Benzodiazepine Requirements Research Articles

Dexmedetomidine for Alcohol Withdrawal Syndrome.

To review available evidence evaluating dexmedetomidine in alcohol withdrawal syndrome (AWS) while identifying gaps in evidence for its use in this setting. A MEDLINE search (1966-August 2015) to identify English-language articles evaluating the efficacy and safety of dexmedetomidine in alcohol withdrawal. Key words included alcohol, withdrawal, delirium tremens, and dexmedetomidine. Additional references were identified from a review of literature citations. All English-language observational studies, retrospective reviews, and clinical trials were included. Case reports and case series describing the use of dexmedetomidine in 10 or fewer patients were excluded. One randomized, controlled trial, 1 prospective observational study, and 6 retrospective reviews were identified. The only randomized, controlled trial identified showed that the addition of dexmedetomidine decreases benzodiazepine requirements more than placebo in the first 24 hours after initiation compared with the 24 hours prior to initiation (-56.8 mg vs -8 mg; P = 0.037). Overall, dexmedetomidine appears to lower benzodiazepine requirements in patients with AWS and decreases the sympathomimetic response seen in these patients. There was no convincing evidence that dexmedetomidine improves clinical endpoints in patients with AWS, such as need for mechanical ventilation or intensive care unit or hospital length of stay. Dexmedetomidine reduces hypertension and tachycardia in AWS and also reduces benzodiazepine requirements; however, the impact of these findings on important clinical endpoints is yet to be determined. Dexmedetomidine may be useful as adjunctive therapy; however, it cannot be recommended as a single agent in the management of AWS.

Levetiracetam as adjunctive therapy for acute alcohol withdrawal syndrome in hospitalized patients.

Benzodiazepines are often considered the standard of care for managing symptoms of acute alcohol withdrawal syndrome. Because of potential adverse effects, other agents have been evaluated in this patient population. Previous studies have produced mixed results on the efficacy of levetiracetam in alcohol withdrawal. The objective of this study was to determine whether adjunctive levetiracetam reduces the amount of symptom-triggered benzodiazepines required by patients experiencing symptoms of alcohol withdrawal. We conducted a retrospective chart review of patients who experienced symptoms of alcohol withdrawal while hospitalized. The outcomes of patients who received adjunctive levetiracetam were compared with those of patients who received only the standard of care (control group). Two hundred fifty patients (125 in each cohort) were included. No significant differences were found in the benzodiazepine requirements of the 2 cohorts. The control group required a median average daily dose of 2.0 mg of lorazepam (range, 0.1-17 mg/d) compared with the levetiracetam group, which required a median average daily dose of 1.3 mg of lorazepam (range, 0.0-53.5 mg/d) (P = 0.09). The patients in the control group required a median total of 6 mg of lorazepam during their hospitalization compared with a median total of 5.5 mg in the levetiracetam group. Both cohorts had a median length of stay of 3 days, although those in the levetiracetam group had a shorter length of intensive care unit stay and spent less time mechanically ventilated. The adjunctive use of levetiracetam does not significantly reduce the benzodiazepine requirements of patients experiencing symptoms of alcohol withdrawal in the inpatient setting.

Evaluation of Early Dexmedetomidine Addition to the Standard of Care for Severe Alcohol Withdrawal in the ICU: A Retrospective Controlled Cohort Study.

This study evaluated the impact of dexmedetomidine (DEX) administration on benzodiazepine (BZD) requirements in intensive care unit (ICU) patients experiencing alcohol withdrawal syndrome (AWS). This trial included adults admitted to the ICU for >24 hours for AWS. Early DEX was defined as receiving DEX within 60 hours of hospital admission. The primary outcome was 12-hour BZD requirement from the inflection point or DEX initiation. Secondary outcomes included 24-hour BZD requirements, symptom control, ICU and hospital length of stay, and incidence and duration of mechanical ventilation. Safety outcomes included incidence of bradycardia and hypotension. Twenty patients receiving DEX were matched to 22 control patients. The mean 12-hour change in BZD requirement was significantly different for DEX versus control (-20 vs -8.3 mg, P = .0455) with a trend toward significance at 24 hours (-29.6 vs -11 mg, P = .06). No significant differences were noted in other secondary outcomes. Patients receiving DEX experienced significantly more bradycardia than controls (35% vs 0%, P < .01) but not hypotension. This study suggests DEX is associated with a reduction in BZD requirement when utilized as adjunctive therapy for AWS. A larger prospective trial is needed to evaluate the clinical impact of DEX for AWS.

