientific and practical relevance. Many current studies deal with the implementation of novel medications for sedation, some features of their pharmacodynamic effects in different clinical settings, with advantages and disadvantages of their use in cardiosurgical patients. Recent years have seen an increase in the number of publications on the 2-adrenoceptor agonist dexmedetomidine used for sedation after open-heart surgery. The paper reviews current publications on 2-adrenoceptor agonists used in anesthesiology, considers their physiology and the mechanism of sedative action of dexmedetomidine, its pharmacokinetics and pharmacodynamics. The experience in using dexmedetomidine sedation in clinical practice is discussed in detail, by analyzing the data of current multicenter randomized trials in which this drug was compared with other sedative medications (propofol, midazolam, lorazepam). Some aspects of clinical pharmacology of dexmedetomidine, such as its effect on the sympathoadrenal system, hemodynamics, and respiratory system are analyzed. The clinical value of different receptor-dependent effects of the drug and the specific features of its application in different situations are also discussed. The authors share their own experience on delirium treatment and non-invasive ventilation in patients who receive dexmedetomidine sedation after heart transplantation and cardiac surgery.

In order to reduce the stress response of animals in animal transportation, it is often used to feed the animals with sedative drugs combined with compound vitamin B. In this article, we will randomly divide 16 amur tiger into the control group and the experimental group. The drug intervention is carried out in the experimental group. The sedative is mainly dexmedetomidine, combined with compound vitamin B, while control group did not feed the drug. The urine of two groups of individuals was collected before and after transportation and the cortisol content in urine was determined by radioimmunoassay as an indication of stress. Finally, referring to the changes of cortisol level in amur tiger, we analyzed the effect of vitamin B6 combined with sedative drugs on the anti stress effect of amur tiger. The results showed that the cortisol level in the control group was significantly different (P < 0.05), but there was no significant difference in the cortisol level in the experimental group (P > 0.05). Conclusion: this kind of veterinary medicine which is mainly composed of sedative dexmedetomidine and vitamin B6 is obviously helpful for reducing the stress of the Amur tiger in transferred transportation. [ABSTRACT FROM AUTHOR]

Summary: Background: Biochemical diagnosis of adrenal insufficiency (AI) is difficult in the context of traumatic brain injury (TBI). Aim: To assess the frequency and predictive factors of AI in victims of TBI from Algiers. Methods: Between November 2009 and December 2013, TBI victims had a single 8‐9  am serum cortisol measurement during the acute postinjury period (0‐7 days). AI was defined according to basal cortisol levels of 83, 276 and 414 nmol/L. Variables studied were TBI severity according to Glasgow coma scale, duration of intubation and coma, pupillary status, hypotension, anaemia, brain imaging findings, diabetes insipidus and medication. Insulin tolerance test was performed during the recovery phase, defining AI as peak cortisol <500 nmol/L. Results: Cortisol samples were obtained at median 3 (1‐7) days from 277 patients (257M: 20F) aged 32 (18‐65) years. Acute AI frequency was 8 (2.8%), 20 (21%) and 35 (37%), respectively using the three cortisol cut‐offs. Factors predicting AI were diastolic hypotension, sedative medication, diabetes insipidus, skull base fracture and intraparenchymal haematoma. Mortality was highest in patients with acute cortisol <276 nmol/L (44.6% with OR for death 1.64, 95% CI 0.92‐3.0, P = .12). During the recovery phase, AI was present in 3 of 3, 12 of 24, 4 of 16 and 20 of 66 patients with week 1 cortisol <83, 83‐276, 277‐414 and >414 nmol/L. Conclusion: Hydrocortisone replacement is advised in TBI patients with morning cortisol <276 nmol/L or those <414 nmol/L with additional risk factors for AI. As acute and subsequent AI are poorly correlated, patients with moderate/severe TBI require adrenal re‐evaluation during the recovery phase. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to describe current sedative drug utilization patterns in critically ill patients undergoing mechanical ventilation (MV) in intensive care units (ICUs) in Japanese hospitals and to elucidate the relationship of these utilization patterns with patient clinical outcomes. Method: Analysis of hospital claims data derived from the Quality Indicator/Improvement Project identified 12,395 critically ill adult patients who had undergone MV while hospitalized in the ICUs of 114 Japanese hospitals and had been discharged between April 2008 and March 2010. Descriptive statistics were calculated for the daily utilization of sedative drugs, opioids, and muscle relaxants in this patient sample, and the relationship between drug utilization and patient outcomes using Cox proportional hazards analysis were examined. Results: Of the 12,395 patients included in the analysis, 7300 (58.9 %), 580 (4.7 %), and 671 (5.4 %) received sedative drugs, opioids, and muscle relaxants, respectively, for ≥2 days after intubation. Compared to the other patient groups, there was a higher proportion of males in the group given sedative drugs and the patients were significantly younger ( P < 0.001). Propofol was the most frequently used sedative drug, followed by benzodiazepines, barbiturates, and dexmedetomidine. The mortality rate was lower and ventilator weaning was earlier among patients who received only propofol than among those who received only benzodiazepines. Muscle relaxants were associated with increased duration of MV. Conclusions: This is the first study based on a large-scale analysis in Japan to elucidate sedative drug utilization patterns and their relationship with outcomes in critically ill patients. The most commonly used sedative was propofol, which was associated with favorable patient outcomes. Further prospective research must be conducted to discern effective sedative drug utilization. [ABSTRACT FROM AUTHOR]

