Alexander P J Vlaar, Pearl Toy, Mark Fung, Mark R Looney, Nicole P Juffermans, Juergen Bux, Paula Bolton-Maggs, Anna L Peters, Christopher C Silliman, Daryl J Kor, Steve Kleinman
A consensus redefinition of transfusion-related acute lung injury.
Transfusion. 2019 Jul;59(7):2465-2476. doi: 10.1111/trf.15311. Epub 2019 Apr 16.
Abstract/Text
BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life-threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI.
STUDY DESIGN AND METHODS: An international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases.
RESULTS: In the redefinition, the term "possible TRALI" has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies.
CONCLUSIONS: Clinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion-associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.
© 2019 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.
Rutger A Middelburg, Daniëlle van Stein, Ernest Briët, Johanna G van der Bom
The role of donor antibodies in the pathogenesis of transfusion-related acute lung injury: a systematic review.
Transfusion. 2008 Oct;48(10):2167-76. doi: 10.1111/j.1537-2995.2008.01810.x. Epub 2008 Jun 28.
Abstract/Text
BACKGROUND: The majority of cases of transfusion-related acute lung injury (TRALI) are thought to be caused by the presence of leukocyte antibodies in the blood of the donor. We performed a systematic search of the literature to quantify the contribution of donor antibodies to the occurrence of TRALI.
STUDY DESIGN AND METHODS: We conducted a systematic search of the PubMed and EMBASE databases. Retrieved articles were judged by three authors independently. Reference lists of all articles were subsequently screened for relevant references. All articles in English, German, French, and Dutch, published at any time before December 2007, were eligible for inclusion.
RESULTS: Of 77 articles on leukocyte antibodies in donors involved in a case of TRALI, 14 articles contained sufficient data. These 14 articles reported leukocyte antibodies in 24 of 51 donors (47%) associated with 24 of 28 TRALI cases (86%). Of 15 articles that reported the prevalence of leukocyte antibodies in the general donor population, 2 articles reported a prevalence of 17 percent in (452) randomly selected donors. The odds ratio for developing TRALI was 15 (95% confidence interval [CI], 5.1-45) for patients who received a transfusion from a donor who tested positive for the presence of leukocyte antibodies, compared to donors who tested negative. Leukocyte antibodies contributed to 80 percent (95% CI, 51%-92%) of all TRALI cases.
CONCLUSION: Leukocyte antibodies were more prevalent in donors involved in TRALI cases than among randomly selected donors. These findings suggest that donor antibodies contribute to four-fifths of all TRALI cases.
Steven H Kleinman, Darrell J Triulzi, Edward L Murphy, Patricia M Carey, Jerome L Gottschall, John D Roback, Danielle Carrick, Sunitha Mathew, David J Wright, Ritchard Cable, Paul Ness, Ognjen Gajic, Rolf D Hubmayr, Mark R Looney, Ram M Kakaiya, National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study-II
The Leukocyte Antibody Prevalence Study-II (LAPS-II): a retrospective cohort study of transfusion-related acute lung injury in recipients of high-plasma-volume human leukocyte antigen antibody-positive or -negative components.
Transfusion. 2011 Oct;51(10):2078-91. doi: 10.1111/j.1537-2995.2011.03120.x. Epub 2011 Mar 29.
Abstract/Text
BACKGROUND: We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI.
STUDY DESIGN AND METHODS: In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of 2596 plasma-rich blood components (transfusable plasma and plateletpheresis) sent to participating hospitals; half of the components were collected from anti-HLA-positive donors (study arm) and half from anti-HLA-negative donors (control arm) matched by sex, parity, and blood center. A staged medical record review process was used. Final recipient diagnosis was based on case review by a blinded expert panel of pulmonary or critical care physicians.
