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.

Evaluation of the Impact of ABCDEF Bundle Compliance Rates on Postintensive Care Syndrome: A Secondary Analysis Study.

OBJECTIVES: This study aimed to examine the association between ABCDEF bundles and long-term postintensive care syndrome (PICS)-related outcomes. DESIGN: Secondary analysis of the J-PICS study. SETTING: This study was simultaneously conducted in 14 centers and 16 ICUs in Japan between April 1, 2019, and September 30, 2019. PATIENTS: Adult ICU patients who were expected to be on a ventilator for at least 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Bundle compliance for the last 24 hours was recorded using a checklist at 8:00 am The bundle compliance rate was defined as the 3-day average of the number of bundles performed each day divided by the total number of bundles. The relationship between the bundle compliance rate and PICS prevalence (defined by the 36-item Short Form Physical Component Scale, Mental Component Scale, and Short Memory Questionnaire) was examined. A total of 191 patients were included in this study. Of these, 33 patients (17.3%) died in-hospital and 48 (25.1%) died within 6 months. Of the 96 patients with 6-month outcome data, 61 patients (63.5%) had PICS and 35 (36.5%) were non-PICS. The total bundle compliance rate was 69.8%; the rate was significantly lower in the 6-month mortality group (66.6% vs 71.6%, p = 0.031). Bundle compliance rates in patients with and without PICS were 71.3% and 69.9%, respectively ( p = 0.61). After adjusting for confounding variables, bundle compliance rates were not significantly different in the context of PICS prevalence ( p = 0.56). A strong negative correlation between the bundle compliance rate and PICS prevalence ( r = -0.84, R 2 = 0.71, p = 0.035) was observed in high-volume centers. CONCLUSIONS: The bundle compliance rate was not associated with PICS prevalence. However, 6-month mortality was lower with a higher bundle compliance rate. A trend toward a lower PICS prevalence was associated with higher bundle compliance in high-volume centers.

A burden of fluid, sodium, and chloride due to intravenous fluid therapy in patients with respiratory support: a post-hoc analysis of a multicenter cohort study.

BACKGROUND: Fluid creep, including fluids administered as drug diluents and for the maintenance of catheter patency, is the major source of fluid intake in critically ill patients. Although hypoxemia may lead to fluid restriction, the epidemiology of fluid creep in patients with hypoxemia is unclear. This study aimed to address the burden due to fluid creep among patients with respiratory support according to oxygenation status. METHODS: We conducted a post-hoc analysis of a prospective multicenter cohort study conducted in 23 intensive care units (ICUs) in Japan from January to March 2018. Consecutive adult patients who underwent invasive or noninvasive ventilation upon ICU admission and stayed in the ICU for more than 24 h were included. We excluded the following patients when no fluids were administered within 24 h of ICU admission and no records of the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We investigated fluid therapy until 7 days after ICU admission according to oxygenation status. Fluid creep was defined as the fluids administered as drug diluents and for the maintenance of catheter patency when administered at ≤ 20 mL/h. RESULTS: Among the 588 included patients, the median fluid creep within 24 h of ICU admission was 661 mL (25.2% of the total intravenous-fluid volume), and the proportion of fluid creep gradually increased throughout the ICU stay. Fluid creep tended to decrease throughout ICU days in patients without hypoxemia and in those with mild hypoxemia (p < 0.001 in both patients), but no significant trend was observed in those with severe hypoxemia (p = 0.159). Similar trends have been observed in the proportions of sodium and chloride caused by fluid creep. CONCLUSIONS: Fluid creep was the major source of fluid intake among patients with respiratory support, and the burden due to fluid creep was prolonged in those with severe hypoxemia. However, these findings may not be conclusive as this was an observational study. Interventional studies are, therefore, warranted to assess the feasibility of fluid creep restriction. Trial registration UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN 000028019, July 1, 2017).

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.

Accuracy evaluation of mainstream and sidestream end-tidal carbon dioxide monitoring during noninvasive ventilation: a randomized crossover trial (MASCAT-NIV trial).

