Propofol for the promotion of sleep in adults in the intensive care unit.

BACKGROUND: People in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and people perceive the quality of their sleep to be poor whilst in the ICU. Propofol is an anaesthetic agent which can be used in the ICU to maintain patient sedation and some studies suggest it may be a suitable agent to replicate normal sleep. OBJECTIVES: To assess whether the quantity and quality of sleep may be improved by administration of propofol to adults in the ICU and to assess whether propofol given for sleep promotion improves both physical and psychological patient outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 10), MEDLINE (1946 to October 2017), Embase (1974 to October 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to October 2017) and PsycINFO (1806 to October 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials with adults, over the age of 16 years, admitted to the ICU with any diagnoses, given propofol versus a comparator to promote overnight sleep. We included participants who were and were not mechanically ventilated. We included studies that compared the use of propofol, given at an appropriate clinical dose with the intention of promoting night-time sleep, against: no agent; propofol at a different rate or dose; or another agent, administered specifically to promote sleep. We included only studies in which propofol was given during 'normal' sleeping hours (i.e. between 10 pm and 7 am) to promote a sleep-like state with a diurnal rhythm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings. MAIN RESULTS: We included four studies with 149 randomized participants. We identified two studies awaiting classification for which we were unable to assess eligibility and one ongoing study.Participants differed in severity of illness as assessed by APACHE II scores in three studies and further differences existed between comparisons and methods. One study compared propofol versus no agent, one study compared different doses of propofol and two studies compared propofol versus a benzodiazepine (flunitrazepam, one study; midazolam, one study). All studies reported randomization and allocation concealment inadequately. We judged all studies to have high risk of performance bias from personnel who were unblinded. We noted that some study authors had blinded study outcome assessors and participants for relevant outcomes.It was not appropriate to combine data owing to high levels of methodological heterogeneity.One study comparing propofol with no agent (13 participants) measured quantity and quality of sleep using polysomnography; study authors reported no evidence of a difference in duration of sleep or sleep efficiency, and reported disruption to usual REM (rapid eye movement sleep) with propofol.One study comparing different doses of propofol (30 participants) measured quantity and quality of sleep by personnel using the Ramsay Sedation Scale; study authors reported that more participants who were given a higher dose of propofol had a successful diurnal rhythm, and achieved a greater sedation rhythmicity.Two studies comparing propofol with a different agent (106 participants) measured quantity and quality of sleep using the Pittsburgh Sleep Diary and the Hospital Anxiety and Depression Scale; one study reported fewer awakenings of reduced duration with propofol, and similar total sleep time between groups, and one study reported no evidence of a difference in sleep quality. One study comparing propofol with another agent (66 participants) measured quantity and quality of sleep with the Bispectral Index and reported longer time in deep sleep, with fewer arousals. One study comparing propofol with another agent (40 participants) reported higher levels of anxiety and depression in both groups, and no evidence of a difference when participants were given propofol.No studies reported adverse events.We used the GRADE approach to downgrade the certainty of the evidence for each outcome to very low. We identified sparse data with few participants, and methodological differences in study designs and comparative agents introduced inconsistency, and we noted that measurement tools were imprecise or not valid for purpose. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether administration of propofol would improve the quality and quantity of sleep in adults in the ICU. We noted differences in study designs, methodology, comparative agents and illness severity amongst study participants. We did not pool data and we used the GRADE approach to downgrade the certainty of our evidence to very low.

Prevalence and clinical correlates of flunitrazepam-related complex sleep behaviors.

AIM: Complex sleep behaviors (CSB) are often associated with the use of hypnotic drugs. This study investigated the prevalence and correlates of CSB among psychiatric patients who were given flunitrazepam. METHODS: From June 2011 to May 2012, a total of 268 psychiatric outpatients who had received flunitrazepam for at least 3 months were enrolled. Data on occurrence of CSB, demographic characteristics, flunitrazepam dosage and duration of use, psychiatric diagnoses, physical illnesses, and alcohol use were collected. Logistic regression analysis was used to examine the clinical correlates of CSB. RESULTS: Sixty-six participants (24.6%) reported experiencing CSB. Logistic regression analysis showed that a high dosage (>2 mg/day) of flunitrazepam (odds ratio [OR] = 1.941, 95% confidence interval [CI] = 1.090-3.455, P = 0.024) and alcohol use (OR = 1.948, 95%CI = 1.023-3.709, P = 0.042) were significantly associated with the occurrence of CSB. Sex, age, duration of flunitrazepam use, psychiatric diagnoses, and physical illnesses were not significantly associated with the occurrence of CSB. CONCLUSION: CSB among flunitrazepam users should be monitored routinely, especially among those receiving a high dosage who also consume alcohol.

