Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins.

Nociceptive sensitization is accompanied by the upregulation of glycolysis in the central nervous system in neuropathic pain. Growing evidence has demonstrated glycolysis and angiogenesis to be related to the inflammatory processes. This study investigated whether fumagillin inhibits neuropathic pain by regulating glycolysis and angiogenesis. Fumagillin was administered through an intrathecal catheter implanted in rats with chronic constriction injury (CCI) of the sciatic nerve. Nociceptive, behavioral, and immunohistochemical analyses were performed to evaluate the effects of the inhibition of spinal glycolysis-related enzymes and angiogenic factors on CCI-induced neuropathic pain. Fumagillin reduced CCI-induced thermal hyperalgesia and mechanical allodynia from postoperative days (POD) 7 to 14. The expression of angiogenic factors, vascular endothelial growth factor (VEGF) and angiopoietin 2 (ANG2), increased in the ipsilateral lumbar spinal cord dorsal horn (SCDH) following CCI. The glycolysis-related enzymes, pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) significantly increased in the ipsilateral lumbar SCDH following CCI on POD 7 and 14 compared to those in the control rats. Double immunofluorescence staining indicated that VEGF and PKM2 were predominantly expressed in the astrocytes, whereas ANG2 and LDHA were predominantly expressed in the neurons. Intrathecal infusion of fumagillin significantly reduced the expression of angiogenic factors and glycolytic enzymes upregulated by CCI. The expression of hypoxia-inducible factor-1α (HIF-1α), a crucial transcription factor that regulates angiogenesis and glycolysis, was also upregulated after CCI and inhibited by fumagillin. We concluded that intrathecal fumagillin may reduce the expression of ANG2 and LDHA in neurons and VEGF and PKM2 in the astrocytes of the SCDH, further attenuating spinal angiogenesis in neuropathy-induced nociceptive sensitization. Hence, fumagillin may play a role in the inhibition of peripheral neuropathy-induced neuropathic pain by modulating glycolysis and angiogenesis.

Erector spinae plane block level does not impact analgesic efficacy in enhanced recovery for lumbar spine surgery.

BACKGROUND CONTEXT: Postoperative pain control following spine surgery can be difficult. The Enhanced Recovery After Surgery (ERAS) programs use multimodal approaches to manage postoperative pain. While an erector spinae plane block (ESPB) is commonly utilized, the ideal distance for injection from the incision, referred to as the ES (ESPB to mid-surgical level) distance, remains undetermined. PURPOSE: We evaluated the impact of varying ES distances for ESPB on Numerical Rating Scale (NRS) measures of postoperative pain within the ERAS protocol. STUDY DESIGN/SETTING: Retrospective observational study. PATIENT SAMPLE: Adult patients who underwent elective lumbar spine fusion surgery. OUTCOME MEASURES: Primary outcome measures include the comparative postoperative NRS scores across groups at immediate (T1), 24 (T2), 48 (T3), and 72 (T4) hours postsurgery. For secondary outcomes, a propensity matching analysis compared these outcomes between the ERAS and non-ERAS groups, with opioid-related recovery metrics also assessed. METHODS: All included patients were assigned to one of three ERAS groups according to the ES distance: Group 1 (G1, ES > 3 segments), Group 2 (G2, ES = 2-3 segments), and Group 3 (G3, ES<2 segments). Each patient underwent a bilateral ultrasound-guided ESPB with 60 mL of diluted ropivacaine or bupivacaine. RESULTS: Patients within the ERAS cohort reported mild pain (NRS < 3), with no significant NRS variation across G1 to G3 at any time. Sixty-five patients were matched across ERAS and non-ERAS groups. The ERAS group exhibited significantly lower NRS scores from T1 to T3 than the non-ERAS group. Total morphine consumption during hospitalization was 26.7 mg for ERAS and 41.5 mg for non-ERAS patients. The ERAS group resumed water and food intake sooner and had less postoperative nausea and vomiting. CONCLUSIONS: ESPBs can be effectively administered at or near the mid-surgical level to the low thoracic region for lumbar spine surgeries. Given challenges with sonovisualization, a lumbar ESPB may be preferred to minimize the risk of inadvertent pleural injury.

