Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning
Introduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion...
| Główni autorzy: | , , , , , , |
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| Format: | Artykuł |
| Język: | English |
| Wydane: |
eScholarship Publishing, University of California
2023-09-01
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| Seria: | Western Journal of Emergency Medicine |
| Dostęp online: | https://escholarship.org/uc/item/15z8n18j |
| _version_ | 1827386531964256256 |
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| author | Jon B. Cole Carrie L. Oakland Samantha C. Lee Kelly A. Considine Maria I. Rudis Alison L. Swanson Travis D. Olives |
| author_facet | Jon B. Cole Carrie L. Oakland Samantha C. Lee Kelly A. Considine Maria I. Rudis Alison L. Swanson Travis D. Olives |
| author_sort | Jon B. Cole |
| collection | DOAJ |
| description | Introduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC. Methods: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration. Results: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC. Conclusion: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy. |
| first_indexed | 2024-03-08T15:46:42Z |
| format | Article |
| id | doaj.art-569efb0e67744b6e977a8d29f36fbcd6 |
| institution | Directory Open Access Journal |
| issn | 1936-900X 1936-9018 |
| language | English |
| last_indexed | 2024-03-08T15:46:42Z |
| publishDate | 2023-09-01 |
| publisher | eScholarship Publishing, University of California |
| record_format | Article |
| series | Western Journal of Emergency Medicine |
| spelling | doaj.art-569efb0e67744b6e977a8d29f36fbcd62024-01-09T10:34:55ZengeScholarship Publishing, University of CaliforniaWestern Journal of Emergency Medicine1936-900X1936-90182023-09-012461131114510.5811/westjem.5909959099Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen PoisoningJon B. Cole0Carrie L. Oakland1Samantha C. Lee2Kelly A. Considine3Maria I. Rudis4Alison L. Swanson5Travis D. Olives6Hennepin Healthcare, Department of Emergency Medicine, Minneapolis, MinnesotaMinnesota Poison Control System, Minneapolis, MinnesotaMinnesota Poison Control System, Minneapolis, MinnesotaHennepin Healthcare, Medical Intensive Care Unit, Department of Pharmacy, Minneapolis, MinnesotaMayo Clinic, Department of Pharmacy, Rochester, MinnesotaChildren’s Hospitals and Clinics of Minnesota, Department of Pharmacy, Minneapolis, MinnesotaHennepin Healthcare, Department of Emergency Medicine, Minneapolis, MinnesotaIntroduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC. Methods: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration. Results: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC. Conclusion: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.https://escholarship.org/uc/item/15z8n18j |
| spellingShingle | Jon B. Cole Carrie L. Oakland Samantha C. Lee Kelly A. Considine Maria I. Rudis Alison L. Swanson Travis D. Olives Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning Western Journal of Emergency Medicine |
| title | Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning |
| title_full | Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning |
| title_fullStr | Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning |
| title_full_unstemmed | Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning |
| title_short | Is Two Better Than Three? A Systematic Review of Two-bag Intravenous N-acetylcysteine Regimens for Acetaminophen Poisoning |
| title_sort | is two better than three a systematic review of two bag intravenous n acetylcysteine regimens for acetaminophen poisoning |
| url | https://escholarship.org/uc/item/15z8n18j |
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