AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The chemical warfare agents diphenylchlorarsine (DA), diphenylcyanoarsine (DC), and diphenylaminearsine (DM, adamsite) belong to a group of chemicals classified as vomiting agents. DA appears as colorless crystals, DC as a white solid, and DM as light yellow-to-green crystals. DA and DM are odorless, and DC reportedly has an odor similar to garlic or bitter almonds. All 3 agents are insoluble in water.

The synthesis of these agents dates back to the early 20th century. In 1915, Wieland, a German chemist, synthesized the agent DM. Three years later, a US chemist, Robert Adams, independently developed this same compound and named it adamsite. Since that time, these agents have been produced for 2 purposes, as riot-control agents and as emesis-inducing agents to promote removal of personal protective gear during chemical warfare.

Pathophysiology

Vomiting agents typically are disseminated as aerosols. The primary route of absorption is through the respiratory system. Exposure also can occur by ingestion, dermal absorption, or eye impact.

The effects of the vomiting agents by any route of exposure are slower in onset and longer in duration than typical riot control agents (eg, CS). On initial exposure, vomiting agents are irritants. This irritation is delayed for several minutes after contact. As a result of this delay, less early warning properties are present for those exposed. By the time symptoms of irritation occur and personnel consider donning their protective equipment, significant contamination already may have occurred. Systemic signs and symptoms subsequently follow the initial irritation and consist of headache, nausea, vomiting, diarrhea, abdominal cramps, and mental status changes. Symptoms typically persist for several hours after exposure. Death has been reported with excessive exposure.

Frequency

United States

The use of vomiting agents within the United States against civilians never has been reported. Currently, the US government is funding numerous programs to prepare the nation for potential chemical terrorist attacks against its citizens and military.

International

The use of vomiting agents has been reported during international conflicts. DA first was used by German troops in 1917. DA was not well filtered by the standard issue gas masks at that time. It resulted in nausea and vomiting, causing enemy troops to remove their masks. This rendered those personnel vulnerable to the toxic effects of other agents such as phosgene and chlorine gas. The Germans also produced DC and DM, but limited documentation exists for use of these agents during World War I. Questionable reports exist of vomiting agents used in other countries as riot control agents. No recent use of vomiting agents is documented.

Mortality/Morbidity

DM is the most toxic agent of this group, with an estimated LCt50 of 11,000 mg·min/m³ (eg, an estimated 50% lethality for a group of patients breathing air with a concentration of 11,000 mg/m³ for 1 min). Other factors also are important, such as the exposed patient's preexisting health status and the time from exposure to medical care. The dose at which vomiting reportedly begins for DM is estimated as 370 mg·min/m³.

Race

No published studies demonstrate a significant difference in effects of vomiting agents on various races.

Sex

No published studies demonstrate a significant difference in effects of vomiting agents by gender.

Age

Intuitively, those at the extremes of age would be less tolerant of exposure to these 3 chemical agents. However, no published studies prove this.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• A history of exposure to an aerosolized substance that resulted in ophthalmic and pulmonary irritation and then progressed to nausea, vomiting, abdominal cramps, and headache suggests exposure to a vomiting agent.
• In the early phases of an emergency response, the toxin's identification would be unknown and the history misleading and inaccurate.
• • Fear, anxiety, and mistrust are likely to affect victims, emergency responders, bystanders, and the entire community after such an incident.
  • Overwhelming emotions in some patients, rescuers, and hospital staff are likely to cause acute anxiety reactions and mass psychogenic illness. Patients truly suffering from vomiting-agent poisoning and those suffering from mass psychogenic illness would be difficult to separate, because the symptoms are similar. Patients with either condition may complain of nausea, vomiting, diarrhea, headache, tearing, dizziness, chest tightness, and shortness of breath.
  • Because differentiating mass hysteria from a true vomiting-agent poisoning may be difficult, treat all patients experiencing symptoms as true toxic emergencies. The potential exists for patients with mass psychogenic illness to overwhelm the entire emergency response system and hinder timely treatment of those with true toxic emergencies.

