-
Epilepsia Oct 2023Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed... (Meta-Analysis)
Meta-Analysis
Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.
Topics: Infant, Newborn; Humans; Anticonvulsants; Levetiracetam; Phenytoin; Consensus; Epilepsy; Seizures
PubMed: 37655702
DOI: 10.1111/epi.17745 -
Journal of Pain and Symptom Management Apr 2021Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed,... (Review)
Review
CONTEXT
Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed, but they are mainly based on expert opinion or retrospective chart reviews. Therefore, evidence for the clinical aspects of palliative sedation is needed.
OBJECTIVES
To explore clinical aspects of palliative sedation in recent prospective studies.
METHODS
Systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at PROSPERO. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014-December 2019), combining sedation, palliative care, and prospective. Article quality was assessed.
RESULTS
Ten prospective articles were included, involving predominantly patients with cancer. Most frequently reported refractory symptoms were delirium (41%-83%), pain (25%-65%), and dyspnea (16%-59%). In some articles, psychological and existential distress were mentioned (16%-59%). Only a few articles specified the tools used to assess symptoms. Level of sedation assessment tools were the Richmond Agitation Sedation Scale, Ramsay Sedation Scale, Glasgow Coma Scale, and Bispectral Index monitoring. The palliative sedation practice shows an underlying need for proportionality in relation to symptom intensity. Midazolam was the main sedative used. Other reported medications were phenobarbital, promethazine, and anesthetic medication-propofol. The only study that reported level of patient's discomfort as a palliative sedation outcome showed a decrease in patient discomfort.
CONCLUSION
Assessment of refractory symptoms should include physical evaluation with standardized tools applied and interviews for psychological and existential evaluation by expert clinicians working in teams. Future research needs to evaluate the effectiveness of palliative sedation for refractory symptom relief.
Topics: Hospice and Palliative Care Nursing; Humans; Hypnotics and Sedatives; Palliative Care; Prospective Studies; Retrospective Studies; Terminal Care
PubMed: 32961218
DOI: 10.1016/j.jpainsymman.2020.09.022 -
Journal of Critical Care Aug 2021Compare outcomes of adult patients admitted to ICU- length of ICU stay, length of mechanical ventilation (MV), and time until extubation- according to the use of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Compare outcomes of adult patients admitted to ICU- length of ICU stay, length of mechanical ventilation (MV), and time until extubation- according to the use of propofol versus midazolam.
METHODS
We searched MEDLINE, EMBASE, LILACS, and Cochrane databases to retrieve RCTs that compared propofol and midazolam used as sedatives in adult ICU patients. We applied a random-effects, meta-analytic model in all calculations. We applied the Cochrane collaboration tool and GRADE. We separated patients into two groups: acute surgical patients (hospitalization up to 24 h) and critically-ill patients (hospitalization over 24 h and whose articles mostly mix surgical, medical and trauma patients).
RESULTS
Globally, propofol was associated with a reduced MV time of 4.46 h (MD: -4.46 [95% CI -7.51 to -1.42] p = 0.004, I2 = 63%, 6 studies) and extubation time of 7.95 h (MD: -7.95 [95% CI -9.86 to -6.03] p < 0.00001, I2 = 98%, 16 studies). Acute surgical patients sedation with propofol compared to midazolam was associated with a reduced ICU stay of 5.07 h (MD: -5.07 [95% CI -8.68 to -1.45] p = 0.006, I2 = 41%, 5 studies), MV time of 4.28 h (MD: -4.28; [95% CI -4.62 to -3.94] p < 0.0001, I2 = 0%, 3 studies), extubation time of 1.92 h (MD: -1.92; [95% CI -2.71 to -1.13] p = 0.00001, I2 = 89%, 9 studies). In critically-ill patients sedation with propofol compared to midazolam was associated with a reduced extubation time of 32.68 h (MD: -32.68 [95% CI -48.37 to -16.98] p = 0.0001, I2 = 97%, 9 studies). GRADE was very low for all outcomes.
