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 agent 3-quinuclidinyl benzilate (QNB, BZ) is an anticholinergic agent that affects both the peripheral and central nervous systems (CNS). It is one of the most potent anticholinergic psychomimetics known, with only small doses necessary to produce incapacitation. It is classified as a hallucinogenic chemical warfare agent. QNB usually is disseminated as an aerosol, and the primary route of absorption is through the respiratory system. Absorption also can occur through the skin or gastrointestinal tract. It is odorless. QNB's pharmacologic activity is similar to other anticholinergic drugs (eg, atropine) but with a much longer duration of action.

Pathophysiology

QNB acts by competitively inhibiting muscarinic receptors. Muscarinic receptors primarily are associated with the parasympathetic nervous system, which innervates numerous organ systems, including the eye, heart, respiratory system, skin, gastrointestinal tract, and bladder. Sweat glands, innervated by the sympathetic nervous system, also are modulated by muscarinic receptors. Effects of QNB by any route of exposure are slow in onset and long in duration. The onset of action is approximately 1 hour, with peak effects occurring 8 hours postexposure. Symptoms gradually subside over 2-4 days. Most of the QNB that enters the body is excreted by the kidneys, making urine the choice for detection.

Frequency

United States

Use of QNB against the United States has never been reported. Currently, the US government is funding numerous programs to prepare the nation for potential chemical terrorist attacks against citizens and the military.

International

Use of QNB has been suggested in a number of international conflicts. In January 1992, soldiers in Mozambique experienced an explosion above their troop formation. Subsequent symptoms resembled those expected from QNB. In July 1995, approximately 15,000 people attempted to walk from the enclave of Srebrenica to the free territory in Bosnia. Many experienced hallucinations during their march that were suspected to be secondary to QNB.

Mortality/Morbidity

The LD50 (lethal dose to 50% of an exposed population) for BZ is estimated to be similar to that of atropine, which is approximately 100 mg. Other factors, such as the exposed patient's preexisting health status and the time from exposure to medical care, are also important.

CLINICAL

Section 3 of 10  

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

History

• An event involving QNB probably would create confusion, panic, multiple seriously ill or dead victims, and a major emergency medical service, police, and/or military response.
• • Large numbers of casualties would overwhelm any community's emergency response.
  • Chaos appropriately would describe events following such an event.
  • In the early phases of an emergency response, the toxin's identification would be unknown, and the history would be misleading and inaccurate.
• Physical examination is the key to diagnosing the causative agent.

Physical

After exposure to QNB, the physical examination is consistent with an anticholinergic syndrome. Characteristics of the anticholinergic syndrome have long been taught using the old medical adage, "dry as a bone, blind as a bat, red as a beet, hot as a hare, and mad as a hatter."

• Central nervous system
• • Depending on the dose and time postexposure, a number of CNS effects may manifest. Restlessness, apprehension, abnormal speech, confusion, agitation, tremor, picking movements, ataxia, stupor, and coma are described.
  • Hallucinations are prominent, and they may be benign, entertaining, or terrifying to the patient experiencing them. Exposed patients may have conversations with hallucinated figures, and/or they may misidentify persons they typically know well.
  • Simple tasks typically performed well by the exposed person may become difficult. Motor coordination, perception, cognition, and new memory formation are altered as CNS muscarinic receptors are inhibited.
• Peripheral nervous system
• • Eye: Mydriasis resulting in photophobia is expected. Impairment of near vision occurs because of loss of accommodation and reduced depth of field secondary to ciliary muscle paralysis and pupillary enlargement. If QNB is splashed into the eye, conjunctival injection and eye pain also occur.
  • Cardiovascular system: Tachycardia is a prominent feature of QNB exposure. Heart rates may be rapid but rarely exceed 150 beats per minute. Exacerbated heart rate responses to exertion also are expected. Systolic and diastolic blood pressure may show moderate elevation. A decrease in capillary tone may cause skin flushing.
  • Gastrointestinal: Intestinal motility slows, and secretions from the stomach, pancreas, and gallbladder decrease. Nausea and vomiting may occur. Decreased or absent bowel sounds are noted on examination.
  • Respiratory: All glandular cells become inhibited, and dry mucus membranes of the mouth and throat are noted. Speech may decrease to a whisper. Breath of the exposed patient may develop a foul odor.
  • Skin: Inhibition of sweating results in dry skin. Place hands directly into the axilla of the exposed patient and note the absence of moisture. Red flushed skin also may occur.
  • Urinary: Urination is difficult or impossible. Subsequent urinary retention may occur, and an enlarged bladder may be palpable on examination.
  • Temperature: The exposed patient's temperature may become elevated from the inability to sweat and dissipate heat. In warm climates such as the desert, this may result in marked hyperthermia.

