Poison Management

Educational Objectives

The goal of this program is to improve management of poisoning in children and management of cyanide (CN) toxic­ity. After hearing and assimilating this program, the clinician will be better able to:

1.   Recognize the signs and symptoms of poisoning due to commonly used products.

2.   Discuss the signs, symptoms, and management of toxicity from ingestion by children of oral hypoglycemic agents and cardiovascular medications.

3.   List possible sources of CN toxicity.

4.   Review the mechanism of action and clinical presentation of CN toxicity.

5.   Differentiate between the available antidotes to CN toxicity and describe the advantages and disadvantages of each.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning com­mittee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Borron is a consuitant for and is on the Speakers’ Bureau of Merck KGaA. Mr. Hughes and the planning committee reported nothing to disclose. In their lectures, the speakers present information that is related to off-label or investigational use of a therapy, product, or device. 

Acknowledgments

Mr. Hughes and Dr. Borron were recorded at Clinical Toxicology, held June 4-5, 2009, in Bloomington, MN, and sponsored by the HealthPartners Institute for Medical Education. The Audio-Digest Foundation thanks the speakers and the Health­Partners Institute for Medical Education for their cooperation in the production of this program.

Monsters and Sheep in Pediatric Poisoning

Kirk Hughes, RN, CSPI, Hennepin County Medical Center/Hennepin Regional Poison Center, Minneapolis, MN

Introduction: »55% of poison exposures reported to poison centers nationally involve children <6 yr of age; subset of children 16 to 22 mo of age most often involved; risk factors for exposures in children  —  improper storage; lack of supervision (most children poisoned between 4 PM and 8 PM on weekdays); look-alike products; serious pediat­ric exposures to prescription medications most common during holidays (when grandparents visit); children’s natu­ral curiosity; suicide; consider each case individually; most children are pleasure seekers, except those with developmental disabilities (eg, trisomy 21,  autism)

Decontamination: previously, gastric lavage used; syrup of ipecac  —  no longer recommended; 33% to 40% efficacy; activated charcoal (AC)  —  single-dose used on rare occasions; may cloud clinical picture; dose 1 g/kg; aqueous formulation preferable to avoid possible exacerbation of vomiting and diarrhea from poison; whole bowel irrigation  —  rarely performed in children; multidose AC  — rarely used

Bleach: household formulation contains 5% to 10% sodium hypochlorite (oxidizer); most common sign and symp­tom immediate vomiting; treat with dilution (water, or other beverage child likes); most of time, 1 to 2 sips of household bleach causes only minor gastrointestinal (GI) upset, and visit to emergency department (ED) rarely re­quired

Silica gel and desiccants: one of top 3 reasons for calls to poison center; packet contains warning stating “not for in­ternal use”; made of silicon dioxide; absorbs moisture; choking hazard for small children (package itself); other desiccants  —  ingredients include clay that absorbs moisture or 99% reduced iron (not bioavailable and not toxic to child)

Diaper rash ointments and creams: active ingredient zinc oxide (11%-40%); little toxicity; GI upset common ad­verse effect

Oral hypoglycemic agents: sulfonylureas  —  most worrisome; cause direct lowering of blood glucose (BG) and im­prove insulin secretion; hypoglycemia may occur at recommended therapeutic dose; as little as 2.5 mg of glyburide produces marked and prolonged hypoglycemia in children; symptoms sometimes delayed for 12 to 24 hr after in­gestion; treatment  —  consider AC on case-by-case basis (generally used only with large and recent ingestion); ob­serve all patients for ³12 hr; intravenous (IV) access for dextrose to treat drop in BG; BG may fluctuate; octreotide effective (suppresses release of insulin); metformin   —  overdose or long-term use can cause lactic acidosis, but sin­gle ingestion does not significantly lower BG (also true for thiazolidinediones); non-sulfonylurea insulin secretagogues  —  new class of medications (eg, nateglinide [Starlix], repaglinide [Prandin]); directly lower BG, but short-acting

