Skip to main content
Top
Published in: Annals of Intensive Care 1/2017

Open Access 01-12-2017 | Research

Antithrombin use and 28-day in-hospital mortality among severe-burn patients: an observational nationwide study

Authors: Takashi Tagami, Hiroki Matsui, Yuuta Moroe, Reo Fukuda, Ami Shibata, Chie Tanaka, Kyoko Unemoto, Kiyohide Fushimi, Hideo Yasunaga

Published in: Annals of Intensive Care | Issue 1/2017

Login to get access

Abstract

Background

Previous studies have suggested that antithrombin may be beneficial for treating coagulopathy in patients with severe burns. However, robust evidence for this idea is lacking. We examined the hypothesis that antithrombin may be effective in treating patients with severe burns.

Methods

We performed propensity score-matched analyses of the nationwide administrative Japanese Diagnosis Procedure Combination inpatient database. We identified patients with severe burns (burn index ≥ 10) who were recorded in the database from 1 July 2010 to 31 March 2013. We compared patients who were administered antithrombin within 2 days of admission (antithrombin group) and those who were not administered antithrombin (control group). The main outcomes were 28-day mortality and ventilator-free days (VFDs).

Results

Eligible patients (n = 3223) from 618 hospitals were categorized into either an antithrombin group (n = 152) or control group (n = 3071). Propensity score matching created a matched cohort of 103 pairs with and without antithrombin. Twenty-eight-day mortality was lower in the antithrombin group compared with the control group in propensity-matched analysis (control vs. antithrombin, 47.6 vs. 33.0%; difference, 14.6%; 95% confidence interval [CI] 1.2–28.0). Cox regression analysis showed a significant difference in 28-day in-hospital mortality between the control and antithrombin propensity-matched groups (hazard ratio 0.58; 95% CI 0.37–0.90). There were significantly more VFDs in the antithrombin compared with the control group in propensity score-matched analysis (control vs. antithrombin, 12.6 vs. 16.4 days; difference −3.7; 95% CI −7.2 to −0.12).

