Role of Tumor Necrosis Factor Receptor 1-Reactive Oxygen Species-Caspase 11 Pathway in Neuropathic Pain Mediated by HIV gp120 With Morphine in Rats.

BACKGROUND: Recent clinical research suggests that repeated use of opioid pain medications can increase neuropathic pain in people living with human immunodeficiency virus (HIV; PLWH). Therefore, it is significant to elucidate the exact mechanisms of HIV-related chronic pain. HIV infection and chronic morphine induce proinflammatory factors, such as tumor necrosis factor (TNF)α acting through tumor necrosis factor receptor I (TNFRI). HIV coat proteins and/or chronic morphine increase mitochondrial superoxide in the spinal cord dorsal horn (SCDH). Recently, emerging cytoplasmic caspase-11 is defined as a noncanonical inflammasome and can be activated by reactive oxygen species (ROS). Here, we tested our hypothesis that HIV coat glycoprotein gp120 with chronic morphine activates a TNFRI-mtROS-caspase-11 pathway in rats, which increases neuroinflammation and neuropathic pain. METHODS: Neuropathic pain was induced by repeated administration of recombinant gp120 with morphine (gp120/M) in rats. Mechanical allodynia was assessed using von Frey filaments, and thermal latency using hotplate test. Protein expression of spinal TNFRI and cleaved caspase-11 was examined using western blots. The image of spinal mitochondrial superoxide was examined using MitoSox Red (mitochondrial superoxide indicator) image assay. Immunohistochemistry was used to examine the location of TNFRI and caspase-11 in the SCDH. Intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) against TNFRI, caspase-11 siRNA, or a scavenger of mitochondrial superoxide was given for antinociceptive effects. Statistical tests were done using analysis of variance (1- or 2-way), or 2-tailed t test. RESULTS: Intrathecal gp120/M induced mechanical allodynia and thermal hyperalgesia lasting for 3 weeks ( P < .001). Gp120/M increased the expression of spinal TNFRI, mitochondrial superoxide, and cleaved caspase-11. Immunohistochemistry showed that TNFRI and caspase-11 were mainly expressed in the neurons of the SCDH. Intrathecal administration of antisense oligonucleotides against TNFRI, Mito-Tempol (a scavenger of mitochondrial superoxide), or caspase-11 siRNA reduced mechanical allodynia and thermal hyperalgesia in the gp120/M neuropathic pain model. Spinal knockdown of TNFRI reduced MitoSox profile cell number in the SCDH; intrathecal Mito-T decreased spinal caspase-11 expression in gp120/M rats. In the cultured B35 neurons treated with TNFα, pretreatment with Mito-Tempol reduced active caspase-11 in the neurons. CONCLUSIONS: These results suggest that spinal TNFRI-mtROS-caspase 11 signal pathway plays a critical role in the HIV-associated neuropathic pain state, providing a novel approach to treating chronic pain in PLWH with opioids.

Recombinant Activated Factor VII in Aortic Surgery for Patients Under Hypothermic Circulatory Arrest.

Purpose: We aimed to identify the risk factors of critical bleeding and investigate the safety of recombinant activated factor VII (rFVIIa) in aortic surgery under hypothermic circulatory arrest (HCA). Patients and Methods: The present single-center retrospective study compared the baseline characteristics of 144 patients who underwent aortic surgery under HCA at our institute. Among the total cohort of 144 patients, 42 received rFVIIa (rFVIIa group), while the remaining 102 patients did not (non-rFVIIa group). Perioperative bleeding and transfusions, postoperative 30-day mortality, and adverse events (AEs) were analyzed in 29 propensity score-matched pairs. Results: Before surgery, the rFVIIa group demonstrated a greater number of shocks (p=0.019), higher JapanSCORE II mortality rate (p=0.033), low platelet count (p=0.015) and fibrinogen (p<0.001) level, prolonged activated partial thromboplastin time (aPTT) (p=0.005) and prothrombin time international normalized ratio (PT-INR) (p=0.006), and longer aortic cross clamp time (p=0.049). Postoperative bleeding, transfusion, 30-day mortality, and AEs were comparable between the groups both in the entire-unmatched cohort and propensity score matching cohort. Conclusion: Preoperative shock, higher JapanSCORE II mortality rates, low platelet and fibrinogen levels, prolonged aPTT and PT-INR, and longer aortic clamping time might be risk factors for excessive bleeding and indicate the need for rFVIIa treatment. The present study suggests that rFVIIa can be safely used to address critical and continuous bleeding in spite of adequate transfusion and supplementation of other coagulation factors in aortic surgery under HCA, without an increase in 30-day mortality and AEs.

