A Review of Ipecac Syrup Anthony S. Manoguerra, Pharm.D., DABAT, FAACT Director, San Diego Division California Poison Control System Associate Dean and Professor of Clinical Pharmacy University of California San Diego, School of Pharmacy and Pharmaceutical Sciences Clinical Professor of Pharmacology and Pediatrics University of California San Diego, School of Medicine

Poison Center Guidelines Consensus Panel Project Joint project of: Joint project of: American Association of Poison Control Centers American Association of Poison Control Centers American Academy of Clinical Toxicology American Academy of Clinical Toxicology American College of Medical Toxicology American College of Medical Toxicology Funded by a project grant from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services. Funded by a project grant from the Maternal and Child Health Bureau, Health Resources and Services Administration, Department of Health and Human Services.

Poison Center Guidelines Consensus Panel Project Membership Gwen Christianson, RN, MSN Indiana Poison Center Indianapolis, IN Richard Dart, MD, PhD Rocky Mountain Poison Center Denver, CO Christopher Keyes, MD, MPH North Texas Poison Center Dallas, TX Michael Shannon, MD Children’s Hospital of Boston Boston, MA Michael McGuigan, MD Long Island Regional Poison Center Mineola, NY Kent Olson, MD California Poison Control System San Francisco, CA Paul Wax, MD Banner Health System Phoenix, AZ Anthony Manoguerra, Pharm.D. California Poison Control System San Diego, CA

Poison Center Guidelines Consensus Panel Project - Charge Review literature evidence Review literature evidence Develop a draft guideline Develop a draft guideline Circulate for secondary review Circulate for secondary review Incorporate review comments Incorporate review comments Develop a final guideline representing the consensus of the panel for approval by the boards of the sponsoring organizations. Develop a final guideline representing the consensus of the panel for approval by the boards of the sponsoring organizations.

Poison Center Guidelines Consensus Panel Project Purpose of the project is to produce guidelines to promote consistency in patient management between poison centers. Purpose of the project is to produce guidelines to promote consistency in patient management between poison centers. Based on the best interpretation of the available literature. Based on the best interpretation of the available literature. Public policy decisions are to be left to the sponsoring organizations. Public policy decisions are to be left to the sponsoring organizations.

Poison Center Guidelines Consensus Panel Project Completed guideline on “ Out-of-hospital Management of the Non-toxic or Sub-toxic Exposure” Completed guideline on “ Out-of-hospital Management of the Non-toxic or Sub-toxic Exposure” In final revision of “Ipecac Syrup in the Out-of- hospital Management of Ingested Poisons” In final revision of “Ipecac Syrup in the Out-of- hospital Management of Ingested Poisons” Currently working on guidelines for: Currently working on guidelines for: Acetaminophen ingestions Acetaminophen ingestions Calcium channel blocker ingestions Calcium channel blocker ingestions Beta-adrenergic blocker ingestions Beta-adrenergic blocker ingestions

Poison Center Guidelines Consensus Panel Project Ipecac guideline is not yet complete. Final draft is currently being written for approval by the panel. Ipecac guideline is not yet complete. Final draft is currently being written for approval by the panel. My comments today are based on the review of the literature, the initial drafts, panel discussions and my personal experience over the past 30 years. My comments today are based on the review of the literature, the initial drafts, panel discussions and my personal experience over the past 30 years. My statements do not represent the official policy of any of the sponsoring organizations at this time. My statements do not represent the official policy of any of the sponsoring organizations at this time.

Pediatric Exposures Reported to US Poison Centers

Use of Ipecac Syrup by US Poison Centers

What is the role of gastrointestinal decontamination in poison management? One of the most controversial topics in clinical toxicology over the past years. One of the most controversial topics in clinical toxicology over the past years. Not complete agreement but a general consensus has been developing in recent years. Not complete agreement but a general consensus has been developing in recent years.

What is the role of gastrointestinal decontamination in poison management? In general: In general: Emesis and gastric lavage are rarely being used. Emesis and gastric lavage are rarely being used. More activated charcoal is being used. More activated charcoal is being used. Use of cathartics has been abandoned. Use of cathartics has been abandoned. These trends are supported by the bulk of literature evidence that is available, although highly rated evidence is lacking. These trends are supported by the bulk of literature evidence that is available, although highly rated evidence is lacking.

