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Death Due to Acute Salicylate Intoxication Despite Dialysis
The Journal of Emergency Medicine, Vol. 40, No. 5, pp. 515–517, 2011 Copyright © 2011 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$–see front matter
doi:10.1016/j.jemermed.2010.02.015
Selected Topics: Toxicology
DEATH DUE TO ACUTE SALICYLATE INTOXICATION DESPITE DIALYSIS Alicia B. Minns,
MD,*
F. Lee Cantrell,
PHARMD,†
and Richard F. Clark,
MD*
*Department of Emergency Medicine, Division of Medical Toxicology and †Department of Clinical Pharmacy, University of California, San Diego, San Diego, California Corresponding Address: Alicia B. Minns, MD, Department of Emergency Medicine, Division of Medical Toxicology, University of California, San Diego, 200 West Arbor Drive, MC 8925, San Diego, CA 92103-8925
e Abstract—Background: Salicylate poisoning is a common problem with appreciable morbidity and mortality. We present a case of a patient with a large aspirin ingestion who expired despite aggressive hemodialysis (HD). Case Report: A 35-year-old man arrived at the Emergency Department 7.5 h after ingesting 400 tablets of 325-mg aspirin. He was afebrile, the respiratory rate (RR) was 30 breaths/ min, heart rate (HR) 120 beats/min, blood pressure (BP) 125/76 mm Hg, and oxygen saturation 99% on room air. His salicylate concentration was 89.6 mg/dL. His initial arterial blood gas: pH 7.48, pCO2 21 mm Hg, PaO2 97 mm Hg, and bicarbonate 15.8 mmol/L. His initial serum chemistry panel was normal. He received activated charcoal and intravenous hydration with sodium bicarbonate. Two hours after arrival, salicylate concentration was 91.6 mg/dL. The patient became agitated and HD was initiated; 22 h after presentation, repeat salicylate concentration was 88.4 mg/dL and his creatinine was 3.9 mg/dL. A second run of HD was performed. After this, his temperature had risen to 39.06°C (102.3°F), BP 122/64 mm Hg, HR 168 beats/min, RR 43 breaths/min, and oxygen saturation 95% (2 L nasal cannula). His confusion increased, and he died 40 h after his ingestion. Conclusion: HD is widely advocated in managing severe salicylate intoxications, however, no consensus exists for the duration and best mode of therapy. Patients with severe salicylate poisonings may require extended durations of HD to effectively mitigate toxicity. Additional study is warranted to determine optimal therapy in severe salicylate intoxications. © 2011 Elsevier Inc.
INTRODUCTION Salicylate poisoning remains a common problem with appreciable morbidity and mortality. This is largely due to the availability of aspirin and its frequent occurrence in sources such as over-the-counter cold and allergy preparations (1). In 2007 there were over 4800 exposures of aspirin alone reported to United States poison centers, with 63 deaths, representing 5% of all human fatalities reported (2). Severe salicylate poisoning can be life threatening, and aggressive treatment is required to reduce absorption and distribution, as well as hasten elimination. In large ingestions or those involving entericcoated tablets, absorption may be variable, or delayed in the setting of concretions or bezoars. In severe cases, hemodialysis may be required to correct acid-base, fluid, and electrolyte disturbances in addition to rapidly clearing the blood of salicylate (3). Generally accepted indications for hemodialysis in the acutely poisoned patient include severe metabolic acidosis refractory to optimal supportive care, evidence of end-organ injury (seizures, renal failure, pulmonary edema, altered mental status), and serum salicylate concentration ⬎ 100 mg/dL (4 – 6). It should also be considered for patients who require endotracheal intubation (6). In assessing the severity of salicylate poisoning, many practitioners rely on serum salicylate concentrations to make treatment decisions. However, data from both the American Association of Poison Control Centers in 2007 and from a 2-year review
e Keywords—salicylate; renal dialysis; charcoal; acidosis; antidote; toxicity
RECEIVED: 14 August 2009; FINAL ACCEPTED: 17 February 2010
SUBMISSION RECEIVED:
11 January 2010; 515
516
A. B. Minns et al.
of salicylate deaths in Ontario, Canada, show that patients die with less appreciably elevated salicylate levels than many clinicians have been taught to anticipate in both acute and chronic ingestions (2,7). We present a case of a patient with a large, acute aspirin ingestion who expired despite treatment with hemodialysis. An exemption from review and monitoring was granted by the Institutional Review Board.
