Brief Reports
AdultRespiratoryDistress SyndromeFrom Poisoning Organophosphate RICHARD MICHAEL
KASS, DO, GURPREET LIPPMAN, MD
KOCHAR,
A 46-year-old man atter an accidental exposure to organophosphates developed florid adult respiratory distress syndrome (ARDS). A markedly suppressed level of pseudocholinestrase and red blood cell chollnestrase with profuse salivation and sweatin confirmed the diapnosis 01 organophosphate poitoniq. Within 46 hours, patient developed respiratory distress needin intubation. Despite maximum ventilatory support and positive end-explratoty pressure, hypoxia persisted, Swan Ganz (Baxter Healthcare Inc, trvlne, CA) pressures showed low pulmonary capillary wedpe pressure and patient died on the third hospital day. An autopsy confirmed the picture of AROS. Other potential causes of ARDS were excluded. Althou9h rare, or6anophesphate poisonin should be added to the list of toxins causin6 ARDS. (Am J Emerg Med 1991;9:32-33. Copyri6ht 0 1991 by W.B. Saunders Company)
The adult respiratory distress syndrome (ARDS) has been associated with various diseases, injuries, exposure to several drugs and toxic substances.’ We describe a case of organophosphate poisoning in which the patient developed a clinical, radiologic, hemodynamic and pathologic picture compatible with ARDS developed in the patient. To our knowledge, this is the first report of ARDS caused by organophosphate poisoning. CASE REPORT A 46-year-old man was brought to the emergency department (ED) comatose with generalized tonic-clonic seizures and acute respiratory failure requiring intubation. His wife gave a history of the patient’s having ingested an unknown liquid 8 hours earlier in the mistaken belief that it was an alcoholic beverage. He was subsequently noted to have fallen to the ground with the development of generalized seizure activity, diaphoresis, urinary incontinence, and increased salivation. He had no significant past medical history. Physical examination on arrival in the ED showed a thin man, comatose with labored breathing, intermittent generalized tonicclonic seizure activity, and smelling strongly of a pungent garlic-like substance. Heart rate was 110 beats/min. His blood pressure was 160/100 mm Hg. Respirations were labored at 20 breaths/min. He From the Department of Medicine, Albert Einstein Medical Center, and Temple University School of Medicine, Philadelphia, PA. Manuscript received September 21, 1989; revision accepted April 1, 1990. Address reprint requests to Dr Kochar: Division of Cardiology, Albert Einstein Medical Center, York & Tabor Rds, Philadelphia, PA 19141. Key Words: Adult respiratory distress syndrome, organophosphate poisoning. Copyright 0 1991 by W.B. Saunders Company 0735-6757/91/0901-0008$5.00/O 32
MD,
was afebrile. There was significant diaphoresis, and a large amount of secretions in the oropharynx. Lung fields were clear; however, copious tracheobronchial secretions were present. Cardiovascular and abdominal examination were normal. Neurologic examination revealed unresponsiveness to physical stimuli; pupils were pinpoint but reactive to light. Doll’s eyes, comeal reflex were intact, and intermittent generalized tonic-clonic seizures were present. Initial laboratory work including complete blood count, electrolytes, glucase, blood urea nitrogen, creatinine level, calcium (serum amylase and lipase) were normal. Admission chest roentgenogram was unremarkable. An electrocardiogram showed sinus tachycardia with no acute changes. Initial blood gas while intubated on 100% oxygen demonstrated a PO, of 149 mm Hg, a Pco, of 19 mm Hg, a pH of 7.53, bicarbonate 16 mEq/L, and 0, saturation of 99%. Toxicologic analyses of blood and urine for ethanol, benzodiazepines, barbiturates, amphetamines, phenothiazines, opiates, and salicylates were negative. A computed tomography scan of the head was unremarkable. A diagnosis of organophosphate poisoning was suspected based