A Somnolent Toddler

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:Welcome to our Episode: A Somnolent Toddler.Here's the case:A 2 yo M presents to the PICU after being found increasingly sleepy throughout the day. The toddler is otherwise previously healthy and was noted to be in his normal state of health prior to today. The mother dropped the toddler off at his Grandmother’s home early this morning. Grandmother states that he was playing throughout the day, and she noticed around lunchtime the toddler stumbles around and acts more sleepy. She states that this was around his nap time so she did not feel it was too out of the ordinary. The toddler 1 hr later was still very sleepy, and the grandmother noticed that the toddler had some shallow breathing. She called mother very concerned as she also found her purse open where she typically keeps her pills. The grandmother has a history of MI and afib as well as hypertension. She is prescribed a multitude of medications. Given the child’s increased lethargy, the grandmother presents the patient to the ED. In the ED, the child is noted to be afebrile with HR 55 & RR of 18. His blood pressure is 78/40. On exam he has minimal reactivity to his pupils, he has shallow breathing and laying still on the bed. A POC glucose is 68 mg/dL. Acute resuscitation is begun and the patient presents to the PICU.To summarize key elements from this case, this patient has:DrowsinessBradycardiaNormotensionThis is in the setting of being at grandma’s home and having access to many medicationsGiven the hemodynamic findings and CNS obtundation, this patient’s presentation brings up concern for a clonidine or beta-blocker ingestion.This episode will be organized:Beta-Blocker poisoningWe will also examine other medications that potentially can be toxic to a toddler (one pill can kill) present in Grandma's purse which include: TCA, CCB, Opioids, oral anti-diabetic agents, digoxin, etc.The presence of a grandparent is a risk factor for unintentional pediatric exposure to pharmaceuticals commonly referred to as the Granny Syndrome. Grandparents’ medications account for 10% to 20% of unintentional pediatric intoxications in the United States. To kids, all pills look like candy.Let’s start with a multiple choice.An overdose of which of the following medications may mimic the presentation of Metoprolol overdose?A. Verapamil toxicityB. Ketamine toxicityC. Valium toxicityD. Lithium toxicityThe correct answer is A, verapamil toxicity.Verapamil is a non DHP CCB.It acts at the level of the SA and AV node similar to Metoprolol, a beta-1-specific antagonist.Both cause bradycardia and AV node block.Valium though a CNS depressant, can cause CV depression as well, however, would have fewer changes on the conduction system compared to a non-DHP CCB. What is the mechanism of toxicity with beta-blockers?Beta-blockers are competitive inhibitors at beta-adrenergic binding sites, which results in decreased production of intracellular cyclic adenosine monophosphate (cAMP) with a resultant blunting of multiple metabolic and cardiovascular effects of circulating catecholamines.They attenuate the effect of adrenergic catecholamines on the heartDecrease inotropic and chronotropic response. Some drugs like Propranolol can act as Na channel blockers (myocyte membrane stabilizing activity) at high doses resulting in arrhythmias and seizures. Toxic doses of drugs like Sotalol can result in K channel blockade giving rise to prolonged QT and risk for torsades.The anti-alpha-adrenergic activity of agents like carvedilol, and labetalol can result in peripheral vasodilation and hypotension.In addition, beta-adrenergic receptor antagonism inhibits both glycogenolysis and gluconeogenesis, which may result in hypoglycemia.Rahul can you tell us about the pharmacokinetics of beta-blockers:Beta-blockers exhibit intraclass pharmacokinetic variability with regards to absorption, bioavailability, hepatic first-pass metabolism, and lipid solubility, protein binding. Drugs like propranolol are lipid soluble with a high volume of distribution and can cross the blood-brain barrier, whereas drugs like atenolol and nadolol are water-soluble and have a low volume of distribution. The onset of action for most immediate release agents is typically 2-6hours.All beta-blockers, regardless of their