Intravenous Lorazepam Research Articles

Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus

BackgroundEarly termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.MethodsThis double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points.ResultsAt the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes. Adverse-event rates were similar in the two groups.ConclusionsFor subjects in status epilepticus, intramuscular midazolam is at least as safe and effective as intravenous lorazepam for prehospital seizure cessation. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, ClinicalTrials.gov NCT00809146.)

New Variant Creutzfeldt-Jacob Disease Presenting With Catatonia: A Rare Presentation

New Variant Creutzfeldt-Jacob Disease Presenting With Catatonia: A Rare Presentation

Density spectral array analysis of SREDA during EEG-video monitoring

ObjectiveTo report the temporal pattern of subclinical rhythmic electrographic discharge of adults (SREDA) and its response to lorazepam during EEG-video monitoring. MethodsWe recorded EEG-video for 3days in a patient with SREDA, who was previously misdiagnosed with generalized epilepsy. Because SREDA had a very prominent signature on density spectral array (DSA), we used DSA to study the pattern of SREDA over the diurnal cycle, and the response to intravenous lorazepam. ResultsSREDA occurred in both waking and sleep, but tended to occur in single bursts in waking and in longer clusters during sleep. Lorazepam suppressed SREDA. ConclusionsThe temporal pattern of SREDA varies during the sleep–wake cycle. Lorazepam appears to suppress SREDA. SignificanceResponse to lorazepam cannot distinguish SREDA from electrographic seizure activity.

Pharmacokinetics of Intravenous Lorazepam in Pediatric Patients with and without Status Epilepticus

To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE. Ten hospitals in the Pediatric Emergency Care Applied Research Network enlisted patients 3 months to 17 years with convulsive SE (status cohort) or for a traditional pharmacokinetics study (elective cohort). Sparse sampling was used for the status cohort, and intensive sampling was used for the elective cohort. Non-compartmental analyses were performed on the elective cohort, and served to nest compartmental population pharmacokinetics analysis for both cohorts. A total of 48 patients in the status cohort and 15 patients in the elective cohort were enrolled. Median age was 7 years, 2 months. The population pharmacokinetics parameters were: clearance, 1.2 mL/min/kg; half-life, 16.8 hours; and volume of distribution, 1.5 L/kg. On the basis of the pharmacokinetics model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations >30 to 50 ng/mL for 6 to 12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg. Lorazepam pharmacokinetics in convulsive SE is similar to earlier pharmacokinetics measured in pediatric patients with cancer, except for longer half-life, and similar to adult pharmacokinetics parameters except for increased clearance.

RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): A double‐blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics

Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting has been shown to be associated with improved outcomes. However, an increasing number of Emergency Medical System (EMS) protocols use an intramuscular (IM) route because it is faster and consistently achievable. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial) is a double-blind randomized clinical trial to determine if the efficacy of IM midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). Children and adults with >5 min of convulsions who are still seizing after paramedic arrival are administered study medication by IM autoinjector or IV infusion. The primary efficacy outcome is absence of seizures at emergency department (ED) arrival, without EMS rescue therapy. Safety outcomes include acute endotracheal intubation and recurrent seizures. Secondary outcomes include timing of treatment and initial seizure cessation. At the time of writing this communication, enrollment of all subjects is near completion and the study data will soon be analyzed.

Status Epilepticus–Induced Hyperemia and Brain Tissue Hypoxia After Cardiac Arrest

To report changes of cerebral blood flow and metabolism associated with status epilepticus after cardiac arrest. Case report. Neurological intensive care unit in a university hospital. An 85-year-old man resuscitated from out-of-hospital cardiac arrest underwent brain multimodality monitoring and treatment with therapeutic hypothermia. Changes of cerebral blood flow and metabolism. Repetitive electrographic seizure activity detected at the start of monitoring was associated with dramatic reductions in brain tissue oxygen tension and striking surges in cerebral blood flow and brain temperature. Intravenous lorazepam and levetiracetam administration resulted in immediate cessation of the seizures and these associated derangements. The lactate to pyruvate ratio was initially elevated and trended down after administration of anticonvulsants. Brain multimodality monitoring is a feasible method for evaluating secondary brain injury associated with seizure activity after cardiac arrest.

