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  1. Assessing and Treating Pediatric Poisonings Caused by One Dose of Adult Medication - Journal of Emergency Medical Services

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White IV, MD, NREMT P , Gabriel De Baltz, NREMT P Photos courtesy Chelsea C. White IV You and your partner are sitting in the station when the familiar sound of the rescue tones goes off. The muffled overhead speech of your dispatcher is barely audible as you start moving toward your rescue, but you do hear that a child has taken something but isn’t initially symptomatic. Thankfully, it’s coded as an omega overdose. The address is in a clean, middle-class neighborhood that isn’t known for problems with violence or illicit drugs, so you turn down the dispatcher’s offer of a simultaneous law enforcement dispatch. As you drive into the narrowed streets with cookie-cutter houses, you see an older man waving to flag you down. He meets you at your rescue door after you park in the driveway. "She’s in the garage with her grandmother. Over there!" Through the maze of vehicles in the driveway, you see Grandma violently shaking and slapping your patient, repeatedly yelling, "Stay awake baby girl!" Your call has just escalated. You reach the patient, a 4-year-old girl lying on top of a city trash collection bin, still being shaken by Grandma. As you gather your patient into your arms, she’s more lifeless than any child you’ve held before, limp and barely breathing. "We think she took a pill." "What kind, when, how much?" "We don’t know." Epidemiology Poison control centers across the country fielded over 440,000 calls in 2013 related to children accidentally taking medications not meant for them. Of these calls, 53% were for children between 1 and 2 years old. 1 Children at these ages are becoming more mobile and exploring—and getting into things, including medications. Most of these children are getting into medications in their own home that parents or other family members haven’t secured. The good news is that most of these exposures aren’t life-threatening, and many are managed over the phone by poison control centers without the need for a hospital visit or 9-1-1 call. [Native Advertisement] However, certain adult medications can cause death or severe illness when ingested by a young child. Some of these poisonings can mimic more common, less severe conditions. Others can have delayed effects, lulling parents and providers into a false sense of security until it’s too late. As an EMS provider, you need to know enough to suspect a significant poisoning and the first steps to take, whether the child is symptomatic yet or not. Poison control centers across the country fielded over 440,000 calls in 2013 related to children accidentally taking medications not meant for them. 1 Case Continued You pull the girl closer and tell the family, "We’re going to the hospital now, if one of you wants to ride with, get in the front with my partner." Your partner sees your new determined pace and asks if he can do anything to help you. "Just drive, now." Once in the back, a rapid primary survey shows a well-kept, well-dressed child without any obvious trauma. She remains nearly lifeless in appearance; just barely opening her eyes to your attempt to gain a response with sternal rubs. She takes a single breath, an action that appears to exhaust her. Something has to be done quickly. You reach up and attach oxygen to the tree and begin to ventilate your patient as the rescue peels away. Your patient reacts in a surprising manner, pushing your hands and the bag-valve mask (BVM) away from her, crying and lightly screaming at you. The response is comforting; perhaps your patient will be fine after all. Then, as quickly as it came, her respiratory effort goes away. She slumps back into near respiratory arrest and breathes maybe 4 times in a minute. As you watch her seemingly hold her breath, you arrive at the rendezvous point your partner has arranged with another ALS crew. The second paramedic jumps in and asks how she can help. Your reply is quick, "Every time she stops breathing, bag her until she cries." With your new partner in the back now controlling the airway, you give the receiving pediatric facility a quick radio report and put the patient on the cardiac monitor. Your 3-lead ECG shows sinus bradycardia, in the low 50s to high 40s—certainly not numbers you expect to see for a 4-year-old child. Poignant Poisoning No single article—or even a single textbook—can fully prepare EMS providers for all types of poisonings. This article intends to heighten your awareness and suspicion of severe pediatric poisonings that can be caused by a single pill. Common examples of each drug class are provided, but these lists aren’t comprehensive—there are less common forms and combination drugs that may have one or more of these classes in a single tablet. Sulfonylureas Sulfonylureas are a class of oral hypoglycemic agents used by many people with diabetes. Medications in this class work by stimulating pancreatic beta cells to release insulin, thereby lowering