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. I'm Rahul Damania from Cleveland Clinic Children’s Hospital and 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: Here's the case presented by Rahul: A 21-month-old girl was brought to an OSH ED for somnolence and difficulty breathing, which developed after she accidentally ingested an unknown amount of liquid medicine that was used by her grandfather. Per the mother, the patient’s grandfather was given the liquid medication for the treatment of his opioid addiction. The patient took some unknown amount from the open bottle that was left on the counter by the grandfather. Immediately after ingestion of the medicine, the patient initially became irritable and had some generalized pruritus. The patient subsequently became sleepy followed by difficulty breathing and her lips turned grey. The patient was rushed to an outside hospital ED for evaluation. OSH ED: The patient arrived unresponsive and blue, she was noted to be sleepy and difficult to arouse on arrival, with pinpoint pupils and hypoxic to 88%. , but After receiving Naloxone, however, she became awake and interactive. Her glucose on presentation was 58 mg/dL and Her initial VBG resulted 7.3/49.6/+2. She continued to have intermittent episodes of somnolence without apnea. Poison control called and recommend starting a naloxone infusion; she was also given dextrose bolus. The patient was admitted to the PICU. To summarize key elements from this case, this patient has: Accidental ingestion of an unknown medication Altered mental status Difficulty breathing—with grey lips suggestive of hypoventilation/hypoxia All of which brings up a concern for a toxidrome which is our topic of discussion for today The typical symptoms seen in our patient of pinpoint pupils, respiratory depression, and a decreased level of consciousness is known as the “opioid overdose triad” Given the history of opioid addiction in the grandfather, the liquid medicine given to him is most likely methadone.In fact, in this case, the mother brought the bottle of medicine, which was subsequently confirmed to be prescription methadone given to prevent opioid withdrawal in the grandfather.   To dive deeper into this episode, let’s start with a multiple choice question: Which of the following opioids carries the greatest risk of QTc prolongation? A. Methadone B. Morphine C. Fentanyl D. Dilaudid The correct answer is methadone. Methadone prolongs QT interval due to its interactions with the cardiac potassium channel (KCNH2) and increases the risk for Torsades in a dose-dependent manner. Besides the effect on cardiac repolarization, methadone is also associated with the development of bradycardia mediated via its anticholinesterase properties and through its action as a calcium channel antagonist. Hypokalemia, hypocalcemia, hypomagnesemia, and concomitant use of other drugs belonging to the family of CYP3A4 system inhibitors such as erythromycin can prolong Qtc. Even in absence of these risk factors, methadone alone can prolong QTc.   Thanks for that, I think it is very important to involve your Pediatric Pharmacy team to also help with management as children may be concurrent qt prolonging meds. Rahul, what are some of the pharmacological and clinical features of methadone poisoning? Methadone is a synthetic opioid analgesic made of a racemic mixture of two enantiomers d-methadone and l-methadone. besides its...