A Review of Ipecac Syrup Anthony S. Manoguerra, Pharm.D., DABAT, FAACT Director, San Diego Division California Poison Control System Associate Dean and

A Review of Ipecac A Review of Ipecac SyrupSyrup

Anthony S. Manoguerra, Pharm.D., DABAT, Anthony S. Manoguerra, Pharm.D., DABAT, FAACTFAACT

Director, San Diego DivisionDirector, San Diego DivisionCalifornia Poison Control SystemCalifornia Poison Control System

Associate Dean and Professor of Clinical Associate Dean and Professor of Clinical PharmacyPharmacy

University of California San Diego, School of University of California San Diego, School of Pharmacy and Pharmaceutical SciencesPharmacy and Pharmaceutical SciencesClinical Professor of Pharmacology and Clinical Professor of Pharmacology and

PediatricsPediatricsUniversity of California San Diego, School of University of California San Diego, School of

MedicineMedicine

Poison Center Guidelines Poison Center Guidelines Consensus Panel ProjectConsensus Panel Project

Joint project of:Joint project of: American Association of Poison Control American Association of Poison Control

CentersCenters American Academy of Clinical American Academy of Clinical

ToxicologyToxicology American College of Medical ToxicologyAmerican College of Medical Toxicology

Funded by a project grant from the Funded by a project grant from the Maternal and Child Health Bureau, Health Maternal and Child Health Bureau, Health Resources and Services Administration, Resources and Services Administration, Department of Health and Human Department of Health and Human Services.Services.

Poison Center Guidelines Poison Center Guidelines Consensus Panel Project Consensus Panel Project

MembershipMembershipGwen Christianson, RN, MSNGwen Christianson, RN, MSNIndiana Poison CenterIndiana Poison CenterIndianapolis, INIndianapolis, IN

Richard Dart, MD, PhDRichard Dart, MD, PhDRocky Mountain Poison Rocky Mountain Poison

CenterCenterDenver, CODenver, CO

Christopher Keyes, MD, MPHChristopher Keyes, MD, MPHNorth Texas Poison CenterNorth Texas Poison CenterDallas, TXDallas, TX

Michael Shannon, MDMichael Shannon, MDChildren’s Hospital of BostonChildren’s Hospital of BostonBoston, MABoston, MA

Michael McGuigan, MDMichael McGuigan, MDLong Island Regional Poison Long Island Regional Poison

CenterCenterMineola, NYMineola, NY

Kent Olson, MDKent Olson, MDCalifornia Poison Control California Poison Control

SystemSystemSan Francisco, CASan Francisco, CA

Paul Wax, MDPaul Wax, MDBanner Health SystemBanner Health SystemPhoenix, AZPhoenix, AZ

Anthony Manoguerra, Pharm.D.Anthony Manoguerra, Pharm.D.California Poison Control California Poison Control

SystemSystemSan Diego, CASan Diego, CA

Poison Center Guidelines Poison Center Guidelines Consensus Panel Project - Consensus Panel Project -

ChargeCharge Review literature evidenceReview literature evidence Develop a draft guidelineDevelop a draft guideline Circulate for secondary reviewCirculate for secondary review Incorporate review commentsIncorporate review comments Develop a final guideline Develop a final guideline

representing the consensus of the representing the consensus of the panel for approval by the boards of panel for approval by the boards of the sponsoring organizations.the sponsoring organizations.


Purpose of the project is to Purpose of the project is to produce guidelines to promote produce guidelines to promote consistency in patient management consistency in patient management between poison centers.between poison centers.

Based on the best interpretation of Based on the best interpretation of the available literature.the available literature.

Public policy decisions are to be Public policy decisions are to be left to the sponsoring left to the sponsoring organizations.organizations.


