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1.
Elie Azoulay Peter Pickkers Marcio Soares Anders Perner Jordi Rello Philippe R. Bauer Andry van de Louw Pleun Hemelaar Virginie Lemiale Fabio Silvio Taccone Ignacio Martin Loeches Tine Sylvest Meyhoff Jorge Salluh Peter Schellongowski Katerina Rusinova Nicolas Terzi Sangeeta Mehta Massimo Antonelli Achille Kouatchet Andreas Barratt-Due Miia Valkonen Precious Pearl Landburg Fabrice Bruneel Ramin Brandt Bukan Frédéric Pène Victoria Metaxa Anne Sophie Moreau Virginie Souppart Gaston Burghi Christophe Girault Ulysses V. A. Silva Luca Montini François Barbier Lene B. Nielsen Benjamin Gaborit Djamel Mokart Sylvie Chevret for the Efraim investigators the Nine-I study group 《Intensive care medicine》2017,43(12):1808-1819
Background
In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV).Methods
To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers).Results
A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86–0.99), day-1 SOFA (1.09/point, 1.06–1.13), day-1 PaO2/FiO2 (1.47, 1.05–2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42–3.14), invasive pulmonary aspergillosis (1.85, 1.21–2.85), and undetermined cause (1.46, 1.09–1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59–1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09–1.27), direct admission to the ICU (0.69, 0.54–0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08–1.16), PaO2/FiO2 < 100 (1.60, 1.03–2.48), and undetermined ARF etiology (1.43, 1.04–1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09–4.91), first-line IMV (2.55, 1.94–3.29), NIV failure (3.65, 2.05–6.53), standard oxygen failure (4.16, 2.91–5.93), and HFNC failure (5.54, 3.27–9.38).Conclusion
HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.2.
Frédéric Vargas Marc Clavel Pascale Sanchez-Verlan Sylvain Garnier Alexandre Boyer Hoang-Nam Bui Benjamin Clouzeau Charline Sazio Aissa Kerchache Olivier Guisset Antoine Benard Julien Asselineau Bernard Gauche Didier Gruson Stein Silva Philippe Vignon Gilles Hilbert 《Intensive care medicine》2017,43(11):1626-1636
Purpose
Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders.Methods
A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852).Results
Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2–6) versus 4 days (IQR 2–7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59–14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07–13.31); p = 0.04].Conclusions
Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.3.
Jun Duan Xiaoli Han Linfu Bai Lintong Zhou Shicong Huang 《Intensive care medicine》2017,43(2):192-199
Purpose
To develop and validate a scale using variables easily obtained at the bedside for prediction of failure of noninvasive ventilation (NIV) in hypoxemic patients.Methods
The test cohort comprised 449 patients with hypoxemia who were receiving NIV. This cohort was used to develop a scale that considers heart rate, acidosis, consciousness, oxygenation, and respiratory rate (referred to as the HACOR scale) to predict NIV failure, defined as need for intubation after NIV intervention. The highest possible score was 25 points. To validate the scale, a separate group of 358 hypoxemic patients were enrolled in the validation cohort.Results
The failure rate of NIV was 47.8 and 39.4% in the test and validation cohorts, respectively. In the test cohort, patients with NIV failure had higher HACOR scores at initiation and after 1, 12, 24, and 48 h of NIV than those with successful NIV. At 1 h of NIV the area under the receiver operating characteristic curve was 0.88, showing good predictive power for NIV failure. Using 5 points as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for NIV failure were 72.6, 90.2, 87.2, 78.1, and 81.8%, respectively. These results were confirmed in the validation cohort. Moreover, the diagnostic accuracy for NIV failure exceeded 80% in subgroups classified by diagnosis, age, or disease severity and also at 1, 12, 24, and 48 h of NIV. Among patients with NIV failure with a HACOR score of >5 at 1 h of NIV, hospital mortality was lower in those who received intubation at ≤12 h of NIV than in those intubated later [58/88 (66%) vs. 138/175 (79%); p = 0.03).Conclusions
The HACOR scale variables are easily obtained at the bedside. The scale appears to be an effective way of predicting NIV failure in hypoxemic patients. Early intubation in high-risk patients may reduce hospital mortality.4.