(102.3°F), BP 122/64 mm Hg, HR 168 beats/min, RR 43 breaths/min, and oxygen saturation 95% (2 L NC). He became progressively more confused, and died early that morning, approximately 40 h after his ingestion. An autopsy was performed and demonstrated pulmonary edema. An antemortem salicylate level was 80 mg/dL.
DISCUSSION CASE REPORT A 35-year-old man arrived at the Emergency Department 7.5 h after reportedly ingesting 400 tablets of regularstrength aspirin. He initially was afebrile, with a respiratory rate (RR) of 30 breaths/min, heart rate (HR) 120 beats/min, blood pressure (BP) 125/76 mm Hg, and oxygen saturation of 99% on room air. He was diaphoretic, and the remainder of his cardiac, pulmonary, abdominal, and neurologic examination was unremarkable. His initial laboratory analysis demonstrated a blood salicylate concentration of 89.6 mg/ dL. His initial arterial blood gas showed a pH of 7.48, pCO2 21 mm Hg, PaO2 97 mm Hg, and bicarbonate 15.8 mmol/L. His initial serum chemistry panel was normal. He was initially given a single dose of oral activated charcoal and started on intravenous (i.v.) hydration dextrose 5% in water with three ampules of sodium bicarbonate and 20 mEq of potassium chloride. Two hours after his initial presentation, a repeat salicylate concentration was 91.6 mg/dL. His serum chemistries demonstrated a sodium of 146 mmol/L, potassium 3.7 mmol/L, chloride 134 mmol/L, bicarbonate 20 mmol/L, blood urea nitrogen (BUN) 10 mg/dL, creatinine 1.3 mg/ dL, and glucose 159 mg/dL. The patient became increasingly agitated and combative. The poison control center was consulted and, out of concern for developing end-organ toxicity, a 4-h run of hemodialysis was initiated. After hemodialysis, his temperature was 38.7°C (101.6°F), BP 94/50 mm Hg, HR 147 beats/min, RR 34 breaths/min, and oxygen saturation 100% on 2 L nasal cannula (NC). His serum salicylate concentration measured at the end of the 4 h of hemodialysis was 85.8 mg/dL. His chemistry panel at that time showed a sodium of 141 mmol/L, potassium 3.7 mmol/L, chloride 124 mmol/L, bicarbonate 17 mmol/L, BUN 14 mg/ dL, creatinine 2.4 mg/dL, and glucose 150 mg/dL. Because his mental status was improving, supportive care was continued, including i.v. fluids with sodium bicarbonate. Approximately 22 h after his initial presentation and 30 h after his ingestion, a repeat salicylate concentration was 88.4 mg/dL and his repeat creatinine had risen to 3.9 mg/dL. A second 4-h run of hemodialysis was then initiated due to the worsening renal function and persistent salicylate concentrations. After completion of his second hemodialysis session, his temperature had risen to 39.06°C
Salicylate poisoning is associated with a relatively large number of fatal outcomes annually in the United States (2). There is no specific antidote, and treatment is directed toward inhibiting further absorption, preventing its entry into the central nervous system, the most vulnerable target organ, and enhancing elimination from the body. Activated charcoal has been shown to effectively reduce the absorption of aspirin from the gastrointestinal tract (8). The patient described in this report did receive a single dose of activated charcoal initially, but did not receive any additional doses due to altered mental status. With an ingestion of over 100 g aspirin, it may have taken up to 1000 g of activated charcoal to bind significant amounts of it before absorption. Aspirin has also been shown to have delayed absorption from the gastrointestinal tract in cases of massive ingestion. The proposed mechanisms for this occurrence include bezoar formation in the stomach or intestines and pylorospasm delaying gastric emptying. This finding has prompted some toxicologists and poison control centers to recommend whole bowel irrigation with an isosmotic isoelectric cathartic in an attempt to move aspirin more rapidly into the large bowel to cut