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The Cochrane Database of Systematic... Sep 2014Status epilepticus is a medical emergency associated with significant mortality and morbidity that requires immediate and effective treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Status epilepticus is a medical emergency associated with significant mortality and morbidity that requires immediate and effective treatment.
OBJECTIVES
(1) To determine whether a particular anticonvulsant is more effective or safer to use in status epilepticus compared to another and compared to placebo.(2) To delineate reasons for disagreement in the literature regarding recommended treatment regimens and to highlight areas for future research.
SEARCH METHODS
For the latest update of this review, the following electronic databases were searched on 15/08/2013: the Cochrane Epilepsy Group's Specialized Register, CENTRAL The Cochrane Library July 2013, Issue 7, and MEDLINE (Ovid) 1946 to 15/08/2013.
SELECTION CRITERIA
Randomised controlled trials of participants with premonitory, early, established or refractory status epilepticus using a truly random or quasi-random allocation of treatments were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trial quality and extracted data.
MAIN RESULTS
Eighteen studies with 2755 participants were included. Few studies used the same interventions. Intravenous diazepam was better than placebo in reducing the risk of non-cessation of seizures (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.57 to 0.92), requirement for ventilatory support (RR 0.39, 95% CI 0.16 to 0.94), or continuation of status epilepticus requiring use of a different drug or general anaesthesia (RR 0.73, 95% CI 0.57 to 0.92). Intravenous lorazepam was better than placebo for risk of non-cessation of seizures (RR 0.52, 95% CI 0.38 to 0.71) and for risk of continuation of status epilepticus requiring a different drug or general anaesthesia (RR 0.52, 95% CI 0.38 to 0.71). Intravenous lorazepam was better than intravenous diazepam for reducing the risk of non-cessation of seizures (RR 0.64, 95% CI 0.45 to 0.90) and had a lower risk for continuation of status epilepticus requiring a different drug or general anaesthesia (RR 0.63, 95% CI 0.45 to 0.88). Intravenous lorazepam was better than intravenous phenytoin for risk of non-cessation of seizures (RR 0.62, 95% CI 0.45 to 0.86). Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures (RR 0.43 95% CI 0.30 to 0.62)For pre-hospital treatment, intramuscular midazolam is at least as effective as (probably more effective than) intravenous lorazepam in control of seizures (RR1.16, 95% CI 1.06 to 1.27) and frequency of hospitalisation (RR 0.88, 95% CI 0.79 to 0.97) or intensive care admissions (RR 0.79, 95% CI 0.65 to 0.96). It was uncertain whether Intravenous valproate was better than intravenous phenytoin in reducing risk of non-cessation of seizures (RR 0.75, 95% CI 0.28 to 2.00). Both levetiracetam and lorazepam were equally effective in aborting seizures (RR 0.97, 95% CI 0.44 to 2.13). Results for other comparisons of anticonvulsant therapies were uncertain due to single studies with few participants.The body of randomised evidence to guide clinical decisions is small. It was uncertain whether any anticonvulsant therapy was better than another in terms of adverse effects, due to few studies and participants identified. The quality of the evidence from the included studies is not strong but appears acceptable. We were unable to make judgements for risk of bias domains incomplete outcome reporting (attrition bias) and selective outcome reporting (selection bias) due to unclear reporting by the study authors.
AUTHORS' CONCLUSIONS
Intravenous lorazepam is better than intravenous diazepam or intravenous phenytoin alone for cessation of seizures. Intravenous lorazepam also carries a lower risk of continuation of status epilepticus requiring a different drug or general anaesthesia compared with intravenous diazepam. Both intravenous lorazepam and diazepam are better than placebo for the same outcomes. For pre hospital management, midazolam IM seemed more effective than lorazepam IV for cessation of seizures, frequency of hospitalisation and ICU admissions however,it was unclear whether the risk of recurrence of seizures differed between treatments. The results of other comparisons of anticonvulsant therapies versus each other were also uncertain. Universally accepted definitions of premonitory, early, established and refractory status epilepticus are required. Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures. Results for other comparisons of anticonvulsant therapies were uncertain due to single studies with few participants.