865

Introduction: Atypical antipsychotics, such as quetiapine, have been suggested as an option for treatment of intensive care unit related delirium by consensus guidelines and are being utilized more frequently in clinical practice as a component of sedation and agitation management in the critically ill. Methods: A retrospective chart review of patients receiving quetiapine in the surgical intensive care unit between May 1, 2010 and January 1, 2013 was conducted. Data collected included the frequency of documented agitation (Sedation Agitation Score > 4), duration of restraint use, and benzodiazepine requirements. Outcomes 72-hours previous to quetiapine administration were compared to outcomes 72-hours after the initiation of quetiapine. The prescribing pattern of quetiapine, including doses selected and duration of treatment, were also determined. Safety was evaluated by assessing the prevalence of QTc prolongation. Results: Seventy patients were included in this study. The median age was 67 years and 52 of the 70 patients (74%) were male. Forty-four (63%) patients were admitted to the surgical intensive care unit secondary to trauma with 34 (77%)of these patients having sustained a traumatic brain injury. On the day of quetiapine initiation, 47 (67%) patients were in some type of restraints. The median frequency of documented agitation was highest 24 hours before and after initiation of quetiapine. A decreasing trend was observed in the median daily benzodiazepines requirements. This effect was most pronounced in patients receiving greater than 10 mg per day of midazolam equivalents prior to quetiapine administration. In this subgroup (n=42), the median midazolam daily dose decreased from 28-mg to 2-mg. The median duration of restraint use was reduced by 24 hours from baseline. Half (35/70) of the patients were discharged from the surgical intensive care unit while receiving quetiapine and of these, two were discharged from the hospital while receiving quetiapine. Three patients experienced a QTc interval greater than 500 msec with no episodes of torsades de pointes noted during the study period. Conclusions: Quetiapine administration may reduce benzodiazepine requirements and duration of restraint use. There is a high prevalence of continuation of quetiapine beyond the intensive care unit environment. This is a potential area for quality improvement with regards to medication reconciliation, limiting adverse effects, drug interactions, and cost. QTc interval should be monitored in patients receiving quetiapine.

874

Introduction: Alcohol withdrawal is associated with increased morbidity and mortality, potential for intubation and mechanical ventilation requiring admission to the intensive care unit (ICU) and prolonged hospital length of stay (LOS). Benzodiazepines are the mainstay of therapy; however several case reports have demonstrated dexmedetomidine can be used as an adjunctive agent for treatment of alcohol withdrawal. Methods: A retrospective review was performed evaluating subjects that received continuous infusion benzodiazepines in addition to dexmedetomidine. The total benzodiazepine dose 24 hours before dexmedetomidine initiation and 2, 12 and 24 hours following was assessed. Additionally, ICU LOS, duration of mechanical ventilation, Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale, and heart rate and blood pressure were collected. Results: Thirty-seven subjects, 92% male, received dexmedetomidine and continuous infusion benzodiazepines. The mean CIWA-Ar score prior to dexmedetomidine was 10.54 and 24 hours post dexmedetomidine initiation and reduced to 7.4 ± 5. Mean heart rate 24 hours after dexmedetomidine was 80 bpm and mean systolic blood pressure (SBP) was 130 mmHg. The average ICU LOS was 10.7 days and 62.2% of subjects were mechanically ventilated for 7.18 ± 4.3 days. There was a statistically significant increase in ICU LOS in those that were mechanically ventilated and received dexmedetomidine (p= 0.017). Although there was a reduction in the benzodiazepine requirement at 2, 12 and 24 hours (3, 2.45, 1.9 mg/hr, respectively) the difference was not statistically significant (p= 0.23). There was a reduction in mean CIWA-Ar scores at 2, 12 and 24 hours (9.71, 8.41, 8.53, respectively); however the reduction was not statistically significant (p= 0.7). Conclusions: Perhaps due to a small sample size, these data do not demonstrate the anticipated decrease in duration of mechanical ventilation or reduction in ICU LOS in subjects that received dexmedetomidine in addition to benzodiazepines.