down on absorption. Despite persistently elevated salicylate concentrations after hemodialysis in our patient, suggesting ongoing absorption, whole bowel irrigation could not be instituted due to the rapid decline in mental status. Endotracheally intubating this patient would have provided more protection from aspiration. However, previous reports document death soon after intubation in acute salicylate toxicity, likely due to hypercarbia, worsening respiratory acidosis, and increased distribution of salicylate into target organs (9). With respect to reducing the distribution of salicylate out of the serum and into the tissues, serum alkalinization was performed. Because aspirin is a weak acid, ionization is increased in an alkaline environment. Alkalinization of the serum with sodium bicarbonate can prevent salicylate from entering the central nervous system. Alkalinization of the urine potentially enhances renal excretion of ionized salicylate. Vree et al. and Prescott et al. both demonstrated that urine alkalinization enhances salicylate clearance (10,11). In 2004, a position paper prepared by the American Academy of Clinical Toxicology and the European Association of Poison
Salicylate Poisoning
517
Centres and Clinical Toxicologists stated, “urine alkalinization should be considered first line in patients with moderately severe salicylate poisoning who do not meet the criteria for hemodialysis” (12). Care should also be taken to avoid complications of alkalinization such as severe alkalemia, hypokalemia, and coronary and cerebral vasoconstriction. The characteristics of aspirin such as the low volume of distribution, low protein binding, small molecular weight, and high water solubility enable it to be removed by dialysis. This has been demonstrated in both animal and human studies (13). In 1955, the first patient who successfully underwent hemodialysis for salicylate poisoning was described by Schreiner et al. (14). Two patients with serum salicylate concentrations of 91 and 90 mg/dL, respectively, were compared. The former underwent hemodialysis for 6 h, whereas the latter was conservatively treated with bicarbonate. The patient who underwent hemodialysis rapidly recovered, whereas the patient who was conservatively treated did not fully recover from the effects of salicylate until 6 days after ingestion. Since then, many publications have attested to the clinical efficacy of hemodialysis in the management of severe salicylate intoxication, however, there is no consensus as to the duration and mode of therapy. Wrathall et al. reported their experience with continuous venovenous hemodiafiltration (CVVHDF) (3). This method of extracorporeal removal may be useful in cases where conventional hemodialysis is not available or the patient is not hemodynamically stable. There are no controlled trials comparing CVVHDF and hemodialysis for salicylate removal and there are no detailed recommendations regarding hemodialysis protocols for salicylate intoxication. Previous studies of charcoal hemoperfusion have demonstrated that salicylate removal is rapid and comparable with hemodialysis (13). However, more rapid correction of metabolic disturbances is attainable with hemodialysis, and charcoal hemoperfusion is no longer readily available (15). Our case illustrates that even in cases in which salicylate poisoning is recognized promptly and dialysis is instituted in a timely manner, end-organ damage can occur. CONCLUSION We present a patient with severe salicylate intoxication who expired despite aggressive therapy with gastrointes-
tinal decontamination, sodium bicarbonate therapy, and hemodialysis. It is unclear whether altering the way in which any of the discussed interventions were utilized would have made a difference in this patient’s outcome. Additional study is warranted to determine and define the optimal treatment regimen for severe salicylate intoxications.