Cardiovascular medications: angiotensin-converting enzyme (ACE) inhibitors, angiotensin-2 antagonists, and most diuretics “not a huge concern” if only 1 to 2 pills ingested

Calcium channel blockers (CCBs): of greater concern due to delayed-release formulations; verapamil and diltiazem responsible for 80% of CCB-related deaths; symptoms — hypotension and bradycardia hallmark symptoms; caused by inotropic effect and induction of peripheral vasodilation; confusion, agitation, dizziness, lethargy, nau­sea, and vomiting also possible; treatment  —  AC, gastric lavage, and whole-bowel irrigation; serious outcomes including death possible; aggressive gastric decontamination necessary; gastric lavage appropriate if child pres­ents £30 min after large ingestion; start IV fluids (fluids and positioning first line of treatment for hypotension); increased intracellular calcium necessary to increase heart rate and cardiac output; calcium gluconate safer; cal­cium chloride more commonly used, but requires central line to administer (also more irritating to cardiac vascu­lature); high-dose insulin (HIE) and euglycemia increasingly used; increasing insulin improves inotropy, but causes hypoglycemia; bolus dose given, then maintenance dose of 0.5 to 2 U/kg per hour; dextrose also given; the sooner treatment initiated, the better the outcome; atropine rarely effective; glucagon and vasopressors also used; new treatment  —  sequestration therapy with 10% IV fat emulsion (Intralipid)

b-blockers: reduce inotropy and chronotropy; patients present with hypotension and bradycardia; slightly better outcomes than with ingestion of CCBs, but still dangerous; propranolol responsible for 70% of deaths from b-blockers; atrioventricular block among possible cardiovascular effects; treatment  —  multiple-dose AC; whole-bowel irrigation if delayed-release formulation ingested; high potential for morbidity and mortality; treat hypo­tension with IV fluids and positioning; HIE used to overcome b-blockade and increase inotropy (not yet main­stream treatment); calcium gluconate and glucagon also used; for bradycardia, atropine and/or pacing; administer sodium bicarbonate for acidosis

Clonidine: used for attention-deficit hyperactivity disorder; narrow safety margin; initially used for hypertension and still used for opioid and alcohol withdrawal; available in pills and patches; significant amount of medication still present in used patches; symptom onset rapid; serious toxicity causes lethargy, coma, and respiratory depres­sion; slows heart rate and produces hypotension; children especially susceptible to toxic effects; £0.3 mg can cause major signs and symptoms; treatment  —  consider AC; observe for ³6 hr; for hypotension, give fluids and dopamine; naloxone has »50% efficacy in reversing respiratory depression and improves hypotension and brady­cardia; hypertension usually early and transient (does not require treatment)

Cyanide Toxicity

Stephen W. Borron, MD, Professor of Emergency Medicine and Medical Toxicology, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, and Associate Medical Director, West Texas Regional Poison Control Center, El Paso

Key points: cyanide (CN)  —  poisoning rare, absent smoke inhalation; two-thirds of smoke inhalation victims found in confined spaces with soot deposits in nose, mouth, and oral secretions and altered mental status have blood CN concentrations in toxic range; important industrial chemical with multiple uses; in enclosed space, effective as chemical weapon (not effective outdoors, as hydrogen CN gas lighter than air and dissipates rapidly); poisoning treated successfully with good supportive care alone or combined with antidotes

Sources of CN: combustion products  —  some artificial (eg, polyacrylonitrile, melamine resin, polyurethane foam) and natural substances (eg, wool, silk, cotton) produce CN when burned; industrial chemicals  —  soluble CN salts; HCN in liquid and gas forms; mercury CN and silver CN released slowly if taken internally; nitriles and cyanogens must be metabolized to produce poisoning; acetonitrile used as standardization agent in laboratories and in artificial fingernail removers; also found in plants and foodstuffs (amygdalin)

Smoke inhalation: any compound that contains carbon and nitrogen can produce CN when burned; amount of CN produced depends on carbon and nitrogen content, temperature of combustion, and available O₂; CN in blood of some fire victims first noted in 1966

