Hrev_master [page 20] [Emergency Care Journal 2021; 17:9941] Emergency Care Journal 2021; volume 17:9941 Abstract The Authors report an accidental gas exposure of Chlorine gas in a worker. This accident is very uncommon and can lead to important life-threatening conditions, such as Reactive Airway Disfunction Syndrome (RADS) and Acute Respiratory Distress Syndrome (ARDS) with important pulmonary disfunctions and even death. This syndrome results are reversible when a quick and appropriate intensive treatment is performed. Case Report A 64 years-old male was admitted to the Emergency Department (ED) after accidental occupational inhalation of Chlorine 60 gas 56% chlorine-based salt used in wool and fabric processing. The patient had been exposed for about 15 minutes to chlorine vapours and the symptoms, mainly of the upper respirato- ry tract (dysphonia and stridor) would have arisen after a few min- utes of contact. The territorial emergency system was immediately alerted and after about 30 minutes the patient was being evaluated in the ED. Upon admission to the Emergency Room (ER), the patient was alert but presented dyspnoea, dysphonia, laryngeal stri- dor, profuse sialorrhea and a low peripheral oxygen saturation (SpO2). His blood pressure was 105/60 mmHg, his heart rate 80 bpm, body temperature was 96.4°F, with a Glasgow Coma Scale (GCS) of 15 and a SpO2 93%. Chest auscultation revealed diffuse decreased breath sounds and wheezing. An arterial blood gas anal- ysis showed a pH of 7.409, PaO2 52 mmHg, PaCO2 68 mmHg, HCO3- 22 Mmol/L, and 0.5 mmol/L lactate room air. Complete blood count showed haematocrit 42.7%, MCV 92.6 fL, MCH 99.9 pg, MCHC 32.3 g/dL, RDW 13.2%, MPV 10 fL, leukocyte count 8.3x109/L (neutrophils 82.4%, lymphocytes 9.3%, monocytes 7.3%, basophils 0.6 %, eosinophils 0.4%) and 210x109/L platelets. Glucose was 102.0 mg/dL, total bilirubin 19 µ/L, LDH was increased (290 U/L), as well as Fibrinogen (659 mg/dL) and CRP (1.06 mg/dL), PTT was 29 seconds, Sodium was 140 mEq/L. Renal function, urea and troponin were normal (CKD-EPI was 70, troponin 18.2 mg/dL, urea 29 mg/dL). Negativity to Sars-Cov2 was Correspondence: Franco Lai, Emergency Department, Ospedale S. Stefano, Azienda USL Toscana Centro, Via Suor Niccolina n° 22, Prato, Italy. E-mail: dott.francolai@gmail.com. Key words: Chlorine gas exposure; Chlorine gas intoxication; RADS; ARDS. Conflict of interest: The authors declare no conflict of interest. Availability of data and materials: All data generated or analyzed during this study are included in this published article. Ethics approval and consent to participate: All patients participating in this study signed a written informed consent form for participating in this study. Informed consent: Written informed consent was obtained from a legal- ly authorized representative(s) for anonymized patient information to be published in this article. Received for publication: 27 June 2021. Revision received: 15 November 2021. Accepted for publication: 22 November 2021. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2021 Licensee PAGEPress, Italy Emergency Care Journal 2021; 17:9941 doi:10.4081/ecj.2021.9941 Acute accidental inhalation of Chlorine gas: A mini review Franco Lai,1 Alessio Baldini,1 Luca Becheroni,1 Iacopo Cappellini,2 Barbara Balzarini,3 Francesco De Antoniis,1 Alessandra Ieri,3 Francesco Gambassi,3 Chiara Pagnini,4 Lorenzo Pelagatti,1,5 Mario Rugna,6 Simone Magazzini7 1Emergency Department, Ospedale S. Stefano, Azienda USL Toscana Centro, Prato; 2Intensive Care Unit, Ospedale S. Stefano, Azienda USL Toscana Centro, Prato; 3Toxicology Unit & Poison Control Centre, Azienda Ospedaliero Universitaria Careggi, Florence; 4Intensive Care Unit, University of Siena, Siena; 5Emergency Department, Azienda Ospedaliero Universitaria Careggi, Florence; 6SOSD for Education Emergency Medical System 118, Azienda USL Toscana Centro, Florence; 7Emergency Departmental Area, Azienda USL Toscana Centro, Florence, Italy Highlights - Chlorine