Smoke Inhalation Injury Medication
- Author: Keith A Lafferty, MD; Chief Editor: Joe Alcock, MD, MS more...
The primary treatment of smoke inhalation injury is oxygen. Bronchodilators may be of benefit in patients displaying bronchospasm. In addition, specific antidotes are methylene blue for methemoglobinemia and thiosulfate/sodium nitrite for cyanide (CN) poisoning. Certain patients with carbon monoxide (CO) toxicity may require hyperbaric oxygen therapy (HBO).
Oxygen is used for any suspected significant inhalation injury. Treat with high concentrations of humidified oxygen en route to the hospital.
Use of high oxygen flow rates and a nonrebreathing-type face mask with a tight seal facilitates delivery of high levels of supplemental oxygen, which helps reverse the oxygenation defect created by ventilation-perfusion mismatch. Inhaled oxygen also helps in the displacement of CO from hemoglobin, decreasing the half-life of carboxyhemoglobin from 4-6 hours in room air to 40-60 min in 100% fractional concentration of oxygen in inspired air (FiO2).
Hyperbaric oxygen therapy
HBO therapy also displaces CO from intracellular stores and may improve mitochondrial function. HBO requires special facilities that are not available at all centers, resulting in a delay in treatment while the patient is transported to facility with HBO.
Hyperbaric therapy should be considered in those patients who have high carboxyhemoglobin levels >25%, who are unconsciousness, have other neurologic findings, or have severe metabolic acidosis (ph < 7.1). The benefit of treating patients 12 hours or more after CO exposure remains unproven.
These agents relieve reversible bronchospasm by relaxing smooth muscles of the bronchi. Increased resistance from airway edema and reflex bronchoconstriction from irritation of airway receptors contribute to airway obstruction.
Bronchodilators are important in the treatment of bronchoconstriction and bronchorrhea. Toxic smokes can cause bronchoconstriction, especially if the exposed individual has underlying asthma or chronic obstructive pulmonary disease (COPD). In patients with profound bronchoconstriction and wheezing, subcutaneous epinephrine has been helpful in stabilizing mast cells and halting or reversing potentially fatal bronchoconstriction.
Albuterol is a beta-agonist that is useful in treatment of bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by acting on beta2-receptors, while having little effect on cardiac muscle contractility. Airway resistance is decreased, and ventilation is improved.
Racemic epinephrine alleviates airway edema and reflex bronchospasm. Although it has not been directly studied in smoke inhalation, inhaled racemic epinephrine can theoretically provide relief from both airway edema and reflex bronchospasm in this setting.
Terbutaline is used for severe bronchoconstriction, especially in patients with underlying reactive airways disease. This agent acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
Epinephrine is used for severe bronchoconstriction, especially in patients with underlying reactive airways disease. This agent has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. The beta-agonist effects of epinephrine include bronchodilation, chronotropic cardiac activity, and positive inotropic effects.
Several CN antidotes exist, which work by different mechanisms of action. Hydroxocobalamin binds to CN to form cyanocobalamin. Amyl nitrite and sodium nitrite convert a portion of circulating hemoglobin to methemoglobin. Sodium thiosulfate allows the production of thiocyanate.
After formation of methemoglobin and production of cyanomethemoglobin, thiosulfate acts as a sulfur donor to the endogenous enzyme rhodanese. This enzyme removes CN from the cyanomethemoglobin complex and forms thiocyanate, which is excreted renally. CN also is removed directly from cytochrome oxidase and is converted to thiocyanate in the presence of thiosulfate via the enzyme rhodanese.
Methylene blue is used to convert methemoglobin to oxyhemoglobin. It contains a tetramethyl thionine chloride moiety that is reduced (it is an electron acceptor) in the presence of nicotinamide adenine dinucleotide phosphate–oxidase (NADPH) and methemoglobin reductase to leukomethylene blue. Leukomethylene blue then becomes available to reduce methemoglobin to oxyhemoglobin.
Methylene blue may be ineffective in treating patients with glucose-6-phosphodiesterase (G-6-PD0 deficiency because, in the hexose monophosphate shunt, G-6-PD is essential for the generation of NADPH. Without NADPH, methylene blue cannot act as a reducing agent in the transformation of methemoglobin to oxyhemoglobin.
