FORUM activated charcoal
Multiple Doses of Activated Charcoal: Time for Reappraisal? Multiple-dose charcoal therapy has become a popular treatment for many overdoses. It is generally perceived as a simple, inexpensive, effective, and safe procedure that decreases morbidity and mortality by enhancing drug excretion. However, increased drug clearance has been shown definitively for only a few drugs, and improved outcome has not been demonstrated conclusively for any overdose. Recently, there have been several reports of complications due to this intervention. The role of this pharmacologic curiosity in the management of the acutely poisoned patient requires reassessment. [Tenenbein M: Multiple doses of activated charcoal: Time for reappraisal? Ann Emerg Med May 1991;20:529-531.] INTRODUCTION In 1980, a Finnish report demonstrated that multiple doses of activated charcoal administered several hours apart enhanced the rate of elimination of therapeutic doses of phenobarbital and carbamazepine from the body and suggested that this might be an effective treatment strategy for some overdoses.~ In 1982 and 1983, reports from Iowa confirmed this observation for phenobarbital~ and demonstrated a similar effect for theophylline. 3 These two reports, along with an accompanying editorial, 4 have had a major influence on the discipline of medical toxicology. Many reports dealing with multiple-dose charcoal therapy ranging from anecdotal case reports to controlled studies and from commentaries to reviews have been published.5-m
Milton Tenenbein, MD, FRCPC Winnipeg, Manitoba, Canada From the Departments of Pediatrics, Pharmacology, and Medicine, University of Manitoba; and the Manitoba Poison Control Centre, Winnipeg, Manitoba, Canada. Received for publication February 26, 1990. Revisions received July 19, and September 4, 1990. Accepted for publication October 23, 1990. Address for reprints: Milton Tenenbein, MD, Children's Hospital, 840 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1S1.
C U R R E N T STATUS I N M E D I C A L T O X I C O L O G Y This flurry of medical literature has resulted in frequent recommendations for the use of this intervention in poisoned patients. These have ranged from promoting its use in virtually all poisonings 7 to reserving it for selected situations. 6 If it is to be used, the latter approach appears to be more prudent. A pharmacologically sound study of imipramine did not demonstrate a positive result, It and two controlled studies of digoxin resuited in opposite conclusionsA2,13 In addition, recent controlled studies with subtoxic salicylate body burdens did not support the use of multipledose charcoal therapy for this poisoning.14, is Nevertheless, this intervention is now frequently used in the management of many overdosed patients, in large part because this therapy is innately attractive to clinicians. It is reasonable to expect that an increased clearance of a toxin from the body should result in a decreased duration of toxicity. Furthermore, this therapy is generally perceived as a simple, inexpensive, effective, and safe procedure that may obviate the need for other invasive modalities lacking in the above positive features. However, these impressions may not be valid; if so, a reappraisal of the role of multipledose charcoal in the treatment of acutely poisoned patients is in order. Multiple-dose charcoal therapy is a simple procedure, particularly compared with other methods of enhancing the clearance of poisons (hemodialysis and hemoperfusion). In addition, it is inexpensive. Direct costs are low (a few dollars) and include the price of the charcoal and of simple equipment that may be required for its administration (syringes and nasogastric tubes). Indirect costs would be accrued if a complication of ther-' apy should occur.
