nach oben

Intensive Care Medicine

Erschienen in:

16.10.2020 | Narrative Review

Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality: a hypothesis generating review

verfasst von: Stijn Blot

Erschienen in: Intensive Care Medicine | Ausgabe 1/2021

Einloggen, um Zugang zu erhalten

Abstract

Meta-analyses and several large cohort studies have demonstrated that antiseptic mouthwashes are associated with mortality in hospitalized patients. A clear pathogenic mechanism is lacking, leading to controversy and a reluctance to abandon or limit the use of antiseptic mouthwashes. Here, we generate the hypothesis that a disturbance in nitric oxide homeostasis by antiseptic mouthwashes may be responsible for the observed increase in mortality risk. Nitric oxide is essential in multiple physiological processes, and a reduction in nitric oxide bioavailability is associated with the occurrence or worsening of pathologies, such as atherosclerosis, diabetes, and sepsis. Oral facultative anaerobic bacteria are essential for the enterosalivary nitrate–nitrite–nitric oxide pathway due to their capacity to reduce nitrate to nitrite. Nitrate originates from dietary sources or from the active uptake by salivary glands of circulating nitrate, which is then excreted in the saliva. Because antiseptic mouthwashes eradicate the oral bacterial flora, this nitric oxide-generating pathway is abolished, which may result in nitric oxide-deficient conditions potentially leading to life-threatening complications such as ischaemic heart events or sepsis.

Seymour GJ (2007) You cannot have good general health without good oral health. N Z Dent J 103:26–27PubMed

Chadwick B, White D, Lader D, Pitts N (2011) Preventive behaviour and risks to oral health – a report from the Adult Dental Health Survey 2009. NHS Information Centre for Health and Social Care, London

Preshaw PM (2018) Mouthwash use and risk of diabetes. Br Dent J 225:923–926. https://doi.org/10.1038/sj.bdj.2018.1020CrossRefPubMed

Seymour GJ, Ford PJ, Cullinan MP et al (2007) Relationship between periodontal infections and systemic disease. Clin Microbiol Infect 13(Suppl 4):3–10. https://doi.org/10.1111/j.1469-0691.2007.01798.xCrossRefPubMed

Maeda K, Mori N (2020) Poor oral health and mortality in geriatric patients admitted to an acute hospital: an observational study. BMC Geriatr 20:26–27. https://doi.org/10.1186/s12877-020-1429-zCrossRefPubMedPubMedCentral

Hollaar V, van der Maarel-Wierink C, van der Putten G-J et al (2015) Effect of daily application of a 0.05% chlorhexidine solution on the incidence of (aspiration) pneumonia in care home residents: design of a multicentre cluster randomised controlled clinical trial. BMJ Open 5:e007889. https://doi.org/10.1136/bmjopen-2015-007889CrossRefPubMedPubMedCentral

Sharif-Abdullah SSB, Chong MC, Surindar-Kaur SS et al (2016) The effect of chlorhexidine in reducing oral colonisation in geriatric patients: a randomised controlled trial. Singap Med J 57:262–266. https://doi.org/10.11622/smedj.2016091CrossRef

Juthani-Mehta M, Van Ness PH, McGloin J et al (2015) A cluster-randomized controlled trial of a multicomponent intervention protocol for pneumonia prevention among nursing home elders. Clin Infect Dis 60:849–857. https://doi.org/10.1093/cid/ciu935CrossRefPubMed

De Siena F, Francetti L, Corbella S et al (2013) Topical application of 1% chlorhexidine gel versus 0.2% mouthwash in the treatment of peri-implant mucositis. An observational study. Int J Dent Hyg 11:41–47. https://doi.org/10.1111/idh.12002CrossRefPubMed

10.

da Costa LFNP, Amaral CDSF, Barbirato DDS et al (2017) Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: A meta-analysis. J Am Dent Assoc 148:308–318. https://doi.org/10.1016/j.adaj.2017.01.021CrossRefPubMed

11.

