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Methanol Intoxication
Correspondence
Methanol Intoxication
Methanol Intoxication
Marco L. A. Sivilotti, MD, MSc
To the Editor: Potential for Duragesic Patch Abuse
Mary Purucker, MD, PhD William Swann, DO Disaster Medical Education for All Physicians and Physician Extenders
Paul Rega, MD Reply
Nicki Pesik, MD Mark Keim, MD Copyright © 2000 by the American College of Emergency Physicians. 0196-0644/2000/$12.00 + 0
Although the case reported by Wang et al 1 (article #99697) in their letter to the editor may well describe a moderately severe case of methanol poisoning, the purported source of methanol does not withstand close scrutiny. The authors base their report on the claim that the patient developed visual impairment after intravenous injection of 250 mL of a solution containing 95% ethanol and 100 ppm of methanol, or a total dose of 20 to 25 mg of methanol. This quantity of methanol, however, is trivial and certainly not toxic. In fact fruit juices contain up to 140 ppm of methanol, and products of natural fermentation may contain as much as 1.500 ppm of methanol. 2 A 12-oz can of diet soda containing 200 mg of aspartame is metabolized to 20 mg of methanol, accounting for an Internet-propagated urban legend. 3
Indeed, much higher doses (10 mg/kg intravenously with ethanol, and 80 mg/kg orally without ethanol) have been used without toxicity in human volunteer studies, including the one cited by the authors. 4 .5 With 100% bioavailability and very rapid absorption via the oral route. there is no evidence to support the authors' claim of significantly different pharmacokinetics after intravenous administration. nor is there evidence to suggest enhanced pharmacodynamic toxicity. Assuming their patient weighed approximately 50 kg. the exposure alleged by the authors would be expected to increase the serum methanol concentration by 0.07 mg/dL (0.02 mmol/L; normal methanol levels $;0.26 mg/dL due to endogenous and dietary sources 6 ). nearly 1.000 times less than concentrations for which hemodialysis and antidotal treatment are recommended. A further margin of safety is afforded by the impressive peak ethanol concentration of more than 500
Guidelines for Letters Annals welcomes correspondence. including observations. opinions. corrections. very brief reports, and comments on published articles. Letters to the editor will not be accepted if they exceed 500 words and 5 references. Two double-spaced copies must be submitted; a computer disk is required. Letters should not contain abbreviations. They must be signed and include a postscript granting permission to publish. Financial associations or other possible conflicts of interest should always be disclosed. Letters discussing an Annals article must be received within 6 weeks of the article's publication. Annals acknowledges receipt of letters with a postcard or e-mail message. and correspondents are notified by postcard when a decision is made. Published letters will be edited and may be shortened. Unpublished letters will not be returned. Authors of articles for which we receive comments will be given the opportunity to reply. The reply will not be shared with the author of the letter before publication. Neither Annals of Emergency Medicine nor the Publisher accepts responsibility for statements made by contributors or advertisers. Acceptance of an advertisment for placement in Annals in no way represents endorsement of a particular product or service by Annals of Emergency Medicine. the American College of Emergency Physicians. or the Publisher.
MARCH 2000
35:3
ANNALS OF EMERGENCY MEDICINE
313
CORRESPONDENCE mg/dL expected in their patient. accounting for the prolonged coma. Given that the funduscopic changes reported are characteristic for methanol poisoning, one must conclude that the patient experienced a second exposure to a more concentrated source of methanol, perhaps by ingesting at least several grams. Thus, the case report is most significant for being the first report of self-administration of antidotal ethanol via the intravenous route. Given the incomplete success, it also serves as evidence to support the admonition, "Don't try this at home!" Marco L.A. Sivilotti, MD, MSc Department of Emergency Medicine Brigham and Womens Hospital Harvard Medical School Boston, MA
47/8/104530 doi:1o. lo67/mem.2ooo. 104530 1. Wang]Y, Lin YF, Lin SoH. Methanol intoxication with retinal injury by intravenous injection [letter). Ann Emerg Med. 1999;34:297-298.
2. Francot P, Geoffroy P. Le methanol dans Ies jus de fruits,
Ies boissons, fermenttes, Ies alcools et spiriteux. Rev Ferment Ind Aliment. 1956;11 :279.