Influence of dexmedetomidine therapy on the management of severe alcohol withdrawal syndrome in critically ill patients

PurposeAlthough benzodiazepines are first-line drugs for alcohol withdrawal syndrome (AWS), rapidly escalating doses may offer little additional benefit and increase complications. The purpose of this study was to evaluate dexmedetomidine's impact on benzodiazepine requirements and hemodynamics in AWS. Materials and MethodsThis retrospective case series evaluated 33 critically ill adults with a primary diagnosis of AWS from 2006 to 2012 at an academic medical center. ResultsDexmedetomidine began a median (interquartile range) of 11 (2, 32) hours into intensive care unit admission and was titrated to an infusion rate of 0.7 (0.4, 0.7) μg kg−1 h−1 to achieve the desired depth of sedation. In the 12 hours after dexmedetomidine began, patients experienced a 20-mg reduction in median cumulative benzodiazepine dose used (P < .001), a 14-mm Hg lower mean arterial pressure (P = .03), and a 17-beats/min reduction in median heart rate (P < .001). Four (12%) patients experienced hypotension (systolic blood pressure <80 mm Hg) during therapy, and there were no cases of bradycardia (heart rate <40 beats/min). ConclusionDexmedetomidine decreased benzodiazepine requirements and improved the overall hemodynamic profile of patients with severe AWS. These results provide promising evidence about the potential benefit of dexmedetomidine for AWS.

PTU-092 The Management of Alcohol Withdrawal in Patients with advanced Liver Disease

IntroductionAlcohol withdrawal syndrome (AWS) is a common reason for hospital admission. However a significant number of these patients have co-existent liver disease or other medical problems. There is little information...

Response to “Benzodiazepine misadventure in acute alcohol withdrawal: the transition from delirium tremens to ICU delirium”

To the Editor: We read with interest the response by Johnson et al. [1] to our article in the May issue of the Journal of Anesthesia, and appreciate their comments [2]. In our retrospective case series, we reported the use of dexmedetomidine for treatment of alcohol withdrawal syndrome (AWS), to avoid mechanical ventilation. We described our protocol, which uses dexmedetomidine as the primary agent for AWS. In addition, adjunctive agents are used at low doses including a benzodiazepine, lorazepam 2 mg intravenously every 6 h, and haloperidol 5 mg intravenously every 6 h. Johnson et al. suggest a secondary benefit of dexmedetomidine is a lower incidence of delirium tremens, and subsequent less progression to ICU delirium. They also describe their experience with a case of severe AWS in a patient requiring over 1000 mg parenteral midazolam and lorazepam during her course in the ICU. After 11 days she was placed on dexmedetomidine, with resolution of her AWS within 34 h. We would like to address the queries in the letter. At the time of our study, we did not have use of the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) in our hospital as a validated delirium assessment tool. The CAM-ICU was recently implemented at our institution, but have not accumulated enough experience to assert that the dexmedetomidine is reducing the incidence of delirium, although the hypothesis is certainly plausible, and merits further study. We did not collect data specifically on the reduction of benzodiazepine requirements subsequent to initiation of the dexmedetomidine. However, Rayner et al. [3] have subsequently reported 61.5 % reduction in benzodiazepines with the use of dexmedetomidine in their series of AWS patients. With experience, we have learned that the dexmedetomidine should be started earlier in these patients, and this serves to shorten the course of the AWS. We have managed cases in which the AWS patient had dexmedetomidine initiated on admission to our emergency department, continued in the SICU, and was off the dexmedetomidine and stable for floor care within 36 h. We have also broadened the use of dexmedetomidine to other withdrawal syndromes, including benzodiazepines, opioids, and cocaine. It has also been particularly effective for the polydrug abuser, a traditionally difficult patient experiencing overlapping withdrawal syndromes.

