Changes of melatonin secretion in the neuropathic pain induced sleep disorder model rat.

Chronic pain due to peripheral neuropathy can lead to sleep disorders that significantly worsen the patient's quality of life. Previously, we conducted brain wave measurements in a rat model of neuropathic pain and identified its potential as a model for sleep disorders associated with chronic pain (reported). In this study, we quantified melatonin secretion and assessed its circadian rhythm in a rat model of pain-induced sleep disorder. To create a model of chronic constriction injury (CCI), rats were loosely tied around the sciatic nerve, with approximately 1 mm spacing, 14 days before the experiment. Rats with no ties around the sciatic nerve were used as controls. Electroencephalograms and electromyograms were recorded for 3 days, and the episodes of waking, REM sleep, and non-REM sleep were compared between the groups. The samples for microanalysis were collected every 30 min and used for melatonin analysis. Compared to the control group, the CCI model group exhibited an increase in wake episodes and a decrease in non-REM sleep episodes. Analysis of the area under the curve of melatonin secretion revealed a significant increase in melatonin secretion and a loss of circadian rhythm in the CCI model group. Melatonin secretion markedly increased accompanied by loss of circadian rhythm in a rat model of CCI. Further studies investigating the causal relationship between neuropathic pain and melatonin secretion are warranted.

[Postoperative care of the elderly].

Number of elderly patients undergoing surgery is increasing in Japan owing to the increasing population over 65. Developments of less invasive surgical techniques and advances in perioperative care may also contribute. Postoperative mortality among elderly patients are higher than that in younger patients due to decreased functional reserves of nervous, cardiovascular, pulmonary, hepatic and renal systems. Physiological changes in vital organs of the elderly and their influences in clinical settings are depicted. Postoperative complications in the elderly, including pneumonia, aspiration, myocardial infarction, delirium, cognitive dysfunction and cerebral infarction are described. Management and preventive strategies of postoperative complications are also discussed.

Machine learning-based causal models for predicting the response of individual patients to dexamethasone treatment as prophylactic antiemetic.

Risk-based strategies are widely used for decision making in the prophylaxis of postoperative nausea and vomiting (PONV), a major complication of general anesthesia. However, whether risk is associated with individual treatment effect remains uncertain. Here, we used machine learning-based algorithms for estimating the conditional average treatment effect (CATE) (double machine learning [DML], doubly robust [DR] learner, forest DML, and generalized random forest) to predict the treatment response heterogeneity of dexamethasone, the first choice for prophylactic antiemetics. Electronic health record data of 2026 adult patients who underwent general anesthesia from January to June 2020 were analyzed. The results indicated that only a small subset of patients respond to dexamethasone treatment, and many patients may be non-responders. Estimated CATE did not correlate with predicted risk, suggesting that risk may not be associated with individual treatment responses. The current study suggests that predicting treatment responders by CATE models may be more appropriate for clinical decision making than conventional risk-based strategy.

Acute hypoxemia due to right-to-left shunt via a patent foramen ovale during left internal thoracic artery to left anterior descending artery anastomosis in off-pump coronary artery bypass grafting: a case report.

BACKGROUND: A right-to-left shunt via a patent foramen ovale (PFO) during off-pump coronary artery bypass (OPCAB) may result in difficulties in oxygenation and circulatory management. We herein present a case of a marked shunt via a PFO during OPCAB. CASE PRESENTATION: A 74-year-old man who had aortic root enlargement, compressing the right atrium, and an atrial septal aneurysm, underwent OPCAB. When the heart was fixed for the anastomosis of the left anterior descending artery, sudden hypoxemia and hypotension were observed. Intraoperative transesophageal echocardiography (TEE) showed a right-to-left shunt via a PFO that was unnoticed preoperatively. After the anastomosis was completed, TEE revealed no shunt through the PFO. CONCLUSIONS: We should check for a PFO in case of an atrial septal aneurysm. Compression of the right atrium is considered an important anatomical risk of the right-to-left shunt in OPCAB.

Preoperative Femoral Nerve Block and Postoperative Sciatic Nerve Block at the Subgluteal Space After Total Knee Arthroplasty: A Retrospective Cohort Study.

Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an unintended result of surgical invasion. This study assessed the benefits of a postoperative SNB at the subgluteal space for patients who underwent TKA. Methodology This was a single-center, retrospective cohort study. Patients who underwent TKA under general anesthesia between May 2018 and June 2019 at the Teikyo University School of Medicine were screened for inclusion. They received either a preoperative femoral nerve block alone (control group; n = 87) or a preoperative femoral nerve block and postoperative SNB at the subgluteal space (post-SNB group; n = 40). The primary outcome was the pain-related Numerical Rating Scale (NRS) scores. The secondary outcomes were postoperative nausea and vomiting (PONV), intravenous patient-controlled analgesia (iv-PCA) suspension, and postoperative complications. Results No significant differences were observed in the characteristics, NRS scores, time to first drug use for pain, and iv-PCA suspension between groups. However, the incidence of PONV was significantly lower in the post-SNB group (p = 0.03). Logistic regression analysis revealed that droperidol doses of iv-PCA and the presence of postoperative SNB were independently associated with PONV occurrence [A1] {(p = 0.008, 95% confidence intervals (CI) [0.46, 0.89] and (p = 0.02, 95% CI [0.25, 0.88])}. Conclusions A postoperative SNB at the subgluteal space following TKA does not improve postoperative pain control; however, it may have contributed to reduced PONV.

Pre-anesthesia systolic blood pressure increases with age regardless of sex.

PURPOSE: Pre-anesthesia hypertension (PAH) is the temporary elevation of blood pressure (BP), compared with normal ambulatory recorded BP or self-measured BP at home, in patients waiting for operation in the operating room (OR) before anesthesia induction. In general, the incidence of sustained hypertension (SH) increases progressively with age and the increase is greater in males than in females. In this study, we investigated the influence of age and sex on PAH. METHODS: Sampling data on consecutive patients who were more than 20 years old and who had undergone surgery under general, intrathecal, or epidural anesthesia were retrospectively collected from hospital records and anesthesia records. Patients with SH, which was defined as a past history of hypertension and taking oral antihypertensive medications, were excluded from the analyses, and the data of 231 patients, 102 males and 129 females, were used for the analyses. RESULTS: The proportions of male and female patients with a systolic BP (sBP) of more than 140 mmHg in the OR before anesthesia induction were 55.9 and 42.6%, respectively. The proportions of male and female patients with a diastolic BP (dBP) of more than 90 mmHg were 34.3 and 23.3%, respectively. There was no difference in the proportions of male and female patients with PAH. The differences in sBP between measurements in the hospital room (HR) before the operation and those in the OR (ΔsBP) in males and females were 22.9 ± 25.6 and 19.0 ± 24.0 mmHg, respectively. The differences in dBP between measurements in the HR and those in the OR (ΔdBP) in males and females were 12.7 ± 16.5 and 8.4 ± 17.9 mmHg, respectively. There were no differences in ΔsBP and ΔdBP between males and females. The sBP in the OR and the ΔsBP increased significantly with age in both males and females. CONCLUSION: Age is an important clinical factor related to PAH. Pre-anesthesia sBP and the change in pre-anesthesia sBP increase progressively with age regardless of sex. These findings suggest that the higher BP seen in the elderly in the OR before anesthesia induction, as reported previously, might be explained in part by a greater impact of PAH in older people.

Changes in platelet function and coagulation after transcatheter aortic valve implantation evaluated with thromboelastography.

