Activation of the ß-adrenergic receptor exacerbates lipopolysaccharide-induced wasting of skeletal muscle cells by increasing interleukin-6 production.

The skeletal muscle mass has been shown to be affected by catecholamines, such as epinephrine (Epi), norepinephrine (NE), and isoproterenol (ISO). On the other hand, lipopolysaccharide (LPS), one of the causative substances of sepsis, induces muscle wasting via toll-like receptors expressed in skeletal muscle. Although catecholamines are frequently administered to critically ill patients, it is still incompletely understood how these drugs affect skeletal muscle during critical illness, including sepsis. Herein, we examined the direct effects of catecholamines on LPS-induced skeletal muscle wasting using the C2C12 myoblast cell line. Muscle wasting induced by catecholamines and/or LPS was analyzed by the use of the differentiated C2C12 myotubes, and its underlying mechanism was explored by immunoblotting analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and the TransAM kit for p-65 NF-κB. Epi augmented myosin heavy chain (MHC) protein loss and reduction of the myotube diameter induced by LPS. LPS induced C/EBPδ protein, Atrogin-1 and inteleukin-6 (IL-6), and these responses were potentiated by Epi. An IL-6 inhibitor, LMT28, suppressed the potentiating effect of Epi on the LPS-induced responses. NF-κB activity was induced by LPS, but was not affected by Epi and recombinant IL-6, and the NF-κB inhibitor, Bay 11-7082, abolished Atrogin-1 mRNA expression induced by LPS with or without Epi. NE and ISO also potentiated LPS-induced IL-6 and Atroign-1 mRNA expression. Carvedilol, a nonselective ß-adrenergic receptor antagonist, suppressed the facilitating effects of Epi on the Atrogin-1 mRNA induction by LPS, and abolished the effects of Epi on the MHC protein loss in the presence of LPS. It was concluded that Epi activates the ß-adrenergic receptors in C2C12 myotubes and the IL-6-STAT3 pathway, leading to the augmentation of LPS-induced activation of the NF-κB- C/EBPδ-Atrogin-1 pathway and to the exacerbation of myotube wasting.

Invasive Respiratory or Vasopressor Support and/or Death as a Proposed Composite Outcome Measure for Perioperative Care Research.

BACKGROUND: There is a need for a clinically relevant and feasible outcome measure to facilitate clinical studies in perioperative care medicine. This large-scale retrospective cohort study proposed a novel composite outcome measure comprising invasive respiratory or vasopressor support (IRVS) and death. We described the prevalence of IRVS in patients undergoing major abdominal surgery and assessed the validity of combining IRVS and death to form a composite outcome measure. METHODS: We retrospectively collected perioperative data for 2776 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or esophageal resection) at Kyoto University Hospital. We defined IRVS as requirement for mechanical ventilation for ≥24 hours postoperatively, postoperative reintubation, or postoperative vasopressor administration. We evaluated the prevalence of IRVS within 30 postoperative days and examined the association between IRVS and subsequent clinical outcomes. The primary outcome of interest was long-term survival. Multivariable Cox proportional regression analysis was performed to adjust for the baseline patient and operative characteristics. The secondary outcomes were length of hospital stay and hospital mortality. RESULTS: In total, 85 patients (3.1%) received IRVS within 30 postoperative days, 15 of whom died by day 30. Patients with IRVS had a lower long-term survival rate (1- and 3-year survival probabilities, 66.1% and 48.5% vs 95.2% and 84.0%, respectively; P < .001, log-rank test) compared to those without IRVS. IRVS was significantly associated with lower long-term survival after adjustment for the baseline patient and operative characteristics (adjusted hazard ratio, 2.72; 95% confidence interval, 1.97-3.77; P < .001). IRVS was associated with a longer hospital stay (median [interquartile range], 65 [39-326] vs 15 [12-24] days; adjusted P < .001) and a higher hospital mortality (24.7% vs 0.5%; adjusted P < .001). Moreover, IRVS was adversely associated with subsequent clinical outcomes including lower long-term survival (adjusted hazard ratio, 1.78; 95% confidence interval, 1.21-2.63; P = .004) when the analyses were restricted to 30-day survivors. CONCLUSIONS: Patients with IRVS can experience ongoing risk of serious morbidity and less long-term survival even if alive at postoperative day 30. Our findings support the validity of using IRVS and/or death as a composite outcome measure for clinical studies in perioperative care medicine.