1991 Baud study: looked at smoke inhalation victims with blood drawn at scene; CN rapidly dissipates from smoke inhalation survivors; of 109 victims, those who survived had blood CN concentrations less than accepted thresh­old for toxicity (<1 mg/L or 39-40 μmol/L); victims who died had high CN levels (>3 mg/L [lethal]); surmised that CN significant factor in death from smoke inhalation; to convert to carboxyhemoglobin (COHb), multiply CN and carbon monoxide (CO) in mmol/L by 11 (represents COHb concentration of 60% [generally accepted le­thal concentration]); deaths also seen with subtoxic CN and CO concentrations, suggesting additive toxicity

Plasma lactate: concentrations >10 mmol/L found in patients with blood CN above toxic levels; better correlated with CN than with CO; study by Benaissa  —  found that even sickest patients with pure CO poisoning had plasma lactate concentrations averaging 2.8 mmol/L

Speaker’s study: similar to 1991 Baud study (69 patients with soot in nose and mouth and altered mental status), but treated with hydroxycobalamin (HCBA) at scene; 67% had blood CN concentrations >1 mg/L (>40 mmol/L); 50 survived and 19 died; blood CN 3 times higher in cardiac arrest victims, compared to those without cardiac ar­rest at scene; in those without CN poisoning, COHb levels lower (suggests correlation between COHb and CN); no correlation seen between CO concentrations and cardiac arrest; comparison with Baud study — in patients with borderline CN toxicity, survival 62% if no antidote given (74% if HCBA given); in those with lethal concen­trations of CN, 0% survival without antidote (50% survival with antidote)

Study by Chou: 150 children treated with hyperbaric O₂ for either pure CO poisoning or smoke inhalation; similar mean COHb in 2 groups; no deaths in pure CO group, while 20% of smoke inhalation victims died; at scene, ini­tial Glasgow Coma Scale (GCS) scores almost normal in pure CO group, 7 in smoke inhalation group; depressed mental status seen in small percentage of pure CO group, and in high percentage of smoke inhalation group; pH normal in CO group (lower in smoke inhalation group); no respiratory or cardiac arrests in pure CO group (70% respiratory and 26% cardiac arrests in smoke inhalation group)

Take-home messages: smoke inhalation not CO poisoning; mortality in smoke inhalation victims associated with prehospital respiratory and cardiac arrest; plasma lactate >10 mmol/L sensitive and specific for CN poisoning in setting of smoke inhalation

CN in foods and drugs: cassava  —  root eaten or  processed into tapioca; causes poisoning if poorly prepared; amygdalin  —  from interior of pits of prunes, peaches, and apricots; substantial amount required to cause poisoning (»1 cup in adults); cycads  —  common plants; seeds eaten in Asia (Taiwan and Korea); also cause poisoning; over­doses of laetrile reported (used as anticancer treatment)

CN in terror and mass poisonings: 2 CN bombs found in Tokyo subway 2 or 3 mo after sarin episode; Jonestown episode (people drank beverage laced with CN)

Mechanism of action: CN attaches to cytochrome aa3 in mitochondria; interference with utilization of O₂ results in abnormally high blood O₂, even on venous side; very slight or almost no difference between arterial and venous O₂ concentrations seen; anaerobic metabolism ensues, and lactic acid accumulates; CN then attaches to cytochrome oxidase system in mitochondria, and causes depletion of adenosine triphosphate; this leads to formation of proteins that cause cellular dysfunction and necrosis; release of apoptosomes from mitochondria activates cascade leading to programmed cell death (apoptosis); nitric oxide  —  essential to control of blood pressure; antidote for CN poison­ing; however, in excess, causes production of peroxynitrite

Clinical presentation: respiratory  —  signs and symptoms include air hunger, tachypnea, hyperpnea, hypopnea, then apnea; central nervous system  —  headache, giddiness, confusion, seizures, and coma; GI  —  nausea, vomiting, and incontinence; cardiovascular  —  hypertension and tachycardia, then hypotension, followed by cardiovascular col­lapse and death; cyanosis rare; expect normal to pinkish skin color

