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Current Anaesthesia & Critical Care 19 (2008) 264–268

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Current Anaesthesia & Critical Care

journal homepage: www.elsevier .com/locate/cacc

FOCUS ON: BURNS CARE

The respiratory insult in burns injury

S. Singh, J. Handy*

Chelsea & Westminster Hospital, Imperial College London, 369 Fulham Road, London SW10 9NH, UK

Keywords:InhalationInjuryBurnManagementSmokeToxins

* Corresponding author.E-mail address: j.m.handy@imperial.ac.uk (J. Hand

0953-7112/$ – see front matter � 2008 Elsevier Ltd.doi:10.1016/j.cacc.2008.09.008

s u m m a r y

Inhalation injury may result from numerous noxious triggers and in association with other injuries, themost common being cutaneous burns. While patients with severe burns often require transfer toa regional unit for specialist management, this is not the case for those with inhalation injury associatedwith minor burns or occurring in isolation. These latter patients may require management in a generalintensive care unit and yet they present some unique challenges to the clinician that may otherwise gounnoticed. The aim of this review is to provide an overview of the pathophysiology, presentation andmanagement of patients with inhalation injury by way of a guide to those who manage such patients onan infrequent basis.

� 2008 Elsevier Ltd. All rights reserved.

1. Introduction

Inhalation injury occurs in approximately 10–20% of patientsadmitted to burn centres, with a report from north west Englandhighlighting an overall hospital admission rate to of 0.29/1000population per year.1 Of the 5000 deaths from burns injuries in theUSA per annum, inhalation injury increases the odds ratio ofmortality independently by 2.6.2 Risk factors include delayedextrication from enclosed or poorly ventilated spaces and the typeand dose of inhaled toxins.

Patients suffering burn injury may develop respiratory insultsfrom several causes: direct airway injury; hypoxic gas mixtureinhalation; inhalation of systemic toxins; inhalation of local (airwayand pulmonary) toxins; and injury resulting from the ensuingSystemic Inflammatory Response Syndrome (SIRS). Despite esca-lating interest and research into the pathophysiological processesand treatments relevant to other forms of lung injury, thereremains a chasm of such knowledge and information when appliedto inhalation injury.3 There is, however, little reason to suppose thatthe development of lung injury as a component of SIRS in thesepatients is any different from that in other critically ill patientgroups.4 For this reason, this article will concentrate on the path-ophysiology, recognition and management of airway and toxin-related changes that occur in inhalation injury.

2. Pathophysiology of inhalation injury

The pathological processes initiated result from causes whichcan be easily remembered using the mnemonic HOTT:

y).

All rights reserved.

� heat� oxygen deficiency� toxins – local� toxins – systemic

2.1. Heat (thermal) injury

Thermal damage to the airway and subsequent airwaymanagement are crucial, early considerations. The temperaturerequired to produce such injury will depend on the heat capacitycharacteristics of the gas or vapour and the duration of exposure,with dry gases having less injurious potential than a similarexposure to saturated vapours. The heat-exchange capabilities ofthe upper airway are so efficient that it is rare to suffer thermalinjury below the glottis unless super-heated particles have beeninhaled. This may occur when particulate matter from soot inha-lation is transported beyond the protective upper airway.

The most significant effect of thermal injury to the upperairways is the development of oedema with the potential for airwayobstruction. Oedema formation develops rapidly following burninjury due to the generation of negative interstitial hydrostaticpressures followed by increases in vascular permeability andpressure.5–8 These changes develop as innate immune cellularinfiltration occurs, with release of oxygen free radicals, histamine,bradykinin and prostaglandins.9–12 The process is less profound indeep burns where the vascular supply is compromised due to thethermal injury.13 In the absence of fluid resuscitation, the reductionin intravascular volume and pressure will result in less oedemaformation than following fluid resuscitation. The use of base deficitto guide resuscitation is associated with greater administeredvolumes than when urine output alone is used and the risk of

S. Singh, J. Handy / Current Anaesthesia & Critical Care 19 (2008) 264–268 265

worsened oedema and tissue oxygenation with over-hydrationhighlights the need for more precise and considered end-points influid resuscitation following burn injury.

