AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center
Coauthor(s):
Andre Pennardt, MD, FACEP, FAAEM, Adjunct Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Emergency Medicine, Aviation Medicine and Dive Medicine, Womack Army Medical Center
Editors: Fred Henretig, MD, Director, Section of Clinical Toxicology, Professor, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Robert G Darling, MD, FACEP, Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Director, Center for Disaster and Humanitarian Assistance Medicine
Author and Editor Disclosure
Synonyms and related keywords:
CX, dichloroformoxime, urticant, nettle agent, chemical warfare agent, chemical burn, chemical exposure, CX exposure, CX injury, urticants, phosgene oxime, vesicant chemical warfare agent, terrorism
Background
Phosgene oxime (CX) is an urticant or nettle agent that causes a corrosive type of skin and tissue injury. Although CX is often grouped with the vesicant chemical warfare agents, it is not a true vesicant because it does not cause blisters. Both vapor and liquid CX cause immediate tissue damage on contact. CX in its pure form is a colorless, crystalline solid at temperatures below 95°F, but the vapor pressure of the solid is high enough to produce symptoms. As a munitions grade compound, CX is in liquid form with a yellowish brown appearance. Although Germany and Russia both developed CX before World War II, no uses of the agent on the battlefield are known. CX is of military interest because it penetrates garments and rubber much more quickly than other chemical agents and it produces a rapid onset of severe and prolonged effects.
For related information, see Medscape's Disaster Preparedness and Aftermath Resource Center.
Pathophysiology
The mechanism of toxicity for CX is uncertain. Possible mechanisms of toxicity include necrotizing effects of the chloride component or a direct effect of the oxime or carbonyl groups. It primarily affects the skin, eyes, respiratory system, and gastrointestinal tract. The agent seems to cause its greatest systemic effects in the first capillary bed encountered. For example, skin exposure or intravenous (IV) injection of CX causes pulmonary edema, while injection into the portal vein produces hepatic necrosis but not pulmonary edema.
Mortality/Morbidity
Morbidity and mortality for exposures to CX are dose dependent. The estimated LCt50 (concentration-time product capable of killing 50% of exposures) for CX vapor is 1500-2000 mg·min/m3. The LD50 (lethal dose for 50% of exposures) for skin exposures is estimated at 25 mg/kg. Skin and mucous membrane irritation can begin within 12 seconds of a vapor exposure of 0.2 mg·min/m3. Unbearable pain and irritation occur within 1 minute of vapor exposure to 3 mg·min/m3.
History
- Important historic features of a potential toxic chemical exposure include the following:
- Estimated time of occurrence
- Duration and circumstances of exposure
- Onset and time course of symptoms
- Odor and/or color of gases or vapors
- Protective clothing worn (if any)
- Effects on surroundings (eg, other human or animal casualties)
- CX casualties typically report unbearable pain in exposed skin and eyes; difficulty with sight or blindness after ocular exposure; and sore throat, hoarseness, dyspnea, chest pain, and cough after respiratory exposure.
- Some casualties may experience a peppery or pungent odor during their initial CX vapor exposure, but this is typically lost quickly because of accommodation.
Physical
- Skin: A blanching, grayish skin lesion surrounded by an erythematous ring can be observed within 30 seconds of exposure. A wheal develops on exposed skin within 30 minutes. The original blanched area acquires a necrotic, brown pigmentation by 24 hours. An eschar forms in the pigmented area by 1 week and sloughs after approximately 3 weeks.
- Eyes: Eye examination typically demonstrates conjunctivitis, lacrimation, lid edema, and blepharospasm after even minute exposures. More severe exposures can result in keratitis, iritis, corneal perforation, and blindness.
- Respiratory: Irritation of the mucous membranes may be observed on examination of the oropharynx and nose. Evidence of pulmonary edema, including rales and wheezes, may be noted on auscultation. Necrotizing bronchiolitis and pulmonary venule thromboses are prominent features of severe CX exposure.
- Gastrointestinal: Some animal data suggest that CX may cause hemorrhagic inflammatory changes in the GI tract.
Causes
Exposures to CX result from its deliberate use as a chemical warfare agent. Since this chemical has no useful industrial applications, accidental exposures are extremely unlikely.
