a) ANIMAL STUDY: In rabbits, delay in irrigation following hypochlorite exposure results in severe corneal and conjunctival edema, and conjunctival hemorrhage, resolving in 1 week (Grant, 1986).

a) Rare cases of cardiovascular collapse and shock are presumed to occur secondary to severe local injury from large amounts or concentrated solutions (Gosselin et al, 1984).
b) CASE REPORT: A 61-year-old woman developed a cardiopulmonary arrest during dialysis when sodium hypochlorite was inadvertently added to the dialysis bath while she was actively being dialyzed (Hoy, 1981).

a) CASE REPORT: An 18-year-old woman with a medical history of depression, anxiety, and chronic Lyme disease developed acute renal injury, intravascular hemolysis, and mild myocardial injury after injecting herself with 100 mL of Clorox(R) Lemon Fresh Bleach (1% to 5% sodium hypochlorite and 0.1% to 1% sodium hydroxide) through a tunneled catheter. She presented with black urine and drowsiness less than 2 hours after self-administration. Laboratory results revealed a troponin of 1.88 ng/mL (normal, less than 0.03). Following supportive care, her hemolysis and myocardial injury resolved over the next 96 hours; however, she continued to be anuric and azotemic. Her renal function gradually recovered after 7 hemodialysis sessions (Verma et al, 2013).

a) CASE REPORT: A 72-year-old woman with a medical history of diabetes, hypertension, and allergic asthma, presented with acute onset dyspnea after inhaling toxic fumes from 2 drain cleaners, one containing sodium hypochlorite/sodium hydroxide and the other possibly hydrochloric acid. An initial resting ECG revealed diffuse ST-elevation, mainly in anterior leads, and diphasic T-waves. Laboratory results showed markedly elevated Nt-proBNP (N-terminal of the prohormone of brain natriuretic peptide) levels (14.435 pg/mL, normal values less than 450) and mildly elevated troponin levels (2.37 ng/mL; normal values less than 0.07). An echocardiograph showed the typical signs of left ventricular apical ballooning with hyperkinesis of left ventricular basal segments (left ventricular ejection fraction 40%). A coronary angiography revealed mild coronary atherosclerosis, not requiring coronary angioplasty. Following supportive care, she was discharged home a week later with near-complete recovery of left ventricular systolic dysfunction (De Gennaro et al, 2015).

a) Dyspnea and cough are common after inhalation of chloramine or chlorine gas formed by mixing bleach with ammonia or acids (De Gennaro et al, 2015; Yigit et al, 2009; Mrvos et al, 1993; Reisz & Gammon, 1986; Gapany-Gapanavicius et al, 1982) . Most common respiratory symptoms included cough, upper respiratory irritation, and dyspnea (Centers for Disease Control and Prevention, 2011).
b) Decreases in FVC, FEV1, and peak expiratory flow rates developed in volunteers exposed to 1 ppm of chlorine gas (Rotman et al, 1983). Patients developing significant pulmonary injury after inhaling chloramine gas from mixing household bleach with ammonia have developed persistent decreases in pulmonary function (Reisz & Gammon, 1986).
c) Another case of significant exposure and acute pulmonary effects did not result in residual pulmonary function abnormalities (Heidemann & Goetting, 1991).
d) Ingestion of pool sterilizing tablets or inhalation of their fumes may produce similar symptoms (Wood et al, 1987; Phillip et al, 1985; Siodlak et al, 1985) .
e) CASE REPORT: A 34-year-old man presented with shortness of breath and first- and second-degree facial burns after a mixture of calcium hypochlorite (65% chlorine) and water exploded. Arterial blood gas analysis showed pH 7.39, pCO2 41 mmHg, pO2 57 mmHg on room air. Following supportive care, including steroid therapy and nebulized short-acting beta-agonists, he recovered and was discharged after 3 days (Yigit et al, 2009).
f) CASE SERIES: In 1 case series (n=24), coughing (n=19; 79%), sneezing (n=18; 75%), wheezing (n=11; 46%), chest tightness (n=7; 29%), and shortness of breath (n=5; 21%) developed after exposure to an indoor motel swimming pool. Inspection of the pool showed several state health code violations, including cloudy water, a free chlorine level (0.8 ppm) less than half the minimum, a chloramine level (4.2 ppm) 8 times the maximum, and a pH (3.95) approximately half the minimum (Center for Disease Control and Prevention, 2007).
g) CASE SERIES: Twenty-five of 48 individuals exposed to chlorine gas released during disinfection of a swimming pool toilet with bleach and sulfuric acid experienced symptoms consisting of tachypnea, wheezing, cough, chest pain, sore throat, nausea, vomiting, conjunctival irritation, or headaches. No residual pulmonary effects occurred (Phillip et al, 1985).
h) CASE SERIES: A retrospective study of 216 cases of chlorine and chloramine gas inhalation resulting from the mixing of cleaning products (hypochlorites with acids, ammonia, or alkalis) reported the following (Mrvos et al, 1993):

