Mg Of Lorazepam Research Articles

Dr. Rummans replies

I thank Drs. Heye and Dunne for their comments about our case of malignant catatonia. We were amiss for not including the results of the electroencephalographic examination that was performed as part of the comprehensive neurologic and medical assessment of our patient. The electroencephalographic findings revealed a dysrhythmia, grade 2, consistent with a diffuse disturbance of cerebral function rather than nonconvulsive status epilepticus. Although our patient did not have nonconvulsive status epilepticus, I agree with Drs. Heye and Dunne that this condition should be considered in the differential diagnosis of a patient whose clinical findings are similar to those of our patient. Consequently, an electroencephalogram should be included as part of the assessment of such patients. Malignant Catatonia or Nonconvulsive Status Epilepticus?Mayo Clinic ProceedingsVol. 70Issue 1PreviewIn the July 1994 issue of the Mayo Clinic Proceedings (pages 645 to 650), Boeve and colleagues diagnosed malignant catatonia in a 69-year-old man with progressive behavioral changes and depression, who ultimately became rigid, tremulous, and mute. He “experienced a striking but shortlived improvement” after 1 mg of lorazepam was given intravenously before lumbar puncture. Later, autonomic instability with blood pressure changes, tachycardia, altered respiration, and fever developed. Emergency electroconvul-sive therapy was necessary. Full-Text PDF

Effects of benzodiazepine during a Wingate test

To assess the effects of benzodiazepine alone and associated with caffeine on performance and substrate responses during supramaximal exercise, seven healthy volunteers performed the Wingate test after ingestion of placebo (Pla), benzodiazepine alone, i.e., 1 mg of lorazepam (Bz), and benzodiazepine followed by 250 mg of caffeine (Bz-Caf). Peak power (PP), mean power (MP), and percentage of power decrease (%PD) were determined, and substrate responses were estimated by blood lactate and catecholamine concentrations. Four hours after Bz ingestion, there was a significant decrease in PP (PPBz: 626 +/- 72 vs PPPla: 669 +/- 78 W), maximal blood lactate (La max) (La maxBz: 9.5 +/- 1.5 vs La maxPla: 12.4 +/- 1.8 mmol.l-1), and end-exercise epinephrine (E) (EBz: 339 +/- 113 vs EPla: 672 +/- 247 ng.l-1). No other changes were noted. Caffeine ingestion 1 h before the test (Bz-Caf) corrected the decrease in La max (La maxBz-Caf: 11.5 +/- 1.4 mmol.l-1) and E (EBz-Caf: 573 +/- 190 ng.l-1) but was unable to prevent the impairment of performance (PPBz-Caf: 625 +/- 68 W vs PPPla). Moderate benzodiazepine intake significantly altered performance and substrate responses during supramaximal exercise. Moderate caffeine intake antagonized the metabolic but not the performance effects of 1 mg of lorazepam.

A Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of Ipsapirone Versus Lorazepam in Patients With Generalized Anxiety Disorder

This multicenter, double-blind, placebo-controlled, randomized study compared the efficacy, safety, and tolerability of ipsapirone (an azapirone anxiolytic) at daily dose levels of 10.0 to 30.0 mg with a daily dose of 2.0 to 6.0 mg of lorazepam (a benzodiazepine) or placebo when given to outpatients with generalized anxiety disorder (GAD) of moderate or greater severity. A total of 317 outpatients with a primary diagnosis of GAD according to DSM-III criteria (at least 1 month's duration) were randomized. Study entry criteria at the time of screening and at baseline included a Hamilton Rating Scale for Anxiety (HAM-A) score of 18 or more, a Covi Anxiety Scale score of 8 or more, and a Raskin Depression Scale score of 7 or less. The study design consisted of a 1-week, single-blind placebo evaluation, a 4-week, double-blind acute treatment period, and a 4-week extension period, followed by a 2-week, single-blind placebo withdrawal period. Efficacy was measured by changes in the HAM-A and Clinical Global Impression Scale and by evaluations of the Hamilton Rating Scale for Depression and Zung-Anxiety Self-Rating scale. The Raskin and Covi scales were performed at screening and baseline only. Withdrawal reactions were assessed during the withdrawal period by the Physician Withdrawal Checklist and by a patient self-rating checklist. Two-hundred sixty-three patients were valid for the analysis of efficacy in the ipsapirone (N = 87), lorazepam (N = 89), and placebo (N = 87) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Compatibility and Stability of Ondansetron Hydrochloride, Dexamethasone, and Lorazepam in Injectable Solutions

