Asynchrony Injures Lung and Diaphragm in Acute Respiratory Distress Syndrome.

OBJECTIVES: Patient-ventilator asynchrony is often observed during mechanical ventilation and is associated with higher mortality. We hypothesized that patient-ventilator asynchrony causes lung and diaphragm injury and dysfunction. DESIGN: Prospective randomized animal study. SETTING: University research laboratory. SUBJECTS: Eighteen New Zealand White rabbits. INTERVENTIONS: Acute respiratory distress syndrome (ARDS) model was established by depleting surfactants. Each group (assist control, breath stacking, and reverse triggering) was simulated by phrenic nerve stimulation. The effects of each group on lung function, lung injury (wet-to-dry lung weight ratio, total protein, and interleukin-6 in bronchoalveolar lavage), diaphragm function (diaphragm force generation curve), and diaphragm injury (cross-sectional area of diaphragm muscle fibers, histology) were measured. Diaphragm RNA sequencing was performed using breath stacking and assist control ( n = 2 each). MEASUREMENTS AND MAIN RESULTS: Inspiratory effort generated by phrenic nerve stimulation was small and similar among groups (esophageal pressure swing ≈ -2.5 cm H 2 O). Breath stacking resulted in the largest tidal volume (>10 mL/kg) and highest inspiratory transpulmonary pressure, leading to worse oxygenation, worse lung compliance, and lung injury. Reverse triggering did not cause lung injury. No asynchrony events were observed in assist control, whereas eccentric contractions occurred in breath stacking and reverse triggering, but more frequently in breath stacking. Breath stacking and reverse triggering significantly reduced diaphragm force generation. Diaphragmatic histology revealed that the area fraction of abnormal muscle was ×2.5 higher in breath stacking (vs assist control) and ×2.1 higher in reverse triggering (vs assist control). Diaphragm RNA sequencing analysis revealed that genes associated with muscle differentiation and contraction were suppressed, whereas cytokine- and chemokine-mediated proinflammatory responses were activated in breath stacking versus assist control. CONCLUSIONS: Breath stacking caused lung and diaphragm injury, whereas reverse triggering caused diaphragm injury. Thus, careful monitoring and management of patient-ventilator asynchrony may be important to minimize lung and diaphragm injury from spontaneous breathing in ARDS.

Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study.

BACKGROUND: Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. METHODS: This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. RESULTS: Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359-1.700, and adjusted HR 1.325, 95% CI 1.076-1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24-48 h, 198 (10.7%) at 48-72 h, 111 (6.0%) at 72-96 h, and 85 (4.6%) at 96-120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72-96 h (adjusted HR 1.528, 95% CI 1.062-2.197, and adjusted HR 1.334, 95% CI 0.756-2.352, respectively; referenced to reintubation within 24 h). CONCLUSIONS: Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation.

Personalized ventilatory strategy based on lung recruitablity in COVID-19-associated acute respiratory distress syndrome: a prospective clinical study.

BACKGROUND: Heterogeneity is an inherent nature of ARDS. Recruitment-to-inflation ratio has been developed to identify the patients who has lung recruitablity. This technique might be useful to identify the patients that match specific interventions, such as higher positive end-expiratory pressure (PEEP) or prone position or both. We aimed to evaluate the physiological effects of PEEP and body position on lung mechanics and regional lung inflation in COVID-19-associated ARDS and to propose the optimal ventilatory strategy based on recruitment-to-inflation ratio. METHODS: Patients with COVID-19-associated ARDS were consecutively enrolled. Lung recruitablity (recruitment-to-inflation ratio) and regional lung inflation (electrical impedance tomography [EIT]) were measured with a combination of body position (supine or prone) and PEEP (low 5 cmH2O or high 15 cmH2O). The utility of recruitment-to-inflation ratio to predict responses to PEEP were examined with EIT. RESULTS: Forty-three patients were included. Recruitment-to-inflation ratio was 0.68 (IQR 0.52-0.84), separating high recruiter versus low recruiter. Oxygenation was the same between two groups. In high recruiter, a combination of high PEEP with prone position achieved the highest oxygenation and less dependent silent spaces in EIT (vs. low PEEP in both positions) without increasing non-dependent silent spaces in EIT. In low recruiter, low PEEP in prone position resulted in better oxygenation (vs. both PEEPs in supine position), less dependent silent spaces (vs. low PEEP in supine position) and less non-dependent silent spaces (vs. high PEEP in both positions). Recruitment-to-inflation ratio was positively correlated with the improvement in oxygenation and respiratory system compliance, the decrease in dependent silent spaces, and was inversely correlated with the increase in non-dependent silent spaces, when applying high PEEP. CONCLUSIONS: Recruitment-to-inflation ratio may be useful to personalize PEEP in COVID-19-associated ARDS. Higher PEEP in prone position and lower PEEP in prone position decreased the amount of dependent silent spaces (suggesting lung collapse) without increasing the amount of non-dependent silent spaces (suggesting overinflation) in high recruiter and in low recruiter, respectively.