a) Airway edema with stridor and bronchospasm may develop after chlorine or chloramine inhalation or ingestion of sterilizing tablets (Heidemann & Goetting, 1991; Reisz & Gammon, 1986; Siodlak et al, 1985; Gapany-Gapanavicius et al, 1982).
b) Supraglottic edema and edema of the aryepiglottic fold and hypopharynx were reported in 2 children who ingested pool sterilizing tablets (Siodlak et al, 1985).
c) Exacerbation of asthma occurred in 1 case exposed to chlorine gas generated from the mixing of sodium hypochlorite and phosphoric acid (MMWR, 1991).

a) Pneumonitis, which can progress to acute respiratory distress syndrome (ARDS), has developed in individuals inhaling chloramine and chlorine gas from mixing cleaning products or inhaling fumes from pool sterilizer tablets (Wood et al, 1987; Reisz & Gammon, 1986; ITI, 1985).
b) Radiographic findings may lag behind clinical symptoms and may resolve slowly (Reisz & Gammon, 1986; Gapany-Gapanavicius et al, 1982a).
c) CASE REPORT: Severe chemical pneumonitis has been reported from chloramine gas produced by mixing household ammonia and bleach in a poorly ventilated area (Gapany-Gapanavicius et al, 1982a).
d) CASE SERIES: Life-threatening pneumonitis, requiring supplemental oxygen or mechanical ventilation, was described in 3 women after prolonged cleaning (3 hours to 3 days) with household ammonia and bleach mixtures. All 3 had residual interstitial infiltrates and dyspnea on exertion on follow-up 21 days to 9 months after discharge (Reisz & Gammon, 1986).

a) Pulmonary edema, which can progress to acute hypoxemic respiratory failure, can occur from chlorine gas inhalation (Heidemann & Goetting, 1991).
b) CASE SERIES: In a case series involving over 500 cases reported to the CDC over a 6 year period, 5 high-severity cases were identified. All patients were exposed to potent hypochlorite solutions which caused cough, dyspnea, upper and lower respiratory irritation, pulmonary edema, and asthma exacerbation. Cyanosis also developed in a 5 year-old boy exposed to calcium hypochlorite (concentration 65%). All patients were treated with supportive medical care and survived (Centers for Disease Control and Prevention, 2011).
c) CASE REPORT: A 33-year-old woman presented to the ED without respiratory symptoms following assault with a bleach solution containing sodium hypochlorite. The initial chest x-ray, performed 2 hours postingestion, showed bilateral bibasilar infiltrates. The patient's condition deteriorated rapidly, necessitating mechanical ventilation. A repeat chest x-ray showed the development of ARDS, worsening over the next 24 hours. She slowly recovered with supportive care (26 days of mechanical ventilation) (Bracco et al, 2005)

a) Acute hypoxemic respiratory failure or respiratory distress syndrome has developed in individuals inhaling chloramine and chlorine gas from mixing cleaning products or from inhaling fumes from pool sterilizer tablets (Heidemann & Goetting, 1991; Wood et al, 1987; Reisz & Gammon, 1986; ITI, 1985) .
b) Criteria for acute hypoxemic respiratory failure has included severe hypoxemia despite oxygen administration, 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 occlusive pressure (Heidemann & Goetting, 1991).

