Poisoning/Insect Bites

From the 30th Annual Las Vegas Seminars, sponsored by the American Academy of Pediatrics and AAP California District IX, Chapters 1,2,3, and 4

Educational Objectives

The goal of this program is to improve the management of the child with known or suspected poisoning, and to pro­vide an overview of insect bites and repellents. After hearing and assimilating this program, the clinician will be bet­ter able to:

1.   Conduct a thorough history and recognize a toxidrome (if present) during initial assessment of a child with known or suspected poisoning.

2.   Implement 5 essential principles of management of poisoning.  

3.   Discuss the role of antidotes in management of poisoning and name several of those currently available.

4.   Describe the new antidotes octreotide, fomepizole, and hyperinsulinemia-euglycemia (HIE) therapy, their clin­ical applications, and the guidelines for their use.

5.   Cite the Environmental Protection Agency and American Academy of Pediatrics recommendations for the use of the insect repellent N,N-diethyl-meta-toluamide (DEET) in children.

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. Mancini has been a consultant for Novartis Corporation. Dr. Shannon and the planning committee re­ported nothing to disclose.

Acknowledgements

Drs. Shannon and Mancini spoke at the 30th Annual Las Vegas Seminars Pediatric Update, held November 20-23, 2008, in Las Vegas, NV, and sponsored by American Academy of Pediatrics (AAP) California District IX, Chapters 1,2,3, and 4, and the American Academy of Pediatrics. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Initial Management of the Poisoned Child

Michael W. Shannon, MD, MPH, Professor of Pediatrics, Harvard Medical School, and Chief, Division of Emergency Medicine, Children’s Hospital, Boston, MA

Initial assessment: gathering history  —  ask about medications in home and in home of other relatives or caretakers; devel­opmental status; past medical history; pica; previous ingestions; recognition of toxidromes  —  complex of symptoms sug­gesting specific type of poisoning; recognizable toxidromes for cholinergic syndrome (salivation; lacrimation; urination; defecation; gastrointestinal [GI] distress; emesis; bronchorrea; bradycardia); anticholinergic syndrome (fever, ileus, flushing, tachycardia, urinary retention; dry skin; blurred vision; mydriasis; decreased bowel sounds; coma; hallucina­tions; seizures); dystonic reaction (torticollis; opisthotnos; intermittent spasm; tongue thrusting); salicylism (hyperpnea, metabolic acidosis, agitation, coma, seizures)

Skin, pupils, and odor: diagnostic clues; skin  —  grey discoloration (silver salts; amiodarone; methemoglobinemia [metHb]); pupils  —  miosis (cholinergics; narcotics); mydriasis (anticholinergics; stimulants); nystagmus (phenyt­oin; phencyclidine; ketamine); diagnostic odors  —  rotten eggs (hydrogen sulfide); garlic (arsenic)

Five essential questions: 1) important stabilization issues? 2) decontamination indicated? 3) laboratory studies indicated? 4) can drug elimination be enhanced? 5) antidote available?

Stabilization: begin with airway, breathing, circulation, drugs (ABCDs); ill-appearing child should receive intrave­nous (IV) fluids and oxygen (O₂), and be placed on monitor; anticipate seizures (have lorazepam at hand)

Decontamination: activated charcoal (AC)  —  highly effective; absorbs virtually all toxins; clearly effective when given within »1 hr, no proven efficacy when given ³1 hr after ingestion; AC in children  —  administered in slurry of water, juice, chocolate syrup, ice cream or any other medium; »60% of children <5 yr of age will not drink AC within »20 min necessary for decontamination and require administration by nasogastric (NG) tube; recommended approach to decontamination in poisoned child; limited role for whole-bowel irrigation

Role of laboratory: toxic screen  —  panel of tests to screen for presence of toxin; blood (test for drugs for which con­centrations interpretable); urine (test for substances of abuse, and toxic metabolites); shortcomings  —  rarely changes management; high false-positive and false-negative rates; highly variable from institution to institution; false-positive test for drug not in child’s environment may indicate another drug that causes a similar reaction (eg, cold medicines produce positive amphetamine urine test); other important tests