INTRODUCTION: The possibility of hypercoagulability during the perioperative period of transcatheter aortic valve implantation (TAVI) has been noted; however, there is still a controversy regarding the appropriate perioperative antithrombotic therapy. The study investigated coagulation and platelet functions during the TAVI perioperative period using thromboelastography (TEG) 6s platelet mapping. METHODS: A prospective observational study was conducted on 25 patients undergoing TAVI. TEG platelet mapping was performed at three time points: on admission to the operating room (before heparinisation), on postoperative day (POD) 1 and on POD 3. Perioperative changes observed included: maximum clot strength (MAHKH), clot strength without platelet function (MAActF), time to initiation of clots formation by coagulation factors (RHKH) and platelet function (Gp). Gp is activated by thrombin, and not affected by antiplatelet agents. It is calculated as [(5000×MAHKH)/(100 - MAHKH)] - [(5000×MAActF)/(100 - MAActF)]. Finally, MAADP/AA and GADP/AA, which reflect clot strength and platelet aggregation mediated by ADP/thromboxane A2 receptors, respectively, were also examined using the same method as for Gp. RESULTS: MAHKH continued to decrease until POD 3, indicating antithrombotic change after TAVI. Gp continuously decreased for 3 days after TAVI, while MAActF increased significantly on POD 3. Furthermore, RHKH shortened on POD 1 and POD 3, suggesting increased coagulation capacity after TAVI. Finally, GADP in clopidogrel-naive patients was reduced for 3 days after TAVI, while GAA in aspirin-naive patients showed no significant change perioperatively. CONCLUSIONS: In this study involving TEG platelet mapping, coagulation capacity increased while platelet function decreased, resulting in antithrombotic change for 3 days after TAVI. The ADP receptor system may be implicated in the decreased platelet function. These results may be useful for considering optimal perioperative antithrombotic therapy in TAVI.

Calcium-induced calcium release from the sarcoplasmic reticulum can be evaluated with a half-logistic function model in aequorin-injected cardiac muscles.

PURPOSE: Release of calcium (Ca(2+)) from the sarcoplasmic reticulum (SR) induced by Ca(2+) influx through voltage-dependent sarcolemmal L-type Ca(2+) channels (CICR) in cardiac muscle cells has been implicated as a potential target contributing to anesthetic-induced myocardial depression. In an earlier study, we found that (1) a half-logistic (h-L) function, which represents a half-curve of a sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phases of the isometric myocardial tension and isovolumic left ventricular (LV) pressure waveforms better than a mono-exponential (m-E) function and (2) the h-L time constants are useful as inotropic indices. We report here our investigation of the potential application of an h-L function to the analysis of the first half of the ascending phase of the Ca(2+) transient curve (faCaT) that precedes and initiates myocardial contraction and the increase in LV pressure. METHODS: Ca(2+) transients (CaT) were measured using the Ca(2+)-sensitive photoprotein aequorin, which was microinjected into seven isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The faCaT data from the beginning of twitch stimulation to the maximum of the first-order time derivative of Ca(2+) concentration (dCa/dt(max)) was curve-fitted by the least-squares method using h-L and m-E function equations. RESULTS: The mean correlation coefficient (r) values of the h-L and m-E curve-fits for the faCaTs were 0.9740 and 0.9654 (P < 0.05) in the rabbit and 0.9895 and 0.9812 (P < 0.0001) in the mouse. CONCLUSION: The h-L curves tracked the amplitudes and time courses of the faCaTs in cardiac muscles more accurately than m-E functions. Based on this result, we suggest that the h-L time constant may be a more reliable index than the m-E time constant for evaluating the rate of CICR from the SR in myocardial Ca(2+) handling. The h-L approach may provide a more useful model for the study of CICR during the contraction process induced by anesthetic agents.

Temporary worsening of mitral regurgitation due to conduction disturbance after transcatheter aortic valve implantation.

BACKGROUND: Mitral regurgitation after transcatheter aortic valve implantation (TAVI) can be caused by various etiologies. CASE PRESENTATION: An 81-year-old woman with mild mitral regurgitation and complete right bundle branch block was scheduled to undergo TAVI under general anesthesia. After the deployment of the prosthetic valve, electrocardiography depicted a wide QRS wave and bradycardia, suggestive of complete atrioventricular block. Although there was no lesion indicative of tissue injury to the valve itself, worsening of mitral regurgitation was identified on transesophageal echocardiography. The hemodynamic condition was stable, and no additional procedure was performed. Electrocardiography depicted a return to a narrow QRS wave 3 days after surgery, and the mitral regurgitation appeared comparable to the preoperative grade. We assumed that the worsening of mitral regurgitation was caused by dyssynchrony in the left ventricle due to the conduction disorder. CONCLUSIONS: Mitral regurgitation after TAVI needs observation, including the determination of the etiology and treatment principle.

