J. Zeballos

Embryonic stem cell-derived motor neurons preserve muscle after peripheral nerve injury

Background: The potential of motor neuron progenitor cell transplants to preserve muscle tissue after denervation was studied in in vivo and in vitro adult mammalian model of peripheral nerve injury. Methods: Embryonic stem cells were differentiated to induce cholinergic motor neuron progenitors. Flourescent-labeled progenitor cells were injected into the gastrocnemius muscle of Sprague-Dawley rats (n = 10) after denervation by ipilateral sciatic nerve transection. Control rats received injections of either a phosphate-buffered saline solution only (n = 12), murine embryonic fibroblast (STO) cells (n= 6), or undifferentiated embryonic stem cells (n= 6). Muscles were weighed and analyzed at 7 and 21 days using histology, histomorphometry, and immunostaining. Results: Seven days after progenitor cell transplant, both muscle mass and myocyte cross-sectional area were preserved, compared with control muscles, which demonstrated muscle mass reduction to 70 percent and reduction of cross-sectional area to 72 percent of normal. Fluorescent microscopy of transplanted muscles confirmed the presence of motor neuron progenitors. Presynaptic neuronal staining of the transplants overlapped with α-bungarotoxin-labeled muscle fibers, revealing the presence of new neuromuscular junctions. By 21 days, muscle atrophy in the experimental muscles was equal to that of controls and no transplanted cells were observed. Co-culture of the motor neuron progenitor cells and myocytes also demonstrated new neuromuscular junctions by immunofluorescence. Conclusions: Transplanted motor neuron progenitors prevent muscle atrophy after denervation for a brief time. These progenitor cell transplants appear to form new neuromuscular junctions with denervated muscle fibers in vivo and with myocytes in vitro.

The ultrasound-guided retrolaminar block

PurposeParavertebral blocks have gained in popularity and offer the possible benefit of reduced adverse effects when compared with epidural analgesia. Nevertheless, pulmonary complications in the form of inadvertent pleural puncture are still a recognized risk. Also, the traditional paravertebral blocks are often technically difficult even with ultrasound guidance and constitute deep non-compressible area injections. We present our experience with the first three patients receiving ultrasound-guided retrolaminar blocks for managing the pain associated with multiple rib fractures.Clinical featuresThe vertebral laminae are identified by ultrasound imaging in a paramedian sagittal plane by sequentially visualizing the pleura and ribs, transverse processes, and the corresponding laminae (from lateral to medial). The block needle is guided to contact the lamina, and the local anesthetic injectate is visualized under real-time imaging. A catheter is inserted and used for continuous analgesia. In three consecutive patients, verbal rating scale (VRS) pain scores were reduced from 10/10 to less than 5/10, and no technical difficulties, complications, or adverse effects were encountered.ConclusionsSuccessful analgesia was achieved in all three cases utilizing continuous infusion and intermittent boluses with ultrasound-guided retrolaminar blocks. These results show the feasibility of this approach for patients with multiple rib fractures.RésuméObjectifLes blocs paravertébraux ont gagné en popularité et offrent l’avantage de réduire potentiellement les effets secondaires comparativement à l’analgésie péridurale. Toutefois, les complications pulmonaires, sous forme de ponction pleurale involontaire, demeurent un risque bien connu. En outre, les blocs paravertébraux conventionnels sont souvent difficiles à réaliser d’un point de vue technique et ce, même sous échoguidage, étant donné qu’il s’agit d’injections profondes réalisées dans des zones non compressibles. Nous rapportons notre expérience auprès des trois premiers patients à recevoir un bloc rétrolaminaire échoguidé pour la prise en charge de la douleur associée à une fracture multiple des côtes.Éléments cliniquesLes lames vertébrales sont identifiées par ultrason dans un plan sagittal paramédian en visualisant la plèvre et les côtes, les apophyses transverses, et les lames correspondantes (des lames latérales aux médiales) séquentiellement. L’aiguille du bloc est guidée jusqu’à ce qu’elle atteigne la lame, et l’anesthésique local injecté est visualisé par imagerie en temps réel. Un cathéter est inséré et utilisé pour l’analgésie en continu. Chez trois patients consécutifs, les scores de douleur sur une échelle visuelle ont baissé de 10/10 à moins de 5/10, et aucune difficulté technique, complication ou effet secondaire n’a été rapporté.ConclusionDans les trois cas, l’analgésie a été réalisée grâce à une perfusion continue et des bolus intermittents avec des blocs rétrolaminaires échoguidés. Ces résultats montrent la faisabilité de cette approche pour les patients présentant des fractures multiples des côtes.

Transversus Abdominis Plane (TAP) Block

: Primarily used for acute postoperative abdominal pain with bilateral blocks covering midline surgical site. Best for incisional pain with unilateral coverage of the abdominal wall from dermatome T7 to L1 (most consistently T10 to L1) with each block. Can be single shot or with catheter deployment for continuous pain control. May also be used as both treatment modality and diagnostic maneuver for anterior cutaneous nerve entrapment syndrome (ACNES).

Ultrasound-guided retrolaminar paravertebral block

would necessarily avoid the drug error described in Muddanna et al.’s letter, and colour-coding of drugs would not have prevented any of our incidents. On our delivery suite, Syntocinon (or carbetocin depending on our guidelines) is never drawn up in advance of caesarean section and when drawn up ahead of administration, we encourage that it is kept separate from all other drugs on a different part of the anaesthetic machine. Even better would be to draw it up at the time it is needed whilst following our ten commandments. There will never be a failsafe method and colour-coding does not solve all problems, but formal teaching of our juniors is a sensible step and stressing our tenth commandment, we hope, will result in extra vigilance by the anaesthetist administering the drug.

Brachial Plexus Blocks

: Typically used as a primary anesthetic or for postoperative pain control for procedures on the upper extremity, with block site dependent on location of procedure. May also be performed for acute pain control associated with trauma or chronic pain (CPRS, Raynaud’s, peripheral neuropathy).

Thoracic Paravertebral Block

: Primarily used for postoperative pain control for procedures at level of thoracic vertebrae, such as mastectomy, open cholecystectomy, or thoracotomy. May also be performed for acute pain control associated with trauma (rib fractures) or chronic pain (herpetic neuralgia, chronic postsurgical pain).

Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery

Introduction In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery. Methods and analysis Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships. Ethics and dissemination Ethical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions. Trial results will be disseminated through scientific conference presentations and by publication in scientific journals. Trial registration number NCT02489526; pre-results.