121

Introduction: Dexmedetomidine is an alpha-2 receptor agonist indicated for intensive care unit and procedural sedation. In addition to its sedative properties, dexmedetomidine has sympatholytic effects that reduce heart rate and blood pressure. Alcohol withdrawal is characterized by agitation, psychosis, and manifestations of autonomic hyperactivity. The objective of this study was to evaluate the use of adjunctive dexmedetomidine for severe alcohol withdrawal. Hypothesis: Addition of dexmedetomidine results in reduced benzodiazepine use, withdrawal symptoms, and causes minimal side effects. Methods: This retrospective study evaluated patients >18 years old with severe alcohol withdrawal treated with dexmedetomidine in conjunction with the standard of care. Patients without a Clinical Institute Withdrawal Assessment (CIWA) score of?8 or those prescribed dexmedetomidine for other indications were excluded. Patient vital signs, CIWA scores, benzodiazepine use, and dexmedetomidine doses and duration were compared pre- and post-dexmedetomidine initiation. Paired t-tests were utilized to compare continuous variables, with p<0.05 considered significant. Results: Sixteen patients were enrolled. The majority of patients were male (94%) with an average age of 44.3 ± 13.6 years. The mean APACHE II score was 16.1 ± 8.2, and mean length of stay in the ICU was 131.8 ± 65.9 hours. Average duration of dexmedetomidine was 40.4 ± 39.2 hours at a mean dose of 0.52 ± 0.23 mcg/kg/hour started 41.7 ± 20.2 hours after admission. Total benzodiazepine exposure, represented by milligrams of lorazepam equivalents, was less after initiating dexmedetomidine (39.4 ± 28 vs 18.2 ± 18; p=0.018), as was the average CIWA score (14.5 ± 4.2 vs 9.0 ± 4.6; p=0.004). Heart rate (106.8 ± 15.9 vs 82.7 ± 12.4; p=0.0001) and systolic blood pressure (135.8 ± 15.2 vs 124.6 ± 20.6; p=0.035) were reduced with the addition of dexmedetomidine. Bradycardia (HR?60) or hypotension (SBP?90) each occurred in 25% of patients and both occurred in 6% of patients. Conclusions: The addition of dexmedetomidine blunts the symptoms of autonomic hyperactivity and reduces benzodiazepine requirements; however, these beneficial effects must be weighed against the risk of bradycardia and hypotension.

Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease*

To evaluate the safety and efficacy of prolonged dexmedetomidine administration (≥ 96 hrs) in critically ill children with heart disease. Retrospective observational study. Cardiovascular intensive care unit in a single, tertiary care, academic children's hospital. None. We conducted a retrospective review of the charts of all critically ill infants and children (up to 18 yrs of age) with congenital or acquired heart disease who received dexmedetomidine for ≥ 96 hrs in our pediatric cardiovascular intensive care unit between January 2009 and March 2010. Patients were divided into two groups for study purposes: the dexmedetomidine group (n = 52) included patients who received a dexmedetomidine infusion along with other conventional sedation agents, and the control group (n = 42) included patients who received conventional sedation agents without the use of dexmedetomidine. Clinical outcomes evaluated in our study included days of mechanical ventilation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. To evaluate the safety of dexmedetomidine, we collected physiologic data, including heart rate, mean arterial pressure, respiratory rate, systemic oxygen saturation by pulse oximetry, and inotrope score. To assess the efficacy of dexmedetomidine, we examined the amount and duration of concomitant sedation and analgesic infusions over a period of 24 hrs in both dexmedetomidine and control groups. We also examined the number of rescue boluses for each category prior to the initiation of sedative infusion, during the sedative infusion, and after the termination of the sedative infusion. The potential side effects evaluated in our study included nausea, vomiting, abdominal distension, dysrhythmias, neurological abnormalities, seizures, and signs and symptoms of withdrawal. Patients' baseline characteristics were similar in the two groups. Patient complexity as measured by Risk-Adjusted Classification for Congenital Heart Surgery-1 score, ventricular ejection fraction, and proportion of patients receiving mechanical ventilatory support at the time of initiation of sedative infusion was also similar. The duration and amount of continuous midazolam and morphine infusions were significantly lower in the dexmedetomidine group when compared to the control group. During dexmedetomidine infusion, there was no statistical difference in the heart rate and blood pressure between the two groups. Inotrope score was significantly lower in the dexmedetomidine group as compared to the control group in the last 6 hrs prior to termination of dexmedetomidine infusion (p < .001), and at 1 hr (p < .001) and 6 hrs (p < .001) after termination of dexmedetomidine infusion. There was no difference in duration of mechanical ventilation (p = .77), cardiovascular intensive care unit length of stay (p = .29), or hospital length of stay (p = .43) in the two groups. One patient experienced junctional rhythm at 130 beats/min requiring temporary pacing. No other significant side effects were noted. A higher proportion of patients in the dexmedetomidine group were administered clonidine when compared to the control group after termination of dexmedetomidine (31% vs. 7%, p = .005). Prolonged dexmedetomidine administration in children with heart disease appears to be safe and is associated with decreased opioid and benzodiazepine requirement and decreased inotropic support.