BACKGROUND: The end-tidal partial pressure of carbon dioxide (PETCO2) can be used to estimate the arterial partial pressure of carbon dioxide (PaCO2) in patients who undergo mechanical ventilation via endotracheal intubation. However, no reliable method for measuring PETCO2 during noninvasive ventilation (NIV) has been established. The purpose of this study was to evaluate the correlation and agreement between PaCO2 and PETCO2 measured by these two methods and to compare them in patients who underwent NIV after extubation. METHODS: This study was a randomized, open-label, crossover trial in a mixed intensive care unit. We included patients who were planned for NIV after extubation and for whom the difference between PETCO2 and PaCO2 was ≤ 5 mmHg. We compared mainstream capnography using an inner cup via face mask (the novel method) with sidestream capnography (the previous method) during NIV. The relationships between PaCO2 and PETCO2 were evaluated by computing the Pearson correlation coefficient, and the agreement between PaCO2 and PETCO2 was estimated using the Bland-Altman method. RESULTS: From April 2020 to October 2021, 60 patients were included to the study. PaCO2 and PETCO2 were well correlated in both methods (the novel methods: r = 0.92, P < 0.001; the previous method: r = 0.79, P < 0.001). Mean bias between PaCO2 and PETCO2 measured using the novel method was 2.70 (95% confidence interval [CI], 2.15-3.26) mmHg with 95% limits of agreement (LoA) ranging from - 1.61 to 7.02 mmHg, similar to the result of measurement during SBT (mean bias, 2.51; 95% CI, 2.00-3.02; 95% LoA, - 1.45 to 6.47 mmHg). In contrast, measurement using the previous method demonstrated a larger difference (mean bias, 6.22; 95% CI, 5.22-7.23; 95% LoA, - 1.54 to 13.99 mmHg). CONCLUSION: The current study demonstrated that the novel PETCO2 measurement was superior to the previous method for PaCO2 prediction. During NIV, the novel method may collect as sufficient exhalation sample as during intubation. Continuous PETCO2 measurement combined with peripheral oxygen saturation monitoring is expected to be useful for early recognition of respiratory failure among high-risk patients after extubation. Trial registration UMIN-CTR UMIN000039459. Registered February 11, 2020.

Prevalence of post-intensive care syndrome among Japanese intensive care unit patients: a prospective, multicenter, observational J-PICS study.

BACKGROUND: Many studies have compared quality of life of post-intensive care syndrome (PICS) patients with age-matched population-based controls. Many studies on PICS used the 36-item Short Form (SF-36) health survey questionnaire version 2, but lack the data for SF-36 values before and after intensive care unit (ICU) admission. Thus, clinically important changes in the parameters of SF-36 are unknown. Therefore, we determined the frequency of co-occurrence of PICS impairments at 6 months after ICU admission. We also evaluated the changes in SF-36 subscales and interpreted the patients' subjective significance of impairment. METHODS: A prospective, multicenter, observational cohort study was conducted in 16 ICUs across 14 hospitals in Japan. Adult ICU patients expected to receive mechanical ventilation for > 48 h were enrolled, and their 6-month outcome was assessed using the questionnaires. PICS definition was based on the physical status, indicated by the change in SF-36 physical component score (PCS) ≥ 10 points; mental status, indicated by the change in SF-36 mental component score (MCS) ≥ 10 points; and cognitive function, indicated by the worsening of Short-Memory Questionnaire (SMQ) score and SMQ score at 6 months < 40. Multivariate logistic regression model was used to identify the factors associated with PICS occurrence. The patients' subjective significance of physical and mental symptoms was assessed using the 7-scale Global Assessment Rating to evaluate minimal clinically important difference (MCID). RESULTS: Among 192 patients, 48 (25%) died at 6 months. Among the survivors at 6 months, 96 patients responded to the questionnaire; ≥ 1 PICS impairment occurred in 61 (63.5%) patients, and ≥ 2 occurred in 17 (17.8%) patients. Physical, mental, and cognitive impairments occurred in 32.3%, 14.6% and 37.5% patients, respectively. Population with only mandatory education was associated with PICS occurrence (odds ratio: 4.0, 95% CI 1.1-18.8, P = 0.029). The MCID of PCS and MCS scores was 6.5 and 8.0, respectively. CONCLUSIONS: Among the survivors who received mechanical ventilation, 64% had PICS at 6 months; co-occurrence of PICS impairments occurred in 20%. PICS was associated with population with only mandatory education. Future studies elucidating the MCID of SF-36 scores among ICU patients and standardizing the PICS definition are required. Trial registration UMIN000034072.