Hydroxocobalamin is a vitamin B-12 precursor that contains a cobalt ion, which has greater affinity for cyanide than does cytochrome oxidase. Binding of cyanide to the cobalt ion results in the formation of cyanocobalamin, which is excreted renally. Hydroxocobalamin has few adverse effects and has the following advantages over other cyanide treatments:
This agent is safe to use in victims of smoke inhalation.[59, 60] Cyanocobalamin is a pigmented compound, and interferes with spectrophotometric tests. Any necessary blood samples should be drawn prior to administration of antidote if possible, because it will not be possible to obtain accurate results for most blood tests afterward.
In the presence of nitrites, hemoglobin is converted to methemoglobin, which has a higher binding affinity for CN than does the cytochrome oxidase complex. Administration of amyl nitrite produces a methemoglobin level of 5% and subsequent formation of cyanomethemoglobin, allowing electron transport and cellular respiration to continue. This medication is given until an IV line is established and sodium nitrite can be administered.
In the presence of nitrites, hemoglobin is converted to methemoglobin that has a higher binding affinity for CN than does the cytochrome oxidase complex. Administration of sodium nitrite produces a methemoglobin level of 20-30% and subsequent formation of cyanomethemoglobin, allowing electron transport and cellular respiration to continue.
Whether corticosteroids are beneficial in toxic smoke inhalation is a matter of some debate, but many experts consider these agents helpful in this setting. Corticosteroids are considered especially useful in metal fume fever, which is believed to be mediated by an inflammatory cascade of events involving cytokines and histamine release.
Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear neutrophils (PMNs) and reversing increased capillary permeability.
No reports exist as to the efficacy of chelating agents; however, dimercaprol and edetate calcium disodium (CaEDTA) have been suggested because of their ability to reduce serum zinc levels. Zinc toxicity may be treated with a combination of dimercaprol and CaEDTA or with EDTA alone. Nausea, vomiting, and elevated liver enzymes occur more commonly with combination therapy.
Dimercaprol is the drug of choice for treatment of mercury toxicity; although not formally indicated for zinc toxicity, its use has been suggested in the setting of severe zinc oxide inhalation injury, since it lowers serum zinc levels. It is administered by deep intramuscular injection.
Although edetate calcium disodium is used mostly in lead chelation, for which it is a second-line agent, treatment with this agent has been associated with lowering of serum zinc levels. Begin therapy 4 h after giving dimercaprol. The IV route is used exclusively, and continuous infusion is recommended.
Adjunctive therapy may be useful in patients with eye irritation accompanying smoke inhalation injury. These agents relax ciliary muscle spasm, which can cause deep aching pain and photophobia.
This agent acts at parasympathetic sites in smooth muscle to block the response to acetylcholine of the sphincter muscle of the iris and the muscle of the ciliary body, causing mydriasis and cycloplegia.
These agents are indicated for topical treatment of patients who have experienced cutaneous exposure to sulfur trioxide or titanium tetrachloride.
Rinse affected skin thoroughly before applying sodium bicarbonate solution. Potential exists for exothermic reaction (burns) whenever a base is mixed with an acid; therefore, after titanium chloride or sulfur trioxide exposure, rinse affected skin thoroughly and copiously with water or saline.
Pharmacists at Walter Reed Medical Center recommend using a 5% solution of sodium bicarbonate to rinse over the affected area, followed by rinsing copiously with water or saline. The author feels that copious irrigation alone with water or saline should be sufficient, along with proper wound care, rather than introducing another chemical onto an already irritated area of skin.
Nebulized sodium bicarbonate may be helpful in cases of chlorine gas inhalation. It should not be used for inhalation of other gases.
Rorison DG, McPherson SJ. Acute toxic inhalations. Emerg Med Clin North Am. 1992 May. 10(2):409-35. [Medline].
de Lange DW, Meulenbelt J. Do corticosteroids have a role in preventing or reducing acute toxic lung injury caused by inhalation of chemical agents?. Clin Toxicol (Phila). 2011 Feb. 49(2):61-71. [Medline].
Bizovi KE, Leikin JD. Smoke inhalation among firefighters. Occup Med. 1995 Oct-Dec. 10(4):721-33. [Medline].
Hall AH, Dart R, Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?. Ann Emerg Med. 2007 Jun. 49(6):806-13. [Medline].