Burns, Chemical
CBRNE - Chemical Warfare Agents
Lab Studies
- An arterial blood gas may be useful only in patients with significant respiratory symptoms after exposure.
Imaging Studies
- Order a chest radiograph to examine for evidence of pulmonary edema in patients with respiratory symptoms after exposure.
Prehospital Care
- The key aspects of prehospital care are removal of casualties from the source of exposure and rapid decontamination. Decontamination consists of removal of all clothing, wiping all gross materials from skin, rinsing with copious amounts of soap and water, washing with 0.5% hypochlorite solution, or use of resin compounds.
- Administer oxygen to patients with significant respiratory distress. Endotracheal intubation and ventilatory support may be required for patients with severe airway exposures or progressive pulmonary symptoms.
- Administer sufficient doses of systemic analgesics as soon as possible.
Emergency Department Care
Emergency department care is a continuation of prehospital care and is supportive in nature. No antidotes exist for phosgene oxime exposure. Although corticosteroid treatment has been given to patients exposed to chlorine gas, which causes a similar syndrome, evidence is limited on its efficacy and safety in the treatment of phosgene exposure. Verify complete decontamination to ensure that no medical personnel become casualties.
- Airway and/or pulmonary
- Be alert to the possible need for airway management in patients with severe exposure.
- Administer oxygen to patients with significant respiratory symptoms.
- Provide supportive care for noncardiogenic pulmonary edema as required.
- Pain management: Pain associated with CX exposure is nearly unbearable. Ensure that adequate systemic, preferably parenteral, analgesics are administered.
- Eyes
- Apply topical antibiotics to reduce risk of infection and adhesions.
- Topical anticholinergics may reduce the risk of future synechiae formation.
- Skin: Initiate wound management as appropriate for any other necrotic and/or ulcerated lesion.
Consultations
- Consult ophthalmology to provide close follow-up care for significant ocular exposures.
- Consult plastic surgery for severe dermal damage.
No medications are specific to the treatment of phosgene oxime exposure. Use analgesics and topical antibiotics as preferred by the emergency department physician.
Drug Category: Parenteral analgesics
CX injuries are extremely painful and require liberal use of parenteral analgesics. No recommendations for specific parenteral analgesics are available. Select a medication (eg, morphine, meperidine) that is readily available and provides adequate pain relief for the patient.
| Drug Name | Morphine sulfate (Duramorph, Astramorph, MS Contin) |
|---|
| Description | An alkaloid of opium and a commonly used systemic narcotic analgesic; a good first choice parenteral medication that may be titrated to patient needs. |
|---|
| Adult Dose | 2-10 mg/70 kg IV over 4-5 min initially; titrate additional doses to effect |
|---|
| Pediatric Dose | 0.1-0.2 mg/kg IV, not to exceed 15 mg IV q4h
|
|---|
| Contraindications | Documented hypersensitivity; acute bronchial asthma; upper airway obstruction |
|---|
| Interactions | Depressant effects are potentiated by other CNS depressants (eg, alcohol, sedatives, antihistamines, psychotropic drugs) |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Closely monitor patients for respiratory depression; morphine-associated pupillary changes may obscure existence, extent, and course of intracranial pathology in patients with head injuries; monitor patients with known seizure disorders for morphine-associated seizure activity; serum half-life may be prolonged in patients with hepatic and renal disease; may precipitate acute respiratory failure in patients with chronic pulmonary disease; may cause urinary retention in patients with disorders of the urinary system; may result in biliary colic in patients with disorders of the biliary system; caution in neonates (monitor respiratory depression) |
|---|
| Drug Name | Meperidine (Demerol) |
|---|
| Description | Narcotic analgesic with multiple actions qualitatively similar to those of morphine, typically administered in conjunction with promethazine. |
|---|
| Adult Dose | 50-150 mg slow IV (diluted) or IM/SC q3-4h prn plus promethazine 25 mg IV/IM |
|---|
| Pediatric Dose | >2 years: 1-1.8 mg/kg slow IV or IM/SC q3-4h prn plus promethazine 0.25-0.5 mg/kg mg IV/IM |
|---|
| Contraindications | Documented hypersensitivity, concurrent use of MAOIs or prior use within past 14 d |
|---|
| Interactions | Depressant effects are potentiated by other CNS depressants; concurrent use may result in respiratory depression, hypotension, and profound sedation or coma |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Not a particularly good analgesic choice for repetitive dosing (seizures have been reported after normeperidine accumulation, which is more likely with quantities of analgesics required to manage CX exposure); may increase intracranial pressure and respiratory depression in patients with head injuries; pupillary changes may mask presence, extent, and course of intracranial pathology; inadvertent arterial injection results in vascular spasm with subsequent distal ischemia; rapid IV injection increases risk of respiratory depression, severe hypotension, and circulatory collapse; may result in acute respiratory failure in patients with chronic pulmonary disease; may result in severe hypotension in patients whose ability to maintain blood pressure is compromised by depleted blood volume or concurrent use of anesthetic agents |
|---|
Drug Category: Topical antibiotic ointments
Indicated for treatment of CX injury of skin and eyes; no specific ointments are recommended; select an available broad-spectrum ophthalmic or skin preparation (eg, bacitracin, Ilotycin).