Use of GABAergic sedatives after subarachnoid hemorrhage is associated with worse outcome-preliminary findings.

STUDY OBJECTIVE: Recent experimental evidence identified GABAergic sedation as a possible cause for deprived neuroregeneration and poor outcome after acute brain injury. Patients with aneurysmal subarachnoid hemorrhage are often sedated, and GABAergic sedation, such as midazolam and propofol, is commonly used. DESIGN: Retrospective cohort study based on a prospectively established database. SETTING: Single-center neurointensive care unit. PATIENTS: Twenty-nine patients after subarachnoid hemorrhage. INTERVENTION: Noninterventional study. MEASUREMENTS: The relationship between mean GABAergic sedative dose during the acute phase and outcome after 6 months according to the Glasgow Outcome Scale, and initial Glasgow Coma Scale was investigated. MAIN RESULTS: Use of GABAergic sedatives was negatively correlated with Glasgow Outcome Scale (r2=0.267; P=.008). Administration of sedatives was independent of the initial Glasgow Coma Scale. GABAergic sedatives flunitrazepam, midazolam, and propofol were used differently during the first 10 days after ictus. CONCLUSION: Administration of GABAergic sedation was associated with an unfavorable outcome after 6 months. To avoid bias (mainly through the indication to use sedation), additional experimental and comparative clinical investigation of, for example, non-GABAergic sedation, and clinical protocols of no sedation is necessary.

Effects of the 5-HT(1A) Receptor Agonist Tandospirone on ACTH-Induced Sleep Disturbance in Rats.

The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.

Dependence, misuse, and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem, estazolam, or flunitrazepam.

INTRODUCTION: To examine the prevalence rates and correlates of dependence on, misuse of, and beliefs regarding use of hypnotics in elderly psychiatric patients with long-term use of zolpidem, estazolam, or flunitrazepam. METHODS: A total of 139 psychiatric outpatients 65 or more years of age who used zolpidem, estazolam, or flunitrazepam for at least 3 months were studied. The levels of hypnotic dependence and beliefs regarding hypnotic use (necessity and concern) were assessed. Three patterns of hypnotic misuse in the past 1 month were also explored. The correlates of high dependence, misuse, and unfavorable attitude and high concern toward hypnotic use were examined using logistic regression analyses. RESULTS: A total of 28.8%, 7.9%, 12.2%, and 22.3% of participants reported high dependence on, misuse of, unfavorable attitude toward, and high concern toward hypnotic use, respectively. Males were more likely to report unfavorable attitude toward hypnotic use than females. Elders with significant depression were more likely to report high concern toward hypnotic use than those without significant depression. Elders with high concern toward hypnotic use were more likely to report high dependence on hypnotics than those with low concern. Elders with significant depression and taking zolpidem were more likely to misuse hypnotics than those without significant depression and taking estazolam or flunitrazepam, respectively. DISCUSSION: Clinicians should monitor the possibility of dependence on and misuse of hypnotics among elderly psychiatric patients who had the correlates identified in this study.

Short and long-term outcomes of endoscopic balloon dilatation for Crohn's disease strictures.