Buyantseva LV, Tulchinsky M, Kapalka GM, et al. Evolution of lower respiratory symptoms in New York police officers after 9/11: a prospective longitudinal study. J Occup Environ Med. 2007 Mar. 49(3):310-7. [Medline].
Thai A, Xiao J, Ammit AJ, Rohanizadeh R. Development of inhalable formulations of anti-inflammatory drugs to potentially treat smoke inhalation injury in burn victims. Int J Pharm. 2010 Apr 15. 389(1-2):41-52. [Medline].
Urbanetti JS. Toxic inhalational injury. Medical Aspects of Chemical and Biological Warfare. 1997. 260-267. [Full Text].
Belli S, Basaran O, Ozdemir BH, et al. Protective role of simvastatin on lung damage caused by burn and cotton smoke inhalation in rats. J Surg Res. 2011 May 15. 167(2):e283-90. [Medline].
Kao LW, Nanagas KA. Toxicity associated with carbon monoxide. Clin Lab Med. 2006 Mar. 26(1):99-125. [Medline].
Goldbaum LR, Ramirez RG, Absalon KB. What is the mechanism of carbon monoxide toxicity?. Aviat Space Environ Med. 1975 Oct. 46(10):1289-91. [Medline].
Lawson-Smith P, Jansen EC, Hyldegaard O. Cyanide intoxication as part of smoke inhalation--a review on diagnosis and treatment from the emergency perspective. Scand J Trauma Resusc Emerg Med. 2011 Mar 3. 19:14. [Medline]. [Full Text].
Stewart RJ, Yamaguchi KT, Knost PM, Mason SW, Roshdieh BB, Samadani S. Effects of ibuprofen on pulmonary oedema in an animal smoke inhalation model. Burns. 1990 Dec. 16(6):409-13. [Medline].
Kimura R, Traber L, Herndon D, Niehaus G, Flynn J, Traber DL. Ibuprofen reduces the lung lymph flow changes associated with inhalation injury. Circ Shock. 1988 Mar. 24(3):183-91. [Medline].
Hill IR. Particulate matter of smoke inhalation. Ann Acad Med Singapore. 1993 Jan. 22(1):119-23. [Medline].
Chian CF, Wu CP, Chen CW, et al. Acute respiratory distress syndrome after zinc chloride inhalation: survival after extracorporeal life support and corticosteroid treatment. Am J Crit Care. 2010 Jan. 19(1):86-90. [Medline].
Hsu HH, Tzao C, Chang WC, Wu CP, Tung HJ, Chen CY, et al. Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high-resolution CT findings, and pulmonary function test results. Chest. 2005 Jun. 127(6):2064-71. [Medline].
Conner MW, Flood WH, Rogers AE, Amdur MO. Lung injury in guinea pigs caused by multiple exposures to ultrafine zinc oxide: changes in pulmonary lavage fluid. J Toxicol Environ Health. 1988. 25(1):57-69. [Medline].
Marrs TC, Colgrave HF, Edginton JA, Brown RF, Cross NL. The repeated dose toxicity of a zinc oxide/hexachloroethane smoke. Arch Toxicol. 1988. 62(2-3):123-32. [Medline].
Loh CH, Chang YW, Liou SH, Chang JH, Chen HI. Case report: hexachloroethane smoke inhalation: a rare cause of severe hepatic injuries. Environ Health Perspect. 2006 May. 114(5):763-5. [Medline]. [Full Text].
Keyes DC. Metal fume fever. Dart RC. Medical Toxicology. 3rd ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2004. 88-89.
Kuschner WG, D'Alessandro A, Wong H, Blanc PD. Early pulmonary cytokine responses to zinc oxide fume inhalation. Environ Res. 1997 Oct. 75(1):7-11. [Medline].
Agency for Toxic Substances & Disease Registry. Sulfur Trioxide & Sulfuric Acid. Toxic Substances Portal. Available at http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=256&tid=47. Accessed: May 9, 2013.
Weiss SM, Lakshminarayan S. Acute inhalation injury. Clin Chest Med. 1994 Mar. 15(1):103-16. [Medline].
Harduar-Morano L, Watkins S. Review of unintentional non-fire-related carbon monoxide poisoning morbidity and mortality in Florida, 1999-2007. Public Health Rep. 2011 Mar-Apr. 126(2):240-50. [Medline]. [Full Text].
