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Alcohol withdrawal syndrome (AWS) continues to be a challenge to manage in the ICU setting, and the ideal pharmacological treatment continues to evolve. Dexmedetomidine is a newer agent approved for short-term sedation in the ICU, but its use in the treatment of AWS has been limited. We report a retrospective case series of ten patients who were identified as receiving dexmedetomidine for AWS as designated by electronic pharmacy records. All subjects were male, with a mean age of 53.6 years, and a mean ICU length of stay of 9.3 days. They were all diagnosed with AWS by DSM-IV criteria. All the study patients received dexmedetomidine during their hospital course as a treatment for AWS. Studied variables included demographic data, dose and duration of dexmedetomidine, other pharmaceutical agents, and hemodynamics. Dexmedetomidine was safe to use in all patients, although mechanical ventilation was still required in three patients. With dexmedetomidine, the autonomic hyperactivity was blunted, with a mean 12.8 % reduction in rate pressure product observed. Consideration should be given to the combined use of dexmedetomidine with benzodiazepines in the treatment of AWS. Keywords Dexmedetomidine * Alcohol withdrawal syndrome * Pharmacological therapy * Alcohol * Critical care, Introduction The treatment of alcohol withdrawal syndrome (AWS) is challenging to intensivists. Benzodiazepines remain the mainstay of treatment [1-3]. Complications of therapy include hemodynamic instability and respiratory depression. Clonidine, a [...]

Byline: Asko Riutta (1), Pauli Ylitalo (1,2), Seppo Kaukinen (3) Keywords: Intensive care; Melatonin; Cortisol; Illness severity; Benzodiazepine; Sedation; Vanillylmandelic acid Abstract: Objective To study the diurnal variation of melatonin and cortisol in critically ill patients and to assess whether the severity of organ dysfunction, sedation and sympathetic activity correlate with the production of these hormones. Design Prospective clinical study. Setting Surgical intensive care unit in a university hospital. Patients Forty non-septic patients without brain injury and treatment with adrenergic agonists or corticosteroids. Twenty-five of the patients were sedated with benzodiazepines. Interventions None. Measurements and results The pattern of melatonin production was monitored by the determination of 6-sulphatoxymelatonin (aMT6s) in urine. The 12-h aMT6s excretions at nights (11.8 +- 8.9 ug, mean +- SD) were higher than in the daytime (6.8 +- 7.5 ug P < 0.0001), and benzodiazepine treatment did not abolish the diurnal periodicity of aMT6s excretion during the entire 3-day study period. Serum cortisol concentrations at noon (524 +- 276 nmol/l, mean +- SD) were higher than at midnight (415 +- 172 nmol/l P < 0.0001), and the decrease at midnight was significant also in the patients treated with benzodiazepines. Sympathetic activity was monitored with urine vanillylmandelic acid (VMA). The 12-h VMA excretions did not show a diurnal variation, but a significant positive relationship between the 12-h VMA and aMT6s excretions was observed. The severity of organ dysfunction did not correlate either with the aMT6s and VMA excretion or with serum cortisol concentration. Conclusions The diurnal variation of melatonin and cortisol is maintained in non-septic intensive care unit patients. Benzodiazepines do not impair the diurnal variation of melatonin and cortisol. Author Affiliation: (1) Department of Pharmacological Sciences, Medical School, University of Tampere, 33014, Tampere, Finland (2) Department of Clinical Chemistry, Tampere University Hospital, Tampere, Finland (3) Department of Anaesthesia and Intensive Care, Tampere University Hospital, Tampere, Finland Article History: Registration Date: 17/06/2009 Received Date: 13/08/2008 Accepted Date: 15/06/2009 Online Date: 04/07/2009

In this article, we report the first randomized double-blind controlled study of the use of psychotropic analgesic nitrous oxide (PAN) vs. a single dose of benzodiazepine (diazepam) for treating acute alcoholic withdrawal states. In previous studies, it was demonstrated that a single treatment of PAN was sufficient to reverse 90% of acute alcoholic withdrawal states within the first 60 minutes of administration with lasting effect in a single-blind manner. Despite the small sample used (n = 23), the gas was significantly more effective than the benzodiazepine at the P = 0.05 level when compared at 120 minutes. This study provides further support for previous findings that show PAN is a safe, rapid and effective therapy for acute mild to moderately severe withdrawal states. Keywords: Nitrous oxide; Benzodiazepine; Double-blind; Alcohol withdrawal