Genovesi A, Barone A, Toti P, Covani U (2017) The efficacy of 0.12% chlorhexidine versus 0.12% chlorhexidine plus hyaluronic acid mouthwash on healing of submerged single implant insertion areas: a short-term randomized controlled clinical trial. Int J Dent Hyg 15:65–72. https://doi.org/10.1111/idh.12158CrossRefPubMed

12.

Labeau SO, Van de Vyver K, Brusselaers N et al (2011) Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis 11:845–854. https://doi.org/10.1016/S1473-3099(11)70127-XCrossRefPubMed

13.

American Thoracic Society, Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416. https://doi.org/10.1164/rccm.200405-644STCrossRef

14.

Healthcare Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention (U.S.) (2004) Guidelines for preventing health-care-associated pneumonia, 2003 recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee. Respir Care 49:926–939

15.

Institute for Healthcare Improvement (2012) How-to guide: prevent ventilator-associated pneumonia. Institute for Healthcare Improvement, Cambridge

16.

Klompas M, Speck K, Howell MD et al (2014) Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis. JAMA Intern Med 174:751–761. https://doi.org/10.1001/jamainternmed.2014.359CrossRefPubMed

17.

Price R, MacLennan G, Glen J, Collaboration SuDDICU (2014) Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ 348:g2197–g2197. https://doi.org/10.1136/bmj.g2197CrossRefPubMedPubMedCentral

18.

Klompas M, Li L, Kleinman K et al (2016) Associations between ventilator bundle components and outcomes. JAMA Intern Med 176:1277–1283. https://doi.org/10.1001/jamainternmed.2016.2427CrossRefPubMed

19.

Torres A, Niederman MS, Chastre J et al (2017) International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 50:1700582. https://doi.org/10.1183/13993003.00582-2017CrossRefPubMed

20.

Deschepper M, Waegeman W, Eeckloo K et al (2018) Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study. Intensive Care Med 44:1017–1026. https://doi.org/10.1007/s00134-018-5171-3CrossRefPubMedPubMedCentral

21.

Parreco J, Soe-Lin H, Byerly S et al (2020) Multi-center outcomes of chlorhexidine oral decontamination in intensive care units. Surg Infect (Larchmt). https://doi.org/10.1089/sur.2019.172CrossRef

22.

Okano M, Nomura M, Hata S et al (1989) Anaphylactic symptoms due to chlorhexidine gluconate. Arch Dermatol 125:50–52CrossRefPubMed

23.

Jee R, Nel L, Gnanakumaran G et al (2009) Four cases of anaphylaxis to chlorhexidine impregnated central venous catheters: a case cluster or the tip of the iceberg? Br J Anaesth 103:614–615. https://doi.org/10.1093/bja/aep248CrossRefPubMed

24.

Stephens R, Mythen M, Kallis P et al (2001) Two episodes of life-threatening anaphylaxis in the same patient to a chlorhexidine-sulphadiazine-coated central venous catheter. Br J Anaesth 87:306–308CrossRefPubMed

25.

Parkes AW, Harper N, Herwadkar A, Pumphrey R (2009) Anaphylaxis to the chlorhexidine component of Instillagel: a case series. Br J Anaesth 102:65–68. https://doi.org/10.1093/bja/aen324CrossRefPubMed

26.

Plantinga NL, Wittekamp BHJ, Leleu K et al (2016) Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. Intensive Care Med 42:620–621. https://doi.org/10.1007/s00134-016-4217-7CrossRefPubMedPubMedCentral

27.

Bellissimo-Rodrigues WT, Menegueti MG, de Macedo LD et al (2019) Oral mucositis as a pathway for fatal outcome among critically ill patients exposed to chlorhexidine: post hoc analysis of a randomized clinical trial. Crit Care 23:382–383. https://doi.org/10.1186/s13054-019-2664-6CrossRefPubMedPubMedCentral

28.

Xue Y, Zhang S, Yang Y et al (2011) Acute pulmonary toxic effects of chlorhexidine (CHX) following an intratracheal instillation in rats. Hum Exp Toxicol 30:1795–1803. https://doi.org/10.1177/0960327111400104CrossRefPubMed

29.

