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Hyperchloremic metabolic acidosis after chlorine inhalation
Hyperchloremic Metabolic Acidosis after Chlorine Inhalation
HAROLD M. SZERLIP, M.D. IRWIN SINGER, M.D. Philadelphia, Pennsylvania
Chlorine gas inhalation is usually accompanied by pulmonary toxicity and hypoxemia; the associated acidemla, when present, has been attributed to lactic acidosis. This case report describes the development of hyperchloremic metabolic acidosis followlng accidental chlorine gas exposure. The mechanism postulated for the productkn of this acidosis is the absorption of hydrochloric acid following the reaction of chlorine gas with tissue water. This may be the first case of chlorine toxicity in which the mechanism of the acidosis has been determined. Exposure to chlorine gas from household cleaning agents [ 1,2], water chlorination system [3,4], or industrial accidents [5,6] is not common. However, even mild cases are generally brought to a physician’s attention because chlorine is an irritant gas that damages the mucous membranes and respiratory epithelia. The sequelae of chlorine inhalation, which depend on the concentration of the gas and the duration of exposure, range from mild bronchopulmonary irritation to noncardiogenic pulmonary edema and death. The “safe” occupational exposure is estimated to be no more than 1 part per million (ppm) for a 40-hour work week [?I. Inhalation of concentrations of pure chlorine gas above 1,000 ppm are reported to be rapidly fatal after even a few breaths [6,9]. Most of the literature dealing with chlorine exposure is concerned with the respiratory effects of acute inhalation. Only one published report of two cases described the development of metabolic acidosis in this setting [3], and the acidosis was not characterized. This report describes a case of hyperchloremic metabolic acidosis following the accidental inhalation of chlorine gas. CASE REPORT
From the Renal-Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Requests for reprints should be addressed to Dr. Irwin Singer, 860 Sates Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. Manuscript accepted December 27, 1983.
A 30-year-old, 60 kg white woman with an unremarkable past medical history accidentally mixed chlorine bleach with phosphoric acid. This resulted in the immediite release of a yellow-green gas, which she inhaled. The patient noted the rapid onset of a burning sensation in her throat, accompanied by a nonproductive cough, chest tightness, and shortness of breath. She presented to the emergency room at the Hospital of the University of Pennsylvania approximately 40 minutes after the inhalation. At that time, she was in moderate respiratory distress, with tachypnea, an injected pharynx, and diffuse inspiratory and expiratory wheezes. The results of the remainder of physical examination and chest radiography were unremarkable. Arterial blood gas determination at this time, with the patient breathing room air, revealed a pH of 7.36, oxygen partial pressure of 50 mm Hg, and carbon dioxide partial pressure of 27 mm Hg; repeated arterial blood gas determination, while 35 percent oxygen was administered by face mask, revealed a pH of 7.35, oxygen partial pressure of 72 mm Hg, and carbon dioxide partial
September 1984
The American Journal of Medlclne
Volume 77
581
HYPERCKOREMIC METABOLIC ACIDOSIS AFTER CHLORINE INHALATION-SZERLIP and SINGER
pressure of 29 mm Hg. The simultaneous serum electrolyte concentrations were sodium 136 meq/liter, potassium 3.6 meq/liter, chloride 108 meq/liter, and total carbon dioxide 16 mmol/llter; the anion gap, calculated as the sodium value minus the sum of the chloride and total carbon dioxide values, was 12 (normal). By the following morning, these abnormalities had resolved without specific treatment: repeated serum electrolyte levels were sodium 141 meq/liter, potassium 3.5 meq/liter, chloride 105 meq/liter, and total carbon dioxide 26 mmol/liter; the calculated anion gap was 10. COMMENTS
