The Opioid Conundrum: Balancing Pain Management and Neurodevelopmental Outcome after Pediatric Cardiac Surgery
Viviane Nasr, Susan Nicolson, Lindsey Loveland, James DiNardo
Before you read today’s PAAD, I’d like to take a moment and send my best wishes to all of our readers for a Happy Halloween and Diwali! This is an unusual day because for the first time that I can remember, Halloween and Diwali overlap. Although they celebrate entirely different things — Halloween the dark and the spooky, Diwali the light and the good they both are celebrations that are just so much fun! If you have pictures you’d like to share of yourselves or of your group in costume please send the JPEGs to me and I will be happy to post…Myron Yaster MD
Today’s by O'Byrne et al1 and its accompanying editorial by Kheir et al.2 was reviewed by the PAAD’s congenital cardiac executive council members who were also involved as senior authors in these articles. The use of high dose opioids and benzodiazepines as well as other anxiolytics, hypnotics and analgesics in the PICU and NICU is not limited to patients with congenital heart disease and remains a therapeutic conundrum for almost every patient in the pediatric ICUs, especially those who are intubated. Not often discussed is why patients in the ICUs require so much drug to produce immobility, sedation, and analgesia in the first place and why the doses used to produce these effects escalate so rapidly. As discussed in several previous PAADs, Dr. Sapna Kudchadkar at Johns Hopkins has theorized that the drugs we use to produce sedation, analgesia and immobility interfere with sleep architecture and the loss pf restorative sleep produces delirium.3,4 Perhaps much of the dose escalation is a response to our initial therapeutic maneuvers or what I like to call “iatrogenesis imperfecta”. She and her colleagues offer simpler approaches like getting children mobilized from bed early and earlier tracheostomy as alternatives. We will continue to highlight these issues in future PAADs. Myron Yaster MD
Original article
O'Byrne ML, Baxelbaum K, Tam V, Griffis H, Pennington ML, Hagerty A, Naim MY, Nicolson SC, Shillingford AJ, Sutherland TN, Hampton LE, Gebregiorgis NG, Nguyen T, Ramos E, Rossano JW. Association of Postnatal Opioid Exposure and 2-Year Neurodevelopmental Outcomes in Infants Undergoing Cardiac Surgery. J Am Coll Cardiol. 2024 Sep 10;84(11):1010-1021. doi: 10.1016/j.jacc.2024.06.033. PMID: 39232628.
Editorial
Kheir JN, Smith TM, DiNardo JA. Pediatric Sedation Gets a Wake-Up Call. J Am Coll Cardiol. 2024 Sep 10;84(11):1022-1024. doi: 10.1016/j.jacc.2024.06.034. PMID: 39232629.
Children in pediatric intensive care units (PICUs) often experience discomfort caused by pain, fear, and anxiety.5,6 Common stressors include being away from family and their home environment, apprehension toward medical equipment and procedures, as well as constant disturbances like noises and alarms, which can impede sleep. This anxiety may necessitate sedation. Pain can arise from surgical interventions or medical procedures, such as suctioning, repositioning, insertion of intravascular catheters or removal of chest tubes. Effectively managing pain and anxiety in these young patients is complicated by the risks related to under- or overtreatment. Insufficient management of pain can lead to behavioral changes and physiological stress responses that might slow healing and stress both patients and their caregivers. Conversely, excessive treatment may prolong recovery, increase the risk of developing drug tolerance, and/or lead to potential withdrawal symptoms upon discontinuation which may be detrimental to neurodevelopment.
In today’s PAAD, a single-center retrospective cohort study was conducted, analyzing data from all consecutive infants under one year of age who underwent heart surgery at the Children’s Hospital of Philadelphia from January 1, 2011, to June 30, 2022.1 Neurodevelopmental assessments were carried out within six months of their second birthday. Infants who had undergone specific procedures such as the ligation of a patent arterial duct, ventricular assist device insertion, or heart transplantation, or those transferred with prior surgeries or lacking follow-up, were excluded from the study.