AIM: To investigate the short and long-term outcomes of endoscopic balloon dilatation (EBD) for Crohn's disease (CD) strictures. METHODS: Between January 1995 and December 2011, 47 EBD procedures were performed in 30 patients (8 females and 22 males) with CD. All patients had strictures through which an endoscope could not pass, and symptoms of these strictures included abdominal pain, abdominal fullness, nausea, and/or vomiting. The 47 strictures included 17 anastomotic and 30 de novo strictures. Endoscopy and dilatation were performed under conscious sedation with intravenous diazepam or flunitrazepam. The dilatations were all performed using through-the-scope balloons with diameters from 8 mm to 20 mm on inflation and lengths of 30-80 mm. Each dilatation session consisted of two to four, 3-min multistep inflations of the balloon, repeated at intervals of 1 wk until adequate dilatation (up to 15-20 mm in diameter) was achieved. The follow-up data were collected from medical records and analyzed retrospectively. Primary success was defined as passage of the scope through the stricture after EBD. Long-term outcomes were analyzed focusing on intervention-free survival and surgery-free survival demonstrated by the Kaplan-Meier method. (Intervention-free meant cases in which neither endoscopic balloon re-dilatation nor surgery was needed after the first dilatation during the observation period). The log rank test was used to evaluate the difference in long-term outcomes between anastomotic and de novo stricture cases. RESULTS: Primary success was achieved in 44 of the 47 strictures (93.6%). Balloon dilatations failed in 3 cases (6.4%). In 1 case, EBD was a technical failure because the guide-wire could not be passed through the stricture which showed severe adhesion and was a flexural lesion of the intestine. In 2 cases, unexpected perforations occurred immediately after balloon dilatation. Of the 47 treatments, complications occurred in 5 (10.6%). All 5 patients had de novo strictures. One suffered bleeding, two high fever and there were colorectal perforations. One of the patients with a colorectal perforation was treated surgically, the other was managed conservatively. These 2 cases correspond to the two aforementioned EBD failures. Long-term outcomes were evaluated for the 44 successfully-treated strictures after a median follow-up of 26 mo (range, 2-172 mo). During the observation period, re-strictures after EBDs occurred in 26 cases (60.5%). Fourteen of these 26 re-stricture cases underwent EBD again, but in two EBD failed and surgery was ultimately performed in both cases. Twelve of the 26 re-stricture cases were initially treated surgically when the re-strictures occurred. Finally, 30 of the 47 strictures (63.8%) were successfully managed with EBD, allowing surgery to be avoided. Intervention-free survival evaluated by the Kaplan-Meier method was 75% at 12 mo, 58% at 24 mo, and 43% at 36 mo. There was no significant difference between the anastomotic strictures (n = 16) and de novo strictures (n = 28) in the intervention-free survival as evaluated by the log-rank test. Surgery-free survival evaluated by the Kaplan-Meier method was 90% at 12 mo, 75% at 24 mo, and 53% at 36 mo. The 16 anastomotic strictures were associated with significantly better surgery-free survivals than the 28 de novo strictures (log-rank test: P < 0.05). CONCLUSION: Anastomotic strictures were associated with better long-term outcomes than de novo strictures, indicating that stricture type might be useful for predicting the long-term outcomes of EBD.

N,N'-dicyclohexylsulfamide and N,N'-diphenethylsulfamide are anticonvulsant sulfamides with affinity for the benzodiazepine binding site of the GABA(A) receptor and anxiolytic activity in mice.

A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-diphenethylsulfamide (10), competitively inhibited the binding of [(3)H]-flunitrazepam to the benzodiazepine binding site with K(i)±SEM values of 27.7±4.5µM (n=3) and 6.0±1.2µM (n=3), respectively. The behavioral actions of these sulfamides, i.p. administered in mice, were examined in the plus-maze, hole-board and locomotor activity assays. Compound 7 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the hole-board test (at 1 and 3mg/kg) and the plus-maze assay (at 1 and 3mg/kg). Compound 10 evidenced anxiolytic activity in the plus-maze and the hole-board tests at 1mg/kg. Locomotor activity of mice was not modified by compound 7 or 10 at the doses tested. Flumazenil, a non selective benzodiazepine binding site antagonist, was able to completely reverse the anxiolytic-like effects of these sulfamides, proving that the GABA(A) receptor is implicated in this action. Anxiety represents a major problem for people with epilepsy. The use of anxiolytic and anticonvulsant sulfamides would be beneficial to individuals who suffer from both disorders.

Monitoring of benzodiazepine diversion using a multi-indicator approach.

Fourteen benzodiazepine (BZD) or BZD-like medications were analyzed with three data sources aiming to assess prescription drug abuse for the year 2008. After a descriptive analysis, a principal component analysis was carried out to explore correlations between seven indicators obtained by different methods using these three different data sources and to compute a composite score of diversion for these drugs. For all the indicators, flunitrazepam appears first with much higher values than the other drugs, whereas clonazepam appears in the second or third place. These methods produce globally correlated indicators and the composite score obtained from principal component analysis ranks the drugs with the highest diversion as follows: flunitrazepam, clonazepam, oxazepam, diazepam, and bromazepam. This study shows that these methods yield consistent results. Their integration into a single multi-indicator approach gives health authorities a global view of different behaviors regarding diversion of a given drug.

Evidence of clonazepam abuse liability: results of the tools developed by the French Centers for Evaluation and Information on Pharmacodependence (CEIP) network.