Completed guideline on “ Out-of-Completed guideline on “ Out-of-hospital Management of the Non-toxic hospital Management of the Non-toxic or Sub-toxic Exposure”or Sub-toxic Exposure”

In final revision of “Ipecac Syrup in In final revision of “Ipecac Syrup in the Out-of-hospital Management of the Out-of-hospital Management of Ingested Poisons”Ingested Poisons”

Currently working on guidelines for:Currently working on guidelines for: Acetaminophen ingestionsAcetaminophen ingestions Calcium channel blocker ingestionsCalcium channel blocker ingestions Beta-adrenergic blocker ingestionsBeta-adrenergic blocker ingestions


Ipecac guideline is not yet complete. Final Ipecac guideline is not yet complete. Final draft is currently being written for approval draft is currently being written for approval by the panel.by the panel.

My comments today are based on the review My comments today are based on the review of the literature, the initial drafts, panel of the literature, the initial drafts, panel discussions and my personal experience over discussions and my personal experience over the past 30 years.the past 30 years.

My statements do not represent My statements do not represent the official policy of any of the the official policy of any of the sponsoring organizations at this sponsoring organizations at this time.time.

Pediatric Exposures Reported to US Pediatric Exposures Reported to US Poison CentersPoison Centers

400000

600000

800000

1000000

1200000

1400000

1600000

86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01

Year

Num

ber o

f Cas

es

Use of Ipecac Syrup by US Poison Use of Ipecac Syrup by US Poison CentersCenters

0

20000

40000

60000

80000

100000

120000

140000

160000

86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01

Year

Num

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f Cas

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What is the role of What is the role of gastrointestinal gastrointestinal

decontamination in poison decontamination in poison management?management?

One of the most controversial One of the most controversial topics in clinical toxicology over topics in clinical toxicology over the past 10-15 years.the past 10-15 years.

Not complete agreement but a Not complete agreement but a general consensus has been general consensus has been developing in recent years.developing in recent years.


decontamination in poison decontamination in poison management?management? In general:In general:

Emesis and gastric lavage are rarely Emesis and gastric lavage are rarely being used.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 These trends are supported by the bulk of literature evidence that is available, literature evidence that is available, although highly rated evidence is lacking.although highly rated evidence is lacking.


decontamination in poison decontamination in poison management?management?

Numerous studies have demonstrated that Numerous studies have demonstrated that activated charcoal is superior to ipecac-activated charcoal is superior to ipecac-induced emesis or gastric lavage in induced emesis or gastric lavage in reducing absorption of drugs in reducing absorption of drugs in experimental situations.experimental situations.

However, there is no convincing evidence However, there is no convincing evidence that emesis, gastric lavage or activated that emesis, gastric lavage or activated charcoal positively affect patient outcome.charcoal positively affect patient outcome.

Literature on the Effectiveness Literature on the Effectiveness of of

Ipecac SyrupIpecac Syrup All of the literature has low All of the literature has low

evidence ratings as the topic evidence ratings as the topic does not lend itself to design of does not lend itself to design of studies classically thought to be studies classically thought to be of the highest level of evidence.of the highest level of evidence.

Most studies are:Most studies are: Animal studiesAnimal studies Retrospective human case seriesRetrospective human case series Volunteer studies using low doses of Volunteer studies using low doses of

marker materialsmarker materials

Summary of Effectiveness ofSummary of Effectiveness of Ipecac Syrup Ipecac Syrup

Ipecac makes approximately 85% of people Ipecac makes approximately 85% of people vomit after one dose and 95% after two vomit after one dose and 95% after two doses.doses.

Onset of emesis is typically within 20-30 Onset of emesis is typically within 20-30 minutes.minutes.

The amount of material removed by ipecac The amount of material removed by ipecac has huge inter-subject variability.has huge inter-subject variability. If given within 5 minutes of ingestion, removes If given within 5 minutes of ingestion, removes

between 0% and 80% of ingested substance. between 0% and 80% of ingested substance. Mean is about 25-30%.Mean is about 25-30%.