Although many cases of chlorine inhalation toxicity have appeared in the literature [i-6,10], the occurrence of metabolic acidosis is described only in the two cases reported by Adelson and Kaufman [3]. These authors attributed the acidosis to hypoxemia, and assumed that lactic acidosis had developed; however, neither serum electrolyte nor lactate levels were reported. We believe that our case is the first documented occurrence of hyperchloremic metabolic acidosis following chlorine inhalation. The mechanism reponsible for the development of the acidosis in this case is not clear. Hyperchloremic acidosis can develop by only three general mechanisms [ 111: (1) dilutional acidosis from the administration of intravenous neutral chloride salts (e.g., NaCI); (2) bicarbonate loss from the kidney or gastrointestinal tract; and (3) administration of HCI or its metabolic equivalent (e.g., NH&I). Since the blood samples were obtained before therapy was instituted, the first mechanism is excluded. Her past medical history and the rapidity of both onset and resolution of the acidosis exclude the second mechanism. The possibility of the third mechanism needs more quantitative consideration. The mixing of sodium hypochlorite (chlorine bleach) with phosphoric acid results in the rapid release of chlorine gas. Chlorine gas combines with tissue water to form HCI and HCIO; however, the latter is unstable, and breaks down into HCI and free oxygen. The net reaction is 2 Hz0 + 2 Cl* -+ 4 HCI -i- O,t. (The major
cytotoxic effects of chlorine gas are thought to be mediated by the oxidizing effects of nascent oxygen
[41-I The approximate amount of acid required to cause a fall in serum total carbon dioxide saturation from 24 mmol/liter (normal range in our laboratory 24 to 28 mmol/liter) to 16 mmol/liter (the admission value in this 60 kg patient) can be estimated by assuming that at an arterial pH of 7.35, about half of the acid load is buffered in the extracellular compartment (estimated at 20 percent body weight, or 12 liters). In this case, approximately 8 X 12 = 96 meq of HCI would have to have been buffered in the extracellular compartment and an equal amount buffered in the intracellular space. The total intake would then have been about 192 meq of HCI. This amount of HCI can be generated by the absorption of at least 96 mmol of Cl* gas, which would be equal to 2.13 liters of pure chlorine gas at standard temperature and pressure and taking into consideration the Van der Waal constants for chlorine [ 121. Although the rapid absorption of 2.13 liters of pure chlorine gas should be fatal, we can provide no better explanation for the development of hyperchloremic metabolic acidosis in this case. The amount of chlorine required can be generated from as little as 270 ml of a standard 5.25 percent solution of sodium hypochlorite, well below the volume of solution likely to have been used in this case. But if the third mechanism is correct, either the system is very far from equilibrium or it is very far from even approximately ideal gas behavior. Nevertheless, it is clear that such an acidosis can occur in the presence of chlorine intoxication, and it should not be assumed that the metabolic acidosis in this setting is due to lactic acid even in the presence of hypoxia. ACKNOWLEDGMENT
We are indebted to George Feldman, M.D. and Pedro Fernandez, M.D., for advice and Ellen K. Shapiro, for secretarial assistance in preparation of this case report.
REFERENCES 1. 2. 3.
4.
5.
6.
582
Faigel HC: Hazards to health: mixtures of household cleaning agents. N Engl J Med 1964; 271: 618. Jones FL: Chlorine poisoning from mixing household cleaners. JAMA 1972; 222: 1312. Adelson L, Kaufman J: Fatal chlorine poisoning: report of two cases with ciinicopathoiogic correlation. Am J Ciin Pathoi 1971; 56: 430-442. Decker WJ, Koch HF: Chlorine poisoning at the swimming pool: an overlooked hazard. Clin Toxicol 1978; 13: 377381. Kaufman J, Burkons D: Clinical, roentologic and physiologic effects of acute chlorine exposure. Arch Environ Health 1971; 23: 29-34. Hedges JR, Morrissey WL: Acute chlorine gas exposure. J Am
September 1984
Coil EmergPhysicians 1979; 8: 59-63. Wheatsr RI+ Hazardsof exposure to chlorine gas. JAMA 1974;
7. 8. 9.
10. 11.
12.
230: 1064. Winternitz MC: Pathology of war gas poisoning. New Haven: Yale University Press, 1920; l-83. Weast RC, ed: Handbook of chemistry and physics. Cieveiand: CRC Press, 1973; BlO. Dixon WM, Drew D: Fatal chlorine poisoning. J Occup Med 1968; 10: 249-251. Cogan MG, Rector FC, Seidin DW: Acid-base disorders. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: WB Saunders, 1981; 841-907. Weast RC, ed: Handbook of chemistry and physics. Cleveland: CRC Press, 1973, D157.