3. Stegink LD. Aspartame metabolism in humans: acute dosing studies. In: Stegink ill, Filer LJ, eds. Aspartame: PhYSiology and Biochemistry. New Yorh, NY: Marcel
Decker: 1984'509. 4. Haffner H-T, Besserer K, Graw M, et al Methanol elimi-
nation in non-alcoholics: inter- and intraindividual variation. Forsensic Sci Int. 1997;86:69-76. 5. Leaf G, Zat?,an Lj. A study of the conditions under which methanol may exert a toxic hazard in industry. Br J Ind Med. 1952;9:19-31.
6. Sedivec V, Mraz M, FlehJ. BiolOgical monitoring of per-
sons exposed to methanol vapours. Int Arch Occup Environ Health. 1981;48:257-71.
Potential for Duragesic Patch Abuse To the Editor: I
We wish to report a case of acute narcotic overdose induced by the intentional oral ingestion 9f a fentanyl (Duragesic) patch. The patient was a 24-year-old woman who presented to the emergency department of a community hospital complaining of severe pain related to an ongoing miscarriage. She also claimed to have chronic pain and muscle spasms caused by multiple sclerosis, for which she required frequent doses
31 4
of narcotic analgesics. The patient's history of narcotic dependence and substance abuse was unknown at that time, but suspected because of inconsistencies in her medical history and her demands for potent narcotic analgesics to treat her pain. She received intramuscular meperidine acutely, and a Duragesic patch (fentanyl transdermal system; Janssen Pharmaceutical at 50 J.!g/h was applied for sustained pain relief. The patient asked to use the lavatory, and shortly after her return was noted by ED staff to be cyanotic and apneic. She was quickly resuscitated, and an empty Duragesic patch was retrieved from her billfold. Bite marks were found at one end of the polyester backing, and the fentanyl-containing gel matrix was completely gone. She required treatment with an intravenous naloxone drip at a rate of 0.8 mg (2 ampules)/h and leu admission for close observation. The patient's polysubstance abuse and extensive psychiatric history were later confirmed. Duragesic is a transdermal system providing continuous systemic delivery of fentanyl, a potent opioid analgesic, for 72 hours. Although it is well recognized that all narcotics have the potential to be abused, the relatively controlled, nonbolus release of fentanyl from this product is believed to reduce this potential by el iminating the euphoria or "high" associated with acute narcotic administration. The patient in this report was able to circumvent this safeguard, and essentially delivered the entire 5.0 mg fentanyl content of the Duragesic 50-J.!g unit directly to her gastrointestinal tract. Although the Warnings and Precautions sections of the Duragesic package insert 1 address the issues of overdose, abuse, and dependence, it contains no information regarding the potential for abuse by individuals using this novel route of administration. A MEDLINE search using the terms "Duragesic" or "fentanyl" paired with "abuse" or "overdose" retrieved no additional reports of abuse of this product using the oral route. An online search of AERS, the FDA Adverse Event Reporting System, retrieved a total of 6 additional reports of Duragesic abuse using a nonapproved route \5 oral and 1 intravenous). Of the 5 oral ingestions, 3 resulted in death and 2 in hospitalization. Two of the 3 deaths appeared to have been successful suicide attempts. One of the 5 reports indicated
that the patient was a known substance abuser, but data on the other 4 were inadequate to make such a determination. One patient had a psychiatric history with frequent inpatient treatments. We urge all practitioners to be aware of the potential for abuse of Duragesic patches. This problem is of particular importance to those practicing in an acute care setting, in which an extensive physician-patient relationship is unlikely to exist. There may be a desire to avoid prescribing narcotic-containing tablets for several days to narcotic-tolerant (or abusing) patients who present with acutely painful, self-limited conditions because of their possible misuse or abuse. On the surface, it would seem that a solution to this dilemma could be the application of a single Duragesic patch of suitable potency. The patient described in this case report would argue that this practice ought to be avoided. Mary Purucker, MD, PhD Department of Critical Care Medicine Suburban Hospital Bethesda, MD Center for Drug Evaluation and Research US Food and Drug Administration Rockville, MD William Swann, DO Department of Emergency Medicine Suburban Hospital Bethesda, MD
47/8/104531 doi:1o.1067/mem.2Doo.lo4531 The views expressed in this letter do not necessarily represent those of nor imply endorsement from the US Food and Drug Administration. 1. DURAGESIC, approved package insert. Titusvtlle, Nj: Janssen Pharmaceutica; 1999.
