Delayed toxicity following acute ingestion of valpromide

Abstract

<jats:p> As valpromide is a prodrug of valproic acid (valproate), the clinical presentation of overdoses with either valpromide or valproate sodium is generally considered similar. Whereas plasma peak levels and signs of central nervous system depression occur within a few hours after the acute ingestion of regular-release forms of valproate sodium, delayed toxicity and time to peak levels following valpromide ingestion can be seen as shown by the three reported cases. They were initially considered as mild because patients presented with no or only moderate symptoms and serum valproate levels were below or at therapeutic levels on admission more than 3 hours post-ingestion in two of the three patients. Serum valproate levels were not monitored until marked deterioration more than 10 hours after ingestion. At the time of deterioration, serum valproate was at toxic level in the three reported cases. Therefore, large intake of valpromide should be closely monitored because no or moderate symptoms together with low plasma levels in the first few hours after ingestion do not exclude a subsequent severe intoxication. Despite the usual favourable outcome and the poor correlation between plasma levels and toxic symptoms, patients should not be discharged until plasma levels are documented to remain at low levels for at least 10 hours after the ingestion of valpromide and the patient asymptomatic. </jats:p>

Neurointensive care management of raised intracranial pressure caused by severe valproic acid intoxication

“…VPAassociated carnitine deficiency has been suggested to be a cause for malignant cerebral oedema in the absence of hepatic failure [15], and carnitine supplementation has been advocated [23]. The delayed neurological deterioration described in the present report is intriguing, but was likely caused by the reappearance of seizures although the complex metabolism of VPA with slow elimination of certain VPA metabolites may have contributed [16,24,25].…”

Valproic acid poisoning: An evidence-based consensus guideline for out-of-hospital management

“…There were six level 4 articles that specifically mentioned delayed onsets of clinical effects after valproic acid ingestion (9,50,66,(72)(73)(74). On closer review, many of these patients had early symptoms followed by delayed deteriorations in their conditions.…”

“…Naloxone There were several level 4 case reports of patients improving significantly after naloxone administration with reversal of coma, respiratory depression, and pinpoint pupils (7-9,40,65,79,80). There were a number of other level 4 or 6 reports in which naloxone had no effect on clinical status (14,19,44,48,52,66,81,82). The doses used were similar to those used in opioid overdose.…”

Adverse Drug Reactions in the ICU

“…Common drugs include anticholinergic, opioid agonists, anesthetics, and other sedatives. In the setting of overdose, absorption can continue longer than predicted by pharmacokinetics, especially for enteric coated or extended release medications, anticholinergics, and/or opioids [207][208][209][210][211][212][213][214][215][216][217][218][219].…”