Recombinant Human-Soluble Thrombomodulin Contributes to Reduced Mortality in Sepsis Patients With Severe Respiratory Failure: A Retrospective Observational Study Using a Multicenter Dataset.

BACKGROUND: Recombinant human-soluble thrombomodulin (rhTM) is a novel class therapeutic agent for managing disseminated intravascular coagulation. The progression of severe respiratory failure may be related to intra-alveolar coagulation/fibrinolytic disorders. We aimed to determine the efficacy of rhTM in treating sepsis patients with severe respiratory failure. METHODS: We performed a retrospective observational study using an existing dataset collected from 42 intensive care units (ICUs) in Japan. Of 3,195 patients with severe sepsis or septic shock from the dataset, we selected sepsis patients with severe respiratory failure, and compared patient outcomes based on the administration of rhTM (rhTM group and no rhTM group). Propensity score analysis was performed between the two groups. Outcomes of interest were ICU mortality, hospital mortality, and ventilator-free days (VFDs). RESULTS: In this study, 1,180 patients (rhTM, n = 356; no rhTM, n = 824) were analyzed. After adjusting for baseline imbalances with propensity score matching, the survival-time analysis revealed a significant difference between the two groups (hazard ratio, 0.654; 95% confidence interval, 0.439-0.974, P = 0.03). ICU mortality was lower in the rhTM group (rhTM: 22.1% [33/149] vs. no rhTM: 36.2% [54/149], P = 0.01). Hospital mortality was also lower in the rhTM group (35.6% [53/149] vs. 49.7% [74/149], P = 0.02). VFDs trended to be higher in the rhTM group than the no rhTM group (12.8 ±â€Š10.1 days vs. 10.6 ±â€Š10.6 days, P = 0.09). CONCLUSIONS: Administration of rhTM was positively correlated with a reduction in mortality in sepsis patients with severe respiratory failure.

Management of spontaneous pneumomediastinum: Are hospitalization and prophylactic antibiotics needed?

BACKGROUND: Spontaneous pneumomediastinum is defined as the presence of free air in the mediastinum without any apparent concomitant factors or disease. It is uncommon but usually benign and self-limiting. Generally, patients with spontaneous pneumomediastinum are admitted to hospital, and occasionally, prophylactic antibiotics are administered to prevent mediastinitis. The purpose of this study was to describe practices concerning the feasibility of outpatient treatment and follow-up of spontaneous pneumomediastinum and the necessity of prophylactic antibiotics. METHODS: We conducted this study in a single emergency medical center located in Kobe, Japan. We retrospectively evaluated patients with spontaneous pneumomediastinum from January 2007 to December 2014. Spontaneous pneumomediastinum was defined as cases in which pneumomediastinum did not occur in the setting of positive pressure ventilation or severe trauma. All case records were carefully reviewed considering the demographic data, symptoms, precipitating events, diagnostic workup performed, use of prophylactic antibiotics, length of hospital stay, and complications. RESULTS: Thirty-four patients who satisfied the inclusion criteria were identified. Twenty-three patients (67.6%) were followed up on an outpatient basis, and 11 patients (32.4%) were admitted to the hospital, with a mean length of stay of 3.4days. Prophylactic antibiotics were orally administered to 2 patients. None of the patients developed complications, such as tension pneumomediastinum, delayed pneumothorax, airway compromise, and mediastinitis. CONCLUSION: Spontaneous pneumomediastinum is a benign condition presenting primarily in young adults, with an uneventful recovery. Therefore, patients may recover from this condition without admission or the need for prophylactic antibiotics.