Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome.

BACKGROUND: The lung microbiome maintains the homeostasis of the immune system within the lungs. In acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-derived bacteria; however, the specific microbiome associated with morbidity and mortality in patients with ARDS remains unclear. This study investigated the specific patterns of the lung microbiome that are correlated with mortality in ARDS patients. METHODS: We analyzed the lung microbiome from the bronchoalveolar lavage fluid (BALF) of patients with ARDS and control subjects. We measured the copy numbers of 16S rRNA and the serum and BALF cytokines (interleukin [IL]-6, IL-8, receptor for advanced glycation end products, and angiopoietin-2). RESULTS: We analyzed 47 mechanically ventilated patients diagnosed with (n = 40) or without (n = 7; control) ARDS. The alpha diversity was significantly decreased in ARDS patients compared with that of the controls (6.24 vs. 8.07, P = 0.03). The 16S rRNA gene copy numbers tended to be increased in the ARDS group compared with the controls (3.83 × 106 vs. 1.01 × 105 copies/mL, P = 0.06). ARDS patients were subdivided into the hospital survivor (n = 24) and non-survivor groups (n = 16). Serum IL-6 levels were significantly higher in the non-survivors than in the survivors (567 vs. 214 pg/mL, P = 0.027). The 16S rRNA copy number was significantly correlated with serum IL-6 levels in non-survivors (r = 0.615, P < 0.05). The copy numbers and relative abundance of betaproteobacteria were significantly lower in the non-survivors than in the survivors (713 vs. 7812, P = 0.012; 1.22% vs. 0.08%, P = 0.02, respectively). Conversely, the copy numbers of Staphylococcus, Streptococcus and Enterobacteriaceae were significantly correlated with serum IL-6 levels in the non-survivors (r = 0.579, P < 0.05; r = 0.604, P < 0.05; r = 0.588, P < 0.05, respectively). CONCLUSIONS: The lung bacterial burden tended to be increased, and the alpha diversity was significantly decreased in ARDS patients. The decreased Betaproteobacteria and increased Staphylococcus, Streptococcus and Enterobacteriaceae might represent a unique microbial community structure correlated with increased serum IL-6 and hospital mortality. TRIAL REGISTRATION: The institutional review boards of Hiroshima University (Trial registration: E-447-4, registered 16 October 2019) and Kyoto Prefectural University of Medicine (Trial registration: ERB-C-973, registered 19 October 2017) approved an opt-out method of informed consent.

Rapid-onset plasma leakage of extracorporeal oxygenation membranes possibly due to hyperbilirubinemia.

Extracorporeal membrane oxygenation (ECMO) is an emerging tool for supporting cardiopulmonary function in patients with cardiorespiratory failure or arrest. The oxygenator of the ECMO circuit requires effective oxygenation and removal of carbon dioxide from the blood. Major problems that can occur with the oxygenator include plasma leakage, one of the late-onset serious complications necessitating device replacement. However, the rapid onset of plasma leakage is rare. We present a 1-year-old boy with acute respiratory failure due to Pneumocystis and Aspergillus pneumonia. He presented with tachypnea, tachycardia, and hypoxemia despite the ventilatory support, and was therefore placed on venoarterial ECMO with a drainage catheter from the right internal jugular vein (12 Fr) and a return catheter to the right internal carotid artery (10 Fr). Extracorporeal circulation was initiated at a blood flow of 1 L/min (145 mL/kg/min) and a sweep gas flow of 1 L/min with FiO2 of 0.7. Although he was successfully weaned from the venoarterial ECMO on day 15 with an improvement of cardiopulmonary function, he was later placed on venoarterial ECMO again because of the progression of pulmonary hypertension. Laboratory tests showed increased concentrations of hepatic enzymes and hyperbilirubinemia (total bilirubin 31.6 mg/dL). Six hours after starting ECMO circulation, plasma leakage from the oxygenator occurred. Although we replaced the oxygenator with a new one, the replacement showed plasma leakage after 6 h. Disassembly of the oxygenator revealed congestion from bilirubin in the membrane fibers. We described a case of repeated, rapid-onset plasma leakage after implementation of ECMO. Hyperbilirubinemia was likely associated with the plasma leakage of this patient.