Hirata K, Kurokawa A (2002) Chlorhexidine gluconate ingestion resulting in fatal respiratory distress syndrome. Vet Hum Toxicol 44:89–91PubMed

30.

Ricard JD, Lisboa T (2018) Caution for chlorhexidine gluconate use for oral care: insufficient data. Intensive Care Med 11:845–853. https://doi.org/10.1007/s00134-018-5217-6CrossRef

31.

Bouadma L, Karpanen T, Elliott T (2018) Chlorhexidine use in adult patients on ICU. Intensive Care Med 30:827–833. https://doi.org/10.1007/s00134-018-5137-5CrossRef

32.

Bouadma L, Klompas M (2018) Oral care with chlorhexidine: beware! Intensive Care Med 35:915–923. https://doi.org/10.1007/s00134-018-5221-xCrossRef

33.

Dale CM, Rose L, Carbone S et al (2019) Protocol for a multi-centered, stepped wedge, cluster randomized controlled trial of the de-adoption of oral chlorhexidine prophylaxis and implementation of an oral care bundle for mechanically ventilated critically ill patients: the CHORAL study. Trials 20:603–608. https://doi.org/10.1186/s13063-019-3673-0CrossRefPubMedPubMedCentral

34.

Klarin B, Adolfsson A, Torstensson A, Larsson A (2018) Can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? A multicentre, prospective, randomised controlled open trial. Crit Care 22:272–310. https://doi.org/10.1186/s13054-018-2209-4CrossRefPubMedPubMedCentral

35.

Hamilton LA, Behal ML (2020) Altering routine intensive care unit practices to support commensalism. Nutr Clin Pract 35:433–441. https://doi.org/10.1002/ncp.10484CrossRefPubMed

36.

Hezel MP, Weitzberg E (2015) The oral microbiome and nitric oxide homoeostasis. Oral Dis 21:7–16. https://doi.org/10.1111/odi.12157CrossRefPubMed

37.

Duncan C, Dougall H, Johnston P et al (1995) Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med 1:546–551. https://doi.org/10.1038/nm0695-546CrossRefPubMed

38.

Bryan NS, Fernandez BO, Bauer SM et al (2005) Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 1:290–297. https://doi.org/10.1038/nchembio734CrossRefPubMed

39.

Bryan NS (2006) Nitrite in nitric oxide biology: cause or consequence? A systems-based review. Free Radic Biol Med 41:691–701. https://doi.org/10.1016/j.freeradbiomed.2006.05.019CrossRefPubMed

40.

Lundberg JO, Weitzberg E, Gladwin MT (2008) The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7:156–167. https://doi.org/10.1038/nrd2466CrossRefPubMed

41.

Lundberg JO, Weitzberg E, Cole JA, Benjamin N (2004) Nitrate, bacteria and human health. Nat Rev Microbiol 2:593–602. https://doi.org/10.1038/nrmicro929CrossRefPubMed

42.

Carnovale CE, Ronco MT (2012) Role of nitric oxide in liver regeneration. Ann Hepatol 11:636–647CrossRefPubMed

43.

Hollenberg SM, Cinel I (2009) Bench-to-bedside review: nitric oxide in critical illness–update 2008. Crit Care 13:218–219. https://doi.org/10.1186/cc7706CrossRefPubMedPubMedCentral

44.

Fang FC (2004) Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol 2:820–832. https://doi.org/10.1038/nrmicro1004CrossRefPubMed

45.

Hall DT, Ma JF, Marco SD, Gallouzi I-E (2011) Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY) 3:702–715. https://doi.org/10.18632/aging.100358CrossRef

46.

Aksu U, Demirci C, Ince C (2011) The pathogenesis of acute kidney injury and the toxic triangle of oxygen, reactive oxygen species and nitric oxide. Contrib Nephrol 174:119–128. https://doi.org/10.1159/000329249CrossRefPubMed

47.

Boehm M, Novoyatleva T, Kojonazarov B et al (2019) Nitric oxide synthase 2 induction promotes right ventricular fibrosis. Am J Respir Cell Mol Biol 60:346–356. https://doi.org/10.1165/rcmb.2018-0069OCCrossRefPubMed

48.