66/529
Annals of Emergency Medicine
20:5 May 1991
MULTIPLE-DOSE CHARCOAL Tenenbein
EFFICACY Is multiple-dose charcoal therapy effective? Specifically, does it result in decreased morbidity and mortality for our patients? This is a reasonable expectation for patients who are poisoned with medications that have been conclusively shown to be more rapidly cleared from the body by this intervention; these drugs include phenobarbital, ~ theophylline, 3 and phenytoin. 16 Except for one study,17 all reports of acutely poisoned patients are anecdotal and use historical controls. The only prospective, controlled study did not demonstrate any benefit, t7 Even though the validity of this study was subsequently debated,18,19 at the very least, this therapy's efficacy has yet to be established. It is also germane to further examine those specific poisonings that would m o s t likely benefit from multiple-dose charcoal therapy. The mortality of phenytoin toxicity is negligible. Its morbidity is not highly significant in that it consists of nuisance s y m p t o m s rather t h a n lifethreatening events. Thus, potential benefits are not great. Although phenobarbital overdose is life-threatening, it is generally well managed with supportive care. Severe cases (ie, patients with unstable vital signs) that may benefit from active toxin removal should be treated with more effective interventions such as hemodialysis or hemoperfusion. Furthermore, no benefit has been shown for cases of moderate phenobarbital toxicity treated with multiple-dose charcoal therapy.17 The other specific intoxication to consider is theophylline. Multipledose c h a r c o a l t h e r a p y is r e c o m mended for mild-to-moderate cases, with c h a r c o a l h e m o p e r f u s i o n reserved for m o r e serious intoxications. 2° The division between moderate and severe is intended to identify those patients at risk for life-threatening events (ie, seizures and arrhythmias). In addition, the duration of theophylline toxicity is measured in several hours rather than in days, making significant shortening of the duration of t o x i c i t y unlikely. For these reasons, it is unlikely that multiple-dose charcoal therapy would result in significant benefit for these patients. F u r t h e r m o r e , because of theophylline-induced vomiting, this therapy is quite difficult to adminis20:5 May 1991
ter,21, 22 especially to patients with acute theophylline toxicity, which raises concerns regarding efficacy, safety, and acceptability. Vomiting has led to innovations such as constant nasogastric infusions of charcoal 23 and a n t i e m e t i c t h e r a p y . 24 Such maneuvers make the procedure less simple and less safe. COMPLICATIONS If an unproven therapy with theoretic benefit is safe, then its use may still be justifiable. Although initially perceived as safe, the increasing use of multiple-dose charcoal therapy has been accompanied by case reports of morbidity and mortality. Two cases of charcoal-induced bowel obstructions 2s,~6 and six cases of fatal pulmonary aspirations involving charcoal h a v e been reported. 27-3° Alt h o u g h it c o u l d be a r g u e d t h a t cathartic therapy would prevent charcoal-induced bowel obstructions, one of these cases was so treated. 2s Furthermore, repeated cathartic therapy is not w i t h o u t risk, including s y m p t o m a t i c h y p e r m a g n e s e m i a , 3~ significant electrolyte disturbances, 32 and even one case of iatrogenic mortality. 33 Aspiration is an even more serious complication. Although charcoal is relatively unreactive and the acidic gastric contents are known to be the cause of the aspiration syndrome, the repeated administration of charcoal risks triggering v o m i t i n g episodes. This is especially true when abnormalities of gastrointestinal function are present, such as the repeated emesis of theophylline toxicity or the decreased motility of phenobarbital poisoning. Perhaps the traditional approach of n o t h i n g by m o u t h is more appropriate for such patients. Furthermore, aspiration can directly result in an immediate cardiorespiratory arrest.Z7, 2s Intubation of the trachea with a cuffed tube would provide protection for the airway from aspiration; this is suggested as a method of increasing the safety of multiple-dose charcoal therapy. However, if otherwise unneeded, it does not appear sensible to perform this invasive procedure to prevent a complication secondary to an intervention of unproven efficacy. T h i s a p p e a r s e s p e c i a l l y illogical when one of the purported benefits is to obviate the need for intubation or shorten its duration. Annals of Emergency Medicine
CONCLUSION For m a n y interventions for acute overdose patients, it is extremely difficult, if not impossible, to provide a definitive answer regarding efficacy. For multiple-dose charcoal therapy, there are strong, controlled data for a few drugs at subtoxic body burdens that show they ought to be effective,2,3,16 and there are strong, controlled data for other drugs that show they ought not to be effective.11,14,15 There are many anecdotal uncontrolled reports in acutely poisoned p a t i e n t s suggesting that m u l t i p l e dose charcoal therapy is effective, but there are no controlled data conclusively showing that it is. One controlled study failed to demonstrate any benefits. 17 Some of the complications cited above were results of improper therapy, but others were not. Nevertheless, it is apparent that multiple-dose charcoal therapy is not as innocuous as originally believed. Although noninvasive, simple, and inexpensive, multiple-dose charcoal t h e r a p y is of u n p r o v e n efficacy. Thus, in the absence of accurate data indicating effectiveness and risk, a sound r e c o m m e n d a t i o n for its use cannot be made. The treating physician must weigh the theoretic benefit against the potential for complications in each patient. The role of this pharmacologic curiosity in the management of the acutely poisoned patient requires reassessment.
