Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012 Sep 12;2012(9):CD006616.
doi: 10.1002/14651858.CD006616.pub2.

N-acetylcysteine for sepsis and systemic inflammatory response in adults

Tamas Szakmany  1 , Balázs Hauser, Peter Radermacher
Affiliations
Meta-Analysis

N-acetylcysteine for sepsis and systemic inflammatory response in adults

Tamas Szakmany et al. Cochrane Database Syst Rev. .

Abstract

Background: Death is common in systemic inflammatory response syndrome (SIRS) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial.

Objectives: We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis.

Search methods: We searched the following databases: Cochrane Central Register of Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue 12); MEDLINE (January 1950 to January 2012); EMBASE (January 1980 to January 2012); CINAHL (1982 to January 2012); the NHS Trusts Clinical Trials Register and Current Controlled Trials (www.controlled-trials.com); LILACS; KoreaMED; MEDCARIB; INDMED; PANTELEIMON; Ingenta; ISI Web of Knowledge and the National Trials Register to identify all relevant randomized controlled trials available for review.

Selection criteria: We included only randomized controlled trials (RCTs) in the meta-analysis.

Data collection and analysis: We independently performed study selection, quality assessment and data extraction. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic.

Main results: We included 41 fully published studies (2768 patients). Mortality was similar in the N-acetylcysteine group and the placebo group (RR 1.06, 95% CI 0.79 to 1.42; I(2) = 0%). Neither did N-acetylcysteine show any significant effect on length of stay, duration of mechanical ventilation or incidence of new organ failure. Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome, nor did late application that is after 24 hours of developing symptoms. Late application was associated with cardiovascular instability.

Authors' conclusions: Overall, this meta-analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis. At best, N-acetylcysteine is ineffective in reducing mortality and complications in this patient population. At worst, it can be harmful, especially when administered later than 24 hours after the onset of symptoms, by causing cardiovascular depression. Unless future RCTs provide evidence of treatment effect, clinicians should not routinely use intravenous N-acetylcysteine in SIRS or sepsis and academics should not promote its use.

PubMed Disclaimer

Conflict of interest statement

Dr Tamas Szakmany: received a Clinical Research Fellowship from the Welsh Assembly Government and numerous travel grants and speaker fees from Edwards Lifesciences, Philips, GSK and B Braun. None of these funds were in relation to the work published here. He conducted clinical trials using N‐acetylcysteine postoperatively (Szakmany 2003).

Dr Balázs Hauser: Grants pending; Young Investigator Award of the European Society of Intensive Care Medicine 2001: Experimental study with N‐acetylcysteine in porcine endotoxaemia; Roman Herzog Research fellowship of the Alexander von Humboldt Stiftung and the Gemeinnützige Hertie Stiftung 2003 to 2005: Experimental studies in porcine endotoxaemia. He has no competing financial interest regarding this manuscript

Prof Peter Radermacher: Prof Radermacher's institution received a research grant from the Deutsche Forschungsgemeinschaft (DFG project Ra 396/3‐2 entitled “ROS, iNOS, and HO‐1 in endotoxic shock”) that allowed a research fellow from his institution to perform a study (Vassilev 2004) on N‐acetylcysteine in porcine endotoxaemia.

Tamas Szakmany, Balázs Hauser and Peter Radermacher conducted animal studies using N‐acetylcysteine.

None of the authors have received financial support from pharmaceutical companies marketing N‐acetylcysteine.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study. +: yes, ‐: no, ?: unclear
3
3
Study flow diagram.
4
4
Funnel plot of comparison: 1 N‐acetylcysteine versus placebo, outcome: 1.1 30‐day all‐cause mortality.
5
5
Funnel plot of comparison: 2 N‐acetylcysteine versus placebo ‐ subgroup analysis, outcome: 2.1 Mortality (all reported time scales).
1.1
1.1. Analysis
Comparison 1 N‐acetylcysteine versus placebo ‐ primary outcome, Outcome 1 30‐day all‐cause Mortality.
2.1
2.1. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 1 Mortality (all reported timescales).
2.2
2.2. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 2 Mortality ‐ Overall risk of bias.
2.3
2.3. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 3 Mortality ‐ adequate sequence generation.
2.4
2.4. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 4 Mortality ‐ Allocation concealment.
2.5
2.5. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 5 Mortality ‐ Blinding.
2.6
2.6. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 6 Mortality ‐ short and long timescales.
2.7
2.7. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 7 Mortality ‐ sepsis or other critical illness (SIRS).
2.8
2.8. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 8 Mortality ‐ medical or surgical patients.
2.9
2.9. Analysis
Comparison 2 N‐acetylcysteine versus placebo ‐ sensitivity and subgroup analysis, Outcome 9 Mortality ‐ early or late administration.
3.1
3.1. Analysis
Comparison 3 N‐acetylcysteine versus placebo, Outcome 1 Duration of mechanical ventilation.
4.1
4.1. Analysis
Comparison 4 N‐acetylcysteine versus placebo, Outcome 1 Length of stay on the intensive care unit.
5.1
5.1. Analysis
Comparison 5 N‐acetylcysteine versus placebo, Outcome 1 Incidence of new organ failure.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD006616