The stability of ondansetron hydrochloride, dexamethasone sodium phosphate, and lorazepam in 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) minibags and glass bottles was studied. Triplicate solutions of 8 or 32 mg of ondansetron (as the hydrochloride salt) mixed with 20 mg of dexamethasone phosphate (as the sodium salt) with or without 2 mg of lorazepam were compounded in 50-mL PVC minibags and glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection and stored at 23-25 degrees C. Duplicate measurements were performed when drugs were added and at 1, 2, 4, 8, and 24 hours after addition. Samples of the 32-mg ondansetron admixtures were collected under aseptic conditions to inspect for precipitation and to count particles with a laser particle analyzer. Samples of all admixtures were evaluated for chemical stability by stability-indicating high-performance liquid chromatography. Ondansetron hydrochloride and dexamethasone were physically compatible and chemically stable for up to 24 hours under the study conditions. The concentration of lorazepam in PVC containers dropped below 90% of the original concentration within four hours. In addition, particle counts in lorazepam-containing solutions were higher when 0.9% sodium chloride injection was the diluent than when 5% dextrose injection was the diluent. In admixtures containing all drugs, ondansetron hydrochloride and dexamethasone sodium phosphate in 5% dextrose injection or 0.9% sodium chloride injection were stable for up to 24 hours when stored in PVC bags or glass bottles.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased Systemic Clearance of Lorazepam in Humans With Spinal Cord Injury

Serum concentration-time course profiles, serum protein binding, and disposition parameters of lorazepam (LRZ), a benzodiazepine with sedative-hypnotic, anxiolytic, and anti-seizure properties, were studied as part of a systematic effort to define population-specific pharmacokinetic behavior in humans with chronic spinal cord injury (SCI). Twenty-four healthy subjects (nine tetraplegic, six paraplegic, nine able-bodied) were given an IV bolus of 2.0 mg of LRZ. Noncompartmental estimation of pharmacokinetic parameters disclosed a 37% decrease in the total systemic clearance (CL) of LRZ in tetraplegic patients. Altered LRZ clearance was observed independently of significant changes in volume of distribution or serum protein binding. The early elimination of LRZ (0-10 hr) was characterized by wide fluctuations in serum concentration suggestive of impaired enterohepatic circulation and could be distinguished from LRZ elimination observed in able-bodied subjects. We conclude that decreased systemic CL and the altered terminal elimination profile of LRZ are attributable to the pathophysiology of SCI.

Alprazolam withdrawal presenting as delirium after cardiac surgery

A 4%year-old white man experienced delirium after coronary revascularization. The patient had had increasing frequency of exertional angina over a 4-month period. His past medical history included an uncomplicated inferior wal1 myocardial infarction (MI) 2 years prior to admission for which he had been treated with diltiazem, 60 mg, four times daily, atenolol, 50 mg, twice daily, and isosorbide dinitrate, 30 mg, four times daily. He also quit smoking at that time. At the time of this admission, he was exercising regularly and appeared to be an exceptionally fit, yet anxious individual. He weighed 76 kg and was 178 cm tal], had a normal physical examination, and had no other medical conditions or cardiac risk factors. He reported an allergy to penicillin, minimal alcohol use, and no recreational drug use. Cardiac catheterization showed lesions in the left anterior descending, total occlusion of the distal circumflex, and total occlusion of the posterior descending and posterior lateral right coronary systems. He desired the operation and was scheduled for coronary revascularization involving three distal grafts. Premedication consisted of 2 mg of lorazepam, orally, the night prior to surgery, nifedipine, 30 mg, propranolol, 30 mg, isosorbide dinitrate, 30 mg, morphine, 5 mg, intramuscularly (IM), and an additiona12 mg of lorazepam the morning of operation. On arrival in the operating room, the patient appeared drowsy, yet claimed to be fully alert. Blood pressure (BP) varied between 110170 and 80/40 mm Hg with a heart rate (HR) of 55 beats/min, and arterial oxygen saturation was 97% by pulse oximeter. Invasive monitors were placed without incident during which time an additional 3 mg of lorazepam was given for sedation. Pulmonary artery pressure (PAP), pulmonary capillaty wedge pressure (PCWP), and cardiac output (CO) were 26/15 mm Hg, 12 mm Hg, and 5.6 Umin, respectively. Mixed venous oxygen saturation was 81% at the time of the pulmonary artery catheter insertion, and increased to 91% with intubation, after anesthesia was uneventfully induced with 1,000 ug of fentanyl, 4 mg of midazolam, and 8 mg of vecuronium. Nitroglycerin, 0.5 &kg/min, was given intravenously prior to and during induction. One unit of blood was phlebotomized at that