Topics: Anticonvulsants; Diazepam; Humans; Injections, Intravenous; Lorazepam; Midazolam; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 25207925
DOI: 10.1002/14651858.CD003723.pub3 -
The Cochrane Database of Systematic... Oct 2016The long-term risk of stroke increases with age, and stroke is a common cause of disability in the community. Spasticity is considered a significantly disabling... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The long-term risk of stroke increases with age, and stroke is a common cause of disability in the community. Spasticity is considered a significantly disabling impairment that develops in people who have had a stroke. The burden of care is higher in stroke survivors who have spasticity when compared with stroke survivors without spasticity with regard to treatment costs, quality of life, and caregiver burden.
OBJECTIVES
To assess if pharmacological interventions for spasticity are more effective than no intervention, normal practice, or control at improving function following stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 5), MEDLINE (1946 to May 2016), Embase (2008 to May 2016), CINAHL (1982 to May 2016), AMED (1985 to May 2016), and eight further databases and trial registers. In an effort to identify further studies, we undertook handsearches of reference lists and contacted study authors and commercial companies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any systemically acting or locally acting drug versus placebo, control, or comparative drug with the aim of treating spasticity.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion and extracted the data. We assessed the included studies for both quality and risk of bias. We contacted study authors to request further information when necessary.
MAIN RESULTS
We included seven RCTs with a total 403 participants. We found a high risk of bias in all but one RCT. Two of the seven RCTs assessed a systemic drug versus placebo. We pooled data on an indirect measure of spasticity (160 participants) from these two studies but found no significant effect (odds ratio (OR) 1.66, 95% confidence interval (CI) 0.21 to 13.07; I = 85%). We identified a significant risk of adverse events per participant occurring in the treatment group versus placebo group (risk ratio (RR) 1.65, 95% CI 1.12 to 2.42; 160 participants; I = 0%). Only one of these studies used a functional outcome measure, and we found no significant difference between groups.Of the other five studies, two assessed a systemic drug versus another systemic drug, one assessed a systemic drug versus local drug, and the final two assessed a local drug versus another local drug.
AUTHORS' CONCLUSIONS
The lack of high-quality RCTs limited our ability to make specific conclusions. Evidence is insufficient to determine if systemic antispasmodics are effective at improving function following stroke.
Topics: Baclofen; Botulinum Toxins, Type A; Clonidine; Diazepam; Humans; Muscle Relaxants, Central; Muscle Spasticity; Randomized Controlled Trials as Topic; Stroke; Tolperisone
PubMed: 27711973
DOI: 10.1002/14651858.CD010362.pub2 -
The Cochrane Database of Systematic... Oct 2016Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal models of cerebrovascular disease. However, the sedative effects of GABA receptor agonists have limited their wider application in people with acute stroke, due to the potential risk of stupor. This is an update of a Cochrane review first published in 2013, and previously updated in 2014.
OBJECTIVES
To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (accessed March 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) 2016, Issue 3, part of the Cochrane Library (accessed March 2016), MEDLINE (from 1949 to March 2016), Embase (from 1980 to March 2016), CINAHL (from 1982 to March 2016), AMED (from 1985 to March 2016), and 11 Chinese databases (accessed March 2016). In an effort to identify further published, unpublished, and ongoing trials we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating GABA receptor agonists versus placebo for people with acute stroke (within 12 hours after stroke onset), with the primary outcomes of efficacy and safety.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed the risk of bias.
MAIN RESULTS
We included five trials with 3838 participants (3758 analyzed). The methodological quality of the included trials was generally good, with an unclear risk for selection bias only. Four trials (N = 2909) measured death and dependency at three months for chlormethiazole versus placebo; pooled results did not find a significant difference (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.96 to 1.11). One trial (N = 849) measured this outcome for diazepam versus placebo (RR 0.94, 95% CI 0.82 to 1.07). The most frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; N = 2527) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46; two trials; N = 2527).
AUTHORS' CONCLUSIONS
This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke. More well-designed RCTs with large samples of participants with total anterior circulation syndrome are required to determine if there are benefits for this subgroup. Somnolence and rhinitis are frequent adverse events related to chlormethiazole.