Near-infrared spectroscopy underestimates cerebral oxygenation in hemodialysis patients.

Regional cerebral oxygen saturation (rSO2) measured using near-infrared spectroscopy has been reported to be significantly lower in hemodialysis (HD) patients than in non-HD ones, but the mechanisms are unknown. The aim of this prospective study was to assess the accuracy of near-infrared spectroscopy to estimate cerebral oxygenation in HD patients undergoing cardiovascular surgery. Our hypothesis was that rSO2 values would underestimate cerebral oxygenation in HD patients. This study included 113 patients (7 HD patients and 106 non-HD ones) undergoing cardiac or major aortic surgery between December 2015 and November 2017. We evaluated the validity of rSO2 by comparing it with ipsilateral jugular venous oxygen saturation (SjvO2). In HD and non-HD patients, rSO2 and SjvO2 showed a weak correlation (R2: 0.46 and 0.28 in HD and non-HD patients, respectively). Bland-Altman analysis revealed that bias (95% limits of agreement) of rSO2 compared to SjvO2 was - 19.2% ( - 41.7-3.3%) in HD patients and - 1.9% (- 19.3-15.5%) in non-HD ones. The large negative bias suggests that the rSO2 values measured using near-infrared spectroscopy substantially underestimate cerebral oxygenation in HD patients.

Rapid bacterial identification by direct PCR amplification of 16S rRNA genes using the MinION™ nanopore sequencer.

Rapid identification of bacterial pathogens is crucial for appropriate and adequate antibiotic treatment, which significantly improves patient outcomes. 16S ribosomal RNA (rRNA) gene amplicon sequencing has proven to be a powerful strategy for diagnosing bacterial infections. We have recently established a sequencing method and bioinformatics pipeline for 16S rRNA gene analysis utilizing the Oxford Nanopore Technologies MinION™ sequencer. In combination with our taxonomy annotation analysis pipeline, the system enabled the molecular detection of bacterial DNA in a reasonable time frame for diagnostic purposes. However, purification of bacterial DNA from specimens remains a rate-limiting step in the workflow. To further accelerate the process of sample preparation, we adopted a direct PCR strategy that amplifies 16S rRNA genes from bacterial cell suspensions without DNA purification. Our results indicate that differences in cell wall morphology significantly affect direct PCR efficiency and sequencing data. Notably, mechanical cell disruption preceding direct PCR was indispensable for obtaining an accurate representation of the specimen bacterial composition. Furthermore, 16S rRNA gene analysis of mock polymicrobial samples indicated that primer sequence optimization is required to avoid preferential detection of particular taxa and to cover a broad range of bacterial species. This study establishes a relatively simple workflow for rapid bacterial identification via MinION™ sequencing, which reduces the turnaround time from sample to result, and provides a reliable method that may be applicable to clinical settings.

Transient acute kidney injury after major abdominal surgery increases chronic kidney disease risk and 1-year mortality.

PURPOSE: We conducted a retrospective cohort study to determine incidences of transient and persistent acute kidney injury (AKI) after major abdominal surgery and their impacts on long-term outcome. MATERIALS AND METHODS: We enrolled 3751 patients undergoing major abdominal surgery. Postoperative AKI was classified as transient or persistent based on the return of serum creatinine to the non-AKI range within 7 days post-surgery. Primary outcome was mortality within 1 year. We used multivariable Cox proportional hazard regression analysis to assess independent associations between AKI type and mortality. RESULTS: Most patients with AKI were classified as transient (84%). Compared to patients without AKI, both patients with transient and persistent AKI demonstrated elevated 1-year mortality rates [adjusted hazard ratio (95% confidence interval): 2.01 (1.34-2.93); P = 0.001, and 6.20 (3.00-11.43); P < 0.001, respectively] and greater risk of chronic kidney disease progression at 1 year [adjusted odds ratio (95% confidence interval): 3.87 (2.12-7.08) and 23.70 (9.64-58.22), respectively; both P < 0.001]. CONCLUSIONS: Although most AKI cases after major abdominal surgery recover completely within 7 days, even these patients with transient AKI are at higher risk for 1-year mortality and chronic kidney disease progression compared to patients without AKI.

