Transition from intravenous to enteral ketamine for treatment of nonconvulsive status epilepticus.
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ABSTRACT:
SUBMITTER: Pizzi MA
PROVIDER: S-EPMC5549373 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:PurposeTo examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE).MethodsMulticenter retrospective review of medical records and electroencephalography (EEG) reports in 10 academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE that were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury.Key findingsPermanent control of RSE was achieved in 57% (34 of 60) of episodes. Ketamine was felt to have contributed to permanent control ("possible" or "likely" responses) in 32% (19 of 60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with postanoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9 mg/kg/h, when ketamine was introduced at least 8 days after SE onset, or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26 of 60), but was lower when SE was controlled within 24 h of ketamine initiation (16% vs. 56%, p = 0.0047).SignificanceKetamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE.
| S-EPMC3731413 | biostudies-literature
Project description:Status epilepticus (SE) and cluster seizures (CS) are common occurrences in veterinary neurology and frequent reasons of admission to veterinary hospitals. With prolonged seizure activity, gamma amino-butyric acid (GABA) receptors (GABAa receptors) become inactive, leading to a state of pharmacoresistance to benzodiazepines and other GABAergic medications, which is called refractory status epilepticus (RSE). Prolonged seizure activity is also associated with overexpression of N-methyl-D-aspartic (NMDA) receptors. Rodent models have shown the efficacy of ketamine (KET) in treating RSE, and its use has been reported in one canine case of RSE. Boluses of KET 5 mg/kg IV have become the preferred treatment for RSE in our hospital. A retrospective study was performed to evaluate and report our experience with KET IV bolus to treat prolonged and/or repeated seizure activity in cases of canine CS, SE, and RSE. A total of 15 dogs were retrieved, for 20 hospitalizations and 28 KET IV injections over 3 years. KET IV boluses were used 12 times for RSE (9 generalized seizures, 3 focal seizures) and KET terminated the episode of RSE 12/12 times (100%); however, seizures recurred 4/12 times (33%) within ≤6 h of KET IV bolus. When used for CS apart from episodes of RSE, KET IV bolus was associated with termination of the CS episode only 4/14 times (29%). Only 4/28 (14%) KET IV boluses were associated with adverse effects imputable only to the use of KET. One dog experienced a short, self-limited seizure activity during administration of KET IV, which was most likely related to a pre-mature use of KET IV (i.e., before GABAergic resistance and NMDA receptor overexpression had taken place). This study indicates that KET 5 mg/kg IV bolus may be successful for the treatment of RSE in dogs.
| S-EPMC7925624 | biostudies-literature
Project description:ObjectiveTo test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE), we studied patients with SRSE who were treated with ketamine retrospectively. We also studied the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM).MethodsWe studied a consecutive series of 68 patients with SRSE who were admitted between 2009 and 2018, treated with ketamine, and monitored with scalp EEG. Eleven of these patients underwent MMM at the time of ketamine administration. We compared patients who had seizure cessation after ketamine initiation to those who did not.ResultsMean age was 53 ± 18 years and 46% of patients were female. Seizure burden decreased by at least 50% within 24 hours of starting ketamine in 55 (81%) patients, with complete cessation in 43 (63%). Average dose of ketamine infusion was 2.2 ± 1.8 mg/kg/h, with median duration of 2 (1-4) days. Average dose of midazolam was 1.0 ± 0.8 mg/kg/h at the time of ketamine initiation and was started at a median of 0.4 (0.1-1.0) days before ketamine. Using a generalized linear mixed effect model, ketamine was associated with stable mean arterial pressure (odds ratio 1.39, 95% confidence interval 1.38-1.40) and with decreased vasopressor requirements over time. We found no effect on intracranial pressure, cerebral blood flow, or cerebral perfusion pressure.ConclusionKetamine treatment was associated with a decrease in seizure burden in patients with SRSE. Our data support the notion that high-dose ketamine infusions are associated with decreased vasopressor requirements without increased intracranial pressure.Classification of evidenceThis study provides Class IV evidence that ketamine decreases seizures in patients with SRSE.
| S-EPMC7713785 | biostudies-literature
Project description:Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route.This 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.At 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.For 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.).