RESULTS: TRALI incidence was 0.59% (seven cases) in study arm recipients versus 0.16% (two cases) in control arm recipients for an odds ratio (OR) of 3.6 (95% confidence interval [CI], 0.7-17.4; p = 0.10). For possible TRALI cases (nine study arm, eight control arm), the OR was 1.2 (95% CI, 0.4-3.0; p = 0.81), and for TRALI and possible TRALI aggregated together, it was 1.7 (95% CI, 0.7-3.7; p = 0.24). Transfusion-associated circulatory overload incidence was identical in the two arms (1.17 and 1.22%, respectively; OR, 1.0; p = 1.0).
CONCLUSIONS: TRALI incidence in recipients of anti-HLA-positive components was relatively low for a lookback study (1 in 170) and was higher than in the control arm, but did not reach significance. Based on this trend, the data are consistent with the likelihood that TRALI risk is decreased by selecting high-volume plasma components for transfusion from donors at low risk of having HLA antibodies.
© 2011 American Association of Blood Banks.
Shiho Hashimoto, Fumiaki Nakajima, Hiromi Kamada, Kumiko Kawamura, Masahiro Satake, Kenji Tadokoro, Hitoshi Okazaki
Relationship of donor HLA antibody strength to the development of transfusion-related acute lung injury.
Transfusion. 2010 Dec;50(12):2582-91. doi: 10.1111/j.1537-2995.2010.02779.x.
Abstract/Text
BACKGROUND: Antibodies against the human leukocyte antigen (HLA) in donors' blood are implicated in the development of transfusion-related acute lung injury (TRALI). Screening of female donors for HLA antibodies has been introduced to prevent TRALI; however, the relationship of HLA antibody strength in the transfused components to the development of TRALI has not been evaluated in detail.
STUDY DESIGN AND METHODS: Donors involved in 1038 cases of nonhemolytic transfusion reactions (NHTRs) including 283 cases of TRALI were screened for HLA antibodies by the fluorescence beads method. HLA antibody specificity and strength were analyzed in detail. The usefulness of enzyme-linked immunosorbent assay (ELISA) for screening HLA antibodies was also evaluated.
RESULT: Among 21 cases of TRALI, four cases of possible TRALI, and five cases of other NHTRs, the sum of mean fluorescence intensity (MFI) of donors' HLA antibodies to patients' cognate antigen(s) was determined in 18, four, and three cases, respectively. The sum of MFI in TRALI cases was significantly higher than that in other NHTR cases (p<0.05). When HLA antibody-positive samples were reevaluated by ELISA, the ELISA optical density ratio was significantly higher in donors' samples associated with TRALI than in those associated with other NHTRs (p<0.01)
CONCLUSIONS: A correlation between the HLA antibody strength and development of TRALI was indicated. The antibody strength measured by ELISA could be used as the basis for the screening of HLA antibodies in place of the fluorescence beads method. This study provided clues to the establishment of a cutoff value for HLA antibody screening in an evidence-based manner for the prevention of TRALI.
© 2010 American Association of Blood Banks.
Johanna C Wiersum-Osselton, Barbee Whitaker, Sharran Grey, Kevin Land, Gabriela Perez, Srijana Rajbhandary, Chester Andrzejewski, Paula Bolton-Maggs, Harriet Lucero, Philippe Renaudier, Pierre Robillard, Matilde Santos, Martin Schipperus
Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study.
Lancet Haematol. 2019 Jul;6(7):e350-e358. doi: 10.1016/S2352-3026(19)30080-8. Epub 2019 May 9.
Abstract/Text
BACKGROUND: Transfusion-associated circulatory overload (TACO) is a major cause of transfusion-related morbidity and mortality in countries with well developed transfusion services. The International Society of Blood Transfusion, the International Haemovigilance Network, and AABB (formerly American Association of Blood Banks), have developed and validated a revised definition of TACO.
METHODS: International Haemovigilance Network-member haemovigilance systems (Australia, Austria, Denmark, Finland, Greece, India, Ireland, Italy, Japan, Malta, Netherlands, New Zealand, Norway, Slovenia, United Kingdom and United States) provided cases of respiratory complications categorised by their systems, including clinical parameters listed in the 2017 draft definition (part 1). Individual transfusion professionals were then invited to assess 24 case descriptions according to the draft definition (part 2). Positive and negative agreement and inter-rater agreement (κ) were calculated. Based on validation results, cases were reanalysed and slight adjustments made to yield the final 2018 TACO definition.
