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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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: The diagnosis of mesenteric ischemia in critically ill patients remains challenging; however, the aquarium sign, comprising a large number of bubble images in the right cardiac chambers on echocardiography, may be used as a point-of-care ultrasound finding to diagnose acute mesenteric ischemia (AMI)., Patient Concerns: A 65-year-old woman diagnosed with lymphoma was urgently admitted to the intensive care unit with suspected tumor lysis syndrome. High-dose vasopressor and inotropic agents were required to manage the patient's shock with marked lactic acidosis and peripheral hypoperfusion with mottled skin, and multidisciplinary treatment was initiated. By day 6, the lactate levels normalized and there were no abnormal abdominal findings. An echocardiogram was performed to examine the mass lesion associated with lymphoma in the right atrium and evaluate the hemodynamics; it revealed an "aquarium sign." Similar findings were found in the inferior vena cava and portal vein., Diagnoses: Contrast-enhanced computed tomography of the abdomen revealed hepatic portal vein gas, poor contrast of the colon wall, and intramural emphysema, and a diagnosis of AMI was made. Lower gastrointestinal endoscopy showed necrosis of the colon., Interventions: The patient underwent urgent subtotal colorectal resection., Outcomes: Although a tracheostomy was required, the patient's general condition improved after surgery, and she was discharged to the ward without mechanical ventilatory support in the intensive care unit on Day 19., Lessons: In patients with risk factors for AMI, repeated evaluation for the presence of aquarium signs by echocardiography may be warranted, even if there are no abdominal findings or abnormalities in biomarkers, such as lactate levels and trends. When the aquarium sign is found, AMI should be aggressively suspected, and a definitive diagnosis should be made to initiate early therapeutic intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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 ± 7.4 mm Hg, P < .0001) and HH (46.3 ± 6.8 mm Hg, P < .0001) were significantly lower than those at CM + HME (55.9 ± 7.9 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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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 β1-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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown., Methods: We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality., Results: Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29)., Conclusions: Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

In head and neck surgery where the oropharyngeal area is the operative field, postoperative respiratory depression and upper airway obstruction are common. Therefore, supplemental oxygen is administered to prevent severe postoperative early hypoxemia. However, a high concentration of oxygen increases the likelihood of secondary complications, such as carbon dioxide (CO2) narcosis. Nasal high-flow (NHF) therapy generates high flows (≤60 L/min) of heated and humidified gas delivered via nasal cannula and provides respiratory support by generating positive airway pressure, clearance of dead space and reduction of work of breathing. This study aims to determine whether the postoperative hypoxemia and hypercapnia can be prevented by NHF without the requirement of supplemental oxygen. The study will recruit adult patients undergoing planned oral surgery under general anesthesia at Nagasaki University Hospital. It is a randomized parallel group comparative study with 3 groups: NHF with room air only and no supplemental oxygen, no respiratory support, and face mask oxygen administration. The study protocol will begin at the time that the patient is returned to the general ward and will finish 3 hours later. The primary endpoint is the time-weighted average of transcutaneous O2 over the 180 minutes and secondary endpoints are the time-weighted average of transcutaneous CO2 (tcpCO2), SpO2, and respiratory rate, incidence rate of marked hypercapnia (tcpCO2 ≥60 mm Hg for 5 minutes or longer), incidence rate of moderate hypercapnia (tcpCO2 ≥50 mm Hg for 5 minutes or longer) and the percentage of time that SpO2 is <90%. Included also is a group in which the postoperative management is performed only by spontaneous breathing without performing respiratory support such as oxygen administration, to investigate the efficacy and necessity of conventional oxygen administration. This exploratory study will investigate the use of NHF without supplemental oxygen as an effective respiratory support during the acute postoperative period. TRIAL REGISTRATION:: The study was registered the jRCTs072200018. URL https://jrct.niph.go.jp/latest-detail/jRCTs072200018.

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.

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.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

Background: Pharmacological blockade of the renin-angiotensin system is thought to maintain gut perfusion during circulatory stress and thereby avoid later failure of distant organs. In this controlled experimental study, we investigated the effects of carperitide, a synthetic atrial natriuretic peptide that inhibits the renin-angiotensin system, on the systemic and splanchnic circulation during fluid-resuscitated endotoxemia in pigs., Methods: Sixteen domestic pigs of both sexes were randomly divided into 2 groups. The pigs were anesthetized and their lungs ventilated before receiving either saline (Group A: n = 8) or carperitide (Group B: n = 8). After a baseline measurement was taken, the pigs from both groups received a continuous infusion (1.7 microg x kg(-1) x h(-1)) of endotoxin for 240 min. Group B received a continuous infusion of carperitide (0.05 microg x kg(-1) x min(-1)) starting 30 min before the endotoxin infusion and lasting until the end of the study, whereas Group A received the same volume of saline. Fluid resuscitation was titrated to maintain pulmonary artery wedge pressure between 10 and 12 mm Hg. Systemic and regional hemodynamics, oxygenation variables, and the arterial-to-intestinal PCO(2) gap were measured at baseline and after endotoxin infusion for 240 min. The primary end points were cardiac index, superior mesenteric artery flow index, and PCO(2) gap at the end of this study (T240)., Results: Cardiac index and superior mesenteric artery flow index in Group B were significantly higher than those in Group A at T240 (83 +/- 15 vs 135 +/- 23 mL x kg(-1) x min(-1), P < 0.001; 2.6 +/- 1.4 vs 7.9 +/- 4.8, P = 0.01), respectively. Carperitide administration resulted in a significantly better maintenance of intestinal mucosal perfusion assessed by the PCO(2) gap at T240 (33.0 +/- 14.5 vs 11.6 +/- 10.0 mm Hg, P = 0.004). The PaO(2)/FIO(2) ratio in Group B was significantly greater than that in Group A from T60 to T240., Conclusions: In this porcine fluid-resuscitated endotoxemia model, a low dose of carperitide administered before endotoxemia maintained systemic and splanchnic circulation, and prevented the deterioration of oxygenation. Atrial natriuretic peptide infusion is a potentially beneficial therapy with respect to systemic and splanchnic circulation as well as the respiratory system during sepsis.

We previously demonstrated that late electromyographic responses with a latency of 100 ms were evoked bilaterally in soleus muscles following transcranial magnetic stimulation over the left cerebellum. Efferent fibers from the left cerebellum modulate vestibulospinal tract influences on the extensor muscles of the left hindlimb. Here, we investigated whether the vestibulospinal tract mediates this late response. We activated the vestibulospinal tract by optokinetic stimulation. Our results show that the latency of the soleus electromyographic response is shortened by optokinetic stimulation, but the latency of the motor response evoked by the corticospinal tract is unchanged. These findings support our hypothesis that vestibulospinal tracts mediate late electromyographic responses, and allow the development of techniques to assess the human vestibulospinal system function.