Pediatric cardiorespiratory failure successfully managed with venoarterial-venous extracorporeal membrane oxygenation: a case report.

BACKGROUND: Venoarterial-venous extracorporeal membrane oxygenation (VAV ECMO) configuration is a combined procedure of extracorporeal membrane oxygenation (ECMO). The proportion of cardiac and respiratory support can be controlled by adjusting arterial and venous return. Therefore, VAV ECMO can be applicable as a bridging therapy in the transition from venoarterial (VA) to venovenous (VV) ECMO. CASE PRESENTATION: We present an 11-year-old girl with chemotherapy-induced myocarditis requiring extracorporeal cardiorespiratory support. She showed progressive hypotension, tachycardia, hyperlactemia, and tachypnea under support of catecholamines. Echocardiography showed severe left ventricular hypokinesis with an ejection fraction of 30 %. She was placed on VA ECMO with a drainage catheter from the right femoral vein (19.5 Fr) and a return catheter to the right femoral artery (16.5 Fr). Extracorporeal circulation was initiated at a blood flow of 2.0 L/min (59 mL/kg/min). On day 31, although cardiac function had improved, persistent pulmonary failure made weaning from VA ECMO difficult. We planned transition from VA ECMO to VAV ECMO to ensure gradual tapering of extracorporeal cardiac support while evaluating cardiopulmonary function. An additional return cannula (13.5 Fr) was inserted from the right internal jugular vein, which was connected to the circuit branch from the original returning cannula. We then gradually shifted the blood from the femoral artery to the right internal jugular vein over 24 h. She was successfully switched from VA to VV ECMO via VAV ECMO. CONCLUSIONS: VAV ECMO might be an option in ensuring oxygenation to the coronary circulation and allowing time to adequately evaluate cardiac function during transition from VA to VV ECMO. Further investigations using larger cohorts are necessary to validate the efficacy of VAV ECMO as a bridging therapy in the transition from VA to VV ECMO.

Influence of clinical experience of the Macintosh laryngoscope on performance with the Pentax-AWS Airway Scope(®), a rigid video-laryngoscope, by paramedics in Japan.

PURPOSE: We sought to establish the clinical utility of the Pentax-AWS Airway Scope(®) (AWS) when used by paramedics to intubate the trachea, and to evaluate whether their performance was influenced by previous clinical experience with the Macintosh laryngoscope (ML). METHODS: Twenty paramedics attempted tracheal intubation using the AWS in five patients each in the operating room. We recorded the success rate, the number of intubation attempts, and the time for intubation and adverse events, and compared these based on the paramedics' previous clinical experience with the ML. Ten paramedics had no prior clinical experience of the ML (group A) and 10 had used it on more than 30 occasions (group B). RESULTS: The intubation success rate was 99 % (99/100). Notably, 96 % (47/49) of intubations were achieved on the first attempt by the inexperienced paramedics in group A, compared with 64 % (32/50) by the experienced paramedics in group B (p = 0.0001). The time to intubation (mean ± SD) was significantly shorter in group A than in group B (37 ± 24 vs. 48 ± 21 s, p = 0.002). There were marked variations in the times taken to intubate, but no apparent improvement as the intubators gained experience between their first and fifth cases. No complications were encountered in either group. CONCLUSION: We found that paramedics could achieve a high tracheal intubation success rate using the AWS independent of previous airway management experience. Better intubation performance with the AWS was observed in paramedics without clinical experience with the ML.