Disaster Medical Education for All Physicians and Physician Extenders To the Editor: The article by Pesik et all (article #99873) presents a sobering picture concerning the state of disaster medicine within the specialty of emergency medicine. Not only does
ANNALS OF EMERGENCY MEDICINE
353 MARCH 2000
Methanol Intoxication
Methanol Intoxication
Marco L. A. Sivilotti, MD, MSc
To the Editor: Potential for Duragesic Patch Abuse
Mary Purucker, MD, PhD William Swann, DO Disaster Medical Education for All Physicians and Physician Extenders
Paul Rega, MD Reply
Nicki Pesik, MD Mark Keim, MD Copyright © 2000 by the American College of Emergency Physicians. 0196-0644/2000/$12.00 + 0
Although the case reported by Wang et al 1 (article #99697) in their letter to the editor may well describe a moderately severe case of methanol poisoning, the purported source of methanol does not withstand close scrutiny. The authors base their report on the claim that the patient developed visual impairment after intravenous injection of 250 mL of a solution containing 95% ethanol and 100 ppm of methanol, or a total dose of 20 to 25 mg of methanol. This quantity of methanol, however, is trivial and certainly not toxic. In fact fruit juices contain up to 140 ppm of methanol, and products of natural fermentation may contain as much as 1.500 ppm of methanol. 2 A 12-oz can of diet soda containing 200 mg of aspartame is metabolized to 20 mg of methanol, accounting for an Internet-propagated urban legend. 3
Indeed, much higher doses (10 mg/kg intravenously with ethanol, and 80 mg/kg orally without ethanol) have been used without toxicity in human volunteer studies, including the one cited by the authors. 4 .5 With 100% bioavailability and very rapid absorption via the oral route. there is no evidence to support the authors' claim of significantly different pharmacokinetics after intravenous administration. nor is there evidence to suggest enhanced pharmacodynamic toxicity. Assuming their patient weighed approximately 50 kg. the exposure alleged by the authors would be expected to increase the serum methanol concentration by 0.07 mg/dL (0.02 mmol/L; normal methanol levels $;0.26 mg/dL due to endogenous and dietary sources 6 ). nearly 1.000 times less than concentrations for which hemodialysis and antidotal treatment are recommended. A further margin of safety is afforded by the impressive peak ethanol concentration of more than 500
Guidelines for Letters Annals welcomes correspondence. including observations. opinions. corrections. very brief reports, and comments on published articles. Letters to the editor will not be accepted if they exceed 500 words and 5 references. Two double-spaced copies must be submitted; a computer disk is required. Letters should not contain abbreviations. They must be signed and include a postscript granting permission to publish. Financial associations or other possible conflicts of interest should always be disclosed. Letters discussing an Annals article must be received within 6 weeks of the article's publication. Annals acknowledges receipt of letters with a postcard or e-mail message. and correspondents are notified by postcard when a decision is made. Published letters will be edited and may be shortened. Unpublished letters will not be returned. Authors of articles for which we receive comments will be given the opportunity to reply. The reply will not be shared with the author of the letter before publication. Neither Annals of Emergency Medicine nor the Publisher accepts responsibility for statements made by contributors or advertisers. Acceptance of an advertisment for placement in Annals in no way represents endorsement of a particular product or service by Annals of Emergency Medicine. the American College of Emergency Physicians. or the Publisher.
MARCH 2000
35:3
ANNALS OF EMERGENCY MEDICINE
313
CORRESPONDENCE mg/dL expected in their patient. accounting for the prolonged coma. Given that the funduscopic changes reported are characteristic for methanol poisoning, one must conclude that the patient experienced a second exposure to a more concentrated source of methanol, perhaps by ingesting at least several grams. Thus, the case report is most significant for being the first report of self-administration of antidotal ethanol via the intravenous route. Given the incomplete success, it also serves as evidence to support the admonition, "Don't try this at home!" Marco L.A. Sivilotti, MD, MSc Department of Emergency Medicine Brigham and Womens Hospital Harvard Medical School Boston, MA
47/8/104530 doi:1o. lo67/mem.2ooo. 104530 1. Wang]Y, Lin YF, Lin SoH. Methanol intoxication with retinal injury by intravenous injection [letter). Ann Emerg Med. 1999;34:297-298.
2. Francot P, Geoffroy P. Le methanol dans Ies jus de fruits,
Ies boissons, fermenttes, Ies alcools et spiriteux. Rev Ferment Ind Aliment. 1956;11 :279.