Topics: Acute Disease; Chlormethiazole; Diazepam; Disorders of Excessive Somnolence; GABA Agonists; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic; Rhinitis; Stroke
PubMed: 27701753
DOI: 10.1002/14651858.CD009622.pub4 -
Epilepsy & Behavior : E&B Oct 2016The aim of this review was to systematically examine safety and efficacy outcomes, as well as patient/caregiver satisfaction, from clinical studies in pediatric and... (Review)
Review
PURPOSE
The aim of this review was to systematically examine safety and efficacy outcomes, as well as patient/caregiver satisfaction, from clinical studies in pediatric and adult patients treated with benzodiazepines (BZDs) through various administration routes in response to seizure emergencies.
METHODS
A literature search was conducted to identify articles describing the use of various routes of administration (RoAs) of BZDs for the treatment of seizure emergencies through April 21, 2015, using Embase™ and PubMed®. Eligible studies included (a) randomized controlled trials or (b) controlled nonrandomized clinical trials, either retrospective or prospective. Outcome assessments reviewed were 1) time to administration, 2) time to seizure termination, 3) rate of treatment failure, 4) prevention of seizure recurrence, 5) patient and caregiver treatment satisfaction, 6) adverse events related to BDZ treatment or RoA, and 7) respiratory adverse events.
RESULTS
Seventy-five studies evaluated safety and efficacy using individual or comparator BDZs of various RoAs for treating seizure emergencies in all-aged patients with epilepsy. Buccal, intranasal (IN), or intramuscular (IM) BZDs were often more rapidly administered compared with rectal and intravenous (IV) formulations. Time to seizure termination, seizure recurrence rates, and adverse events were generally similar among RoAs, whereas nonrectal RoAs resulted in greater patient and caregiver satisfaction compared with rectal RoA.
SIGNIFICANCE
Results of this systematic literature review suggest that nonrectal and non-IV BZD formulations provide equal or improved efficacy and safety outcomes compared with rectal and IV formulations for the treatment of seizure emergencies.
Topics: Adult; Anticonvulsants; Benzodiazepines; Child; Emergencies; Female; Humans; Male; Patient Satisfaction; Seizures; Treatment Outcome
PubMed: 27611828
DOI: 10.1016/j.yebeh.2016.07.018 -
Epilepsy Research May 2016To explore the existing evidence for anti-convulsant drugs and their routes of administration in treating acute seizures in children and adults when intravenous access... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To explore the existing evidence for anti-convulsant drugs and their routes of administration in treating acute seizures in children and adults when intravenous access is not available.
METHODS
All major databases including Medline via Ovid, PubMed, Cochrane CENTRAL, Embase, and Google Scholar were searched till May 2015. Randomized and quasi-randomized controlled trials comparing two anti-convulsant drugs (at least one comparator being administered through non-intravenous route) for treatment of acute seizures were included.
OUTCOME MEASURES
Primary outcome measure was proportion of children with clinical seizure cessation within 10min of drug administration. Secondary outcome measures were time taken to clinical seizure cessation from the time of admission and from the time of drug administration, and incidence of significant adverse effects.
RESULTS
Out of the 19,165 citations, 26 studies were finally included. Regarding the primary outcome measure, the quality of evidence was 'moderate' for following 3 comparisons: buccal midazolam being superior to per-rectal diazepam (RR 1.14; 95% CI, 1.06-1.24), intra-nasal lorazepam being same as intravenous lorazepam (RR 1.04; 95% CI, 0.89-1.22) and intramuscular paraldehyde (RR 1.22; 95% CI, 0.99-1.52). The quality of evidence was 'very-low' for 1 comparison: per-rectal lorazepam being superior to per-rectal diazepam (RR 3.17; 95% CI, 1.63-6.14). The quality of evidence was 'low' for following 2 comparisons: sub-lingual lorazepam being inferior to rectal diazepam (RR 0.71; 95% CI, 0.62-0.81), and intranasal midazolam being superior to per-rectal diazepam (RR 1.14; 95% CI, 1.05-1.25). The rest of the comparisons did not show any difference, but the quality of evidence was 'low' to 'very low'. The time to seizure cessation after drug administration was lower in the intravenous group. However, time to seizure cessation after presentation (includes time for drug administration) was lower in the non-intravenous group. Significant adverse effects were infrequently reported and when present, were similar in both the groups.
CONCLUSIONS
When intravenous access is not available, non-intravenous routes of administration of benzodiazepines should be considered for the control of acute seizures in children/adults. The preference may be guided by availability, expertise and social preference. [PROSPERO No: CRD42015019012].
