2026/03/10 by Chia‐Hao Ho, Cheng‐Wei Lu · 1 voice
Environmental Science · Medicine · #Anesthesia and Sedative Agents #Antibiotics Pharmacokinetics and Efficacy #Pharmaceutical and Antibiotic Environmental Impacts
paper · doi:10.1111/anae.70199
openalex publication_date 2026/03/10 · openalex created_date 2026/03/11 · openalex updated_date 2026/06/18
Environmental sustainability is a major priority in modern anaesthesia [1]. Currently, total intravenous anaesthesia (TIVA) is often considered more environmentally friendly than volatile inhalational anaesthesia because it has reduced greenhouse gas emissions. However, this view ignores the potential water pollution caused by intravenous drugs. Propofol, used widely in TIVA, is a phenol derivative that is detected frequently in hospital wastewater due to significant clinical wastage [2]. As a lipophilic compound, propofol may accumulate in aquatic organisms, posing a risk to the ecosystem. The introduction of remimazolam, an ultra-short-acting benzodiazepine, offers a potential alternative for TIVA. Unlike propofol, remimazolam is hydrolysed rapidly by tissue esterases into a carboxylic acid metabolite (CNS 7054) [3]. The environmental impact of this metabolite is not well understood. The aim of this study was to utilise in-silico quantitative structure–activity relationship modelling to compare the predicted aquatic toxicity of propofol and the remimazolam metabolite, providing a more complete ecological assessment. Aquatic toxicity was evaluated using the Ecological Structure Activity Relationships Class Program (Version 2.2; United States Environmental Protection Agency) [4]. This in-silico methodology aligns with ‘replacement, reduction and refinement’ principles, offering an ethical alternative to in-vivo animal testing for risk assessment [5]. We retrieved the chemical structures of propofol and the remimazolam metabolite (CNS 7054) from the PubChem database and converted them into Simplified Molecular Input Line Entry System codes. The model predicts toxicity based on structure-specific regression equations derived from measured data. We analysed the octanol–water partition coefficient (LogKow) to estimate bioaccumulation potential and calculated standard acute toxicity endpoints (LC50 and EC50) for fish, daphnids and green algae. Propofol is characterised by a high octanol–water partition coefficient (LogKow 3.79), classifying it as a lipophilic substance with significant bioaccumulation potential. In contrast, CNS 7054 exhibits a low LogKow of 1.25, indicating high water solubility and minimal risk of bioaccumulation. In terms of acute toxicity, propofol was predicted to be toxic to aquatic organisms, with 96-h LC50 values of 4.6 mg.l-1 for fish and 48-h LC50 values of 0.85 mg.l-1 for daphnids. Conversely, CNS 7054 was predicted to be practically non-toxic across all trophic levels, with estimated lethal concentrations exceeding 100 mg.l-1 (Table 1). While propofol is favoured for its lack of greenhouse gas emissions, our data suggest it poses a persistent threat to aquatic ecosystems due to its lipophilic nature and potential for bioaccumulation. In recent years, remimazolam has emerged as a valuable drug for procedural sedation and general anaesthesia [6, 7]. As its clinical use expands, its environmental profile becomes increasingly relevant. Remimazolam appears to exemplify the principles of ‘benign-by-design’ pharmaceuticals. Its rapid hydrolysis into a highly polar, hydrophilic metabolite ensures that the excreted compound does not accumulate in aquatic organisms and is virtually non-toxic. We acknowledge several limitations in this study. First, the results are based on in-silico predictions rather than in-vivo biological assays. However, the quantitative structure–activity relationship is a validated tool for initial risk screening [5]. Second, we focused solely on the excretion phase. A complete life-cycle assessment is necessary to determine the total carbon footprint. Crucially, such future comparisons must ensure clinical equipotency. Since remimazolam often exhibits higher bispectral index values than propofol at equivalent sedation levels [7], strictly adhering to traditional bispectral index targets may lead to overdosing and an unfair inflation of its environmental impact. We recommend that future comparative studies standardise anaesthetic depth using multiparametric monitoring to ensure a fair ecological comparison. In conclusion, while propofol remains a cornerstone of TIVA, its environmental footprint extends into the water cycle. Remimazolam offers a promising alternative with a significantly more favourable aquatic safety profile. Future ‘green anaesthesia’ strategies should adopt a holistic view, balancing carbon mitigation with the protection of water resources. No external funding or competing interests declared.