High-dose Lorazepam Research Articles

Adolescents and Young Adults With Anti-N-methyl-D-aspartate Receptor Encephalitis With Excited Catatonia: Literature Review and 2Illustrative Cases.

Catatonia is a complex neuropsychiatric syndrome that can be associated with several underlying etiologies including primary psychiatric and autoimmune disorders. Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune disorder typically characterized by seizures, movement abnormalities, and behavioral changes. Anti-N-methyl-D-aspartate can present with complex neuropsychiatric symptoms including catatonia which can be challenging for clinicians to identify as excited catatonia can mimic delirium and psychiatric disorders such as psychosis and mania. To identify and present cases of anti-N-methyl-D-aspartate receptor encephalitis where excited catatonia is the presenting symptom. We present 2 case studies of agitation and disinhibition in an adolescent and young adult that were ultimately found to be secondary to autoimmune receptor encephalitis, in both cases, confirmed by cerebrospinal fluid analysis to be due to anti-N-methyl-D-aspartate receptor antibodies. Excited catatonia was suspected and initially treated with immunological therapy and high doses of lorazepam. As the severity of catatonia progressed with limited improvement with lorazepam, both cases were ultimately effectively treated with electroconvulsive therapy. Excited catatonia should be considered with presentations of bizarre behavior, agitation, disinhibition, and other psychotic symptoms in patients with no prior psychiatric history. Although the primary treatment for catatonia associated with anti-N-methyl-D-aspartate receptor encephalitis is immunomodulatory therapy paired with benzodiazepines, electroconvulsive therapy has been shown to be an effective and safe adjuvant treatment that is especially useful for management of excited catatonia.

Catatonia in Obsessive-Compulsive Disorder: A case study and literature review

Introduction There are extremely few reported cases of OCD causing catatonia and some of those cases are possibly associated with the somewhat contentious diagnosis of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus. As there is a symptom overlap between OCD and catatonia some cases of catatonia are possibly being missed, warranting discussion regarding differential diagnosis, symptomatology, and treatment of catatonia and OCD.ObjectivesWe describe a case of a 18-year-old patient who developed severe catatonia secondary to OCD, possibly related to PANDAS/PANS. We discuss the complex work-up, differential diagnosis, and treatment of this patient.MethodsDiscussion of a single case and a review of catatonia literature as it relates to OCD and autoimmune disorders.ResultsOur patient was an 18-year-old Ukrainian male who presented with sub-acute onset of decreased movement, decreased oral intake, and inability to speak. He was diagnosed with catatonia of an unclear etiology and treated with high-dose lorazepam at an outside hospital then transferred to our care. Presenting symptoms were then clarified and found to be consistent with OCD, upon which OCD treatment was initiated. The patient’s sub-acute and severe onset of OCD raised the question of a PANDAS/PANS diagnosis, which was further investigated. Ultimately, his symptoms improved with ongoing lorazepam and he was transferred to another hospital for ECT treatment.ConclusionsOCD has been observed to cause catatonia in extremely rare cases. Diagnosing catatonia associated with OCD is challenging and important as catatonia is associated with significant morbidity and mortality if left untreated. Our patient improved with concurrent treatment of catatonia and OCD.DisclosureNo significant relationships.

Informal Caregivers' Administration of Hospice Prescribed Lorazepam to Homecare Patients With Anxiety.

A growing number of informal caregivers (IFCs) manage hospice patients' anxiety by administering lorazepam (Ativan), yet little is known about prescribing practices in home care or the extent to which IFCs carry out regimens. Data on hospice prescribed lorazepam was determined through a retrospective review of medication records from 216 deceased patients. The dose of lorazepam and type of regimen (i.e., scheduled, PRN, combination) as well as frequency with which it was administered by IFCs was calculated upon admission to a residential care home and on patients' day of death. The majority (63.1%) of patients were prescribed lorazepam on admission to the home, and more (79.5%) were prescribed lorazepam on the day of death. While higher doses of lorazepam were prescribed and administered on the day of death, the percentage of medication consumed was low on admission (17%) and day of death (27%). Nearly all (92.8%) prescribed lorazepam on the day of death were allowed PRN medication. For PRN only regimens, less than a quarter (24.4%) of patients were given lorazepam on admission with less than half (40.4%) given it while dying. Highest lorazepam administration rates (91.2%) occurred on the day of death when lorazepam was prescribed under a combined regimen. The high frequency of PRN regimens reveal that IFCs are frequently tasked with making decisions about if and when to administer lorazepam. Low overall lorazepam administration suggests a closer monitoring of lorazepam use and enhanced support of IFCs may be needed.