Objective: To investigate the prevalence of long-term benzodiazepine use in an elderly community sample, and factors associated with such use. Method: Data came from the Sydney Older Persons Study, a longitudinal study of people aged 75 or over. There were 337 subjects who were interviewed in 1991-93, and subsequently followed up after three and 4.5 years. At the first interview, subjects were assessed for sociodemographic characteristics, physical and mental health, and use of health services. At the first and subsequent interviews, subjects were asked about use of medications, including benzodiazepines. Results: There were 16.6% who were using benzodiazepines at the time of all three interviews, while a further 19.6% were using them at one or two interviews. In a multivariate ordered logit regression model, long-term benzodiazepine use was associated with treatment for nervous conditions, restless sleep, being female, being divorced and greater contact with medical services. Conclusions: The prevalence of benzodiazepine use in the elderly is high and much of this use is long term. The high prevalence of benzodiazepine use stands in contrast to the findings from national surveys that the elderly living in the community tend to have better mental health than younger age groups. Implications: Efforts are needed to reduce the number of elderly people becoming long-term users. The use of benzodiazepines in this age group is of particular concern, because they may be a risk factor for falls and for cognitive impairment in the elderly.

Use of benzodiazepines has been discussed extensively both among the public and within the medical society. The aim of this study was to explore the quality of dilemmas experienced by physicians when prescribing benzodiazepines. A questionnaire was sent to 213 Swedish General Practitioners. The critical incident technique was chosen as an appropriate method for surveying professional experiences. Concern for the patient and threats to the integrity of the physician were common dilemmas. The physicians did not believe that the patients were telling the truth or did not trust the patients' ability to handle the medicine. The most frequent consequences of the dilemmas were worry about a disturbed relationship with patients indicating an uncertainty as to how to create a good relationship with them. The participants in the study were aware of the national guidelines for prescribing benzodiazepines, but due to insufficient time a prescription was often chosen as a way to handle the dilemmas. Improvement in the rational use of benzodiazepines is not achieved by the medical board making new rules but rather by offering physicians education in communication and negotiating skills as well as more time with the individual patient who is requesting benzodiazepines. Keywords: Benzodiazepines; Dilemma; Physician; Prescription; Primary health care: Sweden

Status epilepticus is a life-threatening condition of continuous or rapidly recurring seizures without return to consciousness. Patients may exhibit twitching and jerking movements of the limbs, face, or eyes and will show signs of seizure when brain waves are monitored. Status epilepticus may develop in patients with established epilepsy, or from electrolyte disturbances, infection, head trauma, drug toxicity, or lack of oxygen. Treatment requires maintenance of a clear airway and rapid administration of sedating and antiseizure medication.

Benzodiazepines appear to be the most effective drugs in treating alcohol withdrawal. Members of the American Society of Addiction Medicine came to this conclusion after reviewing 134 articles on the treatment of alcohol withdrawal, 65 of which were controlled trials covering 42 different drugs. Long-acting benzodiazepines may be more effective but also have the potential for abuse and excessive sedation. Using a structured assessment scale to provide drugs only when symptoms become severe can reduce the length of treatment and the dosage of drugs used., Objective.--To provide an evidence-based practice guideline on the pharmacological management of alcohol withdrawal. Data Sources.--English-language articles published before July 1, 1995, identified through MEDLINE search on "substance withdrawal--ethyl alcohol" and review of references from identified articles. Study Selection.--Articles with original data on human subjects. Data Abstraction.--Stuctured review to determine study design, sample size, interventions used, and outcomes of withdrawal severity, delirium, seizures, completion of withdrawal, entry into rehabilitation, adverse effects, and costs. Data from prospective controlled trials with methodologically sound end points corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were abstracted by 2 independent reviewers and underwent meta-analysis. Data Synthesis.--Benzodiazepines reduce withdrawal severity, reduce incidence of delirium (-4.9 cases per 100 patients; 95% confidence interval, -9.0 to -0.7; P = .04), and reduce seizures (-7.7 seizures per 100 patients; 95% confidence interval, -12.0 to -3.5; P = .003). Individualizing therapy with withdrawal scales results in administration of significantly less medication and shorter treatment (P [is less than] .001). [Beta]-Blockers, clonidine, and carbamazepine ameliorate withdrawal severity, but evidence is inadequate to determine their effect on delirium and seizures. Phenothiazines ameliorate withdrawal but are less effective than benzodiazepines in reducing delirium (P = .002) or seizures (P [is less than] .001). Conclusions.--Benzodiazepines are suitable agents for alcohol withdrawal, with choice among different agents guided by duration of action, rapidity of onset, and cost. Dosage should be individualized, based on withdrawal severity measured by withdrawal scales, comorbid illness, and history of withdrawal seizures. [Beta]-Blockers, clonidine, carbamazepine, and neuroleptics may be used as adjunctive therapy but are not recommended as monotherapy. JAMA. 1997;278:144-151