2.2. Oxygen deficiency

Hypoxia is multi-factorial during inhalation injury and may beimmediate or delayed. During the burn incident:

� oxygen is consumed by combustion and thus ambient oxygenconcentrations can drop to potentially lethal levels� airway obstruction due to oedema or loss of consciousness can

occur� cytotoxic hypoxia may develop as a result of the inhalation of

carbon monoxide or hydrogen cyanide (discussed in Section2.4)

Lung injury often takes between 24 and 48 h to develop andthus results in delayed hypoxaemia. This is significant as it usuallycoincides with the period of maximal tissue oedema. The combi-nation of low capillary oxygen tension and reduced tissue oxygendiffusion will compound tissue hypoxia and subsequent ‘reperfu-sion’ may result in worsening of the injury.

2.3. Toxins – local (respiratory)

Smoke inhalation occurs through the inhalation of the productsof combustion of burning fuels. The two processes involved areoxidation and pyrolysis (direct melting).

Many lower molecular weight constituents of smoke are toxic tothe lower airways and gas-exchange lung units as a result of theirpH or free radical potential. These include acrolein, formaldehyde,chlorine, phosgene, perfluoroisobutylene, SO2, NO, and NO2. Sootcontains elemental carbon, and can adsorb toxins, therebyincreasing their distal delivery. Particles less than 4 mm in diameterhave greater propensity to reach the distal airways than the largersmoke particles.14

2.4. Toxins – systemic

Smoke inhalation may lead to the absorption of carbonmonoxide and hydrogen cyanide. These molecules impair thedelivery and/or utilisation of oxygen and may result in systemictissue hypoxia and rapid death.

2.4.1. Carbon monoxideCarbon monoxide is the leading cause of smoke-related fatali-

ties (up to 80% of deaths).14,15 The number of injuries directlyrelated to cyanide poisoning is less clearly defined, but its toxicity issynergistic with that of carbon monoxide, and exposure may bemore common as parent compounds such as polyurethane, acry-lonitrile, and nylon find increasingly numerous applications.

2.4.2. CyanideHydrogen cyanide is a highly toxic compound that can be

formed in the high temperature combustion/pyrolysis of a numberof common materials such as polyurethane, acrylonitrile, nylon,wool, and cotton. Cyanide binds to a variety of iron-containingenzymes, the most important of which is the cytochrome a–a3complex; this complex is critical for electron transport duringoxidative phosphorylation. By binding to this molecule, minuteamounts of cyanide can inhibit aerobic metabolism and rapidlyresult in death.

3. Clinical presentation

Respiratory complications are more common following closedspace fires than after fires in the open. Risk factors for respiratorycomplications include loss of consciousness and death of anothervictim. Obvious signs on admission include facial burns or soot inthe nares or mouth, cutaneous burns on the neck, carbonaceoussputum and wheezes or crackles on auscultation. Presence orabsence of these signs does not reliably predict the extent ofinhalation injury, nor the type of insult.16

The clinical effects of inhalation injury may be simplisticallydivided into:

� effects above and below the glottis� systemic effects

Particularly worrying signs are:

� any signs of upper airway compromise� any neurological features that may indicate CO or cyanide

toxicity

The following features raise concern of thermal injury and itsattendant risk of asphyxiation:

� stridor� use of accessory respiratory muscles� respiratory distress� hypoxia or hypercapnia� deep burns to the face or neck� blistering or oedema of the oropharynx

3.1. Carbon monoxide toxicity

Carbon monoxide (CO) is an odourless, tasteless, colourless,non-irritating gas formed by the incomplete combustion of carbon-containing compounds.14 The clinical findings of CO toxicity arehighly variable and largely non-specific. Symptoms and signs mayinclude headache, nausea, malaise, altered cognition, dyspnoea,angina, seizures, cardiac dysrhythmias, congestive heart failure,and/or coma.

