Neuronal Nitric Oxide Synthase Suppression Confers the Prolonged Analgesic Effect of Sciatic Nerve Block With Perineural Dexamethasone in Postoperative Pain Model Mice.

Dexamethasone supplementation to local anesthetics prolongs its action, yet the underlying mechanism is unclear. Previous studies have reported that increased p-p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglia (DRG) is associated with pain-associated behavior and that nitric oxide (NO), which is known to be a pronociceptive substance, directly inhibits sciatic nerve conduction. Here, we investigated the temporal changes in the hyperalgesic effect and p-p38 MAPK and NO synthase (NOS) expression levels in the DRG when dexamethasone was added to ropivacaine used for a sciatic nerve block (SNB) in postoperative pain model mice. Dexamethasone supplementation to ropivacaine significantly prolonged the analgesic effect of SNB via glucocorticoid receptor activation. Histological examination revealed that ropivacaine suppressed p-p38 MAPK expression in the DRG regardless of dexamethasone supplementation, suggesting that p-p38 MAPK was not involved in the prolonging effect of dexamethasone on nerve block. Contrastingly, plantar incision markedly increased the expression of neuronal NOS (nNOS) in DRG, and dexamethasone supplementation to ropivacaine significantly suppressed nNOS expression. Supplementation of L-NAME, an inhibitor of NOS, to ropivacaine markedly prolonged the effect of SNB, similar to dexamethasone. These results suggest that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting nNOS activity. PERSPECTIVE: The current study revealed that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting the activity of neuronal NOS and that p-p38 MAPK may not be involved in this phenomenon. Our findings offer a new target for the discovery of long-acting local anesthetics.

Serotonin Plays a Key Role in the Development of Opioid-Induced Hyperalgesia in Mice.

Opioid usage for pain therapy is limited by its undesirable clinical effects, including paradoxical hyperalgesia, also known as opioid-induced hyperalgesia (OIH). However, the mechanisms associated with the development and maintenance of OIH remain unclear. Here, we investigated the effect of serotonin inhibition by the 5-HT3 receptor antagonist, ondansetron (OND), as well as serotonin deprivation via its synthesis inhibitor para-chlorophenylalanine, on mouse OIH models, with particular focus on astrocyte activation. Co-administering of OND and morphine, in combination with serotonin depletion, inhibited mechanical hyperalgesia and astrocyte activation in the spinal dorsal horn of mouse OIH models. Although previous studies have suggested that activation of astrocytes in the spinal dorsal horn is essential for the development and maintenance of OIH, herein, treatment with carbenoxolone (CBX), a gap junction inhibitor that suppresses astrocyte activation, did not ameliorate mechanical hyperalgesia in mouse OIH models. These results indicate that serotonin in the spinal dorsal horn, and activation of the 5-HT3 receptor play essential roles in OIH induced by chronic morphine, while astrocyte activation in the spinal dorsal horn serves as a secondary effect of OIH. Our findings further suggest that serotonergic regulation in the spinal dorsal horn may be a therapeutic target of OIH. PERSPECTIVE: The current study revealed that the descending serotonergic pain-facilitatory system in the spinal dorsal horn is crucial in OIH, and that activation of astrocytes is a secondary phenotype of OIH. Our study offers new therapeutic targets for OIH and may help reduce inappropriate opioid use.

Precaution: Oximetry central venous catheter shaft is no longer waterproof when cut.

his letter discusses precautions regarding the waterproof structure of the oximetry central venous catheter (CVC) shaft and the risk of blood reflux and leakage that can occur when the catheter shaft is cut. To assess oxygen supply-demand balance [1] and haemodynamics [2], the Swan-Ganz pulmonary artery catheter has been used for perioperative and postoperative management and treatment of critically ill patients for a half a century. In current clinical practice, haemodynamic parameters such as stroke volume (SV) and cardiac output (CO), as well as central venous oxygen saturation (ScvO2), can be measured continuously using a combination of FloTrac Sensor (Edwards Lifesciences Japan Ltd., Tokyo, Japan) [3], Edwards PreSep Oximetry Catheter (Edwards Lifesciences Japan Ltd., Tokyo, Japan) [4], and EV1000 Clinical Platform (Edwards Lifesciences Japan Ltd., Tokyo, Japan) or Vigileo Monitor (Edwards Lifesciences Japan Ltd., Tokyo, Japan) [5, 6]. These methods are less invasive than the Swan-Ganz pulmonary artery catheter, and the changes in the parameter values can be used as an index for perioperative management in both cardiovascular and non-cardiovascular surgeries. In addition, they can be used for the treatment of critically ill patients in the intensive care unit, enabling proactive determination of an appropriate therapy [7]. Compared to intermittent sampling and traditional vital signs alone, continuous ScvO2 monitoring is a more sensitive indicator of tissue perfusion because it reveals the true adequacy of tissue oxygenation, enabling early detection and assessment of clinical response to intervention [7, 8].