REFERENCES 1. Chan TYK. The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin. Postgrad Med J 1996; 72:109 –12. 2. Bronstein AC, Spyker DA, Cantilena LR, et al. 2007 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 25th annual report. Clin Toxicol (Phila) 2008;46:927–1057. 3. Wrathall G, Sinclair R, Moore A, Pogson D. Three case reports of the use of haemodiafiltration in the treatment of salicylate overdose. Hum Exp Toxicol 2001;20:491–5. 4. Cohen DL, Post J, Ferroggiaro AA, Perrone J, Foster MH. Chronic salicylism resulting in noncardiogenic pulmonary edema requiring hemodialysis. Am J Kidney Dis 2000;36:1– 4. 5. Fertel BS, Nelson LS, Goldfarb DS. The underutilization of hemodialysis in patients with salicylate poisoning. Kidney Int 2009; 75:1349 –53. 6. O’Malley GF. Emergency department management of the salicylatepoisoned patient. Emerg Med Clin North Am 2007;25:333– 46. 7. McGuigan MA. A two-year review of salicylate deaths in Ontario. Arch Intern Med 1987;147:510 –2. 8. Dillon EC Jr, Wilton JH, Barlow JC, Watson WA. Large surface area activated charcoal and the inhibition of aspirin absorption. Ann Emerg Med 1989;18:547–52. 9. Stolback AI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with academia in a case series of salicylate-poisoned patients. Acad Emerg Med 2008;15:866 –9. 10. Vree TB, Van Ewijk-Beneken Kolmer EM, Verwey-Van Wissen CP, Hekster YA. Effect of urinary pH on the pharmacokinetics of salicylic acid, with its glycine and glucuronide conjugates in human. Int J Clin Pharmacol Ther 1994;32:550 – 8. 11. Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT. Diuresis or urinary alkalinisation for salicylate poisoning? Br Med J (Clin Res Ed) 1982;285:1383– 6. 12. Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol 2004;42:1–26. 13. Winchester JF, Gelfand MC, Helliwell M, Vale JA, Goulding R, Schreiner GE. Extracorporeal treatment of salicylate or acetaminophen poisoning—is there a role? Arch Intern Med 1981;141: 370 – 4. 14. Schreiner GE, Berman LB, Griffin J, Feys J. Specific therapy for salicylism. N Engl J Med 1955;253:213–17. 15. Jacobsen D, Wiik-Larsen E, Bredesen JE. Haemodialysis or haemoperfusion in severe salicylate poisoning? Hum Toxicol 1988;7: 161–3.
doi:10.1016/j.jemermed.2010.02.015
Selected Topics: Toxicology
DEATH DUE TO ACUTE SALICYLATE INTOXICATION DESPITE DIALYSIS Alicia B. Minns,
MD,*
F. Lee Cantrell,
PHARMD,†
and Richard F. Clark,
MD*
*Department of Emergency Medicine, Division of Medical Toxicology and †Department of Clinical Pharmacy, University of California, San Diego, San Diego, California Corresponding Address: Alicia B. Minns, MD, Department of Emergency Medicine, Division of Medical Toxicology, University of California, San Diego, 200 West Arbor Drive, MC 8925, San Diego, CA 92103-8925
e Abstract—Background: Salicylate poisoning is a common problem with appreciable morbidity and mortality. We present a case of a patient with a large aspirin ingestion who expired despite aggressive hemodialysis (HD). Case Report: A 35-year-old man arrived at the Emergency Department 7.5 h after ingesting 400 tablets of 325-mg aspirin. He was afebrile, the respiratory rate (RR) was 30 breaths/ min, heart rate (HR) 120 beats/min, blood pressure (BP) 125/76 mm Hg, and oxygen saturation 99% on room air. His salicylate concentration was 89.6 mg/dL. His initial arterial blood gas: pH 7.48, pCO2 21 mm Hg, PaO2 97 mm Hg, and bicarbonate 15.8 mmol/L. His initial serum chemistry panel was normal. He received activated charcoal and intravenous hydration with sodium bicarbonate. Two hours after arrival, salicylate concentration was 91.6 mg/dL. The patient became agitated and HD was initiated; 22 h after presentation, repeat salicylate concentration was 88.4 mg/dL and his creatinine was 3.9 mg/dL. A second run of HD was performed. After this, his temperature had risen to 39.06°C (102.3°F), BP 122/64 mm Hg, HR 168 beats/min, RR 43 breaths/min, and oxygen saturation 95% (2 L nasal cannula). His confusion increased, and he died 40 h after his ingestion. Conclusion: HD is widely advocated in managing severe salicylate intoxications, however, no consensus exists for the duration and best mode of therapy. Patients with severe salicylate poisonings may require extended durations of HD to effectively mitigate toxicity. Additional study is warranted to determine optimal therapy in severe salicylate intoxications. © 2011 Elsevier Inc.