Carboxyhaemoglobin levels correlate imprecisely with thedegree of poisoning and are not predictive of delayed neurologicsequelae. Neurologic findings, particularly loss of consciousness,impart a poorer prognosis.17

3.2. Cyanide toxicity

The typical clinical syndrome due to cyanide poisoning is one ofrapidly developing coma, apneoa, cardiac dysfunction, and severelactic acidosis in conjunction with a high mixed venous O2 anda low arteriovenous O2 content difference.18

The toxicities of breathing hypoxic air (which decreases O2

supply), carbon monoxide (which primarily affects O2 delivery andto a lesser extent O2 utilisation), and cyanide (which primarilyaffects O2 utilisation) are synergistic. Some studies have docu-mented levels of COHb and whole blood cyanide that are eachsublethal but appear fatal in combination.

4. Management

The ABCDE approach of a trauma primary survey is advisable forassessment and management. Thus, immediate attention to theadequacy of airway, breathing, and circulation is mandatory, whilstspecific causes of hypoxia should be sought and treated.

S. Singh, J. Handy / Current Anaesthesia & Critical Care 19 (2008) 264–268266

4.1. Airway

The possibility of pending airway compromise must be consid-ered continuously while administering high concentrations ofhumidified oxygen. Airway oedema may not be maximal until up to24 h after injury and is often precipitous following fluidresuscitation.

If airway compromise develops or is anticipated, early endo-tracheal intubation should be performed by experienced personnelwith prior preparation for the management of a difficult intubationand surgical airway.

4.1.1. Airway obstruction is a clinical diagnosisThere is no place for pulse oximetry and blood gas analysis to

guide the need for intubation on the grounds of airway compromisealone, as the latter will only show abnormalities at a pre-terminalstage. Clinical signs that should alert the clinician to potentialairway obstruction include erythema and oedema of the mucosa inthe mouth; significant facial burns; carbonaceous sputum on deepcough; singed nasal hair and hoarse voice.

Imminent signs of airway obstruction include:

� tracheal tug� intercostal recession� paradoxical (see-saw) breathing pattern

There is little substitute for repeated, meticulous assessments ofthe airway, in particular with respect to voice quality as this notonly allows early recognition of airway inadequacy but can alsoprevent unnecessary intubation and ventilation. Such clinicalmonitoring should, however be performed in an environmentwhere the appropriate equipment, drugs and personnel areimmediately available should the need for definitive airwaymanagement arise.

4.1.2. When to intubate?If the findings of upper airway compromise are absent, the

oropharynx should be examined for erythema and laryngoscopyperformed. If oedema or blistering of the upper airway is appreci-ated on laryngoscopic exam, intubation should be performedwithout delay. In the absence of such findings, close observation iswarranted for 24 h with a low threshold to proceed to seriallaryngoscopies if there is a change in status.

If intubation is performed, a large lumen endotracheal tube(ETT) should be placed to enable optimal management of secre-tions, and oxygen should be humidified to avoid inspissation.Changing the ETT in the presence of upper airway oedema isdangerous, and the tube should be left in place until resolution ofupper airway oedema (generally 3–5 days). Repeated surgery orpersisting respiratory compromise may necessitate earlytracheostomy.

4.2. Breathing

Lung injury usually takes several hours or even days to progressand the clinical course may reflect this. Radiographic changes oftendo not appear until 24 h or more after the insult and thus a normalchest radiograph at presentation does not exclude a significantinhalation injury. Arterial blood gas analysis is invaluable for:

� assessing the state of respiratory adequacy� excluding carbon monoxide toxicity� raising suspicion of cyanide poisoning

Pulse oximetry should be performed continuously (this maygive an inappropriately high reading in the presence of

carboxyhaemoglobin.) The diagnosis of direct toxin damage isbased upon a compatible history, findings of bronchorrhea andbronchospasm, and/or bronchoscopic visualisation of damagedairway mucosa. Treatment involves aerosolised bronchodilators;corticosteroids have no proven benefit in this setting.19

4.2.1. Carboxyhaemoglobin (COHb)COHb levels greater than 10% should be treated with 100%

inspired oxygen therapy. The half life of COHb is reduced from240 min at an inspired oxygen concentration (FiO2) of 21% to about80 min at a FiO2 of 100%. Hyperbaric therapy should be consideredin patients with COHb greater than 40% or 20% if pregnant and inpatients who have had lowered conscious level from no othercause. In practice though, due in part to logistic and technicaldifficulties, hyperbaric therapy is rarely performed.

