Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty adult patients with partial motor status epilepticus were treated with a single intravenous (i.v.) injection of diphenylhydantoin (DPH), 20 mg/kg body weight at a rate of 1 mg/kg/min. Seizures were controlled in 32 patients (64%) during the injection or within the following hour; in 13 of them previous (i.v.) injections out of benzodiazepines had been ineffective. DPH was effective in 10 patients of 11 with a previous history of epileptic seizures and without problems of consciousness during their epileptic status. In contrast, 13 failures out of 18 concern occasional status in patients deeply comatose because of head trauma, neurosurgical operation or intracerebral hemorrhage. Total plasmatic levels of DPH, when measured 24 h after the injection, were found between 38 mumol/l in all patients, and were in the range of 40 mumol/l-100 mumol/l in 77% of cases. Adverse effects were: pain at the injection site (6 cases), horizontal nystagmus during injection (5 cases), transient cerebellar symptoms (3 cases). This study confirms that single loading doses of DPH can maintain DPH plasmatic levels within the therapeutic range during 24 h, with minor or transient side effects, provided that cardiovascular contra-indications are respected.
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PMID:[Treatment of partial motor status epilepticus in adults with intravenous diphenylhydantoin (DPH). Prospective study of 50 cases]. 644 81

Giving a definition of analgesia in ICU needs to answer several questions: Why sedation? Which drugs can we use? How can we deal with sedation? (monitoring, continuous administration, weaning...)? Two different types of sedation must be considered: treatment-sedation (status epilepticus, tetanus, intracranial hypertension...) and comfort-sedation in anxious and/or restless and/or painful patients and in those necessitating mechanical ventilation. Analgesic consumptions vary widely with diseases and their outcome, background diseases and ICU environment. Several studies have shown that pain and analgesia are frequently neglected in ICU. The authors review the different drugs in use, with their advantages and drawbacks. A particular place is reserved to regional techniques, often underused in ICU. Indications are then fully discussed, according to several specific pathological conditions. Monitoring and weaning of sedation are also discussed at the end of the review.
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PMID:[Role of analgesia for sedation in intensive care medicine]. 776 33

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate (Glu) receptor have become the focus of considerable attention as potential neurotherapeutic agents in view of mounting evidence implicating NMDA receptors in acute central nervous system (CNS) injury syndromes such as stroke, trauma, and status epilepticus. In addition, NMDA receptor antagonists are of potential interest for the clinical management of neuropathic pain and preventing the development of tolerance to opiate analgesics. A potentially serious obstacle to the development of NMDA antagonists as neurotherapeutic drugs is the paradoxical fact that whereas these agents do have significant neurotherapeutic potential, they also have psychotogenic and neurotoxic properties. We have been intensively investigating the mechanisms underlying these adverse properties and have discovered several methods of suppressing or preventing their expression. In addition, we have been exploring the possibility that a common mechanism may underlie the psychotogenic and neurotoxic actions of these agents and that this mechanism may have relevance to the pathogenesis of idiopathic psychotic processes such as schizophrenia. In this chapter, we will review our findings pertaining to NMDA antagonists in the dual context of their value as tools for exploring mechanisms underlying neuropsychiatric disturbances, particularly schizophrenia, and their potential promise as therapeutic agents. For additional references and a more complete elaboration of our hypothesis pertaining to NMDA receptor dysfunction and schizophrenia, please see a recent review (Olney and Farber 1995).
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PMID:NMDA antagonists as neurotherapeutic drugs, psychotogens, neurotoxins, and research tools for studying schizophrenia. 874 58

Fosphenytoin is a phosphate ester prodrug of phenytoin developed as a replacement for standard injectable sodium phenytoin. After absorption, phenytoin is cleaved (conversion half-life 8-15 min) from fosphenytoin. Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions (including standard intravenous solutions) and rapidly absorbed by the intramuscular route. Fosphenytoin has been tested successfully for three indications in humans: intramuscular maintenance dosing, intramuscular loading dose administration, and intravenous treatment of status epilepticus. Local toxicity (pain, burning, itching) is less by the intramuscular or intravenous route for fosphenytoin than for standard injectable sodium phenytoin. Systemic toxicity is similar with both preparations except that hypotension is less common and paresthesias are more common with fosphenytoin.
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PMID:Fosphenytoin (Cerebyx). 903 68

