Inhalation Inhalation InjuryInjury

Arek Wiktor M.D.Arek Wiktor M.D.

Burn FellowBurn Fellow

University of Colorado University of Colorado HospitalHospital

OutlineOutline BackgroundBackground SmokeSmoke PathophysiologyPathophysiology DiagnosisDiagnosis TreatmentTreatment Specific Lethal CompoundsSpecific Lethal Compounds

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Learning ObjectivesLearning Objectives

Describe the pathophysiology of Describe the pathophysiology of inhalation injuryinhalation injury

How is inhalation injury diagnosed?How is inhalation injury diagnosed? What adjunctive measures are used What adjunctive measures are used

to treat inhalation injury?to treat inhalation injury? What is the treatment for carbon What is the treatment for carbon

monoxide and cyanide poisoning?monoxide and cyanide poisoning?

A Sunday afternoon stroll thru A Sunday afternoon stroll thru the fire…the fire…

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EpidemiologyEpidemiology

15-30% of burn admissions have 15-30% of burn admissions have inhalation injuryinhalation injury

Independent predictor of mortality, Independent predictor of mortality, ↑ by 20%↑ by 20%

Increases pneumonia riskIncreases pneumonia risk Leading diagnosis of those Leading diagnosis of those

hospitalized and treated on 9/11, hospitalized and treated on 9/11, World Trade Center attackWorld Trade Center attack

Anatomic ClassificationAnatomic Classification

Upper airwayUpper airway Lower airwayLower airway Systemic toxicitySystemic toxicity

http://www.monroecc.edu/depts/pstc/backup/parasan4.htm

SMOKESMOKE

Variable, changes with time burningVariable, changes with time burning Toxic gases and low ambient oxygenToxic gases and low ambient oxygen Ingredients:Ingredients:

Aldehydes (formaldehyde, acrolein), ammonia, Aldehydes (formaldehyde, acrolein), ammonia, hydrogen sulfide, sulfur dioxide, hydrogen chloride, hydrogen sulfide, sulfur dioxide, hydrogen chloride, hydrogen fluoride, phosgene, nitrogen dioxide, organic hydrogen fluoride, phosgene, nitrogen dioxide, organic nitrilesnitriles

Particulate matter Particulate matter

Prien et al. Burns 1988; 14:451-460

PathophysiologyPathophysiology

Cilia loss, respiratory epithelial Cilia loss, respiratory epithelial sloughingsloughing

Neutrophilic infiltrationNeutrophilic infiltration Atelectasis, occlusion by Atelectasis, occlusion by

debris/edemadebris/edema PseudomembranesPseudomembranes Bacterial colonization at 72 hrsBacterial colonization at 72 hrs

Hubbard et al. J Trauma 1991; 31:1477-1486

Bartley et al. Drug Design, Development and Therapy. 2008; 2: 9–16.

Secondary Lung InjurySecondary Lung Injury

Unilateral smoke inhalation damages Unilateral smoke inhalation damages contralateralcontralateral lung lung

Immune response, increased Immune response, increased permeabilitypermeability

Oxygen-derived free radicalsOxygen-derived free radicals NO mediated damage (chemotactic NO mediated damage (chemotactic

factor neuts)factor neuts) Eiscosanoids (TXA2→TXB2)Eiscosanoids (TXA2→TXB2) Reduced phagocytosis in macrophagesReduced phagocytosis in macrophages

Systemic EffectsSystemic Effects

Larger fluid resuscitation Larger fluid resuscitation (2→5cc/kg/%)(2→5cc/kg/%)

Additive effect to burnsAdditive effect to burns 12% pts inhalation injury alone 12% pts inhalation injury alone

require intubationrequire intubation**

62% pts burn + inhalation injury 62% pts burn + inhalation injury intubatedintubated**

Clark et al. J Burn Care Rehabilitation, 1990; 11:121-134

Miller et al. Journal of Burn Care Research. 2009; 30(2) 249-256

DiagnosisDiagnosis Clinical findings:Clinical findings:

Facial burns (96%)Facial burns (96%) Wheezing (47%)Wheezing (47%) Carbonaceous sputum (39%)Carbonaceous sputum (39%) Rales (35%)Rales (35%) Dyspnea (27%)Dyspnea (27%) Hoarsness (26%)Hoarsness (26%) Tachypnea (26%)Tachypnea (26%) Cough (26%)Cough (26%) Cough and hypersecretion (26%)Cough and hypersecretion (26%)

DiVincenti et al. Journal of Trauma, 1971; 11:109-117

NO NO ONEONE FINDING IS FINDING IS SUFFICIENTLY SUFFICIENTLY SENSITIVE OR SENSITIVE OR

SPECIFIC!SPECIFIC!