Anesthetic Requirements during Electromagnetic Extracorporeal Shock Wave Lithotripsy

An important aspect of modern extracorporeal shock wave lithotripsy is the ability to perform the procedure without anesthesia. Between June 1987 and April 1990, a total of 7,500 treatments were performed in our Lithotripsy Unit, using the Lithostar (Siemens AG, Erlangen, FRG): moreover 80% of the treatments were carried out as an anesthesia-free outpatient service. All treatments were reviewed for anesthetic requirements. Epidural anesthesia was performed in 74/7,500 (0.98%) treatments: during the initial period, the first 70 procedures were systematically performed under epidural anesthesia, and in 4 later cases of simultaneous endoscopic stone manipulation. Local skin infiltration was applied at the coupling site in 658/7,500 (8.7%) treatments. With increasing experience and technological improvement, 6,229/7,500 (83%) procedures were performed later on with only mild sedation: 1 mg of lorazepam orally 30 min before the treatment. Intravenous sedation was required in 510/7,500 (6.8%) cases because of painful local irritation, especially when treating calculi close to sites where shock waves can progress along the ribs. General anesthesia was required in all 28 children (0.4%).

Low Incidence of Extrapyramidal Symptoms in Treatment of Delirium with Intravenous Haloperidol and Lorazepam in the Intensive Care Unit

We retrospectively reviewed 11 patients in an intensive care unit who were treated for delirium with intrave nously administered haloperidol and lorazepam. The cu mulative doses for each episode of delirium ranged from 25.5 to 1,929 mg of haloperidol and 19.5 to 2,274 mg of lorazepam. Neuroleptic-induced rigidity developed in 1 patient. After administration of the neuroleptic was dis continued, there were no residual extrapyramidal symp toms.

Studies on Lorazepam as a Premedicant for Thiopental Anaesthesia in the Dog

Four mg of lorazepam was given intravenously 5 min prior to thiopental anaesthesia in 5 clinically healthy dogs weighing 14 +/- 2 kg and aged about 10-12 months. Animals required only 7.0 +/- 1.5 ml of 5% thiopental sodium to achieve surgical anaesthesia which lasted about 30.4 +/- 3.3 minutes. There was adequate muscle relaxation and loss of pedal and palpebral reflexes. Five min after administration of lorazepam, there was no appreciable change in various cardiopulmonary dynamics. However, there was moderate arterial hypertension, tachycardia and arterial hypoxemia 15 min after the onset of the thiopental anaesthesia. There was no respiratory depression. The lorazepam-thiopental combination was also attempted in 16 clinical cases varying from repair of fractures of long bones (9), mammary tumour (2), ear haematoma (1), ear cropping (1), tail gangrene (2) and rectal prolapse (1). This combination of anaesthesia proved extremely useful for orthopaedic surgery as the muscle relaxation was adequate and reduction of the fractured ends was comparatively easier.