gas was first used as a chemical weapon on a large- scale during World War I, and the War in Iraq. Other sources of chlorine gas exposure are workplace or industrial accidents: hypochlorite is available in many detergents and chlorine- based bleach, and when mixed with household acids, it releases chlorine gas. - Most common symptoms include irritant effect on mucous membranes and may produce wheezing and other respiratory symptoms as cough, upper respiratory irritation, dyspnoea, stridor and bronchospasm. - Pneumonitis, which can progress to Acute Respiratory Distress Syndrome (ARDS) may develop in severe exposure. - Treat patients following the ABCDE approach. Non commercial use only established through a nose pharyngeal swab. No pathological changes were observed on the ECG. A prompt sedation and analgesia were induced with PROPO- FOL 1,5 mg/kg and FENTANYL100 mcg intravenously (iv). Then, a paralytic agent, ROCURONIUM 50 mg iv, was adminis- tered to facilitate advanced airway management. Endotracheal intubation and aspiration were performed, and invasive mechani- cal ventilation was then started. Next step was the insertion of cen- tral venous catheter and arterial cannulation to achieve advance monitoring of hemodynamic and respiratory parameters. After initial treatment in the ER, the patient conditions were stable, mainly in gas exchange (pH 7.46, PaO2 98 mmHg, PaCO2 mmHg, HCO3-26 Mmol/L). Then, the patient was transferred to Intensive Care Unit (ICU) for the specific treatments. After two days of ICU, the patient showed a gradual improvement in both respiratory and haemodynamic parameters and was therefore extu- bated and finally transferred to medical setting. As suggested by the Florence Toxicology Unit and Poison Control Centre specialist, we administered Methylprednisolone 125 mg iv, Atropine 1 mg iv, Salbutamol endotracheal and Omeprazole 40 mg iv. This therapeutic management is definitely in line with proto- cols proposed in literature. In case of intoxication with chlorine gas, the use of bronchodilators associated with corticosteroids is commonly accepted. In our case, moreover, atropine found its rational as a therapy for the profuse sialorrhea. The patient underwent a chest and abdomen CT scan with iod- inated contrast medium, whit finding of limited parenchymal thickening in left lung lower lobe, no signs of pneumothorax, pneumomediastinum or pleural-pericardial effusion. Spleen, pan- creas and kidneys were regular. Mediastinal and retroperitoneal lymphadenopathy were absent. An ecstatic appearance of both common iliac arteries was observed. Discussion The victim was manipulating a bucket of Chlorine (Zawa GmbH), a biocide containing 3 kg of pure sodium 1,1-dichlor-iso- cyanurat dihydrate (chlorine 56%), in a soluble granular form, use- ful to degrease and wash the shearer wool first to be colored and spun. The product’s composition was not registered in European Chemical Agency (ECHA) database, neither in the Istituto Superiore di Sanità (ISS) database (Archivio Prodotti Pericolosi), disregarding UE REACH and CLP regulations. Furthermore, its MSDS (Material Safety Data Sheet) was not available on the web, and the label only in German language, with pictograms referring generic health hazard and hazardous to environment. Sodium 1,1-dichlor-isocyanurate dihydrate is an agent related to hypochlorite by the toxicological point of view. Most household bleach solutions contain 3% to 5% hypochlorite, while swimming pool disinfectants and industrial strength cleaners may contain up to 20% hypochlorite. The manual addition of an acid to a hypochlorite solution may release chlorine gas, while the ammonia may react with hypochlorite solutions to release chloramine, a gas with properties like chlorine. This scenario most often develops when several different household cleaning products are mixed. In case of contact with chlorine, it should be added that inges- tion of dilute (3% to 5%) hypochlorite liquid solutions will cause immediate