Hypothermic circulatory arrest does not induce coagulopathy in vitro.

Hypothermic circulatory arrest (HCA) is an essential procedure during aortic surgery to protect organs; however, hypothermia is believed to cause coagulopathy, which is a major fatal complication. This study aimed to clarify the impact of hypothermia on coagulation by eliminating clinical biases in vitro. In the hypothermic storage study, blood samples from five healthy volunteers were stored at 37 â„ƒ (group N) for 3 h or at 20 â„ƒ for 2 h, followed by 1 h of rewarming at 37 â„ƒ (group H). Thromboelastography was performed before and after 3 h of storage. In the mock circulation loop (MCL) study, blood samples were placed in the MCL and (a) maintained at 37 â„ƒ for 4 h (group N, n = 5), or (b) cooled to 20 â„ƒ to simulate HCA with a 0.1 L/min flow rate for 3 h and then rewarmed to 37 â„ƒ (group H, n = 5). The total MCL duration was 4 h, and the flow rate was maintained at 1 L/min, except during HCA. Blood samples collected 15 min after the beginning and end of MCL were subjected to standard laboratory tests and rotational thromboelastometry analyses. Hypothermia had no impact on coagulation in both the hypothermic storage and MCL studies. MCL significantly decreased the platelet counts and clot elasticity in the INTEM and EXTEM assays; however, there was no effect on fibrinogen contribution measured by FIBTEM. Hypothermia does not cause irreversible coagulopathy in vitro; however, MCL decreases coagulation due to the deterioration of platelets.

Awake Intubation for a Case of Giant Parapharyngeal Space Tumor Using McGrath MAC® Video Laryngoscope.

PURPOSE: Intubation and ventilation cannot be performed in cases of parapharyngeal space tumors as the enlargement of the upper airway leads to the obstruction and hindrance of the intubation procedure. However, there is limited literature on anesthetic management, including the airway, in this disease. Herein, we report a successful case of awake intubation in a patient with parapharyngeal space tumor. CASE PRESENTATION: A 64-year-old man with a history of giant parapharyngeal space tumor was scheduled for bilateral endoscopic sinus surgery and nasal septoplasty. We performed awake intubation using the McGrath® video laryngoscope, which resulted in excellent laryngeal deployment and a smooth procedure. CONCLUSION: We report the anesthetic management of a giant parapharyngeal space tumor with the potential for difficult airway management to maintain spontaneous breathing. Awake intubation was useful in maintaining ventilation and intubation in this case. The preparation of a cricothyroid puncture is needed in cases of intubation failure.

Comparing Conscious Sedation With Regional Anesthesia Versus General Anesthesia in Minimally Invasive Mitral Valve Surgery With Right-Sided Minithoracotomy: A Retrospective Study.