Recent observations suggest the existence of clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all clonazepam data of several epidemiological tools of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. In OSIAP survey, the proportion of clonazepam falsified prescriptions among all BZD falsified prescriptions increased. During the 2006 OPPIDUM survey, the analysis of the BZD modalities of use highlights clonazepam abuse liability (for example 23% of illegal acquisition), in second rank after flunitrazepam. Studies based on data from the French health reimbursed system show that 1.5% of subjects with clonazepam dispensing had a deviant behaviour. Among BZD, clonazepam has the second most important doctor-shopping indicator (3%) after flunitrazepam. All these data provide some arguments in favour of clonazepam abuse liability in real life and the necessity to reinforce its monitoring.

[Sedation in palliative medicine: Guidelines for the use of sedation in palliative care : European Association for Palliative Care (EAPC)]. / Sedierung in der Palliativmedizin*: Leitlinie für den Einsatz sedierender Massnahmen in der Palliativversorgung : European Association for Palliative Care (EAPC).

The European Association for Palliative Care (EAPC) considers sedation to be an important and necessary therapy option in the care of selected palliative care patients with otherwise refractory distress. Prudent application of this approach requires due caution and good clinical practice. Inattention to potential risks and problematic practices can lead to harmful and unethical practice which may undermine the credibility and reputation of the responsible clinicians and institutions as well as the discipline of palliative medicine more generally. Procedural guidelines are helpful to educate medical providers, set standards for best practice, promote optimal care and convey the important message to staff, patients and families that palliative sedation is an accepted, ethical practice when used in appropriate situations. EAPC aims to facilitate the development of such guidelines by presenting a 10-point framework that is based on the pre-existing guidelines and literature and extensive peer review.

Neuropharmacological screening of two 1,5-benzodiazepine compounds in mice.

This work investigates whether the two 1,5-benzodiazepine compounds: 4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-one (RG0501) and Benzopyrano [4,3-c] 1,5-benzodiazepine (RG0502) have any neuropharmacological activities. Diazepam and Flunitrazepam were used as drug references. The investigational 1,5-BDZ were tested in vivo for potentiating hexobarbital-induced sleep and pentylenetetrazole (PTZ)-induced seizures. Our study demonstrated that the increase of sleep duration was significantly higher with RG0501 as compared to RG0502. However, RG0502 anticonvulsant effect was more pronounced than that of RG0501 in the range dose of 6.25-37.5 mg.kg(-1). From the 50 mg.kg(-1) dose, RG0502 offered a protection against clonic-tonic seizures as well as lethality (p< or =0.05). The results showed that the required doses to obtain a pharmacological activity were more than those of the references. This difference could be related to the lack of specific substituants responsible for the pharmacological activity in the tested compounds.

Effects of some antipsychotics and a benzodiazepine hypnotic on the sleep-wake pattern in an animal model of schizophrenia.

We studied the effects of antipsychotics and a hypnotic on sleep disturbance in schizophrenia using an animal model of the disease. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalograph for 6 h (10:00 - 16:00). SleepSign ver. 2.0 was used for EEG and EMG analysis. Haloperidol and olanzapine had an antagonizing effect on the increases in sleep latency and total awake time and the decrease in total non-rapid eye movement (NREM) sleep time induced by MK-801. Olanzapine also antagonized the decrease in total rapid eye movement (REM) sleep time induced by MK-801. Aripiprazole antagonized only the increase in sleep latency induced by MK-801, whereas, risperidone, quetiapine, and flunitrazepam had no effect in the changes of sleep-wake pattern induced by MK-801. Olanzapine increased delta activity and decreased beta activity during NREM sleep. In contrast, flunitrazepam had an opposite effect. It was clarified that haloperidol and olanzapine were effective for decrease of sleep time in this animal model of schizophrenia. In addition, aripiprazole showed a sleep-inducing effect in schizophrenia model rat. On the other hand, flunitrazepam showed no beneficial effect on sleep disturbance in schizophrenia model rat.

Impact of the use of propofol remifentanil goal-directed sedation adapted by nurses on the time to extubation in mechanically ventilated ICU patients: the experience of a French ICU.