Benzodiazepines that have a long half-life may increase the risk of traffic accidents in elderly people who take them. These drugs are commonly used to treat anxiety and insomnia in the elderly. Researchers analyzed benzodiazepine use among 5,579 elderly drivers who had been involved in a car crash that resulted in injuries. Those who used benzodiazepines with a long half-life were involved in about 50% more crashes than a comparison group of 13,256 drivers. However, the crash rate was no higher in those who took benzodiazepines with a short half-life., Context. -- Benzodiazepines, used by a sizable number of the elderly population, may affect the ability to drive and thus increase the risk of a motor vehicle crash. Epidemiologic studies of this question have produced inconsistent results that may be due to the different effects of long- and short-half-life benzodiazepines and variations in their duration of use. Objective. -- To determine whether the use of benzodiazepines of either long- or short-elimination half-life is associated with the risk of injurious motor vehicle crash in the elderly. Design and Setting. -- Nested case-control design within a cohort of 224734 drivers from the Canadian province of Quebec, aged 67 to 84 years, followed up from 1990 to 1993. Computerized data for the study were obtained from provincial driver&apos;s license files, police reports of injurious crashes, and health insurance records. Patients. -- We identified all 5579 drivers involved in an injurious crash (cases) and a random sample of 10 controls per case selected from a subcohort of 13 256 subjects. Main Outcome. -- Involvement of a cohort member as a driver in a motor vehicle crash in which at least 1 person (not necessarily the driver) sustained bodily injury. Results. -- The adjusted rate ratio of crash involvement within the first week of long-half-life benzodiazepine use was 1.45 (95% confidence interval [CI], 1.04-2.03). The rate ratio for continuous use of longer duration up to 1 year was slightly lower but remained significant (rate ratio, 1.26; 95% CI, 1.09-1.45). In contrast, there was no increased risk after the initiation of treatment with short-half-life benzodiazepines (rate ratio, 1.04; 95% CI, 0.81-1.34) or with their continued use (rate ratio, 0.91; 95% CI, 0.82-1.01). Conclusions. -- Brief or extended periods of exposure to long-half-life benzodiazepines are associated with an increased risk of motor vehicle crash involvement in the elderly population. There is no such elevated risk for short-half-life benzodiazepines.

Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, tolerance, dependence, and the potential for drug abuse plague the clinical use of anxiolytic benzodiazepines. Benzodiazepine and non-benzodiazepine ligands that are in current clinical use act as full allosteric modulators of GABA-gated Cl-channels, and on chronic administration trigger compensatory changes in the subunit expression of [GABA.sub.A] receptors. In these putative abnormal receptors, full allosteric modulators have low intrinsic activity and potency, and tolerance and dependence ensue. In this review, Erminio Costa and Alessandro Guidotti discuss the development of partial allosteric modulators, such as imidazenil, which have high potency and low intrinsic activity at GABA-gated Cl- channels. Since in animals tolerant to full allosteric modulators imidazenil also fails to show cross-tolerance, it is an example of a new type of anxiolytic and anticonvulsant drug acting at [GABA.sub.A] receptors via benzodiazepine recognition sites.

NMDA and non-NMDA (AMPA/kainate) antagonists have potential in the treatment of a diverse group of neurological disorders associated with excessive activation of excitatory amino acid receptors. Here Michael Rogawski reviews recent progress in the development of therapeutically useful NMDA receptor channel blockers and a new class of selective AMPA/kainate receptor antagonists, the 2,3-benzodiazepines. Research on these novel noncompetitive excitatory amino acid antagonists has opened promising new avenues for the development of drugs to treat epilepsy, ischaemia, neuro-degeneration and Parkinson's disease.