OBJECTIVES: The aims of the present study were to evaluate and compare the safety and feasibility, including hospitalization, intensive care unit (ICU) stay, frequency of conversion to general anesthesia (GA), pH, PaCO2, and PaO2, of selected patients who underwent minimally invasive mitral valve surgery (MIMVS) via a right minithoracotomy under conscious sedation (CS) to avoid GA. The authors also aimed to evaluate the perioperative management of spontaneous breathing. DESIGN: A retrospective, observational study. SETTING: Single-center. PARTICIPANTS: This study enrolled 101 patients who underwent MIMVS under CS or GA. INTERVENTIONS: The patients who underwent MIMVS were managed under CS or GA according to indication criteria. MEASUREMENTS AND MAIN RESULTS: ICU stay (p = 0.010), postoperative time until first fluid intake (p < 0.0001), and duration of mechanical ventilation (p = 0.004) were shorter in the CS group than in the GA group. No patients converted to GA from CS. PaCO2 during cardiopulmonary bypass (CPB) in the CS group was significantly lower than that in the GA group. However, PaCO2 at the termination of CPB in the CS group was significantly higher than that in the GA group. CONCLUSIONS: In the CS group, advanced-age patients with comorbidities underwent mitral surgery without postoperative complications. The authors' findings suggested that MIMVS under CS could be a potentially less-invasive method, providing a quicker recovery than MIMVS under GA.

The Association Between Intraoperative Objective Neuromuscular Monitoring and Rocuronium Consumption During Laparoscopic Abdominal Surgery: A Single-Center Retrospective Analysis.

Background Rocuronium consumption with or without intraoperative objective neuromuscular monitoring in clinical settings of unrestricted use of sugammadex and neuromuscular monitoring has not been reported earlier. The study aimed to investigate the association between the use of intraoperative objective neuromuscular monitoring and rocuronium consumption in patients undergoing laparoscopic abdominal surgery. Methods Data were collected by reviewing electronic medical records of patients who received laparoscopic abdominal surgery under general anesthesia with rocuronium and reversal with sugammadex at a university teaching hospital between May 2017 and April 2018. A multivariate linear regression model was developed to compare the amount of rocuronium consumption (mg) per weight (kg) per hour (mg/kg/h) between the group in which intraoperative objective neuromuscular monitoring was used (NMM+ group) and the group in which intraoperative neuromuscular monitoring was not used (NMM- group). Additionally, we performed an interaction test. Results A total of 429 patients were evaluated, with 371 patients (86%) included in the NMM+ group and 58 patients (14%) in the NMM- group. Log-transformed rocuronium consumption between the NMM+ group and NMM- group was not significantly different (back-transformed ß coefficients [95% CI]: 1.080 [0.951-1.226]; P = 0.23). Male sex and body mass index (BMI) were independent factors associated with 15% (0.853 [0.788-0.924]; P < 0.001) and 3% (for every 1 kg/m2 increase in BMI) (0.971 [0.963-0.979]; P < 0.001) decrease in intraoperative rocuronium consumption, respectively. A significant interaction was detected only between the use of neuromuscular monitoring and age ≥65 years (ß: 0.803 [0.662-0.974]; P = 0.026). Conclusions Although the use of intraoperative objective neuromuscular monitoring was not an individual factor influencing intraoperative rocuronium consumption, this retrospective study demonstrated that the use of intraoperative neuromuscular monitoring reduced rocuronium consumption for approximately 20% of elderly patients (age ≥65 years) undergoing laparoscopic abdominal surgery.

Clinical Application of Laser Speckle Flowgraphy to Assess Changes in Blood Flow to the Foot After a Lumbar Sympathetic Ganglion Block: A Case Report.

BACKGROUND: The lumbar sympathetic ganglion block (LSGB) has been used as a diagnostic and therapeutic procedure for treating pain conditions such as neuropathic and ischemia-related pain, affecting the lower extremities. In general, an increase in skin temperature is useful in confirming the effectiveness of the sympathetic nerve block in clinical settings. However, the assessment of skin temperature in patients with peripheral arterial disease (PAD) occasionally provides false negatives. CASE PRESENTATION: A novel technology, laser speckle flowgraphy (LSFG) enables noninvasive quantitative and qualitative blood flow assessments. LSFG is a novel neuro-monitor for quantitative blood flow detection in the optic nerve head during cardiac surgery. Herein, we report on measuring foot blood flow using LSFG before and after LSGB in a PAD patient. This research aimed to determine whether LSFG could detect any improvement in the dynamics of foot blood flow after an LSGB in a situation where changes in skin temperature alone could not determine the procedure's outcome. CONCLUSION: LSFG can be used to assess blood flow changes in a foot with PAD, following a LSGB.