Intramuscular Lorazepam for Status Epilepticus in Children With Complex Medical and Physical Disabilities.

A protocol was developed to achieve status epilepticus (SE) resolution: step 1, intramuscular (IM) lorazepam; step 2, repeat IM lorazepam; step 3, rectal diazepam. The primary objective was to identify the number of patients with SE resolution after step 1. Secondary objectives included categorization of mean number of IM doses per episode and patient factors associated with SE resolution. This was a retrospective study of patients <21 years old with complex medical and physical disabilities admitted over 5 years. For analysis, IM dosing was categorized as high dose (>0.05 mg/kg/dose) and low dose (≤0.05 mg/kg/dose). A generalized linear mixed-model regression was used to assess the relationship with SE resolution at step 1 and patient characteristics. A total of 44 patients were included (n = 162 episodes). SE resolution was noted in 68.5% of episodes after step 1. Models were stratified by gender to present odds of SE resolution at step 1 versus step 2/3. For women, no covariate was significant. For men, the odds of SE resolution at step 1 were 14.9 times higher in those receiving 2 versus 4 maintenance antiepileptics, adjusting for covariates. Additionally, odds of resolution at step 1 was 3.1 times higher for high-dose versus low-dose lorazepam in males, adjusting for covariates, but was not statistically significant. SE resolution was noted in 68.5% after step 1. Unadjusted, females had a higher odds of SE resolution at step 1 than males. In males, high-dose lorazepam had higher odds of SE resolution at step 1 than low-dose lorazepam, though not significantly different.

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting.

Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient's therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient's empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription

Objectives:To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction.Methods:We present a case report of a patient who developed this syndrome with various sequelae.Results:The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery.Conclusions:This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

Positive Propylene Glycol Result in a Patient with Ethylene Glycol Poisoning

A 61-year-old man presented with an increased anion-gap metabolic acidosis, an increased serum osmolal gap, and a negative result in an alcohol screen. Gas chromatography revealed an increased ethylene glycol (EG)2 concentration (22 mg/dL) and a propylene glycol (PG) result that was below the lower limit of quantification (<5 mg/dL) (Fig. 1A). The patient was treated with hemodialysis, followed by phenytoin and a high-dose lorazepam infusion for a witnessed seizure. …

A Systematic Review of Interventions Used to Treat Catatonic Symptoms in People with Autistic Spectrum Disorders

A systematic review was conducted to examine the efficacy of a range of treatments for autistic catatonia. The review identified 22 relevant papers, reporting a total of 28 cases including both adult and paediatric patients. Treatment methods included electroconvulsive therapy (ECT), medication, behavioural and sensory interventions. Quality assessment found the standard of the existing literature to be generally poor, with particular limitations in treatment description and outcome measurement. There is some limited evidence to support the use of ECT, high dose lorazepam and behavioural interventions for people with autistic catatonia. However, there is a need for controlled, high-quality trials. Reporting of side effects and adverse events should also be improved, in order to better evaluate the safety of these treatments.

1018 – Long-term efficacy and safety study of pregabalin in subjects with generalised anxiety disorder (GAD)