on the presence of a strong characteristic odor and signs of cholinergic hyperstimulation. This diagnosis was confirmed by analysis of gastric contents revealing malathion in concentration of 176 pg/mL. A serum pseudocholinesterase level was 100 p&L (normal range 2,436 to 4,827 c~g/L)and red blood cell cholinesterase level was 1030 kg/L (normal range 3,590 to 6,666 pg/L). Serum and gastric analysis were negative for the presence of any other pesticide, although contribution by hydrocarbons in solvent could not be excluded with certainty. In the ED he was initially stabilized, intubated and given activated charcoal, intravenous (IV) naloxone and 50% dextrose. Gastric lavage returned a large amount of guaiac positive material. He received 2 mg of IV a&opine every 30 minutes for 2 hours in the ED. He was transferred to the intensive care unit where he continued to receive atropine 2 mg every 15 minutes for two hours. After a total dose of 24 mg of IV atropine, patient appeared adequately atropinized clinically as evidenced by mydriasis and tachycardia at a heart rate of 160 beats/min. In addition the patient received I gm of pralidoxime 16 hours after the exposure to organophosphates. He responded very well over the first day, becoming fully alert and coherent with decreased pulmonary secretions. Blood gases on FiO, of 40% were adequate and the patient was extubated 20 hours after admission. However, only 1 hour later his condition markedly deteriorated with increasing respiratory distress requiring reintubation, progressive lethargy, and development of hypotension requiring IV fluids and pressers. Chest roentgenogram at this time demonstrated no evidence of pulmonary edema or infiltrates. Arterial blood gases on 100% FiO, revealed hypoxia with respiratory acidosis (Table 1). A Swan-Ganz catheter (Baxter Healthcare, Inc. Irvine, CA) was placed at this time and showed a mean right atrial pressure of 8 mm Hg, pulmonary arterial pressure of 2617 mm Hg, and a pulmonary
KASS, KOCHAR, AND LIPPMAN
TABLE1.
n ARDS FROM ORGANOPHOSPHATE
Mechanical Ventilator Data O2 Sat.
Day
FiO,
pH
Pcop
PO,
(%)
PCWP (mm Hg)
Normal
0 1 2
100% 40% 100%
7.53 7.41 7.15
19 31 49
149 99 72
99 98 87
-
2
100% PEEP 10
7.26
27
63
69
13
ABBREVIATIONS:PCWP, pulmonary itive end-expiratory pressure.
capillary
Chest Roentgenogram
7
Bibasaiar diffuse shadows Worsening pulmonic shadows
wedge pressure;
PEEP, pos-
capillary wedge pressure (PCWP) of 7 mm Hg with a cardiac output of 5 Limin. He was given 2 liters of normal saline with correction of his hypotension to baseline blood pressure within 2 hours. A second chest roentgenogram 36 hours after admission showed diffuse extensive bilateral shadowing with no Kerley B lines or pleural effusion. He was empirically treated with broad spectrum antibiotics including aminoglycosides for suspected septicemia. However, all the cultures (blood, urine, sputum) drawn before antibiotics did not grow any organisms. His hospital course was complicated by continued hypoxemia despite positive end-expiratory pressure (PEEP) and maximum ventilatory support (Table 1). Serial chest roentgenograms showing worsening bilateral shadowing with consistently low PCWP and refractory hypoxemia led to the diagnosis of ARDS. Patient developed full blown picture of ARDS 20 to 30 hours after completion of the dose of atropine and pralidoxime. The patient continued to deteriorate, and eventually died on the third hospital day. An autopsy was performed. Gross pathology of the lungs showed enlarged wet, firm lungs bilaterally, weighing an average of 1,300 g each. Sections of both lungs showed markedly congested dark reddish-black parenchymal surfaces that exuded bloody fluid freely, indicative of severe congestion and edema. No granulomatous or neoplastic alteration was noted. Microscopic examination showed marked congestion and edema with thickened alveolar walls. Early hyaline membrane formation was noted.