REFERENCES 1. Neuvonen PJ, Elonen E: Effect of activated charcoal on absorption and elimination of phenobarbitone, carbamazepine and phenylbutazone in man. Eur J Clin Pharmacol 1980;17:51-57. 2. Berg MI, Berlinger WG, Goldberg MJ, et al: Acceleration of the body clearance of phenobarbital by oral activated charcoal. N Engl J Med 1982;307:642-644. 3. Berlinger WG, Spector R, Goldberg MJ, et al: Enhancement of theophylline clearance by oral activated charcoal. Clin Pharmacoi Ther 1983;33:351-354. 4. Levy G: Gastrointestinal clearance of drugs with activated charcoal. N Engl J Med 1982;307:676-678. 5. Derlet RW, Albertson TE: Activated charcoal Past, present and future. West J Med 1986;145:493-496. 6. Pond SM: Role of repeated oral doses of activated charcoal in clinical toxicology. Med Toxicol 1986~1:3-11. 7. Jones J, McMullen ML Dougherty J, et al: Repetitive doses of activated charcoal in the treatment of poisoning. A m J Emerg Med 1987;5:305-310. 8. Katona BG, Siegel EG, Cluxton RJ Jr: The new black magic: Activated charcoal and new therapeutic uses. J Emerg Med 1987;5:9-18. 9. Neuvonen PJ, Olkkola KT: Oral activated charcoal in the treatment of intoxications: Role of single and repeated doses. Med Toxicol 1988;3:33-58. 10. Park GD, Spector R, Goldberg MJ, et al: Expanded role of charcoal therapy in the poisoned and overdosed patient. Arch Intern Med 1986;146:969-973. 11. Goldberg MJ, Park GD, Spector R, et al: Lack of ef-
530/67
MULTIPLE-DOSE CHARCOAL Tenenbein
feet of oral activated charcoal on imipramine clearance. Clin Pharmacol Ther 1985~38:350-353. 12. Lalonde RL, Deshpande R, Hamilton PP, et al: Ac celeration of digoxin clearance by activated charcoal. Clin Pharmacol Ther 1985;37:367-371. 13. Park GD, Goldberg M[, Spector R, et al: The effects of activated charcoal on digoxin and digitoxin clearance. Drug Inteli Glin Pharm 1985;19:937-941. 14. Ho JL, Tierney MG, Dickinson GE: An evaluation of the effect of repeated doses of oral activated charcoal on salicylate elimination. J Clin Pharmacoi 1989; 29:366-369. 15. Kirshenbaum LA, Mathews SC, Sitar DS, et al: Does multiple-dose charcoal therapy enhance salicylate ex cretion? Arch Intern Med 1990;150:1281-1283. 16. Mauro L8, Mauro VF, Brown DL, et al: Enhancement of phenytoin elimination by multiple dose acti vated charcoal. Ann Emerg Med 1987;16:1132-1135. 17. Pond SM, Olson KR, Osterloh JD, et ah Randomized study of the treatment of phenobarbital overdose with repeated doses of activated charcoal. JAMA 1984;251: 3104-3108. 18. Goldberg MJ, Berlinger WG, Park GD: Activated charcoal in phenobarbital overdose (letter). JAMA
68/531
1985;253:1120-1121. 19. Pond SM, Osterloh JD, Olson KR, et ah Activated charcoal in phenobarbital overdose (letter}. JAMA 1985~253:1121. 20. Goldberg MI, Spector R, Park GD, et al: An approach to the management of the poisoned patient. Arch Intern Med 1986~146:1381-1385. 2l. Sessler CN, Glauser FL, Cooper KR: Treatment of theophylline toxicity w i t h oral activated charcoal. , Chest 1985;87:325~329. 22. Sessler CN: Poor tolerance of oral activated charcoal w i t h theophylline overdose. A m J Emerg Med 1987~5:492-495.