burning in the mouth and throat, but no further injury would be expected, while more concentrated solutions may cause significant oesophageal and gastric burns, and patients may mani- fest dysphagia, drooling, and severe throat, chest, and abdominal pain. Hematemesis and gastrointestinal perforations can occur. Brief toxo-dynamic consideration Chlorine gas is an intermediate water-soluble irritant gas. After contact with airways, it dissolves with H2O present on mucous membranes of airways responsible of irritant and corrosive local toxic effects and respiratory symptoms (Irritant Gas Syndrome). Chlorine is an irritant gas whose toxicity depends on concen- tration, duration of exposure, sex of the exposed victims, their sus- ceptibility due to underlying lung disease and smoking.1,2 Acute effects range from irritation of the conjunctivae and upper respiratory airways to acute lung injury, which can lead to pulmonary obstruction, reactive airway dysfunction syndrome, acute respiratory distress syndrome and, rarely, death.3-7 The toxicity of chlorine is due to its oxidizing potential, and higher solubility in water. Once inhaled, chlorine is hydrolysed to hydrochloric acid and hypochlorous acid (HOCl) and hypochlo- rite. These species of strong oxidants lead to bronchoalveolar inflammation and bronchoconstriction. At low concentrations (40 ppm) chlorine, distal areas of lungs are reached, leading to pul- monary edema, toxic pneumonitis and death, if the exposure is too long (>30 min at 430 ppm) or too intense (>1000 ppm).6,8,9 Long-term damage may occur with migration and activation of inflammatory cells, within the airway epithelium.5 The frequency of chlorine accidents and post-chlorine exposure management is of major public health concern.10-16 In 2014, the American Association of Poison Control Centers reported that about 6,000 exposures to chlorine gas in the US in 2013, compared with 13,600 exposures to carbon monoxide, which was the most common poison gas exposure; the year before they reported about 5,500 cases of chlorine gas poisoning com- pared with around 14,300 cases of carbon monoxide poisoning.17 Chlorine gas was first used as a chemical weapon on a large- scale during World War I in the Second Battle of Ypres and is con- sidered a choking agent. Protocol by the League of Nations prohib- ited the use of chemical and biological weapons.3 However, chlo- rine gas was again used by insurgents during the Iraq War and on a larger scale during the Syrian Civil War. Other sources of chlo- rine gas exposure are workplace or industrial accidents. The largest accident so far happened on 6 January 2005, in Graniteville, South Carolina, USA. There, two trains collided, one of them transport- ing chlorine gas, sodium hydroxide and cresol. Approximately 60 tons of chlorine gas were released. A total of 529 people sought medical care in local EDs, further 311 patients were treated by local physicians and another approximately 220 patients developed mild symptoms but did not seek treatment.6 Many victims with ini- tially only mild complains had symptoms like cough and shortness of breath from a prolonged period of time, up to 8-10 months post exposure.5,6 Hypochlorite is available in many detergents and chlorine- based bleach, and when mixed with household acids, it releases chlorine gas. Therefore, household accidents with chlorine gas exposure are common. Furthermore swimming-pool tablets are often based on chlorine. The American Association of Poison Control Centers reports 4.305 chlorine gas exposures and another 2.284 from mixing hypochlorite with acids in 2017 alone with one reported fatality.7 Florence PCC (2018-2021) registered 272 exposures, out of these 92% originated mixing bleach with acids for household cleaning improperly, while only 8% by professional use. According to Poison Severity Score (PSS), 7% of exposed had no problems, 46% showed mild, 15% moderate and 1% severe symp- Mini Review [Emergency Care Journal 2021; 17:9941] [page 21] Non