blood glucose levels. One pill can create severe hypoglycemia in a child, both due to vigorous insulin release and a child’s limited ability to regenerate glucose. The effects can be immediate or may take more than eight hours to develop, so transport for treatment and observation is a necessity. Symptoms can be vague, and can include fussiness and altered mentation, dizziness, seizures, unconsciousness and many other abnormalities. Measuring blood glucose should be a part of the workup for all sick and abnormal pediatric presentations, and may provide an important clue as well as point to a treatment. Hypoglycemia should be treated with IV dextrose according to your protocol, and for long transports, additional doses may be necessary. Glucagon may not be effective. Severe cases may require octreotide, a somatostatin analog that suppresses insulin secretion. Though octreotide isn’t a common prehospital medication, you may be called for an interfacility transport for child who has received octreotide prior to transfer. 2 Common sulfonylureas: glimepiride (Amyrl), glyburide (Diabeta, Micronase), glipizide (Glucotrol), chlorpropamide (Diabinese), glyburide/metformin (Glucovance), glipizide/metformin (Metaglip). Beta-Blockers & Calcium Channel Blockers Beta-blockers and calcium channel blockers are two common classes of antihypertensive medications. Both classes can cause severe, life-threatening symptoms of cardiogenic shock in children after small ingestions. Both classes block myocardial and vascular calcium channels—calcium channel blockers directly, beta-blockers indirectly—so overdoses of both classes look similar. Patients may appear altered and lethargic, with marked hypotension and bradycardia. Heart blocks may develop as well. Pupils are generally reactive, and not significantly constricted or dilated. Blood glucose may be low with beta-blocker overdoses. In contrast, blood glucose may be normal or elevated in calcium channel blocker overdoses. EMS treatment is primarily supportive and based on presenting symptoms. Typical bradycardia and hypotension treatments, such as IV fluids, atropine, epinephrine and/or pacing, may not work, depending on the severity of the overdose. In-hospital treatments (and some prehospital protocols) include high-dose IV glucagon and IV calcium. High-dose insulin infusions may be used for cases refractory to other methods, though the mechanism of action is unclear. 3,4 Hyperinsulinemia-euglycemia therapy (HIE) combines an insulin infusion with dextrose (as needed) to maintain normal blood glucose. This therapy can be used for overdoses of both beta-blockers and calcium channel blockers.5 HIE only affects the blood pressure; attempts at pacing may still be necessary (and more effective) with HIE therapy. Critical care transport teams and air medical teams may encounter this therapy for interfacility transports. Typical HIE dosing includes a D50W bolus, followed by a bolus of 1 U/kg of regular insulin. A regular insulin drip is then started at 1 U/kg/hr; dosing adjustments are made based on patient response. Providers need to maintain a high degree of suspicion and look for clues that may suggest poisoning while simultaneously treating the patient. Common beta blockers: atenolol (Tenormin), carvedilol (Coreg), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal), timolol (Blocadren). Common calcium channel blockers: amlodipine (Norvasc), amlodipine/atorvastatin (Caduet), amlodipine/benazepril (Lotrel), amlodipine/valsartan (Exforge), diltiazem (Cardizem, Tiazac), felodipine (Plendil), isradipine (Dynacirc), nicar tdipine (Cardene), nifedipine (Procardia), nimodipine (Nimotop), verapamil (Calan, Covera, Verelan). Opioids Opioids and their effects are well-known to EMS providers, and in injectable form, provide the backbone of prehospital pain control. Opioids come in many oral and even transdermal forms that are easy for a small child to accidentally ingest. Depending on the specific medication and dose, a single pill can produce profound respiratory depression or arrest. Nonfatal and not-yet-fatal signs of opioid ingestion include fussiness or altered mentation, dizziness or balance abnormalities, and nausea/vomiting. Many opioid preparations include acetaminophen as well, like Vicodin and Percocet, which can add to toxicity, particularly when more than one pill is ingested. EMS care is primarily supportive and related to airway and respiratory support, using BVM and naloxone as necessary and as guided by protocol. Though symptoms may improve with naloxone, an opioid receptor antagonist, naloxone has a half-life of 30–90 minutes. Many oral opioids have much longer duration of action, meaning the child may redevelop symptoms once the naloxone wears off. 6,7 Common opioids: oxycodone (OxyContin), oxycodone/acetaminophen (Percocet), morphine sulfate (MS Contin), oxymorphone (Opana), hydrocodone/acetaminophen (Vicodin), buprenorphine (Suboxone), methadone (Methadose), hydromorphone (Dilaudid), fentanyl (Duragesic patch). Central Alpha-2 Agonists Clonidine and other central alpha-2 agonists are common antihypertensive