The American Journalof Medlclne Volume 77
HAROLD M. SZERLIP, M.D. IRWIN SINGER, M.D. Philadelphia, Pennsylvania
Chlorine gas inhalation is usually accompanied by pulmonary toxicity and hypoxemia; the associated acidemla, when present, has been attributed to lactic acidosis. This case report describes the development of hyperchloremic metabolic acidosis followlng accidental chlorine gas exposure. The mechanism postulated for the productkn of this acidosis is the absorption of hydrochloric acid following the reaction of chlorine gas with tissue water. This may be the first case of chlorine toxicity in which the mechanism of the acidosis has been determined. Exposure to chlorine gas from household cleaning agents [ 1,2], water chlorination system [3,4], or industrial accidents [5,6] is not common. However, even mild cases are generally brought to a physician’s attention because chlorine is an irritant gas that damages the mucous membranes and respiratory epithelia. The sequelae of chlorine inhalation, which depend on the concentration of the gas and the duration of exposure, range from mild bronchopulmonary irritation to noncardiogenic pulmonary edema and death. The “safe” occupational exposure is estimated to be no more than 1 part per million (ppm) for a 40-hour work week [?I. Inhalation of concentrations of pure chlorine gas above 1,000 ppm are reported to be rapidly fatal after even a few breaths [6,9]. Most of the literature dealing with chlorine exposure is concerned with the respiratory effects of acute inhalation. Only one published report of two cases described the development of metabolic acidosis in this setting [3], and the acidosis was not characterized. This report describes a case of hyperchloremic metabolic acidosis following the accidental inhalation of chlorine gas. CASE REPORT
From the Renal-Electrolyte Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Requests for reprints should be addressed to Dr. Irwin Singer, 860 Sates Building, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. Manuscript accepted December 27, 1983.
A 30-year-old, 60 kg white woman with an unremarkable past medical history accidentally mixed chlorine bleach with phosphoric acid. This resulted in the immediite release of a yellow-green gas, which she inhaled. The patient noted the rapid onset of a burning sensation in her throat, accompanied by a nonproductive cough, chest tightness, and shortness of breath. She presented to the emergency room at the Hospital of the University of Pennsylvania approximately 40 minutes after the inhalation. At that time, she was in moderate respiratory distress, with tachypnea, an injected pharynx, and diffuse inspiratory and expiratory wheezes. The results of the remainder of physical examination and chest radiography were unremarkable. Arterial blood gas determination at this time, with the patient breathing room air, revealed a pH of 7.36, oxygen partial pressure of 50 mm Hg, and carbon dioxide partial pressure of 27 mm Hg; repeated arterial blood gas determination, while 35 percent oxygen was administered by face mask, revealed a pH of 7.35, oxygen partial pressure of 72 mm Hg, and carbon dioxide partial
September 1984
The American Journal of Medlclne
Volume 77
581
HYPERCKOREMIC METABOLIC ACIDOSIS AFTER CHLORINE INHALATION-SZERLIP and SINGER
pressure of 29 mm Hg. The simultaneous serum electrolyte concentrations were sodium 136 meq/liter, potassium 3.6 meq/liter, chloride 108 meq/liter, and total carbon dioxide 16 mmol/llter; the anion gap, calculated as the sodium value minus the sum of the chloride and total carbon dioxide values, was 12 (normal). By the following morning, these abnormalities had resolved without specific treatment: repeated serum electrolyte levels were sodium 141 meq/liter, potassium 3.5 meq/liter, chloride 105 meq/liter, and total carbon dioxide 26 mmol/liter; the calculated anion gap was 10. COMMENTS
