Respiratory, neuromuscular, and cardiovascular effects of neosaxitoxin in isoflurane-anesthetized sheep

Regional Anesthesia and Pain Medicine
Matthew C WylieCharles B Berde

Abstract

Neosaxitoxin (NeoSTX) is a potent site-1 sodium-channel blocker being developed as a local anesthetic. Doses of 100 μg have been used by local infiltration in anesthetized adult humans without adverse effect. We hypothesized that similar doses could cause significant respiratory, neuromuscular, and cardiovascular impairment and sought to test this hypothesis in sheep. Procedures were approved by the Institutional Animal Care and Use Committee. In neuromuscular/respiratory experiments, 33 intubated, isoflurane-anesthetized sheep were randomized to 6 NeoSTX treatment groups: saline control, 1 μg/kg subcutaneous (SC), 1 μg/kg intravenous (IV), 2 μg/kg SC, 2 μg/kg SC with bupivacaine 0.25%, and 3 μg/kg SC. Primary outcome measures were doxapram-stimulated inspired volume (DSIV) and quantitative limb acceleration. In cardiovascular experiments, 8 sheep received escalating IV doses of NeoSTX (1, 2, and 3 μg), with hemodynamic and electrocardiographic measurements. Data were analyzed using repeated-measures analysis of variance with post hoc Bonferroni-corrected comparisons. NeoSTX 1 μg/kg IV and SC produced no significant reduction in DSIV or limb acceleration compared with baseline. NeoSTX 2 μg/kg SC produced clinically mild reducti...Continue Reading

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Citations

Apr 30, 2017·Anesthesia and Analgesia·Claudia M SantamariaDaniel S Kohane
Mar 20, 2015·Anesthesia and Analgesia·Charles Berde
May 1, 2021·Animals : an Open Access Journal From MDPI·Alison SmallIan Colditz
Nov 30, 2021·Expert Opinion on Emerging Drugs·Esra Kutlu YalcinAlparslan Turan

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