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General Anesthesia and Systemic Hyperosmolality Modulate Lumbar Intrathecal Drug Distribution in Female Rats
Niklas Daniel Åke Persson1, Terhi J Lohela2, Jenni E Anttila3
1Individualized Drug Therapy Research Program and Department of Pharmacology, Faculty of Medicine, and Division of Pharmacology and Pharmacotherapy, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Anesthesiology
|October 9, 2025
Summary
Anesthesia and hypertonic saline (HTS) significantly alter how spinal drugs distribute in the central nervous system (CNS). Ketamine-dexmedetomidine anesthesia enhanced spinal drug delivery while reducing brain exposure, unlike isoflurane.
Area of Science:
- Neuroscience
- Pharmacology
- Drug Delivery
Background:
- Spinal drug administration bypasses the blood-brain barrier for direct central nervous system (CNS) access.
- Current lumbar intrathecal delivery methods have limited brain penetration, and intracranial methods pose risks.
- Pharmacological modification of cerebrospinal fluid flow, including by anesthetics and hypertonic saline (HTS), is understudied for spinal drug distribution.
Purpose of the Study:
- To investigate the influence of two anesthetic regimens (ketamine-dexmedetomidine and isoflurane) and HTS on the distribution of spinally administered drugs.
- To assess how these interventions affect drug concentration at spinal and intracranial levels.
Main Methods:
- Female rats received either ketamine-dexmedetomidine or isoflurane anesthesia.
- Hypertonic saline (HTS) or isotonic saline (ITS) was administered intraperitoneally.
- The distribution of a radiolabeled tracer (technetium-99m albumin nanocolloid) administered intrathecally was assessed using single-photon emission computed tomography (SPECT).
- Magnetic resonance imaging (MRI) was used to evaluate anesthetic-induced changes in spinal subarachnoid space volume.
Main Results:
- Ketamine-dexmedetomidine anesthesia increased spinal tracer availability and decreased intracranial exposure compared to isoflurane in rats given ITS.
- Ketamine-dexmedetomidine significantly increased spinal subarachnoid space volume compared to isoflurane.
- HTS markedly enhanced intracranial tracer availability during ketamine-dexmedetomidine anesthesia and prolonged CNS retention in awake rats.
Conclusions:
- Anesthesia choice critically modulates the distribution of intrathecally administered drugs.
- Systemic HTS administration can increase intracranial drug availability from spinal delivery during specific anesthesias and prolong CNS drug presence.
- These findings suggest potential strategies for optimizing spinal drug delivery efficacy and safety in clinical applications.
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