Intraoperative cardiac arrest caused by unexpected vasospastic angina requiring prolonged resuscitation using extracorporeal membrane oxygenation: a case report.

BACKGROUND: Vasospastic angina (VSA) occurring during surgery is rare but can lead to sudden intraoperative cardiac arrest. CASE PRESENTATION: A 77-year-old man with hypertension, and no history of coronary artery disease, displayed an abrupt ST-segment elevation on the electrocardiogram (ECG) during laparoscopic inguinal hernia surgery under general anesthesia. Subsequently, ventricular fibrillation (VF) occurred, with a finding suggesting ischemic myocardial contracture by transesophageal echocardiography. VF was refractory to cardiopulmonary resuscitation (CPR), and veno-arterial extracorporeal membrane oxygenation (VA ECMO) was introduced. Spontaneous circulation resumed 77 min post-cardiac arrest. VSA was confirmed through the patient's clinical course and coronary angiography. Subsequently, VA ECMO was terminated, and the patient was discharged uneventfully. CONCLUSIONS: Extracorporeal CPR may be a valuable alternative to extended resuscitation for refractory ventricular arrhythmias by VSA.

Intraoperative serum lactate levels as a prognostic predictor of outcome for emergency abdominal surgery: a retrospective study.

BACKGROUND: The relationship between intraoperative lactate levels and prognosis after emergency gastrointestinal surgery remains unclear. The purpose of this study was to investigate the prognostic value of intraoperative lactate levels for predicting in-hospital mortality, and to examine intraoperative hemodynamic managements. METHODS: We conducted a retrospective observational study of emergency GI surgeries performed at our institution between 2011 and 2020. The study group comprised patients admitted to intensive care units postoperatively, and whose intraoperative and postoperative lactate levels were available. Intraoperative peak lactate levels (intra-LACs) were selected for analysis, and in-hospital mortality was set as the primary outcome. The prognostic value of intra-LAC was assessed using logistic regression and receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 551 patients included in the study, 120 died postoperatively. Intra-LAC in the group who survived and the group that died was 1.80 [interquartile range [IQR], 1.19-3.01] mmol/L and 4.22 [IQR, 2.15-7.13] mmol/L (P < 0.001), respectively. Patients who died had larger volumes of red blood cell (RBC) transfusions and fluid administration, and were administered higher doses of vasoactive drugs. Logistic regression analysis showed that intra-LAC was an independent predictor of postoperative mortality (odds ratio [OR] 1.210, 95% CI 1.070 -1.360, P = 0.002). The volume of RBCs, fluids transfused, and the amount of vasoactive agents administered were not independent predictors. The area under the curve (AUC) of the ROC curve for intra-LAC for in-hospital mortality was 0.762 (95% confidence interval [CI], 0.711-0.812), with a cutoff value of 3.68 mmol/L by Youden index. CONCLUSIONS: Intraoperative lactate levels, but not hemodynamic management, were independently associated with increased in-hospital mortality after emergency GI surgery.

Therapeutic Effects of Hyaluronic Acid Against Cytotoxic Extracellular Vesicles Released During Pseudomonas Aeruginosa Pneumonia.

ABSTRACT: Extracellular vesicles (EVs) have now been recognized as important mediators of cellular communication during injury and repair. We previously found that plasma EVs isolated from ex vivo perfused human lungs injured with Escherichia coli bacterial pneumonia were inflammatory, and exogenous administration of high molecular weight (HMW) hyaluronic acid (HA) as therapy bound to these EVs, decreasing inflammation and injury. In the current study, we studied the role of EVs released during severe Pseudomonas aeruginosa (PA) pneumonia in mice and determined whether intravenous administration of exogenous HMW HA would have therapeutic effects against the bacterial pneumonia. EVs were collected from the bronchoalveolar lavage fluid (BALF) of mice infected with PA103 by ultracentrifugation and analyzed by NanoSight and flow cytometry. In a cytotoxicity assay, administration of EVs released from infected mice (I-EVs) decreased the viability of A549 cells compared to EV isolated from sham control mice (C-EVs). Either exogenous HMW HA or an anti-CD44 antibody, when co-incubated with I-EVs, significantly improved the viability of the A549 cells. In mice with PA103 pneumonia, administration of HMW HA improved pulmonary edema and bacterial count in the lungs and decreased TNF-α and caspase-3 levels in the supernatant of lung homogenates. In conclusion, EVs isolated from BALF of mice with P. aeruginosa pneumonia were cytotoxic and inflammatory, and intravenous HMW HA administration was protective against P. aeruginosa pneumonia.

Role of CD44 in increasing the potency of mesenchymal stem cell extracellular vesicles by hyaluronic acid in severe pneumonia.

