C.J. Kazina

Electroconvulsive therapy for refractory status epilepticus: A systematic review

BACKGROUND Our goal was to perform an extensive systematic review of the literature on the use of electroconvulsive therapy (ECT) for refractory status epilepticus (RSE). METHODS Articles from MEDLINE, BIOSIS, EMBASE, Healthstar, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS We identified 14 original articles with a total of 19 patients receiving ECT for RSE. Of the 19 patients, 15 were adult, and 4 were pediatric. All studies were retrospective in nature. Seizure reduction/control with the application of ECT occurred in 11 of the 19 patients (57.9%), with 4 (21.0%) and 7 (36.8%) displaying partial and complete responses respectively. Seizures control lasted for variable duration, with the most commonly quoted duration ranging from 2 weeks to 3 months. Data on patient functional outcome was available in 13 patients, with 10 patients falling into the categories of dead or severely disabled. All studies were an Oxford level 4, GRADE D level of evidence. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest an improvement in seizure control with ECT application for RSE. Routine use of ECT cannot be recommended at this time. Further prospective study of this therapy is required in order to determine its efficacy in this setting.

The Cerebrovascular Response to Ketamine: A Systematic Review of the Animal and Human Literature.

Background: The aim of the study was to perform a systematic review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of ketamine in both animal and human subjects. Materials and Methods: We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2014. Two reviewers independently identified all manuscripts pertaining to the administration of ketamine in both human and animal subjects in which the impact on CBF/cerebral vasculature was recorded by means of functional magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, xenon computed tomography, transcranial Doppler velocities, arteriovenous difference in N2O method of CBF measurement, cerebral digital subtraction angiography, or any other objective means of CBF determination. Results: We identified 38 animal studies with various animal models studied. Overall there was a trend to a direct vasodilatory effect of ketamine on the cerebral vasculature, with a trend in most studies to an increase or regional CBF (rCBF) or global CBF. Twenty human studies were identified. The majority displayed an increase in rCBF and global CBF on imaging in patients without neurological illness. Conclusions: Animal models indicate an increase in global CBF and rCBF with ketamine administration, with a trend to vasodilation of medium-sized intracranial vessels through a calcium-dependent mechanism. Human studies display an Oxford 2b, Grading of Recommendation Assessment Development and Education C, level of evidence to support a trend to increased global CBF and rCBF with ketamine administration in both healthy volunteers and elective surgical patients without neurological illness.

Lidocaine for status epilepticus in adults

INTRODUCTION Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in adults for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. METHODS All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Overall, 13 studies were identified, with 11 manuscripts and 2 meeting abstracts. Seventy-six adult patients were treated for 82 episodes of SE/RSE. Patients had varying numbers of anti-epileptic drugs (AEDs), 1-12, on board prior to lidocaine therapy. During 69 of the 82 (84.1%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some utilizing bolus dosing alone; others utilizing a combination of bolus and infusion therapy. Overall, 70.7% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 64.1% and 6.1% respectively. Patient outcomes were sparingly reported. CONCLUSIONS There currently exists level 4, GRADE C evidence to support the consideration of lidocaine for SE and RSE in the adult population. Thus there is currently weak evidence to support the use of lidocaine in this context. Further prospective studies of lidocaine administration in this setting are warranted.

Lidocaine for Status Epilepticus in Pediatrics

BACKGROUND Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in pediatrics for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. METHODS All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendations Assessment, Development, and Evaluation methodologies by two independent reviewers. RESULTS Overall, 20 original studies were identified, with 19 manuscripts and one meeting abstract. Two hundred and thirty-five pediatric patients were treated for 252 episodes of SE/RSE. Patients had varying numbers of antiepileptic drugs (two to eight) on board before lidocaine therapy. During 20 of the 252 (7.9%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some using bolus dosing alone; others used a combination of bolus and infusion therapy. Overall, 60.0% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 57.6% and 12.3%, respectively. Patient outcomes were sparingly reported. CONCLUSIONS There currently exists Oxford level 2b, Grading of Recommendations Assessment Development, and Evaluation C evidence to support the consideration of lidocaine for SE and RSE in the pediatric population. Further prospective studies of lidocaine administration in this setting are warranted.

Magnesium sulfate for non-eclamptic status epilepticus.