Although many cases of chlorine inhalation toxicity have appeared in the literature [i-6,10], the occurrence of metabolic acidosis is described only in the two cases reported by Adelson and Kaufman [3]. These authors attributed the acidosis to hypoxemia, and assumed that lactic acidosis had developed; however, neither serum electrolyte nor lactate levels were reported. We believe that our case is the first documented occurrence of hyperchloremic metabolic acidosis following chlorine inhalation. The mechanism reponsible for the development of the acidosis in this case is not clear. Hyperchloremic acidosis can develop by only three general mechanisms [ 111: (1) dilutional acidosis from the administration of intravenous neutral chloride salts (e.g., NaCI); (2) bicarbonate loss from the kidney or gastrointestinal tract; and (3) administration of HCI or its metabolic equivalent (e.g., NH&I). Since the blood samples were obtained before therapy was instituted, the first mechanism is excluded. Her past medical history and the rapidity of both onset and resolution of the acidosis exclude the second mechanism. The possibility of the third mechanism needs more quantitative consideration. The mixing of sodium hypochlorite (chlorine bleach) with phosphoric acid results in the rapid release of chlorine gas. Chlorine gas combines with tissue water to form HCI and HCIO; however, the latter is unstable, and breaks down into HCI and free oxygen. The net reaction is 2 Hz0 + 2 Cl* -+ 4 HCI -i- O,t. (The major
cytotoxic effects of chlorine gas are thought to be mediated by the oxidizing effects of nascent oxygen
[41-I The approximate amount of acid required to cause a fall in serum total carbon dioxide saturation from 24 mmol/liter (normal range in our laboratory 24 to 28 mmol/liter) to 16 mmol/liter (the admission value in this 60 kg patient) can be estimated by assuming that at an arterial pH of 7.35, about half of the acid load is buffered in the extracellular compartment (estimated at 20 percent body weight, or 12 liters). In this case, approximately 8 X 12 = 96 meq of HCI would have to have been buffered in the extracellular compartment and an equal amount buffered in the intracellular space. The total intake would then have been about 192 meq of HCI. This amount of HCI can be generated by the absorption of at least 96 mmol of Cl* gas, which would be equal to 2.13 liters of pure chlorine gas at standard temperature and pressure and taking into consideration the Van der Waal constants for chlorine [ 121. Although the rapid absorption of 2.13 liters of pure chlorine gas should be fatal, we can provide no better explanation for the development of hyperchloremic metabolic acidosis in this case. The amount of chlorine required can be generated from as little as 270 ml of a standard 5.25 percent solution of sodium hypochlorite, well below the volume of solution likely to have been used in this case. But if the third mechanism is correct, either the system is very far from equilibrium or it is very far from even approximately ideal gas behavior. Nevertheless, it is clear that such an acidosis can occur in the presence of chlorine intoxication, and it should not be assumed that the metabolic acidosis in this setting is due to lactic acid even in the presence of hypoxia. ACKNOWLEDGMENT
We are indebted to George Feldman, M.D. and Pedro Fernandez, M.D., for advice and Ellen K. Shapiro, for secretarial assistance in preparation of this case report.
REFERENCES 1. 2. 3.
4.
5.
6.
582
Faigel HC: Hazards to health: mixtures of household cleaning agents. N Engl J Med 1964; 271: 618. Jones FL: Chlorine poisoning from mixing household cleaners. JAMA 1972; 222: 1312. Adelson L, Kaufman J: Fatal chlorine poisoning: report of two cases with ciinicopathoiogic correlation. Am J Ciin Pathoi 1971; 56: 430-442. Decker WJ, Koch HF: Chlorine poisoning at the swimming pool: an overlooked hazard. Clin Toxicol 1978; 13: 377381. Kaufman J, Burkons D: Clinical, roentologic and physiologic effects of acute chlorine exposure. Arch Environ Health 1971; 23: 29-34. Hedges JR, Morrissey WL: Acute chlorine gas exposure. J Am
September 1984
Coil EmergPhysicians 1979; 8: 59-63. Wheatsr RI+ Hazardsof exposure to chlorine gas. JAMA 1974;
7. 8. 9.
10. 11.
12.
230: 1064. Winternitz MC: Pathology of war gas poisoning. New Haven: Yale University Press, 1920; l-83. Weast RC, ed: Handbook of chemistry and physics. Cieveiand: CRC Press, 1973; BlO. Dixon WM, Drew D: Fatal chlorine poisoning. J Occup Med 1968; 10: 249-251. Cogan MG, Rector FC, Seidin DW: Acid-base disorders. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: WB Saunders, 1981; 841-907. Weast RC, ed: Handbook of chemistry and physics. Cleveland: CRC Press, 1973, D157.
The American Journalof Medlclne Volume 77