Establishment and clinical application of SARS-CoV-2 catch column.

BACKGROUND: A certain number of patients with coronavirus disease 2019 (COVID-19), particularly those who test positive for SARS-CoV-2 in the serum, are hospitalized. Further, some even die. We examined the effect of blood adsorption therapy using columns that can eliminate SARS-CoV-2 on the improvement of the prognosis of severe COVID-19 patients. METHODS: This study enrolled seven patients receiving mechanical ventilation. The patients received viral adsorption therapy using SARS-catch column for 3 days. The SARS-catch column was developed by immobilizing a specific peptide, designed based on the sequence of human angiotensin-converting enzyme 2 (hACE2), to an endotoxin adsorption column (PMX). In total, eight types of SARS-CoV-2-catch (SCC) candidate peptides were developed. Then, a clinical study on the effects of blood adsorption therapy using the SARS-catch column in patients with severe COVID-19 was performed, and the data in the present study were compared with historical data of severe COVID-19 patients. RESULTS: Among all SCC candidate peptides, SCC-4N had the best adsorption activity against SARS-CoV-2. The SARS-catch column using SCC-4N removed 65% more SARS-CoV-2 than PMX. Compared with historical data, the weaning time from mechanical ventilation was faster in the present study. In addition, the rate of negative blood viral load in the present study was higher than that in the historical data. CONCLUSION: The timely treatment with virus adsorption therapy may eliminate serum SARS-CoV-2 and improve the prognosis of patients with severe COVID-19. However, large-scale studies must be performed in the future to further assess the finding of this study (jRCTs052200134).

Control of blood glucose levels by an artificial pancreas in patients with severe coronavirus disease 2019 pneumonia.

BACKGROUND: Many patients with severe coronavirus disease 2019 (COVID-19) pneumonia experience hyperglycemia. It is often difficult to control blood glucose (BG) levels in such patients using standard intravenous insulin infusion therapy. Therefore, we used an artificial pancreas. This study aimed to compare the BG status of the artificial pancreas with that of standard therapy. METHODS: Fifteen patients were included in the study. BG values and the infusion speed of insulin and glucose by the artificial pancreas were collected. Arterial BG and administration rates of insulin, parenteral sugar, and enteral sugar were recorded during the artificial pancreas and standard therapy. The target BG level was 200 mg/dl. RESULTS: Arterial BG was highly correlated with BG data from the artificial pancreas. A higher BG slightly increased the difference between the BG data from the artificial pancreas and arterial BS. No significant difference in arterial BG was observed between the artificial pancreas and standard therapy. However, the standard deviation with the artificial pancreas was smaller than that under standard therapy (p < 0.0001). More points within the target BG range were achieved with the artificial pancreas (180-220 mg/dl) than under standard therapy. The hyperglycemic index of the artificial pancreas (8.7 ± 15.6 mg/dl) was lower than that of standard therapy (16.0 ± 21.5 mg/dl) (p = 0.0387). No incidence of hypoglycemia occurred under the artificial pancreas. CONCLUSIONS: The rate of achieving target BG was higher using artificial pancreas than with standard therapy. An artificial pancreas helps to control BG in critically ill patients.

Noninvasive blood pressure measurement in patients with continuous-flow left ventricular assist devices.

