ARDS AMONG CUTANEOUS BURN PATIENTS COMBINED WITH INHALATION INJURY… · 2019. 6. 1. · SDRA CHEZ LES BRÛLÉS INTOXIQUÉS PAR LES FUMÉES: SURVENUE PRÉCOCE ET MAUVAIS PRONOSTIC

ARDS AMONG CUTANEOUS BURN PATIENTS COMBINED WITHINHALATION INJURY: EARLY ONSET AND BAD OUTCOME

SDRA CHEZ LES BRÛLÉS INTOXIQUÉS PAR LES FUMÉES: SURVENUEPRÉCOCE ET MAUVAIS PRONOSTIC

Lam N.N.,* Hung T.D.

National Burns Hospital, Hanoi, Vietnam

SUMMARY. Our aims are to determine the clinical and preclinical characteristics and outcome of ARDSamong burn patients with inhalation injury. A retrospective study was conducted on 66 selected patients withARDS, treated in the ICU of the National Burns Hospital from 11/2013 to 10/2016. The patients were dividedinto two groups and matched by age and burn extent: the study group consisted of 33 patients with inhalationinjury and the control group 33 patients without inhalation injury. Outcome measures included blood gas cri-teria and oxygenation state at ARDS onset, mechanical ventilation duration, length of stay in the ICU and inthe hospital, ventilation-free time and mortality rate until 28 days postburn. Results showed that ARDS onsetwas earlier in the study group (5.9 ±.7 vs. 9.2 ± .9 days postburn respectively; p < 0.01) and blood oxygenationdisorder was more severe (PaO2/FiO2: 117.8 ± 6.1 vs. 125.9 ± 6.5 respectively; p < .01). There was no sig-nificant difference between the two groups (p > .05) regarding incidence of complications, ventilation time,ventilation-free duration, and length of stay in the ICU and in the hospital. Mortality rate until 28 days postburn was significantly higher among the study group (69.7% vs. 54.6% respectively; p < .001). In addition,time from admission and from ARDS onset to death was shorter in the study group (P < .05). In conclusion,compared to cutaneous burn-induced ARDS, ARDS in patients with inhalation injury has earlier onset,causes more severe oxygenation disorder and has a higher mortality rate.

Keywords: acute respiratory distress syndrome, inhalation injury, cutaneous burn

RÉSUMÉ. Cette étude rétrospective avait pour but d’étudier les caractéristiques des SDRA survenant chezles patients brûlés ayant inhalé des fumées. Elle a été réalisée sur 66 patients en SDRA hospitalisés dansl’hôpital brûlologique national entre novembre 2013 et octobre 2016. Il ont été répartis en 2 groupes de 33(avec – groupe à l’étude E- et sans inhalation de fumées- groupe témoin T) appariés sur l’âge et la surfacebrûlée. Les variables étudiées étaient la gazométrie et l’oxygénation lors du diagnostic de SDRA, la duréede ventilation mécanique, la durée sans ventilation, les durées de séjour en réanimation et à l’hôpital, lamortalité à J28. Le SDRA était plus précoce (5,85 +/- 0,65 j VS 9,15 +/- 0,92 ; p<0,01) et plus grave (P/F117,8 +/- 6,1 VS 125,9 +/- 6,5 ; p<0,01) dans le groupe E. Les durées de ventilation et sans ventilation, deséjour en réanimation comme à l’hôpital et le nombre de complications étaient comparables. La mortalitéà J28 était plus élevée dans le groupe E (69,7 VS 54,6% ; p< 0,001), plus précoce après la survenue duSDRA (p<0,05). Les patients brûlés ayant inhalé ont des SDRA plus précoces, plus hypoxémiants et plussouvent mortels que ceux n’ayant pas inhalé.