medications that have both oral and transdermal (patch) forms. Central alpha-2 agonists block the release of catecholamines like norepinephrine and adrenaline from the brain. When ingested by a child, these medications can cause an opioid-like toxidrome. Symptoms include respiratory depression, miosis and depressed mental status, as well as hypotension and bradycardia. A single pill can be enough to cause respiratory arrest, and if a patch is ingested, it can continue to secrete medication for several days. EMS treatment should be supportive and based on symptoms. As with the patient in our case, vigorous stimulation can transiently improve bradycardia and hypotension. High doses of naloxone may improve symptoms, though not as reliably as with opioids. Atropine and epinephrine may be needed for severe bradycardia and/or hypotension. If the patient is symptomatic and alpha-2 agonist overdose is suspected, it’s reasonable to try naloxone, but be prepared for ineffective results. Airway management may be necessary. Common central alpha-2 agonist forms: clonidine tablet (Catapres, Kapvay), transdermal patch (Catapres-TTS), guanfacine (Tenex), tizanidine (Zanaflex, Sirdalud). Tricyclic Antidepressants Though tricyclic antidepressants (TCA) are no longer first-line treatment for depression, they’re still used for other conditions, such as neuropathic pain and migraine headaches. Toxicity occurs primarily due to sodium channel blockade and anticholingeric effects, and a single adult dose can be fatal to a small child. Like many other overdoses, a child who has ingested a TCA may appear altered or lethargic. Seizures and ventricular arrhythmias may develop, particularly v tach. QRS widening may be seen due to sodium channel blockade, and indicates severe (and worsening) symptoms. Seizures should be treated with benzodiazepines, and QRS complexes > 100 ms should be treated with sodium bicarbonate, per protocol or online medical control. BLS and ILS crews facing long transport times should consider ALS intercept if available, since the patients can deteriorate rapidly and may develop v fib refractory to defibrillation. 8,9 Common tricyclic antidepressants: amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), trimipramine (Surmontil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil). Antidepressants The "atypical antidepressants" are a new generation of medications belonging to several different drug classes that have largely replaced TCAs in the treatment of depression. Bupropion, a monocyclic antidepressant with an unclear mechanism of action, is commonly prescribed for depression and for smoking cessation. A single dose of bupropion can be life-threatening for a small child. Symptoms include hallucinations, agitation, altered mental status, and seizures (bupropion lowers the seizure threshold even at normal doses.) Seizures are often generalized and may develop into status epilepticus. Tachycardia and ventricular arrhythmias may develop, and both QRS and QT intervals may become prolonged. Prehospital and in-hospital treatment is largely supportive. No specific antidote or treatment exists for bupropion overdoses—seizures should be treated aggressively with benzodiazepines, and life-threatening arrhythmias should be treated according to ACLS protocols. 10,11 Common antidepressants: bupropion (Aplenzin, Buproban, Wellbutrin, Zyban, Budeprion).   EMS treatment is primarily supportive and based on presenting symptoms. Discussion Although calls for pediatric ingestions are common, a life-threatening ingestion can be difficult for even the most experienced EMS providers. It’s impossible for one provider to know and remember the effects and specific treatments for all types of overdoses—poison control centers and the subspecialty of medical toxicology exist for this very reason. "At the poison center, we take calls from frightened parents to seasoned physicians caring for complex ingestions. We are here to help you 24/7, 365, and the service is free," says Brandon J. Warrick, MD, associate medical director of the New Mexico Poison and Drug Information Center. "The nearest poison center can be reached at 800-222-1222 from anywhere in the United States. Program this number into your phone, and feel free to contact us as soon as time permits." Symptoms of poisoning are similar to other more common pediatric illnesses and conditions. Many 9-1-1 calls are for symptoms: unresponsive, altered mental status, vomiting, etc., and not as a known poisoning or overdose. Calls for such complaints aren’t usually poisonings, but providers need to maintain a high degree of suspicion and look for clues that may suggest poisoning while simultaneously treating the patient. The best way to approach a poisoned patient—or any patient, for that matter—is to treat the patient in front of you: Monitor and protect the airway, support breathing if needed, and address circulatory issues. A 12-lead ECG can reveal wide QRS and long QT; glucometry can reveal additional clues (and potential need for glucose). Treat abnormalities as you find them, such as seizures and hypoglycemia. Unless