DISCUSSION Organophosphate poisoning has been associated with bronchoconstriction, increased bronchopharyngeal secretions, and respiratory muscle paralysis.* Pulmonary edema has also been described. 3-5 We describe a case of organophosphate poisoning in which the patient developed a clinical picture compatible with ARDS, a noncardiogenic pulmonary edema associated with organophosphate toxicity. Pulmonary edema has been described as an early manifestation of organophosphate toxicity.3 However, the pulmonary edema described in these patients was only a transient event, seen on the admission chest roentgenograms that resolved over the course of one day.3 In addition, no hemodynamic measurements with Swan-Ganz catheter were obtained to substantiate evidence of noncardiogentic pulmonary edema. In one series of 150 suicidal poisonings with organophosphates,6 postmortem specimens showed edematous lungs with fluid fiied alveoli. Muscarinic hypersecretion was implicated as the cause of the observed pulmonary edema. Our case demonstrates many of the features of ARDS. This patient with no prior history of pulmonary or cardiac
POISONING
33
disease, developed refractory hypoxemia despite maximal ventilatory support with PEEP and 100% oxygen after a lethal dose of an organophosphate. In addition, serial chest roentgenograms with worsening pulmonary shadows and continued low PCWP throughout the hospitalization were consistent with ARDS. Both pseudocholinesterase and red blood cell cholinesterase levels were substantially suppressed. Gastric contents aspirated on admission also showed significant amounts of malathion. ARDS as seen in this patient seems to have been a direct consequence of organophosphate poisoning. No other agents were ingested that could be responsible for permeability pulmonary edema, and there was no evidence of septicemia with negative blood cultures. Neurologic events have been linked with the development of ARDS. This patient did have seizures on presentation to the ED; however, there was no evidence of seizure activity or focal neurologic findings on electroencephalography (EEG) or CT of the head, and no subsequent acute neurologic events noted during hospitalization. In addition, in this case, fulminant ARDS developed 48 hours after admission and after all seizure activity had ceased. Neurogenic pulmonary edema usually occurs simultaneously with seizure activity and resolves rapidly.’ Peripheral vasodilatation probably from excessive cholinergic response and hypovolemia seem to be additional explanations for the observed hypotension. The hypotension per se was of short duration (only 2 hours) to cause ARDS. The mechanisms of organophosphate pulmonary toxicity remains speculative. The possibilities include muscarinic hyperstimulation,6 increased vagal tone,’ and excessive catecholamine release.’ This case demonstrates that ARDS may be an ominous complication of organophosphate poisoning that should be anticipated early and considered in the differential diagnosis of toxins causing ARDS. The authors
thank Walter Levy, MD, for reviewing
the pathology.
REFERENCES 1. Rinaldo JE, Rogers RM: Adult respiratory distress syndrome: Changing concepts of lung injury and sepsis. N Engl J Med 1962;306:900-909 2. Taufri RJ: Organophosphate poisoning. Ann Emerg Med 1967;16:193-202 3. Bledsoe PH, et al: Acute pulmonary edema associated with parathion poisoning. Radiolbgy 1972;iO4:53-56 4. Bernstein S. Gould JH. DePalma A: Parathion ooisonina in children. Two rec&eries and one fatality. J Med Soc’New Jerley, May 1966;65:199-203 5. Grob D, Garlick WL, Harvey AM: The toxic effects in man of the anticholinesterase insecticide parathion (p-nitropheynyl diethyl thionophosphate). Bull Johns Hopkins Hasp, Aug 1950;67:106-129 6. Wadia RS, Sadagopan C: Organophosphates and pulmonary edema. (Letter) N Engl J Med 1963;269(2):104 7. Colice GL: Neurogenic pulmonary edema. Clinics in Chest Med, Sept 1965;6(3):473-469 6. Harrison W, Liebow AA: The effects of increased intracranial pressure on the pulmonary circulation in relation to pulmonary edema. Circulation 1952;5:624-632 9. Mackessie RC, Christensen JM, Pitts ZH, et al: Pulmonary extravascular fluid accumulation following intracranial injury. J Trauma 1963;23:966-974