Vincent JL, Zhang H, Szabo C, Preiser JC (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161:1781–1785. https://doi.org/10.1164/ajrccm.161.6.9812004CrossRefPubMed

49.

Rosen H, Crowley JR, Heinecke JW (2002) Human neutrophils use the myeloperoxidase-hydrogen peroxide-chloride system to chlorinate but not nitrate bacterial proteins during phagocytosis. J Biol Chem 277:30463–30468. https://doi.org/10.1074/jbc.M202331200CrossRefPubMed

50.

Goya T, Morisaki T, Torisu M (1994) Immunologic assessment of host defense impairment in patients with septic multiple organ failure: relationship between complement activation and changes in neutrophil function. Surgery 115:145–155PubMed

51.

Linares E, Giorgio S, Mortara RA et al (2001) Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation. Free Radic Biol Med 30:1234–1242. https://doi.org/10.1016/s0891-5849(01)00516-0CrossRefPubMed

52.

Bryan NS, Calvert JW, Elrod JW et al (2007) Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Proc Natl Acad Sci USA 104:19144–19149. https://doi.org/10.1073/pnas.0706579104CrossRefPubMedPubMedCentral

53.

Bryan NS, Ivy JL (2015) Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients. Nutr Res 35:643–654. https://doi.org/10.1016/j.nutres.2015.06.001CrossRefPubMed

54.

Petersson J, Carlström M, Schreiber O et al (2009) Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Free Radic Biol Med 46:1068–1075. https://doi.org/10.1016/j.freeradbiomed.2009.01.011CrossRefPubMed

55.

Larsen FJ, Ekblom B, Sahlin K et al (2006) Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 355:2792–2793. https://doi.org/10.1056/NEJMc062800CrossRefPubMed

56.

Webb A, Bond R, McLean P et al (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA 101:13683–13688. https://doi.org/10.1073/pnas.0402927101CrossRefPubMedPubMedCentral

57.

Duranski MR, Greer JJM, Dejam A et al (2005) Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115:1232–1240. https://doi.org/10.1172/JCI22493CrossRefPubMedPubMedCentral

58.

Bryan NS, Tribble G, Angelov N (2017) Oral microbiome and nitric oxide: the missing link in the management of blood pressure. Curr Hypertens Rep 19:33. https://doi.org/10.1007/s11906-017-0725-2CrossRefPubMed

59.

Hendgen-Cotta UB, Luedike P, Totzeck M et al (2012) Dietary nitrate supplementation improves revascularization in chronic ischemia. Circulation 126:1983–1992. https://doi.org/10.1161/CIRCULATIONAHA.112.112912CrossRefPubMed

60.

Gorabi AM, Kiaie N, Hajighasemi S et al (2019) Statin-induced nitric oxide signaling: mechanisms and therapeutic implications. J Clin Med 8:2051. https://doi.org/10.3390/jcm8122051CrossRefPubMedCentral

61.

Hou H-T, Wang J, Zhang X et al (2018) Endothelial nitric oxide synthase enhancer AVE3085 reverses endothelial dysfunction induced by homocysteine in human internal mammary arteries. Nitric Oxide 81:21–27. https://doi.org/10.1016/j.niox.2018.10.001CrossRefPubMed

62.

Björne HH, Petersson J, Phillipson M et al (2004) Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J Clin Invest 113:106–114. https://doi.org/10.1172/JCI19019CrossRefPubMedCentral

63.

Dougall HT, Smith L, Duncan C, Benjamin N (1995) The effect of amoxycillin on salivary nitrite concentrations: an important mechanism of adverse reactions? Br J Clin Pharmacol 39:460–462. https://doi.org/10.1111/j.1365-2125.1995.tb04479.xCrossRefPubMedPubMedCentral

64.

Shapiro KB, Hotchkiss JH, Roe DA (1991) Quantitative relationship between oral nitrate-reducing activity and the endogenous formation of N-nitrosoamino acids in humans. Food Chem Toxicol 29:751–755. https://doi.org/10.1016/0278-6915(91)90183-8CrossRefPubMed

65.

