Nebulized heparin for inhalation injury in burn patients: a systematic review and meta-analysis

Xiaodong Lan , Zhiyong Huang , Ziming Tan , Zhenjia Huang , Dehuai Wang , Yuesheng Huang

Burns & Trauma ›› 2020, Vol. 8 ›› Issue (1) : tkaa015

PDF (961KB)
Burns & Trauma ›› 2020, Vol. 8 ›› Issue (1) :tkaa015 DOI: 10.1093/burnst/tkaa015
Research Article
research-article
Nebulized heparin for inhalation injury in burn patients: a systematic review and meta-analysis
Author information +
History +
PDF (961KB)

Abstract

Background: Smoke inhalation injury increases overall burn mortality. Locally applied heparin attenuates lung injury in burn animal models of smoke inhalation. It is uncertain whether local treatment of heparin is benefit for burn patients with inhalation trauma. We systematically reviewed published clinical trial data to evaluate the effectiveness of nebulized heparin in treating burn patients with inhalation injury. Methods: A systematic search was undertaken in PubMed, the Cochrane Library, Embase, Web of Science, the Chinese Journals Full-text Database, the China Biomedical Literature Database and the Wanfang Database to obtain clinical controlled trails evaluating nebulized heparin in the treatment of burn patients with inhalation injury. Patient and clinical characteristics, interventions and physiological and clinical outcomes were recorded. Cochrane Risk of Bias Evaluation Tool and the Newcastle–Ottawa Scale were used to evaluate data quality. Potential publication bias was assessed by Egger’s test. A sensitivity analysis was conducted to assess the stability of the results. The meta-analysis was conducted in R 3.5.1 software. Results: Nine trials were eligible for the systematic review and meta-analysis. Nebulized heparin can reduce lung injury and improve lung function in burn patients with inhalation injury without abnormal coagulation or bleeding, but the findings are still controversial. Mortality in the heparin-treated group was lower than that of the traditional treatment group (relative risk (RR) 0.75). The duration of mechanical ventilation (DOMV) was shorter in the heparin-treated group compared to the traditional treatment group (standardized mean difference (SMD) −0.78). Length of hospital stay was significantly shorter than that in the traditional treatment group (SMD −0.42), but incidence rates of pneumonia and unplanned reintubation were not significantly different in the study groups (RRs 0.97 and 0.88, respectively). No statistically significant publication biases were detected for the above clinical endpoints (p > 0.05). Conclusions: Based on conventional aerosol therapy, heparin nebulization can further reduce lung injury, improve lung function, shorten DOMV and length of hospital stay, and reduce mortality, although it does not reduce the incidence of pneumonia and/or the unplanned reintubation rate.

Keywords

Burns / Inhalation injury / Heparin / Systematic review

Cite this article

Download citation ▾
Xiaodong Lan, Zhiyong Huang, Ziming Tan, Zhenjia Huang, Dehuai Wang, Yuesheng Huang. Nebulized heparin for inhalation injury in burn patients: a systematic review and meta-analysis. Burns & Trauma, 2020, 8 (1) : tkaa015 DOI:10.1093/burnst/tkaa015

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Guo G, Zhu F, Huang Y, Wu J, Sun Y, Xia Z, et al. National Expert Consensus on clinical diagnosis and treatment of inhalation injury (2018). Chin J Burns. 2018; 34(11): 770-5.

[2]

Gupta K, Mehrotra M, Kumar P, Gogia AR, Prasad A, Fisher JA. Smoke inhalation injury: Etiopathogenesis, diagnosis, and management. Indian J Crit Care Med. 2018; 22: 180-8.

[3]

Foncerrada G, Culnan DM, Capek KD, Gonzalez-Trejo S, Cambiaso-Daniel J, Woodson LC, et al. Inhalation injury in the burned patient. Ann Plast Surg. 2018; 80: S98-105.

[4]

Glas GJ, Levi M, Schultz MJ. Coagulopathy and its management in patients with severe burns. J Thromb Haemost. 2016; 14: 865-74.

[5]

Turnage RH, Nwariaku F, Murphy J. Mechanism of pulmonary microvascular dysfunction during severe burn injury. World J Surg. 2002; 26: 848-53.

[6]

Enkhbaatar P, Pruitt BA, Suman O, Mlcak R, Wolf SE, Sakurai H, et al. Challenges in research on the pathophysiology of smoke inhalation injury and its clinical management. Lancet. 2016; 388: 1437-46.

[7]

Nishimura N, Hiranuma N. Respiratory changes after major burn injury. Crit Care Med 1982; 102: 25-8.

[8]

Mulloy B, Hogwood J, Gray E, Lever R, Page CP. Pharmacology of heparin and related drugs. Pharmacol Rev. 2016; 68: 76-141.

[9]

Cassinelli G, Naggi A. Old and new applications of non-anticoagulant heparin. Int J Cardiol. 2016; 212: S14-21.

[10]

Saliba MJ. Heparin in the treatment of burns: a review. 2001; 27: 349-58.

[11]

Yildiz-Pekoz A, Ozsoy Y. Inhaled heparin: therapeutic efficacy and recent formulations. J Aerosol Med Pulm Drug Deliv. 2017; 30: 143-56.

[12]

Enkhbaatar P, Cox RA, Traber LD, Westphal M, Aimalohi E, Morita N, et al. Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation. Crit Care Med. 2007; 35: 2805-10.

[13]

Enkhbaatar P, Esechie A, Wang J, Cox RA, Nakano Y, Hamahata A, et al. Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation. Clin Sci (Lond). 2008; 114: 321-9.