Physical

The signs and symptoms encountered in a person exposed to a vomiting agent may vary. Factors that determine clinical effects include the amount of the agent encountered and the route of exposure. Depending on these variables, the progression of signs and symptoms can range from mild mucosal irritation to cardiovascular collapse and death. The following list constitutes findings that may be noted on physical examination following exposure to vomiting agents:

• Eye - Conjunctival injection, tearing, and blepharospasm
• Nose - Excessive nasal discharge, sneezing, mucosal injection, and edema
• Throat - Mucosal injection and edema
• Lungs - Excessive cough, wheezing, rhonchi, prolonged expiratory phase, and tachypnea
• Heart - Tachycardia
• Abdomen - Hyperactive bowel sounds, intestinal cramps, emesis, and diarrhea
• Skin - Erythema and edema at the site of dermal contact
• Mental status - Central nervous system depression, syncope, and death (possible with significant exposure)

Causes

Human exposures to vomiting agents rarely have been reported. Potential causes of exposure to these agents are laboratory accidents, terrorist events, or military conflicts.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No rapid tests are available that enable health care providers to definitively determine exposure to vomiting agents. Consider these agents when exposure to an unknown substance inflicts pulmonary and ophthalmic irritation and then progresses to nausea, vomiting, abdominal cramps, and diarrhea.
• Obtain a complete blood count, electrolytes, clotting studies, and renal and liver function tests in any person who potentially was exposed to a chemical warfare agent.
• If a patient is markedly agitated or comatose, obtain a urine myoglobin and/or creatine phosphokinase to exclude rhabdomyolysis.
• If considering chemical warfare agent poisoning in the differential, obtain extra blood and urine samples for subsequent toxicologic testing.

Imaging Studies

• A chest radiograph may need to be obtained to exclude chemical pneumonitis in a patient exposed to vomiting agents who presents with marked pulmonary irritation.
• Rarely, vomiting agents may cause altered mental status. If the etiology is uncertain, obtain a head CT scan to exclude other intracranial pathology.

Other Tests

• ECG: Vomiting agents are not reported to cause significant cardiac dysrhythmias. Sinus tachycardia may result from the stress of the event. In symptomatic persons at risk for coronary artery disease or in those with preexisting disease, obtain an ECG to exclude evidence of ischemia. When the causative agent is not identified definitively, obtaining an ECG is a reasonable approach to exclude conductive disturbances induced by other toxins.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• A military or terrorist event involving the exposure of military personnel or civilians to vomiting agents would create confusion and panic. Large numbers of potential casualties may overwhelm emergency response teams. Chaos may occur.
• Prehospital care providers must place their personal safety first before the treatment of potentially contaminated patients. With aerosolized exposure, secondary contamination of health care providers is unlikely.
• Perform general supportive measures such as obtaining intravenous (IV) access and administering oxygen to those with signs of respiratory irritation.

Emergency Department Care

The initial care of patients exposed to vomiting agents primarily is supportive. No specific antidotes are available. Focus care on relieving irritant and systemic effects.

• Respiratory irritation
• • These effects typically are transient and resolve soon after exposure ceases. Duration of irritation depends on the dose of agent inhaled and the premorbid status of the patient.
  • Patients with preexisting lung disease (eg, asthma, emphysema) may develop exacerbations of these diseases that are slow to resolve.
  • If a patient has dyspnea with wheezing, albuterol nebulizations may be necessary. Steroids may be considered.
  • In most patients without preexisting lung disease, symptoms abate spontaneously.
• Ophthalmic irritation
• • Consider eye irrigation in patients sustaining chemical exposure and subsequent ocular irritation. Appropriate irrigant choices include water, normal saline, and lactated Ringer solution.
  • The objective of irrigation is to dilute the offending agent and remove it. Perform irrigation with 1-2 L of irrigant per affected eye.
  • Examine the eyes using a slit lamp and fluorescein.
  • If a corneal abrasion is noted, consider cycloplegics and topical antibiotics.
• Emesis: Treat patients with repetitive emesis with IV hydration and antiemetics. Numerous antiemetics are available. No specific agent is documented as superior.
• Central nervous system depression
• • Acute mental status changes rarely have been reported. One death after DM exposure is documented, but complete information on this fatality has not been released.
  • If a patient presents in marked respiratory distress with mental status changes, intubation and mechanical ventilation may be necessary.