Oscillatory blood pressure (OBP) with a slow cuff-deflation system has been proposed as noninvasive measurement of mean arterial pressure (MAP) in patients with continuous-flow left ventricular assist devices (LVADs). However, the challenge is that the measurement is not obtainable in certain patients. We hypothesized that the combined use of color Doppler imaging during OBP measurement (CDBP) could derive MAP accurately. We conducted a prospective observational study in critically ill patients (30 patients with continuous-flow LVADs and 30 control patients without LVADs). Triplicate OBP and CDBP measurements were performed and invasive blood pressure (IBP) was recorded. The overall success rate of OBP was 63.3% in the LVAD group and 98.9% in the control group. The CDBP was successfully obtained in 100% of all study patients. The CDBP in the LVAD group was closest to the MAP of measured IBP, while that in the control group was closest to the systolic IBP. The mean absolute differences in OBP and CDBP from the closest IBP were similar in both the control and LVAD groups. In nonpulsatile LVAD patients with a pulse pressure IBP < 10 mmHg, the success rate of OBP measurement was only 10.0%, and CDBP showed significantly reduced error in MAP measurement (mean absolute difference: OBP 23.2 ± 8.7 vs CDBP 5.2 ± 3.6 mmHg, p < 0.001). The validity of OBP measurement with a slow cuff-deflation system limited particularly in nonpulsatile LVAD patients. The concurrent use of color Doppler imaging is encouraged for more accurate measurement of MAP in patients with continuous-flow LVADs.

Prolonged corticosteroid therapy and cytomegalovirus infection in patients with severe COVID-19.

Systemic corticosteroid therapy is frequently used to treat coronavirus disease 2019 (COVID-19). However, its maximum duration without secondary infections remains unclear. We aimed to evaluate the utility of monitoring cytomegalovirus (CMV) infection in patients with COVID-19 and estimate the maximum duration of systemic corticosteroid therapy without secondary infections. We included 59 patients with severe COVID-19 without CMV infection on admission to the intensive care unit (ICU). All patients received systemic corticosteroid therapy under invasive mechanical ventilation, with examination for plasma CMV-deoxyribonucleic acid (DNA) levels during the ICU stay. We analyzed the correlations among patient characteristics, CMV infection, diseases, and patient mortality. CMV infections were newly identified in 15 (25.4%) patients; moreover, anti-CMV treatment was administered to six (10.2%) patients during the ICU stay. Four (6.8%) patients had secondary infection-related mortality. The cumulative incidences of CMV infection and anti-CMV treatment during the ICU stay were 26.8% (95% confidence interval [CI], 15.8%-39.0%) and 12.3% (95% CI, 4.8%-23.4%), respectively. Furthermore, the median duration of systemic corticosteroid therapy without CMV infection was 15 days (95% CI, 13-16 days). The presence of CMV infection was associated with mortality during the ICU stay (p = 0.003). Monitoring plasma CMV-DNA levels could facilitate the detection of secondary CMV infection due to prolonged systemic corticosteroid therapy. The duration of systemic corticosteroid therapy for COVID-19 should be limited.

Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis.

INTRODUCTION: COVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patients. The objective of this study was to evaluate whether ivermectin has effects on gastrointestinal complications and ventilator-free days in ventilated patients with COVID-19. METHODS: COVID-19 patients who were mechanically ventilated in the ICU were included in this study. The ventilated patients who received ivermectin within 3 days after admission were assigned to the Ivermectin group, and the others were assigned to the Control group. Patients in the Ivermectin group received ivermectin 200 µg/kg via nasal tube. The incidence of gastrointestinal complications and ventilator-free days within 4 weeks from admission were evaluated as clinical outcomes using a propensity score with the inverse probability weighting method. RESULTS: We included 88 patients in this study, of whom 39 patients were classified into the Ivermectin group, and 49 patients were classified into the Control group. The hazard ratio for gastrointestinal complications in the Ivermectin group as compared with the Control group was 0.221 (95% confidence interval [CI], 0.057 to 0.855; p = 0.029) in a Cox proportional-hazard regression model. The odds ratio for ventilator-free days as compared with the Control group was 1.920 (95% CI, 1.076 to 3.425; p = 0.027) in a proportional odds logistic regression model. CONCLUSIONS: Ivermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.

High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

RATIONALE: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. OBJECTIVES: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). METHODS: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. MEASUREMENTS AND MAIN RESULTS: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). CONCLUSIONS: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

Predictors of Successful Extubation in Reintubated Patients: The Impact of Fluid Balance during the 24 Hours Prior to Extubation.

How to cite this article: Tanaka A, Yamashita T, Koyama Y, Uchiyama A, Fujino Y. Predictors of Successful Extubation in Reintubated Patients: The Impact of Fluid Balance during the 24 Hours Prior to Extubation. Indian J Crit Care Med 2019;23(7):344-345.

Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort.