Topics: Anticonvulsants; Humans; Randomized Controlled Trials as Topic; Seizures
PubMed: 26922313
DOI: 10.1016/j.eplepsyres.2016.02.006 -
Surgical Technology International Dec 2023To systematically evaluate cases of local anaesthetic systemic toxicity (LAST) in adult urological patients.
OBJECTIVE
To systematically evaluate cases of local anaesthetic systemic toxicity (LAST) in adult urological patients.
METHODS
A search of the Cochrane, Embase, and Medline databases as well as grey literature from 1 January 1974 to 1 February 2023 was performed using reported methods. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Eligible studies were published in English, described LAST secondary to local anaesthetic administration by urological medical staff to an adult patient, and reported >1 symptom of LAST.
RESULTS
One hundred fifty-seven publications were screened, and six eligible studies (all case reports) were identified, representing six cases of LAST in adult urological patients. Patients were aged 29-54 years and one was female. Cases occurred secondary to penile dorsal nerve block (two cases), scrotal self-injection (two), circumcision (one) or trans-vaginal tape insertion (one). Causative drugs were lidocaine (three patients; median dose 600mg) and bupivacaine (three; 200mg). While one patient was found deceased at home and received no treatment, five experienced LAST as inpatients and were discharged with no deficit. Three patients (50%) experienced a state of reduced consciousness or seizures, one experienced psychosis and one had asymptomatic tachyarrhythmia. Management consisted of supportive management (five patients), intravenous lipid emulsion (three) or intravenous thiopental and diazepam (one). Recommended tools suggested that two of these studies were at moderate or high risk of bias.
CONCLUSION
LAST is seen only rarely in adult urology. Most iatrogenic cases occur due to penile dorsal nerve block and most patients have no long-term sequelae. Urologists should be familiar with its presentation and management, and minimise risk by adhering to local anaesthetic maximum safe dose ranges.
PubMed: 38237111
DOI: 10.52198/23.STI.43.UR1725 -
The Cochrane Database of Systematic... Jun 2020As a retained placenta is a potential life-threatening obstetrical complication, effective and timely management is important. The estimated mortality rates from a...
BACKGROUND
As a retained placenta is a potential life-threatening obstetrical complication, effective and timely management is important. The estimated mortality rates from a retained placenta in developing countries range from 3% to 9%. One possible factor contributing to the high mortality rates is a delay in initiating manual removal of the placenta. Effective anaesthesia or analgesia during this procedure will provide adequate uterine relaxation and pain control, enabling it to be carried out effectively.
OBJECTIVES
To assess the effectiveness and safety of general, regional, and local anaesthesia or analgesia during manual removal of a retained placenta.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform to 30 September 2019, and reference lists of retrieved studies.
SELECTION CRITERIA
We sought randomised controlled trials (RCTs), quasi-randomised controlled trials, and cluster-randomised trials that compared different methods of preoperative or intraoperative anaesthetic or analgesic, administered during the manual removal of a retained placenta.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the study reports for inclusion, and risk of bias, extracted data and checked them for accuracy. We followed standard Cochrane methodology.
MAIN RESULTS
We identified only one randomised controlled trial (N = 30 women) that evaluated the effect of paracervical block on women undergoing manual removal of a retained placenta compared with intravenous pethidine and diazepam. The study was conducted in a hospital in Papua New Guinea. The study was at high risk of bias of performance bias and detection bias, low risk of attrition bias, and an unclear risk of selection bias, reporting bias, and other bias. The included study did not measure this review's primary outcomes of pain intensity and adverse events. The study reported that there were no women, in either group, who experienced an estimated postpartum blood loss of more than 500 mL. We are uncertain about the providers' satisfaction with the procedure, defined as their perception of achieving good pain relief during the procedure (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.71 to 3.16, one study, 30 women; very low quality evidence). We are also uncertain about the women's satisfaction with the procedure, defined as their perception of achieving good pain relief during the procedure (RR 0.82, 95% CI 0.49 to 1.37; one study, 30 women; very low quality evidence). The included study did not report on any of our other outcomes of interest.