FINDINGS: In part 1, 16 (44%) of 36 haemovigilance systems provided 178 cases, including 126 TACO cases. By use of the 2018 definition, 96 (76%) of 126 cases of TACO were in positive agreement. 19 (37%) of 52 cases were recognised as non-TACO respiratory complications. In part 2 (47 experts from 20 countries), moderate all-case agreement (κ=0·43) and TACO-specific agreement (κ=0·54) were observed. Excluding cases missing some clinical information (eg, N terminal pro-brain natriuretic peptide, distinctive chest x-ray findings, and relationship with existing respiratory co-morbidities like pneumonia and chronic obstructive pulmonary disease) improved all-case agreement to κ=0·50 (moderate) and κ=0·65 (good) for TACO cases.
INTERPRETATION: The two-part validation exercise showed that the revised 2018 TACO surveillance case definition captures 76% of cases endorsed as TACO by participating haemovigilance systems. This definition can become the basis for internationally consistent surveillance reporting and contribute towards increased awareness and mitigation of TACO. Further research will require reporting more complete clinical information to haemovigilance systems and should focus on improved distinction between TACO and other transfusion respiratory complications.
FUNDING: International Society of Blood Transfusion, International Haemovigilance Network, and AABB.
Copyright © 2019 Elsevier Ltd. All rights reserved.
日本循環器学会 / 日本心不全学会合同ガイドライン 急性・慢性心不全診療ガイドライン（2017年改訂版） Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Failure （JCS 2017/JHFS 2017）https://www.j-circ.or.jp/cms/wp-content/uploads/2017/06/JCS2017_tsutsui_h.pdf.
Lan Zhou, Donald Giacherio, Laura Cooling, Robertson D Davenport
Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion-associated circulatory overload.
Transfusion. 2005 Jul;45(7):1056-63. doi: 10.1111/j.1537-2995.2005.04326.x.
Abstract/Text
BACKGROUND: Transfusion-associated circulatory overload (TACO) occurs when the transfusion rate or volume exceeds the capacity of a compromised cardiovascular system. Characteristic symptoms and signs associated with TACO are neither sensitive nor specific. B-natriuretic peptide (BNP) is a 32-amino-acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. This study was performed to explore the usage of BNP in the differential diagnosis of TACO.
STUDY DESIGN AND METHODS: Pre- and posttransfusion BNP levels were determined in 21 patients with suspected TACO and 19 control patients. The BNP was considered significant if the posttransfusion-to-pretransfusion ratio was at least 1.5 and the posttransfusion BNP level was at least 100 pg per mL.
RESULTS: The BNP test has a sensitivity and specificity of 81 and 89 percent, respectively, in diagnosis of TACO. It has a positive predictive value of 89 percent, a negative predictive value of 81 percent, and an accuracy of 87 percent. In logistic regression analysis, BNP was found to have significant predictive power independent of other clinical variables in models predicting which patients had TACO.
CONCLUSIONS: Our study suggests that in patients who present symptoms suggestive of TACO, BNP can be a useful adjunct marker in confirming volume overload as the cause of acute dyspnea and symptoms related to cardiovascular compromise.
Aaron A R Tobian, Lori J Sokoll, Daniel J Tisch, Paul M Ness, Hua Shan
N-terminal pro-brain natriuretic peptide is a useful diagnostic marker for transfusion-associated circulatory overload.
Transfusion. 2008 Jun;48(6):1143-50. doi: 10.1111/j.1537-2995.2008.01656.x. Epub 2008 Feb 22.