RATIONALE: Spontaneous breathing during mechanical ventilation increases transpulmonary pressure and Vt, and worsens lung injury. Intuitively, controlling Vt and transpulmonary pressure might limit injury caused by added spontaneous effort. OBJECTIVES: To test the hypothesis that, during spontaneous effort in injured lungs, limitation of Vt and transpulmonary pressure by volume-controlled ventilation results in less injurious patterns of inflation. METHODS: Dynamic computed tomography was used to determine patterns of regional inflation in rabbits with injured lungs during volume-controlled or pressure-controlled ventilation. Transpulmonary pressure was estimated by using esophageal balloon manometry [Pl(es)] with and without spontaneous effort. Local dependent lung stress was estimated as the swing (inspiratory change) in transpulmonary pressure measured by intrapleural manometry in dependent lung and was compared with the swing in Pl(es). Electrical impedance tomography was performed to evaluate the inflation pattern in a larger animal (pig) and in a patient with acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing in injured lungs increased Pl(es) during pressure-controlled (but not volume-controlled) ventilation, but the pattern of dependent lung inflation was the same in both modes. In volume-controlled ventilation, spontaneous effort caused greater inflation and tidal recruitment of dorsal regions (greater than twofold) compared with during muscle paralysis, despite the same Vt and Pl(es). This was caused by higher local dependent lung stress (measured by intrapleural manometry). In injured lungs, esophageal manometry underestimated local dependent pleural pressure changes during spontaneous effort. CONCLUSIONS: Limitation of Vt and Pl(es) by volume-controlled ventilation could not eliminate harm caused by spontaneous breathing unless the level of spontaneous effort was lowered and local dependent lung stress was reduced.

Factors Related to the Severity of Early Postoperative Infection After Heart Transplantation in Patients Surviving Prolonged Mechanical Support Periods: Experience at a Single University.

OBJECTIVE: The authors examined the effect of prolonged support with continuous-flow ventricular assist devices (CF-VADs) and other related factors on the severity of infections within 30 days of heart transplantation (HTx). DESIGN: A retrospective analysis of consecutive HTx procedures. SETTING: University hospital, between 2010 and 2016. PARTICIPANTS: A cohort of 53 heart transplantation recipients (median age, 38.5 yr; interquartile range [IQR], 30.3-49.2 yr; women, 34%). INTERVENTIONS: Forty-nine patients required CF-VAD support (median duration, 946 d; IQR, 600-1,132 d). MEASUREMENTS AND MAIN RESULTS: Severity of postoperative infections was categorized as follows: no infection, minor infection (resolved within 14 days), major infection (resolved after >14 days), and severe infection (septic shock). Results were expressed as number (frequency) and median with IQR. Potential risk factors for increased infection severity were expressed as odds ratio (OR) with 95% confidence interval (CI). Postoperatively, no infection, minor infection, major infection, and severe infection occurred in 32 (60.4%), 8 (15.1%), 8 (15.1%), and 5 patients (9.4%), respectively. Active ventricular assist device (VAD)-specific infections at the time of HTx occurred in 37.7% of patients. Moderate-to-severe primary graft dysfunction occurred in 26.4% of the patients. Multivariable analysis indicated that risk factors for increased infection severity included active VAD-specific infection (OR 4.8; 95% CI 2.3-11.2) and moderate-to-severe primary graft dysfunction (OR 8.8; 95% CI 2.1-42.5) but not duration of CF-VAD support (OR 1.0; 95% CI 1.0-1.0). CONCLUSION: Active VAD-specific infection and poor graft function likely contribute to the severity of early postoperative infections after HTx.

Perioperative factors related to the severity of vocal cord paralysis after thoracic cardiovascular surgery: A retrospective review.