AUTHORS' CONCLUSIONS
There is insufficient evidence from one small study to evaluate the effectiveness and safety of anaesthesia or analgesia during the manual removal of a retained placenta. The quality of the available evidence was very low. We downgraded based on issues of limitations in study design (risk of bias) and imprecision (single study with small sample size, few or no events, and wide confidence intervals). There is a need for well-designed, multi-centre, randomised, controlled trials to evaluate the effectiveness and safety of different types of anaesthesia and analgesia during manual removal of a retained placenta. These studies could report on the important outcomes outlined in this review.
Topics: Analgesia, Obstetrical; Anesthesia, Obstetrical; Female; Humans; Job Satisfaction; Nerve Block; Pain, Procedural; Patient Satisfaction; Placenta, Retained; Pregnancy
PubMed: 32529658
DOI: 10.1002/14651858.CD013013.pub2 -
Developmental Medicine and Child... Dec 2017To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP). (Review)
Review
AIM
To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP).
METHOD
A systematic review was performed according to the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Articles were searched for in PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, Database of Reviews of Effectiveness, OTSeeker, Physiotherapy Evidence Database, REHABDATA, and ClinicalTrials.gov.
RESULTS
Sixteen articles met the eligibility criteria. Eight studies on trihexyphenidyl and two on levodopa showed contradictory results. Low efficacy was reported for diazepam, dantrolene sodium, perphenazine, and etybenzatropine. Tetrabenazine, gabapentin and levetiracetam should be studied in more detail. The updated available evidence does not support any therapeutic algorithm for the management of dyskinetic CP.
INTERPRETATION
This lack of evidence is partially owing to the inconsistency of classifications of patients and of outcome measures used in the reviewed studies. Further randomized, double-blind, placebo-controlled pharmacological trials, optimized for different age groups, based on valid, reliable, and disease-specific rating scales are strongly needed. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health.
WHAT THIS PAPER ADDS
Evidence to prove (or disprove) the efficacy of oral drugs in dyskinetic cerebral palsy is low. The most investigated drugs, trihexyphenidyl and levodopa, show contradictory results. Tetrabenazine, levetiracetam, and gabapentin efficacy should be studied in more detail. Lack of evidence is partially due to the inconsistency of classifications and outcome measures used. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health in next clinical trials.
Topics: Anticonvulsants; Cerebral Palsy; Dyskinesias; Humans; Neurotransmitter Agents; Outcome Assessment, Health Care
PubMed: 28872668
DOI: 10.1111/dmcn.13532 -
Anesthesia and Pain Medicine Jan 2021Postoperative delirium (POD) is a condition of cerebral dysfunction and a common complication after surgery. This study aimed to compare and determine the relative...
BACKGROUND
Postoperative delirium (POD) is a condition of cerebral dysfunction and a common complication after surgery. This study aimed to compare and determine the relative efficacy of pharmacological interventions for preventing POD using a network meta-analysis.
METHODS
We performed a systematic and comprehensive search to identify and analyze all randomized controlled trials until June 29, 2020, comparing two or more pharmacological interventions, including placebo, to prevent or reduce POD. The primary outcome was the incidence of POD. We performed a network meta-analysis and used the surface under the cumulative ranking curve (SUCRA) values and rankograms to present the hierarchy of the pharmacological interventions evaluated.
RESULTS
According to the SUCRA value, the incidence of POD decreased in the following order: the combination of propofol and acetaminophen (86.1%), combination of ketamine and dexmedetomidine (86.0%), combination of diazepam, flunitrazepam, and pethidine (84.8%), and olanzapine (75.6%) after all types of anesthesia; combination of propofol and acetaminophen (85.9%), combination of ketamine and dexmedetomidine (83.2%), gabapentin (82.2%), and combination of diazepam, flunitrazepam, and pethidine (79.7%) after general anesthesia; and ketamine (87.1%), combination of propofol and acetaminophen (86.0%), and combination of dexmedetomidine and acetaminophen (66.3%) after cardiac surgery. However, only the dexmedetomidine group showed a lower incidence of POD than the control group after all types of anesthesia and after general anesthesia.
CONCLUSIONS
Dexmedetomidine reduced POD compared with the control group. The combination of propofol and acetaminophen and the combination of ketamine and dexmedetomidine seemed to be effective in preventing POD. However, further studies are needed to determine the optimal pharmacological intervention to prevent POD.
PubMed: 33445233
DOI: 10.17085/apm.20079 -
The Cochrane Database of Systematic... Feb 2017Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs.