AdultRespiratoryDistress SyndromeFrom Poisoning Organophosphate RICHARD MICHAEL
KASS, DO, GURPREET LIPPMAN, MD
KOCHAR,
A 46-year-old man atter an accidental exposure to organophosphates developed florid adult respiratory distress syndrome (ARDS). A markedly suppressed level of pseudocholinestrase and red blood cell chollnestrase with profuse salivation and sweatin confirmed the diapnosis 01 organophosphate poitoniq. Within 46 hours, patient developed respiratory distress needin intubation. Despite maximum ventilatory support and positive end-explratoty pressure, hypoxia persisted, Swan Ganz (Baxter Healthcare Inc, trvlne, CA) pressures showed low pulmonary capillary wedpe pressure and patient died on the third hospital day. An autopsy confirmed the picture of AROS. Other potential causes of ARDS were excluded. Althou9h rare, or6anophesphate poisonin should be added to the list of toxins causin6 ARDS. (Am J Emerg Med 1991;9:32-33. Copyri6ht 0 1991 by W.B. Saunders Company)
The adult respiratory distress syndrome (ARDS) has been associated with various diseases, injuries, exposure to several drugs and toxic substances.’ We describe a case of organophosphate poisoning in which the patient developed a clinical, radiologic, hemodynamic and pathologic picture compatible with ARDS developed in the patient. To our knowledge, this is the first report of ARDS caused by organophosphate poisoning. CASE REPORT A 46-year-old man was brought to the emergency department (ED) comatose with generalized tonic-clonic seizures and acute respiratory failure requiring intubation. His wife gave a history of the patient’s having ingested an unknown liquid 8 hours earlier in the mistaken belief that it was an alcoholic beverage. He was subsequently noted to have fallen to the ground with the development of generalized seizure activity, diaphoresis, urinary incontinence, and increased salivation. He had no significant past medical history. Physical examination on arrival in the ED showed a thin man, comatose with labored breathing, intermittent generalized tonicclonic seizure activity, and smelling strongly of a pungent garlic-like substance. Heart rate was 110 beats/min. His blood pressure was 160/100 mm Hg. Respirations were labored at 20 breaths/min. He From the Department of Medicine, Albert Einstein Medical Center, and Temple University School of Medicine, Philadelphia, PA. Manuscript received September 21, 1989; revision accepted April 1, 1990. Address reprint requests to Dr Kochar: Division of Cardiology, Albert Einstein Medical Center, York & Tabor Rds, Philadelphia, PA 19141. Key Words: Adult respiratory distress syndrome, organophosphate poisoning. Copyright 0 1991 by W.B. Saunders Company 0735-6757/91/0901-0008$5.00/O 32
MD,
was afebrile. There was significant diaphoresis, and a large amount of secretions in the oropharynx. Lung fields were clear; however, copious tracheobronchial secretions were present. Cardiovascular and abdominal examination were normal. Neurologic examination revealed unresponsiveness to physical stimuli; pupils were pinpoint but reactive to light. Doll’s eyes, comeal reflex were intact, and intermittent generalized tonic-clonic seizures were present. Initial laboratory work including complete blood count, electrolytes, glucase, blood urea nitrogen, creatinine level, calcium (serum amylase and lipase) were normal. Admission chest roentgenogram was unremarkable. An electrocardiogram showed sinus tachycardia with no acute changes. Initial blood gas while intubated on 100% oxygen demonstrated a PO, of 149 mm Hg, a Pco, of 19 mm Hg, a pH of 7.53, bicarbonate 16 mEq/L, and 0, saturation of 99%. Toxicologic analyses of blood and urine for ethanol, benzodiazepines, barbiturates, amphetamines, phenothiazines, opiates, and salicylates were negative. A computed