Conclusions

This nationwide database study demonstrated that antithrombin use may improve 28-day survival and increase VFDs in patients with severe burns. Further prospective studies are required to confirm these results.
Appendix
Available only for authorised users
Literature
1.
go back to reference Peck MD. Epidemiology of burns throughout the world. Part I: Distribution and risk factors. Burns. 2011;37(7):1087–100.CrossRefPubMed Peck MD. Epidemiology of burns throughout the world. Part I: Distribution and risk factors. Burns. 2011;37(7):1087–100.CrossRefPubMed
2.
go back to reference Lavrentieva A, Kontakiotis T, Bitzani M, Papaioannou-Gaki G, Parlapani A, Thomareis O, et al. Early coagulation disorders after severe burn injury: impact on mortality. Intensive Care Med. 2008;34(4):700–6.CrossRefPubMed Lavrentieva A, Kontakiotis T, Bitzani M, Papaioannou-Gaki G, Parlapani A, Thomareis O, et al. Early coagulation disorders after severe burn injury: impact on mortality. Intensive Care Med. 2008;34(4):700–6.CrossRefPubMed
3.
go back to reference Lippi G, Ippolito L, Cervellin G. Disseminated intravascular coagulation in burn injury. Semin Thromb Hemost. 2010;36(4):429–36.CrossRefPubMed Lippi G, Ippolito L, Cervellin G. Disseminated intravascular coagulation in burn injury. Semin Thromb Hemost. 2010;36(4):429–36.CrossRefPubMed
4.
go back to reference Glas GJ, Levi M, Schultz MJ. Coagulopathy and its management in patients with severe burns. J Thromb Haemost. 2016;14(5):865–74.CrossRefPubMed Glas GJ, Levi M, Schultz MJ. Coagulopathy and its management in patients with severe burns. J Thromb Haemost. 2016;14(5):865–74.CrossRefPubMed
5.
go back to reference Sherren PB, Hussey J, Martin R, Kundishora T, Parker M, Emerson B. Acute burn induced coagulopathy. Burns. 2013;39(6):1157–61.CrossRefPubMed Sherren PB, Hussey J, Martin R, Kundishora T, Parker M, Emerson B. Acute burn induced coagulopathy. Burns. 2013;39(6):1157–61.CrossRefPubMed
6.
go back to reference Kowal-Vern A, Walenga JM, McGill V, Gamelli RL. The impact of antithrombin(H) concentrate infusions on pulmonary function in the acute phase of thermal injury. Burns. 2001;27(1):52–60.CrossRefPubMed Kowal-Vern A, Walenga JM, McGill V, Gamelli RL. The impact of antithrombin(H) concentrate infusions on pulmonary function in the acute phase of thermal injury. Burns. 2001;27(1):52–60.CrossRefPubMed
7.
go back to reference Herek O, Yilmaz M, Kaleli I, Cevahir N, Demirkan N. Antithrombin III prevents early bacterial translocation in burn injury. Ann Burns Fire Disasters. 2006;19(4):196–200.PubMedPubMedCentral Herek O, Yilmaz M, Kaleli I, Cevahir N, Demirkan N. Antithrombin III prevents early bacterial translocation in burn injury. Ann Burns Fire Disasters. 2006;19(4):196–200.PubMedPubMedCentral
8.
go back to reference Rehberg S, Yamamoto Y, Bartha E, Sousse LE, Jonkam C, Zhu Y, et al. Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study. Crit Care. 2013;17(3):R86.CrossRefPubMedPubMedCentral Rehberg S, Yamamoto Y, Bartha E, Sousse LE, Jonkam C, Zhu Y, et al. Antithrombin attenuates myocardial dysfunction and reverses systemic fluid accumulation following burn and smoke inhalation injury: a randomized, controlled, experimental study. Crit Care. 2013;17(3):R86.CrossRefPubMedPubMedCentral
9.
go back to reference Lavrentieva A, Kontakiotis T, Bitzani M, Parlapani A, Thomareis O, Scourtis H, et al. The efficacy of antithrombin administration in the acute phase of burn injury. Thromb Haemost. 2008;100(2):286–90.PubMed Lavrentieva A, Kontakiotis T, Bitzani M, Parlapani A, Thomareis O, Scourtis H, et al. The efficacy of antithrombin administration in the acute phase of burn injury. Thromb Haemost. 2008;100(2):286–90.PubMed
10.
go back to reference Kowal-Vern A, McGill V, Walenga JM, Gamelli RL. Antithrombin(H) concentrate infusions are safe and effective in patients with thermal injuries. J Burn Care Rehabil. 2000;21(2):115–27.CrossRefPubMed Kowal-Vern A, McGill V, Walenga JM, Gamelli RL. Antithrombin(H) concentrate infusions are safe and effective in patients with thermal injuries. J Burn Care Rehabil. 2000;21(2):115–27.CrossRefPubMed
11.
go back to reference Kowal-Vern A, McGill V, Walenga JM, Gamelli RL. Antithrombin III concentrate in the acute phase of thermal injury. Burns. 2000;26(1):97–101.CrossRefPubMed Kowal-Vern A, McGill V, Walenga JM, Gamelli RL. Antithrombin III concentrate in the acute phase of thermal injury. Burns. 2000;26(1):97–101.CrossRefPubMed
12.
go back to reference Danielsson P, Nilsson L, Nettelblad H, Sjoberg F. Is there a need for antithrombin III substitution early after burn injury? Burns. 1997;23(4):300–5.CrossRefPubMed Danielsson P, Nilsson L, Nettelblad H, Sjoberg F. Is there a need for antithrombin III substitution early after burn injury? Burns. 1997;23(4):300–5.CrossRefPubMed
13.
go back to reference Niedermayr M, Schramm W, Kamolz L, Andel D, Romer W, Hoerauf K, et al. Antithrombin deficiency and its relationship to severe burns. Burns. 2007;33(2):173–8.CrossRefPubMed Niedermayr M, Schramm W, Kamolz L, Andel D, Romer W, Hoerauf K, et al. Antithrombin deficiency and its relationship to severe burns. Burns. 2007;33(2):173–8.CrossRefPubMed