Abstract/Text
BACKGROUND: Transfusion-associated circulatory overload (TACO) can be difficult to diagnose and distinguish from transfusion-related acute lung injury (TRALI), but is a relatively common complication that occurs when increases in blood volume overwhelm the cardiovascular system. Brain natriuretic peptide (BNP) has been shown to be a functional marker for TACO. N-terminal pro-brain natriuretic peptide (NT-proBNP) is another marker that could be more helpful than BNP since it has a longer half-life in circulation and is also much more stable in laboratory samples. In this study, whether NT-proBNP is a useful diagnostic marker for TACO was evaluated.
STUDY DESIGN AND METHODS: Forty patients were enrolled into a case-control study (16 patients with TACO and 24 control patients) and had pre- and posttransfusion NT-proBNP concentrations evaluated from submitted type-and-screen blood samples.
RESULTS: The sensitivity of elevated posttransfusion NT-proBNP to diagnose TACO was 93.8 percent, the specificity was 83.8 percent, and the accuracy was 87.5 percent. Elevated posttransfusion NT-proBNP is the only independent variable for the diagnosis of TACO based on multivariate logistic regression.
CONCLUSION: NT-proBNP is both a sensitive and a specific marker for TACO and can be helpful in confirming transfusion associated fluid overload. This study also demonstrates that many patients who experience TACO may already be in a state of excess volume. Clinicians should be aware that many asymptomatic patients have excess fluid and transfusion may cause these patients to become symptomatic.
Guangxi Li, Craig E Daniels, Marija Kojicic, Tami Krpata, Greg A Wilson, Jeffrey L Winters, S Breanndan Moore, Ognjen Gajic
The accuracy of natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic) in the differentiation between transfusion-related acute lung injury and transfusion-related circulatory overload in the critically ill.
Transfusion. 2009 Jan;49(1):13-20. doi: 10.1111/j.1537-2995.2008.01941.x. Epub 2008 Oct 14.
Abstract/Text
BACKGROUND: The diagnostic workup of transfusion-related acute lung injury (TRALI) requires an exclusion of transfusion-associated circulatory overload (TACO). Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic (NT-pro-BNP) accurately diagnosed TACO in preliminary studies that did not include patients with TRALI.
STUDY DESIGN AND METHODS: In this prospective cohort study, two critical care experts blinded to serum levels of BNP and NT-pro-BNP determined the diagnosis of TRALI, TACO, and possible TRALI based on the consensus conference definitions. The accuracy of BNP and NT-pro-BNP was assessed based on the area under the receiver operating curve (AUC).
RESULTS: Of 115 patients who developed acute pulmonary edema after transfusion, 34 were identified with TRALI, 31 with possible TRALI, and 50 with TACO. Median BNP was 375 pg per mL (interquartile range [IQR], 123 to 781 pg/mL) in TRALI, 446 pg per mL (IQR, 128 to 743 pg/mL) in possible TRALI, and 559 pg per mL (IQR, 288 to 1348 pg/mL) in TACO patients (p = 0.038). The NT-pro-BNP levels among patients with TRALI, possible TRALI, and TACO differed significantly with a median value of 1559 pg per mL (IQR, 629 to 5114 pg/mL), 2349 pg/mL (IQR, 919 to 4610 pg/mL), and 5197 pg/mL (IQR, 1695 to 15,714 pg/mL; p = 0.004), respectively. The accuracy of BNP and NT-pro-BNP to diagnose TACO was moderate with an AUC of 0.63 (95% confidence interval [CI], 0.51-0.74) and 0.70 (95% CI, 0.59 to 0.80).
CONCLUSIONS: Natriuretic peptides are of limited diagnostic value in a differential diagnosis of pulmonary edema after transfusion in the critically ill patients.
A Sheikh, Y A Shehata, S G A Brown, F E R Simons
Adrenaline for the treatment of anaphylaxis: cochrane systematic review.
Allergy. 2009 Feb;64(2):204-12. doi: 10.1111/j.1398-9995.2008.01926.x.
Abstract/Text
BACKGROUND: Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Adrenaline is recommended as the initial treatment of choice for anaphylaxis.