The objective of the research was to examine the correlation between cumulative exposure to opioids during hospital stays (both OR and ICU) I in the first year of life and subsequent neurodevelopmental outcomes.7,8 The primary measure of neurodevelopment utilized the Bayley Scales of Infant and Toddler Development – Third and Fourth Editions (Bayley-III/IV). Of the 2,735 neonates and infants who underwent surgery within the study period, 526 met the inclusion criteria. The study found that higher cumulative opioid exposure was linked to poorer neurodevelopmental performance at two years, with negative impacts on cognitive, language, and motor skills after accounting for various other influential factors.
This retrospective study has several limitations including selection bias, limited ability to disentangle potential covariates, poor prognostication about ultimate neurodevelopmental outcomes using Bayley’s testing at 2 years of age, the unique practices at a single center and the fact that correlation is not causation.
Despite the limitations the finding highlights the importance for healthcare teams in PICU settings to consider the impact of opioid use, particularly after surgery for congenital heart lesions.
Several strategies to optimize opioid exposure are outlined in an accompanying editorial2 include:
1. Standardizing and continuously refining analgesia and sedation protocols in ICU settings to reduce drug exposure and improve patient comfort, while minimizing withdrawal symptoms, delirium, and promoting early mobility and rehabilitation. Despite evidence showing benefits, such as lowered opioid use and shortened mechanical ventilation, maintaining adherence to protocols is challenging.
2. Only a fraction of morphine doses post-surgery lead to improved comfort for the patient. By documenting individual patients' responses to sedatives or employing predictive models for drug reactions, unnecessary medication exposure might decrease.
3. Objective and validated measures for assessing sedation levels must be enhanced in clinical trials, potentially using tools like electroencephalography, heart rate variability, or movement monitoring technologies.
4. Non-pharmaceutical interventions tailored to each child's developmental stage should be emphasized in care routines to promote comfort and potentially decrease the need for sedatives. These can include measures such as limiting disruptive environmental stimuli, incorporating parental voices, gentle physical contact like swaddling, and clustering interventions to minimize the number of disruptions.
As Dr. Shafer eloquently remarked in a previous PAAD, completely eliminating opioids is not a practical goal nor is it compassionate. The aim should be to manage pain through alternative means such that the need for opioids during hospital stay is minimized and that their administration can be promptly discontinued when they no longer provide any therapeutic benefit.
Send your thoughts and comments to Myron who will post in a Friday Reader response.
References:
1. O'Byrne ML, Baxelbaum K, Tam V, et al. Association of Postnatal Opioid Exposure and 2-Year Neurodevelopmental Outcomes in Infants Undergoing Cardiac Surgery. Journal of the American College of Cardiology 2024;84(11):1010-1021. (In eng). DOI: 10.1016/j.jacc.2024.06.033.
2. Kheir JN, Smith TM, DiNardo JA. Pediatric Sedation Gets a Wake-Up Call. Journal of the American College of Cardiology 2024;84(11):1022-1024. (In eng). DOI: 10.1016/j.jacc.2024.06.034.
3. Ista E, Redivo J, Kananur P, et al. ABCDEF Bundle Practices for Critically Ill Children: An International Survey of 161 PICUs in 18 Countries. Critical care medicine 2022;50(1):114-125. (In eng). DOI: 10.1097/ccm.0000000000005168.
4. Berger J, Zaidi M, Halferty I, Kudchadkar SR. Sleep in the Hospitalized Child: A Contemporary Review. Chest 2021;160(3):1064-1074. (In eng). DOI: 10.1016/j.chest.2021.04.024.
5. Lucas SS, Nasr VG, Ng AJ, Joe C, Bond M, DiNardo JA. Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care: Sedation, Analgesia and Muscle Relaxant. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2016;17(3 Suppl 1):S3-s15. (In eng). DOI: 10.1097/pcc.0000000000000619.
6. Nasr VG, DiNardo JA. Sedation and Analgesia in Pediatric Cardiac Critical Care. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 2016;17(8 Suppl 1):S225-31. (In eng). DOI: 10.1097/pcc.0000000000000756.
7. Simpao AF, Randazzo IR, Chittams JL, et al. Anesthesia and sedation exposure and neurodevelopmental outcomes in infants undergoing congenital cardiac surgery: a retrospective cohort study. Anesthesiology 2023 (In eng). DOI: 10.1097/aln.0000000000004684.
8. Andropoulos DB, Ahmad HB, Haq T, et al. The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study. Paediatric anaesthesia 2014;24(3):266-74. (In eng). DOI: 10.1111/pan.12350.