Pain control is of high importance in dentistry. Prescribing sedatives such a"nDiazepam, as an anti-depressant and pain threshold elevator drug is able to influence the patient's reaction to"npain and reduce it."nPurpose: The aim of the current study was to evaluate the effect of Diazepam in pain reduction following"nmandibular impacted third molar surgery."nMaterials and Methods: In this study, which was conducted in the department of Oral and Maxillofacial"nsurgery Faculty of Dentistry, Tehran University of Medical sciences. The patients were divided into two equal"ngroups (n=30). For controls, antibiotics and analgesics were prescribed after surgery. However, except the"naforementioned drugs, Diazepam (5mg), three times per day, was prescribed for the experimental group. The"namount of mouth opening was also measured as an auxiliary sign after one week. The data were compared by"nX2 test after one week."nResults: 60% of the experimental group and 13.8% of the control group felt a weak pain. Statistically"nsignificant differences were observed regarding pain feeling between two groups (P

Regional anesthesia is commonly used technique for various surgical procedures to provide excellent intraoperative surgical conditions and postoperative analgesia with few limitations like awareness during surgery. But judicious use of sedation these days has markedly increased patient's comfort and acceptance towards RA. This review has discussed emerging trends in use of sedation during RA with first section highlighting the advantages of RA and need for sedation during RA. We have also discussed various techniques used to deliver sedation to patients and methods for assessment of sedation during RA. A brief review regarding current status of different drugs used for sedation during RA is also provided. [ABSTRACT FROM AUTHOR]

The problem of sedation in intensive care units has obvious scientific-and-practical relevance. Many current studies deal with the practical introduction of novel medications for sedation, with the specific features of their pharmacodynamic effects in different clinical situations, with the advantages and disadvantages of their use. Recent years are marked by an increase in the number of publications on the o^-adrenoceptor agonist dexmedetomidine used for sedation. The paper reviews current publications on o^-adrenoceptor agonists used in anesthesiology and resuscitation, considers their physiology and the mechanism of sedative action of dexmedetomidine, its pharmacokinetics and pharmacodynamics at different plasma concentrations of the drug. The experience in using dexmedetomidine sedation in clinical practice is discussed in detail, by analyzing the data of current multicenter randomized trials in which the drug has been compared with other sedative medications (propofol, midazolam, lorazepam). Some aspects of the clinical pharmacology of dexmedetomidine, such as its effect on the brain and its blood flow, nociception, sympathoadrenal system, hemodynamics, respiratory system, thermoregulation, immunity, and neuroendocrine system, are analyzed. The clinical value of different receptor-dependent effects of the drug and the specific features of its application in different situations are also analyzed. Key words: dexmedetomidine; sedation in intensive care patients; sedative drugs; o^-adrenoceptor agonists; delirium in intensive care unit patients.