the patient is displaying one of the few toxidromes for which you have an antidote, supportive care of the patient is the rule. Though not flashy or exciting, simply informing the receiving ED that the patient may have been poisoned is often the most important action the EMS crew can provide. Bringing in the bottle, a picture of a label, or even the names of "Grandma’s medications" can be of significant help. In many cases, your observations and suspicions can be the critical link in the patient’s recovery. Case Conclusion You hand your patient off to a gathering team in the pediatric ED. "Four-year-old female who took an unknown amount of an unknown prescription medication. She’s without trauma, keeps becoming apneic and is bradycardic. She remains mostly unresponsive unless you ventilate her with the BVM." You feel both relieved and helpless as you watch them go to work. Later in the shift, your medical director calls to tell you your patient is now in the pediatric ICU (PICU). The emergency physicians gave her several doses of naloxone with no effect, and ultimately had to intubate her and start an epinephrine drip. Her blood glucose was normal and her vital signs had stabilized—but the offending agent was still unknown. Several days later, you learn that, with help from social workers and family members, the PICU team suspects a clonidine overdose. Luckily, your patient will soon be well enough to go home. Good news, of course, but by then you will have thoroughly familiarized yourself with clonidine and other medications that are dangerous to children, even in small doses. Acknowledgment: The authors wish to thank Brandon J. Warrick, MD, for his help reviewing this article. References 1. Ferguson R, Osterthaler K, Kaminski S, et al. Medicine safety for children: An in-depth look at poison center calls. Safe Kids Worldwide: Washington, D.C., pp. 5–7, 2015. 2. Eldridge D, Mutter K, Holstege C. An evidence-based review of single pills and swallows that can kill a child. Ped Emerg Med Prac. 2010;7(3):1–12. 3. Boyer E, Duic P, Evans A. Hyperinsulinemia/euglycemia therapy for calcium channel blocker poisoning. Ped Emerg Care. 2002;18(1):36–37. 4. Woodward C, Ali Pourmand A, Mazer-Amirshahi M. High dose insulin therapy, an evidence based approach to beta blocker/calcium channel blocker toxicity. DARU. 2014;22(1):36. 5. Page C, Hacket L, Isbister G, et al. The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: A case report. J of Med Tox. 2009;5(3):139–143. 6. Wermeling D. Review of naloxone safety for opioid overdose: Practical considerations for new technology and expanded public access. Ther Adv Drug Saf. 2015;6(1):20–31. 7. Boyer E. Management of opioid analgesic overdose. N Engl J Med. 2012;367(2):146–155. 8. Hendron D, Menagh G, Sandilands E, et al. Tricyclic antidepressant overdose in a toddler treated with intravenous lipid emulsion. Pediatrics. 2011;128(6):1628–1632. 9. Woolf A, Erdman A, Nelson L, et al. Tricyclic antidepressant poisoning: An evidence-based consensus guideline for out-ofhospital management. Clin Toxicol. 2007;45(3):203–233. 10. Jepsen F, Matthews J, Andrews F. Sustained release bupropion overdose: An important cause of prolonged symptoms after an overdose. Emerg Med J. 2003;20(6):560–561. 11. Finkelstein Y, Hutson J, Freedman S, et al. Drug-induced seizures in children and adolescents presenting for emergency care: Current and emerging trends. Clin Toxicol. 2013;51(8):761–766.     By Chelsea C. White IV, MD, NREMT P Chelsea C. White IV, MD, NREMT-P, is a board-certified emergency physician and EMS physician in the University of New Mexico Department of Emergency Medicine. He’s the medical director for the Bernalillo County (N.M.) Fire Department, Acoma Pueblo Fire Department, Laguna Pueblo Fire Department, and the TóHajiilee Field Office of Navajo Nation EMS. Gabriel De Baltz, NREMT P Gabriel De Baltz, NREMT-P, is a paramedic and firefighter with the Bernalillo County Fire Department. Sponsored Content is made possible by our sponsor; it does not necessarily reflect the views of our editorial staff. Subscribe today to  JEMS In EMS, you never know what you'll be faced with as each new shift begins. The Journal of Emergency Medical Services (JEMS) is real-world EMS. It's informative, practical and an outstanding educational resource for EMS professionals. We're here to help you do your job more effectively, with content from writers who are EMS professionals in the field: Breakthrough Clinical Concepts Cutting-Edge Technology Annual Salary Survey Leadership & Professionalism Fundamental Assessment Tips New Product Reviews Compelling Case Studies and more... SUBSCRIBE DIGITAL EDITION   RECENT ARTICLES Treating Pediatric Summertime Emergencies Summer, a much-anticipated season of the year for both adults and children, is unfortunately a time for significant unintentional injury and death to kids. Child Abuse Laws Must Be Taught to All EMS Providers Additional hours of training are needed to engrain the responsibility we in EMS have toward our most vulnerable patients. 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