Duclos P, Sanderson LM, Lipsett M. The 1987 forest fire disaster in California: assessment of emergency room visits. Arch Environ Health. 1990 Jan-Feb. 45(1):53-8. [Medline].
US Fire Administration’s (USFA’s) National Fire Incident Reporting System (NFIRS). Fatal Fires in Residential Buildings. US Department of Homeland Security, US Fire Administration. August 2010. Available at http://www.usfa.fema.gov/downloads/pdf/statistics/v11i2.pdf.
Barillo DJ, Goode R. Fire fatality study: demographics of fire victims. Burns. 1996 Mar. 22(2):85-8. [Medline].
Karter MJ Jr. Fire Loss in the United States during 2011. National Fire Protection Association, September 2012. Pediatrics. Available at http://www.nfpa.org/assets/files/pdf/os.fireloss.pdf. Accessed: May 14, 2013.
Istre GR, McCoy MA, Osborn L, Barnard JJ, Bolton A. Deaths and injuries from house fires. N Engl J Med. 2001 Jun 21. 344(25):1911-6. [Medline].
Large AA, Owens GR, Hoffman LA. The short-term effects of smoke exposure on the pulmonary function of firefighters. Chest. 1990 Apr. 97(4):806-9. [Medline].
Hoyert DL, Xu. Deaths: Preliminary Data for 2011. National Vital Statistics Reports. Available at http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf. Accessed: May 14, 2013.
Marshall SW, Runyan CW, Bangdiwala SI, Linzer MA, Sacks JJ, Butts JD. Fatal residential fires: who dies and who survives?. JAMA. 1998 May 27. 279(20):1633-7. [Medline].
Muller MJ, Pegg SP, Rule MR. Determinants of death following burn injury. Br J Surg. 2001 Apr. 88(4):583-7. [Medline].
Chou KJ, Fisher JL, Silver EJ. Characteristics and outcome of children with carbon monoxide poisoning with and without smoke exposure referred for hyperbaric oxygen therapy. Pediatr Emerg Care. 2000 Jun. 16(3):151-5. [Medline].
Whitelock-Jones L, Bass DH, Millar AJ, Rode H. Inhalation burns in children. Pediatr Surg Int. 1999. 15(1):50-5. [Medline].
Roney N, Smith CV, Williams M. Toxicological Profile for Zinc (Update). US Dept of Health & Human Services. 2007. Available at http://www.atsdr.cdc.gov/toxprofiles/tp60.html#bookmark07.
Baud FJ, Barriot P, Toffis V, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med. 1991 Dec 19. 325(25):1761-6. [Medline].
Lahn M, Sing W, Nazario S, Fosberg D, Bijur P, Gallagher EJ. Increased blood lead levels in severe smoke inhalation. Am J Emerg Med. 2003 Oct. 21(6):458-60. [Medline].
Chou CH, Kao TW, Liou SH, Chen HI, Ku HY, Chuang HJ, et al. Hematological abnormalities of acute exposure to hexachloroethane smoke inhalation. Inhal Toxicol. 2010 May. 22(6):486-92. [Medline].
Koljonen V, Maisniemi K, Virtanen K, Koivikko M. Multi-detector computed tomography demonstrates smoke inhalation injury at early stage. Emerg Radiol. 2007 Jun. 14(2):113-6. [Medline].
Agee RN, Long JM 3rd, Hunt JL, Petroff PA, Lull RJ, Mason AD Jr, et al. Use of 133xenon in early diagnosis of inhalation injury. J Trauma. 1976 Mar. 16(3):218-24. [Medline].
Carr JA, Phillips BD, Bowling WM. The utility of bronchoscopy after inhalation injury complicated by pneumonia in burn patients: results from the National Burn Repository. J Burn Care Res. 2009 Nov-Dec. 30(6):967-74. [Medline].
Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002 Oct 3. 347(14):1057-67. [Medline].
Wolf SJ, Lavonas EJ, Sloan EP, Jagoda AS. Clinical policy: Critical issues in the management of adult patients presenting to the emergency department with acute carbon monoxide poisoning. Ann Emerg Med. 2008 Feb. 51(2):138-52. [Medline].
Kung SW, Chan YC, Lau FL. Hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2008 Jan. 51(1):108; author reply 108-9. [Medline].