Introduction Pregabalin is indicated for the treatment of GAD in adults in Europe. The efficacy and safety of pregabalin for the treatment of adults and elderly patients with GAD has been demonstrated in 6 of 7 short-term clinical trials of 4 to 8 weeks. Aims/objectives To characterise the long-term efficacy and safety of pregabalin in subjects with GAD. Methods Subjects were randomised to double-blind treatment with either high-dose pregabalin (450-600 mg/d), low-dose pregabalin (150-300 mg/d), or lorazepam (3-4 mg/d) for 3 months. Treatment was extended with drug or blinded placebo for a further 3 months. Results At 3 months, mean change from baseline Hamilton Anxiety Rating Scale (HAM-A) for pregabalin high- and low-dose, and for lorazepam ranged from -16.0 to -17.4. Mean change from baseline Clinical Global Impression-Severity (CGI-S) scores ranged from -2.1 to -2.3 and mean CGI-Improvement (CGI-I) scores were 1.9 for each active treatment group. At 6 months, improvement was retained for all 3 active drug groups, even when switched to placebo. HAM-A and CGI-S change from baseline scores ranged from -14.9 to -19.0 and -2.0 to -2.5, respectively. Mean CGI-I scores ranged from 1.5 to 2.3. The most frequently reported adverse events were insomnia, fatigue, dizziness, headache, and somnolence. Conclusions Efficacy was observed at 3 months, with maintained improvement in anxiety symptoms over 6 months of treatment. These results are consistent with previously reported efficacy and safety trials of shorter duration with pregabalin and lorazepam in subjects with GAD. This study was funded by Pfizer Inc.

Delirious Mania

Delirious mania is a severe but under-recognized neuropsychiatric syndrome characterized by the rapid onset of delirium, mania, and psychosis, not associated with a prior toxicity, physical illness, or mental disorder. Catatonia is often a prominent feature of the syndrome. While initially believed to be rare, recent reports suggest that delirious mania may constitute up to 15% of all acute mania cases. When delirious mania is unrecognized or improperly treated, it can progress rapidly in severity and can become life-threatening. This article reviews the pathophysiology, diagnosis, and treatment of delirious mania and includes a detailed case report. Delirious mania is robustly responsive to high-dose lorazepam or electroconvulsive therapy (ECT); thus, early recognition and definitive treatment can be life-saving.

Unpredictable Absorption of Oral Opioid Medications in a Quadriplegic Patient With Chronic Enterocutaneous Fistulas

ABSTRACTAlthough there is an abundance of literature on the acute management of enterocutaneous fistulas, there is a paucity of data on the chronic management of enterocutaneous fistulas. Their impact on oral pharmacotherapy, including their effect on the bioavailability of oral medications, is poorly understood. This case describes a 23-year-old quadriplegic male with a complex history of multiple abdominal surgeries presented with three persistent enterocutaneous fistulas. Diazepam and furosemide were among the patient's oral medications and had sufficient bioavailability to show efficacy on anxiety and pedal edema, respectively. Conversely, oral oxycodone and methadone were ineffective in controlling chronic pain despite high doses and aggressive titration. Due to inadequate pain control, the patient supplemented opioid medications with high doses of lorazepam and diazepam to augment psychological comfort. A trial of subcutaneous morphine successfully produced immediate analgesia, causing a marked reduction in benzodiazepine use. Enterocutaneous fistulas may reduce the bioavailability of oral medications to various degrees depending upon the medication. Further research is needed to elucidate the effect chronic enterocutaneous fistulas have on the bioavailability of oral medications. It is therefore important for clinicians to question the bioavailability of medications in the setting of enterocutaneous fistulas and poor clinical response.

Propylene Glycol Accumulation in Critically III Patients Receiving Continuous Intravenous Lorazepam Infusions

Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered. To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration. A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24-48 hours after continuous-infusion lorazepam was initiated and every 3-5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses. Forty-eight propylene glycol serum samples were obtained from 33 patients. Fourteen (42%) patients had propylene glycol accumulation, representing 23 (48%) serum samples. Univariate analyses showed the following factors were related to propylene glycol accumulation: baseline renal dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling demonstrated that propylene glycol concentration was strongly associated with the continuous infusion rate and 24-hour dose (adjusted r(2) > or = 0.77; p < 0.001). Independent correlation analyses showed that these 2 variables were so strongly associated with propylene glycol concentration (r(2) > or = 0.71; p < 0.001) that they alone predicted propylene glycol concentration. Seven (21%) patients developed renal dysfunction after continuous-infusion lorazepam was initiated, but associated causes were indeterminable. Other possible propylene glycol-associated adverse effects were not observed. The continuous infusion rate and cumulative 24-hour lorazepam dose are strongly associated with and independently predict propylene glycol concentrations. Despite the absence of confirmed propylene glycol-associated adverse effects, clinicians should be aware that propylene glycol accumulation may occur with continuous-infusion lorazepam.