The horse with stripes: a case of anti-NMDA receptor encephalitis.

The horse with stripes: a case of anti-NMDA receptor encephalitis.

The Horse With Stripes

The Horse With Stripes

Involuntary Movements Associated with Cetirizine Use

Back to table of contents Previous article Next article Communications and UpdatesFull AccessInvoluntary Movements Associated with Cetirizine UseCandace A. Romo, M.D., Kaustubh G. Joshi, M.D., and Brian M. Waters, M.D.Candace A. RomoSan Antonio, Tex.Search for more papers by this author, M.D., Kaustubh G. JoshiSan Antonio, Tex.Search for more papers by this author, M.D., and Brian M. WatersSan Antonio, Tex.Search for more papers by this author, M.D.Published Online:1 Aug 2011https://doi.org/10.1176/appi.ajp.2011.11040534AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Cetirizine is approved by the U.S. Food and Drug Administration (FDA) for allergic rhinitis in all age groups (1). Published reports have described cetirizine-induced dystonic reactions in the pediatric patient population and in one adult (2–4). We present the case of an adult who developed involuntary movements associated with cetirizine use and discontinuation.Case ReportA 24-year-old Caucasian woman presented to the local hospital emergency department with a nose laceration she sustained from walking into a glass window after acute alcohol intoxication (her blood alcohol level was 140 mg/dL). She reported taking 10 mg/day of cetirizine for 3 months, daily valacyclovir (for herpes simplex virus 1), and depot medroxyprogesterone. She denied a history of medication side effects, denied taking more than the recommended dosage, and was not taking over-the-counter or herbal products. She denied a history of head injuries, seizures, or loss of consciousness, and she also denied treatment with psychotropic medications. Initially, results from her physical examination were unremarkable with the exception of a superficial laceration on her nose. The results of laboratory testing, including thyroid-stimulating hormone and urine toxicology, were all within normal limits or negative.While in the emergency department, the patient developed acute involuntary “bizarre grimacing” and dysarthria. There was no evidence of oculogyric crisis, torticollis, tongue protrusions, opisthotonos, gait disturbances, or weakness in her extremities. She did not lose consciousness, and results of her neurological examination were negative. She was given intravenous diphenhydramine (50 mg), benztropine (2 mg), and lorazepam (2 mg). Neuroimaging results of her head and spine were negative, and her dystonia had resolved by the time a neurologist arrived at her bedside.A follow-up call 1 month later revealed that the patient had stopped taking cetirizine after she was discharged from the emergency department. She reported facial twitching on the day after discharge. Over the course of the month, she experienced two episodes of difficulty walking, hand “discoordination,” and “muscle jerks of her throat.” These episodes lasted approximately 20 minutes. An outpatient neurology consultation was arranged at the time of the call, but it is not known whether she kept that appointment.DiscussionCetirizine is a carboxylated metabolite of hydroxyzine (a piperazine histamine H1 receptor antagonist) (1). Piperazines have central dopamine D2 receptor blockade (5). Cetirizine's large size, lipophobic nature, and greater affinity for peripheral H1 receptors are believed to reduce CNS penetration and central side effects (2). However, one positron emission tomography study of cetirizine revealed approximately 30% H1 receptor binding in the cerebral cortex (1, 2). Cetirizine has negligible anticholinergic activity (6). We speculate that as a piperazine derivative, cetirizine blocked the striatal D2 receptors and resulted in an acute dystonic reaction in our patient. In addition, we also speculate that our patient's 3-month cetirizine use resulted in D2 receptor hypersensitivity similar to that observed in long-term antipsychotic use, with subsequent involuntary movements after its discontinuation. It is also possible that her cetirizine use and the subsequent development of involuntary movements are independent events. More research is needed to clarify cetirizine's effect on central D2 receptors.San Antonio, Tex.The authors report no financial relationships with commercial interests. The opinions expressed in this letter do not reflect those of the Department of Defense or the United States Air Force.This letter was accepted for publication in May 2011.