Acute kidney injury after pediatric liver transplantation: incidence, risk factors, and association with outcome.

PURPOSE: Data on the incidence of, risk factors for, and association with outcomes of acute kidney injury (AKI) after pediatric liver transplantation are scarce. We conducted a retrospective cohort study to determine the incidence of AKI after pediatric liver transplantation. In addition, we examined risk factors for AKI and association of AKI with outcomes. METHODS: This study included 156 children aged between 3 months and 18 years undergoing liver transplantation at Kyoto University Hospital. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines based on serum creatinine and urine output. We used multivariable logistic regression with stepwise variable selection to identify independent risk factors for AKI. RESULTS: AKI occurred in 72 patients (46.2%); 34 (21.8%) had stage 1, 32 (20.5%) had stage 2, and 6 (3.8%) had stage 3 AKI. Factors independently associated with the development of AKI were increased preoperative total bilirubin level (adjusted odds ratio, 1.04 per 1 mg/dl; 95% confidence interval, 1.01-1.09; P = 0.026) and increased intraoperative blood loss (adjusted odds ratio, 1.03 per 10 ml/kg; 95% confidence interval, 1.00-1.06; P = 0.022). AKI was significantly associated with prolonged hospitalization (median, 61 vs. 46 days; P = 0.028). In-hospital mortality rate was 4.2% in patients with AKI and 3.6% in those without AKI (P = 1.000). CONCLUSION: The incidence of AKI after pediatric liver transplantation was 46.2%. Increased preoperative total bilirubin level and increased intraoperative blood loss were independently associated with the development of AKI. AKI was associated with prolonged hospitalization.

Relationship Between Intraoperative Hypotension and Acute Kidney Injury After Living Donor Liver Transplantation: A Retrospective Analysis.

OBJECTIVE: Acute kidney injury (AKI) is common after liver transplantation (LT) and has a significant impact on outcomes. Although several risk factors for post-LT AKI have been identified, the effect of intraoperative hemodynamic status on post-LT AKI remains unknown. Therefore, the authors aimed to investigate the relationship between hemodynamic parameters during LT and postoperative AKI. DESIGN: A retrospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent living donor LT (n = 231). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severe AKI (stages 2-3 according to recent guidelines) was the primary outcome. Multivariable logistic regression analysis was used to control for confounding variables to obtain the independent relationship between intraoperative hemodynamic parameters (mean arterial pressure [MAP] and cardiac index) and severe AKI. The prevalence of severe AKI was 30.7%. Nadir MAP during the surgery was independently predictive of severe AKI (adjusted odds ratio, 2.11 [95% confidence interval, 1.32-3.47] per 10-mmHg decrease; p = 0.002). Subgroup analyses based on various patient or operative variables and extensive sensitivity analyses showed substantially similar results. Severe hypotension (MAP<40 mmHg), even for fewer than 10 minutes, was related significantly to severe AKI (adjusted odds ratio, 3.80 [95% confidence interval, 1.17-12.30]; p = 0.026). In contrast, nadir cardiac index was not related significantly to severe AKI. CONCLUSIONS: The authors found an independent relationship between degree of intraoperative hypotension and risk of severe AKI in living donor LT recipients. Severe hypotension, even for a short duration, was related significantly to severe AKI.

Low preoperative regional cerebral oxygen saturation in hemodialysis patients.

BACKGROUND: Regional cerebral oxygen saturation (rSO2) monitoring by near-infrared spectroscopy provides valuable information regarding cerebral oxygen delivery, and it has been increasingly used in cardiovascular surgery. Although it has been shown that dialysis-dependent patients [hemodialysis (HD) patients] suffer from low cerebral perfusion, limited information is available on cerebral tissue oxygenation levels in HD patients. FINDINGS: In this retrospective study, the preoperative rSO2 values in 9 HD patients undergoing coronary artery bypass graft surgery were compared with those in 40 non-HD patients. HD patients had lower preoperative rSO2 values than non-HD patients (median: 46 vs. 68%, respectively, P < 0.001). Despite adjusting for age, hemoglobin concentration, and left ventricular ejection fraction using multivariable linear regression, HD showed a strong association with low rSO2 (estimated coefficient: -20.4, P < 0.001). CONCLUSIONS: HD showed a strong association with low preoperative rSO2 values in patients undergoing coronary artery bypass graft surgery, even after adjusting for known factors that affect rSO2 values, including age, hemoglobin concentration, and cardiac systolic function. Further research is required to elucidate the mechanisms decreasing rSO2 values in HD patients.