Fosphenytoin, a prodrug of phenytoin, is rapidly and completely converted to phenytoin in adults after intravenous or intramuscular administration and is significantly better tolerated than parenteral phenytoin. Fosphenytoin is highly plasma-protein bound and, when present in sufficient concentration, will displace phenytoin from plasma proteins. The clinical utility is that fosphenytoin may be used to achieve therapeutic phenytoin concentrations more rapidly than intravenous phenytoin infused at its maximum recommended rate. In a clinical study of generalized convulsive status epilepticus, fosphenytoin, with or without benzodiazepine pretreatment, controlled seizures in 76 (93.8%) of 81 patients. In other studies, fosphenytoin maintained seizure control when substituted for oral phenytoin and for seizure prophylaxis in neurosurgery and trauma patients. Adverse events associated with fosphenytoin generally were related to the central nervous system and were similar to those associated with phenytoin, except for a higher incidence of transient pruritus with fosphenytoin. Intravenous fosphenytoin has significant advantages over intravenous phenytoin: It requires a shorter infusion time and fewer intravenous disruptions, causes less pain and burning at the infusion site and minimal consequences in case of intravenous infiltration, allows longer maintenance of intravenous sites, and has better intravenous fluid compatibility and stability. In contrast to intramuscular phenytoin, intramuscular fosphenytoin is well tolerated in both large loading doses and maintenance doses.
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PMID:Clinical experience with fosphenytoin in adults: pharmacokinetics, safety, and efficacy. 979 47

Pain and its treatment are known to have adverse effects on the organism, including deterioration in myocardial, diaphragmatic, and small bowel function. The provision of adequate intravenous analgesia, and the choice of agent, can ameliorate or exacerbate these manifestations of the stress response. The choice of agent, opioid or non-opioid, has in some respects become more difficult as more information has become available regarding the merits and adverse effects of each. Increased awareness of the frequency of hypoxemia secondary to the opioids' ability to cause an obstructive sleep apnea picture, and the cost efficiency of ketorolac through a reduction in opioid toxicity, contrast with recent studies which suggest that the gastrotoxic and nephrotoxic effects of ketorolac may occur earlier than previously suspected. The suitability of using the dissociative anesthetic agent ketamine in critically ill patients remains to be proven. Ketamine provides intense analgesia at subanesthetic doses. Its centrally mediated sympathomimetic action encourages hemodynamic stability, and it is relatively devoid of respiratory depressant activity. Increasing experience with ketamine outside the operating room has resulted in its successful use in cases of severe bronchospasm and status epilepticus.
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PMID:Intravenous analgesia. 992 88

Although midazolam has been proposed for the treatment of a variety of conditions such as anxiety, dyspnoea, hiccups and status epilepticus, terminal agitation is the only condition where its use is based on a reasonably large number of published clinical studies. A causal approach is generally recommended. Whenever possible, the aetiological condition (pain, fever, constipation, etc.) should be corrected. Such general measures as ensuring a peaceful, familiar environment, and the use of a night light, fluid therapy to counteract dehydration, and antipyretics for fever are beneficial. When symptomatic treatment is needed, drugs with little anticholinergic effect are to be recommended. The use of benzodiazepines as single drug treatment may exacerbate the condition. Haloperidol or risperidone (which has fewer side effects) are recommended. If the agitation is marked, a common strategy is to add lorazepam. Chlormethiazole is an alternative. Subcutaneous midazolam should be reserved for refractory cases. Attention should be paid to dosage, reduced doses being given to the elderly, patients on opioid medication, and patients with impaired liver or renal function. Overdosage may induce deep sedation, and result in carbon dioxide retention and subsequently heart failure and pulmonary oedema which may be fatal.
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PMID:[Midazolam (Dormicum) in terminal anxiety and agitation. The last choice alternative in palliative care]. 1035 70