a) Pneumomediastinum developed in 2 patients who inhaled chlorine gas after mixing sodium hypochlorite with acid (Gapany-Gapanavicius et al, 1982b).
b) CASE SERIES: Cleaning workers exposed to lower airborne concentration (0.4 ppm) of sodium hypochlorite (bleach) experienced decreased FEV1 measurements (Sastre et al, 2011).

a) CASE REPORT: A 53-year-old woman developed shortness of breath after cleaning with liquid ammonia and bleach in a closed walk-in freezer. She progressed to throat tightness and inability to speak despite treatment with nebulized albuterol, racemic epinephrine, and intravenous steroids. Rapid sequence intubation was unsuccessful secondary to upper airway edema, and she required emergency tracheostomy. She developed radiographic evidence of pneumonitis over 4 hours and recovered over the next 7 days (Tanen et al, 1999).
b) CASE REPORT: An 18-month-old child developed vomiting and coughing immediately after ingesting household bleach. She progressed to stridor and wheezing, initially responsive to racemic epinephrine and dexamethasone. Stridor increased despite continuous racemic epinephrine, and laryngoscopy revealed glottic and subglottic edema without supraglottic swelling. She was intubated for 72 hours and recovered with supportive care (Babl et al, 1998).

a) Lethargy occurs in patients with severe pneumonitis and hypoxia following inhalation of chlorine or chloramine gas (Wood et al, 1987; Reisz & Gammon, 1986).

a) Coma occurred in an 18-month-old female following ingestion of several tablespoonfuls of household bleach and treatment with vinegar lavage (Gosselin et al, 1984a).
b) Coma developed in a 12-year-old after inhalation of chlorine gas, which resulted in pulmonary edema and respiratory failure (Heidemann & Goetting, 1991).

a) Seizures developed in an adult following ingestion of 121 g of sodium hypochlorite in solution (Hilbert & Bedry, 1994).

a) NERVE BLOCK: Anesthesia and paresthesia of the mental nerve have developed after injection of sodium hypochlorite beyond the root apex during root canal procedures. Return of normal sensation may take months (Becking, 1991).
b) CASE REPORTS: Paresthesia of the right infraorbital nerve with weakness of the buccal branch of the facial nerve resulting in some loss of cheek and upper lip function was observed in 1 patient after inadvertent extrusion of sodium hypochlorite following a root canal procedure. Complete resolution occurred after approximately 6 months. In another patient, paresthesia of the right infraorbital nerve distribution with weakness of the buccal branch of the facial nerve resulting in drooping of the right corner of the mouth was reported after extrusion of sodium hypochlorite following a root canal procedure. At 3 months, both facial weakness and paresthesia had completely resolved (Witton et al, 2005).

a) CASE SERIES: In 1 case series (n=24), headache developed in 18 persons (75%) after exposure to an indoor motel swimming pool. Inspection of the pool showed several state health code violations, including cloudy water, a free chlorine level (0.8 ppm) less than half the minimum, a chloramine level (4.2 ppm) 8 times the maximum, and a pH (3.95) approximately half the minimum (Center for Disease Control and Prevention, 2007).

a) CASE SERIES: In 1 case series (n=24), dry mouth (n=8; 33%), nausea (n=7; 29%), diarrhea (n=7; 29%), vomiting (n=4; 17%), and abdominal cramping (n=2; 18%) developed after exposure to an indoor motel swimming pool. Inspection of the pool showed several state health code violations, including cloudy water, a free chlorine level (0.8 ppm) less than half the minimum, a chloramine level (4.2 ppm) 8 times the maximum, and a pH (3.95) approximately half the minimum (Center for Disease Control and Prevention, 2007).