Awake Surgical Mitral Valve Repair after Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement has become a popular choice for cases with severe aortic stenosis. However, when severe mitral regurgitation is comorbid in high-risk patients with severe aortic stenosis, therapeutic options must be weighed for each case. Here we present a very frail 88-year-old patient with severe aortic stenosis and severe mitral valve regurgitation who underwent a successful awake minimally invasive mitral valve repair after transcatheter aortic valve replacement.

Does a Small Body Have a Negative Impact on Minimally Invasive Mitral Valve Surgery?

BACKGROUNDS: Minimally invasive mitral valve surgery (MIMVS) in patients with a small body presents surgeons with a technically difficult surgical maneuver. We hypothesized that physique might negatively influence the safety and technical complexity of MIMVS. METHODS: One hundred and twenty-one patients underwent MIMVS in our institution between May 2014 and April 2020. These patients were categorized into two groups. The first group was the small physique group (n = 20) consisting of patients with a stature <150 cm. The second group was the normal physique group (n = 101) consisting of patients with a stature >150 cm. The primary endpoint was freedom from death and major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoint was freedom from moderate or severe mitral regurgitation. RESULTS: Cardiopulmonary bypass time (130 ± 29 vs. 156 ± 55 min, p = 0.02) and aortic cross-clamp time (75 ± 27 vs. 95 ± 39 min, p = 0.03) were significantly shorter in the small physique group. Both in the early and midterm periods, there was no significant difference in the mortality (early, 5.0 vs. 1.0%, p = 0.30. midterm, 5.0 vs. 1.0%, p = 0.09), MACCE (early, 5.0 vs. 6.9%, p = 0.65. midterm, 5.0 vs. 5.9%, p = 0.93) and the residual MR (early, 0 vs. 1.0%, p = 0.66. midterm, 5.0 vs. 4.9%, p = 0.93) between the two groups. CONCLUSIONS: Small physique is not a hurdle for MIMVS in terms of the safety of the operation.

Comparison of Right Ventricular Function Between Three-Dimensional Transesophageal Echocardiography and Pulmonary Artery Catheter.

OBJECTIVE: This study aimed to compare measurements of right ventricular function using three-dimensional transesophageal echocardiography (3D TEE), and pulmonary artery catheters (PACs) in patients undergoing cardiac surgery. The authors examined the practicality of using the 3D TEE. DESIGN: Prospective observational. SETTING: Cardiac operating room at a single university hospital. PARTICIPANTS: All adult patients undergoing elective cardiac surgery at a single tertiary care university hospital over two years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), stroke volume (SV), and right ventricular ejection fraction (RVEF) were measured with both 3D TEE and PACs. Assessments were performed using correlation coefficients, paired t tests, and Bland-Altman plots. Thirty-one patients participated in this study. Each measurement showed good agreement. RVEDV and RVESV were slightly lower on 3D TEE than on PAC (205.9 mL v 220.2 mL, p = 0.0018; 143.0 mL v 155.5 mL, p = 0.0143, respectively), whereas no significant differences were observed for SV and RVEF (31.0% v 31.1%, p = 0.0569; 61.6 mL v 66.9 mL, p = 0.92, respectively). Linear regression analysis showed high correlation between 3D TEE and PAC for RVEDV (r = 0.87) and RVESV (r = 0.81), and moderate correlation for SV (r = 0.67) and RVEF (r = 0.67). In the Bland-Altman plot, most patients were within the 95% limits of the agreement throughout all measurements. CONCLUSION: A high correlation was found between measurements made with a PAC and with 3D TEE in the assessment of right ventricular function. Three-dimensional TEE would be a potential alternative to PAC for assessment of right ventricular function during intraoperative periods.

Correction to: Hypothermic circulatory arrest induced coagulopathy: rotational thromboelastometry analysis.