References

References to studies included in this review

Andersen 2005 {published data only}
    1. Andersen LW, Thiis J, Kharazmi A, Rygg I. The role of N‐acetylcystein administration on the oxidative response of neutrophils during cardiopulmonary bypass. Perfusion 2005;10:21‐6. [DOI: 10.1177/026765919501000105] - DOI - PubMed
Bernard 1997 {published data only}
    1. Bernard GR, Wheeler AP, Arons MM, Morris PE, Paz HL, Russell JA, et al. A trial of antioxidants N‐acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest 1997;112:164‐72. [PUBMED: 9228372] - PubMed
Bromley 1995 {published data only}
    1. Bromley PN, Cottam SJ, Hilmi I, Tan KC, Heaton N, Ginsburg R, et al. Effects of intraoperative N‐acetylcysteine in orthotopic liver transplantation. British Journal of Anaesthesia 1995;75(3):352‐4. [PUBMED: 7547057] - PubMed
Burns 2005 {published data only}
    1. Burns KE, Chu MW, Novick RJ, Fox SA, Gallo K, Martin CM, et al. Perioperative N‐acetylcysteine to prevent renal dysfunction in high‐risk patients undergoing cabg surgery: a randomized controlled trial. JAMA 2005;294(3):342‐50. [PUBMED: 16030279] - PubMed
Burns 2010 {published data only}
    1. Burns KE, Priestap F, Martin C. N‐acetylcysteine in critically ill patients undergoing contrast‐enhanced computed tomography: a randomized trial. Clinical Nephrology 2010;74(4):323‐6. - PubMed
Charunwatthana 2009 {published data only}
    1. Charunwatthana P, Abul Faiz M, Ruangveerayut R, Maude RJ, Rahman MR, Roberts LJ 2nd, et al. N‐acetylcysteine as adjunctive treatment in severe malaria: a randomized, double‐blinded placebo‐controlled clinical trial. Critical Care Medicine 2009;37(2):516‐22. [DOI: 10.1097/CCM.0b013e3181958dfd] - DOI - PMC - PubMed
Csontos 2011 {published data only}
    1. Csontos C, Rezman B, Foldi V, Bogar L, Drenkovics L, Röth E, et al. Effect of N‐acetylcysteine treatment on oxidative stress and inflammation after severe burn. Burns 2011;38(3):428‐37. [DOI: ; PUBMED: 21978796] - PubMed
De Backer 1996 {published data only}
    1. Backer WA, Amsel B, Jorens PG, Bossaert L, Hiemstra PS, Noort P, et al. N‐acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid. Intensive Care Medicine 1996;22(9):900‐8. [PUBMED: 8905424] - PubMed
Domenighetti 1997 {published data only}
    1. Domenighetti G, Suter PM, Schaller MD, Ritz R, Perret C. Treatment with N‐acetylcysteine during acute respiratory distress syndrome: a randomized, double‐blind, placebo‐controlled clinical study. Journal of Critical Care 1997;12(4):177‐82. [PUBMED: 9459113 ] - PubMed
El‐Hamamsy 2007 {published data only}
    1. El‐Hamamsy I, Stevens LM, Carrier M, Pellerin M, Bouchard D, Demers P, et al. Effect of intravenous N‐acetylcysteine on outcomes after coronary artery bypass surgery: a randomized, double‐blind, placebo‐controlled clinical trial. The Journal of Thoracic and Cardiovascular Surgery 2007;133:7‐12. [PUBMED: 17198774] - PubMed
Emet 2004 {published data only}
    1. Emet S, Memis D, Pamukçu Z. The influence of N‐acetyl‐L‐cystein infusion on cytokine levels and gastric intramucosal pH during severe sepsis. Critical Care 2004;8(4):229‐30. [DOI: 10.1186/cc2866] - DOI - PMC - PubMed
Eren 2003 {published data only}
    1. Eren N, Cakir O, Oruc A, Kaya Z, Erdinc L. Effects of N‐acetylcysteine on pulmonary function in patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Perfusion 2003;18(6):345‐50. [DOI: 10.1191/0267659103pf696oa] - DOI - PubMed
Haase 2007 {published data only}
    1. Haase M, Haase‐Fielitz A, Bagshaw SM, Reade MC, Morgera S, Seevenayagam S, et al. Phase II, randomized, controlled trial of high‐dose N‐acetylcysteine in high‐risk cardiac surgery patients. Critical Care Medicine 2007;35(5):1324‐31. [DOI: 10.1097/01.CCM.0000261887.69976.12] - DOI - PubMed
Hilmi 2010 {published data only}
    1. Hilmi IA, Peng, Z, Planinsic RM, Damian D, Dai F, Tyurina YY, Kagan VE, Kellum JA. N‐acetylcysteine does not prevent hepatorenal ischaemia–reperfusion injury in patients undergoing orthotopic liver transplantation. Nephrology, Dialysis, Transplantation 2010;25:2328‐2333. [DOI: 10.1093/ndt/gfq077] - DOI - PubMed
