Chemotherapy-induced peripheral neuropathy in a dish: dorsal root ganglion cells treated in vitro with paclitaxel show biochemical and physiological responses parallel to that seen in vivo.

The mechanisms underlying chemotherapy-induced peripheral neuropathy have yet to be fully elucidated, but primary afferent neurons have emerged as an especially vulnerable initiating pathophysiological target. An important recent study has also shown that the initial toxicity produced by paclitaxel in patients was highly predictive of long-term outcome. In this study, we therefore focused on defining the mechanisms of acute toxicity produced by paclitaxel treatment on primary sensory neurons under in vitro conditions. In primary rat dorsal root ganglion (DRG) culture with paclitaxel, an increase of pERK and pp38 was observed at 2 hours, and this was accompanied by an increase in expression and release of C-C chemokine ligand 2 (CCL2). There was no change in pJNK. The increase in pERK was sustained at 48 hours of exposure when the expression of TLR4, MyD88, and IL-6 was also increased. IL-6 and CCL2 were colocalized to TLR4-positive cells, and all these responses were prevented by coincubation with a TLR4 antagonist (LPS-RS). Whole-cell patch-clamp recordings revealed that DRG neurons developed spontaneous depolarizing fluctuations (DSFs) in membrane potential and hyperexcitability to current injection but no ectopic action potential activity at 24 and 48 hours of paclitaxel incubation. However, CCL2 applied to cultured neurons not only induced DSFs but also evoked action potentials. Evidence of oxidative stress and mitotoxicity was observed at 48 hours of exposure. These results closely parallel the responses measured in the DRG with paclitaxel exposure in vivo and so indicate that acute toxicity of paclitaxel on the DRG can be modelled using an in vitro approach.

Anesthetic management of pediatric patients undergoing intrathecal nusinersen administration for treatment of spinal muscular atrophy: A single-center experience.

BACKGROUND: Spinal muscular atrophy is a group of autosomal recessive inherited neurological disorders secondary to a genetic mutation that leads to progressive muscle weakness and atrophy. Recently approved by the Food and Drug Administration, Nusinersen is the first treatment specifically for spinal muscular atrophy. This drug must be administered intrathecally, as it does not cross the blood-brain barrier. AIMS: Retrospective review of the individualized perioperative care of spinal muscular atrophy type I and II patients for intrathecal Nusinersen injection. METHODS: After approval from the Institutional Review Board and obtaining informed written consent from parents, we reviewed the anesthetic charts of nine patients who underwent 58 Nusinersen injections over a 23-month period from February 2017 to December 2018. An individualized anesthetic plan was formulated based on the patient's disease severity, anxiety level, and comfort of parents as well as the provider performing the procedure. Patients underwent intrathecal Nusinersen injection under fluoroscopic guidance, with either general anesthesia, monitored anesthesia care with medications or monitored anesthesia care without medications. Patients recovered in the postanesthesia care unit for a minimum of 1 hour after injection, irrespective of the anesthetic method utilized. Analysis included patient demographics, anesthesia type relative to spinal muscular atrophy type I vs. II, and postanesthesia recovery. RESULTS: Nine patients with spinal muscular atrophy types I and II underwent 58 encounters. Five spinal muscular atrophy type I patients underwent 31 encounters, general anesthesia (9), monitored anesthesia care with medications (2), and monitored anesthesia care without medications (20). Four spinal muscular atrophy type II patients underwent 27 encounters, general anesthesia (22), monitored anesthesia care with medications (2), and monitored anesthesia care without medications (3). There were no perioperative complications. CONCLUSION: The anesthetic plan for Nusinersen injections must be individualized to the patient's specific needs and clinical manifestations of the disease. When carefully tailored to each patient, anesthetic care is safe and successful.

Quadratus Lumborum 2 Block as the Sole Anesthetic Technique for Open Hernia Repair in Multimorbid Patients.

Ultrasound-guided quadratus lumborum (QL, QL1-3) blocks have been used extensively for perioperative pain control for patients undergoing abdominal procedures. These blocks provide a more widespread and longer-lasting analgesic effect compared to the transversus abdominis plane (TAP) block. While QL blocks have been used as an adjunct in multimodal postoperative pain control, they are rarely used as the sole anesthetic technique for abdominal surgeries. We report the cases of two high-risk multimorbid patients requiring urgent open umbilical hernia repairs secondary to incarceration or obstruction. Bilateral QL2 blocks were utilized as the sole anesthetic technique to reduce anesthetic risk, with positive outcomes.  Utilization of the QL2 block technique for our patients enabled avoidance of general anesthesia in these high-risk patients because of the extensive area of anesthesia they provide when compared with the TAP and QL1 block techniques. The advantages of the QL2 block for high-risk patients include immediate perioperative pain control, reduced use of muscle relaxants, reduced opioid analgesic requirement for postoperative pain management, and enhanced postoperative recovery. Disadvantages include potential for local anesthetic toxicity, neural injury, or failure of the block. While regional anesthetic techniques may be beneficial options for those patients who are not candidates for general anesthesia, more studies in which these techniques are used need to be performed to determine the widespread efficacy and adequacy of this method.