Enhancement of elimination: only 2 ways to accelerate elimination of drug circulating in blood; for many agents, repeated doses of AC every 2 to 4 hr enhance elimination; hemodialysis treatment of choice with toxic alcohols, lithium, aspirin, and phenobarbital; hemoperfusion rarely used

Antidote: »30 available; clinicians should have working knowledge of them and/or know where to get that informa­tion quickly; important to know which antidotes at hand (many local hospitals carry only 2 or 3), and to join with others (consortium of hospitals or local poison center) to have regional depot

Management of case 1: 20-month-old child brought to emergency department (ED) by grandparents; on physical ex­amination (PE), child noted to be lethargic and tachypneic; slightly tachycardic; no rash; neurologic examination symmetric; no odors; history unrevealing; toxidrome recognized during physical assessment; assess stabilization needs (no need for airway or blood pressure (BP) support; begin IV fluids and place child on monitor); assess need for decontamination (no role for AC); order laboratory tests (blood and urine toxic screen); results (venous blood gas [VBG] and electrolytes) indicate aspirin poisoning (serum aspirin level of 75 mg/dL); child requires stabiliza­tion and supportive care in intensive care unit [ICU]); drug elimination enhancement possible; no available antidote

Management of case 2: 16-yr-old brought to office for evaluation of fever and agitation; has history of attention-def­icit/hyperactivity disorder and depression for which he takes methylphenidate and citalopram; on PE, has general­ized hypertonia (worse in lower extremities); history not useful; recognizable toxidrome during physical assessment; stabilization (vital signs acceptable, although BP requires close monitoring); decontamination (no indi­cation for AC); laboratory tests (electrolytes, liver function tests, complete blood cell count , serum and urine toxic screens; electrocardiography ]) all normal; suggests serotonin syndrome (not overdose [OD], but adverse drug reac­tion to medication taken as prescribed); drug elimination cannot be enhanced; antidote available (cyproheptadine)

Management of case 3: 3-yr-old brought to ED for evaluation of lethargy, vomiting, and diarrhea; slightly low tem­perature and pulse; skin cool and clammy; pupils small without nystagmus; bedside glucose test normal; child has recognizable toxidrome; history unrevealing; ultimately diagnosed as organophosphate poisoning (partially chewed flea collar found underneath child’s bed)

Important New Antidotes

Dr. Shannon

Role of antidotes in poisoning management: specific antidote available for only 10% to 15% of poisonings; when available, antidote must be administered properly and promptly; knowledge about antidotes (and when and how to use them) essential for all ED physicians and clinicians responsible for managing childhood poisonings  

Antidotes: N-acetylcysteine  —  for acetaminophen; sodium nitrite or thiosulfate  —  for cyanide; flumazenil  —  for any benzodiazepine; physostigmine  —  for any anticholinergic agent; phentolamine  —  for accidental autoinjection of digit with epinephrine; pyridoxine  —  for isoniazid (INH)

Case example: 2-yr-old ingests unknown amount of mother’s glipizide; on arrival at ED, child alert and appropriate; AC not administered; »2 hr after arrival, child becomes lethargic, very hypoglycemic (bedside glucose »45 mg/dL)

Sulfonylureas (eg, glipizide:) unique hypoglycemic agents (stimulate insulin release from pancreatic b-cells; OD produces severe and often prolonged or recurrent hypoglycemia)

Conventional treatment of sulfonylurea OD: stabilization (ABCs); IV dextrose for hypoglycemia (causes insulin surge which may promote further hypoglycemia); glucagon; corticosteroids; diazoxide

Octreotide: hormone (somatostatin analogue); mechanism of action unclear, but known to be potent promoter of eu­glycemia; highly effective for sulfonylurea OD (eliminates need for IV dextrose; often effective after single dose; eliminates recurrent and rebound hypoglycemia); treatment of choice for sulfonylurea-induced hypoglycemia; 1 µg/kg in continuous infusion or repeat bolus doses

Case example: 2-yr-old found in garage near open bottle of antifreeze; taken to local ED; child noted to be lethargic; serum osmolality elevated (»350 mOsm/L), serum pH normal (»7.35)

Toxic alcohols: methanol and ethylene glycol (EG) most lethal; both common ingestions (important causes of mor­bidity and mortality in adults and children) and rare examples of drug toxification (parent drug relatively non­toxic; metabolism via alcohol dehydrogenase [ADH] converts it into toxic metabolite)