Successful treatment of bepridil-induced intraoperative torsades de pointes by isoproterenol infusion.

BACKGROUND: Several types of antiarrhythmic drugs are known to induce QT prolongation and torsades de pointes. CASE PRESENTATION: An 84-year-old man was scheduled for open gastrectomy for residual cancer. He had been prescribed bepridil for atrial fibrillation that converted to sinus rhythm with prolonged QT interval in the operating room. After the surgery was initiated under general and epidural anesthesia, the patient's heart rate decreased to 50/min and multifocal premature ventricular contractions appeared, followed by several episodes of torsades de pointes, each lasting for 5 to 15 s. Infusion of isoproterenol was started (0.01 µg/kg/min), and the heart rate was maintained at around 80/min. Premature ventricular contractions disappeared, and torsades de pointes did not recur during the surgery. The operation was completed uneventfully. The serum bepridil concentration was found to be extremely high postoperatively. CONCLUSIONS: Bepridil-induced intraoperative episodes of torsades de pointes were successfully treated by increasing the heart rate with isoproterenol.

Airway emergency during general anesthesia in a child with plastic bronchitis following Fontan surgery: a case report.

BACKGROUND: Plastic bronchitis (PB) is a complication of Fontan surgery, results in the formation of mucus plug in the tracheobronchial tree, causing potentially fatal airway obstruction. We report critical airway emergency during general anesthesia in a child with plastic bronchitis. CASE PRESENTATION: A 5-year-old boy was scheduled for intrapulmonary lymphatic embolization through percutaneous catheterization under general anesthesia. He underwent Fontan surgery at the age of 2 and frequently developed respiratory failure due to plastic bronchitis. After induction of general anesthesia and tracheal intubation, mechanical ventilation became difficult even with an inspiratory pressure ≥ 50 mmHg due to airway obstruction. He expectorated a large mucus plug through the tracheal tube after administration of sugammadex, naloxone, and flumazenil, and respiratory condition was stabilized thereafter. CONCLUSION: General anesthesia for a patient with plastic bronchitis should be planned with extracorporeal membrane oxygenation or cardiopulmonary bypass stand by.

High-intensity transient signals during transcatheter aortic valve implantation assessed by ultrasonic carotid artery blood-flow monitoring: A single center prospective observational study.

BACKGROUND: No reports to date have assessed the procedural patterns of high-intensity transient signals (HITS) by monitoring blood flow in cervical arteries. The aim of this study was to examine the sequential distribution of HITS in each procedural phase and predictive factors for HITS during transcatheter aortic valve implantation (TAVI) by monitoring blood flow in the common carotid artery. METHODS: This prospective observational study included 73 patients who underwent TAVI via the transfemoral artery approach. We continuously evaluated and analyzed HITS from administration of heparin to valve implantation. RESULTS: HITS peaked during balloon valvuloplasty (BAV), amounting to almost 30% of the total HITS count, followed by valve implantation [BAV 141 (73-186) and valve implantation 86 (64-126), respectively]. In univariate and multivariate analysis, the Agatston score of the aortic valve and low-density lipoprotein were confirmed as independent predictors of HITS frequency with logarithmically converted coefficients of 0.00015 (p < 0.001) and 0.0032 (p = 0.027), respectively. CONCLUSIONS: These results provide the first evidence that micro-emboli deriving from calcified burden were scattered primally during BAV, followed by valve implantation. The Agatston score may be a predictor for the amount of HITS.

Cesarean section under spinal anesthesia in acquired complete atrioventricular block without a pacemaker: A case report.

Pregnancy with complete atrioventricular block is rare, and its perioperative management is controversial. We successfully managed cesarean section in a pregnancy with acquired complete atrioventricular block under spinal anesthesia without a pacemaker. Asymptomatic pregnant women with acquired complete atrioventricular block can tolerate cesarean section under spinal anesthesia without a pacemaker.