Rapid reduction in removal with time. No better Rapid reduction in removal with time. No better than control if given 30 minutes after ingestion.than control if given 30 minutes after ingestion.

Summary of Effectiveness ofSummary of Effectiveness of Ipecac Syrup Ipecac Syrup

There are 7 papers that examined the There are 7 papers that examined the impact of emesis, gastric lavage and/or impact of emesis, gastric lavage and/or activated charcoal on the outcome of activated charcoal on the outcome of poisoned patients.poisoned patients.

Most of the authors concluded that there Most of the authors concluded that there was no difference between the treatments was no difference between the treatments or that activated charcoal was more or that activated charcoal was more efficacious. efficacious.

Most had significant methodological flaws Most had significant methodological flaws that affect interpretation of the results.that affect interpretation of the results.

There is no conclusive evidence that There is no conclusive evidence that ipecac or any of the other ipecac or any of the other decontamination methods positively decontamination methods positively affect patient outcome.affect patient outcome.

The glass is 1/4 full…The glass is 1/4 full…

““I can get out 25-30% of an I can get out 25-30% of an ingested substance with the use ingested substance with the use of ipecac syrup!!”of ipecac syrup!!”

The glass is 3/4 empty…The glass is 3/4 empty…

““I can only get out 25-30% of an I can only get out 25-30% of an ingested substance with ipecac ingested substance with ipecac syrup.”syrup.”

Risks of Ipecac Syrup UseRisks of Ipecac Syrup Use

Considering the thousands of Considering the thousands of doses of ipecac syrup that have doses of ipecac syrup that have been administered over the past been administered over the past 30-40 years, the occurrence of 30-40 years, the occurrence of adverse events from therapeutic adverse events from therapeutic use is low.use is low.


Adverse effects reported from Adverse effects reported from therapeutic use include:therapeutic use include: Common effects:Common effects:

Sedation/Drowsiness: 12-25%Sedation/Drowsiness: 12-25%Diarrhea: 17-30%Diarrhea: 17-30%Prolonged and repeated Prolonged and repeated emesis beyond one hour: 10-emesis beyond one hour: 10-18%18%


Uncommon Events – Case ReportsUncommon Events – Case Reports Aspiration pneumonitisAspiration pneumonitis Mallory-Weiss tears and Mallory-Weiss tears and

perforationsperforations PneumomediastinumPneumomediastinum Gastric ruptureGastric rupture Diaphragmatic ruptureDiaphragmatic rupture Intracranial hemorrhageIntracranial hemorrhage Allergic reactions – rash, urticariaAllergic reactions – rash, urticaria

Acute Dose-related ToxicityAcute Dose-related Toxicity

Acute dose-related toxicity has Acute dose-related toxicity has not been seen with ipecac syrup.not been seen with ipecac syrup.

Acute toxicity has only been Acute toxicity has only been reported following the ingestion reported following the ingestion of the fluid extract of ipecac of the fluid extract of ipecac which has approximately 14 which has approximately 14 times the alkaloidal content of times the alkaloidal content of the syrup. (Production ceased in the syrup. (Production ceased in 1970).1970).

Chronic Dose-related ToxicityChronic Dose-related Toxicity

Emetine has well documented Emetine has well documented chronic, dose-related toxic effects on chronic, dose-related toxic effects on skeletal and cardiac muscle leading skeletal and cardiac muscle leading to myopathy.to myopathy.

Pattern of myopathy seen with Pattern of myopathy seen with chronic ipecac syrup ingestion is chronic ipecac syrup ingestion is similar.similar.

Contribution of other alkaloids, such Contribution of other alkaloids, such as cephaline, psychotrine, as cephaline, psychotrine, emetamine, and others is unknown.emetamine, and others is unknown.

