title: Efficacy and safety of anti-epileptic drugs in patients with active convulsive seizures when no IV access is available: Systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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].
authors.affiliation: Division of Pediatric Neurology, Department of Neonatal, Pediatric and Adolescent Medicine, BL Kapur (BLK) Super Speciality Hospital, Pusa Road, New Delhi 110005, India. Electronic address: puneet_mpa@yahoo.com.
authors.forename: Puneet
authors.initials: P
authors.lastname: Jain
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi 110001, India. Electronic address: sharma.suvasini@gmail.com.
authors.forename: Suvasini
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Programme for Neurological Diseases and Neuroscience Evidence, Research and Action on Mental and Brain Disorders (MER), Department of Mental Health and Substance Abuse, World Health Organization. Electronic address: duat@who.int.
authors.forename: Tarun
authors.initials: T
authors.lastname: Dua
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, University of Verona, Italy. Electronic address: corrado.barbui@univr.it.
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
authors.affiliation: Department of Pediatrics, All India Institute of Medical Sciences, Bhuvaneshwar, Odisha, India. Electronic address: rrdas05@gmail.com.
authors.forename: Rashmi Ranjan
authors.initials: RR
authors.lastname: Das
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi 110001, India. Electronic address: drsaneja@gmail.com.
authors.forename: Satinder
authors.initials: S
authors.lastname: Aneja
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants
keywords: Acute seizures; Benzodiazepines; Convulsive seizures; Pre-hospital; Status epilepticus