Sufentanil–Esketamine PCIA Mixtures Remain Stable for 14 Days in Refrigeration, shows study

Are you preparing sufentanil and esketamine mixtures for patient-controlled intravenous analgesia (PCIA) and wondering how long these solutions stay stable? Recent research provides much-needed clarity on their physicochemical compatibility and shelf life under clinical conditions.

Background: The Need for Evidence on PCIA Mixture Stability

Combining sufentanil (a potent μ-opioid agonist) with esketamine (an NMDA receptor antagonist) in PCIA is increasingly common for multimodal postoperative pain management. This approach can improve analgesia and reduce opioid-related side effects. However, no commercial admixture exists, and until now, no published data addressed the stability of these drugs when mixed in 0.9% sodium chloride and stored in polyvinyl chloride (PVC) bags.

Study Design: Rigorous Assessment of Physical and Chemical Stability

Researchers aseptically mixed 1.0 µg/mL sufentanil with esketamine at 0.25, 0.5, or 1.0 mg/mL in 0.9% sodium chloride. The mixtures were stored in 100 mL PVC bags at room temperature (25°C) and refrigeration (4°C).

Room temp stability: Assessed over 48 hours

Refrigerated stability: Assessed over 14 days

Physical stability was monitored by visual inspection (for precipitation, turbidity, discoloration) and pH measurement. Chemical stability was measured using validated liquid chromatography–tandem mass spectrometry (LC-MS/MS), with stability defined as ≥90% retention of initial drug concentration.

Findings: Consistent Stability Across Conditions

All tested sufentanil–esketamine mixtures remained physically and chemically stable throughout the study:

No precipitation, turbidity, or color change observed at any time point.

pH values remained between 4.87 and 5.68, varying by less than 0.8 units.

Both drugs retained at least 95% of initial concentration under all conditions (well above the 90% threshold).

This stability held true for up to 48 hours at room temperature and 14 days under refrigeration, regardless of light exposure.

Clinical Implications: Safe Centralized Preparation and Extended Storage

These findings support the centralized batch preparation of sufentanil/esketamine PCIA mixtures, including advance compounding in hospital pharmacy settings. This can:

Improve operational efficiency and timely drug distribution

Enhance safety by standardizing admixture protocols

Reduce error rates in clinical workflows

However, clinicians should adhere to sterile compounding standards (e.g., USP 797) to mitigate infection risks, as this study did not assess microbial contamination.

Limitations and Recommendations

The study focused on physicochemical stability but did not include forced degradation or microbial testing. Results are specific to PVC containers and 0.9% sodium chloride as the diluent.

Conclusion

Sufentanil (1.0 µg/mL) and esketamine (0.25–1.0 mg/mL) mixtures in 0.9% sodium chloride are stable for up to 14 days in refrigerated PVC bags and for 48 hours at room temperature. These data support safe, efficient, and standardized preparation of PCIA admixtures for postoperative pain management.

Key points

Sufentanil–esketamine PCIA admixtures remain stable in PVC bags for 14 days at 4°C and 48 hours at 25°C.

No significant loss of drug concentration or visible change was observed in any mixture.

pH remained within a physiologically safe range throughout storage.

Findings support centralized, advance preparation of these analgesic combinations.

Adherence to sterile compounding guidelines remains essential for safe clinical use.

Citation:

Yao M, Ma Y, Fang B, Du Y, Liu Y, Chen F. Physicochemical stability of sufentanil and esketamine containing analgesic mixtures applied for patient-controlled intravenous analgesia. BMC Anesthesiol. 2026; [in press]. https://doi.org/10.1186/s12871-026-03914-9