Hynninen 2006 {published data only}
    1. Hynninen MS, Niemi TT, Pöyhiä R, Raininko EI, Salmenperä MT, Lepäntalo MJ, et al. N‐acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double‐blind, placebo‐controlled trial. Anesthesia and Analgesia 2006;102(6):1638‐45. [DOI: 10.1213/01.ANE.0000219590.79796.66] - DOI - PubMed
Jepsen 1992 {published data only}
    1. Jepsen S, Herlevsen P, Knudsen P, Bud MI, Klausen NO. Antioxidant treatment with N‐acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo‐controlled study. Critical Care Medicine 1992;20(7):918‐23. [PUBMED: 1617983] - PubMed
Keays 1991 {published data only}
    1. Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander GJ, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991;303(6809):1026‐9. [PUBMED: 1954453] - PMC - PubMed
Lee 2009 {published data only}
    1. Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, et al. Intravenous N‐acetylcysteine improves transplant‐free survival in early stage non‐acetaminophen acute liver failure. Gastroenterology 2009;137(3):856‐64. [DOI: 10.1053/j.gastro.2009.06.006] - DOI - PMC - PubMed
Macedo 2006 {published data only}
    1. Macedo E, Abdulkader R, Castro I, Sobrinho AC, Yu L, Vieira JM Jr. Lack of protection of N‐acetylcysteine (NAC) in acute renal failure related to elective aortic aneurysm repair‐a randomized controlled trial. Nephrology, Dialysis, Transplantation 2006;21(7):1863‐9. [DOI: 10.1093/ndt/gfl079; PUBMED: 16522657] - DOI - PubMed
Molnar 1999 {published data only}
    1. Molnár Z, Shearer E, Lowe D. N‐Acetylcysteine treatment to prevent the progression of multisystem organ failure: a prospective, randomized, placebo‐controlled study. Critical Care Medicine 1999;27(6):1100‐4. [PUBMED: 10397212] - PubMed
Moradi 2009 {published data only}
    1. Moradi M, Mojtahedzadeh M, Mandegari A, Soltan‐Sharifi MS, Najafi A, Khajavi MR, et al. The role of glutathione‐S‐transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N‐acetylcysteine. Respiratory Medicine 2009;103(3):434‐41. [PUBMED: 18993042] - PubMed
Orhan 2006 {published data only}
    1. Orhan G, Yapici N, Yuksel M, Sargin M, Senay S, Yalcin AS, et al. Effects of N‐acetylcysteine on myocardial ischemia–reperfusion injury in bypass surgery. Heart and Vessels 2006;21:42‐7. [PUBMED: 16440148] - PubMed
Ortolani 2000b {published data only}
    1. Ortolani O, Conti A, Gaudio AR, Masoni M, Novelli G. Protective effects of N‐acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome. Shock 2000;13(1):14‐8. [PUBMED: 10638663] - PubMed
Ozaydin 2008 {published data only}
    1. Ozaydin M, Peker O, Erdogan D, Kapan S, Turker Y, Varol E, et al. N‐acetylcysteine for prevention of postoperative atrial fibrillation: a prospective, randomized, placebo‐controlled pilot study. European Heart Journal 2008;29:625‐31. [DOI: 10.1093/eurheartj/ehn011; PUBMED: 18263874] - DOI - PubMed
Paterson 2003 {published data only}
    1. Paterson RL, Galley HF, Webster NR. The effect of N‐acetylcysteine on nuclear factor‐kappa B activation, interleukin‐6, interleukin‐8, and intercellular adhesion molecule‐1 expression in patients with sepsis. Critical Care Medicine 2003;31(11):2474‐8. [DOI: 10.1097/01.CCM.0000089945.69588.18; PUBMED: 14605526] - DOI - PubMed
Peake 1996 {published data only}
    1. Peake SL, Moran JL, Leppard PI. N‐acetyl‐L‐cysteine depresses cardiac performance in patients with septic shock. Critical Care Medicine 1996;24(8):1302‐10. [PUBMED: 8706483] - PubMed
Peker 2008 {published data only}
    1. Peker O, Peker T, Erdogan D, Ozaydin M, Kapan S, Sutcu R, et al. Effects of intravenous N‐acetylcysteine on periprocedural myocardial injury after on‐pump coronary artery by‐pass grafting. The Journal of Cardiovascular Surgery 2008;49(4):527‐31. [PUBMED: 18665117] - PubMed
Rank 2000 {published data only}
    1. Rank N, Michel C, Haertel C, Lenhart A, Welte M, Meier‐Hellmann A, et al. N‐acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double‐blind study. Critical Care Medicine 2000;28(12):3799‐807. [PUBMED: 11153617] - PubMed
Ristikankare 2006 {published data only}