Neurocognitive Problems in Critically Ill Older Adults: The Importance of History

Older adults are at greater risk for the development of neurocognitive problems during critical illness than are their younger counterparts, particularly if they have preexisting cognitive impairment. Neurocognitive problems result in longer duration of mechanical ventilation and extended intensive care unit (ICU) and hospital lengths of stay. These problems can persist after discharge and affect quality of life for both the patient and family caregivers. Accurate assessment of neurocognitive status necessarily guides selection of interventions. Consider the case of Mrs. Crane, an older woman who developed flank pain, nausea, vomiting, and altered mental status while travelling with her husband. She was first admitted emergently to a community hospital and then transferred to the University Medical Center with a diagnosis of intrahepatic abscesses. She developed septic shock and renal failure and was intubated and mechanically ventilated shortly after admission to the University Hospital. Medical management included vasopressor medications for hypotension and intermittent hemodialysis for acute renal failure. Mrs. Crane’s ICU course was notable for prolonged periods of psychomotor agitation, which were treated with intravenous lorazepam, morphine,and fentanyl. The sedative and analgesic medications were titrated to manage physiologic (hypertension, tachycardia, tachypnea) and behavioral symptoms (head thrashing, active in bed, facial grimacing, pulling at wrist restraints, “bucking” ventilator, wincing, lifting arms and legs off bed, and “resisting care”). Ventilator weaning attempts were avoided or aborted when agitation was associated with a reduction

Intravenous Diazepam, Midazolam and Lorazepam in Acute Seizure Control

To evaluate the safety and efficacy of three benzodiazepine drugs: Lorazepam, Midazolam and Diazepam, when given parenterally in the control of acute seizure. One hundred and twenty children of either sex in the age group 6 month to 14 years brought convulsing to the pediatric emergency services, were enrolled in the study. These were randomised to three equal groups of 40 patients each; Group A-received diazepam, Group B-received midazolam, Group C-received lorazepam. End of seizure episode (clinically) was defined as cessation of visible epileptic phenomenon or return of purposeful response to external stimuli within 15 min of drug administration. A stopwatch was used to measure various time intervals accurately. The patient's vitals were monitored and recorded in a predesigned performa. The primary outcome was the time to seizure cessation and secondary outcome was the side effects of the drugs. Data obtained was analysed statistically using student's t-test and chi-square test. Mean duration to clinical seizure cessation was comparable among the three groups. For diazepam group it was 84.94 ± 38.56 s, for midazolam group it was 92.69 ± 25.97 s, for lorazepam group it was 91.12 ± 23.58 s. Number of patients with any abnormality in seizure cessation were significantly higher in diazepam group [11/40 (27.5%)] when compared to the midazolam [4/40 (10%)] and lorazepam group [2/40 (5%)]. Number of patients requiring 2nd dose to control seizures was significantly higher [4/40 (10%)] in diazepam group when compared to lorazepam group [0/40 (0%)] but diazepam and midazolam and midazolam and lorazepam were comparable in this aspect.All the three drugs were comparable in terms of side effects except excessive somnolence which was significantly higher in diazepam group. All the three groups were comparable in terms of time to clinical seizure cessation, seizure recurrence and uncontrolled seizures after drug administration. However, number of patients requiring second dose to control seizures were significantly higher in diazepam group when compared to lorazepam group. Excessive somnolence and sedation occurred more frequently with diazepam.

Intranasal versus intravenous lorazepam for control of acute seizures in children: A randomized open‐label study

Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6-14 years who presented with acute seizures. This was a randomized open-label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty-one consecutive children aged 6-14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately -9.7%, with an a priori cutoff for noninferiority of -10%. Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.

The serotonin syndrome—the need for physician’s awareness

BackgroundSerotonin syndrome is a potentially life-threatening adverse drug reaction that results from therapeutic drug use, usually of selective serotonin reuptake inhibitors (SSRIs), intentional excessive use or interactions between various drugs.Case presentationA 16-year-old Caucasian boy presented to our emergency department (ED) with alteration in his mental status for 6 h prior to arrival. On physical examination in our ED, he was combative and disoriented to time, place and person. He was febrile, hypertensive and tachycardic as well. He had intermittent rigid extremities with myoclonus of both lower extremities. A diagnosis of serotonin syndrome (SS) was made based on history of intake of fluoxetine and clinical signs, which included presence of inducible clonus and agitation. The child received supportive care involving intravenous fluids and intravenous lorazepam. The child was back to his baseline mental status and had a normal neurological exam by 24 h and was discharged home later for follow-up with a psychiatrist.ConclusionsSS occurs with increasing frequency, and most cases resolve with prompt recognition and supportive care. Failure to make an early diagnosis and to comprehend adverse pharmacological effects of therapy can lead to adverse outcomes.