Causes

Human QNB exposures rarely are reported. Potential causes of exposure to this agent are a laboratory accident, a terrorist event, or a military conflict.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Thyrotoxicosis
Neuroleptic malignant syndrome
Serotonin syndrome
CNS infection
Heat stroke
Sedative-hypnotic withdrawal
Anticholinergic "outbreaks" involving jimsonweed abuse by teenagers, scopolamine-tainted heroin, or alcoholic beverages

WORKUP

Section 5 of 10  

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

Lab Studies

• No rapid tests enable a health care provider to diagnose exposure to QNB. Consider QNB if a number of persons arrive after an exposure to an unknown substance and manifest an anticholinergic syndrome.
• Obtaining a complete blood count, electrolytes, clotting studies, and renal and liver function tests is reasonable in any person who potentially was exposed to a chemical warfare agent.
• If the patient is markedly agitated or comatose, obtaining a urine myoglobin and/or creatine phosphokinase is warranted to exclude rhabdomyolysis. Hyperkalemia, hyperphosphatemia, and hypocalcemia may occur in association with rhabdomyolysis. The agitated patient also may develop an elevated lactate.
• If QNB is considered in the differential, obtain extra blood and urine samples. Tests have been developed to confirm human exposure to QNB.
• Disseminated intravascular coagulation is a potential complication in a patient with marked agitation and/or hyperthermia. Obtain clotting studies (eg, prothrombin time, activated partial thromboplastin time, international normalized ratio) in these patients. If clotting studies are elevated, then fibrinogen, fibrin split products, and a peripheral smear looking for evidence of hemolysis may be necessary.

Imaging Studies

• A patient exposed to QNB who is comatose may be at risk for aspiration pneumonia; obtain a chest radiograph.
• If the etiology of the altered mental status is uncertain, obtaining a head CT scan to exclude other intracranial processes is reasonable.

Other Tests

• ECG: QNB is associated with sinus tachycardia. Patients exposed to QNB who have preexisting cardiac disease may be at risk for cardiac ischemia as their heart rates increase. Other anticholinergic agents are associated with QT prolongation, QRS widening, and various tachydysrhythmias. Obtain an ECG to exclude these potential problems.

TREATMENT

Section 6 of 10  

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

Prehospital Care

• Prehospital care providers must place their personal safety before the treatment of potentially contaminated patients.
• • The US military recommends wearing maximum protection when in contact with QNB contamination. These recommendations include wearing an M9 mask and hood, an M3 butyl rubber suit, M2A1 butyl boots, and M3 or M4 butyl gloves.
  • For civilian paramedics, decontamination of the exposed patients prior to transfer must occur. Dermal absorption and subsequent toxicity is a risk from contact with contaminated patients.
  • Off gassing may occur, and paramedics are at risk for toxicity in the closed confines of an ambulance. Caution must be exercised especially for flight crews, since toxicity of the pilot during mid flight can lead to impaired vision and judgment and subsequent risk of crashing the aircraft.
• Water can be used for decontamination.
• After the patients have been decontaminated, transport them to the nearest hospital facility.
• Perform general supportive measures (eg, intravenous access, airway management).

Emergency Department Care

Once decontamination has occurred, the primary emphasis simply is supportive care of exposed patients. Emergency department staff must be certain that proper decontamination has occurred. Dermal absorption and off gassing of QNB does occur and can pose a risk to hospital personnel.

• In patients who are not protecting their airway, perform intubation and mechanical ventilation.
• Apply soft restraints to patients at risk of harming themselves or health care workers.
• Intravenous hydration may be necessary; maintain adequate urinary output. If urinary retention is suggested, place a Foley catheter.
• For patients experiencing marked agitation, consider benzodiazepine administration.
• In patients with hyperthermia, cooling measures may be necessary.
• • Completely remove the patient's clothing.
  • Insert a Foley catheter or rectal temperature probe.
  • Administer adequate intravenous fluids.
  • Cooling measures such as evaporative cooling using skin wetting with directed circulating fans, ice water immersion, ice packs, and cooling blankets may be necessary.
• Include continuous cardiac and core temperature monitoring.

Consultations

If an exposure to QNB occurs, consider a number of consultations.

• If the cause of the exposure is a terrorist act against civilians, contact the local health department, poison center, and law enforcement agency immediately. Also contact federal agencies, such as the US Federal Bureau of Investigations (FBI).
• If a patient sustained eye contact with QNB and subsequently developed eye pain, change in vision, or marked conjunctival injection, consultation with an ophthalmologist may be necessary.
• For patients requiring intensive care monitoring, consider early consultation with a physician trained in critical medicine.

MEDICATION

Section 7 of 10  

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

No specific antidote has been found to reverse the action of QNB definitively. In the past, physostigmine was used to reverse the effects of anticholinergic agents. However, numerous adverse effects associated with its use in reversing poisonings are reported in the literature. Subsequently, the use of physostigmine has diminished greatly in the setting of acute anticholinergic toxicity. Use of physostigmine in QNB poisoning has been studied. However, its efficacy in QNB intoxication and its adverse effect potential have not been delineated definitively. At this time, supportive care is the mainstay of therapy. If the exposed patient is markedly agitated, consider administration of a benzodiazepine.

