BACKGROUND AND METHODS: Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, double-blind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. RESULTS: Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam plus phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12-hour study period, the incidence of adverse reactions, or the outcome at 30 days. CONCLUSIONS: As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam plus phenytoin, it is easier to use.

PURPOSE: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures. METHODS: Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel-Haenszel analyses; random effects model used if heterogeneity was significant. RESULTS: Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32-0.82) and cerebral malaria (RR, 0.36; CI, 0.23-0.56). Diazepam for contrast media-associated seizures (RR, 0.10; CI, 0.01-0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25-0.71; TBI: RR, 0.33; CI, 0.19-0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17-0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04-0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76-2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75-2.25). CONCLUSIONS: Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out.

PURPOSE: The study reviewed emergent cases of nonconvulsive status epilepticus (NCSE) to evaluate causes of diagnostic and management delay and examined frequent diagnostic features suggestive of NCSE. METHODS: In a retrospective study, we assessed the clinical presentation of 23 patients with one or more NCSE episodes, their medical history, EEG, and antiepileptic drug (AED) treatment. We also evaluated causes of diagnostic delay in patients referred to the emergency room (ER) in confusional states. RESULTS: There was considerable overlap in clinical features of patients with complex partial SE (CPSE) and generalized nonconvulsive SE (GNSE). Delays in seeking medical attention were common. Diagnosis was significantly delayed in 10 patients. Three cases illustrate the possible markedly different presentations of NCSE. CONCLUSIONS: NCSE often goes unrecognized or is mistaken for behavioral or psychiatric disturbance. The pleomorphic clinical presentation of NCSE indicates that EEG and a therapeutic trial of AEDs afford the best diagnostic measures in acute waxing and waning confusional states associated with agitation, bizarre behavior, staring, increased tone, mutism, or subtle myoclonus.

OBJECTIVE: To describe the goals of sedative use in the intensive care unit and review the pharmacology of commonly used sedative drugs as well as to review pertinent publications in the literature concerning the comparative pharmacology of these drugs, with emphasis on outcomes related to sedation and comparative pharmacoeconomics. DATA SOURCES: Publications in the scientific literature. DATA EXTRACTION: Computer search of the literature with selection of representative articles. SYNTHESIS: Proper choice and use of sedative drugs is based on knowledge of the pharmacology of commonly used agents and is an essential component of caring for patients in the intensive care unit. The large variability in pharmacokinetics and pharmacodynamics in the critically ill make it difficult to directly compare agents. Midazolam provides rapid and reliable amnesia, even when administered for low levels of sedation. Propofol may be useful when deeper levels of sedation and more rapid awakening are required. Lorazepam can be used for long-term sedation in more stable patients if rapidity of effect is not required. Further investigation in assessment of depth of sedation in the critically ill is needed. Continued study of costs, side effects, and appropriate dosing strategies of all sedative agents is needed to answer questions not sufficiently addressed in the current literature. Conclusion: An individualized approach to sedation based on knowledge of drug pharmacology is needed because of confounding variables including concurrent patient illness, depth of sedation, and concomitant use of analgesic agents.(Crit Care Med 2000; 28:854-866) KEY WORDS: sedation; anxiolysis; critical care; midazolam; lorazepam; propofol; benzodiazepines; intensive care unit; pharmacoeconomics; critical illness

Presented here are four cases of catatonic reactions which were felt to be neuroleptic induced. Intravenous lorazepam was rapidly effective in reversing the catatonia and attendant symptoms. Lorazepam's previous uses and pharmacological profile are discussed. Reviewed briefly are catatonia and its neuroleptic-induced forms. Possible mechanisms responsible for the therapeutic effect of intravenous lorazepam in these cases are then examined.

A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam, hyoscine butylbromide, and ispaghula husk in 12 randomised blocks of eight patients with the irritable bowel syndrome (IBS). Each of the three agents caused a sustained symptomatic improvement in some of the patients, although only with ispaghula was the difference between the real and dummy preparation statistically significant. When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial. Seven patients improved among the 12 who received potent preparations of all three agents, and between four and six patients improved in the groups receiving one or two of the potent preparations. These therapeutic results, though far from perfect, show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects. Similar combinations of other therapeutic agents may be more effective, but it will be possible to determine this only by carrying out factorial therapeutic trials.

