Failed Bupivacaine Spinal Anesthesia due to Chemical Alteration
Abstract Number: 60
Abstract Type: Original Research
Introduction: Causes of failed block include technical and patient-related factors and have serious clinical consequences. We identified by mass spectrometry a lot-specific, chemically altered bupivacaine spinal solution as the cause of failed spinal anesthesia during cesarean sections.
Clinical Course: We experienced an epidemic of 14 cases of failed spinal anesthetics, clustered over an 8 week period. Failed spinals resulted in inadequate sensory block, prolonged block onset, insufficient block duration, or no block, requiring supplemental regional anesthesia, intravenous sedation, or general anesthesia. Failures were limited to 3 suspect tray lot numbers. The same standardized technique for administering spinal anesthesia was used in all cases. Clustering of these failures suggested altered drug concentration/formulation or drug stability issues in transit/storage. The FDA was contacted. Shipment of suspect spinal kits were typically stored for > 9 hours in a non-environmentally controlled truck at temperatures below freezing before delivery. A negative batch analysis, normal product potency, and unremarkable testing of retained samples by the drug manufacturer led us to suspect drug stability issues in transit/storage. Using mass spectroscopy, we analyzed suspect samples and found the drug had a mass/charge (m/z) ratio of 276 compared to 289 m/z of the control sample (molecular mass is 288; Figure), confirming our suspicion of chemical alteration.
Discussion: Reasons cited for failure include technique-related, patient-related, and catheter-related factors. CSF drug maldistribution or inadequate CSF drug concentration is also cited. Winter low temperatures in Pittsburgh average (19-24˚F). A structural change could have been due to exposure to freezing temperatures during storage/transit. Bupivacaine spinal solution product insert recommends storage at 68-77 ˚F and protection from freezing. As a temporary solution, a separate bupivacaine ampule was included. In the long term, the spinal kit manufacturer now directly drop-ships spinal kits, which decreased the failed spinal anesthetic rate. We are in the process of purchasing a different kit.
Conclusion: Fluctuating environmental conditions during drug transport and storage may have caused a chemical change rendering the drug inactive as evidenced by mass spectroscopy. We are further analyzing and elucidating the chemical alteration.