AIM: Inappropriate sedation could prolong the duration of mechanical ventilation. The present "before-after" study assessed the impact of a goal-directed sedation using an algorithm with a combination of propofol and remifentanil on the time to extubation. METHODS: During 16 months, ICU-patients requiring sedation greater than 24 h were prospectively studied. In the first eight months, sedation was achieved using continuous infusions of a benzodiazepine (flunitrazepam or midazolam) and an opioid (fentanyl or sufentanil). In the following eight months, sedation using a propofol-remifentanil combination was given and adapted by the nurses according to the Ramsay score and a pain scale. The main endpoint was the time to extubation (from the cessation of sedation to extubation). The secondary endpoints were the duration of mechanical ventilation, the length of ICU stay, the ICU mortality rate, the need of vasopressive support, the occurrence of self-extubations and Ventilator-Associated Pneumonia (VAP). RESULTS: Forty-six and 39 patients were included in the first and second periods, respectively. The durations of sedation were similar. The time to extubation was shorter in the second period (10 versus 92h, p<0.0001). The duration of mechanical ventilation, the length of stay in ICU, the mortality rate, the need for vasopressor support and the occurrence of VAP were similar. Five self-extubations occurred in the second period versus one in the first one (p=0.02). CONCLUSION: Sedation with adapted infusions of propofol and remifentanil according to the Ramsay score and a pain scale decreases the time to extubation in ICU patients requiring sedation longer than 24h but increases the rate of self-extubations.

Efficacy, safety, and cost effectiveness of intravenous midazolam and flunitrazepam for primary insomnia in terminally ill patients with cancer: a retrospective multicenter audit study.

BACKGROUND: Although intravenous midazolam and flunitrazepam are frequently administered for primary insomnia in Japan, there is no empirical study on their efficacy and safety. DESIGN AND SUBJECTS: To compare the efficacy, safety, and cost-effectiveness of midazolam and flunitrazepam, a multicenter retrospective audit study was performed on 104 and 59 patients receiving midazolam and flunitrazepam, respectively, from 18 certified palliative care units. RESULTS: Median administration periods were 6 days and 9 days for midazolam and flunitrazepam, respectively. The median initial and maximum doses were 10 mg per night and 18 mg per night for midazolam, and 2 mg per night and 2 mg per night for flunitrazepam, respectively. There were no significant differences in the efficacy (91% in the midazolam group versus 81% in the flunitrazepam group, p = 0.084), hangover effect (34% versus 19%, p = 0.094), delirium at night (12% versus 10%, p = 1.0) and delirium next morning (11% versus 15%, p = 0.33), treatment withdrawal (4.8% versus 1.7%, p = 0.41), and treatment-related death (0% versus 0%, p = 1.0). Flunitrazepam caused respiratory depression defined as physician or nurses records such as apnea, respiratory arrest, decreased respiratory rate, and respiratory depression significantly more frequently than midazolam (17% versus 3.8%, p = 0.0073). The maximum dose was more highly correlated with the administration period in the midazolam group than in the flunitrazepam group (rho = 0.52, versus rho = 0.39), and, for patients treated for 14 days or longer, the daily escalation dose ratio required for maintaining adequate sleep was significantly higher in the midazolam group than in the flunitrazepam group (11% versus 2.6%, p = 0.015). The costs of the initial and maximum administration were significantly higher in the midazolam group than in the flunitrazepam group (p < 0.001). CONCLUSION: Intravenous midazolam and flunitrazepam appeared to be almost equal about efficacy and safety for primary insomnia, but flunitrazepam is less expensive and shows lower risk of tolerance development. A future prospective comparison study is necessary.

Benzodiazepinas y delito. Flunitrazepam: mal uso de una droga legal desde la perspectiva médico pericial / Benzodiazepines and crime. Flunitrazepam: misuse of a legal drug from the medical-legal perspective

El presente trabajo debe encuadrarse en la especialidad de la Medicina Legal. Sin embargo, no deja de implicar un aporte en el aspecto cotidiano asistencial ya que la obtención de psicofármacos requiere, muchas veces, la involuntaria participación del médico en calidad de agente prescriptor de tales drogas. El (mal) uso de las benzodiazepinas por parte de algunos sujetos, concepto distinto al de abuso, es una situación frecuente en el ámbito carcelario. Esta genera especiales y gravísimos conflictos que pueden, y deben, ser minimizados por la simple restricción de la prescripción farmacológica si esta se ajusta a la evidencia científica (prescripción basada en la evidencia) y no a las demandas, muchas veces (in)justificadas de los mismos pacientes-reclusos. La búsqueda y obtención -por parte de ciertos sujetos portadores de una personalidad predisponente- de los efectos paradojales de las benzodiazepinas, particularmente flunitrazepam y clonazepam, constituye un dato de la realidad que no puede ser desconocido ni minimizado por el médico asistencial ni por el experto en Medicina Legal, precisamente por las implicancias éticas, morales, sociales y, sobre todo, jurídicas que este supone, ni debe ser desoída la palabra profesional por los máximos responsables de la institución penitenciaria toda vez que a ellos compete el desarrollo e implementación de políticas tendientes a la cierta (re) socialización y (re) educación de la persona presa. Los destinatarios de este trabajo resultan entonces los médicos en general, con mayor énfasis en quienes trabajan en el medio penitenciario, pero también las autoridades del Servicio Penitenciario en todos sus escalafones y los integrantes del Poder Judicial...