    1. Ristikankare A, Kuitunen T, Kuitunen A, Uotila L, Vento A, Suojaranta‐Ylinen R, et al. Lack of renoprotective effect of i.v. N‐acetylcysteine in patients with chronic renal failure undergoing cardiac surgery. British Journal of Anaesthesia 2006;97(5):611‐6. [DOI: 10.1093/bja/ael224; PUBMED: 16914459] - DOI - PubMed
Sisillo 2008 {published data only}
    1. Sisillo E, Ceriani R, Bortone F, Juliano G, Salvi L, Veglia F, et al. N‐acetylcysteine for prevention of acute renal failure in patients with chronic renal insufficiency undergoing cardiac surgery: a prospective, randomized, clinical trial. Critical Care Medicine 2008;36(1):81‐6. [PUBMED: 18090169] - PubMed
Spapen 1998 {published data only}
    1. Spapen H, Zhang H, Demanet C, Vleminckx W, Vincent JL, Huyghens L. Does N‐acetyl‐L‐cysteine influence cytokine response during early human septic shock?. Chest 1998;113(6):1616‐24. [PUBMED: 9631802] - PubMed
Spapen 2005 {published data only}
    1. Spapen HD, Diltoer MW, Nguyen DN, Hendrickx I, Huyghens LP. Effects of N‐acetylcysteine on microalbuminuria and organ failure in acute severe sepsis: results of a pilot study. Chest 2005;127(4):1413‐9. [PUBMED: 15821223] - PubMed
Spies 1994 {published data only}
    1. Spies CD, Reinhart K, Witt I, Meier‐Hellmann A, Hannemann L, Bredle DL, et al. Influence of N‐acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double‐blind study. Critical Care Medicine 1994;22(11):1738‐46. [PUBMED: 7956276] - PubMed
Spies 1996 {published data only}
    1. Spies C, Giese C, Meier‐Hellmann A, Specht M, Hannemann L, Schaffartzik W, et al. [The effect of prophylactically administered n‐acetylcysteine on clinical indicators for tissue oxygenation during hyperoxic ventilation in cardiac risk patients] [Einflus der prophylaktischen gabe von N‐Azetylzystein auf klinische indikatoren der gewebeoxygenierung unter hyperoxie bei kardialen rizikopatienten]. Anaesthesist 1996;45(4):343‐50. [PUBMED: 8702052] - PubMed
Steib 1998 {published data only}
    1. Steib A, Freys G, Collin F, Launoy A, Mark G, Boudjema K. Does N‐acetylcysteine improve hemodynamics and graft function in liver transplantation?. Liver Transplantation and Surgery 1998;4(2):152‐7. [PUBMED: 9516568] - PubMed
Sucu 2004 {published data only}
    1. Sucu N, Cinel I, Unlu A, Aytacoglu B, Tamer L, Kocak Z, et al. N‐acetylcysteine for preventing pump‐induced oxidoinflammatory response during cardiopulmonary bypass. Surgery Today 2004;34:237‐42. [DOI: 10.1007/s00595-003-2699-8; PUBMED: 14999536] - DOI - PubMed
Suter 1994 {published data only}
    1. Suter PM, Domenighetti G, Schaller MD, Laverrière MC, Ritz R, Perret C. N‐acetylcysteine enhances recovery from acute lung injury in man. A randomized, double‐blind, placebo‐controlled clinical study. Chest 1994;105(1):190‐4. [PUBMED: 8275731 ] - PubMed
Szakmany 2003 {published data only}
    1. Szakmany T, Marton S, Molnar Z. Lack of effect of prophylactic N‐acetylcysteine on postoperative organ dysfunction following major abdominal tumour surgery: a randomized, placebo‐controlled, double‐blinded clinical trial. Anaesthesia and Intensive Care 2003;31(3):267‐71. [PUBMED: 12879670] - PubMed
Tossios 2003 {published data only}
    1. Tossios P, Bloch W, Huebner A, Raji MR, Dodos F, Klass O, et al. N‐acetylcysteine prevents reactive oxygen species‐mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double‐blind, placebo‐controlled clinical trial. The Journal of Thoracic and Cardiovascular Surgery 2003;126(5):1513‐20. [DOI: 10.1016/S0022-5223(03)00968-1; PUBMED: 14666027] - DOI - PubMed
Walsh 1998 {published data only}
    1. Walsh TS, Hopton P, Philips BJ, Mackenzie SJ, Lee A. The effect of N‐acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure. Hepatology 1998;27(5):1332‐40. [PUBMED: 9581688] - PubMed
Wijeysundera 2007 {published data only}
    1. Wijeysundera DN, Beattie WS, Rao V, Granton JT, Chan CT. N‐acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre‐existing moderate renal insufficiency. Canadian Journal of Anaesthesia 2007;54(11):872‐81. [PUBMED: 17975231] - PubMed