A Randomized, Double-Blind Comparison of Lorazepam and Chlordiazepoxide in Patients With Uncomplicated Alcohol Withdrawal

For important reasons, lorazepam (Ativan) and chlordiazepoxide (Librium) are both popular treatments for alcohol-withdrawal syndrome. Nevertheless, there is little literature directly comparing the two drugs. A formal comparison is desirable because of pharmacokinetic and other differences that could affect safety and efficacy considerations relevant to practice in developing countries. One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days. Double-blind assessments of withdrawal-symptom severity and impairing adverse events were obtained during treatment and for 4 days afterward. One chlordiazepoxide patient developed withdrawal delirium. Lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale. During withdrawal, irritability and dizziness were more common with lorazepam, and palpitations were more common with chlordiazepoxide. No difficulties in drug discontinuation or differences in impairing adverse events were observed with either drug. With the treatment schedule used in this study, lorazepam is as effective as the more traditional drug chlordiazepoxide in attenuating uncomplicated alcohol withdrawal. Lorazepam, therefore, could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic. The absence of clinically significant withdrawal complications with lorazepam in this large study contrasts with findings from previously published studies and suggests that higher doses of lorazepam than those formerly used may be necessary during alcohol withdrawal.

Respiratory Dysfunction in Sleep Apnea Associated with Quetiapine

Quetiapine is an atypical antipsychotic with good tolerability, but has recently been associated with respiratory dysfunction. The aim of this work is to report on moderate to severe respiratory dysfunction after normal oral doses of quetiapine in two obese patients with sleep apnea syndrome (SAS). In the first case, acute respiratory failure and coma occurred after a single normal oral dose of quetiapine in combination with lorazepam (although even higher doses of lorazepam alone were tolerated) in a patient with previously unknown SAS. Intensive care treatment and mechanical ventilation led to full recovery. The second case was a patient with an operated obstructive SAS in which quetiapine was associated with nocturnal respiratory dysfunction and confusion. Respiratory function should be monitored when using quetiapine in patients with possible sleep apnea, particularly in obese patients and when given in combination with benzodiazepines.

Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam

A 54-year-old male with a history of multiple admissions for alcohol intoxication was admitted to hospital with right flank pain. He received a high-dose lorazepam infusion for alcohol withdrawal during hospitalization and developed severe hyperosmolality, high anion gap metabolic acidosis, and acute kidney injury on his eighth day of hospitalization. Serum chemistries, arterial blood gas analysis, and measurement of serum propylene glycol, ethylene glycol and methanol levels. Propylene glycol toxicity. Discontinuation of lorazepam infusion, administration of fomepizole, hemodialysis for five consecutive days, hemodynamic support, and follow-up of serum osmolality as a measure of propylene glycol decay.

Topiramate Effect in Catatonia: A Case Series

Topiramate Effect in Catatonia: A Case Series

Topiramate Effect in Catatonia: A Case Series

The authors describe four cases of catatonia in which topiramate treatment was used. Commonly effective therapies, including benzodiazepines and divalproex, were proven refractory. In all four cases, subjects experienced complete remission of catatonic symptoms and tolerated treatment well. In one case, all psychotropic medications were discontinued because the patient became delirious. The delirium resolved after discovery and treatment of a urinary tract infection. Catatonic agitation relapsed when topiramate was withdrawn but remitted again when topiramate and lorazepam therapy was restored. In two cases, continued topiramate therapy was accompanied by sustained remission. These case reports present a novel approach to the treatment of catatonia.

Osmol Gap as a Surrogate Marker for Serum Propylene Glycol Concentrations in Patients Receiving Lorazepam for Sedation