Christophe?Milési Sandrine?Essouri Robin?Pouyau Jean-Michel?Liet Mickael?Afanetti Aurélie?Portefaix Julien?Baleine Sabine?Durand Clémentine?Combes Aymeric?Douillard Gilles?Cambonie Groupe Francophone de Réanimation et d’Urgences Pédiatriques 《Intensive care medicine》2017,43(2):209-216
Purpose
Nasal continuous positive airway pressure (nCPAP) is currently the gold standard for respiratory support for moderate to severe acute viral bronchiolitis (AVB). Although oxygen delivery via high flow nasal cannula (HFNC) is increasingly used, evidence of its efficacy and safety is lacking in infants.Methods
A randomized controlled trial was performed in five pediatric intensive care units (PICUs) to compare 7 cmH2O nCPAP with 2 L/kg/min oxygen therapy administered with HFNC in infants up to 6 months old with moderate to severe AVB. The primary endpoint was the percentage of failure within 24 h of randomization using prespecified criteria. To satisfy noninferiority, the failure rate of HFNC had to lie within 15% of the failure rate of nCPAP. Secondary outcomes included success rate after crossover, intubation rate, length of stay, and serious adverse events.Results
From November 2014 to March 2015, 142 infants were included and equally distributed into groups. The risk difference of ?19% (95% CI ?35 to ?3%) did not allow the conclusion of HFNC noninferiority (p = 0.707). Superiority analysis suggested a relative risk of success 1.63 (95% CI 1.02–2.63) higher with nCPAP. The success rate with the alternative respiratory support, intubation rate, durations of noninvasive and invasive ventilation, skin lesions, and length of PICU stay were comparable between groups. No patient had air leak syndrome or died.Conclusion
In young infants with moderate to severe AVB, initial management with HFNC did not have a failure rate similar to that of nCPAP. This clinical trial was recorded in the National Library of Medicine registry (NCT 02457013).5.
Stephan Ehrmann Ferran Roche-Campo Laetitia Bodet-Contentin Keyvan Razazi Jonathan Dugernier Josep Trenado-Alvarez Alexis Donzeau François Vermeulen David Thévoz Metaxia Papanikolaou Antoine Edelson Héctor León Yoshido Lise Piquilloud Karim Lakhal Carlos Lopes Carlos Vicent Arnaud Desachy Gabriela Apiou-Sbirlea Daniel Isabey Laurent Brochard Reva Research Network AT@ICU Study Group 《Intensive care medicine》2016,42(2):192-201
Purpose
Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice.Methods
Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted.Results
A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22–26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients.Conclusions
Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.6.
Federico Pappalardo Martina Crivellari Ambra L. Di Prima Nataliya Agracheva Malgorzata Celinska-Spodar Rosalba Lembo Daiana Taddeo Giovanni Landoni Alberto Zangrillo 《Intensive care medicine》2016,42(11):1706-1714
Purpose
To determine whether protein C zymogen (protein C concentrates or human protein C) improves clinically relevant outcomes in adult patients with severe sepsis and septic shock.Methods
This is a randomized, double-blind, placebo-controlled, parallel-group trial that from September 2012 to June 2014 enrolled adult patients with severe sepsis or septic shock and high risk of death and of bleeding (e.g., APACHE II greater than 25, extracorporeal membrane oxygenation or disseminated intravascular coagulopathy). All patients completed their follow-up 90 days after randomization and data were analyzed according to the intention-to-treat principle. Follow-up was performed at 30 and 90 days after randomization. The primary endpoint was a composite outcome of prolonged intensive care unit (ICU) stay and/or 30-day mortality. Secondary endpoints included mortality.Results
The study was stopped early in a situation of futility for the composite outcome of prolonged ICU stay and/or 30-day mortality that was 79 % (15 patients) in the protein C zymogen group and 67 % (12 patients) in the placebo group (p = 0.40) and for a concomitant safety issue: ICU mortality was 79 % (15 patients) in the protein C zymogen group vs 39 % (7 patients) in the placebo group (p = 0.020), and 30-day mortality was 68 vs 39 % (p = 0.072).Conclusion
Protein C zymogen did not improve clinically relevant outcomes in severe sepsis and septic shock adult patients. Given its high cost and the potential increase in mortality, the use of this drug in adult patients should be discouraged.7.