References to studies excluded from this review

Adabag 2008 {published data only}
    1. Adabag AS, Ishani A, Koneswaran S, Johnson DJ, Kelly RF, Ward HB, et al. Utility of N‐acetylcysteine to prevent acute kidney injury after cardiac surgery: a randomized controlled trial. American Heart Journal 2008;155(6):1143‐9. [DOI: 10.1016/j.ahj.2008.01.013; NCT00211653; PUBMED: 18513531] - DOI - PubMed
Agusti 1997 {published data only}
    1. Agustí AG, Togores B, Ibañez J, Raurich JM, Maimó A, Bergada J, et al. Effects of N‐acetylcysteine on tissue oxygenation in patients with multiple organ failure and evidence of tissue hypoxia. The European Respiratory Journal 1997;10(9):1962‐6. [DOI: 10.1183/09031936.97.10091962] - DOI - PubMed
Barr 2008 {published data only}
    1. Barr LF, Kolodner K. N‐acetylcysteine and fenoldopam protect the renal function of patients with chronic renal insufficiency undergoing cardiac surgery. Critical Care Medicine 2008;36(5):1427‐35. [PUBMED: 18434903] - PubMed
Csontos 2011b {published data only}
    1. Csontos C, Rezman B, Foldi V, Bogar L, Bognar Z, Drenkovics L, Röth E, Weber G, Lantos J. Effect of N‐acetylcysteine treatment on the expression of leukocyte surface markers after burn injury. Burns 2011;37(3):453‐64. [DOI: 10.1016/j.burns.2010.10.008; PUBMED: 21131132] - DOI - PubMed
De Rosa 2000 {published data only}
    1. Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, et al. N‐acetylcysteine replenishes glutathione in HIV infection. European Journal of Clinical Investigation 2000;30(10):915‐29. [PUBMED: 11029607] - PubMed
Devlin 1997 {published data only}
    1. Devlin J, Ellis AE, McPeake J, Heaton N, Wendon JA, Williams R. N‐acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction. Critical Care Medicine 1997;25(2):236‐42. [PUBMED: 9034257 ] - PubMed
Fischer 2005 {published data only}
    1. Fischer UM, Tossios P, Mehlhorn U. Renal protection by radical scavenging in cardiac surgery patients. Current Medical Research and Opinion 2005;21(8):1161‐4. [PUBMED: 16083524] - PubMed
Fraga 2011 {published data only}
    1. Fraga CM, Tomasi CD, Biff D, Topanotti MFL, Felisberto F, Vuolo F, et al. The effects of N‐acetylcysteine and deferoxamine on plasma cytokine and oxidative damage parameters in critically ill patients with prolonged hypotension: A randomized controlled trial. Journal of Clinical Pharmacology 2011;Nov 1:Epub ahead of print. [PUBMED: 22045831] - PubMed
Haase 2008 {published data only}
    1. Haase M, Haase‐Fielitz A, Ratnaike S, Reade MC, Bagshaw SM, Morgera S, et al. N‐Acetylcysteine does not artifactually lower plasma creatinine concentration. Nephrology, Dialysis, Transplantation 2008;23(5):1581‐7. [DOI: 10.1093/ndt/gfm818] - DOI - PubMed
Heller 2001 {published data only}
    1. Heller AR, Groth G, Heller SC, Breitkreutz R, Nebe T, Quintel M, et al. N‐acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients. Critical Care Medicine 2001;29(2):272‐6. [PUBMED: 11246305] - PubMed
Jepsen 1989 {published data only}
    1. Jepsen S, Klaerke A, Nielsen PH, Nielsen ST, Simonsen O. Systemic administration of N‐acetylcysteine has no effect on postoperative lung function following elective upper laparotomy in lung healthy patients. Acta Anaesthesiologica Scandinavica 1989;33(3):219‐22. [PUBMED: 2658458] - PubMed
Koksal 2008 {published data only}
    1. Köksal H, Rahman A, Burma O, Halifeoglu I, Bayar MK. The effects of low dose N‐acetylcysteine (NAC) as an adjunct to cardioplegia in coronary artery bypass surgery. Anadolu Kardiyoloji Dergisi: AKD = The Anatolian Journal of Cardiology 2008;8(6):437‐43. [PUBMED: 19103540] - PubMed
Komisarof 2007 {published data only}
    1. Komisarof JA, Gilkey GM, Peters DM, Koudelka CW, Meyer MM, Smith SM. N‐acetylcysteine for patients with prolonged hypotension as prophylaxis for acute renal failure (NEPHRON). Critical Care Medicine 2007;35(2):435‐41. [DOI: 10.1097/01.CCM.0000253816.83011.DB] - DOI - PubMed
Koramaz 2006 {published data only}
    1. Koramaz I, Pulathan Z, Usta S, Karahan SC, Alver A, Yaris E, et al. Cardioprotective effect of cold‐blood cardioplegia enriched with N‐acetylcysteine during coronary artery bypass grafting. Annals of Thoracic Surgery 2006;81(2):613‐8. [DOI: 10.1016/j.athoracsur.2005.08.013] - DOI - PubMed
Kurian 2010 {published data only}
    1. Kurian GA, Paddikkala J. N‐acetylcysteine and magnesium improve biochemical abnormalities associated with myocardial ischaemic reperfusion in South Indian patients undergoing coronary artery bypass grafting: a comparative analysis. Singapore Medical Journal 2010;51(5):381‐8. - PubMed
Laurent 1996 {published data only}
    1. Laurent T, Markert M, Feihl F, Schaller MD, Perret C. Oxidant‐antioxidant balance in granulocytes during ARDS. Effect of N‐acetylcysteine. Chest 1996;106(1):163‐6. [PUBMED: 8549180] - PubMed
Lawlor 2007 {published data only}