Treatment with flunitrazepam of continuous spikes and waves during slow wave sleep (CSWS) in children.

We describe our treatment of two boys with continuous spikes and waves during slow wave sleep (CSWS). One of the boys was suffering from non-convulsive status epilepticus and the other from conscious disturbance with automatism. Their ictal EEG readings showed continuous diffuse spike and wave complexes, which were considered to show electrical status. The boys were diagnosed as having CSWS, and were later diagnosed with Landau-Kleffner syndrome (LKS). EEG readings returned to normal on intravenous injection of flunitazepam (FZP) at a dose of 0.02 mg/kg, suggesting that FZP is an effective treatment for CSWS.

Drug-induced sweat gland necrosis in a non-comatose patient: a case presentation.

BACKGROUND: Coma-induced bullae and sweat gland necrosis is a rare clinicopathological entity often associated with drug-induced coma. SUBJECT: We report a case with clinical and histopathologic findings characteristic of blisters and sweat gland necrosis occurring in a non-comatose patient. CONCLUSIONS: Skin blisters with underlying sweat gland necrosis is an entity previously reported to occur in comatose patients, our findings open new questions about the role of the drugs in the pathogenesis of those conditions.

Comparison of hangover effects among triazolam, flunitrazepam and quazepam in healthy subjects: a preliminary report.

The aim of the present study was to compare the hangover effects of night-time administration of triazolam (0.25 mg), flunitrazepam (1 mg) and quazepam (15 mg) in healthy subjects. Daytime sleepiness and performance level following the night-time administration of the drugs were assessed using Standford Sleepiness Scale (SSS), Sleep Evaluation Questionnaire (SEQ), Multiple Sleep Latency Test (MSLT), actigraphy recordings and Continuous Performance Test (CPT). Fifteen healthy volunteers were given one of the three hypnotics at each drug session, which lasted for 1 week, in a single-blind cross-over fashion. No significant between-drug difference was observed for the psychomotor performance assessed by CPT. Subjective hangover effects assessed by SSS and SEQ in the morning were prominent for flunitrazepam and quazepam relative to triazolam, whereas objective indices such as MSLT or activity counts obtained in actigraphy indicated a marked hangover effect of quazepam compared with the other two compounds restrictively in the afternoon, which were nearly in accordance with their pharmacokinetic profiles.

Clonidine premedication improves metabolic control in type 2 diabetic patients during ophthalmic surgery.

BACKGROUND: In stressful conditions, increasing blood glucose concentrations are closely related to an increase in catecholamines and cortisol release. Clonidine, a centrally acting alpha(2)-adrenoceptor agonist, has neuroendocrine effects, including inhibition of sympathoadrenal activity. We therefore evaluated the effect of clonidine on blood glucose control and insulin requirements during ophthalmic surgery when given as premedication in type 2 diabetic patients. METHODS: After randomization, patients were premedicated with clonidine or flunitrazepam (control). Patients were given insulin by continuous i.v. infusion to maintain blood glucose in the range 5.5-11.1 mmol litre(-1). Blood glucose concentrations were measured every 15 min during surgery, and hourly for 6 h after surgery. Plasma C-peptide and counter-regulatory hormones were also measured. RESULTS: Glycaemia was significantly lower in the clonidine group (P<0.01) and the median amount of insulin administered was significantly reduced: clonidine group 9.0 (interquartile range 5.1) units; control 18.6 (10.2) units; P<0.01). Plasma catecholamine concentrations were lower in patients given clonidine (P<0.05) but there was no difference in cortisol concentrations. CONCLUSION: Premedication of type 2 diabetic patients with clonidine 90 min before surgery improves blood glucose control and decreases insulin requirements during ophthalmic surgery.