tomography scan of the head was unremarkable. A diagnosis of organophosphate poisoning was suspected based on the presence of a strong characteristic odor and signs of cholinergic hyperstimulation. This diagnosis was confirmed by analysis of gastric contents revealing malathion in concentration of 176 pg/mL. A serum pseudocholinesterase level was 100 p&L (normal range 2,436 to 4,827 c~g/L)and red blood cell cholinesterase level was 1030 kg/L (normal range 3,590 to 6,666 pg/L). Serum and gastric analysis were negative for the presence of any other pesticide, although contribution by hydrocarbons in solvent could not be excluded with certainty. In the ED he was initially stabilized, intubated and given activated charcoal, intravenous (IV) naloxone and 50% dextrose. Gastric lavage returned a large amount of guaiac positive material. He received 2 mg of IV a&opine every 30 minutes for 2 hours in the ED. He was transferred to the intensive care unit where he continued to receive atropine 2 mg every 15 minutes for two hours. After a total dose of 24 mg of IV atropine, patient appeared adequately atropinized clinically as evidenced by mydriasis and tachycardia at a heart rate of 160 beats/min. In addition the patient received I gm of pralidoxime 16 hours after the exposure to organophosphates. He responded very well over the first day, becoming fully alert and coherent with decreased pulmonary secretions. Blood gases on FiO, of 40% were adequate and the patient was extubated 20 hours after admission. However, only 1 hour later his condition markedly deteriorated with increasing respiratory distress requiring reintubation, progressive lethargy, and development of hypotension requiring IV fluids and pressers. Chest roentgenogram at this time demonstrated no evidence of pulmonary edema or infiltrates. Arterial blood gases on 100% FiO, revealed hypoxia with respiratory acidosis (Table 1). A Swan-Ganz catheter (Baxter Healthcare, Inc. Irvine, CA) was placed at this time and showed a mean right atrial pressure of 8 mm Hg, pulmonary arterial pressure of 2617 mm Hg, and a pulmonary
KASS, KOCHAR, AND LIPPMAN
TABLE1.
n ARDS FROM ORGANOPHOSPHATE
Mechanical Ventilator Data O2 Sat.
Day
FiO,
pH
Pcop
PO,
(%)
PCWP (mm Hg)
Normal
0 1 2
100% 40% 100%
7.53 7.41 7.15
19 31 49
149 99 72
99 98 87
-
2
100% PEEP 10
7.26
27
63
69
13
ABBREVIATIONS:PCWP, pulmonary itive end-expiratory pressure.
capillary
Chest Roentgenogram
7
Bibasaiar diffuse shadows Worsening pulmonic shadows
wedge pressure;
PEEP, pos-
capillary wedge pressure (PCWP) of 7 mm Hg with a cardiac output of 5 Limin. He was given 2 liters of normal saline with correction of his hypotension to baseline blood pressure within 2 hours. A second chest roentgenogram 36 hours after admission showed diffuse extensive bilateral shadowing with no Kerley B lines or pleural effusion. He was empirically treated with broad spectrum antibiotics including aminoglycosides for suspected septicemia. However, all the cultures (blood, urine, sputum) drawn before antibiotics did not grow any organisms. His hospital course was complicated by continued hypoxemia despite positive end-expiratory pressure (PEEP) and maximum ventilatory support (Table 1). Serial chest roentgenograms showing worsening bilateral shadowing with consistently low PCWP and refractory hypoxemia led to the diagnosis of ARDS. Patient developed full blown picture of ARDS 20 to 30 hours after completion of the dose of atropine and pralidoxime. The patient continued to deteriorate, and eventually died on the third hospital day. An autopsy was performed. Gross pathology of the lungs showed enlarged wet, firm lungs bilaterally, weighing an average of 1,300 g each. Sections of both lungs showed markedly congested dark reddish-black parenchymal surfaces that exuded bloody fluid freely, indicative of severe congestion and edema. No granulomatous or neoplastic alteration was noted. Microscopic examination showed marked congestion and edema with thickened alveolar walls. Early hyaline membrane formation was noted.
