Lorazepam Therapy Research Articles

The efficacy and safety of intravenous lorazepam therapy for status epilepticus and repetitive seizures in children with epilepsy

The efficacy and safety of intravenous lorazepam therapy for status epilepticus and repetitive seizures in children with epilepsy

Pharmacokinetic Interactions between Valproic Acid and Lorazepam (PIVOtAL Study): A Review of Site-Specific Practices.

Coadministration of lorazepam and valproic acid is identified by tertiary references as causing a major drug interaction that requires therapy modification and dosage adjustments. The proposed mechanism involves inhibition of lorazepam glucuronidation via direct inhibition of uridine 5'-diphosphate-glucuronosyltransferase enzymes by valproic acid. However, the clinical significance of this interaction is unclear. To identify site-specific practices and assess clinical responses to the interaction between valproic acid and lorazepam. A chart review was conducted for patients over 18 years of age who were admitted, from September 2008 to September 2014 inclusive, to the psychiatry or neurology service at Vancouver General Hospital, Vancouver, British Columbia, and who received concomitant valproic acid and lorazepam therapy. Of the 30 patients included in the chart review, 12 (40%) received an intervention. A total of 8 (27%) patients experienced an adverse drug reaction (ADR), such as drowsiness and dizziness. Seven of these 8 patients were among those who received an intervention. The mean dosage (± standard deviation) of lorazepam was 4.2 ± 1.2 mg per day among patients who experienced an ADR and less than 2 mg per day among those who did not experience an ADR. The current recommendation from tertiary drug references is to reduce the dose of lorazepam by 50% when this drug is coadministered with valproic acid. However, this recommendation could not be validated through an analysis of patients exposed to this interaction in the clinical setting or through a review of the literature. Further clinical and pharmacokinetic studies are required to determine whether concurrent treatment with lorazepam and valproic acid should be considered as causing a major drug interaction. Until more data are available, clinicians should remain cognizant of the potential for a drug-drug interaction and should use the lowest effective dose of lorazepam when this drug is administered concomitantly with valproic acid.

Dexmedetomidine Controls Agitation and Facilitates Reliable, Serial Neurological Examinations in a Non-Intubated Patient with Traumatic Brain Injury

We report the effective use of dexmedetomidine in the treatment of a patient with a history of chronic alcohol abuse and an acute traumatic brain injury who developed agitation that was unresolved if from traumatic brain injury, or alcohol withdrawal or the combination of both. Treatment with benzodiazepines failed; lorazepam therapy obscured our ability to do reliable neurological testing to follow his brain injury and nearly resulted in intubation of the patient secondary to respiratory suppression. Upon admission to hospital, the patient was first treated with intermittent, prophylactic doses of lorazepam for potential alcohol withdrawal based upon our institution's standard of care. His neurological examinations including a motor score of 6 (obeying commands) on his Glasgow Coma Scale testing, laboratory studies, and repeat CT head imaging remained stable. For lack of published literature in diagnosing symptoms of patients with a history of both alcohol withdrawal and traumatic brain injury, a diagnosis of agitation secondary to presumed alcohol withdrawal was made when the patient developed acute onset of tachycardia, confusion, and extreme anxiety with tremor and attempts to climb out of bed requiring him to be restrained. Additional lorazepam doses were administered following a hospital-approved protocol for titration of benzodiazepine therapy for alcohol withdrawal. The patient's mental status and respiratory function deteriorated with the frequent lorazepam dosing needed to control his agitation. Dexmedetomidine IV infusion at a rate of 0.5 mcg/kg/h was then administered and was titrated ultimately to 1.5 mcg/kg/h. After 8 days of therapy with dexmedetomidine, the patient was transferred from the ICU to a step-down unit with an intact neurological examination and no evidence of alcohol withdrawal. Airway intubation was avoided during the patient's entire hospitalization. This case report highlights the intricate balance between the side effects of benzodiazepine sedation for treatment of agitation and the difficulties of monitoring the neurological status of non-intubated patients with traumatic brain injury. Given the large numbers of alcohol-dependent patients who suffer a traumatic brain injury and subsequently develop agitation and alcohol withdrawal in hospital, dexmedetomidine offers a novel strategy to facilitate sedation without neurological or respiratory depression. As this case report demonstrates, dexmedetomidine is an emerging treatment option for agitation in patients who require reliable, serial neurological testing to monitor the course of their traumatic brain injury.