Comparisons in analgesic effects between ultrasound-guided erector spinae plane block and surgical intercostal nerve block after video-assisted thoracoscopic surgery: A randomized controlled trial.

STUDY OBJECTIVE: This study aimed to compare the analgesic effects of anesthesiologist-administrated erector spinae plane block (ESPB) and surgeon-administrated intercostal nerve block (ICNB) following video-assisted thoracoscopic surgery (VATS). DESIGN: Randomized, controlled, double-blinded study. SETTING: Operating room, postoperative recovery room and ward in two centers. PATIENTS: One hundred patients, ASA I-III and scheduled for elective VATS. INTERVENTIONS: The anesthesiologist-administrated ESPB under ultrasound guidance or surgeon-administrated ICNB under video-assisted thoracoscopy was randomly provided during VATS. Regular oral non-opioid analgesic combined with intravenous rescue morphine were prescribed for multimodal analgesia after surgery. MEASUREMENTS: The primary outcomes were the pain score and morphine consumption during 48 h after surgery. Postoperative pain intensity were assessed using the 10-cm visual analogue scale at 1 h, 24 h, and 48 h after surgery. Morphine consumption at these time points was compared between the two study groups. Furthermore, oral weak opioid rescue analgesic was also provided at 24 h after surgery. Postoperative quality of recovery at 24 h was also assessed using the QoR-15 questionnaire, along with duration of chest tube drainage and hospital stay were compared as secondary outcomes. MAIN RESULTS: Patients in the two study groups had comparable baseline characteristics, and surgical types were also similar. Postoperative VAS changes at 1 h, 24 h, and 48 h after surgery were also comparable between the two study groups. Both groups had low median scores (<4.0) at all time points (all p > 0.05). Patients in the ESPB group required statistically non-significant higher 48-h morphine consumption [3 (0-6) vs. 0 (0-6) mg in the ESPB group and ICNB group respectively; p = 0.135] and lower numbers of oral rescue analgesic (0.4 ± 1.2 vs. 1.0 ± 1.8 in the ESPB group and ICNB group respectively; p = 0.059). Additionally, patients in the two study groups had similar QoR15 scores and lengths of hospital stay. CONCLUSIONS: Both anesthesiologist-administered ultrasound-guided ESPB and surgeon-administered VATS ICNB were effective analgesic techniques for patients undergoing VATS for tumor resection.

Fire safety study on high-flow nasal oxygen in shared-airway surgeries with diathermy and laser: simulation based on a physical model.

High-flow nasal oxygen (HFNO) has been used in "tubeless" shared-airway surgeries but whether HFNO increased the fire hazard is yet to be examined. We used a physical model for simulation to explore fire safety through a series of ignition trials. An HFNO device was attached to a 3D-printed nose with nostrils connected to a degutted raw chicken. The HFNO device was set at twenty combinations of different oxygen concentration and gas flow rate. An electrocautery and diode laser were applied separately to a fat cube in the cavity of the chicken. Ten 30 s trials of continuous energy source application were conducted. An additional trial of continuous energy application was conducted if no ignition was observed for all the ten trials. A total of eight short flashes were observed in one hundred electrocautery tests; however, no continuous fire was observed among them. There were thirty-six events of ignition in one hundred trials with laser, twelve of which turned into violent self-sustained fires. The factors found to be related to a significantly increased chance of ignition included laser application, lower gas flow, and higher FiO2. The native tissue and smoke can ignite and turn into violent self-sustained fires under HFNO and continuous laser strikes, even in the absence of combustible materials. The results suggest that airway surgeries must be performed safely with HFNO if only a short intermittent laser is used in low FiO2.

Intercostal Nerve Block Using an Innovative Intraneedle Ultrasound Transducer: A Proof-of-Concept study.