BACKGROUND: Vocal cord paralysis (VCP) is a rare complication of thoracic cardiovascular surgery. In severe cases, life-threatening airway obstruction may occur. OBJECTIVE: To evaluate the incidence and severity of VCP among patients who underwent thoracic cardiovascular surgery and to identify possible risk factors. DESIGN: Single-centre retrospective review of adult patients. SETTING: Osaka University Hospital, Suita, Japan, from January 2013 to August 2015. PATIENTS: We included 688 patients in the final analysis. Preoperative, intraoperative and postoperative data were collected from medical records. Patients with preoperative VCP or tracheostomy prior to extubation were excluded. The VCP severity in relation to functional recovery was graded using the following categories: absent; mild, remission at 6 months; moderate, partial or persistent VCP at 6 months; or severe, airway obstruction after extubation requiring reintubation. An otolaryngologist diagnosed all VCP cases. MAIN OUTCOME MEASURES: The incidence and severity of VCP after extubation. RESULTS: The incidence (number) of VCP was 4.7% (32), with those of mild, moderate and severe VCP being 1.7% (12), 1.5% (10) and 1.5% (10), respectively. The ICU stay was significantly longer in patients with severe VCP than in patients without VCP [12.5 days (interquartile range 5.5 to 25.5) vs. 3 days (interquartile range 2 to 5), P = 0.0002]. In our multivariable analysis, type 2 diabetes mellitus [odds ratio (OR) 1.853, P = 0.009], intubation period (OR per 24 h 1.136, P = 0.014), ascending aortic arch surgery with brachiocephalic artery reconstruction (OR 8.708, P < 0.001) and ventricular assist device implantation (OR 3.460, P = 0.005) were independent predictors for VCP. CONCLUSION: The identification of these risk factors may facilitate screening for VCP before extubation and possibly help anaesthesia personnel to be prepared to treat VCP-related airway obstruction should it occur.

Efficacy and Safety of Landiolol Compared to Amiodarone for the Management of Postoperative Atrial Fibrillation in Intensive Care Patients.

OBJECTIVE: The authors assessed the efficacy and safety of landiolol, an ultra-short-acting beta-blocker, with those of amiodarone in the restoration of sinus rhythm for postoperative atrial fibrillation (POAF) in intensive care unit (ICU) patients. DESIGN: A retrospective data analysis. SETTING: Data were collected from patients admitted to the ICU in a single university hospital between 2012 and 2015. PARTICIPANTS: Records of a total of 276 patients who developed POAF after ICU admission were collected from hospital records. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Treatment success was defined as restoration of sinus rhythm without concomitant therapy within 24 hours of treatment and lasting for more than an hour. The landiolol dosage was in the range of 0.7 µg/kg/min-to-2.5 µg/kg/min. The authors compared a total of 55 patients with POAF who received either landiolol (n = 32) or intravenous amiodarone (n = 23) in the ICU. The major findings were that the median time required for conversion to sinus rhythm was shorter in landiolol patients compared with amiodarone patients (75 v 150 min respectively, p = 0.0355). However, treatment success rates did not differ significantly after 24 hours (odds ratio 1.25, 95% confidence interval 0.17-9.09, p = 0.60). Adverse events with bradycardia leading to drug discontinuation were seen only in the patients receiving amiodarone (n = 3, p = 0.032). CONCLUSIONS: Landiolol achieved swift and safe restoration of sinus rhythm in ICU patients with POAF and could be considered as a favorable drug choice over amiodarone in such patients.

Neutrophil gelatinase-associated lipocalin and liver-type fatty acid-binding protein as biomarkers for acute kidney injury after organ transplantation.

PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) are promising early biomarkers for acute kidney injury (AKI). In organ transplant recipients, AKI predictability based on NGAL and L-FABP remains to be elucidated. Furthermore, the association between serial NGAL and L-FABP measurements and AKI outcome is unknown. Therefore, we conducted a study to evaluate the ability of NGAL and L-FABP to predict AKI after organ transplantation and investigate the association between NGAL, L-FABP and AKI outcome. METHODS: Twenty-five organ transplant recipients admitted to the intensive care unit (ICU) immediately after transplant surgery were studied prospectively. Plasma NGAL (P-NGAL), urinary NGAL (U-NGAL) and L-FABP were measured from ICU admission to ICU discharge. U-NGAL and L-FABP were corrected for dilution/concentration by calculating U-NGAL/urine creatinine ratios (U-NGAL/Cr) and L-FABP/urine creatinine ratios (L-FABP/Cr). AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria. RESULTS: AKI occurred in 11 patients. P-NGAL, U-NGAL/Cr and L-FABP/Cr upon ICU admission were unrelated to AKI development (p = 0.24, 0.22, and 0.53, respectively). There were no differences in P-NGAL, U-NGAL/Cr, and L-FABP/Cr levels from day 1 to day 6 between patients who did not recover from AKI and patients who recovered from AKI (p = 0.82, 0.26, and 0.61, respectively). CONCLUSION: Our findings suggest that NGAL and L-FABP upon ICU admission are not predictive of AKI and serial NGAL and L-FABP measurements may be ineffective for monitoring the status and treatment of post-transplantation AKI.

Early postoperative management of heart transplant recipients with current ventricular assist device support in Japan: experience from a single center.