Consultations

The following consultations may be necessary:

• Intensivist: In the rare event that a patient exposed to vomiting agents presents with acute respiratory distress or acute mental status changes, early consultation with a physician trained in critical care medicine may be necessary.
• Poison control center and/or local health department: Report adverse events caused by toxins to the local poison control center and health department. This allows coordination of information with other health care facilities and expedites assistance in determining the etiology of the poisoning.
• Law enforcement: If the cause of the exposure is unknown or believed to be a terrorist act, contact local and federal law enforcement.
• Ophthalmologist: If significant eye exposure has occurred and the patient develops persistent ophthalmologic signs and symptoms or evidence of corneal damage, contact an ophthalmologist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical therapy focuses on controlling the emesis induced by the agents. Initial antiemetic therapy may begin with routine doses of drugs commonly used to combat vomiting, such as promethazine, prochlorperazine, or droperidol. High doses of metoclopramide may be administered. If these agents are unsuccessful, 5-HT3 receptor antagonists may be administered to control nausea and vomiting. This class of drugs is comparatively expensive but well tolerated with few adverse effects. These agents include dolasetron, ondansetron, and granisetron.

Drug Category: Antiemetics

A common effect of DA, DC, and DM is emesis. Consider antiemetics in patients with persistent vomiting.

Drug Category: 5-HT3 receptor antagonists

A more expensive drug category compared to the other available antiemetics noted above. These agents typically are reserved for severe cases of emesis not responsive to the above medications.

Drug Category: Bronchodilators

Acute bronchospasm may result when exposure occurs to aerosolized chemicals. Bronchodilators are administered to attempt to alleviate bronchospasm that causes decreased pulmonary airflow and wheezing.

Drug Category: Cycloplegics

Eye muscarinic antagonists that cause mydriasis and alleviate ciliary spasm. May alleviate symptoms in patients who develop a chemical conjunctivitis caused by eye exposure.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Inpatient care for patients exposed to vomiting agents is no different than the care discussed in Emergency Department Care.
• Symptomatic patients exposed to these agents should remain in a health care setting until signs and symptoms abate and they are able to take adequate fluid by mouth without repeat emesis. Continued use of IV fluids and antiemetics may be necessary.
• Patients who demonstrate marked bronchospasm may need repeated nebulized albuterol as necessary.

Further Outpatient Care

• Most patients exposed to vomiting agents recover within the first few hours postexposure and demonstrate no further toxicity.
• If marked ocular toxicity occurs and corneal injury is documented, obtain follow-up care with an ophthalmologist to ensure that healing is progressing. Schedule this follow-up visit within 24 hours of discharge.

Transfer

• A health care facility that is unable to adequately provide care for a patient intoxicated with a vomiting agent should consider transfer to a facility that can care for such patients. Health care facilities may be overwhelmed quickly if a large-scale exposure occurs with multiple casualties. Disaster plan implementation and appropriate transfer of patients to less stressed facilities may be necessary.