a) Significant gastrointestinal burns after ingestion of household bleach are unusual, but burns of the stomach and esophagus have been reported (Jakobsson et al, 1991a; Yarington et al, 1964; Strange et al, 1951; French et al, 1970) .
b) CASE REPORT CHILD: A 1-year-old child developed extensive necrosis of the face, nose, oropharynx, esophagus, and stomach after allegedly ingesting a household cleanser containing sodium hypochlorite 4.5%. The presence of the cleaning product in the stomach was confirmed at autopsy. It was believed that the child ingested a large amount of the product in an abusive situation (Jakobsson et al, 1991).
c) CASE REPORT ADULT: A 32-year-old woman developed necrosis of the upper gastrointestinal tract with evidence of esophageal and gastric perforation after ingesting 750 mL of a sodium hypochlorite solution (Hilbert & Bedry, 1994; Hilbert et al, 1997).
d) CASE REPORT: A 66-year-old woman developed hypernatremia (169 mEq/L), hyperchloremia (143 mEq/L), and metabolic acidosis (pH 7.18, pCO2 19, CO2 5 mEq/L) after ingesting half a bottle of 5% to 10% sodium hypochlorite. She presented with slurred speech and a black tongue and rapidly became lethargic, incoherent, and then unresponsive. She developed a hemopneumothorax and gastric perforation and died 5 hours after ingestion (Spiller et al, 1994).
e) CASE SERIES: In a series of 74 children with household bleach ingestion who underwent endoscopy, 8 (10.7%) had grade 1 esophageal burns and the others had no evidence of gastrointestinal injury. No child developed strictures (Kiristioglu et al, 1999).
f) The vast majority of patients ingesting household bleach do not develop significant toxicity (Racioppi et al, 1994).

a) Strictures of the gastrointestinal tract are unusual following ingestion of household bleach (Pike et al, 1963; Landau & Saunders, 1964).
b) There are 2 reports in the literature of esophageal stricture and 2 of gastric outlet obstruction developing after ingestion of bleach. Three of these were deliberate ingestions of large amounts by adults (Van Rhee & Beaumont, 1990; French et al, 1970; Strange et al, 1951) .

a) Spontaneous emesis is common after hypochlorite ingestion or chlorine or chloramine gas inhalation (Mrvos et al, 1993) Galpany-Gapanavicius et al, 1982a;(French et al, 1970).
b) CASE REPORT: A 42-year-old paraplegic man with a history of multiple gunshot wounds and osteomyelitis developed vomiting, pain, and transient rhabdomyolysis (CK 6000 international units/L, urine myoglobin 120 mg/dL) after self-administration of 20 mL of liquid household bleach (sodium hypochlorite 5.25%) into his port-a-cath. Following supportive care, he recovered fully with no permanent sequelae (Tuckler et al, 2002).
c) CASE SERIES: In 1 case series (n=24), vomiting developed in 4 persons (17%) after exposure to an indoor motel swimming pool. Inspection of the pool showed several state health code violations, including cloudy water, a free chlorine level (0.8 ppm) less than half the minimum, a chloramine level (4.2 ppm) 8 times the maximum, and a pH (3.95) approximately half the minimum (Center for Disease Control and Prevention, 2007).

