Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Time to re-think the use of dobutamine in sepsis

Abstract Dobutamine is commonly used worldwide and included in the protocol for early goal-directed therapy (EGDT). Since the use of dobutamine in EGDT was reported, it has been considered to be an important component, especially in the treatment of septic patients with myocardial dysfunction. However, it is questionable whether dobutamine improves the mortality of sepsis and septic shock. In three recent randomized controlled trials (ProCESS, ProMISe, and ARISE trials), the frequency of dobutamine use was significantly higher in the EGDT group than in the standard care group, but there were no significant differences in the mortality between the groups. These results suggested that dobutamine use may have been overemphasized despite its insignificant effect on the mortality in septic patients. Further, a propensity score analysis revealed that dobutamine use was associated with higher mortality in patients with septic shock. Although dobutamine leads to an increase in cardiac index, myocardial oxygen demand also increases, thus increasing the risk of myocardial ischemia and tachyarrhythmia. It is well known that the mortality in sepsis complicated with atrial fibrillation (AFib) is worse than that in sepsis without AFib. A propensity score-matched analysis reported that β-blockers were associated with better survival in patients with sepsis complicated with AFib. Further, a randomized controlled trial reported that a short-acting β-blocker improved the survival in patients with septic shock. These studies also indicated the risk of β-stimulation during sepsis. Notably, improvements in surrogate markers, such as CI, do not always indicate improvements in patient-centered outcomes, such as mortality. Conversely, some evidence indicates the worsening of patient-centered outcomes despite improvements in surrogate markers. Thus, available evidence suggests that the benefits of dobutamine in patients with sepsis are unclear, but its use might be harmful rather than beneficial, considering the beneficial effects of β-blockers in sepsis that have been reported in recent clinical studies. From this perspective, we will soon have to rethink regarding dobutamine use in patients with sepsis

Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection.

Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. TRIAL REGISTRATION:University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748)

Comparison of Patient Characteristics between PMXHP and Conventional Groups

<p>Comparison of Patient Characteristics between PMXHP and Conventional Groups</p

Efficacy of polymyxin B-immobilized fiber hemoperfusion for patients with septic shock caused by Gram-negative bacillus infection

<div><p>Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30–50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81–1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB. Trial registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).</p></div

Primary and Secondary Outcomes

<p>Primary and Secondary Outcomes</p

Multivariate Cox Regression Analysis.

<p>Patients in the polymyxin B hemoperfusion (PMXHP) group received at least one session of direct PMXHP as adjuvant therapy for septic shock.</p

Post-hoc Analysis.

<p>The mortality rates at 28 days after ICU admission across the indicated subgroups were defined according to several baseline characteristics. PMXHP: polymyxin B immobilized fiber hemoperfusion, HR: hazard ratio, CI: confidence interval, AKI: acute kidney injury.</p