Methanol: primary sources Sterno cooking fuel, windshield washing fluid; as little as »1 tsp can be lethal in child; toxic effects (severe metabolic acidosis; pancreatitis; blindness); toxicity appears »12 to 24 hr after ingestion (providing considerable time for assessment and treatment)

EG: primary source antifreeze; as little as »1 tsp potentially lethal; toxic effects (inebriation; seizures; arrhythmias; renal failure); rapid onset of toxicity (EG has half-life of »3 hr; ingestion requires prompt management)

Treatment of methanol/EG toxicity: stabilization and supportive care; aggressive alkalinization; inhibition of me­tabolism of parent drug through blockade of ADH (usually via IV or oral ethanol); in severe or advanced cases, hemodialysis useful

Adverse events associated with ethanol administration: produces inebriation, obtundation (or even coma), and met­abolic disturbances in children; infusion corrosive to small veins; difficulty attaining and maintaining therapeutic serum level (requires frequent ethanol measurements and admission to ICU)

Fomepizole: extremely potent ADH inhibitor; relatively nontoxic (requires no blood sampling or ICU monitoring); experience in children good, but drug not yet approved by FDA for use in children; when administered early, fomepizole’s ability to effectively block metabolism of parent drug eliminates need for hemodialysis; concerns about cost have led to limited availability, even in pediatric centers; however, cost analysis (Boyer et al) showed that treating EG OD with IV fomepizole ultimately less expensive than conventional therapy with IV ethanol; cost containment and cost sharing interventions available; in speaker’s opinion, fomepizole only choice for treatment of children with methanol or EG OD

Case example: 15-yr-old girl brought to ED after ingesting bottle of verapamil; pulse 80 BPM; BP 100/70 mm Hg; shortly after arrival, patient becomes hypotensive, bradycardic, and in obvious shock; given »1.5 L fluid bolus; no improvement in BP

Calcium-channel blockers (CCBs): highly lethal in OD (death results from cardiac events [usually intractable bra­dycardia and hypotension])

Treatment options for CCB OD: ABCs; fluids; vasopressors (ineffective in severe cases); calcium (rarely effective); glucagon (also generally ineffective); hyperinsulinemia/euglycemia (HIE) therapy

HIE therapy: blocks L channels of pancreatic beta cells, thereby halting release of insulin; increasingly used in clin­ical practice; extremely effective (even when all other measures fail) for CCB OD; treatment protocol  —  administer insulin bolus of »1 U/kg; begin insulin infusion at »0.5 U/kg per hr (increase to »1 U/kg as needed); treatment goal normalization of BP; monitor bedside glucose and serum potassium levels; adverse effects  —  no life-threatening toxicity encountered; theoretic risks for hypoglycemia and hypokalemia

Question and answer: what is recommended protocol for fomepizole administration in child with suspected EG ingestion  —  fomepizole too expensive to give presumptively; however, adequate time in case of possible EG inges­tion for laboratory tests to determine whether child’s condition serious enough to require drug; could take same child and monitor pH continuously for signs of decrease

Insect Bites and Repellants

Anthony J. Mancini, MD, Head, Pediatric Dermatology, Children’s Memorial Hospital, Northwestern Univer­sity, Feinberg School of Medicine, Chicago, IL

Mosquitos: huge annoyance (but also of medical significance worldwide); attracted by sight, temperature and smell, with preferences; bite causes hypersensitivity reaction; bites occasionally clustered but tend to be sporadic (edema­tous, uticarial papules with central punctum)

Fleas: bites common in children; dogs, cats, and birds common animal sources; bites often appear in linear group­ings; bite reactions may be bullous

Mites: small arachnids; most lack host specificity; bite reactions papular, urticarial, and numerous; rarely transmit disease; mite-induced dermatitis seen in variety of settings (harbored by pets, rodents, in straw bedding, and in birds’ nests; occasionally identified on tape stripping and vacuum cleaner filters; most sources remain unidentified)

Bedbugs: feed on sleeping humans (emerge only at night); reactions to bites large, urticarial, and generally few; re­cent resurgence in infestation rates related to international tourism; require attachment for »30 min for full feeding; no known transmission of bloodborne pathogens