Safety and Efficacy of Dexmedetomidine in Children With Heart Failure

This retrospective observational study aimed to evaluate the safety and efficacy of dexmedetomidine (DEX) for children with heart failure. The study was conducted in the cardiovascular intensive care unit (CVICU) of a single, tertiary care, academic children's hospital. A retrospective review of the charts for all children (up to 18 years of age) with signs and symptoms consistent with congestive heart failure who received DEX in our CVICU between April 2006 and April 2011 was performed. The patients were divided into two groups for study purposes: the DEX group of 21 patients, who received a DEX infusion together with other conventional sedation agents, and the control group of 23 patients, who received conventional sedation agents without the use of DEX. To evaluate the safety of DEX, physiologic data were collected including heart rate, mean arterial pressure (MAP), and inotrope score. To assess the efficacy of DEX, the amount and duration of concomitant sedation and analgesic infusions in both the DEX and control groups were examined. The numbers of rescue boluses for each category before the initiation of sedative infusion and during the sedative infusion also were examined. The baseline characteristics of the patients in the two groups were similar. There was no effect of DEX infusion on heart rate, MAP, or inotrope score at the termination of infusion. The daily amount of midazolam administered was significantly less during the last 24 h of DEX infusion in the DEX group than in the control group (p = 0.04). The daily amount of morphine infusion did not differ between the DEX and control groups during any period. The numbers of sedation and analgesic rescue boluses were lower in DEX group throughout the infusion. No other significant side effects were noted. Two patients in the DEX group had a 50 % or greater drop in MAP compared with baseline in the first 3 h after initiation of DEX infusion, whereas one patient had a 50 % or greater drop in heart rate compared with baseline in the first 3 h after initiation of DEX infusion. Administration of DEX for children with heart failure appears to be safe but should be used cautiously. Furthermore, DEX use is associated with a decreased opiate and benzodiazepine requirement for children with heart failure.

Benzodiazepine misadventure in acute alcohol withdrawal: the transition from delirium tremens to ICU delirium

To the Editor: In the May issue of the Journal of Anesthesia, Demuro et al. [1] describe a case series of patients receiving dexmedetomidine for alcohol withdrawal. The authors highlight that benzodiazepines may be associated with hemodynamic instability and respiratory depression. An additional complication, intensive care unit (ICU) delirium, may be an underdescribed complication of benzodiazepines in alcohol withdrawal. While not studied in alcohol withdrawal, analysis has shown an association of lorazepam use with the transition to delirium in mechanically ventilated patients, and a higher incidence of delirium with midazolam compared with dexmedetomidine [2, 3]. We recently encountered a case of severe alcohol withdrawal transitioning to ICU delirium following extensive benzodiazepine exposure. We are curious if the authors have any data regarding benzodiazepine requirements or ICU delirium assessment before/after dexmedetomidine initiation. A 38-year-old woman with past medical history of hepatitis C and alcohol abuse presented to the emergency department with pruritus and visual hallucinations after several days of abstaining from alcohol. During the first 8 h of admission, she received 31 mg of intravenous lorazepam with minimal improvement in symptoms. She was transferred to the ICU, where she was intubated and given escalating doses of continuous infusion benzodiazepines with intermittent propofol (Fig. 1). In spite of this intense regimen, the patient remained agitated and conscious enough to exit her ICU bed and stand unassisted with the endotracheal tube (ET) in place. On day 5, adjunctive phenobarbital and clonidine were added. On day 8, it was believed that the patient’s withdrawal syndrome had improved and she was transitioned to scheduled lorazepam bolus doses. However, over the next 3 days she was unable to be liberated from mechanical ventilation due to fluctuating mental status and agitation despite the addition of haloperidol. The patient was positive for ICU delirium as assessed by the confusion assessment method for the ICU (CAM-ICU). In an effort to manage the delirium and agitation, a dexmedetomidine infusion was started on day 11 at 0.2 lg/kg/h and titrated to a dose of 1.0 lg/kg/h. Over the next 24 h, the patient’s agitation improved and she was extubated on day 12. Dexmedetomidine was weaned off after 34 h, and she was transferred to the general medicine floor the following day without further need for any benzodiazepine doses. At the time of discharge from the ICU, the patient had received a total of 183.5 mg intravenous lorazepam, 24 mg oral lorazepam, and 1,221 mg intravenous midazolam. This case illustrates the potential complications of benzodiazepines in severe alcohol withdrawal. We witnessed a patient transition from severe alcohol withdrawal, to delirium tremens, and finally to ICU delirium following M. T. Johnson (&) College of Pharmacy, University of Illinois-Chicago, 833 S. Wood St, 164 Pharm [M/C 886], Chicago, IL 60612, USA e-mail: mtj1636@uic.edu