a) CASE REPORT: An 18-year-old woman with a medical history of depression, anxiety, and chronic Lyme disease developed acute renal injury, intravascular hemolysis, and mild myocardial injury after injecting herself with 100 mL of Clorox(R) Lemon Fresh Bleach (1% to 5% sodium hypochlorite and 0.1% to 1% sodium hydroxide) through a tunneled catheter. She presented with black urine and drowsiness less than 2 hours after self-administration. Laboratory results revealed blood urea nitrogen of 23 mg/dL (normal range, 7 to 23), serum creatinine of 2.99 mg/dL (normal range, 0.5 to 1.2), bilirubin of 2.3 mg/dL (normal range, 0.3 to 1.2), serum lactate dehydrogenase of 1984 international Units/L (normal range, 110 to 240), prothrombin time of 28.5 s (normal range, 9.6 to 12.5), activated partial thromboplastin time of 46 s (normal range, 22.3 to 34), and troponin of 1.88 ng/mL (normal, less than 0.03). Following supportive care, her hemolysis and myocardial injury resolved over the next 96 hours; however, she continued to be anuric and azotemic. On day 4, a kidney biopsy showed extensive loss of the proximal tubular epithelium with anucleate cellular debris compatible with hemolyzed erythrocytes and interstitium containing focal acute inflammatory infiltrates surrounding the necrotic tubules. Her renal function gradually recovered after 7 hemodialysis sessions (starting on day 2) (Verma et al, 2013).

a) CASE REPORT: Hyperchloremic acidosis (pH 7.25) was reported in a 66-year-old woman after massive bleach ingestion (Ward & Routledge, 1988).
b) CASE REPORT: Metabolic acidosis (pH 6.8), in the absence of pulmonary signs or symptoms, was reported in a 40-year-old woman following cleaning of a toilet with bleach and then an acidic detergent for 30 minutes. The sewage tank connected to the toilet contained large amounts of urea and ammonia, thus both chlorine gas and chloramine gas were suspected to have been formed (Minami et al, 1992).
c) CASE REPORT: Metabolic acidosis occurred in a 12-year-old following chlorine gas inhalation, which also produced coma and respiratory failure (Heidemann & Goetting, 1991).
d) CASE REPORT: A 32-year-old woman developed metabolic acidosis (pH 7.15, bicarbonate 12 mmol/L) after ingesting 750 mL of a 13.3% sodium hypochlorite solution (Hilbert et al, 1997).
e) CASE REPORT: A 66-year-old woman developed hypernatremia (169 mEq/L), hyperchloremia (143 mEq/L), and metabolic acidosis (pH 7.18, pCO2 19, CO2 5 mEq/L) after ingesting half a bottle of 5% to 10% sodium hypochlorite. She presented with slurred speech and a black tongue and rapidly became lethargic, incoherent, and then unresponsive. She developed a hemopneumothorax and gastric perforation and died 5 hours after ingestion (Spiller et al, 1994).

a) Significant hemolysis has been reported when public drinking water purified with chloramine was used in home dialysis (Davis et al, 1984; Kjellstrand et al, 1974; Eaton et al, 1973). Sodium hypochlorite introduced into a dialysis bath has produced massive hemolysis (Hoy, 1981).
b) To prevent bacterial contamination, chloramines are usually added to municipal water (acceptable levels less than 0.1 mg/L). Because chloramines can cause red blood cell oxidant damage, resulting in the conversion of hemoglobin to methemoglobin and subsequent hemolysis, these agents should be removed from water in dialysis facilities (De Torres et al, 2002).
c) CASE REPORT: An 18-year-old woman with a medical history of depression, anxiety, and chronic Lyme disease developed acute renal injury, intravascular hemolysis, and mild myocardial injury after injecting herself with 100 mL of Clorox(R) Lemon Fresh Bleach (1% to 5% sodium hypochlorite and 0.1% to 1% sodium hydroxide) through a tunneled catheter. She presented with black urine and drowsiness less than 2 hours after self-administration. Laboratory results revealed blood urea nitrogen of 23 mg/dL (normal range, 7 to 23), serum creatinine of 2.99 mg/dL (normal range, 0.5 to 1.2), bilirubin of 2.3 mg/dL (normal range, 0.3 to 1.2), serum lactate dehydrogenase of 1984 international Units/L (normal range, 110 to 240), prothrombin time of 28.5 s (normal range, 9.6 to 12.5), activated partial thromboplastin time of 46 s (normal range, 22.3 to 34), and troponin of 1.88 ng/mL (normal, less than 0.03). Following supportive care, her hemolysis and myocardial injury resolved over the next 96 hours; however, she continued to be anuric and azotemic. Her renal function gradually recovered after 7 hemodialysis sessions (starting on day 2) (Verma et al, 2013).