designed selectivity, can lose selectivity in overdose.Bradycardia, hypotension & conduction delays are the hallmarks of acute beta-blocker overdose. Hypoglycemia and seizures are also seen in some cases. Risk factors for toxicity include young age (unintentional -primarily seen in children < 6 years or suicidal seen in teenagers ), co-ingestion of other medications such as TCA, Ca channel blockers, and neuroleptic agents, extended-release preparations, and known cardiac disease. In many studies looking at BB overdose, Approximately 80% of exposures were unintentional.Pradip, what would be the typical clinical presentation of a beta-blocker overdose:Rahul, of most the patients we see are toddlers who have had unintentional exposure to the drug such as our case presentation. There is an adult who uses the prescribed medication and the child gets access to the medication. A child can present with depressed mental status, seizures, bradycardia, hypotension, and shock. Very rarely a child with underlying airway hyper-responsiveness can present with bronchospasm. Toxicity with beta-blockers is less severe (compared to channel blocker ingestion) and can be asymptomatic or present with bradycardia and drowsiness. Hypothermia, hypoglycemia, and seizures have been reported in children. Beta-blockers that are not sustained-release formulations are all rapidly absorbed from the gastrointestinal tract. The first critical signs of overdose can appear 20 minutes post-ingestion but are more commonly observed within 1-2 hours. In all clinically significant beta-blocker overdoses, symptoms develop within 6 hours.If you had to work up this patient with a beta-blocker, what would be your diagnostic approach?A good history from caregivers. Exposure to beta-blockers prescribed to a parent or grandparent can lead to the diagnosis.Typical labs sent include: Blood gas (to asses metabolic acidosis), serum lactate, CMP (hypokalemia or hypocalcemia can worsen arrhythmias as well as to evaluate for hypoglycemia)EKG, cEEG in a comatose patientLook for co-ingestions using serum or urine comprehensive toxicological screening.beta-HCG in teenagersWhat is the approach to managing a patient with beta-blocker overdose?The patient needs to be admitted to the PICU for close observation. Contact State Poison control centers for reporting and their management recommendations.Besides the maintenance of patient’s airway and breathing, the goal of therapy is to restore perfusion to critical organ systems by increasing cardiac output. This may be accomplished by improving myocardial contractility, increasing heart rate, or both.Prehospital: Activated charcoal is indicated in the first few hours especially if the patient is not altered.The asymptomatic patient needs observation for at least six hours for immediate release of medications whereas sotalol may require 12 hours.Treatment beyond monitoring is not necessary if the only manifestation is asymptomatic bradycardia.So Rahul, let's say the patient is bradycardic, how would you pivot your management framework?For patient who is bradycardia+hypotension: The first line is the judicious use of crystalloid boluses (patient can develop pulmonary edema with excessive fluids). Atropine may be considered.Glucagon: stimulates adenyl cyclase via the glucagon receptor instead of the blocked beta-adrenergic receptor. The effect is seen within minutes. If no improvement in ten minutes additional dose of glucagon is less likely to be effective. The typical pediatric dose is 50-150 mcg/kg IV bolus.Hyperinsulinemia-euglycemia (HIE) therapy: Insulin increases both inotropy and chronotropy. Regular insulin (range 1-10U/Kg/hr is used.) Start at 1U/Kg/hr and titrate upwards every 30-40 minutes till HD improvement is seen. Add dextrose to counter hypoglycemia: 0.25 g/kg of 25% dextrose IV bolus, and an infusion of 10% dextrose. Need to watch K closely. The clinical effect is typically seen in 15-30minutes.Vasopressors: Use high dose NE or epinephrine. One case series of 20 patients (Musselman M. et al, Ann Emerg Med. 2011) reported no significant difference in mean arterial pressure (from baseline) in patients receiving high-dose insulin euglycaemic therapy in addition to vasopressors compared to vasopressors alone.Lipid Emulsion Therapy: reserved for severe cases refractory to all...