What is the role of gastrointestinal decontamination in poison management? Numerous studies have demonstrated that activated charcoal is superior to ipecac-induced emesis or gastric lavage in reducing absorption of drugs in experimental situations. Numerous studies have demonstrated that activated charcoal is superior to ipecac-induced emesis or gastric lavage in reducing absorption of drugs in experimental situations. However, there is no convincing evidence that emesis, gastric lavage or activated charcoal positively affect patient outcome. However, there is no convincing evidence that emesis, gastric lavage or activated charcoal positively affect patient outcome.

Literature on the Effectiveness of Ipecac Syrup All of the literature has low evidence ratings as the topic does not lend itself to design of studies classically thought to be of the highest level of evidence. All of the literature has low evidence ratings as the topic does not lend itself to design of studies classically thought to be of the highest level of evidence. Most studies are: Most studies are: Animal studies Animal studies Retrospective human case series Retrospective human case series Volunteer studies using low doses of marker materials Volunteer studies using low doses of marker materials

Summary of Effectiveness of Ipecac Syrup Ipecac makes approximately 85% of people vomit after one dose and 95% after two doses. Ipecac makes approximately 85% of people vomit after one dose and 95% after two doses. Onset of emesis is typically within minutes. Onset of emesis is typically within minutes. The amount of material removed by ipecac has huge inter-subject variability. The amount of material removed by ipecac has huge inter-subject variability. If given within 5 minutes of ingestion, removes between 0% and 80% of ingested substance. Mean is about %. If given within 5 minutes of ingestion, removes between 0% and 80% of ingested substance. Mean is about %. Rapid reduction in removal with time. No better than control if given 30 minutes after ingestion. Rapid reduction in removal with time. No better than control if given 30 minutes after ingestion.

Summary of Effectiveness of Ipecac Syrup There are 7 papers that examined the impact of emesis, gastric lavage and/or activated charcoal on the outcome of poisoned patients. There are 7 papers that examined the impact of emesis, gastric lavage and/or activated charcoal on the outcome of poisoned patients. Most of the authors concluded that there was no difference between the treatments or that activated charcoal was more efficacious. Most of the authors concluded that there was no difference between the treatments or that activated charcoal was more efficacious. Most had significant methodological flaws that affect interpretation of the results. Most had significant methodological flaws that affect interpretation of the results. There is no conclusive evidence that ipecac or any of the other decontamination methods positively affect patient outcome. There is no conclusive evidence that ipecac or any of the other decontamination methods positively affect patient outcome.

The glass is 1/4 full… “I can get out 25-30% of an ingested substance with the use of ipecac syrup!!” “I can get out 25-30% of an ingested substance with the use of ipecac syrup!!”

The glass is 3/4 empty… “I can only get out 25-30% of an ingested substance with ipecac syrup.” “I can only get out 25-30% of an ingested substance with ipecac syrup.”

Risks of Ipecac Syrup Use Considering the thousands of doses of ipecac syrup that have been administered over the past years, the occurrence of adverse events from therapeutic use is low. Considering the thousands of doses of ipecac syrup that have been administered over the past years, the occurrence of adverse events from therapeutic use is low.

Risks of Ipecac Syrup Use Adverse effects reported from therapeutic use include: Adverse effects reported from therapeutic use include: Common effects: Common effects: Sedation/Drowsiness: 12-25% Sedation/Drowsiness: 12-25% Diarrhea: 17-30% Diarrhea: 17-30% Prolonged and repeated emesis beyond one hour: 10-18% Prolonged and repeated emesis beyond one hour: 10-18%

Risks of Ipecac Syrup Use Uncommon Events – Case Reports Uncommon Events – Case Reports Aspiration pneumonitis Aspiration pneumonitis Mallory-Weiss tears and perforations Mallory-Weiss tears and perforations Pneumomediastinum Pneumomediastinum Gastric rupture Gastric rupture Diaphragmatic rupture Diaphragmatic rupture Intracranial hemorrhage Intracranial hemorrhage Allergic reactions – rash, urticaria Allergic reactions – rash, urticaria