4.2.2. VentilationSupportive and ventilatory strategies associated with benefit in

non-burns acute lung injury (i.e. avoiding excessive volumes andmaintaining patency of recruited lung, once hypoxaemia has beenovercome) may be considered best clinical practice in the absenceof specific studies of ventilatory strategy in burns inhalationalinjury.20 High-frequency percussive ventilation (HFPV) has beenreported to decrease both the incidence of pulmonary barotraumaand pneumonia in inhalation injury. It has evolved into a ventila-tory modality promoted to rapidly remove airway secretions andimprove survival of patients with smoke inhalation injury.21 Itsfurther evaluation is necessary before any specific recommenda-tions can be made.

The use of vascularly inserted extracorporeal devices that assistin the removal of carbon dioxide, whilst providing some additionaloxygenation are emerging. They are potentially useful in allowinglow tidal volume (LTV) ventilation, whilst maintaining the gas-exchange functions of the lung, as a bridge to recovery. No robustevidence to support their use yet exists, and they should beconsidered only for named patients in a rescue setting. Interest-ingly, a recent animal study of arteriovenous carbon dioxideremoval in conjunction with LTV ventilation showed improvedoutcome over those supported by LTV or HFPV alone.22

Non-invasive positive pressure ventilation (NIV) is an importanttechnique which has been shown to prevent the need for intuba-tion and improve respiratory weaning in a number of criticalpulmonary and cardiac conditions, such as chronic obstructivepulmonary disease, respiratory failure due to pulmonary infectionin immunosuppressed patients and CPAP non-responsive cardio-genic pulmonary oedema. While there is some evidence to supportits use in burned patients with respiratory failure,23 there isa paucity of such evidence specifically aimed at the management ofthose with inhalation injury.

4.2.3. BronchoscopySome centres routinely perform bronchoscopy rather than

laryngoscopy. Although such an approach allows visualisation fromthe mouth to the level of bronchopulmonary subsegments, theappearance of the subglottic airways does not definitively affectmanagement and appears unreliable in predicting the need forventilator support.24,25 Lavage should be performed if pulmonarycontamination is present. Care should be maintained since exces-sive saline lavage may induce lung injury. The safe volume is notdefined.

The use of local airway therapies such as nebulised unfractio-nated heparin (300–1000 IU/kg per day for 3–5 days) or mucolyticssuch as N-acetylcysteine to improve airway clearance of mucusplugs or mucosal webs from sloughed airway lining (and as anti-oxidants), whilst in use sporadically, have not been subjected torigorous trials.

S. Singh, J. Handy / Current Anaesthesia & Critical Care 19 (2008) 264–268 267

4.3. Cardiovascular/disability/exposure

The assessment of these elements within the primary surveywill be greatly influenced by the presence or absence of otherinjuries such as cutaneous burns or multiple trauma. Early clinicalsigns of cardiovascular inadequacy include tachycardia, delayedcapillary return (greater than 2 s) and tachypnoea. Hypotension isa late sign and will often occur with decreased skin perfusion (pale,cold and clammy). Continuous electrocardiography (ECG) andregular blood pressure monitoring should be instituted as a basicstandard of care, with continuous blood pressure monitoringconsidered for the more severely ill. Decreased conscious level inthe absence of head injury should raise the possibility of criticallylow oxygen delivery due to cardiovascular inadequacy or toxicitythrough carbon monoxide or cyanide. In this context it is a pre-terminal sign that warrants immediate action.