Must use clinical Must use clinical judgment!judgment!

Tools for DiagnosisTools for Diagnosis

BronchoscopyBronchoscopy Pulmonary function testingPulmonary function testing XenonXenon133133 lung scan lung scan

Grades of Inhalation Grades of Inhalation InjuryInjury

Endorf and Gamelli. Journal of Burn Care and Research. 2007; 28:80-83

TreatmentsTreatments

Airway ControlAirway Control Chest physiotherapyChest physiotherapy SuctioningSuctioning Therapeutic bronchoscopyTherapeutic bronchoscopy Ventilatory strategiesVentilatory strategies Pharmacologic adjunctsPharmacologic adjuncts

TreatmentTreatment

Control the Control the Airway!!!Airway!!!

≥ ≥ 40% burn40% burn Transport Transport

http://www.burnsurgery.com/Betaweb/Modules/initial/bsinitialsec2.htm

Ventilator StrategiesVentilator Strategies Airway pressure release ventilation Airway pressure release ventilation

(APRV)(APRV) Intrapulmonary percussive Intrapulmonary percussive

ventilation (IPV)ventilation (IPV) High-frequency percussive High-frequency percussive

ventilation (HFPV)ventilation (HFPV) High frequency oscillatory High frequency oscillatory

ventilation (HFOV)ventilation (HFOV)

Chung et al. CCM; 2010: 38(10) 1970-1977

Single center, prospective randomized Single center, prospective randomized trial 2006-2009trial 2006-2009

387 pts screened387 pts screened 31 pts HFPV, 31 pts LTV (ARDSnet)31 pts HFPV, 31 pts LTV (ARDSnet)

ResultsResults No significant difference in mortality or No significant difference in mortality or

ventilator free daysventilator free days Significant difference in “Rescue Significant difference in “Rescue

Therapy”Therapy”

ResultsResults No significant difference in mortality or No significant difference in mortality or

ventilator free daysventilator free days Significant difference in “Rescue Significant difference in “Rescue

Therapy”Therapy”

P/F ratio vs Ventilator P/F ratio vs Ventilator ModeMode

Chung et al. CCM; 2010: 38(10) 1970-1977

Study ConclusionsStudy Conclusions

Study stopped for safety concerns in Study stopped for safety concerns in LTV groupLTV group

Gas exchange goals met in all HFPV Gas exchange goals met in all HFPV pts, and not in 1/3 of LTV ptspts, and not in 1/3 of LTV pts

Trend for less barotrauma, less VAP, Trend for less barotrauma, less VAP, less sedationless sedation

““Strict application of LTV may be Strict application of LTV may be suboptimal in the burn suboptimal in the burn

population”population”

Pharmacologic Pharmacologic InterventionIntervention

Bartley et al. Drug Design, Development and Therapy. 2008; 2: 9–16.

Pharmacologic Pharmacologic InterventionIntervention

Bartley et al. Drug Design, Development and Therapy. 2008; 2: 9–16.

Airway Obstructive CastsAirway Obstructive Casts

Mucus secretionsMucus secretions Denuded airway epithelial cellsDenuded airway epithelial cells Inflammatory cellsInflammatory cells FibrinFibrin

-Solidifies airway content-Solidifies airway content Several studies shown reduction in Several studies shown reduction in

size of casts with fibrinolytic agents size of casts with fibrinolytic agents (tPA)(tPA)

CastsCasts

Enkhbaatar et al., 2007

Theory Behind Inhaled Theory Behind Inhaled HeparinHeparin

Animals with Burn + ARDS have Animals with Burn + ARDS have decreased decreased levels of antithrombin in levels of antithrombin in plasma and BAL specimensplasma and BAL specimens

Heparin potentiates antithrombin by Heparin potentiates antithrombin by 2000x2000x

Prevention of fibrin deposition in lungsPrevention of fibrin deposition in lungs Heparin inhibits antihrombin’s anti-Heparin inhibits antihrombin’s anti-

inflammatory effect - ? systemic rhAT ?inflammatory effect - ? systemic rhAT ?