Kapil V, Haydar SMA, Pearl V et al (2013) Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med 55:93–100. https://doi.org/10.1016/j.freeradbiomed.2012.11.013CrossRefPubMedPubMedCentral

66.

Bondonno CP, Liu AH, Croft KD et al (2015) Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women. Am J Hypertens 28:572–575. https://doi.org/10.1093/ajh/hpu192CrossRefPubMed

67.

Sundqvist ML, Lundberg JO, Weitzberg E (2016) Effects of antiseptic mouthwash on resting metabolic rate: a randomized, double-blind, crossover study. Nitric Oxide 61:38–44. https://doi.org/10.1016/j.niox.2016.10.003CrossRefPubMed

68.

McDonagh STJ, Wylie LJ, Winyard PG et al (2015) The effects of chronic nitrate supplementation and the use of strong and weak antibacterial agents on plasma nitrite concentration and exercise blood pressure. Int J Sports Med 36:1177–1185. https://doi.org/10.1055/s-0035-1554700CrossRefPubMed

69.

Woessner M, Smoliga JM, Tarzia B et al (2016) A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load. Nitric Oxide 54:1–7. https://doi.org/10.1016/j.niox.2016.01.002CrossRefPubMed

70.

Hyde ER, Luk B, Cron S et al (2014) Characterization of the rat oral microbiome and the effects of dietary nitrate. Free Radic Biol Med 77:249–257. https://doi.org/10.1016/j.freeradbiomed.2014.09.017CrossRefPubMed

71.

Pinheiro LC, Ferreira GC, Amaral JH et al (2016) Oral nitrite circumvents antiseptic mouthwash-induced disruption of enterosalivary circuit of nitrate and promotes nitrosation and blood pressure lowering effect. Free Radic Biol Med 101:226–235. https://doi.org/10.1016/j.freeradbiomed.2016.10.013CrossRefPubMed

72.

Senkus KE, Crowe-White KM (2019) Influence of mouth rinse use on the enterosalivary pathway and blood pressure regulation: a systematic review. Crit Rev Food Sci Nutr 28:1–13. https://doi.org/10.1080/10408398.2019.1665495CrossRef

73.

Tribble GD, Angelov N, Weltman R et al (2019) Frequency of tongue cleaning impacts the human tongue microbiome composition and enterosalivary circulation of nitrate. Front Cell Infect Microbiol 9:39. https://doi.org/10.3389/fcimb.2019.00039CrossRefPubMedPubMedCentral

74.

Bescos R, Ashworth A, Cutler C et al (2020) Effects of chlorhexidine mouthwash on the oral microbiome. Sci Rep 10:5254–5258. https://doi.org/10.1038/s41598-020-61912-4CrossRefPubMedPubMedCentral

75.

Joshipura K, Muñoz-Torres F, Fernández-Santiago J et al (2019) Over-the-counter mouthwash use, nitric oxide and hypertension risk. Blood Press 7:1–10. https://doi.org/10.1080/08037051.2019.1680270CrossRef

76.

Joshipura KJ, Muñoz-Torres FJ, Morou-Bermudez E, Patel RP (2017) Over-the-counter mouthwash use and risk of pre-diabetes/diabetes. Nitric Oxide 71:14–20. https://doi.org/10.1016/j.niox.2017.09.004CrossRefPubMedPubMedCentral

77.

Amador-Martínez I, Pérez-Villalva R, Uribe N et al (2019) Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression. Am J Physiol Renal Physiol 317:F275–F285. https://doi.org/10.1152/ajprenal.00020.2019CrossRefPubMed

78.

Acara AC, Bolatkale M (2019) Endothelial nitric oxide level as a predictor of coronary complexity in patients with unstable angina pectoris. Am J Med Sci 357:453–460. https://doi.org/10.1016/j.amjms.2019.02.011CrossRefPubMed

79.

Aydin S (2018) Renalase, catecholamine and nitric oxide changes before and after sodium nitroprusside administration to patients who develop post-coronary artery by-pass (CABG) hypertension. Heart Surg Forum 21:E330–E336. https://doi.org/10.1532/hsf.1998CrossRefPubMed

80.