Effect of arginine vasopressin on systemic and pulmonary arterial pressure in a patient with pulmonary hypertension secondary to pulmonary emphysema: a case report.

Although data from several studies support the use of arginine vasopressin (AVP) for the treatment of hypotension concomitant with pulmonary hypertension (PH) in the cardiac surgery setting, to our knowledge, no previous studies have reported the effect of AVP on the systemic and pulmonary circulation of patients with PH secondary to lung diseases. In this report, we present the hemodynamic responses to bolus administrations of AVP and noradrenaline in a patient with PH secondary to pulmonary emphysema. The patient showed low systemic vascular resistance hypotension during off-pump single-lung transplantation. The bolus administration of AVP (0.5 U) increased systemic arterial pressure by 35.2%, with a minimal change in pulmonary arterial pressure, resulting in a significant decrease in the pulmonary arterial pressure/systemic arterial pressure ratio. In contrast, the bolus administration of noradrenaline (10 or 20 µg) increased both systemic and pulmonary arterial pressures by 14.8 and 6.7%, respectively. In summary, the bolus administration of AVP effectively increased systemic arterial pressure with a minimal effect on pulmonary arterial pressure in a patient with PH secondary to pulmonary emphysema. This case highlights the potential utility of AVP to treat low systemic vascular resistance hypotension in patients with PH secondary to lung diseases.

[Extracorporeal Membrane Oxygenation for Anesthesia Induction in a Patient with Severe Cardiorespiratory Impairment due to Mediastinal Angiosarcoma].

BACKGROUND: Mediastinal angiosarcoma is a rare intrathoracic tumor that can cause severe pleural and pericardial fibrosis. CASE REPORT: We report the anesthetic management for pericardiectomy and pleurolysis in a 33-year-old patient with a mediastinal angiosarcoma. He presented with severe restrictive ventilatory impairment and heart failure due to fibrosis of the pleura and pericardium. Spirometry indicated a forced vital capacity of 0.66 l, while arterial blood gas analysis under noninvasive positive pressure ventilation indicated hypercapnia (pH 7.44; Pa(CO2) 59.2 mmHg). His cardiac index was 1.36 l x min(-1) x m(-2). Anesthesia induction and positive pressure ventilation are associated with an extremely high cardiorespiratory risk; therefore, veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) with femoral cannulation was started prior to anesthesia induction. After achieving a stable circulation and adequate gas exchange, anesthesia was induced, and mechanical ventilation with intratracheal intubation was initiated. With ECMO and inotropic support stable hemodynamics was maintained throughout anesthesia induction and the operation was performed uneventfully under cardiopulmonary bypass. The patient was extubated on the first postoperative day and discharged one month after the operation. CONCLUSION: ECMO is a useful option to secure adequate gas exchange and circulation during anesthesia induction in patients with severe cardiopulmonary problems due to mediastinal tumors.

Preoperative Hypercapnia as a Predictor of Hypotension During Anesthetic Induction in Lung Transplant Recipients.