SUZYTM forceps facilitate nasogastric tube insertion under McGRATHTM MAC videolaryngoscopic guidance: A randomized, controlled trial.

BACKGROUND: Nasogastric tubes can be easily inserted in patients under general anesthesia. However, for difficult cases, insertion techniques that can be used in routine clinical practice are limited. SUZY forceps are designed for the removal of pharyngolaryngeal foreign bodies under guidance of a McGrath videolaryngoscope. We hypothesized that using SUZY forceps under McGrath videolaryngoscopic guidance may facilitate nasogastric tube insertion and tested this in a randomized controlled trial. METHODS: Adult patients who underwent gastrointestinal or hepato-pancreato-biliary surgery were randomly allocated to 2 groups; the SUZY group and the Magill group. Patients, nurses, and all clinical staff except for the attending anesthesiologist were blinded to group assignment throughout the study. After anesthesia induction, insertion of the nasogastric tube was performed by skilled anesthesiologists with either SUZY or Magill forceps according to group allocation under McGrath videolaryngoscopic guidance. The primary endpoint was insertion time which was defined as the time required to advance the nasogastric tube by 55 cm from the nostril. Secondary endpoints were the success rates of the nasogastric tube insertion, which were defined as a 55-cm advancement from the nostril at the 1st, 2nd, and 3rd attempt, proper insertion rate, the severity of pharyngolaryngeal complications, and hemodynamic parameters during nasogastric tube insertion. RESULTS: Sixty patients were randomized and none of these patients were excluded from the final analysis. The median [interquartile range] insertion time was 25 [18-33] seconds in the SUZY group, and 33 [21-54] seconds in the Magill group (P = .02). Success rates were not different between the groups (97% and 80% in the SUZY and Magill group at 1st attempt, respectively, P = .10). Both, the severity score of the mucosal injury and the severity of sore throat were higher in the Magill than in the SUZY group, whereas the degree of hoarseness did not differ between the 2 groups. Hemodynamic parameters were not significantly different between the groups. CONCLUSION: Using SUZY forceps under McGrath videolaryngoscopic guidance reduced the time required to insert a nasogastric tube and the severity of pharyngolaryngeal complications, when compared to using Magill forceps.

Preoperative Implementation of Transverse Thoracic Muscle Plane Block and Rectus Sheath Block Combination for Pediatric Cardiac Surgery.

Systemic intravenous administration of opioids is the main treatment strategy for intraoperative and postoperative pain management in patients undergoing cardiac surgery with sternotomy. However, using lower doses of opioids may achieve the well-established benefits of the fast-track approach, with minimal opioid-related side effects. Postoperative pain is coupled with a long stay in the intensive care unit. Although neuraxial anesthesia has some benefits, its use remains controversial due to the potential development of epidural hematoma after anticoagulation for cardiopulmonary bypass and coagulopathy after cardiac surgery. Therefore, there is a need for other effective postoperative analgesic strategies, such as peripheral nerve blocks other than neuraxial anesthesia, for cardiac surgery with sternotomy. The effects of real-time ultrasound-guided transverse thoracic muscle plane (TTP) block on postoperative pain after sternotomy have been reported; however, the pain and discomfort in the epigastric area caused by chest drainage tubes placed through the rectus abdominis muscle also are major postoperative problems after cardiac surgery. Herein, the authors report on a preoperative combination of TTP block and rectus sheath block (RSB) for postoperative pain management after cardiac surgery with sternotomy that addresses pain in both the chest and epigastric areas. Considering previous studies, it is presumed that preemptive analgesic effects can be expected via a combination of the TTP block and RSB, and indeed, the preemptive effect was observed in the present study's patients. In this article, the procedure and tips for combining the TTP block and RSB are introduced.

[Safety of axillary and subclavian vein cannulation using real-time ultrasound guidance].

BACKGROUND: The safety of real-time ultrasound-guided subclavian and axillary vein cannulation as opposed to ultrasound-guided internal jugular vein cannulation has not received much attention. We retrospectively compared the safety and value of real-time ultrasound-guided cannulation in the subclavian and axillary veins with those of the landmark method. METHODS: We divided 355 patients who had undergone central venous cannulation of the subclavian and axillary vein under local anesthesia into a group that had undergone real-time ultrasound-guided cannulation (Group U), and another group cannulated using the landmark method (Group L). We compared rates of complications and cannulation success as well as average procedural durations between the two groups. RESULTS: The complication rate was significantly lower in Group U (P=0.005). Most of the complications were arterial puncture. Five patients who developed pneumothorax and nerve damage were in Group L. The success rates and average procedural duration did not significantly differ. CONCLUSIONS: Real-time ultrasound-guided subclavian and axillary vein cannulation is associated with a low incidence of complications similar to that of the internal jugular vein when competent individuals with appropriate training apply the technique.