Massive Hemorrhage From the Aorta on Removal of an Anterior Mediastinal Tumor in Spite of Using an Endovascular Stent Graft: A Case Report.

A 68-year-old man was scheduled for mediastinal tumor resection. Aortic invasion was unclear on preoperative computed tomography. Transesophageal echocardiography showed a smooth endothelial border, but the tumor was contiguous with the distal arch, and the adventitial border was unclear. After median sternotomy, the tumor was found to be adherent to the aorta. An endovascular stent graft was placed in the distal arch to protect the aorta, but excessive bleeding occurred from the aortic defect on tumor removal. This case shows that massive hemorrhage can occur during the resection of an aorta-invading tumor despite the use of an endovascular stent graft.

Synergistic cytoprotection by co-treatment with dexamethasone and rapamycin against proinflammatory cytokine-induced alveolar epithelial cell injury.

BACKGROUND: One of the main pathophysiological manifestations during the acute phase of sepsis is massive production of proinflammatory mediators. Clinical trials involving direct suppression of inflammatory mediators to relieve organ dysfunction in sepsis have been extensively performed; however, the clinical outcomes of such trials remain far from satisfactory. Given the need for better sepsis treatments, we have screened various agents with anti-inflammatory properties for cytoprotective effects. In this study, we identified dexamethasone and rapamycin as clinically applicable candidates with favorable synergistic effects against inflammatory cytokine-induced cytotoxicity in vitro and further explored the molecular mechanisms underlying the augmented cytoprotective effects exerted by co-treatment with both drugs. METHODS: Human alveolar epithelial cell-derived A549 cells were stimulated with a mixture of inflammatory cytokines, TNF-alpha, IL-1beta, and IFN-gamma, which induce cellular injury, including apoptosis. This in vitro model was designed to simulate acute lung injury (ALI) associated with sepsis. The cells were co-treated with dexamethasone and rapamycin under cytokine stimulation. Conditioned medium and cell lysates were subjected to further analysis. RESULTS: Either dexamethasone or rapamycin significantly attenuated cytokine-induced cytotoxicity in A549 cells in a dose-dependent manner. In addition, the simultaneous administration of dexamethasone and rapamycin had a synergistic cytoprotective effect. The applied doses of dexamethasone (10 nM) and rapamycin (1 nM) were considerably below the reported plasma concentrations of each drug in clinical setting. Interestingly, distinct augmentation of both of c-Jun inhibition and Akt activation were observed when the cells were co-treated with both drugs under cytokine stimulation. CONCLUSIONS: A synergistic protective effect of dexamethasone and rapamycin was observed against cytokine-induced cytotoxicity in A549 cells. Augmentation of both of c-Jun inhibition and Akt activation were likely responsible for the cytoprotective effect. The combined administration of anti-inflammatory drugs such as dexamethasone and rapamycin offers a promising treatment option for alveolar epithelial injury associated with sepsis.

Successful use of regional anesthesia in non-intubated video-assisted thoracic surgery in patients with cardiopulmonary failure: two case reports.

BACKGROUND: One-lung ventilation under general anesthesia is necessary for thoracic surgery, but this procedure is often difficult in surgery for patients with cardiopulmonary failure. Non-intubated video-assisted thoracic surgery (VATS) is performed under local anesthesia for patients with respiratory failure, but has not been performed for patients with circulatory failure. Here, we report management of two patients with cardiopulmonary failure who underwent non-intubated VATS with paravertebral block and infiltration anesthesia. CASE PRESENTATION: Case 1 was a 79-year-old male with dyspnea at rest due to left large pleural effusion and cardiac dysfunction who underwent thoracoscopic pleural biopsy with paravertebral block under spontaneous breathing. The patient was also receiving dialysis. Case 2 was a 53-year-old male who developed empyema due to large pleural effusion, resulting in a poor general condition and cardiac dysfunction, and underwent video-assisted empyema curettage only with infiltration anesthesia under spontaneous breathing. In both patients, intraoperative respiration and circulation remained stable with values similar to those present preoperatively, and there were no problems after surgery. CONCLUSIONS: We safely anesthetized two patients with difficulty to general anesthesia by ensuring sufficient regional anesthesia during VATS under spontaneous breathing. These cases suggest that regional anesthesia for non-intubated VATS can contribute to maintain intra- and postoperative respiration and circulation in patients with cardiopulmonary failure.