Rate of Increase of Plasma Lorazepam Concentrations; Absence of Influence upon Subjective and Objective Effects

This study was designed to investigate the relationship between subjective and objective effects of a benzodiazepine on the one hand, and the rate of increase of plasma concentration on the other. The pharmacokinetic variables of 10 normal volunteers were calculated following a single intravenous bolus injection of 1 mg of lorazepam, a benzodiazepine devoid of active metabolites. In six of the subjects rates of infusion could be calculated in order to achieve the same plasma concentration after 1 hour and 2 hours. In the main study, lorazepam was infused at two different rates on two separate occasions, with a third placebo infusion occasion. A balanced crossover design was used with single-blind procedures. Plasma concentrations, subjective ratings, quantified EEG recordings, and psychological performance tests were estimated before and at 1, 2, and 3 hours after the start of the infusions. The peak plasma concentrations achieved were the same at the end of the two drug infusions. EEG and some performance tests paralleled the plasma concentrations fairly closely, but subjective effects did not reach their maximum until the 3-hour point and were significantly greater after the 2-hour than after the 1-hour infusion. Drug doses, rate of penetration into the brain, and duration of exposure to the increasing concentrations of lorazepam seem more relevant factors for the time course and the intensity of the various initial effects of the drug than the rate of increase of plasma levels.

Double-blind Study of Lorazepam and Diazepam in Status Epilepticus

Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted.

Double-blind study of lorazepam and diazepam in status epilepticus

Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted. (<i>JAMA</i>1983;249:1452-1454)

Lorazepam Solubility in and Sorption from Intravenous Admixture Solutions

The solubility of lorazepam in aqueous i.v. solutions and the potential for lorazepam sorption from i.v. admixtures in flexible polyvinyl chloride (PVC) bags and tubing were determined. The solubility of triplicate samples containing 15 mg of lorazepam and 20 ml of deionized water, 5% dextrose, lactated Ringer's, or 0.9% sodium chloride injections was determined. The decrease in lorazepam concentration from a 40-micrograms/ml admixture solution in 5% dextrose injection stored in PVC bags was calculated. Duplicate samples of (1) 50 ml in 50-ml PVC bags, (2) 100 ml in 50-ml PVC bags, and (3) 100 ml in 250-ml PVC bags were laid flat to approximate surface areas of 80, 160, and 270 sq cm, respectively, to determine sorptive loss. The continuous flow sorption of lorazepam from duplicate admixtures was tested at three rates through 180- and 350-cm PVC tubing. The solubility of lorazepam in deionized water, 5% dextrose, lactated Ringer's, and 0.9% sodium chloride injections was 0.054, 0.062, 0.055, and 0.027 mg/ml, respectively. Lorazepam solubility was pH dependent. The decrease in lorazepam concentration from the admixture solution stored in PVC bags for up to 121 hours followed biexponential kinetics that account for both the sorptive loss of the drug and the increasing ratio of bag surface area to solution volume. At least 90% of the initial concentration was maintained for five and two hours when the ratio was less than 2.0 and 2.7-2.8 sq cm/ml, respectively. The admixture solution retained a minimum of 95% of initial concentration when 50-ml aliquots were delivered at 600, 200, and 100 ml/hr through both sizes of PVC tubing. Because of its adequate aqueous solubility and slow sorption by PVC delivery components, lorazepam is suited for dilution in i.v. admixtures for treating conditions with intermittent or continuous infusions.

Effects of lorazepam on rate of forgetting, on retrieval from semantic memory and on manual dexterity

Using a double-blind procedure, 16 out of 32 volunteer subjects (students) each took 2.5 mg of lorazepam (Ativan) orally and the remainder took a placebo. To overcome the problem of wide variation in individual tolerance to the drug, impairment on a task unrelated to memory (a manual dexterity task) was used to divide drug subjects into a group appreciably affected by the drug. subgroup 1, and a group minimally affected, subgroup 2. Only subgroup 1 showed consistent impairment of episodic memory. Both subgroups showed some impairment in a semantic memory task (generation of words from a specified category), but this was confined to the rate at which the task was carried out. The main aim of the experiment was to examine the effect of lorazepam on the rate of forgetting of word lists when drug and control subjects' initial recall levels were equalized. There was no evidence that the drug affected rate of forgetting: this suggests that it does not affect retention. There was also no evidence that it affected retrieval, since there was no impairment in the recall of material presented before administration of the drug. Hence its locus of action is attributed to input, specifically to impaired encoding of contextual information.

Anesthesia for outpatient head and neck aesthetic surgery.