Shriners Protocol Shriners Protocol Since 1990 (560+ patients Since 1990 (560+ patients

treated)treated)

Mlcak RP et al. Burns, 2007;33:2-13

Evidence Evidence (Pro)(Pro)

Desai et al. 1998Desai et al. 1998 Pediatric burns (90 pts total)Pediatric burns (90 pts total) 1985-1989 (43) vs 1990-1994 (47pts)1985-1989 (43) vs 1990-1994 (47pts) ↓ ↓ reintubation, atelectasis, and mortalityreintubation, atelectasis, and mortality

Miller et al. 2009Miller et al. 2009 30 patients over 5 years, retrospective review30 patients over 5 years, retrospective review Tx 10,000 units heparin, 20% NA, 0.5 ml AS q4 Tx 10,000 units heparin, 20% NA, 0.5 ml AS q4

hrshrs Survival benefit, improved LIS scores, Survival benefit, improved LIS scores,

compliancecompliance Number needed to treat 2.73Number needed to treat 2.73

Evidence Evidence (Con)(Con)

Holt et al. 2008Holt et al. 2008 Retrospective review 1999-2005, 150 pts totalRetrospective review 1999-2005, 150 pts total Burn size, LOS, time on vent, mortality SAMEBurn size, LOS, time on vent, mortality SAME Only 68% pts had bronchoscopy, Only 68% pts had bronchoscopy, Attending discretion which treatment to useAttending discretion which treatment to use

TOXIC GASESTOXIC GASES

Carbon Monoxide (CO)Carbon Monoxide (CO)

CO from incomplete combustion CO from incomplete combustion CO + Hb → COHb CO + Hb → COHb (affinity 200-250x)(affinity 200-250x)

LEFTLEFT shift of oxy-Hb curve (Haldane shift of oxy-Hb curve (Haldane effect)effect)

CO binding to intracellular cytochromes CO binding to intracellular cytochromes and metalloproteins and metalloproteins (myoglobin)(myoglobin)

““Two compartment” pharmacokineticsTwo compartment” pharmacokinetics Animal experiment 64% COHb transfusionAnimal experiment 64% COHb transfusion

CO Toxicity SymptomsCO Toxicity Symptoms

““Cherry-red lips, cyanosis, retinal Cherry-red lips, cyanosis, retinal hemorrhage”-hemorrhage”- rare rare

CNS and Cardiovascular CNS and Cardiovascular ↑ ↑ RR, ↑HR, dysrhythmias, MI, ↓BP, coma, RR, ↑HR, dysrhythmias, MI, ↓BP, coma,

seizuresseizures Delayed neuropsychiatric syndrome (3-Delayed neuropsychiatric syndrome (3-

240d)240d) Cognitive/personality Cognitive/personality

changes/parkinsonianismchanges/parkinsonianism Spontaneous resolutionSpontaneous resolution

Signs and SymptomsSigns and Symptoms

Weaver LK. N Engl J Med 2009;360:1217-25.

CO Toxicity DiagnosisCO Toxicity Diagnosis Pulse oximetry false Pulse oximetry false

HIGH SpOHIGH SpO22

Need Need cooximetrycooximetry direct measurement direct measurement of COHbof COHb Older ABG analyzers Older ABG analyzers

(estimate off dissolved PO(estimate off dissolved PO22))

MRI – lesions globus MRI – lesions globus pallidus/basal pallidus/basal ganglia/deep white ganglia/deep white mattermatter

COHbCOHb%%

SymptomsSymptoms

0-50-5 NormalNormal

15-2015-20 Headache, Headache, confusion, confusion, fatiguefatigue

20-4020-40 Hallucination, Hallucination, vision vision ΔΔ’s’s

40-6040-60 Combative, Combative, comacoma

60 +60 + CardiopulmonarCardiopulmonary arresty arrest

CO Toxicity DiagnosisCO Toxicity Diagnosis Pulse oximetry false Pulse oximetry false

HIGH SpOHIGH SpO22

Need Need cooximetrycooximetry direct measurement direct measurement of COHbof COHb Older ABG analyzers Older ABG analyzers

(estimate off dissolved PO(estimate off dissolved PO22))

MRI – lesions globus MRI – lesions globus pallidus/basal pallidus/basal ganglia/deep white ganglia/deep white mattermatter

COHbCOHb%%

SymptomsSymptoms

0-50-5 NormalNormal

15-2015-20 Headache, Headache, confusion, confusion, fatiguefatigue

20-4020-40 Hallucination, Hallucination, vision vision ΔΔ’s’s

40-6040-60 Combative, Combative, comacoma

60 +60 + CardiopulmonarCardiopulmonary arresty arrest

CO Toxicity TreatmentCO Toxicity Treatment OXYGENOXYGEN Half-life COHb (min)Half-life COHb (min)

Carbogen – normobaric, normocapnic, Carbogen – normobaric, normocapnic, hyperventilation (4.5-4.8% COhyperventilation (4.5-4.8% CO22))

Hyperbaric oxygen???Hyperbaric oxygen???