commercial use only toms with no deaths. Sixty-two percept (62%) of the victims showed ocular and upper way irritation, 15% dyspnoea, 5% asth- ma/bronchoconstriction. PCC suggested in 37% observation at home, in 26% a medical valuation, in 24% a short observation in ED, in 11% an hospital admission. Symptomatic/supportive thera- py was disposed in 75% of cases (Tables 1, 2, and 3). Symptoms Most common symptoms include irritant effect on mucous membranes (e.g., eyes, nose, and throat)1 and may produce wheez- ing and other respiratory symptoms as cough, upper respiratory irritation, and dyspnoea, particularly in pre-existing diseases such as asthma or COPD. In serious exposures with household products,2 upper airway oedema may cause obstruction, and chem- ical pneumonitis3 may also occur as decreases in FVC, FEV1, and peak expiratory, persistent decreases in pulmonary function air- way. Stridor and bronchospasm may develop after chlorine or chloramine inhalation or ingestion of sterilizing tablets.4 Exacerbation of asthma occurred in 1 case exposed to chlorine gas generated from the mixing of sodium hypochlorite and phosphoric acid Pneumonitis, which can progress to Acute Respiratory Distress Syndrome (ARDS).5 Pulmonary oedema, which can progress to acute hypoxemic respiratory failure, can occur from chlorine gas inhalation.6,7 Criteria for acute hypoxemic respiratory failure has included severe hypoxemia despite oxygen administra- tion, chest x-ray showing diffuse pulmonary infiltrates, decreased lung compliance with intrapulmonary shunt, and normal cardiac function despite low (less than 18 mmHg) pulmonary artery occlu- sive pressure. Pneumomediastinum developed in 2 patients who inhaled chlorine gas after mixing sodium hypochlorite with acid.8 Supraglottic oedema induces shortness of breath, throat tight- ness and inability to speak. Rapid sequence intubation is mandato- ry in secondary to upper airway oedema. Severe respiratory dis- tress requires intubation. For ingestions of hypochlorite solutions greater than 10% or symptoms of severe corrosive injuries (i.e., dysphagia, drooling, pain), flexible endoscopy should be per- formed to evaluate the extent of oesophageal or gastric injury. Chest and abdominal X-rays may be useful to look for mediastinal or intraabdominal free air secondary to perforations in the gas- trointestinal tract, which require surgical intervention. Patients with minimal occasional exposures who remain asymptomatic or develop mild symptoms with spontaneous resolu- tion may remain home. All patients with persistent symptoms or intentional exposures should be sent to a health care facility for observation for the longer of 4 to 6 hours or until symptoms resolve. Criteria for dis- Mini Review Table 2. Distribution of exposure by poison severity score18 and symptoms in patient admitted to Toxicology Unit & Poison Control Centre, Azienda Ospedaliero Universitaria Careggi, Florence, Italy between 1st January 2018 and 31st October 2021. Poison Control Centre Of Florence: Chlorine Gas Exposure 2018-2021 Poison Severity Score IPCS/EAPCCT N of cases % Symptoms N % 0 None 20 7.4 Ocular and upper airway irritation 170 62.5 1 Mild 126 46.3 Dyspnoea 41 15.1 2 Moderate 43 15.8 Bronchoconstriction/Asthma 14 5.1 3 Severe 3 1.1 Laryngospasm 1 0.4 4 Death 0 0 Gastrointestinal 6 2.2 Toxicology Unit & Poison Control Centre, Azienda Ospedaliero Universitaria Careggi, Florence, Italy between 1st January 2018 and 31st October 2021. Table 3. Indications and suggestions for disposition in exposed patients. Source: Toxicology Unit & Poison Control Centre, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. Poison Control Centre Of Florence: Chlorine Gas Exposure 2018-2021 Patient Disposition N % Therapy N % Observation at home 102 37.5 None 67 24.6 Family Doctor Evaluation 52 19.1 Symptomatic or supportive 205 75.4 Envoy in Emergency Department 19 7 Short Observation in Emergency Department 67 24.6 Hospital Admission 31 11.4 Table 1. Distribution