INTRODUCTION Salicylate poisoning remains a common problem with appreciable morbidity and mortality. This is largely due to the availability of aspirin and its frequent occurrence in sources such as over-the-counter cold and allergy preparations (1). In 2007 there were over 4800 exposures of aspirin alone reported to United States poison centers, with 63 deaths, representing 5% of all human fatalities reported (2). Severe salicylate poisoning can be life threatening, and aggressive treatment is required to reduce absorption and distribution, as well as hasten elimination. In large ingestions or those involving entericcoated tablets, absorption may be variable, or delayed in the setting of concretions or bezoars. In severe cases, hemodialysis may be required to correct acid-base, fluid, and electrolyte disturbances in addition to rapidly clearing the blood of salicylate (3). Generally accepted indications for hemodialysis in the acutely poisoned patient include severe metabolic acidosis refractory to optimal supportive care, evidence of end-organ injury (seizures, renal failure, pulmonary edema, altered mental status), and serum salicylate concentration ⬎ 100 mg/dL (4 – 6). It should also be considered for patients who require endotracheal intubation (6). In assessing the severity of salicylate poisoning, many practitioners rely on serum salicylate concentrations to make treatment decisions. However, data from both the American Association of Poison Control Centers in 2007 and from a 2-year review
e Keywords—salicylate; renal dialysis; charcoal; acidosis; antidote; toxicity
RECEIVED: 14 August 2009; FINAL ACCEPTED: 17 February 2010
SUBMISSION RECEIVED:
11 January 2010; 515
516
A. B. Minns et al.
of salicylate deaths in Ontario, Canada, show that patients die with less appreciably elevated salicylate levels than many clinicians have been taught to anticipate in both acute and chronic ingestions (2,7). We present a case of a patient with a large, acute aspirin ingestion who expired despite treatment with hemodialysis. An exemption from review and monitoring was granted by the Institutional Review Board.
(102.3°F), BP 122/64 mm Hg, HR 168 beats/min, RR 43 breaths/min, and oxygen saturation 95% (2 L NC). He became progressively more confused, and died early that morning, approximately 40 h after his ingestion. An autopsy was performed and demonstrated pulmonary edema. An antemortem salicylate level was 80 mg/dL.
DISCUSSION CASE REPORT A 35-year-old man arrived at the Emergency Department 7.5 h after reportedly ingesting 400 tablets of regularstrength aspirin. He initially was afebrile, with a respiratory rate (RR) of 30 breaths/min, heart rate (HR) 120 beats/min, blood pressure (BP) 125/76 mm Hg, and oxygen saturation of 99% on room air. He was diaphoretic, and the remainder of his cardiac, pulmonary, abdominal, and neurologic examination was unremarkable. His initial laboratory analysis demonstrated a blood salicylate concentration of 89.6 mg/ dL. His initial arterial blood gas showed a pH of 7.48, pCO2 21 mm Hg, PaO2 97 mm Hg, and bicarbonate 15.8 mmol/L. His initial serum chemistry panel was normal. He was initially given a single dose of oral activated charcoal and started on intravenous (i.v.) hydration dextrose 5% in water with three ampules of sodium bicarbonate and 20 mEq of potassium chloride. Two hours after his initial presentation, a repeat salicylate concentration was 91.6 mg/dL. His serum chemistries demonstrated a sodium of 146 mmol/L, potassium 3.7 mmol/L, chloride 134 mmol/L, bicarbonate 20 mmol/L, blood urea nitrogen (BUN) 10 mg/dL, creatinine 1.3 mg/ dL, and glucose 159 mg/dL. The patient became increasingly agitated and combative. The poison control center was consulted and, out of concern for developing end-organ toxicity, a 4-h run of hemodialysis was initiated. After hemodialysis, his temperature was 38.7°C (101.6°F), BP 94/50 mm Hg, HR 147 beats/min, RR 34 breaths/min, and oxygen saturation 100% on 2 L nasal cannula (NC). His serum salicylate concentration measured at the end of the 4 h of hemodialysis