Atracurium Besylate
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Atracurium Besylate: From Neuromuscular Blockade to Preeclampsia
One-Sentence Summary
Atracurium besylate is a non-depolarizing neuromuscular blocking agent (NMBA) used in anesthesia practice to facilitate endotracheal intubation and maintain skeletal muscle relaxation during surgery and mechanical ventilation. The TxGNN model predicts it may be effective for Preeclampsia, with 0 clinical trials and 4 publications associated with this pairing — however, critical review indicates the literature reflects atracurium’s role as an anesthetic adjunct in preeclamptic patients undergoing cesarean section, not as a treatment for preeclampsia itself. Across all 10 predicted indications, the overall recommendation is Hold.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Neuromuscular blockade during general anesthesia and mechanical ventilation |
| Predicted New Indication | Preeclampsia |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| Malaysia Market Status | ✓ Marketed |
| Number of Registrations | 10 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from this Evidence Pack. Based on established pharmacology, Atracurium besylate is a competitive (non-depolarizing) NMBA that antagonises nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ), blocking acetylcholine binding and causing reversible skeletal muscle paralysis. Its clearance is unique among NMBAs: it undergoes spontaneous Hofmann elimination and ester hydrolysis, making it independent of hepatic or renal function — a property that renders it particularly attractive in high-risk obstetric settings.
Preeclampsia is a pregnancy-specific disorder driven by placental ischaemia → endothelial dysfunction → systemic hypertension and proteinuria, involving sFlt-1/PlGF imbalance, oxidative stress, and vascular inflammation. Atracurium possesses no antihypertensive, anti-angiogenic, anti-inflammatory, or endothelial-protective mechanism, and therefore has no plausible therapeutic action against preeclampsia pathophysiology.
The literature signal arises from clinical co-occurrence rather than therapeutic relevance: atracurium is routinely used during cesarean section for preeclamptic patients as part of the anaesthetic protocol. A critical safety interaction further explains the co-appearance in literature — concurrent magnesium sulfate (MgSO₄), the first-line treatment for eclamptic seizures, potentiates neuromuscular blockade at the NMJ, necessitating careful dose reduction of atracurium. This pharmacokinetic interaction generates published safety assessments, but the causal direction is opposite to drug repurposing: atracurium requires management because of preeclampsia treatment, it does not treat preeclampsia.
Clinical Trial Evidence
No clinical trials studying Atracurium besylate as a treatment for preeclampsia are currently registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41103680 | 2025 | RCT | Anesthesiology and Pain Medicine | Compared serum IL-6, leptin, and adiponectin after cesarean section under general vs. spinal anaesthesia; atracurium used as part of general anaesthesia protocol — not investigating preeclampsia treatment |
| 9646009 | 1998 | PK Study | Clinical Pharmacokinetics | Pharmacokinetics of atracurium, vecuronium, and pancuronium during pregnancy; atracurium Vss and clearance found unchanged despite 45% plasma volume expansion in pregnancy |
| 3778800 | 1986 | Observational Study | British Journal of Anaesthesia | Direct observational study of atracurium use in pre-eclamptic patients; addresses safety and the MgSO₄–NMJ potentiation interaction, not efficacy in treating preeclampsia |
| 18383970 | 2008 | Case Series | Rev Esp Anestesiol Reanim | Remifentanil bolus for haemodynamic control during cesarean in 12 high-risk patients ineligible for spinal anaesthesia; atracurium included as anaesthetic component |
Malaysia Market Information
Atracurium besylate has 10 registered products in Malaysia. Detailed product-level data (authorization numbers, product names, dosage forms, approved indication text) was not available in this Evidence Pack. Please refer directly to the NPRA database for complete registration details.
Safety Considerations
Detailed warnings and contraindications were not available in this Evidence Pack. Please refer to the approved package insert for comprehensive safety information.
Clinically critical interaction for this predicted indication: Concurrent magnesium sulfate (MgSO₄) — the standard seizure prophylaxis in preeclampsia — significantly potentiates neuromuscular blockade. When atracurium is administered to patients receiving MgSO₄, the dose should be reduced and neuromuscular function closely monitored to avoid prolonged paralysis and respiratory failure.
Conclusion and Next Steps
Decision: Hold
Rationale: Despite a high TxGNN prediction score (99.97%), pharmacological analysis identifies this as a false positive: the prediction is driven by clinical co-occurrence in obstetric anaesthesia settings rather than any mechanistic link between atracurium and preeclampsia. All 10 predicted indications in this Evidence Pack received a Hold recommendation, reflecting a consistent pattern — atracurium’s role as an intraoperative muscle relaxant places it in many clinical contexts without any therapeutic relationship to the associated diseases.
To support a reassessment, the following would be required:
- Identification of a plausible therapeutic mechanism relevant to preeclampsia (e.g., endothelial protection, antihypertensive effect, anti-inflammatory activity) — none currently exists in the literature
- At least one prospective study demonstrating clinical benefit on preeclampsia endpoints (blood pressure control, proteinuria reduction, maternal or fetal outcomes)
- Complete NPRA product registration details for accurate market assessment
- Package insert data (warnings, contraindications, full DDI profile) to support S1 safety screening
⚠️ Disclaimer: This report is intended for research reference only and does not constitute medical advice. Drug repurposing candidates require clinical validation before any therapeutic application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.