Reduction of Benzodiazepine Requirements During Mechanical Ventilation in a Child by Topical Application of Essential Oils

To avoid these complications, many chil-dren require maintenance therapy with long-acting benzodiaz-epines,delayingdischargehome.Benzodiazepinesalsointerferewithrapideyemovementsleeppatterns,resultinginaprofoundsenseoffatigue,andmayleadtodisorientationoragitationafterdays remaining in a drug-induced state of sleep. Prolonged seda-tion leads to postextubation paresis requiring physical therapy.Prolonged periods of stasis lead to lymph edema and third spac-ing, requiring diuretics, which lead to electrolyte derangements.The ability to reduce the amount of benzodiazepines usedduring critical illness may help reduce the incidence or severityof these side effects and sequelae. This article describes a casereport of reduction in benzodiazepine requirements in an intu-bated, sedated child by using topically applied essential oils.

Effect of alcohol withdrawal on liver transaminase levels and markers of liver fibrosis.

Acute alcohol withdrawal causes changes in hepatic blood flow and metabolism that may result in liver damage. This study aims to assess liver function tests and markers of hepatic fibrogenesis following alcohol withdrawal in alcoholics with clinically compensated liver disease. Serial liver function tests and clinical assessments were performed on 22 male alcoholics during alcohol withdrawal. Plasma tissue inhibitor of metalloproteinase 1 (TIMP1), an inhibitor of collagen degradation, and plasma amino-terminal procollagen III peptide (PIIINP), a collagen precursor molecule, were measured in these alcoholics and in 11 control subjects. Transaminase levels did not change significantly over 7 days when all subjects were analyzed together. However, 32% of subjects showed a marked transaminase rise. These subjects did not differ from the others in baseline characteristics or short-term outcome, but had a greater benzodiazepine requirement. Only one subject consumed paracetamol (acetaminophen; 1-2 g/day). He had the largest transaminase rise. By comparing PIIINP assays, intact PIIINP concentration appears to increase following alcohol withdrawal. The TIMP1 levels were elevated in alcoholic subjects, but did not change following withdrawal. Increasing PIIINP suggests that hepatic fibrogenesis increases, or hepatic clearance falls, during acute alcohol withdrawal. The TIMP1 elevation in these alcoholics suggests that the inhibition of collagen degradation occurs while liver disease is still compensated. The period following alcohol withdrawal may be a time of marked increased susceptibility to paracetamol. The biochemical changes we observed were not associated with adverse short-term outcome, but the cumulative effect after repeated episodes of abrupt withdrawal may be of concern.

Impact of Age on the Severity, Course, and Complications of Alcohol Withdrawal

Early identification of alcohol-dependent patients at increased risk for severe or complicated alcohol withdrawal would improve triage and treatment. However, the role of age in predicting alcohol withdrawal outcomes has not been well studied. To assess the impact of age on the severity, course, and complications of alcohol withdrawal. We performed a retrospective cohort study of 284 inpatients admitted for alcohol withdrawal between September 1992 and August 1994. Outcomes included alcohol withdrawal severity measured by the revised Clinical Institute Withdrawal Assessment for Alcohol scale, quantity and duration of benzodiazepine therapy, and complications during withdrawal. Initial and maximal withdrawal severity scores, amount of benzodiazepine administered, and duration of benzodiazepine treatment for elevated withdrawal severity scores did not change significantly with age. However, patients aged 60 years and older had increased risk for delirium (adjusted odds ratio [OR], 4.7; 95% confidence interval [CI], 1.5-15.0; P = .008), falls (OR, 3.1; 95% CI, 0.9-11.2; P = .08), and transient dependency in 2 or more activities of daily living (OR, 5.8; 95% CI, 2.9-11.7; P < .001). As age increased, there were significant increases in length of stay (P < .001) and frequency of discharge to an extended care facility (P < .001). Although alcohol withdrawal severity scores and benzodiazepine requirements were similar across age groups, patients aged 60 years and older were at increased risk for cognitive and functional impairment during withdrawal. These findings support recommendations that older patients with alcohol withdrawal are best treated in closely supervised settings.

