2025 Southeastern Residency Conference

Title: Dose-Dependent QTc Prolongation of Methadone in Pediatric Patients


Authors: Kaitlyn Currie, Justin K. Chen, Janae Townsend, Jillian Mantione


Objective: Determine thedose relationshipfor methadone and QTc prolongation in the pediatric population.


Background: Methadone is a synthetic opioid commonly used to wean patients off continuous opioid infusions to prevent withdrawal. Methadone is associated with prolongation of the QTc intervalon electrocardiogram (EKG). In pediatric patients, the dose-dependent relationship of methadone to QTc prolongation has not been established. The primary aim of this study was to investigate the risk of QTc prolongation in pediatric patients maintained on methadone at Children’s Healthcare of Atlanta. 


Methods: A retrospective chart review of patients less than 18 years old initiated on methadone between January 1, 2023 and April 30, 2024, in the intensive care setting. Patients were excluded if they received methadone for <24 hours, did not have EKG results while on methadone, had a history of long QT syndrome, or if they were on methadone for the following indications: chronic pain, palliative care, and/or addiction.

Results: A total of 79 patients met criteria for inclusion, comprised of 266 EKGs. The median age was 0.91 years (IQR 0.36-5.49) with 40 (50.9%) of patients being male. The median baseline QTc was 424 ms (IQR 408-441) for those who had an EKG prior to methadone initiation. There was no correlation between methadone weight-based dose and length of QTc (r=0.07, p=0.23). An analysis comparing low (<0.25 mg/kg/day), moderate (0.25-0.5 mg/kg/day), and high (>0.5 mg/kg/day) dosing of methadone did not show a difference in QTc among the three groups (p=0.71). A secondary analysis comparing patients with a baseline QTc and their QTc on methadone showed no difference (424 ms versus 430 ms, p=0.24).  

Conclusion: This retrospective analysis could not determine a relationship between weight-based methadone dosing and QTc. Patients did not experience a statistically significant difference between their baseline QTc and their QTc on methadone. 

TITLE: Utility of Clonidine Conversion to Prevent Dexmedetomidine Withdrawal Syndrome in Pediatric Patients
 
AUTHORS: Emily Hardy, Andrea Gerwin, Renee Hughes, Paige Klingborg 
 
BACKGROUND: In 2022, the Society of Critical Care Medicine (SCCM) issued a guideline recommending alpha-2 receptor agonists as the preferred class for sedation in critically ill pediatric patients. Amidst emerging concern regarding potential dexmedetomidine withdrawal in this population, recent evidence has supported the use of clonidine, another alpha-2 agonist, as a bridging agent to mitigate or prevent withdrawal. While some institutions may have implemented the use of clonidine in dexmedetomidine weaning, there is no consensus or validated protocol. This study aimed to examine the relationship between cumulative dexmedetomidine exposure and clonidine requirements and will expand upon a previous analysis at the study site that focused on a period prior to the SCCM guideline update.  

METHODS: This IRB-approved, single center, retrospective observational study focused on patients admitted to the PICU from January 2018 to May 2024. Inclusion criteria included receipt of a continuous dexmedetomidine infusion > 24 hours and enteral clonidine for treatment or prevention of dexmedetomidine withdrawal. Patients were excluded if they used clonidine prior to admission or if clonidine was initiated for an alternate indication. Included patients were divided into two groups – a non-escalation and an escalation group – based on whether the patient received an increase in their clonidine dose (at provider discretion). The primary outcome assessed the relationship between cumulative dexmedetomidine exposure and maximum required clonidine dose. Secondary outcomes included dexmedetomidine withdrawal assessment, rate of clonidine failure following initial clonidine dose, hospital and ICU length of stay, ventilator days, central line days, and incidence of tracheostomy placement.
 
RESULTS: Compared to the non-escalation group, the escalation group had a statistically significant increase in duration of dexmedetomidine (346.4 vs 284.3, p-value=0.0114) and increased cumulative dexmedetomidine dose (341.2 vs 230.8, p-value=0.0128). The difference in initial clonidine dose was not significant (5.7 vs 4.9, p-value=0.7928). The escalation group had a statistically significant increase in hospital LOS (36 vs 27.5, p-value=0.0355) and ICU LOS (27 vs 20.5, p-value=0.0426). There was no statistically significant difference in ventilator days, CVL days, or incidence of tracheostomy.  
 
CONCLUSION: Higher cumulative dexmedetomidine exposure is associated with higher clonidine dose requirements. Both hospital and ICU LOS were significantly decreased in patients who did not require an increase in their clonidine dose. Utilizing cumulative dexmedetomidine exposure to determine initial clonidine dose may be beneficial.