Mots-clés : SDRA, brûlure, inhalation de fumées

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* Corresponding author: Nguyen Nhu Lam MD, PhD, National Burns Hospital, Hanoi, Vietnam. Tel.: +84 948316869; fax: +84 2436883180;email: [email protected]: submitted 03/03/2019, accepted 06/03/2019

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Introduction

Acute respiratory distress syndrome (ARDS) is asevere complication in the intensive care unit (ICU)resulting in almost 75 000 deaths per year in theUnited States. Universally, it is estimated that ARDSdevelops in 10% of patients in the ICU.1 Current re-view indicated that no pharmacologic treatmentswere significantly effective, and that the main man-agement for ARDS is still lung-protective ventilationstrategy.2

ARDS is also one of the leading complicationsamong severe burn patients with or without inhala-tion inury.3,4,5 ARDS among cutaneous burn patientsis due to inflammatory response in the acute phaseof burn or sepsis phase postburn.6,7 Meanwhile, thepathological mechanism of ARDS in patients withinhalation injury is considered as a disorder ofbronchial circulation, impact of Nitric Oxide and ob-struction of the respiratory tract.8 Previous study in-dicated that inhalation injury is an independent riskfactor for the development of ARDS but severity ofinhalation injury assessed by score did not contributeto the development of ARDS.9 Manifestation andoutcome of burn patients with smoke-inducedARDS may be different to that of cutaneous burn-induced ARDS patients. This study compared char-acteristics and outcomes of ARDS among burnpatients with and without inhalation injury, treatedat the National Burns Hospital of Vietnam.

Materials and methods

A retrospective study was conducted on 330 adultburn patients admitted within 48h post burns to theBurn ICU in the National Burns Hospital from11/2013 to 10/2016, with burn extent ≥ 20% totalbody surface area (TBSA). Inhalation injury was di-agnosed if patients had the following symptoms: his-tory of a closed space fire, facial burns with singednasal hair, carbonaceous sputum, hoarseness, stridoror laboured breathing. Bronchoscopy was performedwithin 48h from admission to confirm thediagnosis.10,11,12,13 Diagnosis of ARDS was based onthe Berlin definition and protective ventilation strat-egy with low tidal volume of 6ml/kg of ideal body

weight was applied for all ARDS patients, as recom-mended by the ARDS network.14,15,16 Out of 330 ad-mitted patients, 86 developed ARDS. Thirty-three ofthese patients were diagnosed with inhalation injuryand were selected as the study group. The controlgroup included 33 ARDS patients without inhalationinjury who matched the study group by age (± 5years), burn surface area (± 5%) total body surfacearea (TBSA) and full thickness burn area (± 5%)TBSA (Fig. 1).

Outcome measures included ARDS onset time,blood gas parameters and blood oxygenation state atARDS onset, duration of mechanical ventilation,length of stay in the ICU and in the hospital, venti-lation-free time, complications and mortality rateuntil 28 days postburn. Data were collected and an-alyzed using Stata software version 11.0, with pvalue <.05 regarded as the significant level. Thisstudy was approved by the hospital’s committee forhuman research ethics.

Results

Baseline criteria of patients, including age, burnseverity, gender and admission time from burn oc-currence were not significantly different between the

Fig. 1 - Flow diagram of included and excluded patients


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two groups (Table I). All 66 patients were classifiedas having moderate to severe ARDS. It is noted thatARDS onset postburn was approximately 3 days ear-lier in the study group than in the control group (5.9± .7 days vs. 9.2 ± .9 days; p < .01).

Clinical and preclinical criteria at ARDS onset areindicated in Table II. Common symptoms were fever> 38.50C, increased heart rate > 130bpm, low SpO2,minor anaemia and leukocytosis. No remarkably dif-ferent values were recorded between the two groups(p > .05).

At the time of ARDS diagnosis, data from bloodgas analysis (Table III) indicated significantly lowerPaO2 in the study group (59.4 ± 3.1 vs. 65.6 ± 3.5respectively; p < .05). Higher PaCO2 values and lac-tate levels were also recorded in the study groupwith p <.05. In addition, blood oxygenation was sig-nificantly lower in the study group (PaO2/FiO2:117.8 ± 6.1 vs. 125.9 ± 6.5 mmHg respectively; p <.01).

Common complications recorded were septicshock and multiple organ failure (MOF), followedby acute renal failure and pneumothorax (Table IV).There was no significant difference between the twogroups (p > .05) regarding complication frequency,ventilation time, ventilator-free duration up to the28th day postburn and length of stay in the ICU andin the hospital. Death rate within 28 days post burnwas significantly higher for the study group (69.7%vs. 54.6% respectively; p < .001) and most deathswere due to MOF (data not shown). In addition, timefrom admission and from ARDS onset until deathwas shorter in the study group (P < .05).