| Drug Name | Bacitracin (AK-Tracin, Baciguent) |
|---|
| Description | Broad-spectrum antibiotic topical ointment that is a good first choice for superficial wound care. |
|---|
| Adult Dose | Apply to affected area qd/tid |
|---|
| Pediatric Dose | Administer as in adults |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | None reported |
|---|
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
|---|
| Precautions | Prolonged use may result in overgrowth of nonsusceptible organisms |
|---|
| Drug Name | Erythromycin ophthalmic ointment (Ilotycin, E-mycin) |
|---|
| Description | Broad-spectrum macrolide antibiotic indicated in treatment or prevention of superficial ocular infections. |
|---|
| Adult Dose | 1 cm applied to affected eye; not to exceed 6 times/d |
|---|
| Pediatric Dose | Administer as in adults |
|---|
| Contraindications | Documented hypersensitivity; viral, mycobacterial, or fungal infections of eye; patients using steroid combinations after uncomplicated removal of a foreign body from cornea should avoid using this product |
|---|
| Interactions | None reported |
|---|
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
|---|
| Precautions | Do not use topical antibiotics to treat ocular infections that may become systemic; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and may lead to secondary infection (take appropriate measures if superinfection occurs) |
|---|
Drug Category: Oral analgesics
Patients may be switched from parenteral analgesics to an oral form once their injuries have improved sufficiently to tolerate alternative pain control measures; no specific recommendations are available; use a readily available product (eg, Percocet, Tylenol with codeine) that provides adequate pain relief and is well tolerated by the patient.
| Drug Name | Oxycodone/acetaminophen (Percocet) |
|---|
| Description | Semisynthetic opioid analgesic with multiple actions similar to those of morphine; acetaminophen is a nonopiate nonsalicylate analgesic and antipyretic. |
|---|
| Adult Dose | 1-2 tab PO q6h prn; not to exceed 4 g/d acetaminophen |
|---|
| Pediatric Dose | Not recommended |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | Increased CNS depression may be observed with concomitant use of other opioids, general anesthetics, phenothiazines, sedative-hypnotics, and alcohol; concurrent use of MAOIs or TCAs may increase effect of either antidepressant or oxycodone; concurrent use of anticholinergics may result in paralytic ileus |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Respiratory depression may be enhanced in patients with head injuries; pupillary changes may mask presence, extent, and course of intracranial pathology; administer with caution to certain patients (eg, elderly or debilitated patients; those with severe impairment of hepatic or renal function, hypothyroidism, Addison disease, prostatic hypertrophy, urethral stricture); may cause inability to operate a motor vehicle or dangerous machinery |
|---|
| Drug Name | Acetaminophen/codeine (Tylenol with codeine) |
|---|
| Description | Combines analgesic effects of a centrally acting opium-derived alkaloid (codeine) and a peripherally acting nonopioid analgesic (acetaminophen). |
|---|
| Adult Dose | 1-2 tab Tylenol #3 (30 mg codeine phosphate plus 300 mg acetaminophen) or Tylenol #4 (60 mg codeine phosphate plus 300 mg acetaminophen) PO q4-6h prn, not to exceed 360 mg codeine and 4 g acetaminophen in 24 h |
|---|
| Pediatric Dose | Tylenol with codeine elixir: 0.5-1 mg/kg/dose based on codeine PO q4-6h; 10-15 mg/kg/dose based on acetaminophen content; not to exceed 75 mg/kg/d of acetaminophen
<3 years: Not established
3-6 years: 5 mL (1 tsp) PO qid prn
7-12 years: 10 mL (2 tsp) PO qid prn
>12 years: Administer as in adults |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | Increased CNS depression may be observed in concomitant use with other narcotic analgesics, antipsychotics, antianxiety agents, or other CNS depressants, including alcohol; concurrent use of anticholinergics may result in paralytic ileus |
|---|
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
|---|
| Precautions | Respiratory depression may be enhanced in patients with head injuries; pupillary changes may mask presence, extent, and course of intracranial pathology; administer with caution to certain patients (eg, elderly or debilitated patients; those with severe impairment of renal or hepatic function, hypothyroidism, Addison disease, prostatic hypertrophy, urethral stricture) |
|---|
Further Inpatient Care
- Pain associated with phosgene oxime (CX) exposure typically remains severe for several days. Consider admission for pain control. Admit any patients demonstrating significant respiratory symptoms for observation and supportive care.
