Cardioprotective Effects of Sodium-Glucose Cotransporter Subtype Inhibition on Ischemic and Pharmacological Preconditioning.

BACKGROUND: Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition. METHODS: Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning (IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl). RESULTS: The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group. CONCLUSION: The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

Amniotic fluid embolism rescued using venoarterial extracorporeal membrane oxygenation without initial anticoagulation: A case report and literature review.

RATIONALE: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation. PATIENTS CONCERNS: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced. DIAGNOSIS: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE. INTERVENTIONS: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications. OUTCOMES: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae. LESSONS: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.

Venoarterial extracorporeal membrane oxygenation for group B streptococcal toxic shock syndrome: A case report and literature review.

RATIONALE: Streptococcal toxic shock syndrome (STSS) rapidly leads to refractory shock and multiple organ failure. The mortality rate among patients with STSS is 40%; however, most deaths occur within a few days of onset. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) may help avoid acute death in adult patients with STSS. However, the effectiveness of VA-ECMO is unclear. In this study, we report a case of group B STSS, which was successfully treated with VA-ECMO despite cardiopulmonary arrest (CPA) owing to rapidly progressive refractory shock. PATIENT CONCERNS: A 60-year-old woman was hospitalized because of diarrhea and electrolyte abnormalities owing to chemoradiation therapy for rectal cancer. A sudden deterioration of her condition led to CPA. Conventional cardiopulmonary resuscitation was immediately performed but was ineffective. Therefore, VA-ECMO was initiated. Contrast-enhanced computed tomography revealed duodenal perforation. Hence, septic shock owing to peritonitis was diagnosed, and emergency surgery was performed under VA-ECMO. However, the patient had progressive multiple organ failure and required organ support therapy in the intensive care unit (ICU). DIAGNOSES: On day 2 in the ICU, blood and ascites fluid culture tests revealed beta-hemolytic streptococci, and the patient was finally diagnosed as having STSS caused by Streptococcus agalactiae. INTERVENTIONS: Clindamycin was added to meropenem, vancomycin, and micafungin, which had been administered since the sudden deterioration. In addition, VA-ECMO, mechanical ventilation, blood purification therapy, and treatment for disseminated intravascular coagulation were continued. OUTCOMES: Thereafter, hemodynamics improved rapidly, and the patient was weaned off VA-ECMO on day 5 of ICU admission. She was transferred to a general ward on day 22 in the ICU. LESSONS: In patients with fatal STSS and rapid progressive refractory shock or CPA, VA-ECMO may help to avoid acute death and improve prognosis by ameliorating tissue oxygenation and providing extra time to treat invasive streptococcal infection.

Refractory cardiac arrest caused by type I Kounis syndrome treated with adrenaline and nicorandil: A case report.

RATIONALE: Kounis syndrome is a rare but life-threatening anaphylactic reaction that can lead to acute coronary syndrome and cardiac arrest, and requires prompt diagnosis. Adrenaline, which is used to treat anaphylaxis, may cause coronary vasoconstriction and worsen ischemia, whereas coronary vasodilators may dilate systemic vessels and exacerbate hypotension. Delayed diagnosis of Kounis syndrome and inadequate therapeutic intervention may thus lead to a poor outcome. PATIENT CONCERNS: A 59-year-old man was treated for sepsis due to a liver abscess. Following administration of daptomycin, the patient developed severe anaphylactic shock leading to refractory cardiac arrest. Because conventional cardiopulmonary resuscitation was ineffective, extracorporeal cardiopulmonary resuscitation was considered as an alternative approach. DIAGNOSES: On bedside monitoring during cardiopulmonary resuscitation, unexpected ST-segment elevation was found on lead II electrocardiogram. Accordingly, the patient was clinically diagnosed with Kounis syndrome. INTERVENTIONS: Nicorandil (6 mg/h), a coronary vasodilator with minimal blood pressure effects, was administered along with high doses of vasopressors, including adrenaline 0.2 µg/kg/min. OUTCOMES: After the initiation of nicorandil administration, the patient achieved return of spontaneous circulation and did not require extracorporeal cardiopulmonary resuscitation. Based on the elevated serum tryptase level, normal creatine kinase-MB range, and lack of stenosis on coronary angiography, the patient was definitively diagnosed with type I (coronary vasospasm) Kounis syndrome. He was subsequently transferred to the referring hospital without neurological sequelae. LESSONS: If anaphylaxis leads to refractory shock and cardiac arrest, ischemic changes on the electrocardiogram should be investigated to identify underlying Kounis syndrome. In addition to adrenaline, coronary dilators are the definitive treatment. Nicorandil may be a useful treatment option because of its minimal effect on blood pressure.