Tousoulis D, Koutsogiannis M, Papageorgiou N et al (2010) Endothelial dysfunction: potential clinical implications. Minerva Med 101:271–284PubMed

81.

Papageorgiou N, Androulakis E, Papaioannou S et al (2015) Homoarginine in the shadow of asymmetric dimethylarginine: from nitric oxide to cardiovascular disease. Amino Acids 47:1741–1750. https://doi.org/10.1007/s00726-015-2017-yCrossRefPubMed

82.

Sansbury BE, Hill BG (2014) Regulation of obesity and insulin resistance by nitric oxide. Free Radic Biol Med 73:383–399. https://doi.org/10.1016/j.freeradbiomed.2014.05.016CrossRefPubMed

83.

Gruber H-J, Mayer C, Mangge H et al (2008) Obesity reduces the bioavailability of nitric oxide in juveniles. Int J Obes (Lond) 32:826–831. https://doi.org/10.1038/sj.ijo.0803795CrossRef

84.

Jankovic A, Korac A, Buzadzic B et al (2017) Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management. Br J Pharmacol 174:1570–1590. https://doi.org/10.1111/bph.13498CrossRefPubMed

85.

Beals JW, Binns SE, Davis JL et al (2017) Concurrent beet juice and carbohydrate ingestion: influence on glucose tolerance in obese and nonobese adults. J Nutr Metab 2017:6436783–6436787. https://doi.org/10.1155/2017/6436783CrossRefPubMedPubMedCentral

86.

Carlström M, Larsen FJ, Nyström T et al (2010) Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice. Proc Natl Acad Sci USA 107:17716–17720. https://doi.org/10.1073/pnas.1008872107CrossRefPubMedPubMedCentral

87.

Yamasaki K, Edington HD, McClosky C et al (1998) Reversal of impaired wound repair in iNOS-deficient mice by topical adenoviral-mediated iNOS gene transfer. J Clin Invest 101:967–971. https://doi.org/10.1172/JCI2067CrossRefPubMedPubMedCentral

88.

Krausz A, Friedman AJ (2015) Nitric oxide as a surgical adjuvant. Future Sci OA 1:FSO56. https://doi.org/10.4155/fso.15.56CrossRefPubMedPubMedCentral

89.

Witte MB, Kiyama T, Barbul A (2002) Nitric oxide enhances experimental wound healing in diabetes. Br J Surg 89:1594–1601. https://doi.org/10.1046/j.1365-2168.2002.02263.xCrossRefPubMed

90.

Witte MB, Barbul A (2002) Role of nitric oxide in wound repair. Am J Surg 183:406–412. https://doi.org/10.1016/s0002-9610(02)00815-2CrossRefPubMed

91.

Engelen MPKJ, Klimberg VS, Allasia A, Deutz NEP (2018) Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer. Clin Nutr 37:1645–1653. https://doi.org/10.1016/j.clnu.2017.07.019CrossRefPubMed

92.

Luiking YC, Ten Have GAM, Wolfe RR, Deutz NEP (2012) Arginine de novo and nitric oxide production in disease states. Am J Physiol Endocrinol Metab 303:E1177–E1189. https://doi.org/10.1152/ajpendo.00284.2012CrossRefPubMedPubMedCentral

93.

Fortin CF, McDonald PP, Fülöp T, Lesur O (2010) Sepsis, leukocytes, and nitric oxide (NO): an intricate affair. Shock 33:344–352. https://doi.org/10.1097/SHK.0b013e3181c0f068CrossRefPubMed

94.

Dunn JLM, Hunter RA, Gast K et al (2016) Direct detection of blood nitric oxide reveals a burn-dependent decrease of nitric oxide in response to Pseudomonas aeruginosa infection. Burns 42:1522–1527. https://doi.org/10.1016/j.burns.2016.05.005CrossRefPubMedPubMedCentral

95.

Winkler MS, Kluge S, Holzmann M et al (2017) Markers of nitric oxide are associated with sepsis severity: an observational study. Crit Care 21:189–199. https://doi.org/10.1186/s13054-017-1782-2CrossRefPubMedPubMedCentral

96.

