Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies
Bibliographic record
Abstract
Valproic acid toxicity is not infrequent and is difficult to treat, as there is no specific antidote. In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".