CONCLUSIONS
Sedation with propofol compared to midazolam is associated with improved clinical outcomes in ICU, with reduced ICU stay MV time and extubation time in acute surgical patients and reduced extubation time in critically-ill patients.
Topics: Adult; Critical Care; Humans; Hypnotics and Sedatives; Intensive Care Units; Midazolam; Propofol; Respiration, Artificial
PubMed: 33838522
DOI: 10.1016/j.jcrc.2021.04.001 -
Annals of Internal Medicine Sep 2019Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016.
BACKGROUND
Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016.
PURPOSE
To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults.
DATA SOURCES
MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018.
STUDY SELECTION
Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide.
DATA EXTRACTION
One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy.
DATA SYNTHESIS
Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or crisis planning. The evidence for pharmacologic treatments suggests that ketamine reduces suicidal ideation with minimal adverse events compared with placebo or midazolam. Lithium reduces rates of suicide among patients with unipolar or bipolar mood disorders compared with placebo. However, no differences were observed between lithium and other medications in reducing suicide.
LIMITATION
Qualitative synthesis of new evidence with existing meta-analyses, methodological shortcomings of studies, heterogeneity of nonpharmacologic interventions, and limited evidence for pharmacologic treatments and harms.
CONCLUSION
Both CBT and DBT showed modest benefit in reducing suicidal ideation compared with TAU or wait-list control, and CBT also reduced suicide attempts compared with TAU. Ketamine and lithium reduced the rate of suicide compared with placebo, but there was limited information on harms. Limited data are available to support the efficacy of other nonpharmacologic or pharmacologic interventions.
PRIMARY FUNDING SOURCE
U.S. Department of Veterans Affairs Veterans Health Administration. (PROSPERO: CRD42018104978).
Topics: Antidepressive Agents; Cognitive Behavioral Therapy; Crisis Intervention; Dialectical Behavior Therapy; Humans; Ketamine; Lithium Compounds; Patient Education as Topic; Risk Factors; Suicidal Ideation; Suicide; United States; Suicide Prevention
PubMed: 31450239
DOI: 10.7326/M19-0869 -
Epilepsy & Behavior : E&B Dec 2021Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a venous line may be difficult in children with seizures which would delay the initiation of treatment. Rectal drug administration can be socially awkward for patients and providers. Intranasal (IN) midazolam offers a valuable substitute that is easier and faster to administer.
OBJECTIVE
To assess the efficacy, safety, and acceptability of intranasal midazolam in children with acute seizure when compared to conventional IV or rectal benzodiazepine (BDZ).
METHODS
PubMed, google scholar, websites clinicaltrials.gov and the WHO-international clinical trials registry platform, were searched. Randomized controlled/prospective randomized trials comparing IN midazolam against IV/rectal BDZ in the treatment of acute seizures in pediatric patients were included in the meta-analysis.
RESULTS
Data of 10 studies were quantitatively analyzed. Intranasal midazolam (n = 169) when compared to IV/rectal BDZ (n = 161) has a shorter interval between hospital arrival and seizure cessation {(mean difference = -3.51; 95% CI [-6.84, -0.18]) P = 0.04}. Regarding time to seizure cessation after midazolam (n = 326) or BDZ (n = 322) administration, there is no significant difference between the two groups {(mean difference = -0.03; 95% CI [-1.30, 1.25]), P = 0.97} and both are equally effective for controlling acute seizures (odds ratio = 1.06; 95% CI [0.43, 2.63]; n = 737).
CONCLUSION
In children with acute seizures, IN midazolam is equally effective in aborting seizure and decreases the total time from hospital arrival and cessation of seizures, eventually leading to faster cessation of seizure as compared to IV/rectal BDZ.