Davis JS, Yeo TW, Piera KA et al (2010) Angiopoietin-2 is increased in sepsis and inversely associated with nitric oxide-dependent microvascular reactivity. Crit Care 14:R89–R98. https://doi.org/10.1186/cc9020CrossRefPubMedPubMedCentral

97.

Davis JS, Darcy CJ, Yeo TW et al (2011) Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis. PLoS ONE 6:e17260. https://doi.org/10.1371/journal.pone.0017260CrossRefPubMedPubMedCentral

98.

Winkler MS, Nierhaus A, Rösler G et al (2018) Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival. Crit Care 22:216–310. https://doi.org/10.1186/s13054-018-2090-1CrossRefPubMedPubMedCentral

99.

Hansen MB, Rasmussen LS, Garred P et al (2018) Associations of plasma nitrite, l-arginine and asymmetric dimethylarginine with morbidity and mortality in patients with necrotizing soft tissue infections. Shock 49:667–674. https://doi.org/10.1097/SHK.0000000000000975CrossRefPubMedPubMedCentral

100.

Cauwels A, Buys ES, Thoonen R et al (2009) Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase-dependent manner. J Exp Med 206:2915–2924. https://doi.org/10.1084/jem.20091236CrossRefPubMedPubMedCentral

101.

Cauwels A, Brouckaert P (2011) Nitrite regulation of shock. Cardiovasc Res 89:553–559. https://doi.org/10.1093/cvr/cvq317CrossRefPubMed

102.

Waltz P, Escobar D, Botero AM, Zuckerbraun BS (2015) Nitrate/nitrite as critical mediators to limit oxidative injury and inflammation. Antioxid Redox Signal 23:328–339. https://doi.org/10.1089/ars.2015.6256CrossRefPubMedPubMedCentral

103.

Lewington S, Clarke R, Qizilbash N et al (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360:1903–1913. https://doi.org/10.1016/s0140-6736(02)11911-8CrossRefPubMed

104.

Steitieh D, Amin N (2019) Angina pectoris worsened by mouthwash. Proc Bayl Univ Med Cent 32:570–571. https://doi.org/10.1080/08998280.2019.1631096CrossRefPubMedPubMedCentral

105.

Milstone AM, Passaretti CL, Perl TM (2008) Chlorhexidine: expanding the armamentarium for infection control and prevention. Clin Infect Dis 46:274–281. https://doi.org/10.1086/524736CrossRefPubMed

106.

Zhurakivska K, Troiano G, Caponio VCA et al (2019) Do changes in oral microbiota correlate with plasma nitrite response? A systematic review. Front Physiol 10:1029. https://doi.org/10.3389/fphys.2019.01029CrossRefPubMedPubMedCentral

107.

Oliveira-Paula GH, Pinheiro LC, Tanus-Santos JE (2019) Mechanisms impairing blood pressure responses to nitrite and nitrate. Nitric Oxide 85:35–43. https://doi.org/10.1016/j.niox.2019.01.015CrossRefPubMed

108.

Montenegro MF, Sundqvist ML, Larsen FJ et al (2017) Blood pressure-lowering effect of orally ingested nitrite is abolished by a proton pump inhibitor. Hypertension 69:23–31. https://doi.org/10.1161/HYPERTENSIONAHA.116.08081CrossRefPubMed

109.

Pinheiro LC, Montenegro MF, Amaral JH et al (2012) Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats. Free Radic Biol Med 53:701–709. https://doi.org/10.1016/j.freeradbiomed.2012.06.001CrossRefPubMed

110.

de Smet AMGA, Kluytmans JAJW, Cooper BS et al (2009) Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 360:20–31. https://doi.org/10.1056/NEJMoa0800394CrossRefPubMed

111.

Wittekamp BH, Plantinga NL, Cooper BS et al (2018) Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients: a randomized clinical trial. JAMA 320:2087–2098. https://doi.org/10.1001/jama.2018.13765CrossRefPubMedPubMedCentral

112.