a) Hemodialysis-associated methemoglobinemia, believed to be secondary to chloramine contamination, has been reported in 2 patients with acute renal failure (De Torres et al, 2002).

a) Allergic dermatitis has been reported with several chlorine active compounds (Fisher, 1984).

a) Injection site erythema developed in a 31-year-old man after IV injection of about 0.3 mL of sodium hypochlorite 5.25% into the right and left antecubital vein. Left-sided chest pain, vomiting, and mild hypertension occurred. Blood gases, EKG, electrolytes, and urinalysis were normal; ethanol level was 135 mg/dL. The patient had no serious adverse effects and was released after 6 hours (Morgan, 1992).

a) CASE SERIES: In 1 case series (n=24), skin rash developed in 4 persons (17%) after exposure to an indoor motel swimming pool. Inspection of the pool showed several state health code violations, including cloudy water, a free chlorine level (0.8 parts per million [ppm]) less than half the minimum, a chloramine level (4.2 ppm) 8 times the maximum, and a pH (3.95) approximately half the minimum (Center for Disease Control and Prevention, 2007).

a) CASE REPORT: A 34-year-old man presented with respiratory symptoms and first- and second-degree facial burns after a mixture of calcium hypochlorite (65% chlorine) and water exploded. Following supportive care, he recovered and was discharged after 3 days (Yigit et al, 2009).

a) CASE REPORT: A 42-year-old paraplegic man with a history of multiple gunshot wounds and osteomyelitis developed vomiting, pain, and transient rhabdomyolysis (CK 6,000 international units/L, urine myoglobin 120 mg/dL) after the self-administration of 20 mL of liquid household bleach (sodium hypochlorite 5.25%) into his port-a-cath. Following supportive care, he recovered fully with no permanent sequelae (Tuckler et al, 2002).

a) Pulse oximetry or arterial blood gases and pulmonary function tests should be monitored in patients with significant pulmonary symptoms.
b) Chest radiographs are indicated in patients with significant pulmonary symptoms.
c) Endoscopy is indicated in rare patients with significant symptoms (eg, pain, dysphagia, hematemesis) or with large ingestions. Endoscopy may also be indicated in patients ingesting granular bleach or industrial strength products.

a) Supportive care and removal from exposure or decontamination are the mainstays of treatment. Remove contaminated clothing and copiously irrigate exposed eyes or skin with water or saline. Patients with respiratory exposures should leave the area of exposure immediately and receive supplemental oxygen, bronchodilators, and advanced airway support (eg, intubation) as necessary. Nebulized sodium bicarbonate (3.75%) has been used to treat respiratory irritation after chlorine inhalation in some cases and is suggested by some experts. Dilute with small amounts of milk or water following an ingestion.

a) Standard burn care should be applied for serious ocular and dermal corrosive effects. Severe respiratory distress requires intubation. For ingestions of hypochlorite solutions greater than 10% or symptoms of severe corrosive injuries (ie, dysphagia, drooling, pain), flexible endoscopy should be performed to evaluate the extent of esophageal or gastric injury. Chest and abdominal x-rays may be useful to look for mediastinal or intraabdominal free air secondary to perforations in the gastrointestinal tract, which require surgical intervention.

a) CONTRAINDICATED: Administration of acids or basic substances for neutralization is contraindicated due to the possibility of exothermic reaction and subsequent burning.

a) Administer beta2 adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids. Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as necessary.

a) 2.5 to 5 milligrams diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response, administer 2.5 to 10 milligrams every 1 to 4 hours as needed OR administer 10 to 15 milligrams every hour by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.5 milligram by nebulizer every 30 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).

