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:
 American Association of Poison Control
Centers
 American Academy of Clinical 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.
 Poison Center Guidelines Consensus
Panel Project Membership
Gwen Christianson, RN, MSN Michael McGuigan, MD
Indiana Poison Center Long Island Regional Poison Center
Indianapolis, IN Mineola, NY

Richard Dart, MD, PhD Kent Olson, MD

Rocky Mountain Poison Center California Poison Control System
Denver, CO San Francisco, CA

Christopher Keyes, MD, MPH Paul Wax, MD

North Texas Poison Center Banner Health System
Dallas, TX Phoenix, AZ

Michael Shannon, MD Anthony Manoguerra, Pharm.D.

Children’s Hospital of Boston California Poison Control System
Boston, MA San Diego, CA
 Poison Center Guidelines Consensus
Panel Project - Charge
 Review literature evidence
 Develop a draft guideline
 Circulate for secondary review
 Incorporate review comments
 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.
 Based on the best interpretation of the
available literature.
 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”
 In final revision of “Ipecac Syrup in the Out-of-
hospital Management of Ingested Poisons”
 Currently working on guidelines for:
 Acetaminophen ingestions
 Calcium channel 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.
 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.
Pediatric Exposures Reported to US Poison Centers

1600000

1400000
Number of Cases

1200000

1000000

800000

600000

400000
86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01
Year
 Use of Ipecac Syrup by US Poison Centers

160000
140000
120000
Number of Cases

100000
80000
60000
40000
20000
0
86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01
Year
 What is the role of gastrointestinal
decontamination in poison management?

 One of the most controversial topics in

clinical toxicology over the past 10-15 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:
 Emesis and gastric lavage are rarely being used.

 More activated charcoal is being used.

 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.
 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.
 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.
 Most studies are:
 Animal studies
 Retrospective human case series
 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.
 Onset of emesis is typically within 20-30 minutes.
 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 25-
30%.
 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.
 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.
 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!!”
 The glass is 3/4 empty…

 “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 30-40 years, the occurrence of
adverse events from therapeutic use is low.
 Risks of Ipecac Syrup Use

 Adverse effects reported from therapeutic

use include:
 Common effects:

 Sedation/Drowsiness: 12-25%

 Diarrhea: 17-30%

 Prolonged and repeated emesis beyond

one hour: 10-18%
 Risks of Ipecac Syrup Use

 Uncommon Events – Case Reports

 Aspiration pneumonitis
 Mallory-Weiss tears and perforations
 Pneumomediastinum
 Gastric rupture
 Diaphragmatic rupture
 Intracranial hemorrhage
 Allergic reactions – rash, urticaria
 Acute Dose-related Toxicity

 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).
 Chronic Dose-related Toxicity

 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.
 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.
 Recovery of alkaloids in emesis averaged 45 +/-
33%.
 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.
Ann Emerg Med 1984;13:1100-1102
 Excretion

 Emetine is excreted by the kidney.

 Unchanged emetine can be detected in the
urine 40-60 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.
 6 patients did not develop myopathy and had
resolution of symptoms.
 2 developed skeletal muscle myopathy with
recovery.
 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.
 4 deaths
 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.
 851 patients in an eating disorders clinic
 7.8% had used ipecac (4.7% intermittently, 3.1%
chronically)
 622 patients in an eating disorders clinic
 0.09% of women 9-19 years of age used ipecac
 3.8% of women 10-46 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.
 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.
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 substance ingested is:
 Corrosive (acid or alkali).

 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 emesis may interfere with
administration of oral antidotal therapy.
Example:
 The oral administration of
n-acetylcysteine in acetaminophen
ingestions.
 When Might Ipecac Syrup Be Used?

 When it is not contraindicated.

 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 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.
 For example: Acetaminophen:
 Less than 150 mg/kg: observe at home
 150-200 mg/kg: ipecac at home and observation
 >200 mg/kg: to ED

 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 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.
 Use no GI decontamination procedures.
 Restrict ipecac syrup to prescription
 Decrease availability to the public for abuse or
misuse.
 Reduce availability for use within 30 minutes of
ingestion.
 Allow physicians to prescribe it for specific patient
situations.
 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?