3M Health Information Systems (2003) All Patient Refined Diagnosis Related Groups (APR-DRGs), Version 20.0, Methodology Overview. https://www.hcup-us.ahrq.gov/db/nation/nis/APR-DRGsV20MethodologyOverviewandBibliography.pdf. Accessed 23 May 2017.

113.

Lee S, Lighvan NL, McCredie V et al (2019) Chlorhexidine-related mortality rate in critically ill subjects in intensive care units: a systematic review and meta-analysis. Respir Care 64:337–349. https://doi.org/10.4187/respcare.06434CrossRefPubMed

114.

Blot S, Vandewoude K, Hoste E et al (2003) Absence of excess mortality in critically ill patients with nosocomial Escherichia coli bacteremia. Infect Control Hosp Epidemiol 24:912–915. https://doi.org/10.1086/502159CrossRefPubMed

115.

Kim PW, Perl TM, Keelaghan EF et al (2005) Risk of mortality with a bloodstream infection is higher in the less severely ill at admission. Am J Respir Crit Care Med 171:616–620. https://doi.org/10.1164/rccm.200407-916OCCrossRefPubMed

116.

Bekaert M, Timsit J-F, Vansteelandt S et al (2011) Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med 184:1133–1139. https://doi.org/10.1164/rccm.201105-0867OCCrossRefPubMed

117.

Blot S, Vandewoude K, Hoste E, Colardyn F (2003) Reappraisal of attributable mortality in critically ill patients with nosocomial bacteraemia involving Pseudomonas aeruginosa. J Hosp Infect 53:18–24CrossRefPubMed

Titel: Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality: a hypothesis generating review
verfasst von: Stijn Blot
Publikationsdatum: 16.10.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Intensive Care Medicine / Ausgabe 1/2021
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-020-06276-z

Neu im Fachgebiet AINS

Aquatherapie bei Fibromyalgie wirksamer als Trockenübungen

03.05.2024 Fibromyalgiesyndrom Nachrichten

Bewegungs-, Dehnungs- und Entspannungsübungen im Wasser lindern die Beschwerden von Patientinnen mit Fibromyalgie besser als das Üben auf trockenem Land. Das geht aus einer spanisch-brasilianischen Vergleichsstudie hervor.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärzte und Psychotherapeuten.

Beutel versus Maschine: Beste Beatmungstechnik bei Herzstillstand gesucht

02.05.2024 Kardiopulmonale Reanimation Nachrichten

Stehen die Chancen auf eine Rückkehr der Spontanzirkulation nach Herz-Kreislauf-Stillstand bei manueller oder maschineller Beatmung besser? Und unterscheidet sich das neurologische Outcome nach der Reanimation? Das belgische Herzstillstand-Register liefert die Daten für einen direkten Vergleich zwischen Beutel und Beatmungsgerät.

Tipps für den Umgang mit Behandlungsfehlern

01.05.2024 DGIM 2024 Kongressbericht

Es ist nur eine Frage der Zeit, bis es zu einem Zwischenfall kommt und ein Behandlungsfehler passiert. Doch wenn Ärztinnen und Ärzte gut vorbereitet sind, schaffen es alle Beteiligten den Umständen entsprechend gut durch diese Krise.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

hier abonnieren

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality: a hypothesis generating review

Abstract

Neu im Fachgebiet AINS

Aquatherapie bei Fibromyalgie wirksamer als Trockenübungen

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

Beutel versus Maschine: Beste Beatmungstechnik bei Herzstillstand gesucht

Tipps für den Umgang mit Behandlungsfehlern

Update AINS

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2021

Tranexamic acid in traumatic brain injury: systematic review and meta-analysis trumps a large clinical trial?

Correction to: Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS

Weakness in the ICU: the right weight on the right scale

Impact of late administration of corticosteroids in COVID-19 ARDS

Organizational aspects of care associated with mortality in critically ill COVID-19 patients

Biomarkers in the ICU: less is more? Yes

Neu im Fachgebiet AINS

Aquatherapie bei Fibromyalgie wirksamer als Trockenübungen

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

Beutel versus Maschine: Beste Beatmungstechnik bei Herzstillstand gesucht

Tipps für den Umgang mit Behandlungsfehlern

Update AINS