Both arterial and central venous blood gas analysis provideuseful information pertaining to oxygen delivery:

� increasing base deficit and blood lactate are suggestive ofinadequate tissue oxygenation which in the presence ofdecreased central venous oxygen saturation (ScvO2) is likelydue to cardiovascular insufficiency� if the ScvO2 is raised, cyanide toxicity should be considered and

treated empirically� worsening acidosis; measurement of anion gap (corrected for

albumin and phosphate levels) and osmolar gap will aid in thediagnosis of other acidifying toxins

Whole blood cyanide levels should be sent to confirm thediagnosis, but the results of this test are generally not available ina timely fashion and empiric treatment must be instituted if thediagnosis is suspected.18

Sodium thiosulphate acts slowly by catalysing the metabolismof cyanide. Sodium nitrite reduces cyanide binding by oxidation ofhaemoglobin to methaemoglobin (MetHb). Methaemoglobin levelsof about 40% should be targeted. MetHb levels may require moni-toring cyanide binding agents such as dicobalt edetate or hydrox-ocobalamin may be used, though the former may induce cardiacarrhythmias and instability if used in the absence of cyanidepoisoning. There are suggestions, albeit from one non-randomisedstudy, that early empirical treatment with hydroxycobalamin insuspected cases of burns-related inhalational injury improvessurvival rates.26

4.4. Other aspects of management

The overall management of such patients will largely be dictatedby the organ dysfunction that poses the greatest threat to life.

Standard established practices for the critically ill apply to burnsrespiratory injury too. Thus, chest physiotherapy remains widelyaccepted management despite a lack of evidence to support it.

Therapies employed in the management of long-term critically illand mechanically ventilated patients should be considered. Exam-ples include the use of prophylaxis against venous thrombo-embo-lism and gastrointestinal stress ulceration, and measures to reduceventilator associated pneumonia, (e.g. >30� head up). Patients whohave suffered inhalation injury are at risk of developing pulmonaryinfections but there is no evidence to support the use of prophylacticantibiotics. Meticulous surveillance, appropriate cultures andconservative use of targeted antibiotic courses, with therapy guidedby close liaison with microbiology colleagues is encouraged.

Acute lung injury from any cause is associated with increasedenergy expenditure requiring careful nutritional supplementationin order to avoid protein-calorie malnutrition and its associatedincrease in morbidity and mortality. This situation is significantly

exacerbated by the presence of other injuries; none more so thancutaneous burns. These patients should have regular nutritionalassessment and the involvement of clinicians with appropriatedietetic experience is advised.

4.4.1. Fluid managementThere is little doubt that inhalation injury can result in large

fluid losses which require replacement and resuscitation. Howeverthere is an increasing suggestion that patients with inhalation andburn injury are experiencing over-resuscitation with detrimentalresults. Over-hydration results in increased lung and tissue oedemawith decreased lung and chest wall compliance. These factors willexacerbate existing impairment in gas exchange and ventilationand can lead to worsened outcome. Currently there is interest inutilising different end-points in fluid resuscitation in order to allowa state of ‘permissive hypovolaemia’ for such patients27 thoughthere is an absence of large scale trials examining this strategy.

4.5. Future therapies

Exogenous surfactant, leukotriene inhibitors, and antioxidantsare a few compounds that have been investigated in animal modelsof smoke inhalation. These, and experience extrapolated fromclinical trials (all of them negative) in acute lung injury raise thepossibility of these compounds having a future role in the treat-ment of burns inhalation injury.

4.5.1. Exogenous surfactantExogenous administration of a surfactant preparation to dogs

immediately after wood smoke inhalation injury can improve gasexchange and compliance in the first few hours.28

4.5.2. AntioxidantsThe extent of oxidant stress (i.e. lipid peroxidation) in the lung

and systemically, correlates well with respiratory failure andmortality in a rat model of burns inhalation injury.29 In a sheepmodel, fluid resuscitation with a deferoxamine hetastarch complex(a free iron and hydroxyl radical scavenger) attenuates both airwayand systemic inflammation.30

5. Conclusions

Inhalation injury is a disease process commonly associated withburn injury that may require management in a general intensivecare unit setting. Despite a significant morbidity and mortality,robust research data into the pathophysiology and optimummanagement of this condition is limited. The mainstay of currentcare involves aggressive attention to the trauma primary surveyand consideration and treatment of noxious gaseous toxins. Thisshould be followed by a multi-disciplinary approach with meticu-lous attention to the ‘basics’ of critical care including preventionand limitation of iatrogenic problems, nutritional and systemicsupport and aggressive rehabilitation.

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