Phosgene Toxicity Clinical Manifestations and Treatment: A Systematic Review

Document Type : Systematic Review

Authors

Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

Abstract

Exposure to phosgene, a colourless poisonous gas, can lead to various health issues including eye irritation, a dry
and burning throat, vomiting, coughing, the production of foamy sputum, difficulty in breathing, and chest pain. This
systematic review aims to provide a comprehensive overview of the clinical manifestations and treatment of phosgene
toxicity by systematically analyzing available literature. The search was carried out on various scientific online databases
to include related studies based on inclusion and exclusion criteria with the use of PRISMA guidelines. The quality of
the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Thirteen articles were included in this
study after the screening process. Inhalation was found to be the primary health problem of phosgene exposure with
respiratory symptoms such as coughing and dyspnea. Chest pain and pulmonary oedema were also observed in some
cases. Furthermore, pulmonary crackle was the most common reported physical examination. Beyond respiratory tract
health issues, other organs involvements such as cardiac, skin, eye, and renal were also reported in some studies. The
symptoms can occur within minutes to hours after exposure, and the severity of symptoms depends on the amount of
inhaled phosgene. The findings showed that bronchodilators can alleviate symptoms of bronchoconstriction caused
by phosgene. Oxygen therapy is essential for restoring oxygen levels and improving respiratory function in cases
of hypoxemia. In severe cases, endotracheal intubation and invasive mechanical ventilation are used for artificial
respiration, along with the removal of tracheal secretions and pulmonary oedema fluid through suctioning as crucial
components of supportive therapy.