The article "Hypothermic circulatory arrest induced coagulopathy: rotational thromboelastometry analysis", written by Hayato Ise, Hiroto Kitahara, Kyohei Oyama, Keiya Takahashi, Hirotsugu Kanda, Satoshi Fujii, Takayuki Kunisawa, Hiroyuki Kamiya, was originally published electronically on the publisher's internet portal on 7 June 2020 without open access.

Hypothermic circulatory arrest induced coagulopathy: rotational thromboelastometry analysis.

OBJECTIVES: Hypothermic circulatory arrest (HCA) has been considered to cause coagulopathy during cardiac surgery. However, coagulopathy associated with HCA has not been understood clearly in details. The objective of this study is to analyze the details of coagulopathy related to HCA in cardiac surgery by using rotational thromboelastometry (ROTEM). METHODS: We retrospectively analyzed 38 patients who underwent elective cardiac surgery (HCA group = 12, non-HCA group = 26) in our hospital. Blood samples were collected before and after cardiopulmonary bypass (CPB). Standard laboratory tests (SLTs) and ROTEM were performed. We performed four ROTEM assays (EXTEM, INTEM, HEPTEM and FIBTEM) and analyzed the following ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF) and maximum clot elasticity (MCE). The amount of perioperative bleeding, intraoperative transfusion and perioperative data were compared between the HCA and non-HCA group. RESULTS: Operation time and hemostatic time were significantly longer in the HCA group, whereas CPB time had no difference between the groups. The amount of perioperative bleeding and intraoperative transfusion were much higher in the HCA group. SLTs showed no difference between the groups both after anesthesia induction and after protamine reversal. In ROTEM analysis, MCE contributed by platelet was reduced in the HCA group, whereas MCE contributed by fibrinogen had no difference. CONCLUSION: Our study confirmed that the amount of perioperative bleeding and intraoperative transfusion were significantly higher in the HCA group. ROTEM analysis would indicate that clot firmness contributed by platelet component is reduced by HCA in cardiac surgery.

Comparison of intrathecal morphine with continuous patient-controlled epidural anesthesia versus intrathecal morphine alone for post-cesarean section analgesia: a randomized controlled trial.

BACKGROUND: Several neuraxial techniques have demonstrated effective post-cesarean section analgesia. According to previous reports, it is likely that patient-controlled epidural analgesia (PCEA) without opioids is inferior to intrathecal morphine (IM) alone for post-cesarean section analgesia. However, little is known whether adding PCEA to IM is effective or not. The aim of this study was to compare post-cesarean section analgesia between IM with PCEA and IM alone. METHODS: Fifty patients undergoing elective cesarean section were enrolled in this prospective randomized study. Patients were randomized to one of two groups: IM group and IM + PCEA group. All patients received spinal anesthesia with 12 mg of 0.5% hyperbaric bupivacaine, 10 µg of fentanyl, and 150 µg of morphine. Patients in IM + PCEA group received epidural catheterization through Th11-12 or Th12-L1 before spinal anesthesia and PCEA (basal 0.167% levobupivacaine infusion rate of 6 mL/h, bolus dose of 3 mL in lockout interval of 30 min) was commenced at the end of surgery. A numerical rating scale (NRS) at rest and on movement at 4,8,12,24,48 h after the intrathecal administration of morphine were recorded. In addition, we recorded the incidence of delayed ambulation and the number of patients who requested rescue analgesics. We examined NRS using Bonferroni's multiple comparison test following repeated measures analysis of variance; p < 0.05 was considered as statistically significant. RESULTS: Twenty-three patients in each group were finally analyzed. Mean NRS at rest was significantly higher in IM group than in IM + PCEA group at 4 (2.7 vs 0.6), 8 (2.2 vs 0.6), and 12 h (2.5 vs 0.7), and NRS during mobilization was significantly higher in IM group than in IM + PCEA group at 4 (4.9 vs 1.5), 8 (4.8 vs 1.9), 12 (4.9 vs 2), and 24 h (5.7 vs 3.5). The number of patients who required rescue analgesics during the first 24 h was significantly higher in IM group compared to IM + PCEA group. No significant difference was observed between the groups in incidence of delayed ambulation. CONCLUSIONS: The combined use of PCEA with IM provided better post-cesarean section analgesia compared to IM alone. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000032475). Registered 6 May 2018 - Retrospectively registered.