[14]

Murakami K, McGuire R, Cox RA, Jodoin JM, Bjertnaes LJ, Katahira J, et al. Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep. Shock. 2002; 18: 236-41.

[15]

Rehberg S, Yamamoto Y, Sousse LE, Jonkam C, Zhu Y, Traber LD, et al. Antithrombin attenuates vascular leakage via inhibiting neutrophil activation in acute lung injury. Crit Care Med. 2013; 41: e439-46.

[16]

Enkhbaatar P, Murakami K, Cox R, Westphal M, Morita N, Brantley K, et al. Aerosolized tissue plasminogen inhibitor improves pulmonary function in sheep with burn and smoke inhalation. Shock. 2004; 22: 70-5.

[17]

Enkhbaatar P, Herndon DN, Traber DL. Use of nebulized heparin in the treatment of smoke inhalation injury. J Burn Care Res. 2009; 30: 159-62.

[18]

Higgins JP, Green S, Collaboration C. Cochrane Handbook for Systematic Reviews of Interventions 5: Wiley Online Library, 2008.

[19]

Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M. The Newcastle-Ottawa scale (NOS) for assessing the quality of non-randomized studies in meta-analysis [Internet]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

[20]

Hou X, Shi J, Chen X. How to estimate the mean and standard deviation based on the median, range and sample size when conducting meta-analysis. Chin J Evid-based Med. 2015; 15(4): 484-7.

[21]

Holt J, Saffle JR, Morris SE, Cochran A. Use of inhaled heparin/N-acetylcystine in inhalation injury: does it help? J Burn Care Res. 2008; 29: 192-5.

[22]

Yip LY, Lim YF, Chan HN. Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital burns Centre. Burns. 2011; 37: 1154-60.

[23]

Sharma A, Lunawat A. Role of heparin and N-acetylcystein in prevention of acute respiratory distress syndrome in suspected inhalation injury in burn. Indian Journal of Basic and Applied Medical Research. 2005; 337-43.

[24]

Desai MH, Mlcak R, Richardson J, Nichols R, Herndon DN. Reduction in mortality in pediatric patients with inhalation injury with aerosolized heparin/N-acetylcystine [correction of acetylcystine] therapy. J Burn Care Rehabil. 1998; 19: 210-2.

[25]

McIntire AM, Harris SA, Whitten JA, Fritschle-Hilliard AC, Foster DR, Sood R, et al. Outcomes following the use of nebulized heparin for inhalation injury (HIHI study). J Burn Care Res. 2017; 38: 45-52.

[26]

McGinn KA, Weigartz K, Lintner A, Scalese MJ, Kahn SA. Nebulized heparin with N-Acetylcysteine and albuterol reduces duration of mechanical ventilation in patients with inhalation injury. J Pharm Pract. 2019; 32: 163-6.

[27]

Miller AC, Rivero A, Ziad S, Smith DJ, Elamin EM. Influence of nebulized unfractionated heparin and N-acetylcysteine in acute lung injury after smoke inhalation injury. J Burn Care Res. 2009; 30: 249-56.

[28]

Kashefi NS, Nathan JI, Dissanaike S. Does a nebulized heparin/N-acetylcysteine protocol improve outcomes in adult smoke inhalation? Plast Reconstr Surg Glob Open. 2014; 2: e165.

[29]

Rivero A, Elamin E, Nguyen V, Cruse W, Smith D. Can nebulized heparin and N-acetylcysteine reduce acute lung injury after inhalation lung insult? Chest. 2007.

[30]

Jones SW, Williams FN, Cairns BA, Cartotto R. Inhalation injury: pathophysiology, diagnosis, and treatment. Clin Plast Surg. 2017; 44: 505-11.

[31]

Rello J, Lisboa T, Koulenti D. Respiratory infections in patients undergoing mechanical ventilation. Lancet Respir Med. 2014; 2: 764-74.

[32]

Danielis M, Chiaruttini S, Palese A. Unplanned extubations in an intensive care unit: findings from a critical incident technique. Intensive Crit Care Nurs. 2018; 47: 69-77.

[33]

Keszler M.Mechanical ventilation strategies. Semin Fetal Neonatal Med. 2017; 22: 267-74.

[34]

Glas GJ, Serpa Neto A, Horn J, Cochran A, Dixon B, Elamin EM, et al. Nebulized heparin for patients under mechanical ventilation: an individual patient data meta-analysis. Ann Intensive Care. 2016; 6: 33.

[35]

Miller AC, Elamin EM, Suffredini AF. Inhaled anticoagulation regimens for the treatment of smoke inhalation-associated acute lung injury: a systematic review. Crit Care Med. 2014; 42: 413-9.

[36]

Tuinman PR, Dixon B, Levi M, Juffermans NP, Schultz MJ. Nebulized anticoagulants for acute lung injury-a systematic review of preclinical and clinical investigations. Crit Care. 2012; 16: R70.

[37]

Juschten J, Tuinman PR, Juffermans NP, Dixon B, Levi M, Schultz MJ. Nebulized anticoagulants in lung injury in critically ill patients-an updated systematic review of preclinical and clinical studies. Ann Transl Med. 2017; 5: 444.

[38]

Elsharnouby NM, Eid HE, Abou Elezz NF, Aboelatta YA. Heparin/N-acetylcysteine: an adjuvant in the management of burn inhalation injury: a study of different doses. J Crit Care. 2014; 29: 182.e1-4.

[39]

Anglemyer A, Horvath HT, Bero L. Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials. Cochrane Database Syst Rev. 2014.

PDF (961KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/

〈 〉