Welcome to March 2023 at Pediatric Critical Care Medicine (PCCM). There are three Editor’s Choices articles that each question established opinions and make us delve deeper into the relevant issues and potential implications for practice. The PCCM Connections for Readers focuses on biological mechanism–as a plea to our investigators and research authors, we do need to see more of this type of work at PCCM.
WHAT ABOUT CORTICOSTEROIDS IN SEPSIS AND SEPTIC SHOCK?
Klowak JA, Bijelic V, Barrowman N, et al; Genomics of Pediatric Septic Shock Investigators: The Association of Corticosteroids and Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II Biomarker Risk (1).
Are we any closer to solving the question of using corticosteroid therapy in children presenting with septic shock? In this retrospective study of almost 500 children separated into two categories using the PERSEVERE-II biomarker score, the authors tested whether there was an interaction between grouping, corticosteroid use, and outcome. Our editorial sets this information in a historical context, from 2009 to 2021 (2), and makes us think about precision medicine, endotypes, and the contemporary randomized controlled trial (RCT). This new article and editorial follow a theme in PCCM discussed in the September 2022 issue (3), and readers should review the authors’ other relevant work about the difficulty of RCTs in the septic shock population (4,5).
WHAT ABOUT THE COMPLEXITY OF FACTORS CONTRIBUTING TO OUTCOMES AFTER CARDIAC SURGERY?
Brown KL, Moinuddin M, Jones A, et al: The Relationship Between Postoperative Complications and Children’s Quality of Life: A Mediation Analysis to Explore the Role of Family Factors (6).
In this multicenter research from the United Kingdom, the authors identified a cardiac postoperative group with multiple morbidities and sought to identify a causal mediation analysis of parental health-related quality of life at 6 weeks after cardiac surgery, and their child’s quality of life at 6 months. Over 400 children contributed to the primary outcome and these new data add insight into the complexity of outcomes and the potential scope of psychological interventions to support parents of children who experience perioperative morbidities. Add this reading to the authors’ recent report on postoperative morbidities and neurodevelopment (7), and we are now building a more complete picture of how best to study late outcomes after critical illness (8,9).
WHAT ABOUT THE MEASUREMENT OF CEREBRAL NEAR-INFRARED SPECTROSCOPY IN PEDIATRIC CARDIAC PATIENTS?
Iliopoulis I, Cooper DS, Reagor JA, et al: Absolute Versus Relative Near-Infrared Spectroscopy in Pediatric Cardiac Patients (10).
My third highlighted article is an analysis of near-infrared spectroscopy (NIRS) data: the devices and the validity of the measurements that we use during clinical care (10). Please read the report and even though it’s not what we thought or taught, our editorial writers argue that NIRS monitoring in patients with complex congenital heart disease is here to stay (11). Also, go back to a little-known Letter to the Editor in the January 2006 issue of PCCM with its powerful insights. In the letter, Britton Chance (1913–2010), the American founder of biomedical photonics and National Medal of Science winner in 1974, wrote to PCCM on the topic of quantification of brain oxygenation in humans in vivo (12).
“PCCM CONNECTIONS” FOR READERS
This month there are two other areas of research that pick up on our previous themes. They are of particular interest because they address mechanism, and we need to understand clinical biology if we are to make progress in our field. The first topic is the endothelial glycocalyx. We have previously published a definitive review about the endothelial glycocalyx as a fundamental determinant of vascular permeability in sepsis (13), and a clinical research observation of glycocalyx degradation products contributing to metabolic acidosis following cardiopulmonary bypass (14). In a single-center research study from Colombia, the authors (same ones that wrote the previous PCCM definitive review) look at the time course of glycocalyx degradation in children with sepsis following a bolus of intravenous fluids (15). The article comes with an editorial (16).
The second topic is the morbidity of hyperoxia. In early 2022 we learned that there are 16 pediatric critical care studies with over 27 thousand patients that, collectively, suggests an association between hyperoxia and greater odds of mortality (17). We now have a mechanistic substudy nested within the pilot feasibility RCT of liberal versus conservative oxygenation targeting (i.e., pulse oximetry > 94% versus 88%−92%, respectively) (18). The authors report redox responses and gene expression of hypoxia-inducible factor 1a in the two oxygenation groups. Hopefully, their hypothesis will be tested in the now completed RCT of oxygen targeting and outcome in pediatrics (19).