Acute Dose-related Toxicity Acute dose-related toxicity has not been seen with ipecac syrup. Acute dose-related toxicity has not been seen with ipecac syrup. Acute toxicity has only been reported following the ingestion of the fluid extract of ipecac which has approximately 14 times the alkaloidal content of the syrup. (Production ceased in 1970). Acute toxicity has only been reported following the ingestion of the fluid extract of ipecac which has approximately 14 times the alkaloidal content of the syrup. (Production ceased in 1970).

Chronic Dose-related Toxicity Emetine has well documented chronic, dose-related toxic effects on skeletal and cardiac muscle leading to myopathy. Emetine has well documented chronic, dose-related toxic effects on skeletal and cardiac muscle leading to myopathy. Pattern of myopathy seen with chronic ipecac syrup ingestion is similar. Pattern of myopathy seen with chronic ipecac syrup ingestion is similar. Contribution of other alkaloids, such as cephaline, psychotrine, emetamine, and others is unknown. Contribution of other alkaloids, such as cephaline, psychotrine, emetamine, and others is unknown.

Absorption of Alkaloids from Ipecac Syrup One study examined the absorption of emetine and cephaline in 10 adult patients given 30 mL ipecac syrup. One study examined the absorption of emetine and cephaline in 10 adult patients given 30 mL ipecac syrup. Recovery of alkaloids in emesis averaged 45 +/- 33%. Recovery of alkaloids in emesis averaged 45 +/- 33%. Alkaloid levels were measured in the plasma of all subjects in varying amounts. Alkaloid levels were measured in the plasma of all subjects in varying amounts. Conclusion – all patients given ipecac will absorb alkaloids. Extent is highly variable. Conclusion – all patients given ipecac will absorb alkaloids. Extent is highly variable. Ann Emerg Med 1984;13:

Excretion Emetine is excreted by the kidney. Emetine is excreted by the kidney. Unchanged emetine can be detected in the urine days following the administration of a single dose. Unchanged emetine can be detected in the urine days following the administration of a single dose.

Ipecac Syrup Use in Munchausen Syndrome by Proxy 9 published papers describing 13 cases where ipecac syrup was used in this fashion by caregivers. 9 published papers describing 13 cases where ipecac syrup was used in this fashion by caregivers. 6 patients did not develop myopathy and had resolution of symptoms. 6 patients did not develop myopathy and had resolution of symptoms. 2 developed skeletal muscle myopathy with recovery. 2 developed skeletal muscle myopathy with recovery. 5 developed skeletal and cardiac muscle myopathy. 3 recovered and 2 died. 5 developed skeletal and cardiac muscle myopathy. 3 recovered and 2 died.

Ipecac Syrup Abuse 17 papers in the US literature reporting 20 cases of patients with eating disorders who developed cardiac and skeletal muscle myopathy following use of ipecac syrup multiple times daily for months. 17 papers in the US literature reporting 20 cases of patients with eating disorders who developed cardiac and skeletal muscle myopathy following use of ipecac syrup multiple times daily for months. 4 deaths 4 deaths Other deaths have been reported in the news media. (e.g. Karen Carpenter death is not in the medical literature). Other deaths have been reported in the news media. (e.g. Karen Carpenter death is not in the medical literature).

Ipecac Syrup Abuse Two papers attempted to quantify the extent of ipecac abuse in patients with eating disorders. Two papers attempted to quantify the extent of ipecac abuse in patients with eating disorders. 851 patients in an eating disorders clinic 851 patients in an eating disorders clinic 7.8% had used ipecac (4.7% intermittently, 3.1% chronically) 7.8% had used ipecac (4.7% intermittently, 3.1% chronically) 622 patients in an eating disorders clinic 622 patients in an eating disorders clinic 0.09% of women 9-19 years of age used ipecac 0.09% of women 9-19 years of age used ipecac 3.8% of women years of age used ipecac 3.8% of women years of age used ipecac