Determination of a Lorazepam Dose Threshold for Using the Osmol Gap to Monitor for Propylene Glycol Toxicity

To determine a threshold dose for parenteral lorazepam when screening for propylene glycol toxicity with the osmol gap, and to characterize which osmol gap values are more predictive of toxic propylene glycol concentrations and resultant clinical toxicity. Prospective, two-phase observational study. Thirty-two bed, multidisciplinary intensive care unit. Thirty-five adult patients receiving any dose of parenteral lorazepam (phase 1), and 14 patients receiving lorazepam in doses of 1 mg/kg/day or higher (phase 2). Serum osmolality was measured every other day during lorazepam therapy, and the osmol gap (measured osmolality minus calculated osmolarity) was determined. A serum propylene glycol concentration was obtained when the osmol gap first exceeded 10. In phase 1, 35 patients were monitored for 186 patient-days. Ten patients (29%) developed an osmol gap greater than 10; only one (10%) of these patients had propylene glycol concentrations greater than 18 mg/dl. In phase 2, 14 patients received lorazepam at a median dose of 631 mg (interquartile range [IQR] 437-972 mg) over a median of 5.5 days (IQR 4-8.75 days). Nine patients (64%) had propylene glycol concentrations greater than 18 mg/dl; six (67%) of these nine developed transient acute kidney injury, metabolic acidosis, or both. The correlation between osmol gap and propylene glycol concentration was 0.44 (p=0.006). An osmol gap of 10 or greater had a likelihood ratio of 4.4 to predict a propylene glycol concentration greater than 18 mg/dl. An osmol gap of 12 or greater had a likelihood ratio of 2.7 to predict the development of possible propylene glycol clinical toxicity. Screening for propylene glycol toxicity with the osmol gap may be helpful for patients receiving intravenous lorazepam in doses of 1 mg/kg/day or higher. An osmol gap of 10 or greater was predictive of elevated propylene glycol concentrations, and values of 12 or greater were predictive of clinical changes suggestive of propylene glycol toxicity.

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.

Clinical Experiences High‐flux hemodialysis in the treatment of severe valproic acid overdose: A case report

Introduction: Hemoperfusion, with or without hemodialysis, has been used to treat patients suffering from severe valproic acid poisoning. We report a patient suffering from severe valproic acid intoxication who was treated effectively with high‐flux hemodialysis alone. Case: A 20‐year‐old man with a history of bipolar disorder was admitted after having ingested unknown amounts of valproic acid (Depakote®), prednisone, and erythromycin. He was agitated and obtunded but hemodynamically stable initially. Serum valproic acid level was 1,028 μg/mL. Urine toxicology screen as well as serum levels of ethanol, acetaminophen, and acetylsalicylic acid levels were negative. A gastric lavage was followed by activated charcoal instillation. Subsequent myoclonic twitchings that progressed to continuous seizure activity were managed with intravenous lorazepam therapy and endotracheal intubation. Serum valproic acid value measured two hours after admission remained elevated at 1,046 μg/mL. Hemodialysis was performed continuously for 10.5 hours using a high‐flux, polysulfone dialyzer (Polyflux 21S, Fresenius Medical Care, Lexington, MA), a dialyzer blood flow of 200–300 mL/min, and a dialysate flow of 500 mL/min. The therapy brought about a fall in serum valproic acid level to 110 μg/mL and a complete recovery of the patient. Discussion: Valproic acid (144 Dalton) is 90–95% protein‐bound at therapeutic serum values. However, in the face of an overdose, the unbound fraction rises because of saturation of protein‐binding sites. This unbound fraction is readily dialyzable. We suggest that high‐flux hemodialysis is effective in the treatment of severe valproic acid poisoning.

Convulsive Status Epilepticus.