Finally, another highlight for me is a narrative essay entitled “The Trip of a Lifetime” (20).
1. Klowak JA, Bijelic V, Barrowman N, et al.: Genomics of Pediatric Septic Shock Investigators: The association of corticosteroids and Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II biomarker risk. Pediatr Crit Care Med. 2023; 24:186–193
2. Zimmerman JJ: The classic critical care conundrum encounters precision medicine. Pediatr Crit Care Med. 2023; 24:251–253
3. Tasker RC: Editor’s choice articles for September. Pediatr Crit Care Med. 2022; 23:673–675
4. Kamps NN, Banks R, Reeder RW, et al.: The association of early corticosteroid therapy with clinical and health-related quality of life outcomes in children with septic shock. Pediatr Crit Care Med. 2022; 23:687–697
5. Menon K: Association between early corticosteroids, pediatric septic shock, and outcomes: Not a simple analysis. Pediatr Crit Care Med. 2022; 23:749–751
6. Brown KL, Moinuddin M, Jones A, et al.: The relationship between postoperative complications and children’s quality of life: A mediation analysis to explore the role of family factors. Pediatr Crit Care Med. 2023; 24:194–203
7. Read J, Ridout D, Johnson S, et al.: Postoperative morbidities with infant cardiac surgery and toddlers’ neurodevelopment. Arch Dis Child. 2022; archdischild-2021-322756
8. Verlinden I, Guiza F, Dulfer K, et al.: Physical, emotional/behavioral, and neurocognitive developmental outcomes from 2 to 4 years after PICU admission: A secondary analysis of the early versus late parenteral nutrition randomized controlled trial cohort. Pediatr Crit Care Med. 2022; 23:580–592
9. Pinto NP, Maddux AB, Dervan LA, et al.: A core outcome measurement set for pediatric critical care. Pediatr Crit Care Med. 2022; 23:893–907
10. Iliopoulis I, Cooper DS, Reagor JA, et al.: Absolute versus relative near-infrared spectroscopy in pediatric cardiac patients. Pediatr Crit Care Med. 2023; 24:204–212
11. Rossi AF, Khan DM: Near infrared spectroscopy for monitoring patients with complex congenital heart disease is here to stay. Pediatr Crit Care Med. 2023; 24:254–256
12. Chance B: Quantification of brain oxygenation in humans in vivo. Pediatr Crit Care Med. 2006; 7:93
13. Fernandez-Sarmiento J, Salazar-Pelaez LM, Carcillo JA: The endothelial glycocalyx: A fundamental determinant of vascular permeability in sepsis. Pediatr Crit Care Med. 2020; 21:e291–e300
14. Bangalore H, Carter MJ, Parmar K, et al.: Degradation of the endothelial glycocalyx contributes to metabolic acidosis in children following cardiopulmonary bypass surgery. Pediatr Crit Care Med. 2021; 22:e571–e581
15. Fernandez-Sarmiento J, Salazar-Pelaez LM, Acevedo L, et al.: Endothelial and glycocalyx biomarkers in children with sepsis after one bolus of unbalanced or balanced crystalloids. Pediatr Crit Care Med. 2023; 24:213–221
16. Branco RG: Balancing fluid resuscitation in pediatric sepsis. Pediatr Crit Care Med. 2023; 24:257–259
17. Lilien TA, Groeneveld NS, van Etten-Jamaludin F, et al.: Association of arterial hyperoxia with outcomes in critically ill children: A systematic review and meta-analysis. JAMA Netw Open. 2022; 5:e2142105
18. Jones GAL, Eaton S, Orford M, et al.: Randomization to a liberal versus conservative oxygenation target: Redox responses in critically ill children. Pediatr Crit Care Med. 2023; 24:e137–e146
19. Chang I, Thomas K, O’Neill Gutierrez L, et al.: Protocol for a randomized multiple center trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): Oxygen in pediatric intensive care. Pediatr Crit Care Med. 2022; 23:736–744
20. Bybee JA: The trip of a lifetime. Pediatr Crit Care Med. 2023; 24:243–244