26. Ray MJ, Padin R, Condie JD, et ah Charcoal bezoar: Small-bowel obstruction secondary to amitriptyline overdose therapy. Dig Dis 8ci 1988;33:106-107. 27. Benson B, Van Antwerp M, Hergott T: A fatality resulting from multiple dose activated charcoal therapy (abstract). Vet Hum Toxicoi 1989;31:335. 28. Harsh HH: Aspiration of activated charcoal (letter). N EngI J Med 1986;314:318. 29. Menzies DG, Busuttil A, Prescott LF: Fatal pulmonary aspiration of oral activated charcoal. Br Med J I988;297:459-460. 30. Rau NR, Nagaraj MV, Prakash PS, et ah Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988;297:918-919.
23. Ohning BL, Reed MD, Biumer ]L: Continuous nasogastric administration of activated charcoal for the treatment of theophylline overdose. Pediatr Pharmaco] 1986;5:241-245.
31. Jones 1, Heiselman D, Dougherty J, et al: Catharticinduced magnesium toxicity during overdose management. Azm Emerg Med 1986;15:1214-1218.
24. Amitai Y, Yeung AC, Moye J, et ah Repetitive oral activated charcoal and control of enresis in severe theophylline toxicity. Ann Intern Med 1986;105:386~387.
32. Caldwell JW, Nava AJ, DeHaas DD: Hypernatremia associated with cathartics in overdose management. West [ Med 1987;147:593-596.
25. Watson WA, Cremer KF, Chapman JA: Gastrointes tinal obstruction associated with multiple-dose acti vated charcoal. J Emerg Med 1986;4:40l 407.
33. Brent l, Kulig K, Rumack BH: Iatrogenic death from sorbitol and magnesium sulfate during treatment for salicylism (abstract). Vet Hum Toxicof 1989;31:334.
Annals of Emergency Medicine
20:5 May 1991
Multiple Doses of Activated Charcoal: Time for Reappraisal? Multiple-dose charcoal therapy has become a popular treatment for many overdoses. It is generally perceived as a simple, inexpensive, effective, and safe procedure that decreases morbidity and mortality by enhancing drug excretion. However, increased drug clearance has been shown definitively for only a few drugs, and improved outcome has not been demonstrated conclusively for any overdose. Recently, there have been several reports of complications due to this intervention. The role of this pharmacologic curiosity in the management of the acutely poisoned patient requires reassessment. [Tenenbein M: Multiple doses of activated charcoal: Time for reappraisal? Ann Emerg Med May 1991;20:529-531.] INTRODUCTION In 1980, a Finnish report demonstrated that multiple doses of activated charcoal administered several hours apart enhanced the rate of elimination of therapeutic doses of phenobarbital and carbamazepine from the body and suggested that this might be an effective treatment strategy for some overdoses.~ In 1982 and 1983, reports from Iowa confirmed this observation for phenobarbital~ and demonstrated a similar effect for theophylline. 3 These two reports, along with an accompanying editorial, 4 have had a major influence on the discipline of medical toxicology. Many reports dealing with multiple-dose charcoal therapy ranging from anecdotal case reports to controlled studies and from commentaries to reviews have been published.5-m
Milton Tenenbein, MD, FRCPC Winnipeg, Manitoba, Canada From the Departments of Pediatrics, Pharmacology, and Medicine, University of Manitoba; and the Manitoba Poison Control Centre, Winnipeg, Manitoba, Canada. Received for publication February 26, 1990. Revisions received July 19, and September 4, 1990. Accepted for publication October 23, 1990. Address for reprints: Milton Tenenbein, MD, Children's Hospital, 840 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1S1.