BACKGROUND: Although promising, clinical translation of human mesenchymal stem or stromal cell-derived extracellular vesicles (MSC EV) for acute lung injury is potentially limited by significant production costs. The current study was performed to determine whether pretreatment of MSC EV with high molecular weight hyaluronic acid (HMW HA) would increase the therapeutic potency of MSC EV in severe bacterial pneumonia. METHODS: In vitro experiments were performed to determine the binding affinity of HMW HA to MSC EV and its uptake by human monocytes, and whether HMW HA primed MSC EV would increase bacterial phagocytosis by the monocytes. In addition, the role of CD44 receptor on MSC EV in the therapeutic effects of HMW HA primed MSC EV were investigated. In Pseudomonas aeruginosa (PA) pneumonia in mice, MSC EV primed with or without HMW HA were instilled intravenously 4 h after injury. After 24 h, the bronchoalveolar lavage fluid, blood, and lungs were analyzed for levels of bacteria, inflammation, MSC EV trafficking, and lung pathology. RESULTS: MSC EV bound preferentially to HMW HA at a molecular weight of 1.0 MDa compared with HA with a molecular weight of 40 KDa or 1.5 MDa. HMW HA primed MSC EV further increased MSC EV uptake and bacterial phagocytosis by monocytes compared to treatment with MSC EV alone. In PA pneumonia in mice, instillation of HMW HA primed MSC EV further reduced inflammation and decreased the bacterial load by enhancing the trafficking of MSC EV to the injured alveolus. CD44 siRNA pretreatment of MSC EV prior to incubation with HMW HA eliminated its trafficking to the alveolus and therapeutic effects. CONCLUSIONS: HMW HA primed MSC EV significantly increased the potency of MSC EV in PA pneumonia in part by enhancing the trafficking of MSC EV to the sites of inflammation via the CD44 receptor on MSC EV which was associated with increased antimicrobial activity.

Therapeutic potential of mesenchymal stem/stromal cell-derived secretome and vesicles for lung injury and disease.

Introduction: The acute respiratory distress syndrome (ARDS) is a devastating clinical condition common in patients with respiratory failure. Based largely on numerous preclinical studies and recent Phase I/II clinical trials, administration of stem cells, specifically mesenchymal stem or stromal cells (MSC), as a therapeutic for acute lung injury (ALI) holds great promise. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that stem cell-derived conditioned medium (CM) and/or extracellular vesicles (EV) might constitute compelling alternatives.Areas covered: The current review focuses on the preclinical studies testing MSC CM and/or EV as treatment for ALI and other inflammatory lung diseases.Expert opinion: Clinical application of MSC or their secreted CM may be limited by the cost of growing enough cells, the logistic of MSC storage, and the lack of standardization of what constitutes MSC CM. However, the clinical application of MSC EV remains promising, primarily due to the ability of EV to maintain the functional phenotype of the parent cell as a therapeutic. However, utilization of MSC EV will also require large-scale production, the cost of which may be prohibitive unless the potency of the EV can be increased.

Therapeutic Effects of Hyaluronic Acid in Bacterial Pneumonia in Ex Vivo Perfused Human Lungs.

Rationale: Recent studies have demonstrated that extracellular vesicles (EVs) released during acute lung injury (ALI) were inflammatory.Objectives: The current study was undertaken to test the role of EVs induced and released from severe Escherichia coli pneumonia (E. coli EVs) in the pathogenesis of ALI and to determine whether high-molecular-weight (HMW) hyaluronic acid (HA) administration would suppress lung injury from E. coli EVs or bacterial pneumonia.Methods:E. coli EVs were collected from the perfusate of an ex vivo perfused human lung injured with intrabronchial E. coli bacteria for 6 hours by ultracentrifugation and then given intrabronchially or intravenously to naive human lungs. One hour later, HMW HA was instilled into the perfusate (n = 5-6). In separate experiments, HMW HA was given after E. coli bacterial pneumonia (n = 6-10). In vitro experiments were conducted to evaluate binding of EVs to HMW HA and uptake of EVs by human monocytes.Measurements and Main Results: Administration of HMW HA ameliorated the impairment of alveolar fluid clearance, protein permeability, and acute inflammation from E. coli EVs or pneumonia and reduced total bacteria counts after E. coli pneumonia. HMW HA bound to E. coli EVs, inhibiting the uptake of EVs by human monocytes, an effect associated with reduced TNFα (tumor necrosis factor α) secretion. Surprisingly, HMW HA increased E. coli bacteria phagocytosis by monocytes.Conclusions: EVs induced and released during severe bacterial pneumonia were inflammatory and induced ALI, and HMW HA administration was effective in inhibiting the uptake of EVs by target cells and decreasing lung injury from E. coli EVs or bacterial pneumonia.

Dose of intraoperative remifentanil administration is independently associated with increase in the risk of postoperative nausea and vomiting in elective mastectomy under general anesthesia.

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the common complications in patients who have undergone surgery with general anesthesia. The association of intraoperative use of remifentanil with PONV has remained controversial. The aim of the current study was to determine the association of dose of intraoperative remifentanil administration with incidence of PONV. METHODS: The present study was a single-center retrospective observational study and included 423 female patients with American Society of Anesthesiologists physical status I or II who underwent elective mastectomy under general anesthesia between October 2011 and October 2012. The incidence of PONV within 3 days after the operation was prospectively assessed. The time-weighted average of remifentanil during the operation (twRem) was calculated. We used a multivariate regression model to assess the independent association of the twRem with the incidence of PONV. RESULTS: Among 423 patients, 129 patients (30.5%) had PONV during the study period. Remifentanil was administrated in 355 patients (83.9%). In the multivariate logistic regression model using categories of twRem, we found that increased twRem was independently associated with increase in the risk of PONV (P=.01). There was an independent association between twRem greater than 0.2 µg/kg per minute and increase in the risk of PONV. CONCLUSION: This retrospective observational study revealed a dose-dependent association between dose of intraoperative remifentanil administration and increase in the risk of PONV. Time-weighted average of remifentanil greater than 0.2 µg/kg per minute was independently associated with risk of PONV.