Discussion

Since first described by Ashbaugh et al. in 1967,the definition of ARDS has changed over time. In1994, a formal definition and classification of ARDSwas reported by the American-European ConsensusConference Committee on ARDS (AECC). In 2012,the Berlin definition was introduced with more de-tail, making clinical diagnosis easier.14,17 Over sev-eral decades, despite the great achievements ofresearch and clinical trials, many questions about thepathogenesis and treatment of ARDS remain unan-swered.15,18,19,20

Despite advances in fluid resuscitation, hyperme-tabolic response intervention, early surgical exci-sion, tissue engineering and mechanical ventilation,the mortality rate of burn patients with inhalation in-jury is still high.8,10 Inhaled smoke causes damage tothe airway or lung parenchyma by heat or chemicalsthat occurs in combination with cutaneous burns orseparately. It was reported that there were more than23,000 cases of inhalation injury annually in theUnited States.21

Respiratory dysfunction afterburns is multifactorialand ARDS and inhalation injury are the most importantcauses.22,23,24 To date, significant reports on clinicalcharacteristics, risk factors and outcome of ARDSamongst burn patients have been published.3,4,5,25,26

However, few of these mentioned specific aspects ofARDS in the inhalation injury population.22 For cuta-neous burn patients, the main pathological mechanismof ARDS is an inflammatory response associated withthe burn wound or burn wound infection. In the case

Table I - Patient characteristics


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Table II - Patient features at ARDS onset

Table III - Blood gas parameters and oxygenation state at ARDS onset

Table IV - Complications and outcomes in the two groups


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of inhalation injury, additionally direct lung injury dueto inhaled smoke and fumes is involved. In extensiveburns, increased capillary permeability not only occurslocally but also in all the other organs. This processleads to the leakage of fluid into the interstitial space,and the risk of pulmonary edema becomes more seri-ous due to the combination with inhalation inury.27 Ex-perimental studies reported a 10-fold increase inbronchial blood flow within 20 minutes of smoke in-halation, as well as a six-fold increase in pulmonarytransvascular fluid flux and a fall in PaO2/FiO2 ≤ 200,but these were delayed until 24 hours. Similar findingshave been reported in patients with isolated smoke in-halation or in combination with large cutaneous ther-mal injury.28,29,30 A study on sheep suggested that NOproduced by iNOS plays an important role in thechanges in systemic and pulmonary microvascularpermeability in combined smoke inhalation/third-de-gree burn injury.8,31 There are three types of inhalationinjury: respiratory tract direct thermal injury, tissuedamage due to chemical irritants, and systemic effectsof inhaled toxins.9,10,12 Most patients with inhalationinjury have burns on the face and neck and may havechest burns, so developing local edema can affect therespiratory tract, edema and obstruction due to exu-date, leading to respiratory obstruction during the first48h.7 Chest burn can lead to decreased lung compli-ance, increased relative resistance of the respiratorytract and laboured beathing.11 These all lead to im-paired gas exchange, pneumonia and ARDS.

Current reports indicate that inhalation injury is anindependent risk factor for the development of ARDSamongst burn patients, with early onset and greaterseverity compared to cutaneous burn-inducedARDS.2,26 Our study indicated an earlier onset of 3days and more severe blood oxygenation and bloodgas parameter disorders in ARDS patients with inhala-tion injury compared to the control group. In 2005,Liffner et al. investigated incidence, mortality and timeof onset of ARDS in relation to extent of burn and in-halation injury in patients who required mechanicalventilation. They found that 70% of ARDS patientshad early onset post burn (less than 6 days).9 In 2016,Cartotto et al. reported that ARDS developed in the 1stweek after burn in 86% of cases: worsening severityof ARDS related to inhalation injury also led to alonger duration of mechanical ventilation and a reduc-

tion in ventilator-free days compared to the non in-halation injury-induced ARDS group.4

Common features of postburn ARDS were a largereduction in blood oxygenation measured by PaO2:FiO2 ratio, pulmonary compliance and increasedextra vascular lung water. Mortality rate for ARDSpatients is still high, especially in developing coun-tries.26 The early onset of ARDS, together withorgan dysfunction (reduced platelet count, acute kid-ney injury…) induced by an inflammatory processrelated to burn wound and inhalation injury, leads toa high mortality rate.22 In our study, the death ratewas 61.1%: a significantly higher rate was seen forinhalation injury-induced ARDS (69.7% vs. 54.6%)and time from admission and from ARDS onset untildeath was shorter in the inhaled smoke-inducedARDS group.