PURPOSE: This study reviews our experience with the perioperative management of heart transplant (HT) recipients and explores how prior ventricular assist device (VAD) support affects the requirements for postoperative mechanical ventilation and circulatory support. METHODS AND RESULTS: A retrospective database review was performed from 2007 to 2014. Early postoperative outcomes were compared between VAD and non-VAD groups. Forty-four patients were studied. The mean age was 38 ± 13 years, 30% were female, and 88% experienced non-ischemic heart failure. Forty patients (91%) required VAD support at the time of HT, with a mean duration of 864 ± 351 days. The median postoperative mechanical ventilation times in the VAD and non-VAD groups were 54 [95% confidence interval (CI) 42.9-297.3] and 15 (95% CI 4.8-30.0; p = 0.0199) hours, respectively. The VAD group experienced increased bleeding during the first 48 h after HT (6.7 ± 3.5 vs. 1.8 ± 0.75 l, p = 0.004). Mechanical circulatory support with intra-aortic balloon pumping or venoarterial extracorporeal membrane oxygenation was required in 30% of VAD group patients. Increased bleeding and primary graft failure were the main causes of prolonged mechanical ventilation. CONCLUSIONS: HT recipients with VAD support required longer mechanical ventilation periods and mechanical circulatory support in the postoperative period.

Combined Use of Alkaline Agents With Low-Flow Extracorporeal Carbon Dioxide Removal in Carbon Dioxide Inhalation Models Preserving Inspiratory Efforts.

Background: Low-flow extracorporeal CO 2 removal (ECCO 2 R), managed using a renal replacement platform, is useful in achieving lung-protective ventilation with low tidal volume. However, its capacity for CO 2 elimination is limited. Whether this system is valuable in reducing strong inspiratory efforts in respiratory failure is unclear. The combined use of alkaline agents with low-flow ECCO 2 R might be useful in hypercapnic subjects preserving inspiratory efforts. Methods: This study examined the effects of low-flow ECCO 2 R on respiratory status and investigated the effects of NaHCO 3 , trometamol, and saline on respiratory status during low-flow ECCO 2 R in CO 2 inhalation models. Results: Although low-flow ECCO 2 R did not significantly change the respiratory rate (92.2% ± 24.3% [mean ± standard deviation] of that before ECCO 2 R), it reduced minute ventilation (MV) (78.9% ± 13.5% of that before ECCO 2 R). The addition of NaHCO 3 improved acidemia but did not change MV compared with that of the saline group (0.451 ± 0.026 L/min/kg body weight [BW] vs. 0.556 ± 0.138 L/min/kg BW, respectively). The addition of trometamol improved acidemia and reduced MV compared with that of the saline group (0.381 ± 0.050 L/min/kg BW vs. 0.556 ± 0.138 L/min/kg BW, respectively). The total amounts of CO 2 removed during ECCO 2 R in the NaHCO 3 group were lower than those in the saline and trometamol groups. Conclusion: The low-flow ECCO 2 R reduced MV in subjects preserving spontaneous breathing efforts with CO 2 overload. The addition of NaHCO 3 improved acidemia but did not change MV, whereas the addition of trometamol improved acidemia and reduced MV.

Dysbiosis of gut microbiota in patients with severe COVID-19.

Aim: Altered gut microbiota has been proposed as one of the causes of exacerbation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) from the perspective of the gut-lung axis. We aimed to evaluate gut microbiota in mechanically ventilated patients with COVID-19 prior to using antibiotics. Methods: We retrospectively selected for enrollment COVID-19 patients who required mechanical ventilation on admission but who had not used antibiotics before admission to observe the influence of SARS-Cov-2 on gut microbiota. Fecal samples were collected serially on admission and were evaluated by 16S rRNA gene deep sequencing. Results: The phylum of Bacteroidetes decreased, and those of Firmicutes and Actinobacteria increased in COVID-19 patients compared with those in healthy controls (p < 0.001). The main commensals of Bacteroides, Faecalibacterium, and Blautia at the genus level were significantly decreased in the COVID-19 patients, and opportunistic bacteria including Corynebacterium, Anaerococcus, Finegoldia Peptoniphilus, Actinomyces, and Enterococcus were increased (p < 0.001). α-Diversity and ß-diversity in COVID-19 patients significantly changed compared with those in the healthy controls. Conclusion: The commensal gut microbiota were altered, and opportunistic bacteria increased in patients with severe COVID-19 who required mechanical ventilation on admission.