Biomarkers in acute respiratory failure

Acute respiratory failure (ARF) is the most common type of organ failure leading to the need for intensive care. It is often secondary to acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). ARF, and especially ALI and ARDS, cause increased morbidity, and mortality rates remain high (up to 40%). These disorders are characterised by inflammatory reaction and tissue damage. In some cases, inflammation continues and leads to an overwhelming repair process with ongoing fibrosis, accompanied by organ dysfunction and eventually a loss of function. Measuring the magnitude of the inflammation, and the repair process, would theoretically offer information concerning outcome. Early identification of patients whose disease process is likely to proceed unfavourably, would help clinicians to optimise their treatment. The aim of this study was to evaluate the epidemiology of ARF, its treatment, and outcome in Finland, with special interest in biomarkers, and their value in the prediction of mortality. Altogether, 958 adult patients treated with ventilatory support were prospectively included in this study during an eight week period in 2007 in 25 intensive care units. Plasma aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) was assessed in 602 patients, and plasma cell-free DNA in 580 patients, to evaluate their prognostic value in ARF. Markers of collagen metabolism were studied in longitudinal serum samples in 68 patients in order to evaluate their evolution in ARF and the association to multiple organ dysfunction (MOD). Ventilatory support was used in 39% of all ICU patients. The estimated incidence of ARF was 149.5/100 000 per year. Median tidal volumes used were higher than recommended. Overall mortality at 90 days was 31%. Plasma NT-pro-BNP and cell-free DNA were highly increased in the majority of patients. Both markers were independent predictors of 90-day mortality, but their discriminative power was at most moderate when used separately. The mortality was highest in those patients, in whom both biomarkers were over their separate cut-off values. Thus, combined use of these biomarkers may increase their clinical value in the mortality prediction. The markers of collagen metabolism changed significantly over time in surviving patients. None of these markers did associate with MOD in these patients.Akuutti hengitysvajaus on yleisin tehohoitoon johtava elinhäiriö ja se lisää sairastavuutta ja kuolleisuutta (jopa 40%). Akuuttiin hengitysvajaukseen johtaa usein akuutti keuhkovaurio, jonka tyypillisiä piirteitä ovat tulehdusreaktio ja kudosvaurio. Joskus voimakas tulehdusreaktio johtaa jatkuvaan arpeuttavaan prosessiin ja pahimmassa tapauksessa vaikeaan keuhkojen toiminnanvajaukseen sekä monielinhäiriöön. Tulehdusreaktion sekä siihen liittyvän arpeuttavan prosessin voimakkuutta mittaamalla voitaisiin mahdollisesti tunnistaa ne potilaat, joiden sairaus etenee epätoivotusti. Tämä auttaisi hoidon ja voimavarojen oikeassa kohdentamisessa. Tämän etenevästi toteutetun kohorttitutkimuksen tarkoituksena oli tutkia akuutin hengitysvajauksen yleisyyttä, hoitoa ja ennustetta Suomessa, sekä erityisesti selvittää biologisten merkkiaineiden ennustearvoa. Akuutin hengitysvajauksen ilmaantuvuus oli 149.5/100 000 asukasta vuodessa. Hengityslaitehoitoa tarvitsi 39% kaikista teho-osastoilla hoidetuista potilaista. Näiden potilaiden kuolleisuus 90 päivän kohdalla oli 31%. Hengityslaitehoidossa käytetyt kertahengitystilavuudet olivat suositeltuja suurempia. Sekä plasman B-tyypin N-terminaalinen natriureettinen propeptidi (NT-pro-BNP) että plasman vapaa DNA olivat voimakkaasti koholla suurella osalla potilaista. Molemmat merkkiaineet ennustivat itsenäisesti kuolleisuutta 90 päivän kohdalla, mutta erillisinä mittareina kummankin tilastollinen erottelukyky oli enintään kohtalainen. Kun merkkiaineiden tulokset yhdistettiin, kuolleisuus oli selvästi korkein niillä potilailla, joilla kumpikin merkkiaine oli korkea. Kollageeniaineenvaihdunnan merkkiaineissa tapahtui ajan mittaan merkittävää vaihtelua niillä potilailla, jotka olivat elossa 3 viikon kohdalla. Millään kollageeniaineenvaihdunnan merkkiaineella ei ollut yhteyttä monielinhäiriöön tässä potilasryhmässä

Miten hoidan akuuttia hengitysvajausta?

Teema : tehohoitolääketiede. English summaryPeer reviewe

The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac surgical patients

Background: European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is used for risk stratification before cardiac surgery, but whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) may add prognostic information to EuroSCORE II is not known. Methods: Preoperative (n = 640) and postoperative (n = 629) blood samples were available from cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was also tested in 90 patients with respiratory failure after cardiac surgery (FINNALI study; cohort #2). Results: Sixty-one patients (9.5%) died during follow-up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated (rho = 0.58; p <0.001) and were higher in non-survivors compared to survivors: median 2027 (Q1-3 478-5387) vs. 373 (134-1354) ng/L [NT-proBNP] and 39 (16-191) vs. 13 (8-32) ng/L [hs-TnT]; p <0.001 for both. Preoperative NT-proBNP concentrations were associated with time to death after adjustment for EuroSCORE II (HR [lnNT-proBNP] 1.33 [95% CI 1.08-1.64]), p = 0.008 and reclassified patients on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14-0.64], p = 0.003). Pre-and postoperative NT-proBNP concentrations were closely correlated (rho = 0.80, p <0.001) and postoperative NT-proBNP concentrations were also associated with long-term mortality after adjustment for EuroSCORE II. A parsimonious risk model that included age, creatinine clearance, chronic pulmonary disease, and NT-proBNP measurements provided comparable prognostic accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs-TnT measurements did not add to NT-proBNP measurements Conclusion: NT-proBNP measurements could improve and simplify risk prediction in cardiac surgical patients.Peer reviewe

Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study

Purpose: Circulating chromogranin B (CgB) levels are increased in situations characterized by systemic and myocardial stress, but whether CgB provides prognostic information in patients with acute respiratory failure (ARF) is unknown. Methods: We included 584 patients with ARF, defined as ventilatory support >6 h, and with blood samples available on Intensive Care Unit (ICU) admission and day 3 (n=479). CgB levels were measured by radioimmunoassay and follow-up was 90 days. Results: One-hundred-sixty-nine patients (29%) died during follow-up. Admission CgB levels separated non-survivors from survivors: median 1234 (Q1-3 989-1742) vs. 917 (753-1224) pmol/L, respectively, p<0.001. CgB levels on ICU admission (logarithmically transformed) were associated with time to death after adjustment for established risk indices available on ICU admission, including N-terminal pro-B-type natriuretic levels: HR 2.62 (95% C.I. 1.82-3.77), p<0.001. Admission CgB levels also improved prognostication on top of SOFA and SAPS II scores assessed by Cox regression analyses and the category-free net reclassification index. The area under the curve (AUC) for admission CgB levels to separate survivors and non-survivors was 0.72 (95% CI 0.67-0.76), while the AUC on day 3 was 0.60 (0.54-0.66). Conclusions: CgB levels measured on ICU admission provided additional prognostic information to established risk indices in ARF patients. The final version of this research has been published in Biomarkers. © 2017 Taylor & Franci

Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation : a randomised pilot trial

PurposeWe assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury.MethodsUsing a 2(3) factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7kPa) or high-normal (5.8-6.0kPa) PaCO2 and to normoxia (arterial oxygen tension [PaO2] 10-15kPa) or moderate hyperoxia (PaO2 20-25kPa) and to low-normal or high-normal mean arterial pressure during the first 36h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6months.ResultsIn total 120 patients were included in the analyses. There was a clear separation in PaCO2 (pPeer reviewe

Prognostic Value of Secretoneurin in Patients with Acute Respiratory Failure: Data from the FINNALI Study.

BACKGROUND We examined whether secretoneurin (SN), a biomarker associated with cardiomyocyte Ca(2+) handling, provides prognostic information in patients with acute respiratory failure (ARF). METHODS We included 490 patients with ARF, defined as ventilatory support >6 h, with blood samples available on admission to the intensive care unit (ICU). SN concentrations were measured by RIA. RESULTS A total of 209 patients (43%) were hospitalized with cardiovascular (CV)-related ARF, and 90-day mortality rates were comparable between CV- and non-CV-related ARF (n = 281): 31% vs 24%, P = 0.11. Admission SN concentrations were higher in nonsurvivors than in survivors in both CV-related (median 148 [quartile 1-3, 117-203] vs 108 [87-143] pmol/L, P < 0.001) and non-CV-related ARF (139 [115-184] vs 113 [91-139] pmol/L, P < 0.001). In patients with CV-related ARF, SN concentrations on ICU admission were associated with 90-day mortality [odds ratio (OR) 1.97 (95% CI, 1.04-3.73, P = 0.04)] after adjusting for established risk indices, including N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations. SN also improved patient classification in CV-related ARF as assessed by the net reclassification index: 0.32 (95% CI, 0.04-0.59), P = 0.03. The area under the curve (AUC) of SN to predict mortality in patients with CV-related ARF was 0.72 (95% CI, 0.65-0.79), and the AUC of NT-proBNP was 0.64 (0.56-0.73). In contrast, SN concentrations on ICU admission did not provide incremental prognostic value to established risk indices in patients with non-CV-related ARF, and the AUC was 0.67 (0.60-0.75). CONCLUSIONS SN concentrations measured on ICU admission provided incremental prognostic information to established risk indices in patients with CV-related ARF, but not in patients with non-CV-related ARF

Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage. To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS. Multicenter, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (December 2015-December 2017) that included 301 adults with moderate to severe ARDS according to the Berlin definition. The radiological and partial pressure of oxygen, arterial (Pao2)/fraction of inspired oxygen (Fio2) criteria for ARDS had to be met within a 24-hour period, and the administration of the first dose of the study drug had to occur within 48 hours of the diagnosis of ARDS. The last patient visit was on March 6, 2018. Patients were randomized to receive an intravenous injection of 10 μg of IFN-β-1a (144 patients) or placebo (152 patients) once daily for 6 days. The primary outcome was a score combining death and number of ventilator-free days at day 28 (score ranged from -1 for death to 27 if the patient was off ventilator on the first day). There were 16 secondary outcomes, including 28-day mortality, which were tested hierarchically to control type I error. Among 301 patients who were randomized (mean age, 58 years; 103 women [34.2%]), 296 (98.3%) completed the trial and were included in the primary analysis. At 28 days, the median composite score of death and number of ventilator-free days at day 28 was 10 days (interquartile range, -1 to 20) in the IFN-β-1a group and 8.5 days (interquartile range, 0 to 20) in the placebo group (P = .82). There was no significant difference in 28-day mortality between the IFN-β-1a vs placebo groups (26.4% vs 23.0%; difference, 3.4% [95% CI, -8.1% to 14.8%]; P = .53). Seventy-four patients (25.0%) experienced adverse events considered to be related to treatment during the study (41 patients [28.5%] in the IFN-β-1a group and 33 [21.7%] in the placebo group). Among adults with moderate or severe ARDS, intravenous IFN-β-1a administered for 6 days, compared with placebo, resulted in no significant difference in a composite score that included death and number of ventilator-free days over 28 days. These results do not support the use of IFN-β-1a in the management of ARDS. ClinicalTrials.gov Identifier: NCT02622724