Page 673 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

638 SECTION | IX Gases, Solvents and Other Industrial Toxicants

VetBooks.ir Toxicokinetics and Toxicodynamics Diagnostic Testing
Apart from air sampling/monitoring, there are no specific
NO 2 is relatively water insoluble, and accumulation in the
diagnostic tests. Occasionally, red gaseous material can
upper respiratory tract is limited (Jonas, 1984; Douglas
et al., 1989; Epler, 1989; Gurney et al., 1991; Leavey be observed being released from freshly filled silos and
et al., 2004). The high levels of carbon dioxide present in red staining of surfaces near silo chutes can be observed.
silage gas may stimulate deeper inspiration of the gas,
resulting in a higher delivered dose in the deep lung, i.e., Postmortem Findings
it behaves as a typical EPA Category 1 gas that produces
Chemical pneumonitis and pulmonary edema primarily
site-of-contact effects in the deep lung/gas exchange
located in the deep lung are the predominant findings.
areas. Prolonged and/or high level exposure can also
Emphysema may be present, depending on the duration of
result in systemic effects (notably the formation of nitro-
the toxidrome. Typically, type I pneumocytes, pulmonary
syl hemoglobin and methemoglobinemia).
mast cells, and ciliated airway cells are the most affected
cell types. Delayed effects include bronchiolitis obliterans.
Pathophysiology
NO 2 dissolves in water to produce nitrous and nitric acids, Treatment
which are irritant and corrosive (Jonas, 1984; Douglas
et al., 1989; Epler, 1989; Gurney et al., 1991; Leavey The immediate treatment priority is the prompt removal
et al., 2004). Free radical generation and associated dam- of the patient from the source of exposure. Rescuers need
age are also important parts of the pathophysiology. The to take great care not to become casualties in such cir-
acids are also immunosuppressive and result in a reduced cumstances. The next treatment priority is the administra-
resistance to infection. With prolonged or high levels of tion of 100% oxygen and resuscitation. Pulmonary edema
exposure, NO 2 is absorbed. Absorbed NO 2 binds with may develop up to 48 h following exposure, so volume
high affinity to hemoglobin, forming nitrosyl hemoglobin, expanders and fluid therapy must be used with great cau-
which is further oxidized to methemoglobin. This results tion during this period. Corticosteroids are important for
in chemical asphyxia. Methemoglobinemia produces a reducing the risk of bronchiolitis obliterans. The use of
left shift of the hemoglobin:oxygen disassociation curve, broad-spectrum antibiotics with the objective of prevent-
further impairing tissue oxygen delivery. ing bronchopneumonia may be justified. Subsequent
follow-up management of reactive airway syndromes and
asthma may be required.
Vulnerable Populations
Individuals with preexisting reactive airway disorders, Prognosis
asthma, and lung disease are likely to be at greater risk.
The prognosis depends entirely on the degree of lung dam-
Clinical Presentation age and whether or not bronchiolitis obliterans and restric-
tive lung disease develop (Jonas, 1984; Douglas et al.,
Clinical disease is usually with harvest season and the
1989; Epler, 1989; Gurney et al., 1991; Zwemer et al.,
presentation depends on the concentration and duration of
1992; Leavey et al., 2004). In many cases, the toxidrome is
exposure (Jonas, 1984; Pladson, 1984; Douglas et al.,
mild and self-limiting; however, it may take months for
1989; Epler, 1989; Gurney et al., 1991; do Pico, 1992;
pulmonary function to return to normal. Permanent mild
Zwemer et al., 1992; Stepanek et al., 1998; Leavey et al.,
loss of pulmonary function is relatively common.
2004). High level exposures can produce sudden death
due to bronchiolar spasm, laryngeal spasm, reflex respira-
tory arrest, and/or asphyxia. Lower exposures may be Prevention
asymptomatic, or produce mild, self-limiting effects, or The following methods can prevent exposure: stay out of
result in eye irritation, pulmonary edema, and/or acute silos during the 2-week danger period after the initial fill-
respiratory distress syndromes. Mucous membrane irrita- ing; close all silo doors before filling; use outside ladders
tion is uncommon because NO 2 does not tend to dissolve rather than internal ladders in silos; if the silo is not
onto wet mucous membrane surfaces. completely full, remove the doors that lead down to the
Failure to adequately treat significant NO 2 exposure silage; enter the silo only with a complete oxygen support
with corticosteroids results in bronchiolitis obliterans, system; ventilate the silo by opening the cover flaps and
particularly in the small airways and alveolar ducts, and running the silo blower for 24 48 h before entering; never
permanent restrictive lung disease. Bronchiolitis obliter- enter the silo alone or without a lifeline for rescue during
ans can develop weeks or months following the initial the danger period; use a personal air monitor; and install
exposure. air monitors in areas where NO 2 is likely to concentrate.