Absorption of Alkaloids from Absorption of Alkaloids from Ipecac SyrupIpecac Syrup

One study examined the absorption of One study examined the absorption of emetine and cephaline in 10 adult emetine and cephaline in 10 adult patients given 30 mL ipecac syrup.patients given 30 mL ipecac syrup.

Recovery of alkaloids in emesis averaged Recovery of alkaloids in emesis averaged 45 +/- 33%.45 +/- 33%.

Alkaloid levels were measured in the Alkaloid levels were measured in the plasma of all subjects in varying amounts.plasma of all subjects in varying amounts.

Conclusion – all patients given ipecac will Conclusion – all patients given ipecac will absorb alkaloids. Extent is highly absorb alkaloids. Extent is highly variable.variable.

Ann Emerg Med 1984;13:1100-1102Ann Emerg Med 1984;13:1100-1102

ExcretionExcretion

Emetine is excreted by the Emetine is excreted by the kidney.kidney.

Unchanged emetine can be Unchanged emetine can be detected in the urine 40-60 days detected in the urine 40-60 days following the administration of a following the administration of a single dose.single dose.

Ipecac Syrup Use in Ipecac Syrup Use in Munchausen Syndrome by ProxyMunchausen Syndrome by Proxy

9 published papers describing 13 9 published papers describing 13 cases where ipecac syrup was used cases where ipecac syrup was used in this fashion by caregivers.in this fashion by caregivers.

6 patients did not develop myopathy 6 patients did not develop myopathy and had resolution of symptoms.and had resolution of symptoms.

2 developed skeletal muscle 2 developed skeletal muscle myopathy with recovery.myopathy with recovery.

5 developed skeletal and cardiac 5 developed skeletal and cardiac muscle myopathy. 3 recovered and muscle myopathy. 3 recovered and 2 died.2 died.

Ipecac Syrup AbuseIpecac Syrup Abuse 17 papers in the US literature 17 papers in the US literature

reporting 20 cases of patients with reporting 20 cases of patients with eating disorders who developed cardiac eating disorders who developed cardiac and skeletal muscle myopathy and skeletal muscle myopathy following use of ipecac syrup multiple following use of ipecac syrup multiple times daily for months.times daily for months.

4 deaths4 deaths Other deaths have been reported in the Other deaths have been reported in the

news media. (e.g. Karen Carpenter news media. (e.g. Karen Carpenter death is not in the medical literature).death is not in the medical literature).

Ipecac Syrup AbuseIpecac Syrup Abuse Two papers attempted to quantify the Two papers attempted to quantify the

extent of ipecac abuse in patients with extent of ipecac abuse in patients with eating disorders.eating disorders.

851 patients in an eating disorders clinic851 patients in an eating disorders clinic 7.8% had used ipecac (4.7% intermittently, 7.8% had used ipecac (4.7% intermittently,

3.1% chronically)3.1% chronically) 622 patients in an eating disorders clinic622 patients in an eating disorders clinic

0.09% of women 9-19 years of age used ipecac0.09% of women 9-19 years of age used ipecac 3.8% of women 10-46 years of age used ipecac3.8% of women 10-46 years of age used ipecac

Appropriateness of UseAppropriateness of Use

Only one paper looked at the Only one paper looked at the appropriateness of use of ipecac syrup appropriateness of use of ipecac syrup by physicians. Author concluded that by physicians. Author concluded that use was inappropriate in 20% of uses use was inappropriate in 20% of uses over a 1 year period. Ipecac had been over a 1 year period. Ipecac had been administered to patients in situations administered to patients in situations where it was contraindicated.where it was contraindicated.

There is no systematic examination of There is no systematic examination of the appropriateness of use of ipecac the appropriateness of use of ipecac syrup by the general public.syrup by the general public. Case reports of use of ipecac syrup in Case reports of use of ipecac syrup in

patients with corrosive ingestions.patients with corrosive ingestions.

When is Ipecac Syrup When is Ipecac Syrup Contraindicated?Contraindicated?