Borron SW, Baud FJ, Barriot P, Imbert M, Bismuth C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007 Jun. 49(6):794-801, 801.e1-2. [Medline].
Huzar TF, George T, Cross JM. Carbon monoxide and cyanide toxicity: etiology, pathophysiology and treatment in inhalation injury. Expert Rev Respir Med. 2013 Apr. 7(2):159-70. [Medline].
Oremus M, Hanson MD, Whitlock R, Young E, Archer C, Dal Cin A, et al. A systematic review of heparin to treat burn injury. J Burn Care Res. 2007 Nov-Dec. 28(6):794-804. [Medline].
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 May-Jun. 19(3):210-2. [Medline].
Huang PS, Tang GJ, Chen CH, Kou YR. Whole-body moderate hypothermia confers protection from wood smoke-induced acute lung injury in rats: the therapeutic window. Crit Care Med. 2006 Apr. 34(4):1160-7. [Medline].
Cancio LC. Airway management and smoke inhalation injury in the burn patient. Clin Plast Surg. 2009 Oct. 36(4):555-67. [Medline].
Nieman GF, Cigada M, Paskanik AM, et al. Comparison of high-frequency jet to conventional mechanical ventilation in the treatment of severe smoke inhalation injury. Burns. 1994 Apr. 20(2):157-62. [Medline].
Hall JJ, Hunt JL, Arnoldo BD, Purdue GF. Use of high-frequency percussive ventilation in inhalation injuries. J Burn Care Res. 2007 May-Jun. 28(3):396-400. [Medline].
DiGuiseppi C, Roberts I, Wade A, Sculpher M, Edwards P, Godward C, et al. Incidence of fires and related injuries after giving out free smoke alarms: cluster randomised controlled trial. BMJ. 2002 Nov 2. 325(7371):995. [Medline]. [Full Text].
Hall AH, Saiers J, Baud F. Which cyanide antidote?. Crit Rev Toxicol. 2009. 39(7):541-52. [Medline].
Shepherd G, Velez LI. Role of hydroxocobalamin in acute cyanide poisoning. Ann Pharmacother. 2008 May. 42(5):661-9. [Medline].
|Irritant gases||Ammonia||Fertilizer, refrigerant, manufacturing of dyes, plastics, nylon||Upper airway epithelial damage|
|Chlorine||Bleaching agent, sewage and water disinfectant, cleansing products||Lower airway epithelial damage|
|Sulfur dioxide||Combustion of coal, oil, cooking fuel, smelting||Upper airway epithelial damage|
|Nitrogen dioxide||Combustion of diesel, welding, manufacturing of dyes, lacquers, wall paper||Terminal airway epithelial damage|
|Asphyxiants (mitochondrial toxins)||Carbon monoxidea||Combustion of weeds, coal, gas, heaters||Competes for oxygen sites on hemoglobin, myoglobin, heme-containing intracellular proteins|
|Hydrogen cyanideb||Burning of polyurethane, nitrocellulose (silk, nylon, wool)||Tissue asphyxiation by inhibiting intracellular cytochrome oxidase activity, inhibits ATP production, leads to cellular anoxia|
|Hydrogen sulfidec||Sewage treatment facility, volcanic gases, coal mines, natural hot springs||Similar to cyanide, tissue asphyxiant by inhibition of cytochrome oxidase, leads to disruption of electron transport chain, results in anaerobic metabolism|
|Systemic toxins||Hydrocarbons||Inhalant abuse (toluene, benzene, Freon); aerosols; glue; gasoline; nail polish remover; typewriter correction fluid; ingestion of petroleum solvents, kerosene, liquid polishes||CNS narcosis, anesthetic stats, diffuse GI symptoms, peripheral neuropathy with weakness, coma, sudden death, chemical pneumonitis, CNS abnormalities, GI irritation, cardiomyopathy, renal toxicity|
|Organophosphates||Insecticides, nerve gases||Blocks acetylcholinesterase; cholinergic crisis with increased acetylcholine|
|Metal fumes||Metal oxides of zinc, copper, magnesium, jewelry making||Flulike symptoms, fever, myalgia, weakness|
|a Major component of smoke.
b Smells like almonds, component of smoke from fires.
c Smells like rotten eggs.