Treatment of bites: counterirritants (eg, camphor, menthol, propylene glycol [Sarna]); topical corticosteroids (use potent [class I or II] agent; hydrocortisone ineffective); antihistamines when needed

Prevention: avoidance (when possible); environmental modification (for bedbugs and fleas); protective clothing; in­sect repellants; treat infested animals and living quarters; professional extermination

Insect repellants: 2 ingredients, N,N-diethyl-meta-toluamide (DEET) and picaridin, recommended by Centers for Disease Control and Prevention; applied to exposed skin; other ingredients not nearly as effective

DEET: active ingredient in most commercially available insect repellants; effective against variety of biting insects; reports of toxic encephalopathy usually with very high percentages or incorrect usage; absorbed (»50% may re­main in skin and fat depots for £1 mo); use lowest effective concentration (children, 10%-20%; adults, 10%-30%; camping, 30%-40%; >50% adds little benefit and higher risk)

DEET and children: critical analysis of literature  reveals »10 reports of seizures in children; poison control reports show lower rates of adverse effects in infants and children; Environmental Protection Agency (EPA) and Ameri­can Academy of Pediatrics (AAP) caution against use in children <2 yr of age and in combination with sun pro­tection products; flammable; “arm in cage” studies have proven DEET most effective insect repellant by far; refer parents to National Pesticide Information Center (www.npic.orst.edu)

Picaridin: comparable in efficacy to DEET; first available in United States as 7% formulation (17% concentration now available); variety of products

Other repellants: oil of lemon eucalyptus, citronella (not effective); permethrin (excellent protection against ticks, mosquitos, fleas, and chiggers; comes in aerosol spray [Permanone]; applied to clothing, bedding, and tents)

Protocol of United States Department of Defense: soldiers exposed to multiple arthropod assaults; Armed Forces use permethrin spray on clothing and 35% DEET; recommends keeping shirt tucked in to pants

Suggested Reading

Antwi FB et al: Risk assessments for the insect repellents DEET and picaridin. Regul Toxicol Pharmacol 51:31, 2008; Barry JD: Diagnosis and management of the poisoned child. Pediatr Ann 34:937, 2005; Boyer EW et al: Hyperinsu­linemia/euglycemia therapy for calciumchannel blocker poisoning. Pediatr Emerg Care 18:36, 2002; Brent J: Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med 360:2216, 2009; Brush DE, Boyer EW: Intravenous N-acetyl­cysteine for children. Pediatr Emerg Care 20:649, 2004; Calello DP et al: New and novel antidotes in pediatrics. Pediatr Emerg Care 22:523, 2006; Eldridge DL et al: Pediatric toxicology. Emerg Med Clin North Am 25:283, 2007; Flake ZA et al: Clinical inquiries. Is DEET safe for children? J Fam Pract 54:468, 2005; Fradin MS, Day JF: Greene SL: Relative safety of hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective observational study. Intensive Care Med 33:2019, 2007; Greene SL et al: Acute poisoning: understanding 90% of cases in a nutshell. Postgrad Med J 81:204, 2005; Gul M et al: The effectiveness of various doses of octreotide for sulfonylurea-in­duced hypoglycemia after overdose. Adv Ther 23:878, 2006; Hanhan UA: The poisoned child in the pediatric intensive care unit. Pediatr Clin North Am 55:669, 2008; Hovda KE, Jacobsen D: Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning. Hum Exp Toxicol 27:539, 2008; McGregor T et al: Evaluation and manage­ment of common childhood poisonings. Am Fam Physician 79:397, 2009; Michael JB, Sztajnkrycer MD: Deadly pediat­ric poisons: nine common agents that kill at low doses. Emerg Med Clin North Am 22:1019, 2004; Salhanick SD, Shannon MW: Management of calcium channel antagonist overdose. Drug Saf 26:65, 2003; Schwerk N et al: Successful therapy of paediatric ethylene glycol poisoning: a case report and annual survey by a regional poison centre. Acta Paediatr 96:461, 2007; White ML, Liebelt EL: Update on antidotes for pediatric poisoning. Pediatr Emerg Care 22:740, 2006.