OBJECTIVES: To assess the benefits and harms of adrenaline in the treatment of anaphylaxis.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1966 to March 2007), CINAHL (1982 to March 2007), BIOSIS (to March 2007), ISI Web of Knowledge (to March 2007) and LILACS (to March 2007). We also searched websites listing ongoing trials: http://www.clinicaltrials.gov/, http://www.controlledtrials.com and http://www.actr.org.au/ and contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized controlled trials comparing adrenaline with no intervention, placebo or other adrenergic agonists were eligible for inclusion. Two authors independently assessed articles for inclusion.
RESULTS: We found no studies that satisfied the inclusion criteria.
CONCLUSIONS: On the basis of this review, we are unable to make any new recommendations on the use of adrenaline for the treatment of anaphylaxis. In the absence of appropriate trials, we recommend, albeit on the basis of less than optimal evidence, that adrenaline administration by intramuscular injection should still be regarded as first-line treatment for the management of anaphylaxis.
Terry L Vanden Hoek, Laurie J Morrison, Michael Shuster, Michael Donnino, Elizabeth Sinz, Eric J Lavonas, Farida M Jeejeebhoy, Andrea Gabrielli
Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Circulation. 2010 Nov 2;122(18 Suppl 3):S829-61. doi: 10.1161/CIRCULATIONAHA.110.971069.
Abstract/Text
Jasmeet Soar, Gavin D Perkins, Gamal Abbas, Annette Alfonzo, Alessandro Barelli, Joost J L M Bierens, Hermann Brugger, Charles D Deakin, Joel Dunning, Marios Georgiou, Anthony J Handley, David J Lockey, Peter Paal, Claudio Sandroni, Karl-Christian Thies, David A Zideman, Jerry P Nolan
European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution.
Resuscitation. 2010 Oct;81(10):1400-33. doi: 10.1016/j.resuscitation.2010.08.015.
Abstract/Text
厚生労働省：重篤副作用疾患別対応マニュアル アナフィラキシー．医薬品医療機器総合機構、平成20年3月．.
K J L Choo, E Simons, Aziz Sheikh
Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review.
Allergy. 2010 Oct;65(10):1205-11. doi: 10.1111/j.1398-9995.2010.02424.x. Epub 2010 Jun 18.
Abstract/Text
BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis.
OBJECTIVES: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion.
RESULTS: None of the 2496 reports identified satisfied the inclusion criteria.
CONCLUSIONS: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.
A Sheikh, V Ten Broek, S G A Brown, F E R Simons
H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review.
Allergy. 2007 Aug;62(8):830-7. doi: 10.1111/j.1398-9995.2007.01435.x.
Abstract/Text
BACKGROUND: Anaphylaxis is an acute systemic allergic reaction, which can be life-threatening. H(1)-antihistamines are commonly used as an adjuvant therapy in the treatment of anaphylaxis. We sought to assess the benefits and harm of H(1)-antihistamines in the treatment of anaphylaxis.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library); MEDLINE (1966 to June 2006); EMBASE (1966 to June 2006); CINAHL (1982 to June 2006) and ISI Web of Science (1945 to July 2006). We also contacted pharmaceutical companies and international experts in anaphylaxis in an attempt to locate unpublished material. Randomized and quasi-randomized-controlled trials comparing H(1)-antihistamines with placebo or no intervention were eligible for inclusion. Two authors independently assessed articles for inclusion.
RESULTS: We found no studies that satisfied the inclusion criteria.
CONCLUSIONS: Based on this review, we are unable to make any recommendations for clinical practice. Randomized-controlled trials are needed, although these are likely to prove challenging to design and execute.
Ritesh Agarwal, Alok Nath, Ashutosh N Aggarwal, Dheeraj Gupta
Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis.
Respirology. 2007 Jul;12(4):585-90. doi: 10.1111/j.1440-1843.2007.01060.x.