No improvement in mortality among critically ill patients with carbapenems as initial empirical therapy and more detection of multi-drug resistant pathogens associated with longer use: a post hoc analysis of a prospective cohort study.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

Use of broad-spectrum antimicrobials for more than 72 h and the detection of multidrug-resistant bacteria in Japanese intensive care units: a multicenter retrospective cohort study.

BACKGROUND: Large multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study. METHODS: We analyzed the data of ICU patients in the DIANA study (a multicenter international observational cohort study from Japan). Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann-Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria. RESULTS: A total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h (OR [odds ratio] 3.09, p = 0.047) and cerebrovascular comorbidity on ICU admission (OR 2.91, p = 0.041) were associated with the detection of new MDR bacteria. CONCLUSIONS: Among Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy. Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463.

Tracheal intubation of a difficult airway using Airway Scope, Airtraq, and Macintosh laryngoscope: a comparative manikin study of inexperienced personnel.

BACKGROUND: The Airway Scope (AWS) (Pentax-AWS, Hoya Corp., Tokyo, Japan) and the Airtraq (ATQ) (Prodol, Vizcaya, Spain) have similarities in the novel structures of their blades. In this study, we evaluated the ease of use of the AWS and ATQ compared with the Macintosh laryngoscope (ML) by inexperienced personnel in a simulated manikin difficult airway. METHODS: Twenty-four fifth-year medical students with no previous experience in tracheal intubation participated in this study. We used an advanced patient simulator (SimMan(R), Laerdal Medical, Stavanger, Norway) to simulate difficult airway scenarios including cervical spine rigidity, limited mouth opening, and pharyngeal obstruction. The sequences in selecting devices and scenarios were randomized. Success rates for tracheal intubation, and the time required for visualization of the glottis, tracheal intubation, and inflation of the lungs, and the number of optimization maneuvers and dental click sounds were analyzed. The 3 different intubation devices were tested in 4 different scenarios by 24 students. RESULTS: Both the AWS and ATQ had very high success rates of tracheal intubation compared with the ML (AWS 100%*; ATQ 98%*; and ML 89%; *P < 0.05 AWS, ATQ versus ML). The time to intubation with the AWS was significantly shorter than with the ATQ and ML (AWS 11 +/- 6 seconds; ATQ 16 +/- 12 seconds; and ML 16 +/- 11 seconds; *P < 0.05 AWS versus ATQ, ML). The number of optimization maneuvers with the AWS was significantly lower than with the ATQ and ML. There were significantly more audible dental click sounds with the ML than with the AWS and ATQ. CONCLUSION: Both the AWS and ATQ may be suitable devices for difficult intubation by inexperienced personnel in this manikin simulated scenario. Further studies in a clinical setting are necessary to confirm these findings.

Prognosis of pathogen-proven acute respiratory distress syndrome diagnosed from a protocol that includes bronchoalveolar lavage: a retrospective observational study.

BACKGROUND: To treat patients with acute respiratory distress syndrome (ARDS), it is important to diagnose specific lung diseases and identify common risk factors. Our facility focuses on using bronchoalveolar lavage (BAL) to identify precise risk factors and determine the causative pathogen of ARDS within 24 h of intensive care unit (ICU) admission. This study evaluated the prognoses of pathogen-proven ARDS patients who were diagnosed or identified with risk factors using a diagnostic protocol, which included BAL, compared with the prognoses of pathogen-unproven ARDS patients. METHODS: This retrospective observational study was conducted in the ICU at a tertiary hospital from October 2015 to January 2019. We enrolled patients with respiratory distress who were on mechanical ventilation for more than 24 h in the ICU and who were subjected to our diagnostic protocol. We compared the disease characteristics and mortality rates between pathogen-proven and pathogen-unproven ARDS patients. RESULTS: Seventy ARDS patients were included, of whom, 50 (71%) had pathogen-proven ARDS as per our protocol. Mortality rates in both the ICU and the hospital were significantly lower among pathogen-proven ARDS patients than among pathogen-unproven ARDS patients (10% vs. 50%, p = 0.0006; 18% vs. 55%, p = 0.0038, respectively). Pathogen-proven ARDS patients were independently associated with hospital survival (adjusted hazard ratio, 0.238; 95% confidence interval, 0.096-0.587; p = 0.0021). CONCLUSIONS: Our diagnostic protocol, which included early initiation of BAL, enabled diagnosing pathogen-proven ARDS in 71% of ARDS patients. These patients were significantly associated with higher hospital survival rates. The diagnostic accuracy of our diagnostic protocol, which includes BAL, remains unclear.