Generalized anxiety disorder occurs in 5% to 15% of the population. It is characterized by excessive anxiety, restlessness and fatigue and can also cause heart palpitations, shortness of breath and dizziness. Benzodiazepines are the standard treatment. Despite fears that these drugs are abused, most patients use them responsibly. These drugs are the most commonly prescribed tranquilizers in the US. Alprazolam (Xanax) has replaced diazepam (Valium) as the most commonly prescribed tranquilizer in the US. Common side effects of benzodiazepines are sedation, drowsiness, uncoordinated movements and difficulty with balance. Many users become adapted to these side effects. Many symptoms of anxiety will return when the drugs are discontinued, since they do not cure the illness.

Alcoholics who stop drinking commonly experience anxiety, both in the immediate period of withdrawal from alcohol and later on. Some persons have chronic anxiety, while others have acute attacks of panic. Studies have indicated that anxiety may be more common in alcoholics than in the population as a whole. Alcohol dependence may develop in individuals who find that alcohol reduces their anxiety or panic. Some experts have suggested that treating alcoholics with anti-anxiety drugs may promote the abuse of these drugs, leading to controversy about this mode of treatment. The cases of three alcoholics with diagnosed panic disorder who were successfully treated with clonazepam are discussed. Clonazepam is a long-acting benzodiazepine that is effective in treating panic disorder. Patient 1, a 34-year-old married white man, found that his panic attacks and social phobia (including fear of crowds and public places) were greatly alleviated by clonazepam. The second patient, a 38-year-old married black man, reported feeling much more comfortable in social situations while on clonazepam, after a long history of avoiding such situations due to frequent panic and chronic anxiety. He later resumed drinking and the panic attacks returned, but were less frequent than before. Patient 3, a 64-year-old white married man, experienced complete relief from his chronic anxiety and panic attacks with clonazepam; he also remained sober for a year (the duration of follow-up) with the help of Alcoholics Anonymous. These patients appear to be part of a subgroup of alcoholics who can be safely treated for anxiety and panic disorder with benzodiazepines; they all apparently developed alcohol dependence because they found it reduced or interrupted panic attacks. The results also suggest that benzodiazepine therapy may not always lead sober alcoholics to return to drinking. (Consumer Summary produced by Reliance Medical Information, Inc.), INTRODUCTION Alcoholic patients frequently complain of anxiety, both in the acute withdrawal phase and after several weeks postwithdrawal. Complaints are highly varied and range from pervasive, chronic anxiety to discrete [...]

Insomnia, the inability to sleep, is a common sleep disorder, which may result from several causes and vary extensively in duration and severity. The events in one's life, medications, psychological and medical factors may cause insomnia and should be assessed upon diagnosis. People who usually sleep well but experience stress, environmental change, jet lag or drug side effects may have transient, short-term insomnia, whereas chronic insomnia tends to result from a medical or psychological problems. Treatment should be directed at the underlying causes, and may involve withdrawal of substances causing side effects, management of stress, counseling, and various psychotherapeutic techniques. Sleeping pills may be used for transient, short-term insomnia, but are not recommended for long-term treatment. Benzodiazepines are the drugs of choice for insomnia, and consist of various long- and short-acting forms. Long-acting drugs such as flurazepam produce sedative hangover effects the next day, whereas short-acting agents such as triazolam may worsen the insomnia and cause a form of amnesia. Because side effects are related to dose, the dose should be kept low. When prescribing hypnotics, a physician should take into consideration the patient's age and lifestyle and duration of treatment, and avoid large or renewable prescriptions. Depressed or suicidal patients, alcohol or substance abusers, the elderly and mentally impaired, patients with sleep-related breathing disorders and incurable insomnia, and pregnant women require special attention. (Consumer Summary produced by Reliance Medical Information, Inc.)

Several classes of hypnotic medication are available: the older barbiturates and their derivatives; benzodiazepines; chemically distinct 'z-compounds'; antihistamines and antihistaminic antidepressants; and melatoninergic compounds. The use of hypnotic medications continues [...]