Abstract/Text
BACKGROUND AND OBJECTIVES: Glucocorticoids have been shown to improve survival when used in patients with septic shock. The aim of this study was to analyse the role of glucocorticoids in decreasing mortality in acute respiratory distress syndrome (ARDS) both in the acute and the fibroproliferative phases.
METHODS: We searched the MEDLINE database for relevant studies published between 1980 and 2006, and included studies if the study design was a randomized controlled trial or observational study (comparing historical controls). The study population included patients with ARDS treated with glucocorticoids. We calculated the odds ratio and 95% confidence intervals (CI) for the outcome of mortality.
RESULTS: Six trials met the inclusion criteria; three investigated the role of steroids in early stage disease (n = 300) and three investigated the role of steroids in late stage disease (n = 235). The odds of glucocorticoids decreasing mortality in patients with early ARDS were 0.57 (95% CI: 0.25-1.32) with a number needed to treat of 10 for benefit (818 harm to 5 benefit) whereas the odds of glucocorticoids decreasing mortality in patients with late ARDS was 0.58 (95% CI: 0.22-1.53) with a number needed to treat of 15 for harm (6 harm to 21 benefit). However, there was significant heterogeneity.
CONCLUSIONS: Current evidence does not support a role for corticosteroids in the management of ARDS in either the early or late stages of the disease. More research is required to establish the role of steroids in specific subgroups of patients with severe sepsis and early ARDS who have relative adrenal insufficiency and patients with late ARDS 7-14 days after the onset of disease.
John Victor Peter, Preeta John, Petra L Graham, John L Moran, Ige Abraham George, Andrew Bersten
Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis.
BMJ. 2008 May 3;336(7651):1006-9. doi: 10.1136/bmj.39537.939039.BE. Epub 2008 Apr 23.
Abstract/Text
OBJECTIVE: To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS.
DATA SOURCES: Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects.
DATA EXTRACTION: Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus.
DATA SYNTHESIS: Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be > or =1 or the probability that the mean difference would be > or =0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio > or =1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio > or =1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio > or =1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference > or =0)=97.9%). Steroids were not associated with increase in risk of infection.
CONCLUSIONS: A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults.
G Umberto Meduri, Emmel Golden, Amado X Freire, Edwin Taylor, Muhammad Zaman, Stephanie J Carson, Mary Gibson, Reba Umberger
Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.
Chest. 2007 Apr;131(4):954-63. doi: 10.1378/chest.06-2100.
Abstract/Text
OBJECTIVE: To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: ICUs of five hospitals in Memphis.
PARTICIPANTS: Ninety-one patients with severe early ARDS (INTERVENTIONS: Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.
MAIN OUTCOME MEASURE: The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.
RESULTS: In intention-to-treat analysis, the response of the two groups (63 treated and 28 control) clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever.
CONCLUSIONS: Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay.
一般社団法人日本集中治療医学会/一般社団法人日本呼吸療法医学会ARDS診療ガイドライン作成委員会：ARDS診療ガイドライン2016.
Bernhardt G Zeiher, Antonio Artigas, Jean-Louis Vincent, Alexei Dmitrienko, Kimberley Jackson, B Taylor Thompson, Gordon Bernard, STRIVE Study Group
Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.
Crit Care Med. 2004 Aug;32(8):1695-702.
Abstract/Text
OBJECTIVE: Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury.
DESIGN: Multiple-center, double-blind, placebo-controlled trial administering a continuous infusion of sivelestat at a dose of 0.16 mg.kg(-1)hr(-1).
SETTING: One hundred and five institutions in the United States, Canada, Belgium, Spain, Australia, and New Zealand.
PATIENTS: A total of 492 mechanically ventilated patients with acute lung injury.
INTERVENTIONS: Patients were randomized in a 1:1 fashion to sivelestat or placebo. Study drug was administered as a continuous infusion for the duration of mechanical ventilation plus 24 hrs for a maximum of 14 days. All patients were managed using low tidal volume mechanical ventilation.