BACKGROUND Our goal was to perform a systematic review of the literature on the use of intravenous magnesium sulfate (MgSO4) for non-eclamptic status epilepticus (SE) and refractory status epilepticus (RSE). METHODS Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS We identified 19 original articles. A total of 28 patients were described in these articles with 11 being adult, 9 being pediatric, and 8 of unknown age. Seizure reduction/control with IV MgSO4 occurred in 14 of the 28 patients (50.0%), with 2 (7.1%) and 12 (42.9%) displaying partial and complete responses respectively. Seizures recurred upon withdrawal of MgSO4 therapy in 50% of the patients whom had reduction/control of their SE/RSE. Three patients had recorded adverse events related to MgSO4 therapy. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest a trend towards improved seizure control with the use of intravenous MgSO4 for non-eclamptic RSE. Routine use of IV MgSO4 in non-eclamptic SE/RSE cannot be recommended at this time. Further prospective study of this drug is required in order to determine its efficacy as an anti-epileptic in this setting.

Plasmapheresis for refractory status epilepticus Part II: A scoping systematic review of the pediatric literature

BACKGROUND Our goal was to perform a scoping systematic review of the literature on the use of plasmapheresis or plasma exchange (PE) for refractory status epilepticus (RSE) in children. METHODS Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Twenty-two original articles were identified, with 37 pediatric patients. The mean age of the patients was 8.3 years (age median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%) displaying resolution of seizures and 2 patients (5.4%) displaying a partial reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no response to PE therapy. No adverse events were recorded. CONCLUSIONS Oxford level 4, GRADE D evidence exists to suggest little to no benefit of PE in pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended at this time.

Intravenous immunoglobulins for refractory status epilepticus, part I: A scoping systematic review of the adult literature

PURPOSE Our goal was to perform a scoping systematic review of the literature on the use of intravenous immunoglobulins (IVIG) for refractory status epilepticus (RSE) in adults. METHOD Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS Twenty-four original articles were identified. A total of 33 adult patients were described as receiving IVIG for RSE. Seizure reduction/control with IVIG occurred in 15 of the 33 patients (45.4%), with 1 (3.0%) and 14 (42.4%) displaying partial and complete responses respectively. No adverse events were recorded. CONCLUSION Oxford level 4, GRADE D evidence exists to suggest an unclear impact of IVIG therapy in adult RSE. Routine use of IVIG in adult RSE cannot be recommended at this time.

Indomethacin for Control of ICP

Our goal was to perform a systematic review of the literature on the use of indomethacin and its effects on intracranial pressure (ICP) in patients with neurological illness. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to July 2014), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts utilizing the following inclusion and exclusion criteria. Inclusion criteria: Humans, prospective studies (five or more patients), documented ICP response to indomethacin, and English. Exclusion criteria: non-English, retrospective studies, no documentation of ICP response to indomethacin, and animal studies. A two-tier filter of references was conducted. First, we screened manuscripts by title and abstract. Second, those references passing the first filter were pulled, and the full manuscript was checked to see if it matched the criteria for inclusion. Two reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total of 208 citations. Twelve original articles, 10 manuscripts, and 2 meeting proceeding, were considered for the review with all utilizing indomethacin, while documenting ICP in neurological patients. All studies were prospective. Across all studies, there were a total of 177 patients studied, with 152 receiving indomethacin and 25 serving as controls in a variety of heterogeneous studies. All but one study documented a decrease in ICP with indomethacin administration, with both bolus and continuous infusions. No significant complications were described. There currently exists Oxford level 2b, GRADE C evidence to support that indomethacin reduces ICP in the severe TBI population. Similar conclusions in other populations cannot be made at this time. Comments on its impact, on patient outcome, and side effects cannot be made given the available data. At this time, indomethacin for ICP control remains experimental and further prospective study is warranted.

Neurosurgery (Critical Care/Neuro Trauma): “Novell” medical therapies in ICP management: targeting three brain states

Background: There exists the role for novel agents in the management of refractory intracranial pressure (ICP) via targeting cerebral acidosis, hyperemia, and excitotoxicity. Objective: We performed 4 separate systematic reviews to determine the effect of tromethamine (THAM), indomethacin, and ketamine on ICP. Methods: All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to: February 2014 – THAM, July 2014 – Indomethacin, November 2013 - Ketamine), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Results: Twelve articles were reviewed utilizing THAM while documenting ICP in neurosurgical patients. All but one study documented a decrease in ICP. Twelve original articles were reviewed utilizing indomethacin for ICP in neurological patients. All but one study documented a decrease in ICP. Seven articles were reviewed utilizing ketamine, documenting ICP in TBI patients, with 16 in non-trauma neurological patients. ICP did not increase in the studies during ketamine administration, and trended to decrease ICP. Conclusion: There exists Oxford level 2b, GRADE B evidence that THAM reduces ICP in the TBI and malignant ischemic infarct population. There exists Oxford level 2b, GRADE C evidence that indomethacin and ketamine reduce ICP in the adult severe TBI population.