Our understanding of the mechanisms of fire-re-lated inhalation injury that results in the develop-ment of ARDS is still limited.23 Several challengeshave been encountered when investigating thepathogenesis and the role of smoke toxicants in-volved in the process of ARDS development. More-over, it is difficult for researchers to be exposed tolarge numbers of animals (sheep or dogs) in order toconduct studies on smoke-induced ARDS in a serialmanner.12 However, new treatment interventions arebeing investigated, with promising results. For ex-ample, in 2017 Yang et al. reported the results oftreatment administered to 13 patients with differentdegrees of ARDS caused by inhalation of whitesmoke from a burning smoke bomb. Their resultsshowed that application of glucocorticoid earlyenough and in an uninterrupted manner can signifi-cantly reduce ARDS caused by inhalation of whitesmoke from burning smoke bomb. Sequential appli-cation of glucocorticoid and pirfenidone can effec-tively treat pulmonary fibrosis in the late stage.32

Conclusion

We have shown that ARDS has a significantlyearlier onset, causes more severe blood oxygenationdisorder, and has a higher mortality rate in cutaneousburn patients with inhalation injury than in thosewithout inhalation injury.


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BIBLIOGRAPHY

McNicholas BA, Rooney GM, Laffey JG: Lessons to learn from epidemio-1logic studies in ARDS. Curr Opin Crit Care, 24(1): 41-48, 2018. Rawal G, Yadav S, Kumar R: Acute respiratory distress syndrome: an update2and review. J Translat Intern Med, 6(2): 74-77, 2018. Belenkiy SM, Buel AR, Cannon JW et al.: Acute respiratory distress syn-3drome in wartime military burns: application of the Berlin criteria. J TraumaAcute Care Surg, 76(3): 821-827, 2014.Cartotto R, Li Z, Hanna S, Spano S et al.: The acute respiratory distress syn-4drome (ARDS) in mechanically ventilated burn patients: an analysis of riskfactors, clinical features, and outcomes using the Berlin ARDS definition.Burns, 42(7): 1423-143, 2016. Dancey DR, Hayes J, Gomez M, Schouten D et al.: ARDS in patients with5thermal injury. Intensive Care Med, 25: 1231-1236, 1999.Dushianthan A, Grocott MPW at al.: Acute respiratory distress syndrome and6acute lung injury. Postgrad Med J, 87: 612-622, 2011.EnkhbaaTar P, Traber DL: Pathophysiology of acute lung injury in combined7burn and smoke inhalation injury. Clinical Science, 107(2): 137-143, 2004.Maybauer MO, Rehberg S, Traber DL, Herndon DN, Maybauer DM: Patho-8physiology of acute lung injury in severe burn and smoke inhalation injury.Anaesthesist, 58(8): 805-812, 2009.Liffner G, Bak Z, Reske A, Sjoberg F et al.: Inhalation injury assessed by9score does not contribute to the development of ARDS in burn victim. Burns,31(3): 263-268, 2005.Otterness K, Ahn C: Emergency department management of smoke inhalation10injury in adults. Emerg Med Pract, 20(3): 1-24, 2018.Traber DL, Herndon DN, Enkhbaatar P, Maybauer MO, Maybauer DM: The11pathophysiology of inhalation injury. In: DN Herndon (ed.): “Total BurnCare”, 218-228, Elsevier, Edinburgh, 2012.Woodson LC, Talon M, Traber DL, Herndon DN: Diagnosis and treatment of12inhalation injury. In: DN Herndon (ed.): “Total Burn Care”, 229-238, Elsevier,Edinburgh, 2012.Walker PF, Buehner MF, Wood LA, Boyer NL et al.: Diagnosis and manage-13ment of inhalation injury: an updated review. Crit Care, 19: 351, 2015.ARDS Definition Task Force: Acute Respiratory Distress Syndrome, The Berlin14definition. JAMA, 307(23): 2526-2533, 2002.The Acute Respiratory Distress Syndrome Network: Ventilation with lower15tidal volumes as compared with traditional tidal volumes for acute lung injuryand the acute respiratory distress syndrome. N Engl J Med, 342: 1301-1308,2000.NIH NHLBI ARDS Clinical Network: Mechanical Ventilation Protocol Sum-16mary. http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdfBernard GR, Artigas A, Brigham KL, Carlet J et al.: The American-European17Consensus Conference Committee on ARDS: definitions, mechanisms, rele-vant outcomes and clinical trial coordination. Am J Respir Crit Care Med,149: 818-824, 1994.