Keywords

Main Subjects

References

  1. Nicholson-Roberts TC. Phosgene use in World War 1 and early evaluations of pathophysiology. J R Army Med Corps. 2019; 165(3): 183-187.
  2. Cao C, Zhang L, Shen J. Phosgene-Induced acute lung injury: approaches for mechanism-based treatment strategies. Front Immunol. 2022; 13: 917395.
  3. Graham S, Fairhall S, Rutter S, Auton P, Rendell R, Smith A, et al. Continuous positive airway pressure: An early intervention to prevent phosgene-induced acute lung injury. Toxicol Lett. 2018; 293: 120-126.
  4. Grainge C, Jugg BJ, Smith AJ, Brown RF, Jenner J, Parkhouse DA, et al. Delayed low-dose supplemental oxygen improves survival following phosgene-induced acute lung injury. Inhal Toxicol. 2010; 22(7): 552-560.
  5. Li W, Rosenbruch M, Pauluhn J. Effect of PEEP on phosgene-induced lung edema: pilot study on dogs using protective ventilation strategies. Exp Toxicol Pathol. 2015; 67(2): 109-116.
  6. Nambiema A, Sembajwe G, Lam J, Woodruff T, Mandrioli D, Chartres N, et al. A protocol for the use of case reports/studies and case series in systematic reviews for clinical toxicology. Front Med (Lausanne). 2021; 8: 708380.
  7. Pauluhn J. Acute nose-only inhalation exposure of rats to di- and triphosgene relative to phosgene. Inhal Toxicol. 2011; 23(2): 65-73.
  8. Holmes WW, Keyser BM, Paradiso DC, Ray R, Andres DK, Benton BJ, et al. Conceptual approaches for treatment of phosgene inhalation-induced lung injury. Toxicol Lett. 2016; 244: 8-20.
  9. Lee LY. Respiratory sensations evoked by activation of bronchopulmonary C-fibers. Respir Physiol Neurobiol. 2009; 167(1): 26-35.
  10. Li W, Liu F, Wang C, Truebel H, Pauluhn J. Novel insights into phosgene-induced acute lung injury in rats: role of dysregulated cardiopulmonary reflexes and nitric oxide in lung edema pathogenesis. Toxicol Sci. 2013; 131(2): 612-628.
  11. Ivanhoe F, Meyers FH. Phosgene poisoning as an example of neuroparalytic acute pulmonary edema: the sympathetic vasomotor reflex involveD. Dis Chest. 1964; 46: 211-218.
  12. Pauluhn J. Phosgene inhalation toxicity: update on mechanisms and mechanism-based treatment strategies. Toxicology. 2021; 450: 152682.
  13. Vaish AK, Consul S, Agrawal A, Chaudhary SC, Gutch M, Jain N, et al. Accidental phosgene gas exposure: A review with background study of 10 cases. J Emerg Trauma Shock. 2013; 6(4): 271-275.
  14. Kumar A, Chaudhari S, Kush L, Kumar S, Garg A, Shukla A. Accidental inhalation injury of phosgene gas leading to acute respiratory distress syndrome. Indian J Occup Environ Med. 2012; 16(2): 88-89.
  15. Lo SH, Chan CC, Chen WC, Wang JD. Grand rounds: outbreak of hematologic abnormalities in a community of people exposed to leakage of fire extinguisher gas. Environ Health Perspect. 2006; 114(11): 1713-1717.
  16. Collins JJ, Molenaar DM, Bowler LO, Harbourt TJ, Carson M, Avashia B, et al. Results from the US industry-wide phosgene surveillance: the diller registry. J Occup Environ Med. 2011; 53(3): 239-244.
  17. Wyatt JP, Allister CA. Occupational phosgene poisoning: a case report and review. J Accid Emerg Med. 1995; 12(3): 212-213.
  18. Wells BA. Phosgene: a practitioner’s viewpoint. Toxicol Ind Health. 1985; 1(2): 81-92.
  19. Regan RA. Review of clinical experience in handling phosgene exposure cases. Toxicol Ind Health. 1985; 1(2): 69-72.
  20. Hardison LS Jr, Wright E, Pizon AF. Phosgene exposure: a case of accidental industrial exposure. J Med Toxicol. 2014; 10(1): 51-56.
  21. Ty SH, Sudha Ty DS, Sasanka KK, Nageswar Rao K, T P. Accidental phosgene poisoning: a case report and short review of management. Cureus. 2023; 15(7): e41679.
  22. Everett ED, Overholt EL. Phosgene poisoning. JAMA. 1968; 205(4): 243-245.
  23. Polednak AP. Mortality among men occupationally exposed to phosgene in 1943--1945. Environ Res. 1980; 22(2): 357-367.
  24. Gerritsen WB, Buschmann CH. Phosgene poisoning caused by the use of chemical paint removers containing methylene chloride in ill-ventilated rooms heated by kerosene stoves. Br J Ind Med. 1960; 17(3): 187-189.
  25. Galdston M, Luetscher JA, Longcope WT, Ballich NL, Kremer VL, Filley GL, et al. A study of the residual effects of phosgene poisoning in human subjects. i. after acute exposure. J Clin Invest. 1947; 26(2): 145-168.
  26. Polednak AP, Hollis DR. Mortality and causes of death among workers exposed to phosgene in 1943-45. Toxicol Ind Health. 1985; 1(2): 137-151.
  27. Tiwari RR, Raghavan S. Chronic low-dose exposure to highly toxic gas phosgene and its effect on peak expiratory flow rate. Indian J Occup Environ Med. 2022; 26(3): 189-192.
  28. Grainge C, Brown R, Jugg BJ, Smith AJ, Mann TM, Jenner J, et al. Early treatment with nebulised salbutamol worsens physiological measures and does not improve survival following phosgene induced acute lung injury. J R Army Med Corps. 2009; 155(2): 105- 109.
  29. Jugg B, Jenner J, Rice P. The effect of perfluoroisobutene and phosgene on rat lavage fluid surfactant phospholipids. Hum Exp Toxicol. 1999; 18(11): 659-668.
  30. Lu Q, Huang S, Meng X, Zhang J, Yu S, Li J, et al. Mechanism of phosgene-induced acute lung injury and treatment strategy. Int J Mol Sci. 2021; 22(20): 10933.
  31. He DK, Xu N, Shao YR, Shen J. NLRP3 gene silencing ameliorates phosgene-induced acute lung injury in rats by inhibiting NLRP3 inflammasome and proinflammatory factors, but not anti-inflammatory factors. J Toxicol Sci. 2020; 45(10): 625-637.
  32. Wang P, Ye XL, Liu R, Chen HL, Liang X, Li WL, et al. Mechanism of acute lung injury due to phosgene exposition and its protection by cafeic acid phenethyl ester in the rat. Exp Toxicol Pathol. 2013; 65(3): 311-318.
  33. Jaskot RH, Grose EC, Richards JH, Doerfler DL. Effects of inhaled phosgene on rat lung antioxidant systems. Fundam Appl Toxicol. 1991; 17(4): 666-674.
  34. Rendell R, Fairhall S, Graham S, Rutter S, Auton P, Smith A, et al. Assessment of N-acetylcysteine as a therapy for phosgeneinduced acute lung injury. Toxicol Lett. 2018; 290: 145-152.
  35. Li W, Pauluhn J. Phosgene-induced acute lung injury (ALI): differences from chlorine-induced ALI and attempts to translate toxicology to clinical medicine. Clin Transl Med. 2017; 6(1): 19.
  36. Hobson ST, Richieri RA, Parseghian MH. Phosgene: toxicology, animal models, and medical countermeasures. Toxicol Mech Methods. 2021; 31(4): 293-307.
  37. Borak J, Diller WF. Phosgene exposure: mechanisms of injury and treatment strategies. J Occup Environ Med. 2001; 43(2): 110-119.

Files

Share

How to cite

Statistics