    1. Lawlor DK, Moist L, DeRose G, Harris KA, Lovell MB, Kribs SW, et al. Prevention of contrast‐induced nephropathy in vascular surgery patients. Annals of Vascular Surgery 2007;21(5):593‐7. [PUBMED: 17823041] - PubMed
Milewski 2006 {published data only}
    1. Milewski J, Rydzewska G, Degowska M, Kierzkiewicz M, Rydzewski A. N‐acetylcysteine does not prevent post‐endoscopic retrograde cholangiopancreatography hyperamylasemia and acute pancreatitis. World Journal of Gastroenterology : WJG 2006;12(23):3751‐5. [PUBMED: 16773694] - PMC - PubMed
Molnar 1998 {published data only}
    1. Molnar Z, MacKinnon KL, Shearer E, Lowe D, Watson ID. The effect of N‐acetylcysteine on total serum anti‐oxidant potential and urinary albumin excretion in critically ill patients. Intensive Care Medicine 1998;24(3):230‐5. [PUBMED: 9565804] - PubMed
Molnar 2003 {published data only}
    1. Molnar Z, Szakmany T, Koszegi T. Prophylactic N‐acetylcysteine decreases serum CRP but not PCT levels and microalbuminuria following major abdominal surgery. A prospective, randomised, double‐blinded, placebo‐controlled clinical trial. Intensive Care Medicine 2003;29(5):749‐55. [PUBMED: 12682719] - PubMed
Najafi 2009 {published data only}
    1. Najafi A, MojtahedzadehM, Mahmoodpoor A, Aghamohammadi M, Ahmadi A, Nahreini S, et al. Effect of N‐acetylcysteine on microalbuminuria in patients with acute respiratory distress syndrome. Archives of Medical Science 2009;5(3):408‐14.
Niemi 2006 {published data only}
    1. Niemi TT, Munsterhjelm E, Pöyhiä R, Hynninen MS, Salmenperä MT. The effect of N‐acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm. Blood Coagulation & Fibrinolysis 2006;17(1):29‐34. [PUBMED: 16607076 ] - PubMed
Ortolani 2000a {published data only}
    1. Ortolani O, Conti A, Gaudio AR, Moraldi E, Cantini Q, Novelli G. The effect of glutathione and N‐acetylcysteine on lipoperoxidative damage in patients with early septic shock. American Journal of Respiratory Critical Care Medicine 2000;161(6):1907‐11. [PUBMED: 10852765] - PubMed
Reinhart 1995 {published data only}
    1. Reinhart K, Spies CD, Meier‐Hellmann A, Bredle DL, Hannemann L, Specht M, et al. N‐acetylcysteine preserves oxygen consumption and gastric mucosal pH during hyperoxic ventilation. American Journal of Respiratory and Critical Care Medicine 1995;151:773‐9. [PUBMED: 7881669] - PubMed
Sahib 2010 {published data only}
    1. Sahib AS, Al‐Jawad FH, Alkaisy AA. Effect of antioxidants on the incidence of wound infection in burn patients. Annals of Burns and Fire Disasters 2010;23(4):199‐205. [PUBMED: 21991225] - PMC - PubMed
Saricaoglu 2005 {published data only}
    1. Saricaoglu F, Dal D, Salman AE, Atay OA, Doral MN, Salman MA, et al. Effect of low‐dose N‐acetyl‐cysteine infusion on tourniquet‐induced ischaemia‐reperfusion injury in arthroscopic knee surgery. Acta Anaesthesiologica Scandinavica 2005;49(6):847‐51. [PUBMED: 15954970] - PubMed
Siriwardena 2007 {published data only}
    1. Siriwardena AK, Mason JM, Balachandra S, Bagul A, Galloway S, Formela L, et al. Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis. Gut 2007;56(10):1439‐44. [PUBMED: 17356040] - PMC - PubMed
Soltan‐Sharifi 2007 {published data only}
    1. Soltan‐Sharifi MS, Mojtahedzadeh M, Najafi A, Reza Khajavi M, Reza Rouini M, Moradi M, et al. Improvement by N‐acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti‐oxidant power: evidence for underlying toxicological mechanisms. Human & Experimental Toxicology 2007;26(9):697‐703. [PUBMED: 17984140] - PubMed
Spies 1993 {published data only}
    1. Spies C, Reinhart K, Witt I, Walensky C, Hannemann L, Specht M, et al. Influence of N‐acetylcysteine on O2 consumption and gastric intramucosal pH in septic patients. Critical Care Medicine 1993;21 Suppl 4:183.
Szakmany 2002 {published data only}
    1. Szakmány T, Tóth I, Márton S, Molnár Z. [Effect of prophylactic N‐acetylcysteine on postoperative organ dysfunction and inflammatory markers after major abdominal surgery for cancer. Prospective, randomized, double‐blind, placebo‐controlled clinical trial] [Profilaktikus N‐acetylcysteine kezeles hatasa a posztoperativ szervdiszfunkciora es gyulladasos markerek szintjere kiterjesztett hasi tumorsebeszeti beavatkozasok utan. Prospektiv, randomizalt, kettos‐vak, placebo kontrolalt klinikai tanulmany]. Magyar Sebészet 2002;55(6):369‐74. [PUBMED: 12616822 ] - PubMed
Wijeysundera 2009 {published data only}
    1. Wijeysundera DN, Karkouti K, Rao V, Granton JT, Chan CT, Raban R, et al. N‐acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Critical Care Medicine 2009;37(6):1929‐34. [PUBMED: 19384218] - PubMed
Zingg 2007 {published data only}
    1. Zingg U, Hofer CK, Seifert B, Metzger U, Zollinger A. High dose N‐acetylcysteine to prevent pulmonary complications in partial or total transthoracic esophagectomy: results of a prospective observational study. Diseases of the Esophagus 2007;20(5):399‐405. [PUBMED: 17760653] - PubMed