OBJECTIVES
To evaluate primarily the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures; but also to evaluate any other drug intervention where there was a sound biological rationale for its use.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2016, Issue 7); MEDLINE (1966 to July 2016); Embase (1966 to July 2016); Database of Abstracts of Reviews of Effectiveness (DARE) (July 2016). We imposed no language restrictions. We also contacted researchers in the field to identify continuing or unpublished studies.
SELECTION CRITERIA
Trials using randomised or quasi-randomised participant allocation that compared the use of antiepileptic, antipyretic or other plausible agents with each other, placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors (RN and MO) independently applied predefined criteria to select trials for inclusion and extracted the predefined relevant data, recording methods for randomisation, blinding and exclusions. For the 2016 update a third author (MC) checked all original inclusions, data analyses, and updated the search. Outcomes assessed were seizure recurrence at 6, 12, 18, 24, 36, and 48 months and at age 5 to 6 years in the intervention and non-intervention groups, and adverse medication effects. We assessed the presence of publication bias using funnel plots.
MAIN RESULTS
We included 40 articles describing 30 randomised trials with 4256 randomised participants. We analysed 13 interventions of continuous or intermittent prophylaxis and their control treatments. Methodological quality was moderate to poor in most studies. We found no significant benefit for intermittent phenobarbitone, phenytoin, valproate, pyridoxine, ibuprofen or zinc sulfate versus placebo or no treatment; nor for diclofenac versus placebo followed by ibuprofen, acetaminophen or placebo; nor for continuous phenobarbitone versus diazepam, intermittent rectal diazepam versus intermittent valproate, or oral diazepam versus clobazam.There was a significant reduction of recurrent febrile seizures with intermittent diazepam versus placebo or no treatment, with a risk ratio (RR) of 0.64 (95% confidence interval (CI) 0.48 to 0.85 at six months), RR of 0.69 (95% CI 0.56 to 0.84) at 12 months, RR 0.37 (95% CI 0.23 to 0.60) at 18 months, RR 0.73 (95% CI 0.56 to 0.95) at 24 months, RR 0.58 (95% CI 0.40 to 0.85) at 36 months, RR 0.36 (95% CI 0.15 to 0.89) at 48 months, with no benefit at 60 to 72 months. Phenobarbitone versus placebo or no treatment reduced seizures at 6, 12 and 24 months but not at 18 or 72 month follow-up (RR 0.59 (95% CI 0.42 to 0.83) at 6 months; RR 0.54 (95% CI 0.42 to 0.70) at 12 months; and RR 0.69 (95% CI 0.53 to 0.89) at 24 months). Intermittent clobazam compared to placebo at six months resulted in a RR of 0.36 (95% CI 0.20 to 0.64), an effect found against an extremely high (83.3%) recurrence rate in the controls, which is a result that needs replication.The recording of adverse effects was variable. Lower comprehension scores in phenobarbitone-treated children were found in two studies. In general, adverse effects were recorded in up to 30% of children in the phenobarbitone-treated group and in up to 36% in benzodiazepine-treated groups. We found evidence of publication bias in the meta-analyses of comparisons for phenobarbitone versus placebo (eight studies) at 12 months but not at six months (six studies); and valproate versus placebo (four studies) at 12 months, with too few studies to identify publication bias for the other comparisons.Most of the reviewed antiepileptic drug trials are of a methodological quality graded as low or very low. Methods of randomisation and allocation concealment often do not meet current standards; and treatment versus no treatment is more commonly seen than treatment versus placebo, leading to obvious risks of bias. Trials of antipyretics and zinc were of higher quality.
AUTHORS' CONCLUSIONS
We found reduced recurrence rates for children with febrile seizures for intermittent diazepam and continuous phenobarbitone, with adverse effects in up to 30%. Apparent benefit for clobazam treatment in one trial needs to be replicated to be judged reliable. Given the benign nature of recurrent febrile seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of medical services and information on recurrence, first aid management and, most importantly, the benign nature of the phenomenon.
Topics: Anticonvulsants; Antipyretics; Child; Child, Preschool; Humans; Infant; Randomized Controlled Trials as Topic; Recurrence; Seizures, Febrile
PubMed: 28225210
DOI: 10.1002/14651858.CD003031.pub3