| S-EPMC3307101 | biostudies-literature
Project description:BACKGROUND:Patients in refractory status epilepticus (RSE) may require treatment with continuous intravenous anesthetic drugs (cIVADs) for seizure control. The use of cIVADs, however, was recently associated with poor outcome in status epilepticus (SE), raising the question of whether cIVAD therapy should be delayed for attempts to halt seizures with repeated non-anesthetic antiepileptic drugs. In this study, we aimed to determine the impact of differences in therapeutic approaches on RSE outcome using timing of cIVAD therapy as a surrogate for treatment aggressiveness. METHODS:This was a retrospective cohort study over 14 years (n = 77) comparing patients with RSE treated with cIVADs within and after 48 h after RSE onset, and functional status at last follow-up was the primary outcome (good = return to premorbid baseline or modified Rankin Scale score of less than 3). Secondary outcomes included discharge functional status, in-hospital mortality, RSE termination, induction of burst suppression, use of thiopental, duration of RSE after initiation of cIVADs, duration of mechanical ventilation, and occurrence of super-refractory SE. Analysis was performed on the total cohort and on subgroups defined by RSE severity according to the Status Epilepticus Severity Score (STESS) and by the variables contained therein. RESULTS:Fifty-three (68.8%) patients received cIVADs within the first 48 h. Early cIVAD treatment was independently associated with good outcome (adjusted risk ratio [aRR] 3.175, 95% confidence interval [CI] 1.273-7.918; P = 0.013) as well as lower chance of both induction of burst suppression (aRR 0.661, 95% CI 0.507-0.861; P = 0.002) and use of thiopental (aRR 0.446, 95% CI 0.205-0.874; P = 0.043). RSE duration after cIVAD initiation was shorter in the early cIVAD cohort (hazard ratio 1.796, 95% CI 1.047-3.081; P = 0.033). Timing of cIVAD use did not impact the remaining secondary outcomes. Subgroup analysis revealed early cIVAD impact on the primary outcome to be driven by patients with STESS of less than?3. CONCLUSIONS:Patients with RSE treated with cIVADs may benefit from early initiation of such therapy.
| S-EPMC6249897 | biostudies-other
Project description: Not available
| S-EPMC8366410 | biostudies-literature
Project description:ObjectiveTo 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.Study designTen 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.ResultsA 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.ConclusionsLorazepam 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.
| S-EPMC3274567 | biostudies-literature
Project description:BackgroundKetamine's potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor-dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.MethodsResting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.ResultsA reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.ConclusionsThese preliminary results suggest that the Hb might be involved in ketamine's antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.
| S-EPMC8130203 | biostudies-literature
Project description:BackgroundEvidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE.MethodsWe described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science.ResultsSeven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1-17 months of life.DiscussionNeonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting.ConclusionsKetamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed.
| S-EPMC10275409 | biostudies-literature
Project description:Refractory and super-refractory status epilepticus (SE) are serious illnesses with a high risk of morbidity and even fatality. In the setting of refractory generalized convulsive SE (GCSE), there is ample justification to use continuous infusions of highly sedating medications-usually midazolam, pentobarbital, or propofol. Each of these medications has advantages and disadvantages, and the particulars of their use remain controversial. Continuous EEG monitoring is crucial in guiding the management of these critically ill patients: in diagnosis, in detecting relapse, and in adjusting medications. Forms of SE other than GCSE (and its continuation in a "subtle" or nonconvulsive form) should usually be treated far less aggressively, often with nonsedating anti-seizure drugs (ASDs). Management of "non-classic" NCSE in ICUs is very complicated and controversial, and some cases may require aggressive treatment. One of the largest problems in refractory SE (RSE) treatment is withdrawing coma-inducing drugs, as the prolonged ICU courses they prompt often lead to additional complications. In drug withdrawal after control of convulsive SE, nonsedating ASDs can assist; medical management is crucial; and some brief seizures may have to be tolerated. For the most refractory of cases, immunotherapy, ketamine, ketogenic diet, and focal surgery are among several newer or less standard treatments that can be considered. The morbidity and mortality of RSE is substantial, but many patients survive and even return to normal function, so RSE should be treated promptly and as aggressively as the individual patient and type of SE indicate.
| S-EPMC6095773 | biostudies-literature