Matilde Jo Allingstrup Jens Kondrup Jørgen Wiis Casper Claudius Ulf Gøttrup Pedersen Rikke Hein-Rasmussen Mads Rye Bjerregaard Morten Steensen Tom Hartvig Jensen Theis Lange Martin Bruun Madsen Morten Hylander Møller Anders Perner 《Intensive care medicine》2017,43(11):1637-1647
Purpose
We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients.Methods
We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders.Results
We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein (p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI ?5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days.Conclusions
EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients. Clinicaltrials.gov identifier no. NCT01372176.8.
Emmanuel?Futier Catherine?Paugam-Burtz Thomas?Godet Linda?Khoy-Ear Sacha?Rozencwajg Jean-Marc?Delay Daniel?Verzilli Jeremie?Dupuis Gerald?Chanques Jean-Etienne?Bazin Jean-Michel?Constantin Bruno?Pereira Samir?Jaber
Purpose
High-flow nasal cannula (HFNC) oxygen therapy is attracting increasing interest in acute medicine as an alternative to standard oxygen therapy; however, its use to prevent hypoxaemia after major abdominal surgery has not been evaluated. Our trial was designed to close this evidence gap.Methods
A multicentre randomised controlled trial was carried out at three university hospitals in France. Adult patients at moderate to high risk of postoperative pulmonary complications who had undergone major abdominal surgery using lung-protective ventilation were randomly assigned using a computer-generated sequence to receive either HFNC oxygen therapy or standard oxygen therapy (low-flow oxygen delivered via nasal prongs or facemask) directly after extubation. The primary endpoint was absolute risk reduction (ARR) for hypoxaemia at 1 h after extubation and after treatment discontinuation. Secondary outcomes included occurrence of postoperative pulmonary complications within 7 days after surgery, the duration of hospital stay, and in-hospital mortality. The analysis was performed on data from the modified intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT01887015).Results
Between 6 November 2013 and 1 March 2015, 220 patients were randomly assigned to receive either HFNC (n = 108) or standard oxygen therapy (n = 112); all of these patients completed follow-up. The median duration of the allocated treatment was 16 h (interquartile range 14–18 h) with standard oxygen therapy and 15 h (interquartile range 12–18) with HFNC therapy. Twenty-three (21 %) of the 108 patients treated with HFNC 1 h after extubation and 29 (27 %) of the 108 patients after treatment discontinuation had postextubation hypoxaemia, compared with 27 (24 %) and 34 (30 %) of the 112 patients treated with standard oxygen (ARR 4, 95 % CI –8 to 15 %; p = 0.57; adjusted relative risk [RR] 0.87, 95 % CI 0.53–1.43; p = 0.58). Over the 7-day postoperative follow-up period, there was no statistically significant difference between the groups in the proportion of patients who remained free of any pulmonary complication (ARR 7, 95 % CI –6 to 20 %; p = 0.40). Other secondary outcomes also did not differ significantly between the two groups.Conclusions
Among patients undergoing major abdominal surgery, early preventive application of high-flow nasal cannula oxygen therapy after extubation did not result in improved pulmonary outcomes compared with standard oxygen therapy.9.
Tommaso?Mauri Laura?Alban Cecilia?Turrini Barbara?Cambiaghi Eleonora?Carlesso Paolo?Taccone Nicola?Bottino Alfredo?Lissoni Savino?Spadaro Carlo?Alberto?Volta Luciano?Gattinoni Antonio?Pesenti
Purpose
Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients.Methods
A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300 mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly applied, while maintaining constant FiO2 (20 min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure–time product (PTPPes), and lung volume, by electrical impedance tomography.Results
Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (V T/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, V T/ΔPes and oxygenation improved linearly.Conclusions
In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.10.
