Neurotoxicity with single dose intrathecal midazolam administration

Abstract

Midazolam administered at single dose by the intrathecal route may have neurotoxic effects on the neurons and myelinated axons at 24 h and 6 days following administration.

Addition of midazolam to continuous postoperative epidural bupivacaine infusion reduces requirement for rescue analgesia in children undergoing upper abdominal and flank surgery

“…Neurotoxicity studies of central midazolam in animals have yielded conflicting results. Six studies have found neurotoxicity associated with neuraxial midazolam [18][19][20][21][22][23] whereas 7 others have reported no adverse effect associated with its use [24][25][26][27][28][29][30]. The studies documenting neurotoxicity have a number of limitations that have raised several questions regarding the validity of the results obtained.…”

Midazolam Activates the Intrinsic Pathway of Apoptosis Independent of Benzodiazepine and Death Receptor Signaling

“…14 Severe alteration of cellular integrity was observed after a single dose of intrathecal midazolam using electron microscopy 24 hrs and 6 days after administration. 15 Increasing doses of intrathecal midazolam as well as repeated application led to a dose-and time-dependent increase in myelin separation and interruption as well as increasing vacuoles in neurons. 16 Thus, most in vivo studies show a neurotoxic effect of intrathecally applied midazolam, but the mechanism of toxicity remains unknown.…”

Caudal midazolam does not affect sevoflurane requirements and recovery in pediatric day‐case hernioplasty

“…Some investigators were unable to demonstrate neurotoxic effects after intrathecal administration of midazolam to the rat 18 . Whereas others indicated that midazolam has neurotoxic effects that depend on the dose and the repetition of dosing when it is administered intrathecally, there may be reason to be skeptical of intrathecal use in humans 19–21 . In addition, 10% hydrochloric acid pH 3.3–3.9 used for the midazolam vehicle was considered as the possible cause of neurotoxicity 22,23 .…”