A Review of Ipecac Syrup

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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

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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.

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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
• Childrens 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

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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.

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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.

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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

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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.

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Pediatric Exposures Reported to US Poison Centers
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Use of Ipecac Syrup by US Poison Centers
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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.

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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.

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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.

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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

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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.

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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.

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The glass is 1/4 full

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

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The glass is 3/4 empty

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

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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.

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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

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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

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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).

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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.

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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 1984131100-1102

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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.

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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.

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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).

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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

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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.

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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.

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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.

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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. gt 1
  hour).

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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
• gt200 mg/kg to ED
• In 1990, we eliminated all use of ipecac and
  observed at home the children in that category.

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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.

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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.

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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?