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Evidence summaries

Drug Management for Acute Tonic-Clonic Convulsions in Children

Intravenous (iv.) lorazepam appears to be as effective as iv. diazepam and with fewer adverse events in the treatment of acute tonic-clonic convulsions in children. Buccal midazolam appears to control seizures better than rectal diazepam. Level of evidence: "B"

A Cochrane review [Abstract] 1 included 18 studies with a total of 2199 children. There was a range of drug treatment options, doses and routes of administration.

  • Buccal midazolam with rectal diazepam:Risk ratio (RR) for seizure cessation was 1.25 (95%CI 1.13 to 1.38; 4 trials, n=690).
  • Buccal and intranasal (in.) anticonvulsants vs. iv. anticonvulsants: They lead to similar rates of seizure cessation, e.g. in. lorazepam appears to be as effective as iv. lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial, n=141) and in. midazolam was equivalent to iv. diazepam (RR 0.98, 95% CI 0.91 to 1.06; 2 trials, n=122).
  • Intramuscular (im.) midazolam vs. iv. diazepam: They showed a similar rate of seizure cessation (RR 0.97, 95% CI 0.87 to 1.09; 2 trials, n=105).
  • Iv. routes of administration: Lorazepam appears to be as effective as diazepam in stopping acute tonic clonic convulsions (RR 1.04, 95% CI 0.94 to 1.16; 3 trials, n=414). There was no statistically significant or clinically important differences between iv. midazolam and diazepam (RR for seizure cessation 1.08, 95% CI 0.97 to 1.21; 1 trial, n=80 children) or iv. midazolam and lorazepam (RR for seizure cessation 0.98, 95% CI 0.91 to 1.04; 1 trial, n=80). In general, iv. anticonvulsants led to more rapid seizure cessation but this was usually compromised by the time taken to establish iv. access.
  • In. lorazepam vs. im. paraldehyde: Lorazepam may be more effective than intramuscular paraldehyde in stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 1 trial, n=160).

Respiratory depression (RD) was the most common and most clinically relevant side effect and, where reported, the frequency of this adverse event was observed in 0% to up to 18% of children. None of the studies individually demonstrated any difference in the rates of RD between the different anticonvulsants or their different routes of administration; but when pooled, 3 studies (n=439) showed that lorazepam was significantly associated with fewer occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to 0.93).

Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in patients, settings and interventions).

References

  • McTague A, Martland T, Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev 2018;1():CD001905. [PubMed]

Primary/Secondary Keywords