a) 0.15 milligram/kilogram (minimum 2.5 milligrams) diluted with 4 milliliters of 0.9% saline by nebulizer every 20 minutes for three doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulizer as needed. Consider adding ipratropium to the nebulized albuterol; DOSE: 0.25 to 0.5 milligram by nebulizer every 20 minutes for three doses then every 2 to 4 hours as needed, NOT administered as a single agent (National Heart,Lung,and Blood Institute, 2007).

a) The incidence of adverse effects of beta2-agonists may be increased in older patients, particularly those with pre-existing ischemic heart disease (National Asthma Education and Prevention Program, 2007). Monitor for tachycardia, tremors.

a) Consider systemic corticosteroids in patients with significant bronchospasm. PREDNISONE: ADULT: 40 to 80 milligrams/day in 1 or 2 divided doses. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 or 2 divided doses (National Heart,Lung,and Blood Institute, 2007).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

a) Nebulized sodium bicarbonate (3.75%) has been used to treat respiratory irritation after chlorine inhalation in some cases and is suggested by some experts. Theoretically, the use of sodium bicarbonate may neutralize the acidic products that are formed when the chlorine gas reacts with water (Traub et al, 2002).
b) PREPARATION: A 3.75% solution of sodium bicarbonate can be prepared by diluting 2 mL of the standard 7.5% sodium bicarbonate intravenous solution with 2 mL normal saline (Vinsel, 1990).

a) A double-blind, placebo-controlled study was conducted to determine the efficacy of nebulized sodium bicarbonate for treatment of reactive airways dysfunction syndrome (RADS) following chlorine gas inhalation. Forty-four patients with persistent RADS for at least 3 months with initial onset within 24 hours of chlorine gas inhalation were given either nebulized sodium bicarbonate (n=22) or nebulized placebo (n=22). All patients also received corticosteroids and nebulized short-acting beta-agonists. FEV1 values were significantly higher at 120 and 240 minutes in the nebulized sodium bicarbonate group as compared with the nebulized placebo group (p less than 0.05). The quality of life scores in both groups, determined from questionnaires, also improved significantly following treatment (p less than 0.001), but there was no significant difference between the groups (Aslan et al, 2006).
b) CASE REPORT: A 3-year-old girl developed vomiting and respiratory distress after about 45 seconds of exposure to chlorine gas from 10% to 16% sodium hypochlorite solution and a 15% hydrochloric acid solution, used for pool cleaning. She was treated with nebulized albuterol and was transferred to an emergency department. On presentation, she had cough, tachypnea, increased work of breathing without retractions or wheezing, and a sedate, glassy-eyed look. A chest x-ray showed mild perihilar peribronchial thickening, reportedly consistent with acute or chronic bronchitis. Despite treatment with nebulized albuterol/ipratropium bromide solution, her respiratory distress worsened. Another chest x-ray revealed frank pulmonary edema. At this time, she received nebulized mixture of 3 mL of 8.4% sodium bicarbonate solution and 2 mL of normal saline, resulting in a rapid improvement of breathing. She also received IV corticosteroids an hour later. About 12 hours after sodium bicarbonate use, she was breathing room air (Vajner & Lung, 2013).
c) CASE SERIES: In a retrospective study, 25 soldiers developed coughing and dyspnea after exposure to chlorine gas (from a mixture of sodium hypochlorite with hydrochloric acid) during cleaning activities. All patients were treated with humidified oxygen and nebulized salbutamol. Nineteen patients also received inhaled budesonide and nebulized sodium bicarbonate. Initially, 13 patients were discharged and 12 patients were hospitalized. These patients were discharged after improvement following supportive care (Cevik et al, 2009).
d) CASE REPORTS: Dramatic improvement of early respiratory symptoms was noted following humidification with a 5% sodium bicarbonate solution in an anecdotal report (Done, 1976) and with a 3.75% sodium bicarbonate solution in 3 male patients with mild symptoms in another anecdotal report (Vinsel, 1990).
e) CASE SERIES: In a retrospective review of 86 cases of chlorine gas exposure that were treated with nebulized sodium bicarbonate (3 mL of 8.4% sodium bicarbonate mixed with 2 mL normal saline administered as a nebulizer treatment with oxygen or air), 69 patients were treated and released from the emergency department. Of these, 7 also received inhaled bronchodilators, 1 patient received steroids, 2 were discharged with bronchodilators, and 1 patient was discharged with a course of steroids. Condition was improved on discharge in 53 patients, 23 of whom were asymptomatic. Condition was not specified in 16 patients who were treated and released. Seventeen patients required hospital admission. No patient appeared to suffer an adverse effect that could be attributed to sodium bicarbonate (Bosse, 1994).
f) Steroid and bicarbonate treatments were inadequate supportive therapies for patients with acute chlorine intoxication in a case series of 106 patients (Guloglu et al, 2002).
g) Clinically, humidification with 5% sodium bicarbonate does not seem to produce a notable thermal reaction within the lung parenchyma. This most likely occurs due to the dilute concentration used.