Recognition and treatment of ethanol abuse in trauma patients

To evaluate physicians' recognition of possible ethanol-related complications in trauma patients, and to compare benzodiazepine requirements in patients with positive and negative blood-ethanol concentrations. Retrospective investigation. University medical center (level I trauma center). One hundred thirty-one trauma patients more than 18 years of age who were admitted for at least 24 hours. (1) Physicians' recognition of ethanol (EtOH) as a potential factor complicating patient recovery in trauma patients admitted with positive blood-EtOH concentrations. (2) The amount of benzodiazepines administered to trauma patients with positive EtOH-blood concentrations compared to trauma patients with no detectable EtOH in their blood. The presence of EtOH in the blood or the potential for EtOH withdrawal was mentioned in the progress notes of approximately one fourth of the patients with positive blood-EtOH concentrations. Thiamine was administered in 8.2% of patients with EtOH-related injuries. Benzodiazepine requirements were significantly higher in patients with positive versus negative blood-EtOH concentrations. Prompt recognition and charting of suspected ethanol abuse is recommended, in conjunction with prompt administration of thiamine. It should be anticipated that patients with positive blood-ethanol concentrations will require higher doses of benzodiazepines compared to trauma patients without ethanol-related injuries.

Acute tolerance from benzodiazepine night sedation

The hypothesis that benzodiazepine night sedation causes acute tolerance to benzodiazepine sedation given the following morning was examined in six volunteers in a double blind, randomised, crossover study. Before each of three study days, subjects received midazolam 15 mg or flunitrazepam 2 mg or placebo as oral night sedation. They were then given intravenous midazolam 5 mg the following morning and the resulting sedative effects examined, using an observers sedation scale and a psychomotor test battery (critical flicker fusion frequency, digit-symbol substitution, reflex time, tapping test and a visual analogue sedation scale). Although a consistent pattern emerged with the greatest degree of sedation following the placebo night sedation and the least degree of sedation following the midazolam, with flunitrazepam intermediate, no statistically significant differences were present between the three treatment groups. The results indicate that single use of benzodiazepine night sedation is not an important influence on benzodiazepine requirements for intravenous sedation.

Benzodiazepine Requirements During Alcohol Withdrawal Syndrome

An accurate characterization of the severity of the alcohol withdrawal syndrome is likely to provide clear guidelines for drug therapy in this disorder. We studied (retrospectively) the usefulness of a standardized withdrawal scale on benzodiazepine drug requirements for patients undergoing alcohol detoxification in a general hospital. One hundred thirty-three patients received the revised Clinical Institute withdrawal Assessment Scale for Alcohol and were medicated only if the score was greater than 10. A comparison group of 117 patients was treated without reference to the scale. The groups were evenly matched with respect to age, sex, concurrent drug use, and laboratory abnormalities. Subjects treated according to the scale required less benzodiazepine (median dose, 50 mg diazepam equivalent compared with 75 mg) (p = 0.04). Rates of complications, discharge against medical advice, and length of stay did not differ between the groups. Rank correlation coefficients revealed a closer relationship between the degree of alcohol exposure (as determined by admitting blood alcohol levels, creatine phosphokinase, and SGOT) and benzodiazepine requirements during withdrawal for the group treated with the scale. Findings suggest that when the scale is used, patients with a greater degree of physical dependence receive (appropriately) a higher dose of benzodiazepine and those with a lesser degree of dependence receive (appropriately) a lower dose of benzodiazepine. Use of the scale appears to minimize both under- and overdosing with benzodiazepine for alcohol withdrawal syndrome.

Massive benzodiazepine requirements during acute alcohol withdrawal

Severe alcohol withdrawal developed in an abstinent chronic alcoholic man. Massive doses of benzodiazepines (2,335 mg of diazepam intravenously, 21,225 mg of oxazepam orally) achieved only marginal control of delirium and agitation. Analysis of multiple blood samples drawn during and after the withdrawal episode indicated, as expected, very high concentrations of diazepam and metabolites and of oxazepam. There was no evidence of an abnormal pharmacokinetic profile. Benzodiazepine resistance in withdrawing alcoholics probably reflects a receptor-site phenomenon rather than an abnormal drug disposition.