Topics: Administration, Intranasal; Anticonvulsants; Benzodiazepines; Child; Diazepam; Humans; Midazolam; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus
PubMed: 34740090
DOI: 10.1016/j.yebeh.2021.108390 -
Annals of Medicine and Surgery (2012) Oct 2021Asthma is one of the commonest respiratory illnesses among elderly patients undergoing surgery. Detailed preoperative assessment, pharmacotherapy and safe anaesthetic... (Review)
Review
Asthma is one of the commonest respiratory illnesses among elderly patients undergoing surgery. Detailed preoperative assessment, pharmacotherapy and safe anaesthetic measures throughout perioperative period are the keys to decrease complications. Resistance to expiratory airflow results in positive alveolar pressures at the end of expiration, which causes air-trapping and hyperinflation of the lungs and thorax, increased work of breathing, and alteration of respiratory muscle function. This systematic review was conducted according to the Preferred Reporting Items for systematic review and metanalysis (PRISMA) statement. Search engines like PubMed through HINARI, Cochrane database and Google Scholars were used to find evidences. Low-dose IV ketamine, midazolam, IV lidocaine or combined with salbutamol are recommended to be used as premedication before induction. Propofol, ketamine, halothane, isoflurane and sevoflurane are best induction agents and maintenance for asthmatic surgical patients respectively. Among the muscle relaxants, vecuronium is safe for use in asthmatics. In addition, Succinylcholine and pancronium which releases low levels of histamine has been used safely in asthmatics with little morbidity.
PubMed: 34603720
DOI: 10.1016/j.amsu.2021.102874 -
Medicina Intensiva Apr 2020Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new...
Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.
Topics: Analgesia; Anesthesia; Benzodiazepines; Conscious Sedation; Critical Care; Critical Illness; Delirium; Evidence-Based Medicine; Humans; Hypnotics and Sedatives; Intensive Care Units; Midazolam; Pain Management
PubMed: 31492476
DOI: 10.1016/j.medin.2019.07.013 -
The Cochrane Database of Systematic... Sep 2021Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. This is an update of a review first... (Review)
Review
BACKGROUND
Many studies have recently been conducted to assess the antidepressant efficacy of glutamate modification in mood disorders. This is an update of a review first published in 2015 focusing on the use of glutamate receptor modulators in unipolar depression.
OBJECTIVES
To assess the effects - and review the acceptability and tolerability - of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with unipolar major depressive disorder.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020. We did not apply any restrictions to date, language or publication status.
SELECTION CRITERIA
Double- or single-blinded randomised controlled trials (RCTs) comparing ketamine, memantine, esketamine or other glutamate receptor modulators with placebo (pill or saline infusion), other active psychotropic drugs, or electroconvulsive therapy (ECT) in adults with unipolar major depression.
DATA COLLECTION AND ANALYSIS
Three review authors independently identified studies, assessed trial quality and extracted data. The primary outcomes were response rate (50% reduction on a standardised rating scale) and adverse events. We decided a priori to measure the efficacy outcomes at different time points and run sensitivity/subgroup analyses. Risk of bias was assessed using the Cochrane tool, and certainty of the evidence was assessed using GRADE.
MAIN RESULTS
Thirty-one new studies were identified for inclusion in this updated review. Overall, we included 64 studies (5299 participants) on ketamine (31 trials), esketamine (9), memantine (5), lanicemine (4), D-cycloserine (2), Org26576 (2), riluzole (2), atomoxetine (1), basimglurant (1), citicoline (1), CP-101,606 (1), decoglurant (1), MK-0657 (1), N-acetylcysteine (1), rapastinel (1), and sarcosine (1). Forty-eight studies were placebo-controlled, and 48 were two-arm studies. The majority of trials defined an inclusion criterion for the severity of depressive symptoms at baseline: 29 at least moderate depression; 17 severe depression; and five mild-to-moderate depression. Nineteen studies recruited only patients with treatment-resistant depression, defined as inadequate response to at least two antidepressants. The majority of studies investigating ketamine administered as a single dose, whilst all of the included esketamine studies used a multiple dose regimen (most frequently twice a week for four weeks). Most studies looking at ketamine used intravenous administration, whilst the majority of esketamine trials used intranasal routes. The evidence suggests that ketamine may result in an increase in response and