Intercostal nerve block is a widely used and effective approach to providing regional anesthesia in the thoracic region for pain relief. However, during ultrasound-guided intercostal nerve block, inaccurate identification of the anatomic structures or suboptimal positioning of the needle tip may result in complications and blockade failure. In this study, we designed an intraneedle ultrasound (INUS) system and validated its efficacy in identifying anatomic structures relevant to thoracic region anesthesia. The 20-MHz INUS transducer comprised a single lead magnesium niobate-lead titanate crystal, and gain was set to 20 dB. It fit into a regular 18G needle and emitted radiofrequency-mode ultrasound signals at 1 mm from the needle tip. One hundred intercostal punctures were performed in 10 piglets. Intercostal spaces were identified by surface ultrasound or palpation and located by inserting and advancing the INUS transducer needle until the appropriate anatomy was identified. Blockade success was defined by ideal saline and dye spreading and confirmed by dissection. The pleura had a distinctive ultrasound signal, and successful detection of the intercostal muscles, endothoracic fascia and double-layered parietal and visceral pleura was achieved in all 100 puncture attempts. INUS allows real-time identification of intercostal structures and facilitates successful intercostal nerve blocks.

Previously published drug interaction models predict loss of response for transoesophageal echocardiography sedation well but not response to oesophageal instrumentation.

Response surface models (RSMs) were used to predict effects of multiple drugs interactions. Our study was aimed to validate accuracy of the previous published volunteer models during transoesophageal echocardiography (TEE). This is a cross-sectional study with 20 patients scheduled for transesophageal echocardiography in Taipei Veterans General Hospital, Taiwan. Effect-site concentration pairs of alfentanil and propofol were recorded and converted to equivalent remifentanil and propofol effect-site concentrations. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed every 2 minutes. Using these data, previous published models of loss of response (LOR), intolerable ventilatory depression (IVD), and loss of response to esophageal instrumentation (LREI) were then estimated. Accuracy of prediction is assessed by calculating the difference between the true response and the model-predicted probability. Clinical events such as interruption of TEE were recorded. The average procedure time was 11 minutes. Accuracy for prediction of LOR and LREI is 63.6% and 38.5%, respectively. There were four patients experienced desaturation for less than 1 minute, which were not predicted by IVD model, and one interruption of TEE due to involuntary movement. The previous published drug-interaction RSMs predict LOR well but not LREI for TEE sedation. Further studies using response surface methodology are needed to improve quality for TEE sedation and clinical implementation.

The effect of high-dose nitroglycerin on the cerebral saturation and renal function in cardiac surgery: A propensity score analysis.

BACKGROUND: The aim of the study was to evaluate the effects of high-dose nitroglycerine administered during cardiopulmonary bypass on the intraoperative cerebral saturation and postoperative serum creatinine concentration in cardiac surgery. METHODS: In a retrospective cohort study, a total of 239 patients undergoing cardiac surgery with cardiopulmonary bypass at a tertiary medical center were included. General anesthesia consisted of volatile anesthetic and either intravenous loading of high-dose nitroglycerin (infusion rate 10 to 20 mg·h with a total dose of ≥0.5 mg·kg) starting from rewarming of cardiopulmonary bypass throughout the end of the surgery (NTG group; N = 96) or without high-dose nitroglycerin (control group; N = 143). Data for intraoperative cerebral saturation and serum creatinine concentrations before and after cardiac surgery were collected. Propensity score method was used to adjust for potential confounders. RESULTS: Patients receiving high-dose nitroglycerin had significantly lower mean arterial pressure and hematocrit levels during and after cardiopulmonary bypass. The risk of intraoperative cerebral desaturation was left-sided 23.9% versus 38.5% (p = 0.023), right-sided 28.1% versus 35.7% in the NTG and control groups, respectively. The risk of new-onset stroke and postoperative dialysis was 2.1% versus 6.3% and 1.0% versus 3.5% in the NTG and control groups, respectively. CONCLUSION: An infusion of high-dose nitroglycerin initiating at rewarming of cardiopulmonary bypass and throughout the postbypass interval may induce hypotension and hemodilution in cardiac surgical patients. Cerebral saturation and renal function were well maintained without increasing the risk of stroke and renal replacement therapy after cardiac surgery with cardiopulmonary bypass.