Herpes Encephalitis Presenting With an Opercular Syndrome and Epilepsia Partialis Continua

The opercular syndrome is a rare form of pseudobulbar palsy that is characterized by automatic-voluntary dissociative weakness of the face in addition to weak masticatory and pharyngeal muscles. It is typically seen in the setting of an acute stroke or in association with various congenital malformations of the cortex. It has also been described rarely in association with herpes encephalitis but with an abnormal cerebrospinal fluid (CSF) cell count. We report on a 65-year-old-man with an opercular syndrome associated with epilepsia partialis continua (EPC) secondary to acute herpes simplex virus encephalitis despite an initial near normal CSF analysis. Initial EEG was unremarkable while CSF analysis revealed changes suggestive of a traumatic tap. An opercular syndrome was diagnosed based on the classic presentation of dysarthria, facial diplegia, and hypersalivation, with corresponding MRI brain changes in the operculum. During admission, EPC developed, with continuous right facial twitching and an electroencephalographic correlate in the left centrotemporal region. The EPC initially responded to intravenous lorazepam. Phenytoin was then added for seizure prophylaxis. Herpes virus DNA was later on detected in the CSF. The patient improved with antiviral treatment except for very mild residual dysarthria. Neurologists should be aware of the possible predilection of the herpes simplex virus for the opercular area and the need to empirically treat for herpes encephalitis even in the setting of near normal initial CSF studies in patients with a suggestive clinical presentation.

A case of catatonia secondary to polysubstance abuse and acetaminophen overdose.

To the Editor: Emergency departments have a high turnover of patients with substance abuse and/or dependence problems.1 Compared to the general population, this group has increased risk of suicidal ideation and attempts.2 We present a case of catatonia in the context of polysubstance abuse and acetaminophen overdose. Case report. Mr A, a 41-year-old white man, was brought to the emergency department for medical evaluation in 2007. Earlier during the day, he was noticed “staring” outside a school. Police were called and they found him staring blankly, mute, and “very slow.” In the emergency department, he was lying on bed and staring at the ceiling. Vital signs were stable. He was mute and did not respond to questions or follow any commands. He had mildly dilated pupils, and sluggishly reacted to light. Resistance and rigidity on passive movements and hyperreflexia were noted. When the side rail dropped accidentally, he leaned over the side of bed in a slow motion and then returned back to lying position. Complete blood cell count, comprehensive metabolic panel, chest x-ray, and electrocardiogram revealed no abnormalities. Drug screen was positive for cannabis and cocaine. Computed tomography of the head revealed no abnormalities normal. Creatine kinase was 340 U/L. The patient's identity was established from his driver's license, and his family was contacted. His history was significant for polysubstance dependence (cocaine, intravenous methamphetamine, cannabis, and alcohol) and multiple suicide attempts. He was hepatitis C positive, but had stopped treatment a year ago. Given the history of overdose, testing for serum acetaminophen level was requested; the level was found to be 213 μmol/L. He was treated with N-acetylcysteine and supportive measures. He continued to be in a catatonic state for the next 24 hours. Electroencephalogram showed diffuse slow waves but no epileptiform activity. Catatonic signs started resolving after 36–48 hours, and he admitted to acetaminophen overdose following relapse of drug abuse. Liver enzymes peaked at an aspartate aminotransferase level of 7,170 U/L and an alanine aminotransferase level of 7,903 U/L. The transplant center was contacted, but he was considered a poor candidate given history of hepatitis C, polysubstance dependence, and multiple suicide attempts. Fortunately, liver function tests started to show improvement and the patient recovered without any complications. Catatonia is characterized by motor and behavioral signs. DSM-IV-TR lists motor immobility, excessive purposeless motor activity, extreme negativism or mutism, peculiarities of voluntary movements, echolalia, and/or echopraxia as the signs of catatonia.3 Catatonic features are classified at 3 places in DSM-IV-TR: (1) as secondary to general medical condition, (2) as a subtype of schizophrenia, and (3) as a specifier for mood disorder. Catatonic syndrome is seen in multiple conditions including infectious, metabolic, autoimmune, neurologic, psychiatric, and substance use disorders as well as with endocrinopathies. Neurotransmitters, especially dopamine, γ-aminobutyric acid and glutamate, are involved in the pathogenesis of catatonic signs. Substance intoxication/withdrawal is a well-known cause of catatonia, but the acetaminophen overdose, which was almost overlooked, could have been fatal. Incidence of catatonia is difficult to estimate as many cases are unrecognized and difficult to differentiate from delirium, encephalopathy, and postictal state. The above case illustrates the importance of recognizing catatonia, undertaking a comprehensive history and physical examination, and judicial use of investigations to complete assessment and formulate a management plan. Supportive care and precautions to prevent medical complications such as deep venous thrombosis and aspiration pneumonia are vital. Intravenous and/or intramuscular lorazepam, intravenous divalproate, carbamazepine, topiramate, and electroconvulsive therapy have been used in prolonged catatonia.4