14.
go back to reference Tagami T, Matsui H, Fushimi K, Yasunaga H. Low-dose corticosteroid treatment and mortality in refractory abdominal septic shock after emergency laparotomy. Ann Intensive Care. 2015;5(1):32.CrossRefPubMedPubMedCentral Tagami T, Matsui H, Fushimi K, Yasunaga H. Low-dose corticosteroid treatment and mortality in refractory abdominal septic shock after emergency laparotomy. Ann Intensive Care. 2015;5(1):32.CrossRefPubMedPubMedCentral
15.
go back to reference Tagami T, Matsui H, Fushimi K, Yasunaga H. Validation of the prognostic burn index: a nationwide retrospective study. Burns. 2015;41(6):1169–75.CrossRefPubMed Tagami T, Matsui H, Fushimi K, Yasunaga H. Validation of the prognostic burn index: a nationwide retrospective study. Burns. 2015;41(6):1169–75.CrossRefPubMed
16.
go back to reference Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H. Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost. 2014;12(9):1470–9.CrossRefPubMed Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H. Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost. 2014;12(9):1470–9.CrossRefPubMed
17.
go back to reference Tagami T, Matsui H, Fushimi K, Yasunaga H. Prophylactic antibiotics may improve outcome in patients with severe burns requiring mechanical ventilation: propensity score analysis of a Japanese Nationwide Database. Clin Infect Dis. 2016;62(1):60–6.CrossRefPubMed Tagami T, Matsui H, Fushimi K, Yasunaga H. Prophylactic antibiotics may improve outcome in patients with severe burns requiring mechanical ventilation: propensity score analysis of a Japanese Nationwide Database. Clin Infect Dis. 2016;62(1):60–6.CrossRefPubMed
18.
go back to reference Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H. Recombinant human soluble thrombomodulin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost. 2015;13(1):31–40.CrossRefPubMed Tagami T, Matsui H, Horiguchi H, Fushimi K, Yasunaga H. Recombinant human soluble thrombomodulin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study. J Thromb Haemost. 2015;13(1):31–40.CrossRefPubMed
19.
go back to reference Sheppard NN, Hemington-Gorse S, Shelley OP, Philp B, Dziewulski P. Prognostic scoring systems in burns: a review. Burns. 2011;37(8):1288–95.CrossRefPubMed Sheppard NN, Hemington-Gorse S, Shelley OP, Philp B, Dziewulski P. Prognostic scoring systems in burns: a review. Burns. 2011;37(8):1288–95.CrossRefPubMed
20.
go back to reference Kobayashi K, Ikeda H, Higuchi R, Nozaki M, Yamamoto Y, Urabe M, et al. Epidemiological and outcome characteristics of major burns in Tokyo. Burns. 2005;31(Suppl 1):S3–11.CrossRefPubMed Kobayashi K, Ikeda H, Higuchi R, Nozaki M, Yamamoto Y, Urabe M, et al. Epidemiological and outcome characteristics of major burns in Tokyo. Burns. 2005;31(Suppl 1):S3–11.CrossRefPubMed
21.
go back to reference Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–82.CrossRefPubMed Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–82.CrossRefPubMed
22.
go back to reference Lundgren RS, Kramer CB, Rivara FP, Wang J, Heimbach DM, Gibran NS, et al. Influence of comorbidities and age on outcome following burn injury in older adults. J Burn Care Res. 2009;30(2):307–14.CrossRefPubMedPubMedCentral Lundgren RS, Kramer CB, Rivara FP, Wang J, Heimbach DM, Gibran NS, et al. Influence of comorbidities and age on outcome following burn injury in older adults. J Burn Care Res. 2009;30(2):307–14.CrossRefPubMedPubMedCentral
23.
go back to reference Schoenfeld DA, Bernard GR. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med. 2002;30(8):1772–7.CrossRefPubMed Schoenfeld DA, Bernard GR. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med. 2002;30(8):1772–7.CrossRefPubMed
24.
go back to reference Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242–58.CrossRefPubMed Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242–58.CrossRefPubMed
25.
go back to reference Rosenbaum P, Rubin D. Constructing a control-group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–8. Rosenbaum P, Rubin D. Constructing a control-group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–8.
26.
go back to reference Kowal-Vern A, Gamelli RL, Walenga JM, Hoppensteadt D, Sharp-Pucci M, Schumacher HR. The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state. J Trauma. 1992;33(1):50–6 (discussion 6-7).CrossRefPubMed Kowal-Vern A, Gamelli RL, Walenga JM, Hoppensteadt D, Sharp-Pucci M, Schumacher HR. The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state. J Trauma. 1992;33(1):50–6 (discussion 6-7).CrossRefPubMed
27.
go back to reference Kowal-Vern A, Latenser BA. Antithrombin (human) concentrate infusion in pediatric patients with >50% TBSA burns. Burns. 2003;29(6):615–8.CrossRefPubMed Kowal-Vern A, Latenser BA. Antithrombin (human) concentrate infusion in pediatric patients with >50% TBSA burns. Burns. 2003;29(6):615–8.CrossRefPubMed
28.
go back to reference Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective estimates of the probability of death from burn injuries. N Engl J Med. 1998;338(6):362–6.CrossRefPubMed Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective estimates of the probability of death from burn injuries. N Engl J Med. 1998;338(6):362–6.CrossRefPubMed