C U R R E N T STATUS I N M E D I C A L T O X I C O L O G Y This flurry of medical literature has resulted in frequent recommendations for the use of this intervention in poisoned patients. These have ranged from promoting its use in virtually all poisonings 7 to reserving it for selected situations. 6 If it is to be used, the latter approach appears to be more prudent. A pharmacologically sound study of imipramine did not demonstrate a positive result, It and two controlled studies of digoxin resuited in opposite conclusionsA2,13 In addition, recent controlled studies with subtoxic salicylate body burdens did not support the use of multipledose charcoal therapy for this poisoning.14, is Nevertheless, this intervention is now frequently used in the management of many overdosed patients, in large part because this therapy is innately attractive to clinicians. It is reasonable to expect that an increased clearance of a toxin from the body should result in a decreased duration of toxicity. Furthermore, this therapy is generally perceived as a simple, inexpensive, effective, and safe procedure that may obviate the need for other invasive modalities lacking in the above positive features. However, these impressions may not be valid; if so, a reappraisal of the role of multipledose charcoal in the treatment of acutely poisoned patients is in order. Multiple-dose charcoal therapy is a simple procedure, particularly compared with other methods of enhancing the clearance of poisons (hemodialysis and hemoperfusion). In addition, it is inexpensive. Direct costs are low (a few dollars) and include the price of the charcoal and of simple equipment that may be required for its administration (syringes and nasogastric tubes). Indirect costs would be accrued if a complication of ther-' apy should occur.
66/529
Annals of Emergency Medicine
20:5 May 1991
MULTIPLE-DOSE CHARCOAL Tenenbein
EFFICACY Is multiple-dose charcoal therapy effective? Specifically, does it result in decreased morbidity and mortality for our patients? This is a reasonable expectation for patients who are poisoned with medications that have been conclusively shown to be more rapidly cleared from the body by this intervention; these drugs include phenobarbital, ~ theophylline, 3 and phenytoin. 16 Except for one study,17 all reports of acutely poisoned patients are anecdotal and use historical controls. The only prospective, controlled study did not demonstrate any benefit, t7 Even though the validity of this study was subsequently debated,18,19 at the very least, this therapy's efficacy has yet to be established. It is also germane to further examine those specific poisonings that would m o s t likely benefit from multiple-dose charcoal therapy. The mortality of phenytoin toxicity is negligible. Its morbidity is not highly significant in that it consists of nuisance s y m p t o m s rather t h a n lifethreatening events. Thus, potential benefits are not great. Although phenobarbital overdose is life-threatening, it is generally well managed with supportive care. Severe cases (ie, patients with unstable vital signs) that may benefit from active toxin removal should be treated with more effective interventions such as hemodialysis or hemoperfusion. Furthermore, no benefit has been shown for cases of moderate phenobarbital toxicity treated with multiple-dose charcoal therapy.17 The other specific intoxication to consider is theophylline. Multipledose c h a r c o a l t h e r a p y is r e c o m mended for mild-to-moderate cases, with c h a r c o a l h e m o p e r f u s i o n reserved for m o r e serious intoxications. 2° The division between moderate and severe is intended to identify those patients at risk for life-threatening events (ie, seizures and arrhythmias). In addition, the duration of theophylline toxicity is measured in several hours rather than in days, making significant shortening of the duration of t o x i c i t y unlikely. For these reasons, it is unlikely that multiple-dose charcoal therapy would result in significant benefit for these patients. F u r t h e r m o r e , because of theophylline-induced vomiting, this therapy is quite difficult to adminis20:5 May 1991