DISCUSSION Organophosphate poisoning has been associated with bronchoconstriction, increased bronchopharyngeal secretions, and respiratory muscle paralysis.* Pulmonary edema has also been described. 3-5 We describe a case of organophosphate poisoning in which the patient developed a clinical picture compatible with ARDS, a noncardiogenic pulmonary edema associated with organophosphate toxicity. Pulmonary edema has been described as an early manifestation of organophosphate toxicity.3 However, the pulmonary edema described in these patients was only a transient event, seen on the admission chest roentgenograms that resolved over the course of one day.3 In addition, no hemodynamic measurements with Swan-Ganz catheter were obtained to substantiate evidence of noncardiogentic pulmonary edema. In one series of 150 suicidal poisonings with organophosphates,6 postmortem specimens showed edematous lungs with fluid fiied alveoli. Muscarinic hypersecretion was implicated as the cause of the observed pulmonary edema. Our case demonstrates many of the features of ARDS. This patient with no prior history of pulmonary or cardiac
POISONING
33
disease, developed refractory hypoxemia despite maximal ventilatory support with PEEP and 100% oxygen after a lethal dose of an organophosphate. In addition, serial chest roentgenograms with worsening pulmonary shadows and continued low PCWP throughout the hospitalization were consistent with ARDS. Both pseudocholinesterase and red blood cell cholinesterase levels were substantially suppressed. Gastric contents aspirated on admission also showed significant amounts of malathion. ARDS as seen in this patient seems to have been a direct consequence of organophosphate poisoning. No other agents were ingested that could be responsible for permeability pulmonary edema, and there was no evidence of septicemia with negative blood cultures. Neurologic events have been linked with the development of ARDS. This patient did have seizures on presentation to the ED; however, there was no evidence of seizure activity or focal neurologic findings on electroencephalography (EEG) or CT of the head, and no subsequent acute neurologic events noted during hospitalization. In addition, in this case, fulminant ARDS developed 48 hours after admission and after all seizure activity had ceased. Neurogenic pulmonary edema usually occurs simultaneously with seizure activity and resolves rapidly.’ Peripheral vasodilatation probably from excessive cholinergic response and hypovolemia seem to be additional explanations for the observed hypotension. The hypotension per se was of short duration (only 2 hours) to cause ARDS. The mechanisms of organophosphate pulmonary toxicity remains speculative. The possibilities include muscarinic hyperstimulation,6 increased vagal tone,’ and excessive catecholamine release.’ This case demonstrates that ARDS may be an ominous complication of organophosphate poisoning that should be anticipated early and considered in the differential diagnosis of toxins causing ARDS. The authors
thank Walter Levy, MD, for reviewing
the pathology.
REFERENCES 1. Rinaldo JE, Rogers RM: Adult respiratory distress syndrome: Changing concepts of lung injury and sepsis. N Engl J Med 1962;306:900-909 2. Taufri RJ: Organophosphate poisoning. Ann Emerg Med 1967;16:193-202 3. Bledsoe PH, et al: Acute pulmonary edema associated with parathion poisoning. Radiolbgy 1972;iO4:53-56 4. Bernstein S. Gould JH. DePalma A: Parathion ooisonina in children. Two rec&eries and one fatality. J Med Soc’New Jerley, May 1966;65:199-203 5. Grob D, Garlick WL, Harvey AM: The toxic effects in man of the anticholinesterase insecticide parathion (p-nitropheynyl diethyl thionophosphate). Bull Johns Hopkins Hasp, Aug 1950;67:106-129 6. Wadia RS, Sadagopan C: Organophosphates and pulmonary edema. (Letter) N Engl J Med 1963;269(2):104 7. Colice GL: Neurogenic pulmonary edema. Clinics in Chest Med, Sept 1965;6(3):473-469 6. Harrison W, Liebow AA: The effects of increased intracranial pressure on the pulmonary circulation in relation to pulmonary edema. Circulation 1952;5:624-632 9. Mackessie RC, Christensen JM, Pitts ZH, et al: Pulmonary extravascular fluid accumulation following intracranial injury. J Trauma 1963;23:966-974