Diagnosis: primarily clinical, based on history, physical examination, and high index of suspicion; history  —  chemical or laboratory workers; smoke inhalation; unexplained collapse in otherwise healthy person; sudden col­lapse of multiple persons in industrial or public setting; physical examination  —  altered vital signs and respiratory pattern (tachypnea and hyperpnea, or bradypnea and hypopnea or apnea); dilated pupils (no prognostic signifi­cance); laboratory findings  —  lactic acidosis (>8 mmol/L in pure CN poisoning; >10 mmol/L in smoke inhalation); decrease in arterial and venous O₂ saturation difference on blood gases; do not delay treatment for laboratory test results

Treatment: good supportive care; airway, breathing, and circulation; if patient seen within 1 hr of ingestion, consider gastric emptying and AC; correcting acidosis important; CN does not cross blood-brain barrier as easily if union­ized form decreased in blood; correct hypotension; administer specific antidote if available; antidotes  —  Taylor kit, Pasadena kit or Lilly kit, and Cyanokit; Taylor kit  —  2 agents (2 nitrites [amyl nitrite and sodium nitrite] and so­dium thiosulfate); sodium nitrite forms methemoglobin (metHb) through release of nitrate; metHb binds CN to be­come cyano-metHb (does not carry O₂); sodium thiosulfate replenishes depleted sulfur to create rhodanese (naturally-occurring enzyme) and remove CN from cyano-metHb; thiosulfate then reverts to thiocyanate and cy­ano-metHb reverts to oxyhemoglobin; HCBA (vitamin B_12a)  —  binds in 1-to-1 ratio to CN to form cyanocobalamin (Vitamin B₁₂; harmless in low doses); high efficacy (comparable to CN kits); advantages of CN antidote kit  —  less expensive; amyl nitrite used without vascular access; disadvantages of CN antidote kit  —  nitrites may induce met­hemoglobinemia (less O₂-carrying capacity) and hypotension (use questionable in smoke inhalation); thiosulfate causes vomiting; advantages of HCBA  —  effective; longer shelf life; does not interfere with O₂ transport (safer in smoke inhalation); disadvantages of HCBA  —  more expensive; may aggravate or temporarily induce hypertension; causes prolonged redness of skin, plasma, and urine; administration of CN kit  —  crush amyl nitrite and ventilate pa­tient every minute until IV access available; give IV sodium nitrite slowly, then administer sodium thiosulfate; may repeat half-doses every 30 min as needed; administration of HCBA  —  dilute powder in vial and administer as rap­idly as possible (»15 min); no approved pediatric dose in United States, although Food and Drug Administration al­lowed inclusion of pediatric dose used in Europe in package insert (considered off-label use)

Suggested Reading

Baud FJ et al: Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med 30:2044, 2002; Coco TJ et al: Descriptive epidemiology of infant ingestion calls to a regional poison control center. South Med J 98:779, 2005; James LP et al: A comparison of cathartics in pediatric ingestions. Pediatrics 96:235, 1995; Kerns W 2nd et al: Hydroxocobalamin versus thiosulfate for cyanide poisoning. Ann Emerg Med. 51:338, 2008; Osterhoudt KC et al: Risk factors for emesis after therapeutic use of activated charcoal in acutely poisoned children. Pediatrics 113:806, 2004; Parekh D et al: Transdermal patch medication delivery systems and pediatric poisonings, 2002-2006. Clin Pediatr 47:659, 2008; Quadrani DA et al: Five year retrospective evaluation of sulfonylurea ingestion in children. J Toxicol Clin Toxicol 34:267, 1996; Reith DM et al: Relative toxicity of beta blockers in overdose. J Toxicol Clin Toxicol. 34:273, 1996; Rior­dan M et al: Poisoning in children 3: common medicines. Arch Dis Child 87:400, 2002; Szlatenyi CS et al: Delayed hypo­glycemia in a child after ingestion of a single glipizide tablet. Ann Emerge Med 31:773, 1998; Tenenbein M: Position statement: whole bowel irrigation. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 35:753, 1997.