Additional references

Adabag 2009
    1. Adabag AS, Ishani A, Bloomfield HE, Ngo AK, Wilt TJ. Efficacy of N‐acetylcysteine in preventing renal injury after heart surgery: a systematic review of randomized trials. European Heart Journal 2009;30(15):1910‐7. [PUBMED: 19282300] - PMC - PubMed
Aruoma 1989
    1. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N‐acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radical Biology & Medicine 1989;6:593‐7. [MEDLINE: ] - PubMed
Baker 2009
    1. Baker WL, Anglade MW, Baker EL, White CM, Kluger J, Coleman CI. Use of N‐acetylcysteine to reduce post‐cardiothoracic surgery complications: a meta‐analysis. European Journal of Cardiothoracic Surgery 2009;35(3):521‐7. [PUBMED: 19147369] - PubMed
Bone 1992
    1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644‐55. [MEDLINE: ] - PubMed
Cowley 1996
    1. Cowley HC, Bacon PJ, Goode HF, Webster NR, Jones JG, Menon DK. Plasma antioxidant potential in severe sepsis: a comparison of survivors and nonsurvivors. Critical Care Medicine 1996;24:1179‐83. [MEDLINE: ] - PubMed
Crimi 2006
    1. Crimi E, Sica V, Williams‐Ignarro S, Zhang H, Slutsky AS, Ignarro LJ, Napoli C. The role of oxidative stress in adult critical care. Free Radical Biology & Medicine 2006;40(3):398‐406. [DOI: 10.1016/j.freeradbiomed.2005.10.054; PUBMED: 16443154] - DOI - PubMed
Cross 2006
    1. Cross CE, Asbeck BS, Halliwell B. More antioxidants in sepsis: still paved with uncertainties. Critical Care Medicine 2006;34(2):569‐571. [PUBMED: 16424756] - PubMed
Egger 1997
    1. Egger M, Davey‐Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphic test. BMJ 1997;315:629‐34. [MEDLINE: ] - PMC - PubMed
Engel 2007
    1. Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, Gruendling M, Huhle G, Jaschinski U, John S, Mayer K, Oppert M, Olthoff D, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Bogatsch H, Hartog C, Loeffler M, Reinhart K. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Medicine 2007;33(4):606‐18. [DOI: 10.1007/s00134-006-0517-7; PUBMED: 17323051] - DOI - PubMed
Goetzsche 2000
    1. Gotzsche PC. Why we need a broad perspective on meta‐analysis.It may be crucially important for patients. BMJ 2000;321(7261):585‐6. [PUBMED: 10977820] - PMC - PubMed
Goode 1995
    1. Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Critical Care Medicine 1995;23:646‐51. [MEDLINE: ] - PubMed
Harman 1984
    1. Harman LS, Mottley C, Mason RP. Free radical metabolites of L‐cysteine oxidation. The Journal of Biological Chemistry 1984;259:5606‐11. [PUBMED: 6325443 ] - PubMed
Henderson 1994
    1. Henderson A, Hayes P. Acetylcysteine as a cytoprotective antioxidant in patients with severe sepsis: potential new use for an old drug. The Annals of Pharmacotherapy 1994;28:1086‐8. [MEDLINE: ] - PubMed
Higgins 2002
    1. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Statist Med 2002;21:1539‐58. [DOI: 10.1002/sim.1186] - DOI - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. Available from http://www.cochrane‐handbook.org: The Cochrane Collaboration, 2011.
Ho 2009
    1. Ho KM, Morgan DJ. Meta‐analysis of N‐acetylcysteine to prevent acute renal failure after major surgery. American Journal of Kidney Diseases 2009;53(1):33‐40. [DOI: 10.1053/j.ajkd.2008.05.019; PUBMED: 18649982] - DOI - PubMed
Hollis 1999
    1. Hollis S, Campbell F. What is meant by intention to treat analysis? Survey of published randomised controlled trials. BMJ 1999;319(7211):670‐4. [PUBMED: 10480822] - PMC - PubMed
Hozo 2005
    1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology 2005;5:13‐23. [DOI: 10.1186/1471-2288-5-13] - DOI - PMC - PubMed
Hsu 2004
    1. Hsu BG, Yang FL, Lee RP, Peng TC, Harn HJ, Chen HI. N‐acetylcysteine ameliorates lipopolysaccharide‐induced organ damage in conscious rats. Journal of Biomedical Science 2004;11:152‐62. [MEDLINE: ] - PubMed
Kiefer 2000
    1. Kiefer P, Vogt J, Radermacher P. From mucolytic to antioxidant and liver protection: new aspects in the intensive care unit career of N‐acetylcysteine. Critical Care Medicine 2000;28:3935‐6. [MEDLINE: ] - PubMed
