Emergency management of chlorine gas exposure - a systematic review.

INTRODUCTION: Chlorine exposure can lead to pulmonary obstruction, reactive airway dysfunction syndrome, acute respiratory distress syndrome and, rarely, death.

OBJECTIVE: We performed a systematic review of published animal and human data regarding the management of chlorine exposure.

METHODS: Three databases were searched from 2007 to 2017 using the following keywords "("chlorine gas" OR "chlorine-induced" OR" chlorine-exposed") AND ("therapy" OR "treatment" OR "post-exposure")". Forty-five relevant papers were found: 22 animal studies, 6 reviews, 19 case reports and 1 human randomized controlled study. General management: Once the casualty has been removed from the source of exposure and adequately decontaminated, chlorine-exposed patients should receive supportive care. Humidified oxygen: If dyspnea and hypoxemia are present, humidified oxygen should be administered. Inhaled bronchodilators: The use of nebulized or inhaled bronchodilators to counteract bronchoconstriction is standard therapy, and the combination of ipratropium bromide with beta2 -agonists effectively reversed bronchoconstriction, airway irritation and increased airway resistance in experimental studies. Inhaled sodium bicarbonate: In a randomized controlled trial, humidified oxygen, intravenous prednisolone and inhaled salbutamol were compared with nebulized sodium bicarbonate. The only additional benefit of sodium bicarbonate was to increase the forced expiratory volume in one second, 2 and 4 h after administration. Corticosteroids: Dexamethasone 100 mg/kg intraperitoneally (IP) reduced lung edema when given within 1 h of chlorine inhalation and when administered within 6 h significantly decreased (p < 0.01) the leukocyte count in the bronchoalveolar lavage (BAL). As corticosteroids were never given alone in clinical studies, it is impossible to assess whether they had an additional beneficial effect. Antioxidants: An ascorbic acid/deferoxamine combination (equivalent to 100 mg/kg and 15 mg/kg, respectively) was administered intramuscularly 1 h after chlorine exposure, then every 12 h up to 60 h, then as an aerosol, and produced a significant reduction (p < 0.05) in BAL leukocytes and a significant reduction (p < 0.007) in mortality at 72 h. The single clinical case reported was uninterpretable. Sodium nitrite: Sodium nitrite 10 mg/kg intramuscularly (IM), 30 min post-chlorine exposure in mice and rabbits significantly reduced (p < 0.01) the number of leukocytes and the protein concentration in BAL and completely reversed mortality in rabbits and decreased mortality by about 50% in mice. No clinical studies have reported the use of sodium nitrite. Dimethylthiourea: Dimethylthiourea 100 mg/kg IP significantly decreased (p < 0.05) lymphocytes and neutrophils in BAL fluid 24 h after chlorine exposure in experimental studies. No clinical studies have been undertaken. AEOL 10150: Administration of AEOL10150 5 mg/kg IP at 1 h and 9 h post-chlorine exposure reduced significantly the neutrophil (p < 0.001) and macrophage (p < 0.05) bronchoalveolar cell counts. Transient receptor potential vanilloid 4 (TRPV4): IM or IP TRPV4 reduced significantly (p < 0.001) bronchoalveolar neutrophil and macrophage counts to baseline at 24 h. No clinical studies have been performed. Reparixin and triptolide: In experimental studies, triptolide 100-1000 µg/kg IP 1 h post-exposure caused a significant decrease (p < 0.001) in bronchoalveolar neutrophils, whereas reparixin 15 mg/kg IP 1 h post-exposure produced no benefit. Rolipram: Nanoemulsion formulated rolipram administered intramuscularly returned airway resistance to baseline. Rolipram (40%)/poly(lactic-co-glycolic acid) (60%) 0.36 mg/mouse given intramuscularly 1 h post-exposure significantly reduced (p < 0.05) extravascular lung water by 20% at t + 6 h. Prophylactic antibiotics: Studies in patients have failed to demonstrate benefit. Sevoflurane: Sevoflurane has been used in one intubated patient in addition to beta2 -agonists. Although the peak inspiratory pressure was decreased after 60 min, the role of sevofluorine is not known.

CONCLUSIONS: Various therapies seem promising based on animal studies or case reports. However, these recommendations are based on low-level quality data. A systematic list of outcomes to monitor and improve may help to design optimal therapeutic protocols to manage chlorine-exposed patients.