a) A study in sheep that were exposed to chlorine gas for 4 minutes and then randomized to receive 8 mL of nebulized normal saline or 4% sodium bicarbonate demonstrated a higher PCO2 and lower PO2 in the control group. Sodium bicarbonate did not worsen outcome, as measured by mortality and postmortem pathologic evaluation, and appeared to improve arterial blood gas values (Chisholm et al, 1989).

a) Continue irrigation for at least an hour or until the superior and inferior cul-de-sacs have returned to neutrality (check pH every 30 minutes), pH of 7.0 to 8.0, and remain so for 30 minutes after irrigation is discontinued (Spector & Fernandez, 2008; Brodovsky et al, 2000a). After severe alkaline burns, the pH of the conjunctival sac may only return to a pH of 8 or 8.5 even after extensive irrigation (Grant & Schuman, 1993). Irrigating volumes up to 20 L or more have been used to neutralize the pH (Singh et al, 2013; Fish & Davidson, 2010). Immediate and prolonged irrigation is associated with improved visual acuity, shorter hospital stay and fewer surgical interventions (Kuckelkorn et al, 1995; Saari et al, 1984).
b) Search the conjunctival sac for solid particles and remove them while continuing irrigation (Grant & Schuman, 1993).
c) For significant alkaline or concentrated acid burns with evidence of eye injury irrigation should be continued for at least 2 to 3 hours, potentially as long as 24 to 48 hours if pH not normalized, in an attempt to normalize the pH of the anterior chamber (Smilkstein & Fraunfelder, 2002). Emergent ophthalmologic consultation is needed in these cases (Spector & Fernandez, 2008).

a) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
b) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
c) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
d) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.

a) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
b) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
c) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
d) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
e) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
f) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.

a) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.

a) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

a) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000b; Grant & Schuman, 1993). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

a) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008).

a) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

a) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.

a) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

a) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

a) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).

a) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993a).
b) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
c) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000a).

a) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
b) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
c) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993a). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

a) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
b) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
c) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993a). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

a) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
b) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
c) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).

a) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).

a) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

a) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.

a) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
b) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
c) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
d) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
e) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
f) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993).

1) A 66-year-old woman who ingested 500 mL of sodium hypochlorite 10% bleach was treated with gastric lavage with sodium thiosulfate 2 hours postingestion. Laboratory values at the time showed metabolic acidosis and a serum sodium of 150 mmol/L. Eight hours after admission, the patient's serum sodium was 169 mmol/L and chloride 130 mmol/L. Electrolytes improved over 24 hours.

a) Emesis is likely to be spontaneous. Induced emesis is not recommended. Demulcents such as milk of magnesia (0.2 to 0.3 mL/kg) egg white, corn starch, or powdered milk slurry may be beneficial (Coppock et al, 1988).

1) GENERAL TREATMENT