Koch 1996
    1. Koch T, Heller S, Heissler S, Breil I, Schiefer HG, Ackern K, et al. Effects of N‐acetylcysteine on bacterial clearance. European Journal of Clinical Investigation 1996;26:884‐92. [MEDLINE: ] - PubMed
Magder 2006
    1. Magder S. Reactive oxygen species: toxic molecules or spark of life?. Critical Care 2006;10(1):208. [DOI: 10.1186/cc3992; PUBMED: 16469133] - DOI - PMC - PubMed
Molnar 2008
    1. Molnár Z. N‐acetylcysteine as the magic bullet: too good to be true. Critical Care Medicine 2008;36(2):645‐6. [PUBMED: 18216629] - PubMed
Naughton 2008
    1. Naughton F, Wijeysundera D, Karkouti K, Tait G, Beattie WS. N‐acetylcysteine to reduce renal failure after cardiac surgery: a systematic review and meta‐analysis. Canadian Journal of Anaesthesia 2008;55(12):827‐35. [PUBMED: 19050086] - PubMed
Nigwekar 2009
    1. Nigwekar SU, Kandula P. N‐acetylcysteine in cardiovascular‐surgery‐associated renal failure: a meta‐analysis. Annals of Thoracic Surgery 2009;87(1):139‐47. [PUBMED: 19101287] - PubMed
Ogilvie 1991
    1. Ogilvie AC, Groeneveld AB, Straub JP, Thijs LG. Plasma lipid peroxides and antioxidants in human septic shock. Intensive Care Medicine 1991;17:40‐4. [MEDLINE: ] - PubMed
Oxman 1992
    1. Oxman AD, Guyatt GH. A consumer's guide to subgroup analyses. Annals of Internal Medicine 1992;116:78‐84. [MEDLINE: ] - PubMed
Peristeris 1992
    1. Peristeris P, Clark BD, Gatti S, Faggioni R, Mantovani A, Mengozzi M, et al. N‐acetylcysteine and glutathione as inhibitors of tumor necrosis factor production. Cellular Immunology 1992;140:390‐9. [MEDLINE: ] - PubMed
Pinsky 2003
    1. Pinsky MR. Antioxidant therapy for severe sepsis: promise and perspective. Critical Care Medicine 2003;31:2697‐8. [MEDLINE: ] - PubMed
Prescott 1989
    1. Prescott LF, Donovan JW, Jarvie DR, Proudfoot AT. The disposition and kinetics of intravenous N‐acetylcysteine in patients with paracetamol overdosage.. European Journal of Clinical Pharmacology 1989;37(5):501‐6. [PUBMED: 2598989] - PubMed
Repine 1992
    1. Repine JE. Scientific perspectives on adult respiratory distress syndrome. Lancet 1992;339:466‐9. [MEDLINE: ] - PubMed
RevMan 5.1 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Rücker 2008
    1. Rücker G, Schwarzer G, Carpenter J. Arcsine test for publication bias in meta‐analyses with binary outcomes. Statistics in Medicine 2008;27(5):746‐63. [PUBMED: 17592831] - PubMed
Schmidt 1997
    1. Schmidt H, Schmidt W, Müller T, Böhrer H, Gebhard MM, Martin E. N‐acetylcysteine attenuates endotoxin‐induced leukocyte‐endothelial cell adhesion and macromolecular leakage in vivo. Critical Care Medicine 1997;25:558‐63. [MEDLINE: ] - PubMed
Schmidt 1998
    1. Schmidt W, Walther A, Gebhard MM, Martin E, Schmidt H. Influence of N‐acetylcysteine treatment on endotoxin‐induced microcirculatory disturbances. Intensive Care Medicine 1998;24(9):967‐72. - PubMed
Spapen 2004
    1. Spapen H. N‐acetylcysteine in clinical sepsis: a difficult marriage. Critical Care 2004;8(4):229‐30. - PMC - PubMed
Vassilev 2004
    1. Vassilev D, Hauser B, Bracht H, Iványi Z, Schoaff M, Asfar P, et al. Systemic, pulmonary, and hepatosplanchnic effects of N‐acetylcysteine during long‐term porcine endotoxemia. Critical Care Medicine 2004;32(2):525‐32. [PUBMED: 14758174] - PubMed
Yang 2009
    1. Yang R, Miki K, He X, Killeen ME, Fink MP. Prolonged treatment with N‐acetylcystine delays liver recovery from acetaminophen hepatotoxicity. Critical Care 2009;13(2):R55. [DOI: 10.1186/cc7782; PUBMED: 19358737] - DOI - PMC - PubMed
Zhang 1994a
    1. Zhang H, Spapen H, Benlabed M, Nguyen DN, Buurman WA, Vincent JL. Pentoxifylline improves the tissue oxygen extraction capabilities during endotoxic shock. Shock 1994;2:90‐7. [MEDLINE: ] - PubMed
Zhang 1994b
    1. Zhang H, Spapen H, Nguyen DN, Benlabed M, Buurman WA, Vincent JL. Protective effects of N‐acetyl‐L‐cysteine in endotoxemia. The American Journal of Physiology 1994;266:H1746‐54. [MEDLINE: ] - PubMed

Publication types

MeSH terms