Complications

• Complications are expected to be rare in persons exposed to vomiting agents if rapid and adequate supportive care is initiated. If significant ocular exposure occurs, corneal chemical burns may develop. In persons with preexisting lung disease, exacerbation of the lung disease may occur. If a patient sustains large exposure, coma may develop with subsequent risk of developing anoxic brain injury and aspiration pneumonia.
• • Corneal chemical burns: A significant exposure to vomiting agents can lead to damage of the cornea. If the patient complains of significant eye discomfort, foreign body sensation, photophobia, or decreased visual acuity, consider eye irrigation. Thoroughly examine the eye and include visual acuity testing. Perform slit lamp examination with fluorescein. If a chemical corneal burn is documented, a cycloplegic may be used to reduce pain; apply topical antibiotic ointment. Arrange follow-up care with an ophthalmologist within 24 hours.
  • Acute bronchospasm: As with many types of chemical inhalation exposures, acute bronchospasm may develop. This is especially true of patients with preexisting lung disease (eg, asthma). If acute bronchospasm occurs leading to respiratory distress, treatment with bronchodilators (eg, albuterol) may be necessary.
  • Anoxic brain injury: If an exposed person becomes comatose and loses his or her ability to maintain ventilatory function, hypoxia may develop, leading to anoxic brain injury. Unless massive levels are encountered, this complication is exceedingly rare after exposure to vomiting agents.
  • Aspiration pneumonia: Inability of exposed patients to maintain their airway may result in aspiration of gastric contents into the lungs.

Prognosis

• The prognosis is good for persons exposed to vomiting agents if they do not develop secondary injuries. Full recovery is expected in most patients.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Chemical Warfare and Personal Protective Equipment.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• From a medicolegal standpoint, few pitfalls exist in dealing with patients manifesting signs and symptoms of vomiting agent poisoning. If a physician demonstrates good supportive care, the risk of litigation against the caregiver should be minimal. Call the appropriate authorities if exposure to these agents is believed to have occurred.

Special Concerns

• Currently, no publications address the clinical effects of vomiting agents in special populations. A pregnant female exposed to these agents may be at an increased risk of miscarriage because of the stress of the event. No published studies have been performed on pregnant females, and no study has demonstrated whether these agents are teratogenic. No published studies have demonstrated a difference of clinical effects either on the exposed pediatric or geriatric patient.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Compton, JAF. Military Chemical and Biological Agents: Chemical and Toxicological Properties. 1988:194-204.
• Ellison DH. Vomiting agents. In: Handbook of Chemical and Biological Warfare Agents. 2000:149-150.
• Haas R, Tsivunchyk O, Steinbach K. Conversion of adamsite (phenarsarzin chloride) by fungal manganese peroxidase. Appl Microbiol Biotechnol. Feb 2004;63(5):564-6. [Medline].
• Henriksson J, Johannisson A, Bergqvist PA, Norrgren L. The toxicity of organoarsenic-based warfare agents: in vitro and in vivo studies. Arch Environ Contam Toxicol. Feb 1996;30(2):213-9. [Medline].
• Hu H, Somani SM, eds. Toxicodynamics of riot-control agents (lacrimators). In: Chemical Warfare Agents. 1992:271-288.
• Kohler M, Hofmann K, Volsgen F. Bacterial release of arsenic ions and organoarsenic compounds from soil contaminated by chemical warfare agents. Chemosphere. Feb 2001;42(4):425-9. [Medline].
• Pitten FA, Muller G, Konig P, et al. Risk assessment of a former military base contaminated with organoarsenic-based warfare agents: uptake of arsenic by terrestrial plants. Sci Total Environ. Feb 9 1999;226(2-3):237-45. [Medline].
• Sidell FR. Riot control agents. In: Management of Chemical Warfare Agent Casualties. 1995:93-99.
• Tornes JA, Opstad AM, Johnsen BA. Determination of organoarsenic warfare agents in sediment samples from Skagerrak by gas chromatography-mass spectrometry. Sci Total Environ. Mar 1 2006;356(1-3):235-46. [Medline].
• Zajtchuck R, ed. Riot control agents. In: Textbook of Military Medicine. 1997:308-324.

Article Last Updated: May 24, 2006