Absent right superior vena cava with persistent left superior vena cava in a patient with COVID-19.

Vascular injury associated with cannulation during extracorporeal membrane oxygenation (ECMO) induction is a rare but life-threatening complication. The presence of abnormal vascular anatomy increases the risk of vascular injury and should be recognized before cannulation. We report the case of a patient with coronavirus disease (COVID-19) who was expected to undergo ECMO. By performing computed tomography (CT), we identified the absence of right superior vena cava (RSVC) with a persistent left superior vena cava (PLSVC) that could have caused serious complications associated with ECMO cannulation. PLSVC is observed in less than 0.5% of the general population; however, the combination of PLSVC and an absent RSVC in visceroatrial situs solitus is extremely rare. Attempting cannulation for Veno-venous (VV)-ECMO from the right (or left) internal jugular vein to the right atrium may cause serious complications. Cannulation may fail or lead to complications even in patients with inferior vena cava malformations. Although these vascular abnormalities are rare, it is possible to avoid iatrogenic vascular injury by identifying their presence in advance. Since anatomical variations in the vessels from the deep chest and abdominal cavity cannot be visualized using chest radiography and ultrasonography, we recommend CT, if possible, for patients with severe respiratory failure, including those with COVID-19, who may be considered for VV-ECMO induction.

Association between enterocyte injury and fluid balance in patients with septic shock: a post hoc exploratory analysis of a prospective observational study.

BACKGROUND: The required fluid volume differs among patients with septic shock. Enterocyte injury caused by shock may increase the need for fluid by triggering a systematic inflammatory response or an ischemia-reperfusion injury in the presence of intestinal ischemia/necrosis. This study aimed to evaluate the association between enterocyte injury and positive fluid balance in patients with septic shock. METHODS: This study was a post hoc exploratory analysis of a prospective observational study that assessed the association between serum intestinal fatty acid-binding protein, a biomarker of enterocyte injury, and mortality in patients with septic shock. Intestinal fatty acid-binding protein levels were recorded on intensive care unit admission, and fluid balance was monitored from intensive care unit admission to Day 7. The association between intestinal fatty acid-binding protein levels at admission and the infusion balance during the early period after intensive care unit admission was evaluated. Multiple linear regression analysis, with adjustments for severity score and renal function, was performed. RESULTS: Overall, data of 57 patients were analyzed. Logarithmically transformed intestinal fatty acid-binding protein levels were significantly associated with cumulative fluid balance per body weight at 24 and 72 h post-intensive care unit admission both before (Pearson's r = 0.490 [95% confidence interval: 0.263-0.666]; P < 0.001 and r = 0.479 [95% confidence interval: 0.240-0.664]; P < 0.001, respectively) and after (estimate, 14.4 [95% confidence interval: 4.1-24.7]; P = 0.007 and estimate, 26.9 [95% confidence interval: 11.0-42.7]; P = 0.001, respectively) adjusting for severity score and renal function. CONCLUSIONS: Enterocyte injury was significantly associated with cumulative fluid balance at 24 and 72 h post-intensive care unit admission. Enterocyte injury in patients with septic shock may be related to excessive fluid accumulation during the early period after intensive care unit admission.

Anaphylactic shock in a patient with severe aortic stenosis treated with adrenaline and landiolol for circulatory management: A case report.