was 85.8 mg/dL. His chemistry panel at that time showed a sodium of 141 mmol/L, potassium 3.7 mmol/L, chloride 124 mmol/L, bicarbonate 17 mmol/L, BUN 14 mg/ dL, creatinine 2.4 mg/dL, and glucose 150 mg/dL. Because his mental status was improving, supportive care was continued, including i.v. fluids with sodium bicarbonate. Approximately 22 h after his initial presentation and 30 h after his ingestion, a repeat salicylate concentration was 88.4 mg/dL and his repeat creatinine had risen to 3.9 mg/dL. A second 4-h run of hemodialysis was then initiated due to the worsening renal function and persistent salicylate concentrations. After completion of his second hemodialysis session, his temperature had risen to 39.06°C
Salicylate poisoning is associated with a relatively large number of fatal outcomes annually in the United States (2). There is no specific antidote, and treatment is directed toward inhibiting further absorption, preventing its entry into the central nervous system, the most vulnerable target organ, and enhancing elimination from the body. Activated charcoal has been shown to effectively reduce the absorption of aspirin from the gastrointestinal tract (8). The patient described in this report did receive a single dose of activated charcoal initially, but did not receive any additional doses due to altered mental status. With an ingestion of over 100 g aspirin, it may have taken up to 1000 g of activated charcoal to bind significant amounts of it before absorption. Aspirin has also been shown to have delayed absorption from the gastrointestinal tract in cases of massive ingestion. The proposed mechanisms for this occurrence include bezoar formation in the stomach or intestines and pylorospasm delaying gastric emptying. This finding has prompted some toxicologists and poison control centers to recommend whole bowel irrigation with an isosmotic isoelectric cathartic in an attempt to move aspirin more rapidly into the large bowel to cut down on absorption. Despite persistently elevated salicylate concentrations after hemodialysis in our patient, suggesting ongoing absorption, whole bowel irrigation could not be instituted due to the rapid decline in mental status. Endotracheally intubating this patient would have provided more protection from aspiration. However, previous reports document death soon after intubation in acute salicylate toxicity, likely due to hypercarbia, worsening respiratory acidosis, and increased distribution of salicylate into target organs (9). With respect to reducing the distribution of salicylate out of the serum and into the tissues, serum alkalinization was performed. Because aspirin is a weak acid, ionization is increased in an alkaline environment. Alkalinization of the serum with sodium bicarbonate can prevent salicylate from entering the central nervous system. Alkalinization of the urine potentially enhances renal excretion of ionized salicylate. Vree et al. and Prescott et al. both demonstrated that urine alkalinization enhances salicylate clearance (10,11). In 2004, a position paper prepared by the American Academy of Clinical Toxicology and the European Association of Poison
Salicylate Poisoning
517
Centres and Clinical Toxicologists stated, “urine alkalinization should be considered first line in patients with moderately severe salicylate poisoning who do not meet the criteria for hemodialysis” (12). Care should also be taken to avoid complications of alkalinization such as severe alkalemia, hypokalemia, and coronary and cerebral vasoconstriction. The characteristics of aspirin such as the low volume of distribution, low protein binding, small molecular weight, and high water solubility enable it to be removed by dialysis. This has been demonstrated in both animal and human studies (13). In 1955, the first patient who successfully underwent hemodialysis for salicylate poisoning was described by Schreiner et al. (14). Two patients with serum salicylate concentrations of 91 and 90 mg/dL, respectively, were compared. The former underwent hemodialysis for 6 h, whereas the