RA RA 1AT1ATMM

100100% O% O22

100% 100% OO2 2 2.5 2.5 ATMATM

MaleMale 240240 4747 2222

FemaFemalele

168168 3333 1515

Cyanide (CN)Cyanide (CN)

Combustion of synthetics (plastics, Combustion of synthetics (plastics, foam, varnish, paints, wool, silk)foam, varnish, paints, wool, silk)

Binds to cytochrome c oxidase – dose Binds to cytochrome c oxidase – dose dependentdependent

Uncouple mitochondriaUncouple mitochondria Aerobic → anaerobic = Lactic acidAerobic → anaerobic = Lactic acid Half-life 1-3 hoursHalf-life 1-3 hours

CN Toxicity SymptomsCN Toxicity Symptoms

DyspneaDyspnea TachypneaTachypnea VomitingVomiting BradycardiaBradycardia HypotensionHypotension Giddiness/Coma/SiezuresGiddiness/Coma/Siezures DeathDeath* The smell of bitter almonds on the breath * The smell of bitter almonds on the breath

suggests exposure (cannot be detected by suggests exposure (cannot be detected by 60% of the population)60% of the population)

CN Toxicity DiagnosisCN Toxicity Diagnosis

No rapid assayNo rapid assay High lactate (>10mmol/L) (High lactate (>10mmol/L) (s/s, 87%/94%)s/s, 87%/94%)

Metabolic acidosisMetabolic acidosis ElevatedElevated mixed venous saturation mixed venous saturation

(<10% a-v) difference(<10% a-v) difference High index of suspicionHigh index of suspicion

** Also get: COHb and Methemoglobin ** Also get: COHb and Methemoglobin levelslevels

CN TreatmentCN Treatment

Cyanokit (Hydroxocobalamin)Cyanokit (Hydroxocobalamin) 70mg/kg dose (5g vials)70mg/kg dose (5g vials) Combines with cyanide to from Combines with cyanide to from

cyanocobalamin (Vit B12)cyanocobalamin (Vit B12) Red membranes/urineRed membranes/urine Hypertension, Anaphylaxis Hypertension, Anaphylaxis 5% increase COHb, interfere with HD 5% increase COHb, interfere with HD

LFTs/Cr/Fe levels LFTs/Cr/Fe levels

Cyanide Antidote Kit (CAK)Cyanide Antidote Kit (CAK)Amyl nitrite pearls, sodium nitrite, and sodium thiosulfateAmyl nitrite pearls, sodium nitrite, and sodium thiosulfate

Amyl nitrateAmyl nitrate and and sodium nitratesodium nitrate induce induce methemoglobinmethemoglobin

Methemoglobin+cyanide→releases cyanide from CCMethemoglobin+cyanide→releases cyanide from CC Sodium thiosulfateSodium thiosulfate enhances enhances

cyandide→thiocynate→renal excretioncyandide→thiocynate→renal excretion Avoid nitrate portion in pts with inhalation Avoid nitrate portion in pts with inhalation

injury (COHb >10%)injury (COHb >10%) Vasodilation and hypotensionVasodilation and hypotension

Acquired Acquired MethemolgobinemiaMethemolgobinemia

NO2, NO, benzene gases → oxidation NO2, NO, benzene gases → oxidation of ironof iron

FeFe2+2+ → Fe → Fe3+ 3+

Shift curve to Shift curve to LEFTLEFT Blood Blood “Chocolate brown color”“Chocolate brown color” Normal PaO2, pulse ox >85%Normal PaO2, pulse ox >85% Tx: Tx: Methylene blueMethylene blue (1-2 mg/kg Q (1-2 mg/kg Q

30-60min)30-60min)

Final ThoughtsFinal Thoughts

Inhalation injury is badInhalation injury is bad Support the airwaySupport the airway Frequent bronchoscopy and Frequent bronchoscopy and

monitoringmonitoring Different ventilatory strategiesDifferent ventilatory strategies Adjunctive measures need further Adjunctive measures need further

investigationinvestigation

The Toilet SnorkelThe Toilet Snorkel

http://www.icbe.org/2006/01/18/the-toilet-snorkel/

Thank You!Thank You!

Learning ObjectivesLearning Objectives

Describe the pathophysiology of Describe the pathophysiology of inhalation injuryinhalation injury

How is inhalation injury diagnosed?How is inhalation injury diagnosed? What adjunctive measures are used What adjunctive measures are used

to treat inhalation injury?to treat inhalation injury? What is the treatment for carbon What is the treatment for carbon

monoxide and cyanide poisoning?monoxide and cyanide poisoning?