RATIONALE: We present the first case of a patient with severe aortic stenosis who developed anaphylactic shock and was successfully treated with adrenaline and landiolol, a highly selective ß1-receptor blocker, to prevent disruption of the myocardial oxygen supply-demand balance caused by tachycardia. PATIENT CONCERNS: An 86-year-old woman was scheduled for simultaneous anterior-posterior fixation for a burst fracture of the 12th thoracic vertebra; 200 mg sugammadex, a neuromuscular blocking agent antagonist, was administered postoperatively, and she was extubated without complications. However, 6 min after extubation, her blood pressure decreased abruptly to 55/29 mm Hg, and her heart rate increased to 78 bpm. Then, we intervened with fluid loading, an increased dose of noradrenaline, and phenylephrine administration. However, her blood pressure did not increase. DIAGNOSES: A general observation revealed urticaria on the lower leg; thus, we suspected anaphylactic shock due to sugammadex administration. INTERVENTIONS: We carefully administered 2 doses of 0.05 mg adrenaline and simultaneously administered landiolol at 60 µg/kg/min to suppress adrenaline-induced tachycardia. Adrenaline administration resulted in a rapid increase in blood pressure to 103/66 mm Hg and a maximum heart rate of 100 bpm, suppressing excessive tachycardia. OUTCOMES: The patient's general condition was stable after the intervention, and circulatory agonists could be discontinued the following day. She was discharged from the intensive care unit on the fourth postoperative day. LESSONS: Landiolol may help control the heart rate of patients with aortic stenosis and anaphylactic shock. The combined use of landiolol and adrenaline may improve patient outcomes; however, their efficacy and risks must be evaluated by studying additional cases.

Removal of a catheter mount and heat-and-moisture exchanger improves hypercapnia in patients with acute respiratory distress syndrome: A retrospective observational study.

ABSTRACT: To avoid ventilator-associated lung injury in acute respiratory distress syndrome (ARDS) treatment, respiratory management should be performed at a low tidal volume of 6 to 8 mL/kg and plateau pressure of ≤30 cmH2O. However, such lung-protective ventilation often results in hypercapnia, which is a risk factor for poor outcomes. The purpose of this study was to retrospectively evaluate the effectiveness and safety of the removal of a catheter mount (CM) and using heated humidifiers (HH) instead of a heat-and-moisture exchanger (HME) for reducing the mechanical dead space created by the CM and HME, which may improve hypercapnia in patients with ARDS.This retrospective observational study included adult patients with ARDS, who developed hypercapnia (PaCO2 > 45 mm Hg) during mechanical ventilation, with target tidal volumes between 6 and 8 mL/kg and a plateau pressure of ≤30 cmH2O, and underwent stepwise removal of CM and HME (replaced with HH). The PaCO2 values were measured at 3 points: ventilator circuit with CM and HME (CM + HME) use, with HME (HME), and with HH (HH), and the overall number of accidental extubations was evaluated. Ventilator values (tidal volume, respiratory rate, minutes volume) were evaluated at the same points.A total of 21 patients with mild-to-moderate ARDS who were treated under deep sedation were included. The values of PaCO2 at HME (52.7 ±â€Š7.4 mm Hg, P < .0001) and HH (46.3 ±â€Š6.8 mm Hg, P < .0001) were significantly lower than those at CM + HME (55.9 ±â€Š7.9 mm Hg). Measured ventilator values were similar at CM + HME, HME, and HH. There were no cases of reintubation due to accidental extubation after the removal of CM.The removal of CM and HME reduced PaCO2 values without changing the ventilator settings in deeply sedated patients with mild-to-moderate ARDS on lung-protective ventilation. Caution should be exercised, as the removal of a CM may result in circuit disconnection or accidental extubation. Nevertheless, this intervention may improve hypercapnia and promote lung-protective ventilation.

Allergen-Related Coronary Vasospasm "Kounis Syndrome" Requiring Administration of Epinephrine and a Coronary Vasodilator.

Kounis syndrome is an anaphylactic reaction leading to acute coronary syndrome. The acute treatment of anaphylaxis is epinephrine; however, epinephrine may cause coronary vasoconstriction, reduce coronary blood flow, increase myocardial oxygen demand, and worsen myocardial ischemia. On the other hand, coronary vasodilation, a treatment for acute coronary syndrome, can aggravate hypotension in patients with anaphylaxis. Herein, the authors report a case of type II Kounis syndrome, with vasospasm in a patient with coronary disease, requiring the administration of epinephrine and a coronary vasodilator for resuscitation. The authors administered intravenous epinephrine continuously from lower dosages and performed delicate titration. The coronary vasodilator nicorandil, which has little effect on hemodynamics, also was administered. These treatments improved hemodynamics without complications. Circulatory management that considers both anaphylaxis and coronary lesions is crucial to improve prognosis in this syndrome.

Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock: A posthoc analysis of a prospective observational study.

Endotoxemia often occurs in patients with gram-positive infections. The possible mechanism is thought to be bacterial translocation after enterocyte hypoperfusion injury. However, the association between endotoxemia and enterocyte injury among patients with gram-positive septic shock has never been assessed. The aim of this study was to evaluate the association between endotoxemia and enterocyte injury in gram-positive septic shock patients and to evaluate the association among endotoxemia, subsequent clinical course, and other related factors.This was a posthoc analysis of a prospective observational study that evaluated the capability of intestinal fatty acid-binding protein (I-FABP), an indicator of enterocyte injury, to predict mortality. Among 57 patients in septic shock, those whose causative microorganisms were gram positive were included. The correlation between endotoxin activity (EA), which indicates endotoxemia, and I-FABP levels upon admission to the intensive care unit (ICU), the clinical course, and other related factors were evaluated.A total of 21 patients were examined. One-third of the patients presented with high EA levels at the time of ICU admission. However, there was no significant correlation between EA and I-FABP levels (Spearman ρ = 0.002, P = .993). Additionally, high EA levels were not associated with abdominal complications after ICU admission or mortality. Similarly, high EA levels were not associated with severity scores, inotropic scores, or lactate levels upon ICU admission, which were previously reported to be factors related to high EA levels.In this posthoc analysis, no correlation was observed between endotoxemia and enterocyte injury among patients in gram-positive septic shock. Additionally, high EA levels were not associated with the clinical course and reported factors related to endotoxemia. Although our results need to be validated in a large prospective cohort study, hypoperfusion enterocyte injury might not be a cause of endotoxemia in these patients. Thus, if there is no correlation between EA and I-FABP levels, other mechanisms that induce high EA levels among patients with gram-positive septic shock should be elucidated.

Association Between Macroscopic Tongue Ischemia and Enterocyte Injury and Poor Outcome in Patients With Septic Shock: A Preliminary Observational Study.

A correlation between sublingual and intestinal mucosa microcirculation, and ischemic necrosis of the tongue as a sign of poor prognosis has been reported. However, an association between tongue ischemia and intestinal health and subsequent outcome has never been studied. This preliminary prospective observational study evaluated the association between macroscopic tongue ischemia and enterocyte injury and poor outcome in patients with septic shock. In this study, 57 adults with septic shock on mechanical ventilators were enrolled. Macroscopic tongue ischemia upon intensive care unit (ICU) admission was assessed by two independent intensivists. We used intestinal fatty-acid binding protein (I-FABP) as a biomarker of enterocyte injury and evaluated the association with tongue ischemia. Demographic variables, risk factor data, and 28-day mortality information were also collected. Compared with patients with normal tongues (n = 45), those with ischemic tongues (n = 12) had a significantly higher Acute Physiology and Chronic Health Evaluation II score (29.0 [25.0-34.0] vs. 36.5 [30.5-44.5], P = 0.017), lactate level (2.8 [2.0-5.0] vs. 9.3 [4.5-10.6], P = 0.002), and I-FABP level (1.9 [0.8-4.0] vs. 54.4 [19.5-159.3], P < 0.001) and the all-cause 28-day mortality was significantly higher (7% vs. 83%, P < 0.001). In conclusion, macroscopic tongue ischemia at ICU admission was associated with enterocyte injury and poor outcome in patients with septic shock. Although there is a disadvantage in that assessment of the tongue was subjective, tongue ischemia could be used to gauge the severity of intestinal injury and to estimate poor outcome in the clinical setting.

Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock: A preliminary study.