Generalized convulsive status epilepticus (GCSE) is a medical emergency that must be treated rapidly and aggressively to prevent neuronal damage. Treatment should be initiated with intravenous lorazepam, 0.1 mg/kg, given at a rate of no more than 2 mg/min. If convulsions persist for more than 10 minutes or recur more than 20 minutes after lorazepam therapy is started, then fosphenytoin (20 mg of phenytoin equivalents per kilogram) should be infused at a rate of no more than 150 mg/min. If convulsions still continue, intravenous general anesthesia with pentobarbital, benzodiazepine drip, or propofol should be initiated after respiratory support has been established. All patients with GCSE who do not recover consciousness should be monitored with electroencephalography (EEG), and any residual epileptiform activity on EEG, including periodic epileptiform discharges (PEDs), should be considered evidence of continuing GCSE and treated aggressively.

Myoclonus Associated with Lorazepam Therapy in Very-Low-Birth-Weight Infants

Lorazepam is being used with increasing frequency as a sedative in the newborn and the young infant. Concern has been raised with regard to the safety of lorazepam in this age group, especially in very-low-birth-weight (VLBW; < 1,500 g) infants. Three young infants, all of birth weight < 1,500 g, experienced myoclonus following the intravenous administration of lorazepam. The potential neurotoxic effects of the drug (and its vehicle) in this population are discussed. Injectable lorazepam should be used with caution in VLBW infants.

Lorazepam Toxicity in a Premature Infant

To report a case of lorazepam toxicity in a premature infant and discuss the importance of altered pharmacodynamics and pharmacokinetics in the neonatal population. A 2025-g, 33-weeks' gestation infant was born with respiratory distress syndrome that required mechanical ventilation. Lorazepam was used to establish sedation and prevent asynchronous breathing while the infant was on the ventilator. Shortly after the first dose of lorazepam, the infant experienced a seizure and was subsequently given a loading dose of phenobarbital. Lorazepam therapy was continued for sedation. The patient was transferred to our tertiary care center on day 2 of life for evaluation of possible cardiac disease. Upon arrival, the infant was extremely hypotonic and unresponsive; therefore, all sedative medications were discontinued. Two days after admission, the infant continued to exhibit very little spontaneous activity and a lorazepam serum concentration was obtained (63 h after the last dose). Analysis revealed a toxic lorazepam serum concentration of 4453 nmol/L. The patient eventually was weaned to room air and was transported back to the referring hospital. Lorazepam is commonly prescribed in the pediatric population for sedative, anticonvulsant, anxiolytic, antiemetic, and amnestic activity. Few data exist regarding the safety of long-term lorazepam therapy in the neonatal subpopulation. There have been some reports of neurologic toxicity secondary to lorazepam in preterm infants. Its metabolism depends on glucuronidation, an enzymatic process that is very depressed in the premature infant. Accumulation of the drug in the neonate accompanied by clinical toxicity is highly likely. The inability to establish a clear pharmacokinetic-pharmacodynamic relationship, along with the increased incidence of reported adverse events of lorazepam in neonates, is concerning. Clinicians should be aware of the altered metabolism and elimination of lorazepam in the premature infant.

Lorazepam therapy of status epilepticus in children and adolescents

Parmi les 31 sujets de 2 a 18 ans, atteints de divers types d'epilepsie, le lorazepam, a ete efficace dans 25 cas (pas dans les myoclones) avec latence mais aussi duree d'action prolongee. La meilleure efficacite a ete observee sur les convulsions generalisees et les crises partielles elementaires. Pas de reactions secondaires locales ou systemiques

A pilot study of lorazepam-induced amnesia with cis-platinum-containing chemotherapy

Eighteen patients with advanced epithelial ovarian cancer were given 36 courses of cis-platinum-containing chemotherapy at Cedars-Sinai Medical Center. Patients were given lorazepam (Ativan) prior to chemotherapy. Amnesia for the day of chemotherapy was reported in 29 courses. Lack of recall for the chemotherapy infusion and the subsequent 8 hr or greater was reported in 33 of the 36 courses. In two courses, no amnesia effects were noted. No serious side effects of lorazepam therapy occurred and all patients believed that the amnesic effect was beneficial during chemotherapy. Lorazepam (Ativan) appears to be a safe medication to induce amnesia for cis-platinum chemotherapy and deserves further study to determine its effect on anticipatory vomiting, nausea and vomiting, and patient compliance with continued chemotherapy.