of calls for chlorine gas exposures by year, proveniences and circumstances arrived to Toxicology Unit & Poison Control Centre, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. Poison Control Centre Of Florence: Chlorine Gas Exposure 2018-2021 Year N of cases Provenience of the calls N of calls % Circumstances of exposure N of cases % 2018 77 Private citizens 95 34.9 Houseold 252 92.6 2019 69 Family Doctor 4 1.5 Other 20 7.4 2020 88 Emergency Rescue 44 16.2 2021 36 Emergency Department 128 47.1 TOTAL 272 272 100 272 100 [page 22] [Emergency Care Journal 2021; 17:9941] Non commercial use only charge should include symptom resolution. Patients with persistent symptoms after a period of observation and supportive treatment should be admitted to the hospital. Depending on symptoms severity (e.g., intubation for pulmonary oedema), an ICU bed may be needed. Criteria for hospital dis- charge should be improvement or resolution of symptoms.9 Depending on the route of exposure and symptoms, it may be appropriate to consult a burn specialist, gastroenterologist, oph- thalmologist, or intensivist. For large-scale exposures, public health and hazardous materials personnel should be notified. A poi- son centre, medical toxicologist, or both should be contacted for moderate to severe exposures. Anyway, the management of poisoned patients exposed to irri- tant gases, particularly four aspects that are important for emergen- cy physicians both out-of-hospital and in-hospital management: i) safety: rescuers have to verify to enter a safe scenario (alternative- ly, a level A or B of PPE should be used) and remove the patient from the source; ii) primary care and survey “ABC”: the “A” air- way management is critical in these patients and the initial pres- ence of upper airways symptoms as dysphonia, aphonia, stridor or laryngeal spasm indicate prompt intubation; the “B” breathing management include beta2 agonists as albuterol for bronchospasm, anti-muscarinic agents as atropine or nebulized glycopyrrolate for airway secretions and PEEP support may be indicated in case of ARDS; the “C” cardiovascular monitoring is needed as dysrhyth- mias or hemodynamic instability may occur; iii) decontamination: dry and wet decontamination by undressing the patient and by water skin/eye irrigation respectively should be evaluated in cases of mucous/skin symptoms (eyes lacrimation, skin irritation); iv) prolonged clinical observation could be indicated in severely symptomatic chlorine gas exposed patients. Chlorine gas may pen- etrate lower airways and rarely induce delayed onset ARDS up to 24 hours from acute exposure. For ingestions, lack of significant initial damage in the oropharynx does not mean deeper, significant gastrointestinal injury cannot develop. Physical exertion can exacerbate symptoms during an ongoing respiratory exposure, as the total exposure will increase with increased minute ventilation.10 Conclusions Acute accidental inhalation of Chlorine gas is a rare cause of ED arrival, however it can cause important pulmonary disfunctions and even death. Since the symptoms are reversible it is important to perform a quick and appropriate intensive treatment to make sure that the patient does not establish RADS and ARDS. References 1. Squadrito GL, Postlethwaite EM, Matalon S. Elucidating mechanisms of chlorine toxicity: reaction kinetics, thermody- namics, and physiological implications. Am J Physiol Lung Cell Mol Physiol 2010;299:289–300. 2. 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Mowry JB, Spyker DA, Cantilena LR Jr, et al. 2013 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila) 2014;52:1032-283. 17. Mowry JB, et al 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol 2015;53:962-1147. 18. Casey PB, Dexter EM, Michell J, Vale JA. The prospective value of the IPCS/EC/EAPCCT poisoning severity score in cases of poisoning. J Toxicol Clin Toxicol 1998;36:215-7. Mini Review [Emergency Care Journal 2021; 17:9941] [page 23] Non commercial use only