IV valproate may be given to patients requiring rapid elevation of serum valproate or for patients unable to take oral medication. Previously we established the loading dose of IV valproate needed to achieve serum concentrations of > 100 ug/ml. This study evaluated the safety of rapid infusion of valproate to achieve high therapeutic levels. Twenty-four infusions of IV valproate were carried out electively in twenty-one patients with epilepsy (ages 2-54 years). The dose ranged from 21-28 mg/kg (mean 24.2 mg/kg). Target infusion rates were 3 or 6 mg/kg per min, yielding an infusion duration of 4.17 or 8.34 min. ECG was monitored; blood pressure was measured before and after infusion. Post infusion serum valproate concentrations were 64-204.1 ug/ml (mean 132.6). There were no significant changes in blood pressure and no ECG abnormalities observed. Transient pain occurred at the site of injection in five patients, associated with redness in two. This appeared to related to the concentration of valproic acid in the infusion fluid. We conclude that a loading dose of IV valproate can be administered safely and rapidly. This finding enables further studies evaluating IV valproate as a non-sedative anticonvulsant in the management of status epilepticus.
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PMID:Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients. 1037 67

Acid-sensing ion channels (ASICs) constitute a recently discovered family of excitatory cation channels, structurally related to the superfamily of degenerin/epithelial sodium channels. ASIC1b and ASIC3 are highly expressed in primary sensory neurons and are thought to play a role in pain transmission related to acidosis. ASIC1a, ASIC2a, and ASIC2b are also distributed in the central nervous system where their function remains unclear. We investigated here the regulation of their expression during status epilepticus (SE), a condition in which neuronal overexcitation leads to acidosis. In animals treated with pilocarpine (380 mg/kg) to induce SE, we observed a marked decrease of ASIC2b mRNA levels in all hippocampal areas and of ASIC1a mRNA levels in the CA1-2 fields. These changes were also observed after protective treatment from neuronal cell death with diazepam (10 mg/kg) and pentobarbital (30 mg/kg). These findings suggest a key role of channels containing ASIC1a and ASIC2b subunits in both normal and pathological activity of hippocampus.
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PMID:Regional and subunit-specific downregulation of acid-sensing ion channels in the pilocarpine model of epilepsy. 1116 39

Sedatives continue to be used on a routine basis in critically ill patients. Although many agents are available and some approach an ideal, none are perfect. Patients require continuous reassessment of their pain and need for sedation. Pathophysiologic abnormalities that cause agitation, confusion, or delirium must be identified and treated before unilateral administration of potent sedative agents that may mask potentially lethal insufficiencies. The routine use of standardized and validated sedation scales and monitors is needed. It is hoped that reliable objective monitors of patients' level of consciousness and comfort will be forthcoming. Each sedative agent discussed in this article seems to have a place in the ICU pharmacologic armamentarium to ensure the safe and comfortable delivery of care. Etomidate is an attractive agent for short-term use to provide the rapid onset and offset of sedation in critically ill patients who are at risk for hemodynamic instability but seem to need sedation or anesthesia to perform a procedure or manipulate the airway. Ketamine administered through intramuscular injection or intravenous infusion provides quick, intense analgesia and anesthesia and allows patients to tolerate limited but painful procedures. The risk/benefit ratio associated with the use of this neuroleptic agent must be weighed carefully. Ketamine is contraindicated in patients who lack normal intracranial compliance or who have significant myocardial ischemia. Barbiturates are reserved mainly to induce coma in patients at risk for severe CNS ischemia, which frequently is associated with refractory intracranial hypertension, or in patients with status epilepticus. When administered in high doses, these drugs have prolonged sedative and depressant effects. Judicious hemodynamic monitoring is required when barbiturate coma is induced. Haloperidol is indicated in the treatment of delirium. Patients should be monitored for extrapyramidal side effects and, when they require higher doses, for potential electrocardiographic prolongation of the QT interval. Dexmedetomidine may evolve into an agent with qualities comparable with midazolam and propofol, and it may even become a drug of choice in select patients. Further study is required, however. Propofol has many of the qualities of an ideal sedative agent. Benzodiazepines and narcotics often are used in concert with propofol to provide reliable amnesia and to relieve pain, respectively. Propofol frequently causes hypotension when administered as a bolus or infusion, particularly in patients with limited cardiac reserve or hypovolemia. More data must be obtained to identify potential deleterious effects of hypertriglyceridemia, and further evaluation of the potential benefits in certain patient populations, such as neurosurgical patients, is needed.
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PMID:Use of propofol and other nonbenzodiazepine sedatives in the intensive care unit. 1176 65


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