Drug Category: Benzodiazepines

Consider in patients sustaining exposure to QNB and presenting with marked agitation.

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Inpatient care is no different than that discussed in Emergency Department Care. Keep symptomatic patients who were exposed to QNB in a monitored setting until their symptoms completely resolve. Use of maintenance intravenous fluids and sedatives such as benzodiazepines may be necessary. Prolonged intoxication may occur depending on the dose of QNB absorbed.

Transfer

• Any health care facility that is unable to adequately monitor a patient intoxicated with an anticholinergic should consider transfer to a facility that can care for such patients.
• Smaller health care facilities may be overwhelmed if a large-scale terrorist attack with multiple victims occurs. Disaster plan implementation and appropriate transfer of patients to less stressed facilities may be necessary.

Complications

• Rhabdomyolysis: If a person exposed to QNB develops marked agitation or profound somnolence, tissue necrosis may occur and rhabdomyolysis may develop. If this remains undiagnosed, myoglobinuric renal failure may develop.
• Anoxic brain injury: If an exposed person becomes comatose and loses his or her ability to maintain ventilatory function, hypoxia may develop and lead to anoxic brain injury.
• Aspiration pneumonia: Inability of exposed patients to maintain their airway may result in aspiration of gastric contents into the lungs.
• Ileus: The prolonged anticholinergic effects of QNB may lead to development of an ileus.
• Angle-closure glaucoma: Those patients predisposed may be at risk due to the mydriasis induced by QNB.
• Bleeding diathesis: Disseminated intravascular coagulation may develop in patients with shock and marked hyperthermia.
• Hepatic injury: Hepatic injury may accompany antimuscarinic agent toxicity that involves hyperthermia or shock.

Prognosis

• The prognosis is good for QNB-exposed patients if they do not develop a secondary injury such as the complications noted above. Once they are removed from the exposure and the absorbed QNB is metabolized, they should become more lucid. Full recovery is expected within 4 days. No long-term effects are expected from QNB itself.

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

• Few pitfalls exist from a medicolegal standpoint. Decontamination of patients and avoidance of contamination of health care workers is paramount. If a physician demonstrates good supportive care as discussed in this article, risk of litigation against the caregiver should be minimal.

Special Concerns

• As noted with other antimuscarinic agents, patients at the extremes of age may be more susceptible to toxicity. Other factors expected to predispose a patient to toxicity include heat stress, volume depletion, and concurrent use of medications with antimuscarinic effects.

REFERENCES

Section 10 of 10

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

• Byrd GD, Paule RC, Sander LC, et al. Determination of 3-quinuclidinyl benzilate (QNB) and its major metabolites in urine by isotope dilution gas chromatography/mass spectrometry. J Anal Toxicol. May-Jun 1992;16(3):182-7. [Medline].
• Gibson RE, Rzeszotarski WJ, Jagoda EM, et al. [125I] 3-quinuclidinyl 4-iodobenzilate: a high affinity, high specific activity radioligand for the M1 and M2-acetylcholine receptors. Life Sci. Jun 4 1984;34(23):2287-96. [Medline].
• Glendenning KK. Distribution of muscimol, QNB, and 5HT binding in the vertebrate diencephalon: a comparative study of eight mammals and three non-mammals. Microsc Res Tech. Oct 15 2003;62(3):247-61. [Medline].
• Hay A. Surviving the impossible: the long march from Srebrenica. An investigation of the possible use of chemical warfare agents. Med Confl Surviv. Apr-Jun 1998;14(2):120-55. [Medline].
• Hiramatsu Y, Eckelman WC, Baum BJ. Interaction of iodinated quinuclidinyl benzilate enantiomers with M3 muscarinic receptors. Life Sci. 1994;54(23):1777-83. [Medline].
• Hull LA, Rosenblatt DH, Epstein J. 3-Quinuclidinyl benzilate hydrolysis in dilute aqueous solution. J Pharm Sci. Jul 1979;68(7):856-9. [Medline].
• J R Army Med Corps. Chemical casualties. Centrally acting incapacitants. J R Army Med Corps. Dec 2002;148(4):388-91. [Medline].
• Ketchum JS, Sidell FR. Incapacitating agents. In: Textbook of Military Medicine. 1997:287-305.
• McDonough JH Jr, Shih TM. A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs. Pharmacol Biochem Behav. Jun-Jul 1995;51(2-3):249-53. [Medline].
• Sorger D, Kampfer I, Schliebs R. Iodo-QNB cortical binding and brain perfusion: effects of a cholinergic basal forebrain lesion in the rat. Nucl Med Biol. Jan 1999;26(1):9-16. [Medline].
• US Army Center for Health Promotion and Preventive Medicine. Psychodelic Agent 3 - Quinuclidinyl Benzilate (BZ). The Deputy for Technical Services' Publication: Detailed Chemical Facts Sheets. 1998;[Full Text].

Article Last Updated: May 24, 2006