Fan E, Brodie D, Slutsky AS: Acute respiratory distress syndrome: advances18in diagnosis and treatment. JAMA, 319(7): 698-710, 2018.Fanelli V, Vlachou A, Ghannadian S, Simonetti U et al.: Acute respiratory19distress syndrome: new definition, current and future therapeutic options. JThorac Dis, 5(3): 326-334, 2013.Villar J, Sulemanji D, Kacmarek RM: The acute respiratory distress syn-20drome: incidence and mortality, has it changed? Curr Opin Crit Care, 20(1):3-9, 2014. Alcorta R: Smoke inhalation & acute cyanide poisoning. Hydrogen cyanide21poisoning proves increasingly common in smoke-inhalation victims. Jems,29(8): suppl 6-15; quiz suppl 6-7, 2004.Steinvall I, Bak Z, Sjoberg F: Acute respiratory distress syndrome is as important22as inhalation injury for the development of respiratory dysfunction in major burns.Burns, 34(4): 441-451, 2008.Kimmel EC, Still KR: Acute lung injury, acute respiratory distress syndrome23and inhalation injury: an overview. Drug Chem Toxicol, 22(1): 91-128, 1999.Silva L, Garcia L, Oliveira B, Tanita M et al.: Acute respiratory distress syn-24drome in burn patients: incidence and risk factor analysis. Ann Burns FireDisasters, 29(3): 178-182, 2016.Bhadade RR, Souza de RA, Harde MJ et al.: Clinical characteristics and out-25come of patients with acute lung injury and ARDS. J Postgrad Med, 57: 286-290, 2011.Lam NN, Hung TD, Hung DK: Acute respiratory distress syndrome among26severe burn patients in a developing country: application result of the Berlindefinition. Ann Burns Fire Disasters, 31(1): 9-12, 2018.Traber DL, Hawkins HK, Enkhbaatar P, Cox RA et al.: The role of the27bronchial circulation in the acute lung injury resulting from burn and smokeinhalation. Pulm Pharmacol Ther, 20(2): 163-6, 2007.Magno MG, Fishman AP: Origin, distribution, and blood flow of bronchial28circulation in anesthetized sheep. J Appl Physiol, 53: 272-279, 1982.Abdi S, Herndon D, Mcguire J et al.: Time course of alterations in lung lymph29and bronchial blood flows after inhalation injury. J Burn Care Rehabil, 11:510-515, 1990.Herndon DN, Barrow RE, Traber DL et al.: Extravascular lung water changes30following smoke inhalation and massive burn injury. Surgery, 102: 341-349,1987.Soejima K, Traber LD, Schmalstieg FC, Hawkins H et al.: Role of nitric oxide31in vascular permeability after combined burns and smoke inhalation injury.Am J Respir Crit Care Med, 163(3 Pt 1): 745-52, 2001.Yang FW, Xin HM, Zhu JH, Feng XY et al.: Treatment of patients with dif-32ferent degree of acute respiratory distress syndrome caused by inhalation ofwhite smoke. Zhonghua Shao Shang Za Zhi, 33(12): 760-765, 2017.

Acknowledgement. We are grateful to all the staff of the NationalBurns Hospital, Hanoi, for helping us to collect data

ARDS AMONG CUTANEOUS BURN PATIENTS COMBINED WITH INHALATION INJURY… · 2019. 6. 1. · SDRA CHEZ LES BRÛLÉS INTOXIQUÉS PAR LES FUMÉES: SURVENUE PRÉCOCE ET MAUVAIS PRONOSTIC

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