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. 2018 Jan;58(1):107-116.
doi: 10.1165/rcmb.2016-0223OC.

Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats

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Free PMC article

Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats

Obiefuna C Okponyia et al. Am J Respir Cell Mol Biol. .
Free PMC article

Abstract

Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD58-67) in a whole-body exposure chamber, and given oxygen (0.8 FiO2) or air (0.21 FiO2) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

Keywords: chlorine gas; hypoxemia; oxygen; respiratory distress; seizure.

Figures

Figure 1.
Figure 1.
Effect of oxygen administration on survival (to 6 h) after chlorine (LD58) inhalation exposure in rats. (A) Lethal-dose evaluation of escalating doses of chlorine gas in rats (LD17, n = 6; LD58, n = 12; LD75, n = 8). (B) Effects of oxygen treatment on survival after high-level chlorine (LD58) inhalation exposure. Oxygen treatment (0.8 fraction of inspired oxygen [FiO2], dashed line; n = 8) improved survival after chlorine inhalation exposure compared with control (solid line; n = 12). P = 0.0467, log-rank, Mantel–Cox test.
Figure 2.
Figure 2.
Effects of oxygen administration (0.8 FiO2) on arterial blood pH, arterial partial pressure of carbon dioxide (PaCO2), and lactate levels after LD58 inhalation exposure in rats, obtained at 2 hours. (A) Arterial pH in oxygen-treated versus untreated groups after chlorine exposure, compared with naive values over time. Note the severe blood acidosis after chlorine exposure, which significantly worsened with oxygen therapy at both 2 hours and 6 hours (P < 0.01). Horizontal dotted lines show clinical grades of acidosis severity. (B) PaCO2 in oxygen-treated versus untreated groups after chlorine exposure compared with naive values over time. Note the severely increased PaCO2 at 2 hours after chlorine exposure, which significantly worsened with oxygen therapy (P < 0.001) and sustained to above respiratory failure levels at 6 hours. Horizontal dotted lines show clinical grades of CO2 retention severity. (C) Lactate levels in oxygen-treated versus untreated groups after chlorine exposure compared with naive values over time. Note the increased lactate levels after chlorine exposure, which improved with oxygen therapy (P = 0.0001) at 2 hours but worsened with oxygen at 6 hours. Values represent means ± SEM; ANOVA for repeated measures, Tukey’s post hoc analysis; ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05. n = 4 per group at 2 hours, n = 7 per group at 6 hours.
Figure 3.
Figure 3.
Peripheral oxygen saturation (SpO2) and partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) trends after LD58 inhalation exposure with and without oxygen administration (0.8 FiO2), obtained at Denver altitude. (A) SpO2 values obtained hourly after chlorine inhalation with and without oxygen therapy. Oxygen administration (squares with dashed line) significantly improved SpO2 to near-normal levels compared with untreated controls (triangles with solid line) throughout the entire study (P < 0.0001). (B) PaO2/FiO2 ratios calculated hourly after chlorine inhalation with (triangles with solid line) and without (squares with dashed line) oxygen therapy. Note the worsening of PaO2/FiO2 ratios immediately after chlorine exposure, which worsened with oxygen therapy. Values represent means ± SEM; statistical analysis via unpaired t test; ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05. n = 8 per group.
Figure 4.
Figure 4.
Respiratory parameters after LD58 inhalation exposure with and without oxygen administration (0.8 FiO2). (A) Variations in the respiratory rate with oxygen before, during, and after chlorine inhalation. Chlorine exposure resulted in severe bradypnea (triangles with solid line), with slow improvement over 6 hours, and oxygen administration (squares with dashed line) did not improve respiratory rates throughout the study. (B) The respiratory distress score, a measure of the work of breathing, was obtained hourly after chlorine inhalation. Note the worsening of respiratory distress scores immediately after chlorine exposure, which did not improve with oxygen therapy (squares with dashed line) compared with untreated controls (triangles with solid line). Values represent means ± SEM; statistical analysis via unpaired t test; ****P < 0.0001; *P < 0.05. n = 8 per group.
Figure 5.
Figure 5.
Neuromuscular scores after LD58 inhalation exposure with and without oxygen administration (0.8 FiO2). Neuromuscular scores (observation scoring of ataxia, posture, tone, and seizure activity) were persistently elevated after chlorine inhalation (triangles with solid line) and minimally improved with oxygen therapy (squares with dashed line). Values represent means ± SEM; statistical analysis via unpaired t test; ****P < 0.0001; **P < 0.01. n = 12 per group.
Figure 6.
Figure 6.
Cardiovascular parameters obtained after LD67 inhalation exposure in invasively catheterized rats with oxygen administration (0.8 FiO2, squares with dashed line) compared with untreated controls (triangles with solid line). (A) Cardiac output (CO) measurements obtained via the hemodilution method after chlorine inhalation. Note the precipitous decline in CO in both groups after exposure, with no improvement noted after oxygen administration. (B) Heart rates (HRs) obtained hourly after chlorine inhalation. Note the immediate and sustained decline in HR in both groups. (C) Stroke volumes (SVs) obtained after chlorine inhalation. SVs were not significantly altered at any time point after chlorine exposure and only tended to mildly decrease after oxygen therapy. Values represent means ± SEM; statistical analysis via unpaired t test; ****P < 0.0001; *P < 0.05. n = 5 in control group, n = 6 in oxygen-treated group. ns = not significant.
Figure 7.
Figure 7.
Pulmonary and systemic arterial pressures after LD67 inhalation exposure in invasively catheterized rats with oxygen administration (0.8 FiO2, squares with dashed line) compared with untreated controls (triangles with solid line). (A) The mean pulmonary artery pressure (MPAP) was obtained hourly after chlorine inhalation exposure with and without oxygen administration. Note the abrupt increase in MPAP early after chlorine inhalation, with oxygen therapy tending to normalize MPAP after administration (not significant). (B) Mean systemic artery pressure (MAP) obtained hourly after chlorine inhalation exposure with and without oxygen. No significant change occurred in MAP after chlorine inhalation or with oxygen. Values represent means ± SEM; statistical analysis via unpaired t test; *P < 0.05. n = 14 in control group, n = 5 in oxygen-treated group.

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