PURPOSE: We sought to evaluate the levels of intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, as a predictor of 28-day mortality and bowel ischemia in septic shock patients. MATERIAL AND METHODS: In this preliminary prospective observational study, 57 adult septic shock patients under mechanical ventilation were enrolled. Serum I-FABP levels and prognostic biomarkers were recorded upon intensive care unit (ICU) admission. RESULTS: The overall 28-day mortality rate of participants was 23% (13/57). Non-survivors displayed significantly higher lactate (p=0.009), I-FABP (p=0.012), and N-terminal pro-B-type natriuretic peptide (p=0.039) levels compared to survivors. Only I-FABP was associated with 28-day mortality (odds ratio, 1.036; 95% confidence interval, 1.003-1.069; p=0.031) in a multiple logistic regression analysis adjusted for the Acute Physiology and Chronic Health Evaluation II score. When divided into low and high I-FABP groups based on the optimum cut-off value of 19.0ng/mL for predicting 28-day mortality, high-I-FABP patients had a significantly higher incidence of non-occlusive mesenteric ischemia (NOMI) (2% [1/43] vs 29% [4/14]; p=0.011). CONCLUSIONS: I-FABP level at ICU admission can serve as a predictor of 28-day mortality in septic shock patients and is associated with the incidence of NOMI.

[Analysis of the Factors in Successful Helmet Non-invasive Positive Pressure Ventilation].

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) reduces the incidences of ventilator-associated pneumonia, the duration of ICU stay and the mortality rate compared with conventional respiratory management of the patients with acute respiratory failure (ARF). Recently, helmet NPPV equipment became available. Because of the high tolerability, the helmet seems to be the best NPPV interface when prolonged and continuous assistance is needed. In this study, we analyzed several factors related to failure of helmet NPPV in ARF patients in intensive care unit (ICU), retrospectively. METHODS: Institutional Research Committee of Nagasaki Rosai Hospital approved this study. We studied consecutive patients with ARF who needed ventilator support in ICU from February 2012 to February 2013. We excluded the patients whose trachea had been intubated before admission to ICU and comatose patients. After admission to ICU, all ARF-patients received helmet NPPV and conventional intensive care therapy including sedation with dexmedetomidine and vasoactive agents. General clinical data including blood gas analysis were recorded at admission to ICU and during ICU stay. Patient's tracheas were intubated if they met at least one of the following criteria, as judged after they had received helmet NPPV: lack of improvement in arterial blood pH or PaCO2; changes in mental status, in patients unable to tolerate noninvasive ventilation; a decrease in SaO2 to less than 85% despite the use of a high FIO2. The final decision of endotracheal intubation was made by a staff intensivist. We defined the failure of helmet NPPV as the execution of endotracheal intubation. The data were presented as median (IQR), and statistical analysis was performed using Mann-Whitney U-test and Fisher's exact probability test at the P<0.05 level of significance. RESULTS: The subjects were 36 patients (25 males and 11 females) aged 27 to 94 years, including 6 patients with acute heart failure (AHF), 8 with pneumonia, 6 with aspiration pneumonia, 2 with hemothorax, 10 with acute respiratory distress syndrome (ARDS), 1 with asthma, and 3 with acute exacerbation of chronic obstructive pulmonary disease (COPD). NPPV was successful in 29 (19 males and 10 females), but unsuccessful in 7 patients (6 males and 1 female). There were no significant differences in demographic data and the variables before induction of NPPV between the successful and unsuccessful groups. The P/F ratio was improved from 133 (99,167) to 209 (143,274) in the successful group, and from 93 (81,157) to 188 (129,271) in the unsuccessful group after the induction of NPPV, but there was no significant difference between the two groups. In the patients with unsuccessful NPPV, expiratory positive airway pressure, inspiratory positive airway pressure, respiratory rate, body temperature and FIO2 before removing NPPV were significantly higher, and ICU stay was longer compared with the patients with successful NPPV. Furthermore, marked excretion of sputum was observed in 4 of the 7 patients with unsuccessful NPPV. CONCLUSIONS: Helmet NPPV improved oxygenation in ARF patients immediately after induction of NPPV. Although there were no significant predictable parameters of unsuccessful NPPV before induction of NPPV, a lot of excretion of sputum might be suggested as a risk factor.