Practical use of airway pressure release ventilation for severe ARDS--a preliminary report in comparison with a conventional ventilatory support.

Airway pressure release ventilation (APRV) is a ventilatory mode that allows unsupported spontaneous breathing at any phase of the ventilatory cycle with high mean airway pressures. We hypothesized that use of APRV might produce potential beneficial effects on oxygenation, reducing mortality in patients with severe acute respiratory distress syndrome (ARDS) in comparison with synchronized intermittent mandatory ventilation (SIMV) as a conventional mode of ventilation. We retrospectively reviewed data of 58 patients with severe ARDS (the ratios of partial arterial oxygen tension to fraction of inspired oxygen, PaO2/F(I)O2 ratio <150). The patients' data were divided into two groups: SIMV-group and APRV-group. Patients' backgrounds, oxygenation on day 0, 1, 3, 5 and 7 following initiation of each mode, vasopressor dependence, duration of ventilation, duration of ICU stay, and mortality in ICU were analyzed. PaO2/F(I)O2 ratios were statistically higher in the APRV-group (APRV vs. SIMV on day 1, 3, 5, 7: 201.6 +/- 76 vs.150 +/- 59.1, 256.7 +/- 71.5 vs.182.1 +/- 65.4, 268.8 +/- 73.3 vs. 204.6 +/- 72.8, and 263 +/- 74.5 vs. 204.1 +/- 67.1, respectively, p<0.05). Vasopressors were less used (p=0.018), and mortality in ICU tended to be lower in the APRV group (31%) than in the SIMV group (59%) (p=0.050). Use of APRV in patients with severe ARDS appears to be associated with improvements in oxygenation, and a trend toward lower mortality in ICU. No significant adverse effects were observed. Prospective controlled studies are required to confirm the benefits of this ventilatory mode in comparison with conventional methods for severe ARDS.

High serum potassium level is associated with successful electrical cardioversion for new-onset atrial fibrillation in the intensive care unit: A retrospective observational study.

Electrical cardioversion (ECV) is a potentially life-saving treatment for haemodynamically unstable new-onset atrial fibrillation (AF); however, its efficacy is unsatisfactory. We aimed to elucidate the factors associated with successful ECV and prognosis in patients with AF. This retrospective observational study was conducted in two mixed intensive care units (ICUs) in a university hospital. Patients with new-onset AF who received ECV in the ICU were enrolled. We defined an ECV session as consecutive shocks within 15 minutes. The success of ECV was evaluated five minutes after the session. We analysed the factors associated with successful ECV and ICU mortality. Eighty-five AF patients who received ECV were included. ECV was successful in 41 (48%) patients, and 11 patients (13%) maintained sinus rhythm until ICU discharge. A serum potassium level ≥3.8 mol/L was independently associated with successful ECV in multivariate analysis (odds ratio (OR), 3.13; 95% confidence interval (CI), 1.07-9.11; p = 0.04). Maintenance of sinus rhythm until ICU discharge was significantly associated with ICU survival (OR 9.35; 95% CI 1.02-85.78, p = 0.048). ECV was successful in 48% of patients with new-onset AF developed in the ICU. A serum potassium level ≥3.8 mol/L was independently associated with successful ECV, and sinus rhythm maintained until ICU discharge was independently associated with ICU survival. These results suggested that maintaining a high serum potassium level may be important when considering the effectiveness of ECV for AF in the ICU.