When the patient is comatose, When the patient is comatose, lethargic, having convulsions, lethargic, having convulsions, unable to protect his/her airway unable to protect his/her airway and aspiration of stomach contents and aspiration of stomach contents is possible.is possible.

When the substance ingested is:When the substance ingested is: Corrosive (acid or alkali).Corrosive (acid or alkali). Petroleum distillate of low Petroleum distillate of low

viscosity and high aspiration risk.viscosity and high aspiration risk.

When is Ipecac Syrup When is Ipecac Syrup Contraindicated?Contraindicated?

When the substance is likely to When the substance is likely to cause loss of consciousness, coma or cause loss of consciousness, coma or convulsions while vomiting is convulsions while vomiting is occurring. occurring.

When emesis may interfere with When emesis may interfere with administration of oral antidotal administration of oral antidotal therapy. therapy. Example: Example:

The oral administration of The oral administration of n-acetylcysteine in n-acetylcysteine in acetaminophen ingestions.acetaminophen ingestions.

When Might Ipecac Syrup Be When Might Ipecac Syrup Be Used?Used?

When it is not contraindicated.When it is not contraindicated. When it can be administered soon after When it can be administered soon after

ingestion and no later than 30 minutes ingestion and no later than 30 minutes of ingestion.of ingestion.

When removal of 25-30% of the When removal of 25-30% of the ingested dose may have a significant ingested dose may have a significant influence on patient outcome.influence on patient outcome.

When there will be a long delay in the When there will be a long delay in the arrival of a patient at a health care arrival of a patient at a health care facility (e.g. > 1 hour).facility (e.g. > 1 hour).

What Have We What Have We DoneDone in San in San Diego?Diego?

From 1977 through 1990, we had From 1977 through 1990, we had protocols that specified when ipecac protocols that specified when ipecac should be used.should be used.

For example: Acetaminophen:For example: Acetaminophen: Less than 150 mg/kg: observe at homeLess than 150 mg/kg: observe at home 150-200 mg/kg: ipecac at home and 150-200 mg/kg: ipecac at home and

observationobservation >200 mg/kg: to ED>200 mg/kg: to ED

In 1990, we eliminated all use of In 1990, we eliminated all use of ipecac and observed at home the ipecac and observed at home the children in that category.children in that category.

What Have We Done in San What Have We Done in San Diego?Diego?

We observed no change in the We observed no change in the number of children that required number of children that required referral to a healthcare facility.referral to a healthcare facility.

We were taking children who We were taking children who were not likely to develop were not likely to develop symptoms from their ingestion symptoms from their ingestion and we were making them and we were making them symptomatic with ipecac.symptomatic with ipecac.

AlternativesAlternatives Activated charcoal – difficult to administer in Activated charcoal – difficult to administer in

the home setting. Proof of benefit also lacking.the home setting. Proof of benefit also lacking. Use no GI decontamination procedures.Use no GI decontamination procedures. Restrict ipecac syrup to prescriptionRestrict ipecac syrup to prescription

Decrease availability to the public for abuse Decrease availability to the public for abuse or misuse.or misuse.

Reduce availability for use within 30 minutes Reduce availability for use within 30 minutes of ingestion.of ingestion.

Allow physicians to prescribe it for specific Allow physicians to prescribe it for specific patient situations.patient situations.

Allow EMS to make it available in rural Allow EMS to make it available in rural areas.areas.

The Ultimate QuestionsThe Ultimate Questions

Does the benefit that accrues to poisoned Does the benefit that accrues to poisoned patients through the use of ipecac patients through the use of ipecac syrup outweigh the potential adverse syrup outweigh the potential adverse events that may infrequently occur?events that may infrequently occur?

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

Documents

A Review of Ipecac Syrup Anthony S. Manoguerra, Pharm.D., DABAT, FAACT Director, San Diego Division California Poison Control System Associate Dean and