Neuropeptide glutamic acid-isoleucine (NEI)-induced paradoxical sleep in rats.

Neuropeptideglutamic acid-isoleucine (NEI) as well as melanin concentrating hormone (MCH) is cleaved from the 165 amino acid protein, prepro-melanin concentrating hormone (prepro-MCH). Among many physiological roles of MCH, we demonstrated that intracerebroventricular (icv) injection of MCH induced increases in REM sleep episodes as well as in non REM sleep episodes. However, there are no studies on the effect of NEI on the sleep-wake cycle. As for the sites of action of MCH for induction of REM sleep, the ventrolateral periaqueductal gray (vlPAG) has been reported to be one of its site of action. Although MCH neurons contain NEI, GABA, MCH, and other neuropeptides, we do not know which transmitter(s) might induce REM sleep by acting on the vlPAG. Thus, we first examined the effect of icv injection of NEI on the sleep-wake cycle, and investigated how microinjection of either NEI, MCH, or GABA into the vlPAG affected REM sleep in rats. Icv injection of NEI (0.61µg/5µl: n=7) significantly increased the time spent in REM episodes compared to control (saline: 5µl; n=6). Microinjection of either NEI (61ng/0.2µl: n=7), MCH (100ng/0.2µl: n=6) or GABA (250mM/0.2µl: n=7) into the vlPAG significantly increased the time spent in REM episodes and the AUC. Precise hourly analysis of REM sleep also revealed that after those microinjections, NEI and MCH increased REM episodes at the latter phase, compared to GABA which increased REM episodes at the earlier phase. This result suggests that NEI and MCH may induce sustained REM sleep, while GABA may initiate REM sleep. In conclusion, our findings demonstrate that NEI, a cleaved peptide from the same precursor, prepro-MCH, as MCH, induce REM sleep at least in part through acting on the vlPAG.

[Tension pneumothorax associated with re-intubation through percutaneous tracheostoma site].

Percutaneous tracheostomy (PT) has become popular recently, but occasionally cannula exchange can be difficult and hazardous. A 55-year-old woman with pontine hemorrhage was admitted to our ICU after oral intubation. On the 3 rd day, PT was performed with no complication to prepare for prolonged airway management. On the 14 th day, surgical removal of the pontine hematoma was scheduled. Since our neurosurgeon requested a prone position with maximal neck anteflexion, she was re-intubated orally and the tracheostomy cannula was removed during the operation. At the end of the operation, the tracheostoma had already been narrowed and re-insertion of a narrower tracheostomy cannula was unsuccessful even with bronchoscopic guidance. Following several attempts, her Spo2 gradually decreased and her blood pressure dropped. A chest X-ray showed right pneumothorax and a chest drainage tube was inserted. Posterior tracheal wall injury was suspected, though the exact injury site was not identified bronchoscopically. She was treated conservatively because no air leak was observed after advancing the oral tube. Three weeks later, surgical tracheostomy was performed without major abnormal findings. A small tracheostoma characteristic of PT might be associated with an increased risk of delayed airway complication. Cannula exchange should be performed more carefully after PT compared with surgical tracheostomy.

A case of malignant hyperthermia that was difficult to be differentiated from oral antipsychotic polypharmacy-associated neuroleptic malignant syndrome.

Malignant hyperthermia (MH) occurred during anesthesia with volatile inhalation anesthetics in a patient under treatment with multiple oral antipsychotic drugs and with a history of multi-acting receptor-targeted antipsychotic drug (MARTA)-induced elevation of serum creatine kinase (CK). Since the patient was considered to be at high risk for neuroleptic malignant syndrome (NMS) based on this history, differential diagnosis between MH and NMS was difficult at the time of onset. Later, the patient was found to be predisposed to MH based on abnormal high rate of the Ca2+-induced Ca2+ release (CICR). We concluded that MH was induced by the volatile inhalation anesthetics.