OBJECTIVE: To determine the incidence and predisposing factors of hypotension during anesthetic induction in lung transplant recipients. DESIGN: Retrospective study. SETTING: University hospital. PARTICIPANTS: Patients who underwent lung transplantation between 2008 and 2013 (n = 68). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed the mean arterial pressure (MAP) from administration of anesthetic drugs to 10 minutes after endotracheal intubation (ie, the anesthetic induction) among participants who underwent lung transplantation. Patients were considered to have clinically significant hypotension (CSH) when the following criteria were fulfilled: An MAP decrease of>40% from baseline and MAP of<60 mmHg. Overall, 41.2% of patients experienced CSH during the induction of anesthesia. The preoperative partial pressure of carbon dioxide (PaCO2) was significantly higher in patients who experienced CSH during anesthetic induction than in those who did not (p = 0.005). Preoperative PaCO2 predicted the development of CSH during anesthetic induction (area under the curve = 0.702; p = 0.002), with an optimal cut-off point of 55 mmHg determined by maximizing the Youden index. The incidences of CSH during anesthetic induction for patients with (PaCO2 ≥ 55) and without (PaCO2<55) preoperative hypercapnia were 75.0% (95% confidence interval [CI] [53.8-89.2]) and 30.8% (95% CI 26.4-37.3), respectively. After adjustment for known predicting factors, the odds ratio for the relationship between preoperative hypercapnia and CSH during anesthetic induction was 12.54 (95% CI 3.10-66.66). CONCLUSIONS: Hypotension during anesthetic induction is common in lung transplant recipients, and is independently predicted by preoperative hypercapnia.

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PURPOSE: We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. METHODS: Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. RESULTS: The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. CONCLUSIONS: Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

[Appropriate dose of remifentanil to blunt tracheal intubation stress response in patients with severe aortic stenosis].

BACKGROUND: In anesthetic induction of patients with severe aortic stenosis, maintenance of normal heart rate and blood pressure is critical. Remifentanil can blunt cardiovascular responses to tracheal intubation, but may cause circulatory collapse due to potent vasodilating effect. We studied retrospectively the optimal dose of remifentanil, which blunts cardiovascular responses to tracheal intubation and provides the hemodynamic stability to patients with severe aortic stenosis. METHODS: We administerd remifentanil with three different doses (0.3 microg x kg(-1) x min(-1) : n=4, 0.5 microg x kg(-1) x min(-1): n=7, 1 microg x kg(-1) x min(-1): n=7) in anesthetic induction of patients with aortic stenosis. Systolic arterial blood pressure and heart rate before and after the tracheal intubation were recorded. The degree of change of post to pre-intubation of systolic arterial pressure and heart rate was calculated and compared among groups. RESULTS: There were no significant differences in background among the groups. The ratio between before and after tracheal intubation of systolic arterial pressure was significantly lower in the group of 0.5 microg x kg(-1) x min(-1) and 1 microg x kg(-1) x min(-1). There was no significant hypotension or bradycardia which may lead to severe cardiovascular depression. CONCLUSIONS: We found that more than 0.5 microg x kg(-1) x min(-1) of remifentanil can blunt cardiovascular responses to tracheal intubation without severe cardiovascular depression.

Delayed chest closure assessed by transesophageal echocardiogram in single-lobe lung transplantation.

A 6-year-old girl with idiopathic interstitial pneumonia successfully underwent living-donor right single-lobe lung transplantation from her mother. Her mother's right lower lobe was 207% bigger than her right chest cavity, and attempting chest closure caused significant compression and narrowing of the right pulmonary vein anastomosis, as assessed by transesophageal echocardiogram. Her chest was temporarily closed without rib approximation. The following day, her chest could be completely closed. The pulmonary vein anastomosis, confirmed by transesophageal echocardiogram, was now patent. Currently, 7 months after the transplantation, she is well without limitations.

[Successful anesthetic management of tracheal reconstruction and omentopexy with thoracic epidural anesthesia and transversus abdominis plane block].

A 64-year-old man was diagnosed to have a tracheal tumor 2 cm proximal to the carina. He was scheduled for tracheal resection and reconstruction with omentopexy. An epidual tube was placed at the level of T5-6. After induction of anesthesia by propofol and remifentanil, a tracheal tube was inserted with the aid of bronchofiberscopy. Bilateral transversus abdominis plane block (TAPB) was performed with 0.5% ropivacaine 40 ml under ultrasound guidance. Anesthesia was maintained by sevoflurane and remifentanil, together with epidural infusion of ropivacaine and fentanyl. During tracheal resection and reconstruction, his left main bronchus was intubated directly from the cutting edge. After the operation, he was extubated under anesthesia without coughing. No pain was complained during postoperative course. Epidural anesthesia combined with TAPB provided sufficient postoperative analgesia, especially in tracheal resection and reconstruction with omentopexy.