Appropriateness of Use Only one paper looked at the appropriateness of use of ipecac syrup by physicians. Author concluded that use was inappropriate in 20% of uses over a 1 year period. Ipecac had been administered to patients in situations where it was contraindicated. Only one paper looked at the appropriateness of use of ipecac syrup by physicians. Author concluded that use was inappropriate in 20% of uses over a 1 year period. Ipecac had been administered to patients in situations where it was contraindicated. There is no systematic examination of the appropriateness of use of ipecac syrup by the general public. There is no systematic examination of the appropriateness of use of ipecac syrup by the general public. Case reports of use of ipecac syrup in patients with corrosive ingestions. Case reports of use of ipecac syrup in patients with corrosive ingestions.

When is Ipecac Syrup Contraindicated? When the patient is comatose, lethargic, having convulsions, unable to protect his/her airway and aspiration of stomach contents is possible. When the patient is comatose, lethargic, having convulsions, unable to protect his/her airway and aspiration of stomach contents is possible. When the substance ingested is: When the substance ingested is: Corrosive (acid or alkali). Corrosive (acid or alkali). Petroleum distillate of low viscosity and high aspiration risk. Petroleum distillate of low viscosity and high aspiration risk.

When is Ipecac Syrup Contraindicated? When the substance is likely to cause loss of consciousness, coma or convulsions while vomiting is occurring. When the substance is likely to cause loss of consciousness, coma or convulsions while vomiting is occurring. When emesis may interfere with administration of oral antidotal therapy. When emesis may interfere with administration of oral antidotal therapy.Example: The oral administration of The oral administration of n-acetylcysteine in acetaminophen ingestions.

When Might Ipecac Syrup Be Used? When it is not contraindicated. When it is not contraindicated. When it can be administered soon after ingestion and no later than 30 minutes of ingestion. When it can be administered soon after ingestion and no later than 30 minutes of ingestion. When removal of 25-30% of the ingested dose may have a significant influence on patient outcome. When removal of 25-30% of the ingested dose may have a significant influence on patient outcome. When there will be a long delay in the arrival of a patient at a health care facility (e.g. > 1 hour). When there will be a long delay in the arrival of a patient at a health care facility (e.g. > 1 hour).

What Have We Done in San Diego? From 1977 through 1990, we had protocols that specified when ipecac should be used. From 1977 through 1990, we had protocols that specified when ipecac should be used. For example: Acetaminophen: For example: Acetaminophen: Less than 150 mg/kg: observe at home Less than 150 mg/kg: observe at home mg/kg: ipecac at home and observation mg/kg: ipecac at home and observation >200 mg/kg: to ED >200 mg/kg: to ED In 1990, we eliminated all use of ipecac and observed at home the children in that category. In 1990, we eliminated all use of ipecac and observed at home the children in that category.

What Have We Done in San Diego? We observed no change in the number of children that required referral to a healthcare facility. We observed no change in the number of children that required referral to a healthcare facility. We were taking children who were not likely to develop symptoms from their ingestion and we were making them symptomatic with ipecac. We were taking children who were not likely to develop symptoms from their ingestion and we were making them symptomatic with ipecac.

Alternatives Activated charcoal – difficult to administer in the home setting. Proof of benefit also lacking. Activated charcoal – difficult to administer in the home setting. Proof of benefit also lacking. Use no GI decontamination procedures. Use no GI decontamination procedures. Restrict ipecac syrup to prescription Restrict ipecac syrup to prescription Decrease availability to the public for abuse or misuse. Decrease availability to the public for abuse or misuse. Reduce availability for use within 30 minutes of ingestion. Reduce availability for use within 30 minutes of ingestion. Allow physicians to prescribe it for specific patient situations. Allow physicians to prescribe it for specific patient situations. Allow EMS to make it available in rural areas. Allow EMS to make it available in rural areas.

The Ultimate Questions Does the benefit that accrues to poisoned patients through the use of ipecac syrup outweigh the potential adverse events that may infrequently occur? Does the benefit that accrues to poisoned patients from the OTC availability of ipecac syrup outweigh the potential adverse events that result from the improper use of the drug and abuse of the drug by patients with eating disorders?