Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS. METHODS: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao2, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo2], 88 to 92%) or liberal oxygen therapy (target Pao2, 90 to 105 mm Hg; Spo2, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days. RESULTS: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group. CONCLUSIONS: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao2 between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO2 ClinicalTrials.gov number, NCT02713451.).

Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial.

RATIONALE: There are no randomized controlled trials comparing different oxygenation targets for intensive care unit (ICU) patients. OBJECTIVES: To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV). METHODS: At four multidisciplinary ICUs, 103 adult patients deemed likely to require IMV for greater than or equal to 24 hours were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51). MEASUREMENTS AND MAIN RESULTS: The mean area under the curve and 95% confidence interval (CI) for SpO2 (93.4% [92.9-93.9%] vs. 97% [96.5-97.5%]), SaO2 (93.5% [93.1-94%] vs. 96.8% [96.3-97.3%]), PaO2 (70 [68-73] mm Hg vs. 92 [89-96] mm Hg), and FiO2 (0.26 [0.25-0.28] vs. 0.36 [0.34-0.39) in the conservative versus liberal oxygenation arm were significantly different (P < 0.0001 for all). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. The percentage time spent with SpO2 less than 88% in conservative versus liberal arm was 1% versus 0.3% (P = 0.03), and percentage time spent with SpO2 greater than 98% in conservative versus liberal arm was 4% versus 22% (P < 0.001). The adjusted hazard ratio for 90-day mortality in the conservative arm was 0.77 (95% CI, 0.40-1.50; P = 0.44) overall and 0.49 (95% CI, 0.20-1.17; P = 0.10) in the prespecified subgroup of patients with a baseline PaO2/FiO2 less than 300. CONCLUSIONS: Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12613000505707).

Oxygenation target in acute respiratory distress syndrome.

Determining oxygenation targets in acute respiratory distress syndrome (ARDS) remains a challenge. Although oxygenation targets have been used since ARDS was first described, they have not been investigated in detail. However, recent retrospective and prospective trials have evaluated the optimal oxygenation threshold in patients admitted to the general intensive care unit. In view of the lack of prospective data, clinicians continue to rely on data from the few available trials to identify the optimal oxygenation strategy. Assessment of the cost-benefit ratio of the fraction of inspired oxygen (FiO2) to the partial pressure of oxygen in the arterial blood (PaO2) is an additional challenge. A high FiO2 has been found to be responsible for respiratory failure and deaths in numerous animal models. Low and high PaO2 values have also been demonstrated to be potential risk factors in experimental and clinical situations. The findings from this literature review suggest that PaO2 values ranging between 80 mmHg and 90 mmHg are acceptable in patients with ARDS. The costs of rescue maneuvers needed to reach these targets have been discussed. Several recent papers have highlighted the risk of disagreement between arterial oxygen saturation (SaO2) and peripheral oxygen saturation (SpO2) values. In order to avoid discrepancies and hidden hypoxemia, SpO2 readings need to be compared with those of SaO2. Higher SpO2 values may be needed to achieve the recommended PaO2 and SaO2 values.

Enterocyte Damage: A Piece in the Puzzle of Post-Cardiac Arrest Syndrome.

Cardiac arrest is considered to be a cause of small bowel ischemia, but the consequences of cardiac arrest on the human small bowel have been rarely studied. Plasma citrulline concentration is a marker of functional enterocyte mass, and plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to measure enterocyte biomarkers after cardiac arrest and to study the prognostic value of biomarker abnormalities. This is a prospective, observational, single-center study of patients admitted to the intensive care unit (ICU) for cardiac arrest, evaluating plasma citrulline and I-FABP concentrations at admission and after 24  h and variables according to the Utstein criteria. Variables according to 28-day Cerebral Performance Category score of 1 to 2 (good neurological outcome) versus 3 to 5 (poor neurological outcome) were compared. Sixty-nine patients with cardiac arrest of both cardiac and hypoxic origin were included. At ICU admission, plasma citrulline concentration was low in 65% and plasma I-FABP was elevated in 82% of the patients. After 24  h, plasma citrulline was low in 82% and I-FABP was normal in 60% of the patients. Patients with a poor neurological outcome had a lower plasma citrulline concentration and a higher I-FABP concentration at ICU admission. By multivariate analysis, plasma citrulline levels of 13.1  µmol L or less and I-FABP more than 260  pg mL were independently associated with a poor neurological outcome (odds ratio, 21.9 [2.2-215], and odds ratio, 13.6 [1.4-129], respectively). Cardiac arrest resuscitation is associated with evidence of small bowel mucosal damage in most patients, with a short and intense I-FABP elevation at admission and a decrease in citrulline concentration during the first day. In this study, low plasma citrulline and high I-FABP concentrations at ICU admission were predictive of a poor neurological outcome. This study confirms that cardiac arrest is a model of small bowel mucosal ischemia and suggests that enterocyte damage is a piece in the puzzle of post-cardiac arrest syndrome.

Capillary lactate as a tool for the triage nurse among patients with SIRS at emergency department presentation: a preliminary report.

BACKGROUND: The triage nurse is involved in the early identification of the most severe patients at emergency department (ED) presentation. However, clinical criteria alone may be insufficient to identify them correctly. Measurement of capillary lactate concentration at ED presentation may help to discriminate these patients. The primary objective of this study was to identify the prognostic value of capillary lactate concentration measured by the triage nurse among patients presenting to the ED. METHODS: This was a prospective observational study, performed in the ED of a university hospital. At ED presentation, capillary lactate measurement was performed by the triage nurse among patients presenting with a clinical criteria of systemic inflammatory response syndrome (SIRS). Clinical variables usually used to determine severity were collected at presentation. Twenty-eight-day mortality and MEDS score were recorded. RESULTS: One hundred seventy-six patients with clinical SIRS presented to the ED. Median age was 72 years, and 28-day mortality was 16%. Capillary lactate at ED presentation was significantly higher among 28-day non-survivors than among survivors (5.7 mmol.L(-1) [3.2 to 7.4] vs 2.9 mmol.L(-1) [1.9 to 5.2], p = 0.003). A score based on mottling and capillary lactate concentration >3.6 mmol.L(-1) was significantly associated with 28-day mortality (area under curve, AUC = 0.75), independently of the MEDS score (AUC = 0.79) for the prediction of 28-day mortality (AUC global model 0.87). CONCLUSIONS: A high capillary lactate concentration measured by the triage nurse among patients presenting to the ED with clinical SIRS is associated with a high risk of death. A score calculated by the triage nurse, based on mottling and capillary lactate concentration, appears to be useful for identifying the most severe patients.