ter,21, 22 especially to patients with acute theophylline toxicity, which raises concerns regarding efficacy, safety, and acceptability. Vomiting has led to innovations such as constant nasogastric infusions of charcoal 23 and a n t i e m e t i c t h e r a p y . 24 Such maneuvers make the procedure less simple and less safe. COMPLICATIONS If an unproven therapy with theoretic benefit is safe, then its use may still be justifiable. Although initially perceived as safe, the increasing use of multiple-dose charcoal therapy has been accompanied by case reports of morbidity and mortality. Two cases of charcoal-induced bowel obstructions 2s,~6 and six cases of fatal pulmonary aspirations involving charcoal h a v e been reported. 27-3° Alt h o u g h it c o u l d be a r g u e d t h a t cathartic therapy would prevent charcoal-induced bowel obstructions, one of these cases was so treated. 2s Furthermore, repeated cathartic therapy is not w i t h o u t risk, including s y m p t o m a t i c h y p e r m a g n e s e m i a , 3~ significant electrolyte disturbances, 32 and even one case of iatrogenic mortality. 33 Aspiration is an even more serious complication. Although charcoal is relatively unreactive and the acidic gastric contents are known to be the cause of the aspiration syndrome, the repeated administration of charcoal risks triggering v o m i t i n g episodes. This is especially true when abnormalities of gastrointestinal function are present, such as the repeated emesis of theophylline toxicity or the decreased motility of phenobarbital poisoning. Perhaps the traditional approach of n o t h i n g by m o u t h is more appropriate for such patients. Furthermore, aspiration can directly result in an immediate cardiorespiratory arrest.Z7, 2s Intubation of the trachea with a cuffed tube would provide protection for the airway from aspiration; this is suggested as a method of increasing the safety of multiple-dose charcoal therapy. However, if otherwise unneeded, it does not appear sensible to perform this invasive procedure to prevent a complication secondary to an intervention of unproven efficacy. T h i s a p p e a r s e s p e c i a l l y illogical when one of the purported benefits is to obviate the need for intubation or shorten its duration. Annals of Emergency Medicine
CONCLUSION For m a n y interventions for acute overdose patients, it is extremely difficult, if not impossible, to provide a definitive answer regarding efficacy. For multiple-dose charcoal therapy, there are strong, controlled data for a few drugs at subtoxic body burdens that show they ought to be effective,2,3,16 and there are strong, controlled data for other drugs that show they ought not to be effective.11,14,15 There are many anecdotal uncontrolled reports in acutely poisoned p a t i e n t s suggesting that m u l t i p l e dose charcoal therapy is effective, but there are no controlled data conclusively showing that it is. One controlled study failed to demonstrate any benefits. 17 Some of the complications cited above were results of improper therapy, but others were not. Nevertheless, it is apparent that multiple-dose charcoal therapy is not as innocuous as originally believed. Although noninvasive, simple, and inexpensive, multiple-dose charcoal t h e r a p y is of u n p r o v e n efficacy. Thus, in the absence of accurate data indicating effectiveness and risk, a sound r e c o m m e n d a t i o n for its use cannot be made. The treating physician must weigh the theoretic benefit against the potential for complications in each patient. The role of this pharmacologic curiosity in the management of the acutely poisoned patient requires reassessment.