Stephan Braune Annekatrin Sieweke Franz Brettner Thomas Staudinger Michael Joannidis Serge Verbrugge Daniel Frings Axel Nierhaus Karl Wegscheider Stefan Kluge 《Intensive care medicine》2016,42(9):1437-1444
Introduction
The aim of the study was to evaluate the feasibility and safety of avoiding invasive mechanical ventilation (IMV) by using extracorporeal CO2 removal (ECCO2R) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure refractory to noninvasive ventilation (NIV).Methods
Case–control study. Patients with acute hypercapnic respiratory failure refractory to NIV being treated with a pump-driven veno-venous ECCO2R system (iLA-Activve®; Novalung, Heilbronn, Germany) were prospectively observed in five European intensive care units (ICU). Inclusion criteria were respiratory acidosis (pH ≤ 7.35, PaCO2 > 45 mmHg) with predefined criteria for endotracheal intubation (ClinicalTrials.gov NCT01784367). The historical controls were patients with acute hypercapnic respiratory failure refractory to NIV who were treated with IMV. The matching criteria were main diagnosis, age, SAPS-II score and pH.Results
Twenty-five cases (48.0 % male, mean age 67.3 years) were matched with 25 controls. Intubation was avoided in 14 patients (56.0 %) in the ECCO2R group with a mean extracorporeal blood flow of 1.3 L/min. Seven patients were intubated because of progressive hypoxaemia and four owing to ventilatory failure despite ECCO2R and NIV. Relevant ECCO2R-associated adverse events were observed in 11 patients (44.0 %), of whom 9 (36.0 %) suffered major bleeding complications. The mean time on IMV, ICU stay and hospital stay in the case and control groups were 8.3 vs. 13.7, 28.9 vs. 24.0 and 36.9 vs. 37.0 days, respectively, and the 90-day mortality rates were 28.0 vs. 28.0 %.Conclusions
The use of veno-venous ECCO2R to avoid invasive mechanical ventilation was successful in just over half of the cases. However, relevant ECCO2R-associated complications occurred in over one-third of cases. Despite the shorter period of IMV in the ECCO2R group there were no significant differences in length of stay or in 28- and 90-day mortality rates between the two groups. Larger, randomised studies are warranted for further assessment of the effectiveness of ECCO2R.11.
Ippei Ikushima Lene Jensen Anne Flint Tomoyuki Nishida Jeppe Zacho Shin Irie 《Advances in therapy》2018,35(4):531-544
Introduction
Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.Methods
In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC0–168h)].Results
Steady-state exposure of semaglutide was similar for both populations: AUC0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (Cmax) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC0–168h ERR 1.11; Cmax ERR 1.14). Dose-dependent increases in AUC0–168h and Cmax occurred in both populations. Accumulation was as expected, based on the half-life (t1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.Conclusions
The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.Funding
Novo Nordisk A/S, Denmark.Trial registration
ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.12.
Importance
Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness.Objective
To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients.Design, setting, and participants
Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days.Interventions
Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care.Main outcomes and measures
Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function.Results
474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI ?0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m2 (95 % CI 1.0–14.5 mL/min/1.73 m2, P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145–455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21).Conclusion and relevance
Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction.Trial registration
anzctr.org.au Identifier: ACTRN12609001015235.13.
Sebastian A. Haas Theresa Lange Bernd Saugel Martin Petzoldt Valentin Fuhrmann Maria Metschke Stefan Kluge 《Intensive care medicine》2016,42(2):202-210
Purpose
Hyperlactatemia may occur for a variety of reasons and is a predictor of poor clinical outcome. However, only limited data are available on the underlying causes of hyperlactatemia and the mortality rates associated with severe hyperlactatemia in critically ill patients. We therefore aimed to evaluate the etiology of severe hyperlactatemia (defined as a lactate level >10 mmol/L) in a large cohort of unselected ICU patients. We also aimed to evaluate the association between severe hyperlactatemia and lactate clearance with ICU mortality.Methods
In this retrospective, observational study at an University hospital department with 11 ICUs during the study period between 1 April 2011 and 28 February 2013, we screened 14,040 ICU patients for severe hyperlactatemia (lactate >10 mmol/L).Results
Overall mortality in the 14,040 ICU patients was 9.8 %. Of these, 400 patients had severe hyperlactatemia and ICU mortality in this group was 78.2 %. Hyperlactatemia was associated with death in the ICU [odds ratio 1.35 (95 % CI 1.23; 1.49; p < 0.001)]. The main etiology for severe hyperlactatemia was sepsis (34.0 %), followed by cardiogenic shock (19.3 %), and cardiopulmonary resuscitation (13.8 %). Patients developing severe hyperlactatemia >24 h of ICU treatment had a significantly higher ICU mortality (89.1 %, 155 of 174 patients) than patients developing severe hyperlactatemia ≤24 h of ICU treatment (69.9 %, 158 of 226 patients; p < 0.0001). Lactate clearance after 12 h showed a receiver-operating-characteristics area under the curve (ROC-AUC) value of 0.91 to predict ICU mortality (cut-off showing highest sensitivity and specifity was a 12 h lactate clearance of 32.8 %, Youden Index 0.72). In 268 patients having a 12-h lactate clearance <32.8 % ICU mortality was 96.6 %.Conclusions
Severe hyperlactatemia (>10 mmol/L) is associated with extremely high ICU mortality especially when there is no marked lactate clearance within 12 h. In such situations, the benefit of continued ICU therapy should be evaluated.14.
Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study 总被引:1,自引:1,他引:0
Objective
To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.Design and setting
Prospective crossover interventional study in an intensive care unit of a university hospital.Patients
Twenty patients.Interventions
After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.Measurements and results
During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO2 decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.Conclusions
The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.15.
Martin B. Madsen Peter B. Hjortrup Marco B. Hansen Theis Lange Anna Norrby-Teglund Ole Hyldegaard Anders Perner 《Intensive care medicine》2017,43(11):1585-1593
Purpose
The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI).Methods
We randomised 100 patients with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation; patients who had died were given the lowest possible score (zero).Results
Of the 100 patients randomised, 87 were included in the intention-to-treat analysis of the PCS score, 42 patients (84%) in the IVIG group and 45 patients (90%) in the placebo group. The two intervention groups had similar baseline characteristics with the exception of IVIG use before randomisation (1 dose was allowed) and rates of acute kidney injury. Median PCS scores were 36 (interquartile range 0–43) in the group assigned to IVIG and 31 (0–47) in the group assigned to placebo (mean adjusted difference 1 (95% confidence interval ?7 to 10), p = 0.81). The result was supported by analyses adjusted for baseline prognostics, those in the per protocol populations, in the subgroups (site of NSTI) and those done post hoc adjusted for IVIG use before randomisation.Conclusions
In ICU patients with NSTI, we observed no apparent effects of adjuvant IVIG on self-reported physical functioning at 6 months. Trial registration: NCT02111161.16.
Introduction
This study aimed to compare the efficacy and safety of two mesalazine formulations in the treatment of Chinese patients with ulcerative colitis (UC) in the remission phase.Methods
In this multicenter, single-blind, randomized controlled study conducted from November 2010 to August 2012, 251 patients with UC from 18 hospitals were enrolled. The patients were randomized to treatment with mesalazine modified-release tablets (MR group, n = 126) or other enteric-coated tablets (EC group, n = 125), at 800 mg three-times daily for 48 weeks. The primary efficacy parameter was the rate of non-emergence of bloody stool. If the lower limit of the 95% confidence interval (CI) of the primary efficacy measure was over ?10%, the modified-release tablets were considered non-inferior to the enteric-coated tablets. The secondary efficacy parameters included the period of non-emergence of bloody stool and the period of non-recurrence of UC. The incidences of adverse events and adverse drug reactions were compared between the two groups.Results
At 48 weeks of maintenance treatment, the rates of non-emergence of bloody stool were 82.99% (95% CI 73.53–92.45%) and 73.30% (95% CI 64.04–82.56%) in the MR and EC groups, respectively, and the difference between the two groups was 9.69% (95% CI ?1.15–20.53%). There was no significant difference in the period of non-emergence of bloody stool and the period of non-recurrence of UC between the two groups (P > 0.05). The incidences of adverse events were 48.78% (60/123) and 48.00% (60/125) in the MR and EC groups, respectively (P = 0.902). The incidences of adverse drug reactions were 16.26% (20/123) and 13.60% (17/125) in the MR and EC groups, respectively (P = 0.556).Conclusion
Mesalazine modified-release tablets were non-inferior to the enteric-coated tablets and may be considered an effective and safe treatment alternative for the maintenance of remission in Chinese patients with UC.Trial registration
ClinicalTrials.gov identifier: NCT01257399.Funding
Tillotts Pharma AG.17.
Maximilian Petri Ingo Stoffels Klaus Griewank Jithin Jose Peter Engels Andrea Schulz Harald Pötzschke Philipp Jansen Dirk Schadendorf Joachim Dissemond Joachim Klode 《Molecular imaging and biology》2018,20(1):124-130
Purpose
Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies.Procedures
Photoacoustic imaging was used to measure the local oxygen saturation (StO2) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination.Results
Measuring 49 patients, an increase in StO2 after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO2 (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted.Conclusion
Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO2 after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy.Trial Registration
German Clinical Trials Register: DRKS0000599318.