3. Stegink LD. Aspartame metabolism in humans: acute dosing studies. In: Stegink ill, Filer LJ, eds. Aspartame: PhYSiology and Biochemistry. New Yorh, NY: Marcel
Decker: 1984'509. 4. Haffner H-T, Besserer K, Graw M, et al Methanol elimi-
nation in non-alcoholics: inter- and intraindividual variation. Forsensic Sci Int. 1997;86:69-76. 5. Leaf G, Zat?,an Lj. A study of the conditions under which methanol may exert a toxic hazard in industry. Br J Ind Med. 1952;9:19-31.
6. Sedivec V, Mraz M, FlehJ. BiolOgical monitoring of per-
sons exposed to methanol vapours. Int Arch Occup Environ Health. 1981;48:257-71.
Potential for Duragesic Patch Abuse To the Editor: I
We wish to report a case of acute narcotic overdose induced by the intentional oral ingestion 9f a fentanyl (Duragesic) patch. The patient was a 24-year-old woman who presented to the emergency department of a community hospital complaining of severe pain related to an ongoing miscarriage. She also claimed to have chronic pain and muscle spasms caused by multiple sclerosis, for which she required frequent doses
31 4
of narcotic analgesics. The patient's history of narcotic dependence and substance abuse was unknown at that time, but suspected because of inconsistencies in her medical history and her demands for potent narcotic analgesics to treat her pain. She received intramuscular meperidine acutely, and a Duragesic patch (fentanyl transdermal system; Janssen Pharmaceutical at 50 J.!g/h was applied for sustained pain relief. The patient asked to use the lavatory, and shortly after her return was noted by ED staff to be cyanotic and apneic. She was quickly resuscitated, and an empty Duragesic patch was retrieved from her billfold. Bite marks were found at one end of the polyester backing, and the fentanyl-containing gel matrix was completely gone. She required treatment with an intravenous naloxone drip at a rate of 0.8 mg (2 ampules)/h and leu admission for close observation. The patient's polysubstance abuse and extensive psychiatric history were later confirmed. Duragesic is a transdermal system providing continuous systemic delivery of fentanyl, a potent opioid analgesic, for 72 hours. Although it is well recognized that all narcotics have the potential to be abused, the relatively controlled, nonbolus release of fentanyl from this product is believed to reduce this potential by el iminating the euphoria or "high" associated with acute narcotic administration. The patient in this report was able to circumvent this safeguard, and essentially delivered the entire 5.0 mg fentanyl content of the Duragesic 50-J.!g unit directly to her gastrointestinal tract. Although the Warnings and Precautions sections of the Duragesic package insert 1 address the issues of overdose, abuse, and dependence, it contains no information regarding the potential for abuse by individuals using this novel route of administration. A MEDLINE search using the terms "Duragesic" or "fentanyl" paired with "abuse" or "overdose" retrieved no additional reports of abuse of this product using the oral route. An online search of AERS, the FDA Adverse Event Reporting System, retrieved a total of 6 additional reports of Duragesic abuse using a nonapproved route \5 oral and 1 intravenous). Of the 5 oral ingestions, 3 resulted in death and 2 in hospitalization. Two of the 3 deaths appeared to have been successful suicide attempts. One of the 5 reports indicated
that the patient was a known substance abuser, but data on the other 4 were inadequate to make such a determination. One patient had a psychiatric history with frequent inpatient treatments. We urge all practitioners to be aware of the potential for abuse of Duragesic patches. This problem is of particular importance to those practicing in an acute care setting, in which an extensive physician-patient relationship is unlikely to exist. There may be a desire to avoid prescribing narcotic-containing tablets for several days to narcotic-tolerant (or abusing) patients who present with acutely painful, self-limited conditions because of their possible misuse or abuse. On the surface, it would seem that a solution to this dilemma could be the application of a single Duragesic patch of suitable potency. The patient described in this case report would argue that this practice ought to be avoided. Mary Purucker, MD, PhD Department of Critical Care Medicine Suburban Hospital Bethesda, MD Center for Drug Evaluation and Research US Food and Drug Administration Rockville, MD William Swann, DO Department of Emergency Medicine Suburban Hospital Bethesda, MD
47/8/104531 doi:1o.1067/mem.2Doo.lo4531 The views expressed in this letter do not necessarily represent those of nor imply endorsement from the US Food and Drug Administration. 1. DURAGESIC, approved package insert. Titusvtlle, Nj: Janssen Pharmaceutica; 1999.
Disaster Medical Education for All Physicians and Physician Extenders To the Editor: The article by Pesik et all (article #99873) presents a sobering picture concerning the state of disaster medicine within the specialty of emergency medicine. Not only does
ANNALS OF EMERGENCY MEDICINE
353 MARCH 2000