A previous therapeutic trial of factorial design showed that a combination of a psychotropic drug, a smooth-muscle relaxant, and a bulk former (lorazepam, hyoscine hydrobromide, and ispaghula husk) relieved symptoms of the irritable bowel syndrome more effectively than the same agents given singly. Another trial of similar design was undertaken to compare each of these three agents with another having the equivalent clinical actions--namely, Motival (fluphenazine/nortriptylene mixture), mebeverine, and bran. Ninety-six patients took part; all received three agents, one from each of the three pairs being compared, and no placebos were used. Fifty-six patients reported a sustained symptomatic improvement, which was a significantly higher incidence than in the previous trial, when placebos were used. Ispaghula was significantly more effective than bran. The combination of ispaghula, Motival, and mebeverine improved 11 out of 12 patients--significantly more than bran, Motival, and hyoscine (five improved), or bran, lorazepam, and mebeverine (four improved). Mebeverine was significantly more effective when combined with Motival (18 out of 24 improved) than with lorazepam (10 improved). These results confirm the value of a combined therapeutic approach to the relief of the irritable bowel syndrome and suggest the possibility of synergism between agents.

There is evidence for two types of sleep spindle activity, one with a frequency of about 12 cycles/s (cps) and the other of about 14 cps. Visual examination indicates that both spindle types occur independently, whereby the 12-cps spindles are more pronounced in the frontal and the 14-cps spindles in the parietal region. The purpose of this paper is to provide more information about the exact topography of these patterns. First the occurrence of distinct signals in anterior and posterior brain regions was verified using pattern recognition techniques based on matched filtering. Thus the existence of two distinct sources of activity located in the frontal and parietal region of the brain, respectively, was demonstrated using EEG frequency mapping. Evaluation of sleep recordings showed high stability both in the frequency and location of the presumed spindle generators across sleep. Pharmacological effects of lormetazepam and zopiclone on both spindle types were investigated. Both substances enhanced the sleep spindle activity recorded from the frontal and parietal electrodes, but this increase was more pronounced in the parietal brain region.

OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. DESIGN: This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). SETTING: A university medical center substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. RESULTS: Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Status epilepticus (SE) is one of the most common neurologic emergencies in children, adolescents, and young adults. SE may be due to acute neurologic conditions such as meningitis, encephalitis, or stroke, complicated febrile seizures, intractable epilepsy, degenerative diseases, intoxication, or may be the first manifestation of epilepsy. Initial treatment of convulsive SE is usually with an intravenous benzodiazepine (BZD)[lorazepam (LZP) or diazepam (DZP)], phenobarbital (PB), or phenytoin (PHT). LZP is less likely to cause respiratory depression than DZP and is therefore preferred. Sequelae and risk for recurrence of SE are primarily related to the underlying cause. Refractory SE (RSE) is most often symptomatic of an acute neurologic condition or neurodegenerative disease. Treatment for RSE is difficult, usually requiring intensive support of vital functions. Reported treatments for RSE include very high dose PB, continuous infusions of pentobarbital or BZDs (DZP, midazolam), lidocaine, inhalation anesthesia, and propofol. Outcome is related to underlying cause. Nonconvulsive SE may present as confusion or may mimic psychiatric illness. Response to BZDs is usually rapid but may not be sustained. Rapid initiation of oral or rectal valproate may be useful. Epilepsia partialis continua (EPC) is almost always due to an acute or chronic destructive lesion. Surgical treatment may be the only effective modality in some children with EPC. Acute treatment of breakthrough seizures and clusters of seizures at home with rectal BZDs (usually DZP, 0.2-0.5 mg/kg) may prevent progression to SE in some children and adolescents and reduce the need for visits to emergency facilities.