John Muscedere Braden Waters Aditya Varambally Sean M. Bagshaw J. Gordon Boyd David Maslove Stephanie Sibley Kenneth Rockwood 《Intensive care medicine》2017,43(8):1105-1122
Purpose
Functional status and chronic health status are important baseline characteristics of critically ill patients. The assessment of frailty on admission to the intensive care unit (ICU) may provide objective, prognostic information on baseline health. To determine the impact of frailty on the outcome of critically ill patients, we performed a systematic review and meta-analysis comparing clinical outcomes in frail and non-frail patients admitted to ICU.Methods
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, and Clinicaltrials.gov. All study designs with the exception of narrative reviews, case reports, and editorials were included. Included studies assessed frailty in patients greater than 18 years of age admitted to an ICU and compared outcomes between fit and frail patients. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were hospital and long-term mortality. We also determined the prevalence of frailty, the impact on other patient-centered outcomes such as discharge disposition, and health service utilization such as length of stay.Results
Ten observational studies enrolling a total of 3030 patients (927 frail and 2103 fit patients) were included. The overall quality of studies was moderate. Frailty was associated with higher hospital mortality [relative risk (RR) 1.71; 95% CI 1.43, 2.05; p < 0.00001; I 2 = 32%] and long-term mortality (RR 1.53; 95% CI 1.40, 1.68; p < 0.00001; I 2 = 0%). The pooled prevalence of frailty was 30% (95% CI 29–32%). Frail patients were less likely to be discharged home than fit patients (RR 0.59; 95% CI 0.49, 0.71; p < 0.00001; I 2 = 12%).Conclusions
Frailty is common in patients admitted to ICU and is associated with worsened outcomes. Identification of this previously unrecognized and vulnerable ICU population should act as the impetus for investigating and implementing appropriate care plans for critically ill frail patients. Registration: PROSPERO (ID: CRD42016053910).19.
Introduction
This study compared the efficacy and safety of two mesalazine formulations in the treatment of Chinese patients with mildly to moderately active ulcerative colitis (UC).Methods
In this multicenter, single-blind, randomized controlled study of 251 patients with active UC conducted from November 2010 to January 2012, subjects were randomized to treatment with mesalazine modified-release tablets (MR group, n = 123) or enteric-coated tablets (EC group, n = 128) at 800 mg three-times daily for 8 weeks. The primary efficacy measure was the decrease in UC Disease Activity Index (UCDAI) at final evaluation. If the 95% confidence interval (CI) lower limit of the difference of the decrease in UCDAI between groups was over ?1.0, mesalazine modified-release tablets were considered non-inferior to mesalazine enteric-coated tablets. The change in UCDAI in patients with mild and moderate (UCDAI 3–5 and 6–8 at enrollment, respectively) UC was analyzed. Secondary efficacy measures were remission and efficacy rates. Incidences of adverse drug reactions (ADRs) were calculated.Results
The decreases in UCDAI at final evaluation were 2.84 and 2.56 in the MR and EC groups, respectively, with a difference of 0.27 between groups (95% CI ?0.34, 0.88). The remission rates were 48.33% (58/120) and 55.65% (69/124), and the efficacy rates were 63.33% (76/120) and 66.94% (83/124) in the MR and EC groups, respectively (all P > 0.05). In patients with mild UC, the decreases in UCDAI were 2.16 and 2.05 in the MR and EC groups, respectively, while in patients with moderate UC they were 3.49 and 3.03, respectively (all P > 0.05). The incidences of ADRs in the MR and EC groups were 6.61% (8/121) and 10.24% (13/127), respectively (P > 0.05). No serious ADRs were reported during the study.Conclusion
Mesalazine modified-release tablets are non-inferior to enteric-coated tablets and are an effective and safe treatment option in Chinese patients with mildly to moderately active UC.Trial registration
ClinicalTrials.gov identifier: NCT01257386.Funding
Tillotts Pharma AG.20.
Silvia Calviño Günther Carole Schwebel Rebecca Hamidfar-Roy Agnès Bonadona Maxime Lugosi Claire Ara-Somohano Clémence Minet Leïla Potton Jean-Charles Cartier Aurelien Vésin Magalie Chautemps Lenka Styfalova Stephane Ruckly Jean-François Timsit 《Intensive care medicine》2016,42(11):1753-1765