remission compared with placebo at 24 hours odds ratio (OR) 3.94, 95% confidence interval (CI) 1.54 to 10.10; n = 185, studies = 7, very low-certainty evidence). Ketamine may reduce depression rating scale scores over placebo at 24 hours, but the evidence is very uncertain (standardised mean difference (SMD) -0.87, 95% CI -1.26 to -0.48; n = 231, studies = 8, very low-certainty evidence). There was no difference in the number of participants assigned to ketamine or placebo who dropped out for any reason (OR 1.25, 95% CI 0.19 to 8.28; n = 201, studies = 6, very low-certainty evidence). When compared with midazolam, the evidence showed that ketamine increases remission rates at 24 hours (OR 2.21, 95% CI 0.67 to 7.32; n = 122,studies = 2, low-certainty evidence). The evidence is very uncertain about the response efficacy of ketamine at 24 hours in comparison with midazolam, and its ability to reduce depression rating scale scores at the same time point (OR 2.48, 95% CI 1.00 to 6.18; n = 296, studies = 4,very low-certainty evidence). There was no difference in the number of participants who dropped out of studies for any reason between ketamine and placebo (OR 0.33, 95% CI 0.05 to 2.09; n = 72, studies = 1, low-certainty evidence). Esketamine treatment likely results in a large increase in participants achieving remission at 24 hours compared with placebo (OR 2.74, 95% CI 1.71 to 4.40; n = 894, studies = 5, moderate-certainty evidence). Esketamine probably results in decreases in depression rating scale scores at 24 hours compared with placebo (SMD -0.31, 95% CI -0.45 to -0.17; n = 824, studies = 4, moderate-certainty evidence). Our findings show that esketamine increased response rates, although this evidence is uncertain (OR 2.11, 95% CI 1.20 to 3.68; n = 1071, studies = 5, low-certainty evidence). There was no evidence that participants assigned to esketamine treatment dropped out of trials more frequently than those assigned to placebo for any reason (OR 1.58, 95% CI 0.92 to 2.73; n = 773, studies = 4,moderate-certainty evidence). We found very little evidence for the remaining glutamate receptor modulators. We rated the risk of bias as low or unclear for most domains, though lack of detail regarding masking of treatment in the studies reduced our certainty in the effect for all outcomes.
AUTHORS' CONCLUSIONS
Our findings show that ketamine and esketamine may be more efficacious than placebo at 24 hours. How these findings translate into clinical practice, however, is not entirely clear. The evidence for use of the remaining glutamate receptor modulators is limited as very few trials were included in the meta-analyses for each comparison and the majority of comparisons included only one study. Long term non-inferiority RCTs comparing repeated ketamine and esketamine, and rigorous real-world monitoring are needed to establish comprehensive data on safety and efficacy.
Topics: Adult; Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Ketamine; Receptors, Glutamate
PubMed: 34510411
DOI: 10.1002/14651858.CD011612.pub3 -
The Cochrane Database of Systematic... Dec 2020Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods.
OBJECTIVES
To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines.
SEARCH METHODS
We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform.
SELECTION CRITERIA
We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia.
DATA COLLECTION AND ANALYSIS
One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures.
MAIN RESULTS
We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines.
AUTHORS' CONCLUSIONS
When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.
Topics: Adult; Aged; Aged, 80 and over; Alprazolam; Anti-Anxiety Agents; Anxiety; Bias; Clonidine; Drug Administration Schedule; Humans; Melatonin; Midazolam; Middle Aged; Oxazepam; Postoperative Care; Postoperative Complications; Preoperative Care; Publication Bias; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 33319916
DOI: 10.1002/14651858.CD009861.pub3 -
Health Technology Assessment... Mar 2022Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded...
BACKGROUND
Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting.
OBJECTIVES
To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.
DATA SOURCES
We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020.
REVIEW METHODS
Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively.
RESULTS
Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness.
LIMITATIONS
The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.
CONCLUSIONS
Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020201953.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in ; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.
Topics: Adult; Anticonvulsants; Emergency Service, Hospital; Hospitals; Humans; Retrospective Studies; Status Epilepticus
PubMed: 35333156
DOI: 10.3310/RSVK2062