Disease versus Dimension in Diagnosis

Edward Shorter, PhD, FRSC1; Herman M van Praag, MD, PhD2 Can J Psychiatry. 2010;55(2):59-64. The Argument for Disease It is chimerical to think that psychiatric illness can be collapsed into couple of smooth dimensions. This is conceit that comes to us from psychoanalysis, which was uninterested in specificity of treatment. In reality, just as there are discrete diseases of the kidney, there are discrete diseases of the brain that produce behavioural symptoms. These can no more be scaled than renal tuberculosis and renal carcinoma can be arrayed onto single dimension. Let us consider the view, articulated by Samuel Guze1 in 1992, that psychiatry is branch of medicine. If we are to regard psychiatric diagnoses as medical diagnoses, how might they be constructed? Building on Guze,1 Max Fink and Michael Alan Taylor2 have proposed 3-fold basis for carving out discrete psychiatric illnesses: describing an illness entity in well-circumscribed Psychopathologie terms; verifying its existence with laboratory measures; and, validating it with distinctive response to treatment. Based on this triune measure of what one might call disease-ness, what solid disease diagnoses does psychiatry possess? Melancholia Out of the soup of depression, it is possible to fish several solid diagnoses that fulfill the above criteria. The major depression of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) is nondisease and should be divided into melancholia and nonmelancholia.3 Nonmelancholia is anything but discrete disease entity, while melancholia is probably the most solid disease that psychiatry possesses, characterized, in psychopathological terms, by psychomotor change and profound neurovegetative disturbances, and verified by such biological markers as positive response to the dexamethasone suppression test (in contrast to nonmelancholia), by REM latency, and by blunted thyroid-stimulating hormone response to exogenous thyrotropin-releasing hormone.4 Finally, melancholia is validated by distinctive response to tricyclic antidepressants (TCAs) and to electroconvulsive therapy (ECT). Not all patients with purported melancholia will display these biological markers, but it is profoundly interesting that within the melancholia diagnosis there is psychopathological core of patients possessing this biological homogeneity. (Atypical depression neither shows the typical neurovegetative signs of melancholia nor responds well to ECT.) These cases of melancholia cannot be arrayed on dimensional scale, except in the trivial sense that the disease waxes and wanes. Catatonia Formerly, catatonia was considered subtype of schizophrenia. DSM-IV conceded that features5' p 417 might characterize mood disorder as well. Seldom has catatonia been seen as an independent illness entity worthy of a home of its own, as Fink and Taylor6 put it (in the title of their article). Nevertheless, clearly it belongs on the list of genuine psychiatric diseases because its psychopathology is well specified and has rating scale of its own. To be sure, it does not possess biological marker (verification), but in intravenous lorazepam, catatonia possesses differential treatment response (validation). (No other psychotic illness responds to lorazepam; symptoms of catatonia are also relieved with ECT.) Catatonia has no dimensional features: the diagnosis is made with the presence of 2 or more signs, and the score on the catatonia rating scale does not influence the response to treatment. It would be incorrect to say, as the dimensional argument might put it, that all of us possess embryonic catatonic symptoms that then aggravate under stress. Atypical Depression Atypical depression is less clearly delineated than melancholia and catatonia, in psychopathological terms, but nonetheless displays some underlying biological unity. …

A case of cyclic vomiting syndrome responding to gonadotropin-releasing hormone analogue.

Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent episodes of incapacitating nausea and vomiting interspersed with symptom free periods. Common triggers of cyclic vomiting include noxious stress, excitement, fatigue and menstrual period. Here, we report a case of cyclic vomiting syndrome in adult patient characterized by stereotypical vomiting attack, occurring in every menstruation period. Recurrent vomiting episodes began 6 years ago and we treated this patient with subcutaneous injection of goserelin, a gonadotropin-releasing hormone analogue (GnRHa) and oral estrogen. After 4 months of therapy, she was symptom free for the following 5 years, even with the resumed normal menstruation. Recurrence of vomiting attack with same pattern occurred 1 month before readmission. Treatment with intravenous lorazepam aborted vomiting, but could not prevent recurrences of vomiting and epigastric pain. We treated the patient with GnRHa and oral estradiol again which effectively prevented recurrence of the symptoms.

A 16-year old male with cortical blindness and focal motor seizures

A 16-year old male with cortical blindness and focal motor seizures

Cochrane review: Drug management for acute tonic‐clonic convulsions including convulsive status epilepticus in children

AbstractBackgroundTonic‐clonic (grand mal) convulsions and convulsive status epilepticus (currently defined as a grand mal convulsion lasting at least 30 minutes) are medical emergencies and demand urgent and appropriate anticonvulsant treatment. Benzodiazepines (midazolam, diazepam, lorazepam), phenobarbitone, phenytoin and paraldehyde may all be regarded as drugs of first choice. This is an update of a Cochrane review first published in 2002 and previously updated in 2005.ObjectivesTo review the evidence comparing the efficacy and safety of midazolam, diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in treating acute tonic‐clonic convulsions and convulsive status epilepticus in children treated in hospital.Search strategyWe searched the Cochrane Epilepsy Group's Specialized Register (1st July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), and MEDLINE (1966 to July 2007).Selection criteriaRandomized and quasi‐randomized controlled trials comparing any anticonvulsant drugs used for the treatment of an acute tonic‐clonic convulsion including convulsive status epilepticus in children.Data collection and analysisTwo review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information.Main resultsFour trials involving 383 participants were included.(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions, 19/27 (70%) versus 22/34 (65%), RR 1.09 (95% CI 0.77 to 1.54), has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam, 6/6 versus 6/19 (31%), RR 3.17 (95% CI 1.63 to 6.14)(2) Buccal midazolam controlled seizures in 61/109 (56%) compared with 30/110 (27%) of rectal diazepam treated episodes with acute tonic‐clonic convulsions, RR 2.05 ( 95% CI 1.45 to 2.91)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile convulsions, 23/26 (88%) versus 24/26 (92%), RR 0.96 (95% CI 0.8 to 1.14)(4) There is moderate evidence that intranasal lorazepam is more effective than intramuscular paraldehyde for acute tonic‐clonic convulsions and patients treated with intranasal lorazepam are significantly less likely to require further anticonvulsants to control continuing seizures, 8/80 (10%) versus 21/80 (26%), RR 0.58 (95% CI 0.42 to 0.79).Authors' conclusionsThe conclusions of this update have changed to suggest that intravenous lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic‐clonic convulsions. Where intravenous access is unavailable there is evidence from one trial that buccal midazolam is the treatment of choice.Plain Language SummaryDrug management for acute tonic‐clonic convulsions including convulsive status epilepticus in childrenTonic‐clonic convulsions and convulsive status epilepticus are medical emergencies. In children, initial treatment is usually given in the Accident and Emergency (A&amp;E) department of a hospital. Initial treatment may be administered in a number of ways including into a vein (intravenously), into the nasal or oral cavities (buccally) or into the rectum (rectally). The first choice anticonvulsant should be effective, work rapidly and not be associated with any serious adverse effects.Four trials involving 383 participants were included. A review of two trials in children found evidence to inform a choice of intravenous lorazepam over intravenous diazepam as first line treatment for children presenting to an A&amp;E department in an acute tonic‐clonic convulsion. There is evidence from one trial to suggest that buccal midazolam is more effective than rectal diazepam in the initial management of convulsive status epilepticus in childhood where intravenous access is unavailable/unobtainable.

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.