Transfer of a minimally invasive mitral valve repair program from a high-volume center to a very low volume center: how many cases are necessary to maintain acceptable results?

OBJECTIVE: To investigate whether minimally invasive mitral valve repair (MIMVR) can be transferred from a high-volume center into a very small volume center and to clarify how many cases are necessary for maintenance of this program, early outcomes of MIMVR in Asahikawa Medical University were compared with those results in patients operated by a single surgeon in Duesseldorf University Hospital. METHODS: Sixty-five patients who underwent MIMVR in Asahikawa Medical University (group A) between May 2014 and July 2018 and 134 patients who underwent MIMVR in Duesseldorf University Hospital (group D) between September 2009 and January 2014 by a surgeon who started MIMVS later in Asahikawa were retrospectively analyzed. RESULTS: In group D, there were more patients with ischemic mitral valve regurgitation and with annular calcification than in group A. Survival rate at 6 months and 1 year was 98.5% and 98.5% in group A and 92.9% and 91.3% in group D, respectively. EuroSCORE II was significantly higher in patients dead within 30 days and within the first year. CONCLUSIONS: The present study demonstrated that MIMVR programs can be transferred with acceptable early results into very low volume centers, if the team is developed by surgeons who are well trained and experienced in MIMVR. Moreover, the present study suggested that case number for maintenance of acceptable results may be obviously less than the previous recognition that this kind of specialized surgery could be maintained with at least 50 cases annually. However, meticulous preparations for surgery are essential for satisfactory surgical outcomes.

Cerebral Circulation During Retrograde Cerebral Perfusion: Evaluation Using Laser Speckle Flowgraphy.

BACKGROUND: The cerebroprotective effect of retrograde cerebral perfusion (RCP) and selective antegrade cerebral perfusion (SCP) still remains controversial. Laser speckle flowgraphy has shown much promise for novel perioperative neuromonitoring by assessing blood flow of the optic nerve head. This study aimed to evaluate the cerebral microcirculation in humans using laser speckle flowgraphy during simple circulatory arrest, RCP, and SCP under moderate hypothermia and to investigate whether RCP under moderate hypothermia is a reliable method of cerebral protection. METHODS: A total of 23 consecutive patients who underwent a scheduled aortic arch or hemiarch surgical procedure on thoracic aorta aneurysm were enrolled. The laser speckle flowgraphy measurement that calculates mean blur ratio, a parameter of cerebral circulation, was obtained 6 times: after induction of anesthesia, baseline (T1), after initiation of cardiopulmonary bypass with cardiac arrest (T2), simple circulatory arrest (T3), RCP (T4), SCP (T5), and after the termination of cardiopulmonary bypass (T6). RESULTS: Both mean blur ratios of simple circulatory arrest and RCP were significantly decreased compared with baseline. In contrast, no significant differences were observed between simple circulatory arrest and RCP. The mean blur ratio of SCP was significantly increased compared with both simple circulatory arrest and RCP. CONCLUSIONS: In conclusion, no significant difference was observed in the cerebral circulation between RCP and simple circulatory arrest without adjunctive strategy under moderate hypothermia. In contrast, the cerebral circulation during SCP was significantly higher than simple circulatory arrest and RCP. These results suggest that cerebral microcirculation may not be adequate during RCP compared with SCP under moderate hypothermia.

Minimally Invasive Awake Mitral Valve Surgery and Cardiopulmonary Bypass Without General Anesthesia.

Herein, we report the case of a 49-year-old man with a potentially fatal allergy to propofol and remifentanil who underwent awake minimally invasive mitral valve surgery with cardiopulmonary bypass using thoracic epidural anesthesia, without the need for endotracheal general anesthesia. The aim was the management of spontaneous respiration during cardiopulmonary bypass surgery in an awake patient.