29.
go back to reference Tagami T, Matsui H, Fushimi K, Yasunaga H. Supplemental dose of antithrombin use in disseminated intravascular coagulation patients after abdominal sepsis. Thromb Haemost. 2015;114(3):537–45.CrossRefPubMed Tagami T, Matsui H, Fushimi K, Yasunaga H. Supplemental dose of antithrombin use in disseminated intravascular coagulation patients after abdominal sepsis. Thromb Haemost. 2015;114(3):537–45.CrossRefPubMed
30.
go back to reference Aikawa N, Wakabayashi G, Ueda M, Shinozawa Y. Regulation of renal function in thermal injury. J Trauma. 1990;30(12 Suppl):S174–8.CrossRefPubMed Aikawa N, Wakabayashi G, Ueda M, Shinozawa Y. Regulation of renal function in thermal injury. J Trauma. 1990;30(12 Suppl):S174–8.CrossRefPubMed
31.
go back to reference Yoshioka T, Sugimoto T, Ukai T, Oshiro T. Haptoglobin therapy for possible prevention of renal failure following thermal injury: a clinical study. J Trauma. 1985;25(4):281–7.CrossRefPubMed Yoshioka T, Sugimoto T, Ukai T, Oshiro T. Haptoglobin therapy for possible prevention of renal failure following thermal injury: a clinical study. J Trauma. 1985;25(4):281–7.CrossRefPubMed
32.
go back to reference Mitra B, Wasiak J, Cameron PA, O’Reilly G, Dobson H, Cleland H. Early coagulopathy of major burns. Injury. 2013;44(1):40–3.CrossRefPubMed Mitra B, Wasiak J, Cameron PA, O’Reilly G, Dobson H, Cleland H. Early coagulopathy of major burns. Injury. 2013;44(1):40–3.CrossRefPubMed
33.
go back to reference Iba T, Saito D, Wada H, Asakura H. Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res. 2012;130(3):e129–33.CrossRefPubMed Iba T, Saito D, Wada H, Asakura H. Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey. Thromb Res. 2012;130(3):e129–33.CrossRefPubMed
34.
go back to reference Iba T, Thachil J. Present and future of anticoagulant therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a perspective from Japan. Int J Hematol. 2016;103(3):253–61.CrossRefPubMed Iba T, Thachil J. Present and future of anticoagulant therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a perspective from Japan. Int J Hematol. 2016;103(3):253–61.CrossRefPubMed
35.
go back to reference Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation. 2004;109(22):2698–704.CrossRefPubMed Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation. 2004;109(22):2698–704.CrossRefPubMed
36.
go back to reference Wada H, Asakura H, Okamoto K, Iba T, Uchiyama T, Kawasugi K, et al. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125(1):6–11.CrossRefPubMed Wada H, Asakura H, Okamoto K, Iba T, Uchiyama T, Kawasugi K, et al. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125(1):6–11.CrossRefPubMed
37.
38.
go back to reference Yoshino Y, Ohtsuka M, Kawaguchi M, Sakai K, Hashimoto A, Hayashi M, et al. The wound/burn guidelines—6: guidelines for the management of burns. J Dermatol. 2016;43(9):989–1010.CrossRefPubMed Yoshino Y, Ohtsuka M, Kawaguchi M, Sakai K, Hashimoto A, Hayashi M, et al. The wound/burn guidelines—6: guidelines for the management of burns. J Dermatol. 2016;43(9):989–1010.CrossRefPubMed
39.
go back to reference Pham TN, Cancio LC, Gibran NS, American BA. American Burn Association practice guidelines burn shock resuscitation. J Burn Care Res. 2008;29(1):257–66.CrossRefPubMed Pham TN, Cancio LC, Gibran NS, American BA. American Burn Association practice guidelines burn shock resuscitation. J Burn Care Res. 2008;29(1):257–66.CrossRefPubMed
40.
go back to reference Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, et al. Management of bleeding following major trauma: an updated European guideline. Crit Care. 2010;14(2):R52.CrossRefPubMedPubMedCentral Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, et al. Management of bleeding following major trauma: an updated European guideline. Crit Care. 2010;14(2):R52.CrossRefPubMedPubMedCentral
41.
go back to reference Hofstra JJ, Vlaar AP, Knape P, Mackie DP, Determann RM, Choi G, et al. Pulmonary activation of coagulation and inhibition of fibrinolysis after burn injuries and inhalation trauma. J Trauma. 2011;70(6):1389–97.CrossRefPubMed Hofstra JJ, Vlaar AP, Knape P, Mackie DP, Determann RM, Choi G, et al. Pulmonary activation of coagulation and inhibition of fibrinolysis after burn injuries and inhalation trauma. J Trauma. 2011;70(6):1389–97.CrossRefPubMed
42.
go back to reference 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(12):e439–46.CrossRefPubMedPubMedCentral 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(12):e439–46.CrossRefPubMedPubMedCentral
Metadata
Title
Antithrombin use and 28-day in-hospital mortality among severe-burn patients: an observational nationwide study
Authors
Takashi Tagami
Hiroki Matsui
Yuuta Moroe
Reo Fukuda
Ami Shibata
Chie Tanaka
Kyoko Unemoto
Kiyohide Fushimi
Hideo Yasunaga
Publication date
01-12-2017
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2017
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-017-0244-y

Other articles of this Issue 1/2017

Annals of Intensive Care 1/2017 Go to the issue