Retrospective immunohistological study of autopsied lungs in patients with acute exacerbation of interstitial pneumonia managed with extracorporeal membrane oxygenation.

BACKGROUND: Acute exacerbation of interstitial pneumonia (AE-IP) is a life-threatening pulmonary condition that involves various pathogeneses. In patients with AE-IP who need mechanical ventilation with high driving pressure and oxygen concentration, veno-venous extracorporeal membrane oxygenation (V-V ECMO) may diminish alveolar epithelial damage by decreasing ventilator settings. The pathophysiological benefit of this therapeutic option is not well investigated. METHODS: We retrospectively collected 15 autopsied patients with AE-IP who were treated with mechanical ventilation in the intensive care unit (ICU) at Hiroshima University Hospital (Hiroshima, Japan) between 2010 and 2016. The patients were grouped by whether they were managed with mechanical ventilation only (the ventilator group, n=6) or with mechanical ventilation and V-V ECMO (the ECMO group, n=9). RESULTS: The median age of the ventilator and ECMO group patients were similar (65 and 64 years, respectively). The severity score APACHE II in the ECMO group (35.0) is significantly higher than that of ventilator group (14.5) (P=0.006). Ventilator days were significantly shorter in the ventilator group (17.5 days) than in the ECMO group (30.0 days) (P=0.04). Compared with the ECMO group, the ventilator group had a stronger Masson-trichrome stain grade (4 vs. 6, P=0.04) and higher immunoreactivity grades for Krebs von den Lungen-6 (4 vs. 6, P=0.04) and IL-8 (3 vs. 6, P=0.02). Between the ventilator and ECMO groups, the immunoreactivity grades of angiopoietin 2 (4 vs. 1, P=0.08) and receptor for advanced glycation end products (2 vs. 1, P=0.52) did not differ. CONCLUSIONS: The lungs of mechanically ventilated AE-IP patients treated with V-V ECMO had decreased fibrosis, endothelial injury, and inflammation. This finding suggests the lung-protective efficacy of adjunctive V-V ECMO therapy.

A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia.

BACKGROUND: Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. CASE PRESENTATION: Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. CONCLUSION: A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.

KL-6, a Human MUC1 Mucin, as a prognostic marker for diffuse alveolar hemorrhage syndrome.

BACKGROUND: Diffuse alveolar hemorrhage syndrome is a life threatening condition with diverse etiologies. Sensitive prognostic markers for diffuse alveolar hemorrhage have not been well investigated. Serum KL-6 is a biomarker for various interstitial lung disease associated with disease activity and prognosis. The purpose of the present study was to evaluate the clinical utility of serum KL-6 level as a prognostic marker for diffuse alveolar hemorrhage. METHODS: We retrospectively collected 41 consecutive patients clinically diagnosed as having diffuse alveolar hemorrhage who were admitted to the Intensive Care Unit of Hiroshima University Hospital between 2004 and 2011. Correlation between prognosis and age, sex, laboratory findings including serum KL-6, radiological findings, ventilatory modes or therapeutic regimens were evaluated. RESULTS: Baseline and peak serum KL-6 levels were significantly higher in non-survivors compared with survivors. An increase in KL-6 levels during the initial week was associated with a subsequent deterioration of the oxygenation index. Higher baseline KL-6 levels and higher peak KL-6 levels were strongly correlated with death. With a cut-off level of 700 U/mL for peak KL-6, the sensitivity, specificity and accuracy for non-survival were 75%, 85% and 78%, respectively. In the multivariate analysis, only the peak KL-6 level ≥ 700 U/ml was an independent poor prognostic factor for diffuse alveolar hemorrhage. CONCLUSIONS: Peak serum KL-6 level ≥ 700 U/ml may become a clinically useful marker of poor prognosis for diffuse alveolar hemorrhage.