An approach to outpatient anesthesia using drugs that have reversible or very short-acting effects is described, along with a method of monitoring patients using pulse rate to assess tranquility. Preoperatively, the patient is given 1 mg of lorazepam the evening before surgery and sublingual lorazepam 1 mg combined with hydroxyzine 50 mg intramuscularly one hour before surgery. Before infiltration of local anesthesia, intravenous diazepam in 2.5 mg increments is given if needed, followed by a mixture of meperidine and pentazocine intravenously in exactly a 10:1 ratio. If hypnosis is needed, methohexital can be administered using a 0.2% drip by infusion pump. If respiratory depression is seen, intravenous naloxone, 0.2 to 0.4 mg, can be given to reverse any residual effects of meperidine and pentazocine, or, if large doses of intravenous diazepam have been used in a very agitated patient, one can administer physostigmine 1 to 2 mg.

Clinical pharmacokinetics of lorazepam. II. Intramuscular injection.

A single dose of 4 mg of lorazepam was injected into the deltoid muscles of six healthy male volunteers. Multiple venous blood samples were drawn during 48 hr after the dose and all urine was collected for 24 hr after the dose. Concentrations of lorazepam and its major metabolite, lorazepam glucuronide, were determined by electron-capture gas-liquid chromatography. Lorazepam was rapidly absorbed from the injection site, reaching peak concentrations within 3 hr. Mean pharmacokinetic pamrameters for unchanged lorazepam were: apparent absorption half-life: 21.2 min; elimination half-life: 13.6 hr; volume of distribution: 0.9 L/kg; total clearance: 58.2 ml/min. Lorazepam glucuronide rapidly appeared in plasma, reached peak concentrations within 12 hr of the dose, then was eliminated approximately in parallel with the parent drug. Within 24 hr a mean of 47.6% of the dose was recovered in the urine as lorazepam glucuronide and less than 0.5% was recovered as unchanged lorazepam.

Lorazepam as a premedicant for day‐case surgery: an assessment

The sedative effect of 2 mg of lorazepam was assessed in eleven patients undergoing minor "day case" surgery and the results compared with a control group of eleven patients receiving a placebo. Sedation was assessed by a scoring method and quantified in terms of change in plasma cortisol levels. The results indicate that 2 mg of oral lorazepam produces good sedation (superior to nitrazepam in terms of plasma cortisol reduction) and has a postoperative anti-emetic effect but its prolonged duration of action makes it unsuitable for patients returning home within 8 hours of premedication.

Drug induced hypovigilance identification by means of an EEG Fractal Dimension Classifier

Event Abstract Back to Event Drug induced hypovigilance identification by means of an EEG Fractal Dimension Classifier Emmanouil Michail1*, Ioanna Chouvarda1 and Nicos Maglaveras1 1 Magdeburg University, Germany Aim: This work aims at identifying drug induced hypovigilance caused by lorazepam administration, a psychoactive drug with hypnotic effects (1). The main objective is to classify subjects who have taken 2.5 mg of lorazepam or placebo based on the brain activity changes that drug administration induces. Methods: EEG data were recorded from 14 healthy male subjects aged between 18 and 40 years. For each subject two different conditions were examined: lorazepam 2.5 mg single administration (verum state) and placebo administration (placebo state) early in the morning. For each of these two conditions EEG was recorded with eyes closed during 3 minutes in resting condition at a sampling frequency of 256Hz. 20 EEG channels were recorded at different times during the first and the second day of the experiment. After artefact removal and filtering, a single Fractal Dimension value was extracted for each 3-minute recording. Higuchi’s method (2) was used, with maximum time interval kmax=15. A linear classifier was applied to FD values of the same time period and EEG channel, in order to automatically classify between placebo and verum state. “Leave one out” cross validation approach was adopted. Results: In almost all subjects, FD has a higher value in verum case than in placebo case at the first 8 hours after drug intake. Some leftover effects are still noticeable 12 hrs after drug administration but not during next morning. Best discriminant results occur 2 hours after drug administration. At that time, classifier reaches 100% accuracy for channels F3, Fz and P4. At the same time, mean specificity over all channels was 97.5% and maximum specificity was 100% whereas, mean sensitivity over all channels was 85% and maximum sensitivity was 92.8571%. Conclusion: The practical application of these findings would be an automatic system able to detect if a subject is under the influence of psychoactive drugs that cause sleepiness. Acknowledgments: Special thanks to the research group of FORENAP for making available the dataset used in this study.