Bioactive Adrenomedullin, Organ Support Therapies, and Survival in the Critically Ill: Results from the French and European Outcome Registry in ICU Study.

OBJECTIVES: Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin. DESIGN: Prospective multicenter observational cohort study. SETTING: Data from the French and euRopean Outcome reGistry in ICUs study. PATIENTS: Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included. INTERVENTIONS: Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality. MEASUREMENTS AND MAIN RESULTS: Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92). CONCLUSIONS: Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients.

Etiology and prognosis of acute respiratory failure in patients with primary malignant brain tumors admitted to the intensive care unit.

PURPOSE: Acute respiratory failure (ARF) is common and potentially fatal in patients with primary malignant brain tumors (PMBT). However, few data are available regarding its precipitating factors and prognosis. We sought to: (1) compare the causes of ARF and the outcome between patients with PMBT and patients with other peripheral solid tumors (PST), (2) identify the factors influencing ICU survival in PMBT patients. METHODS: Two-center retrospective case-control study from March 1996 to May 2014. Primary central nervous system lymphomas were also included. RESULTS: Eighty-four patients with PMBT and 133 patients with PST were included. Acute infectious pneumonia was more frequent in PMBT than PST patients (77 vs. 36%, p < 0.001). Pulmonary embolism was also more frequent in PMBT patients (13% vs. 5%, p = 0.042), while cardiogenic pulmonary edema and acute-on-chronic respiratory failure were more frequent in PST patients (37 vs. 10%, p < 0.001). Among acute infectious pneumonia, Pneumocystis pneumonia and aspiration pneumonia were more frequent in PMBT patients (19 vs. 2%, p < 0.001 and 19 vs. 8%, p < 0.001, respectively). ICU mortality was similar between PMBT and PST patients (24% vs. 24%, p = 0.966). In multivariate analysis, cancer progression (OR 7.25 95% CI 1.13-46.45, p = 0.034), need for intubation (OR 7.01 95% CI 1.29-38.54, p = 0.022), were independently associated with ICU mortality in PMBT patients. CONCLUSIONS: The cause of ARF in patients with PMBT differs significantly than those with PST and up to 50% may have been prevented. Mortality did not differ between the two groups. These results suggest that PMBT alone is not a relevant criterion for ICU recusal.

Methods used to assess the performance of biomarkers for the diagnosis of acute kidney injury: a systematic review and meta-analysis.

PURPOSE: Methods used to explore biomarkers for acute kidney injury (AKI) might have a major impact on the results and the use of these biomarkers. We evaluated the methods used to investigate biomarkers of AKI. MATERIALS AND METHODS: A systematic review and meta-analysis were performed using a computerized search of the MEDLINE and the EMBASE databases (PROSPERO CRD42017059618). Articles reporting biomarker's performance to diagnose AKI were included. The outcome included a description of the methods used to assess the performance of biomarkers to diagnose AKI. RESULTS: Among the 295 included studies, assessment of biomarkers was the primary endpoint in 284 with sample size calculation in only 8% of cases. Eighty-five percent of the studies summarized the performance of biomarkers with receiver operating characteristic (ROC) curves; however, 74 studies (25%) did not provide the threshold, sensibility or specificity. A total of 176 studies evaluated more than one biomarker, and only 25% combined biomarkers to increase diagnostic performance. We determined that the definition of AKI and study design impacted the diagnostic performance using uNGAL (urinary neutrophil gelatinase-associated lipocalin) as an example. Major publication bias was identified. CONCLUSIONS: Most articles that reported biomarkers of AKI performance present methodological weaknesses. Basic rules should be provided to increase the quality of reporting in this area.

Influence of Fraction of Inspired Oxygen on Noninvasive Hemoglobin Measurement: Parallel Assessment of 2 Monitors.

BACKGROUND: Previous reports have brought specific attention to the relationship between oxygenation of the patient and the accuracy of noninvasive measurement of hemoglobin (Hb) using an optical sensor. This study aimed to assess prospectively the relationship between fraction of inspired oxygen (FIO2) and the bias of the measurement of Hb by the use of 2 different noninvasive monitors compared with the classic invasive technique. METHODS: Forty-four patients were included prospectively. In each individual, Hb level was determined noninvasively by monitor Pronto-7™ (Masimo Corporation, Irvine, CA) and by monitor NBM-200MP™ (OrSense Ltd, Petah-Tikva, Israel), with the probe placed on 2 fingers on the same hand of the patient. Three measures were performed, first under breathing air and 2 others when fraction of expired oxygen rose to 50% ± 5% and to 90 ± 5%. Simultaneously, a nurse collected a venous blood sample, which was sent immediately to the hematology laboratory for Hb measurement. The main outcome measurement was the mean bias between noninvasive and invasive measurements. RESULTS: Results show no change in median bias [interquartile range] with FIO2 for Pronto-7 (from 1.1 g/dL [0.0-2.0] in FIO2 21% to 1.0 g/dL [0.2-1.5] in FIO2 100%), but increasingly negative median bias with increasing FIO2 for NBM-200MP (from -0.3 g/dL [-1.3 to 0.3] in FIO2 21% to -0.8 g/dL [-1.5 to -0.1] in FIO2 100%, P = .04). DISCUSSION: This study showed that noninvasive measurement of Hb could be influenced by inspired fraction of oxygen when the monitor NBM-200MP is used.

Fiber optic bronchoscopy and remifentanil target-controlled infusion in critically ill patients with acute hypoxaemic respiratory failure: A descriptive study.

INTRODUCTION: Sedation optimizes patient comfort and ease of execution during fiber optic bronchoscopy (FOB). Our objective was to describe the safety and efficacy of remifentanil-TCI during FOB in non-intubated, hypoxaemic, thoracic surgery ICU patients. METHODS: Consecutive spontaneously breathing adults requiring FOB after thoracic surgery were included if they had hypoxaemia (PaO2/FiO2<300mmHg or need for non-invasive ventilation [NIV]) and prior FOB failure under topical anaesthesia. The remifentanil initial target was chosen at 1ng/mL brain effect-site concentration (Cet), then titrated to 0.5ng/mL Cet increments according to patient comfort and coughing. Outcomes were patient-reported pain and discomfort (Visual Analogue Scale scores), ventilatory support intensification within 24hours after bronchoscopy, and ease of FOB execution. RESULTS: Thirty-nine patients were included; all had a successful FOB. Their median PO2/FiO2 before starting FOB was 187±84mmHg and 24 patients received NIV. Median [interquartile range] pain scores were not different before and after FOB (1.0 [0.0-3.0] and 0.0 [0.0-2.0], respectively). Discomfort was reported as absent or minimal by 27 patients (69%; 95% confidence interval [95% CI], 54-81%) and as bothersome but tolerable by 12 patients (31%; 95% CI, 19-46%). Mean FiO2 returned to baseline within 2hours after FOB in 30 patients; the remaining 9 patients (23%; 95% CI, 13-38%) received ventilatory support intensification. Ease of execution was good or very good in 34 patients (87%; 95% CI, 73-94%), acceptable in 4 patients, and poor in 1 patient (persistent cough). CONCLUSION: Sedation with remifentanil-TCI during FOB with prior failure under topical anaesthesia alone was effective and acceptably safe in non-intubated hypoxaemic thoracic surgery patients.