REFERENCES 1. Neuvonen PJ, Elonen E: Effect of activated charcoal on absorption and elimination of phenobarbitone, carbamazepine and phenylbutazone in man. Eur J Clin Pharmacol 1980;17:51-57. 2. Berg MI, Berlinger WG, Goldberg MJ, et al: Acceleration of the body clearance of phenobarbital by oral activated charcoal. N Engl J Med 1982;307:642-644. 3. Berlinger WG, Spector R, Goldberg MJ, et al: Enhancement of theophylline clearance by oral activated charcoal. Clin Pharmacoi Ther 1983;33:351-354. 4. Levy G: Gastrointestinal clearance of drugs with activated charcoal. N Engl J Med 1982;307:676-678. 5. Derlet RW, Albertson TE: Activated charcoal Past, present and future. West J Med 1986;145:493-496. 6. Pond SM: Role of repeated oral doses of activated charcoal in clinical toxicology. Med Toxicol 1986~1:3-11. 7. Jones J, McMullen ML Dougherty J, et al: Repetitive doses of activated charcoal in the treatment of poisoning. A m J Emerg Med 1987;5:305-310. 8. Katona BG, Siegel EG, Cluxton RJ Jr: The new black magic: Activated charcoal and new therapeutic uses. J Emerg Med 1987;5:9-18. 9. Neuvonen PJ, Olkkola KT: Oral activated charcoal in the treatment of intoxications: Role of single and repeated doses. Med Toxicol 1988;3:33-58. 10. Park GD, Spector R, Goldberg MJ, et al: Expanded role of charcoal therapy in the poisoned and overdosed patient. Arch Intern Med 1986;146:969-973. 11. Goldberg MJ, Park GD, Spector R, et al: Lack of ef-
530/67
MULTIPLE-DOSE CHARCOAL Tenenbein
feet of oral activated charcoal on imipramine clearance. Clin Pharmacol Ther 1985~38:350-353. 12. Lalonde RL, Deshpande R, Hamilton PP, et al: Ac celeration of digoxin clearance by activated charcoal. Clin Pharmacol Ther 1985;37:367-371. 13. Park GD, Goldberg M[, Spector R, et al: The effects of activated charcoal on digoxin and digitoxin clearance. Drug Inteli Glin Pharm 1985;19:937-941. 14. Ho JL, Tierney MG, Dickinson GE: An evaluation of the effect of repeated doses of oral activated charcoal on salicylate elimination. J Clin Pharmacoi 1989; 29:366-369. 15. Kirshenbaum LA, Mathews SC, Sitar DS, et al: Does multiple-dose charcoal therapy enhance salicylate ex cretion? Arch Intern Med 1990;150:1281-1283. 16. Mauro L8, Mauro VF, Brown DL, et al: Enhancement of phenytoin elimination by multiple dose acti vated charcoal. Ann Emerg Med 1987;16:1132-1135. 17. Pond SM, Olson KR, Osterloh JD, et ah Randomized study of the treatment of phenobarbital overdose with repeated doses of activated charcoal. JAMA 1984;251: 3104-3108. 18. Goldberg MJ, Berlinger WG, Park GD: Activated charcoal in phenobarbital overdose (letter). JAMA
68/531
1985;253:1120-1121. 19. Pond SM, Osterloh JD, Olson KR, et ah Activated charcoal in phenobarbital overdose (letter}. JAMA 1985~253:1121. 20. Goldberg MI, Spector R, Park GD, et al: An approach to the management of the poisoned patient. Arch Intern Med 1986~146:1381-1385. 2l. Sessler CN, Glauser FL, Cooper KR: Treatment of theophylline toxicity w i t h oral activated charcoal. , Chest 1985;87:325~329. 22. Sessler CN: Poor tolerance of oral activated charcoal w i t h theophylline overdose. A m J Emerg Med 1987~5:492-495.
26. Ray MJ, Padin R, Condie JD, et ah Charcoal bezoar: Small-bowel obstruction secondary to amitriptyline overdose therapy. Dig Dis 8ci 1988;33:106-107. 27. Benson B, Van Antwerp M, Hergott T: A fatality resulting from multiple dose activated charcoal therapy (abstract). Vet Hum Toxicoi 1989;31:335. 28. Harsh HH: Aspiration of activated charcoal (letter). N EngI J Med 1986;314:318. 29. Menzies DG, Busuttil A, Prescott LF: Fatal pulmonary aspiration of oral activated charcoal. Br Med J I988;297:459-460. 30. Rau NR, Nagaraj MV, Prakash PS, et ah Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988;297:918-919.
23. Ohning BL, Reed MD, Biumer ]L: Continuous nasogastric administration of activated charcoal for the treatment of theophylline overdose. Pediatr Pharmaco] 1986;5:241-245.
31. Jones 1, Heiselman D, Dougherty J, et al: Catharticinduced magnesium toxicity during overdose management. Azm Emerg Med 1986;15:1214-1218.
24. Amitai Y, Yeung AC, Moye J, et ah Repetitive oral activated charcoal and control of enresis in severe theophylline toxicity. Ann Intern Med 1986;105:386~387.
32. Caldwell JW, Nava AJ, DeHaas DD: Hypernatremia associated with cathartics in overdose management. West [ Med 1987;147:593-596.
25. Watson WA, Cremer KF, Chapman JA: Gastrointes tinal obstruction associated with multiple-dose acti vated charcoal. J Emerg Med 1986;4:40l 407.
33. Brent l, Kulig K, Rumack BH: Iatrogenic death from sorbitol and magnesium sulfate during treatment for salicylism (abstract). Vet Hum Toxicof 1989;31:334.
Annals of Emergency Medicine
20:5 May 1991
