Authors: Persson, Niklas Daniel Åke et al.
Anesthesiology October 2025 | DOI: 10.1097/ALN.0000000000005794
This preclinical imaging study investigated how anesthesia type and systemic hyperosmolality affect the central nervous system (CNS) distribution of intrathecally administered drugs. The researchers examined the pharmacokinetics of a high–molecular weight spinal tracer (technetium-99m–labeled human serum albumin nanocolloid, 66.5 kDa) in female rats to evaluate whether general anesthetics and hypertonic saline (HTS) could alter cerebrospinal fluid (CSF) transport along glymphatic pathways.
Animals were anesthetized with either ketamine–dexmedetomidine (K/DEX) or isoflurane and received intraperitoneal injections of either hypertonic saline (40 mOsm/kg) or isotonic saline. Whole-body tracer kinetics were tracked using in vivo single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) was used to assess spinal subarachnoid space volume.
Compared with isoflurane, K/DEX anesthesia increased local spinal tracer concentration (AUC₀–₁₁₆ ratio = 1.78, P = 0.0016) while reducing its spread to the brain (P = 0.026). K/DEX also enlarged the spinal subarachnoid space by 46%, suggesting an enhanced reservoir effect at the spinal level. When hypertonic saline was administered under K/DEX anesthesia, intracranial tracer delivery and CNS retention were significantly elevated (P = 0.0047), whereas this effect was not significant under isoflurane.
These results demonstrate that both anesthetic choice and systemic osmotic conditions markedly influence intrathecal drug biodistribution. Hyperosmolar therapy can enhance rostral drug transport along CSF pathways, potentially enabling improved brain delivery of spinal medications.
What You Should Know
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The type of anesthesia alters intrathecal drug distribution—K/DEX enhances spinal concentration and changes CSF dynamics compared with isoflurane.
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Hypertonic saline increases the movement of spinally administered agents into the brain and prolongs CNS exposure.
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These findings highlight new avenues for optimizing intrathecal therapy through anesthetic selection and osmotic modulation.
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