MEASUREMENTS AND MAIN RESULTS: The study was stopped prematurely at the recommendation of an external Data and Safety Monitoring Board, which noted a negative trend in long-term mortality rate. Final analysis revealed no effect of sivelestat on the primary end points of ventilator-free days (day 1-day 28) or 28-day all-cause mortality. There were 64 deaths in each treatment group within the 28-day study period, and the mean number of ventilator-free days was 11.4 and 11.9 in the sivelestat and placebo treatment groups, respectively (p =.536). There was no evidence of effect on measures of pulmonary function, including Pao2/Fio2, static lung compliance, and time to meeting weaning criteria. There was no difference in adverse events or serious adverse events between treatment groups. A comparison of the Kaplan-Meier 180-day survival curves showed no difference between treatment groups (p =.102), but there was an increase in 180-day all-cause mortality in the sivelestat treatment group compared with the placebo group (p =.006).
CONCLUSIONS: Intravenous sivelestat had no effect on 28-day all-cause mortality or ventilator-free days in a heterogeneous acute lung injury patient population managed with low tidal volume mechanical ventilation.
Kentaro Iwata, Asako Doi, Goh Ohji, Hideaki Oka, Yuichiro Oba, Kohei Takimoto, Wataru Igarashi, David H Gremillion, Toshihiko Shimada
Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis.
Intern Med. 2010;49(22):2423-32. Epub 2010 Nov 15.
Abstract/Text
INTRODUCTION: Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated.
METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model.
RESULTS: 8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias.
CONCLUSION: Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network.
N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
Abstract/Text
BACKGROUND: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients.
METHODS: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28.
RESULTS: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively.
CONCLUSIONS: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
Peter Q Eichacker, Eric P Gerstenberger, Steven M Banks, Xizhong Cui, Charles Natanson
Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes.
Am J Respir Crit Care Med. 2002 Dec 1;166(11):1510-4. doi: 10.1164/rccm.200208-956OC. Epub 2002 Aug 28.
Abstract/Text
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Arthur P Wheeler, Gordon R Bernard, B Taylor Thompson, David Schoenfeld, Herbert P Wiedemann, Ben deBoisblanc, Alfred F Connors, R Duncan Hite, Andrea L Harabin
Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury.
N Engl J Med. 2006 May 25;354(21):2213-24. doi: 10.1056/NEJMoa061895. Epub 2006 May 21.
Abstract/Text
BACKGROUND: The balance between the benefits and the risks of pulmonary-artery catheters (PACs) has not been established.
METHODS: We evaluated the relationship of benefits and risks of PACs in 1000 patients with established acute lung injury in a randomized trial comparing hemodynamic management guided by a PAC with hemodynamic management guided by a central venous catheter (CVC) using an explicit management protocol. Mortality during the first 60 days before discharge home was the primary outcome.
RESULTS: The groups had similar baseline characteristics. The rates of death during the first 60 days before discharge home were similar in the PAC and CVC groups (27.4 percent and 26.3 percent, respectively; P=0.69; absolute difference, 1.1 percent; 95 percent confidence interval, -4.4 to 6.6 percent), as were the mean (+/-SE) numbers of both ventilator-free days (13.2+/-0.5 and 13.5+/-0.5; P=0.58) and days not spent in the intensive care unit (12.0+/-0.4 and 12.5+/-0.5; P=0.40) to day 28. PAC-guided therapy did not improve these measures for patients in shock at the time of enrollment. There were no significant differences between groups in lung or kidney function, rates of hypotension, ventilator settings, or use of dialysis or vasopressors. Approximately 90 percent of protocol instructions were followed in both groups, with a 1 percent rate of crossover from CVC- to PAC-guided therapy. Fluid balance was similar in the two groups, as was the proportion of instructions given for fluid and diuretics. Dobutamine use was uncommon. The PAC group had approximately twice as many catheter-related complications (predominantly arrhythmias).
CONCLUSIONS: PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury. (ClinicalTrials.gov number, NCT00281268.).
Copyright 2006 Massachusetts Medical Society.