Further Outpatient Care
- Patients may be treated on an outpatient basis once respiratory symptoms have resolved and nonparenteral analgesics are adequate for pain control.
- Instruct the patient on appropriate wound care techniques and provide close follow-up care to the patient to ensure adequate healing.
- Ophthalmology follow-up care to ensure resolution of ocular injuries also is important.
In/Out Patient Meds
- Inpatient medications include parenteral analgesics (eg, morphine, meperidine), broad-spectrum ophthalmic antibiotic ointments for eye injuries, and broad-spectrum skin antibiotic ointments for skin burns.
- Outpatient medications include oral analgesics (eg, codeine, oxycodone) if continued pain management is required after discharge and continued antibiotic ointments for eye and skin injuries until full healing has occurred.
Transfer
- Transfer to a higher medical center may be required for severe pulmonary CX injuries if the initial hospital is unable to provide the necessary intensive care support. Secure the airway and initiate ventilatory support prior to transfer.
Complications
- Potential complications include scarring, wound infections, loss of vision, and death from severe respiratory injury.
Prognosis
- Prognosis is generally good for minimal exposures. Severe and early respiratory distress portends a poor prognosis.
Patient Education
Medical/Legal Pitfalls
- Failure to provide rapid, early decontamination
- Failure to provide early airway support measures in patients with severe pulmonary exposures
- Failure to provide adequate pain management to patients
| Media file 1:
Anteroposterior portable chest radiograph in a male patient who developed phosgene-induced adult respiratory distress syndrome. Notice the bilateral infiltrates and ground glass appearance. |
 |  View Full Size Image | |
Media type: X-RAY
|
| Media file 2:
Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html. |
 | View Full Size Image | |
Media type: Image
|
- ATSDR. Medical management guidelines for phosgene oxime. [Full Text].
- Armstrong J. Chemical warfare. RN. Apr 2002;65(4):32-9. [Medline].
- Dang C. Chemical warfare agents. Top Emerg Med. 2002;24(2):25-39.
- Department of the Army. Phosgene oxime. In: Field Manual 8-285: Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries. 1995:IV-17-22.
- McAdams AJ Jr, Joffe MH. A Toxico-pathologic Study of Phosgene Oxime. 1955. Army Medical Laboratories Research Report 381.
- McManus J, Huebner K. Vesicants. Crit Care Clin. Oct 2005;21(4):707-18, vi. [Medline].
- Rosenbloom M, Leikin JB, Vogel SN, Chaudry ZA. Biological and chemical agents: a brief synopsis. Am J Ther. Jan-Feb 2002;9(1):5-14. [Medline].
- USAMRICD. Phosgene oxime. In: Medical Management of Chemical Casualties Handbook. 3rd ed. 2000:96-101.
- Zajtchuk R, Bellamy RF, eds. Phosgene oxime. In: Textbook of Military Medicine Part I: Medical Aspects of Chemical and Biological Warfare. 1997:220-222.
- Russell D, Blain PG, Rice P. Clinical management of casualties exposed to lung damaging agents: a critical review. Emerg Med J. Jun 2006;23(6):421-4. [Medline].
CBRNE - Urticants, Phosgene Oxime excerpt Article Last Updated: Mar 11, 2008
|