latter was conservatively treated with bicarbonate. The patient who underwent hemodialysis rapidly recovered, whereas the patient who was conservatively treated did not fully recover from the effects of salicylate until 6 days after ingestion. Since then, many publications have attested to the clinical efficacy of hemodialysis in the management of severe salicylate intoxication, however, there is no consensus as to the duration and mode of therapy. Wrathall et al. reported their experience with continuous venovenous hemodiafiltration (CVVHDF) (3). This method of extracorporeal removal may be useful in cases where conventional hemodialysis is not available or the patient is not hemodynamically stable. There are no controlled trials comparing CVVHDF and hemodialysis for salicylate removal and there are no detailed recommendations regarding hemodialysis protocols for salicylate intoxication. Previous studies of charcoal hemoperfusion have demonstrated that salicylate removal is rapid and comparable with hemodialysis (13). However, more rapid correction of metabolic disturbances is attainable with hemodialysis, and charcoal hemoperfusion is no longer readily available (15). Our case illustrates that even in cases in which salicylate poisoning is recognized promptly and dialysis is instituted in a timely manner, end-organ damage can occur. CONCLUSION We present a patient with severe salicylate intoxication who expired despite aggressive therapy with gastrointes-
tinal decontamination, sodium bicarbonate therapy, and hemodialysis. It is unclear whether altering the way in which any of the discussed interventions were utilized would have made a difference in this patient’s outcome. Additional study is warranted to determine and define the optimal treatment regimen for severe salicylate intoxications.
REFERENCES 1. Chan TYK. The risk of severe salicylate poisoning following the ingestion of topical medicaments or aspirin. Postgrad Med J 1996; 72:109 –12. 2. Bronstein AC, Spyker DA, Cantilena LR, et al. 2007 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 25th annual report. Clin Toxicol (Phila) 2008;46:927–1057. 3. Wrathall G, Sinclair R, Moore A, Pogson D. Three case reports of the use of haemodiafiltration in the treatment of salicylate overdose. Hum Exp Toxicol 2001;20:491–5. 4. Cohen DL, Post J, Ferroggiaro AA, Perrone J, Foster MH. Chronic salicylism resulting in noncardiogenic pulmonary edema requiring hemodialysis. Am J Kidney Dis 2000;36:1– 4. 5. Fertel BS, Nelson LS, Goldfarb DS. The underutilization of hemodialysis in patients with salicylate poisoning. Kidney Int 2009; 75:1349 –53. 6. O’Malley GF. Emergency department management of the salicylatepoisoned patient. Emerg Med Clin North Am 2007;25:333– 46. 7. McGuigan MA. A two-year review of salicylate deaths in Ontario. Arch Intern Med 1987;147:510 –2. 8. Dillon EC Jr, Wilton JH, Barlow JC, Watson WA. Large surface area activated charcoal and the inhibition of aspirin absorption. Ann Emerg Med 1989;18:547–52. 9. Stolback AI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with academia in a case series of salicylate-poisoned patients. Acad Emerg Med 2008;15:866 –9. 10. Vree TB, Van Ewijk-Beneken Kolmer EM, Verwey-Van Wissen CP, Hekster YA. Effect of urinary pH on the pharmacokinetics of salicylic acid, with its glycine and glucuronide conjugates in human. Int J Clin Pharmacol Ther 1994;32:550 – 8. 11. Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT. Diuresis or urinary alkalinisation for salicylate poisoning? Br Med J (Clin Res Ed) 1982;285:1383– 6. 12. Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol 2004;42:1–26. 13. Winchester JF, Gelfand MC, Helliwell M, Vale JA, Goulding R, Schreiner GE. Extracorporeal treatment of salicylate or acetaminophen poisoning—is there a role? Arch Intern Med 1981;141: 370 – 4. 14. Schreiner GE, Berman LB, Griffin J, Feys J. Specific therapy for salicylism. N Engl J Med 1955;253:213–17. 15. Jacobsen D, Wiik-Larsen E, Bredesen JE. Haemodialysis or haemoperfusion in severe salicylate poisoning? Hum Toxicol 1988;7: 161–3.