To correlate serum propylene glycol concentration with osmol gap, serum lactate concentration, and amount of propylene glycol administered to mechanically ventilated patients receiving continuous infusions of lorazepam (80% propylene glycol by weight), and to characterize the prevalence of hyperosmolality and range of serum propylene glycol concentrations in this patient population. Prospective, controlled, observational study. Adult surgical and cardiothoracic intensive care units (ICUs) of a 1200-bed, urban, tertiary care, teaching hospital. Sixty-four consecutively enrolled intensive care patients requiring mechanical ventilation and pharmacologic sedation. Thirteen patients received continuous infusions of high-dose lorazepam (> or = 6 mg/hr) for a minimum of 36 hours, and 26 received continuous infusions of low-dose lorazepam (2-5.99 mg/hr) for 36 hours. Twenty-five control patients received sedatives that did not contain propylene glycol. Serum propylene glycol and lactate concentrations, osmolality, and basic metabolic profiles were obtained 72-108 hours after ICU admission. Clinical data, drug administration, and severity of illness scores were recorded. Osmol gap and the amount of propylene glycol administered before serum sampling predicted propylene glycol concentrations (r(2)=0.692, p<0.05). Osmol gap alone also predicted serum propylene glycol concentrations (r(2)=0.532, p<0.05). Serum lactate concentrations did not correlate with serum propylene glycol concentrations. Unlike the low-dose and control patients, eight (62%) of 13 high-dose patients had osmol gaps above 10. All 13 high-dose patients had serum propylene glycol concentrations previously associated with toxicity. Osmol gap can be used as a surrogate marker for serum propylene glycol concentration. In critically ill patients receiving lorazepam for sedation, an osmol gap above 10 was associated with concentrations previously reported to cause toxicity.

Sedative clearance during extracorporeal membrane oxygenation

The effects of polyvinyl chloride (PVC) tubing and membrane oxygenator (MO) on the concentrations of lorazepam and morphine in the neonatal extracorporeal membrane oxygenation (ECMO) circuit were evaluated using an in vitro model that included a closed ECMO circuit with a MO, heat exchanger, bladder and PVC tubing. The circuit was primed with blood, electrolytes, albumin and heparin and maintained at physiologic pH and temperature throughout by frequent measurement of blood gas pH and a temperature probe. Lorazepam and morphine were each studied separately in three separate, but identical circuits for 6 h on the day of circuit prime (new circuit) and then again for 6 h at 24 h (old circuit). Each circuit (new and old) was spiked once with lorazepam to a final concentration of 250 ng/mL or with morphine to a final concentration of 70 ng/mL in the circuit. Serial samples were drawn at baseline and every 30-60 min for 6 h at the site of injection and pre- and post-MO for each circuit. Lorazepam and morphine concentrations were analysed using gas chromatography with electron capture and gas chromatography with mass spectrometry, respectively. The concentrations of morphine and lorazepam at various sample sites and time points were expressed as a percentage of the original concentration. This single-dose study shows that up to 50% of a dose of lorazepam and 40% of a dose of morphine may be extracted by PVC and MO during bypass, depending on the age of the circuit. As the circuits become older, this amount could increase. These data may explain, in part, the higher doses of lorazepam and morphine required to sedate patients during ECMO.

Propylene Glycol–Induced Lactic Acidosis in a Patient with Normal Renal Function: A Proposed Mechanism and Monitoring Recommendations

To report a case of severe propylene glycol-induced lactic acidosis not attributable to renal dysfunction that was secondary to administration of high-dose intravenous lorazepam. A 24-year-old female with community-acquired pneumonia presented with severe acute respiratory distress syndrome. To maintain adequate sedation and ventilation and reduce airway pressure, several relaxation strategies were used including high-dose intravenous lorazepam, fentanyl, and cisatracurium. After 18 days of high-dose continuous infusion of lorazepam (maximum dose 50 mg/h), the patient developed severe lactic acidosis secondary to propylene glycol toxicity, the main diluent of lorazepam. The acidosis temporarily resolved with bicarbonate administration and discontinuation of lorazepam. Her renal function remained stable for a time (serum creatinine 0.5 mg/dL, blood urea nitrogen 10 mg/dL, urine output 100-200 mL/h). However, after several more days, the patient's condition deteriorated, and she ultimately died. Previous cases of propylene glycol toxicity secondary to high-dose lorazepam infusion have occurred in patients with compromised renal function. Our patient's renal function remained stable throughout the hospital course, which caused us to look further for an explanation for the propylene glycol-induced lactic acidosis. Based on the Naranjo probability scale, propylene glycol was determined to be the probable cause of lactic acidosis. Since this case occurred, our intensive care unit has instituted recommendations for the prevention of lorazepam-associated propylene glycol toxicity. Our case highlights the development of propylene glycol-induced lactic acidosis secondary to high-dose lorazepam infusion not associated with renal dysfunction.