Summary: We have experimentally shown that thalidomide has strong anticonvulsant properties. In an open label study, eight male patients with refractory epilepsy received thalidomide at daily-doses of 200mg during 1 year, frequency of seizures before and during treatment were compared. The mean number of seizures before thalidomide administration was 26±4 per month; it decreased to 7±1 along thalidomide therapy. Our results indicate that thalidomide has strong therapeutic effects in refractory epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Apoptosis occurs physiologically in the mammalian brain during the period of the growth spurt, which in human starts in the 3rd trimester of gestation and ends by the third year of life. Environmental factors can interact with programmed cell death mechanisms to increase the number of neurons undergoing apoptosis and thus produce neuropathological sequelae in the brain. In a series of studies it could be shown that classes of drugs which block N-methyl-d-aspartate (NMDA) glutamate receptors, promote γ-aminobutyric-acid (GABAA) receptor activation or block voltage gated sodium channels, when administered to immature rodents during the period of the brain growth spurt, trigger widespread apoptotic neurodegeneration throughout the developing brain. Studies have also shown that short exposures to non-physiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Pathomechanisms involved in the proapoptotic action of sedative and anticonvulsant drugs and oxygen include decreased expression of neurotrophins, inactivation of survival signaling proteins, activation of inflammatory cytokines as well as oxidative stress. These findings raise concerns pertaining to the treatment of infants and young children with sedative and anticonvulsant drugs and premature infants with oxygen. The experimental findings imply that new approaches should be developed for patients within these vulnerable age groups. [Copyright &y& Elsevier]

The assessment of drug effects on attention is important in non-clinical pharmacology, for both evaluation of safety and therapeutic efficacy of medicinal products. In the present study, we have developed a two-lever choice behavioral test to assess drug effects on attentional performance in monkeys. In each trial of this experiment, one of two lamps in front of a monkey was randomly illuminated for a brief period of time and the monkey was required to press a lever beneath the lamp 30 times to obtain a food reward. The percentage of correct responses, response latency of correct choice responses and response speed were measured. Using this test, we examined the effects of three sedative drugs, diazepam (0.25, 1 and 4 mg/kg, i.g.), ethanol (0.5, 1 and 2 g/kg, i.g.), and pentobarbital (0.25, 1 and 4 mg/kg, i.v.). Diazepam and pentoarbital lengthened response latency without significantly affecting the percentage of correct responses, response and response speed, suggesting selective disruptive effects on attentional performance. In contrast, ethanol at the high dose tested caused deterioration in all three measurements, which is thought to reflect a general sedative effect including motor impairment as reflected by lenghtening response speed. It is suggested that the present behavioural test method could detect drug effects on attentional performance in monkeys and could be a useful tool for safety assessment in drug development. [ABSTRACT FROM AUTHOR]

To investigate the effects of using propofol for medium and long-term sedation on mortality and length of intensive care unit (ICU) stay of critically ill adult patients. Randomised controlled studies comparing propofol with an alternative sedative agent in critically ill adult patients were included without language restriction from the Cochrane Controlled Trial Register (2007 issue 3), EMBASE, and MEDLINE databases (1966 to 1 December 2007). Two reviewers reviewed the quality of the studies and performed data extraction independently. Sixteen randomised controlled studies with a total of 1,386 critically ill adult patients were considered. Nine of the pooled studies (56%) limited the doses of propofol infusion to <6 mg/kg h−1. Mortality was not significantly different between patients sedated with propofol, or an alternative sedative agent (odds ratio [OR] 1.05, 95% confidence interval [CI] 0.80–1.38, P = 0.74; I 2 = 0%). Using propofol for medium and long-term sedation was associated with a significant reduction in length of ICU stay (overall weighted-mean-difference [WMD] in days −0.99, 95%CI −1.51 to −0.47, P = 0.0002; I 2 = 82.26%) when compared to an alternative sedative agent; however, this benefit became insignificant (overall WMD in days −0.98, 95%CI −2.86 to 0.89, P = 0.30; I 2 = 78.8%) when the comparison was limited to between propofol and midazolam. Using propofol for prolonged sedation in critically ill patients appears to be safe and may reduce duration of mechanical ventilation. It reduces the length of ICU stay when compared to long acting benzodiazepines, but not when compared to midazolam. [ABSTRACT FROM AUTHOR]

Abstract: Drug screening methods were developed to detect alprazolam, clobazam, clonazepam, diazepam, midazolam, oxazepam, temazepam, triazolam, zopiclone, and selected metabolites in human hair and nail samples employing liquid–liquid extraction and tandem liquid chromatography–mass spectrometry (LC–MS–MS). Hair and nail samples were obtained from patients who had recently discontinued or were currently prescribed one or more of the targeted drugs. Prazepam was used as the internal standard for all compounds. Some components in the hair matrix gave the same transitions as some of the analytes but did not compromise the analyses because their retention times differed from those for the target compounds. The analytical run time was 8–10min. Results of the hair analysis of a DFSA victim are also presented. [Copyright &y& Elsevier]

There are different methods of medical treatment in Menière's disease. [ABSTRACT FROM AUTHOR]