Hyperoxia in Pediatric Anesthesia and Critical Care Medicine
Ethan Sanford MD, Shawn Jackson MD PhD, Justin L. Lockman MD MSEd
Original Article:
Peters MJ, Gould DW, Ray S, Thomas K, Chang I, Orzol M, O'Neill L, Agbeko R, Au C, Draper E, Elliot-Major L, Giallongo E, Jones GAL, Lampro L, Lillie J, Pappachan J, Peters S, Ramnarayan P, Sadique Z, Rowan KM, Harrison DA, Mouncey PR; Oxy-PICU Investigators of the Paediatric Critical Care Society Study Group (PCCS-SG). Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial. Lancet. 2024 Jan 27;403(10424):355-364. doi: 10.1016/S0140-6736(23)01968-2.
At the most recent Society for Pediatric Anesthesia meeting, Dr. Patrick Ross gave a fantastic presentation on the anesthetic management of children with acute respiratory distress syndrome (ARDS). Subsequent discussions on social media mentioned today’s PAAD, the Oxy-PICU trial1, and questioned whether we should target low FiO2 or lower blood oxygen content in perioperative care. The question is apt. Hyperoxia is fascinating as a condition that was impossible until recent times (i.e., does not exist in nature). Humans have not adapted to this physiologic state; hyperoxia-induced reactive oxygen species are known to harm cellular function and impair cellular signaling. Data have accumulated suggesting worsened outcomes with hyperoxia in critically ill adults and children2. This presents a key question for our readership: is hyperoxia harmful for children receiving an anesthetic?
The Oxy-PICU trial is a pragmatic multicenter, open-label, randomized controlled trial of target oxygen saturation 88-92% (conservative group) versus >94% (liberal group) among children invasively ventilated for any reason except brain pathology, congenital heart disease, or pulmonary hypertension. The primary outcome was the degree of organ support required and utilized a score between 1 and 31 with death counting as a score of 31. Impressively, 1872 children were enrolled and split between conservative and liberal oxygen targets. 30-40% had bronchiolitis and (importantly for the PAAD readership) only ~5% were post-operative patients. The study achieved good separation in oxygen saturation and FiO2 between the conservative versus liberal oxygenation groups, meaning the intervention actually caused differences in management. However, ventilation parameters for the groups are not well delineated. A small difference in median days of organ support or death at 30 days was detected (5 [IQR 3-9] in conservative versus 5 [IQR 3 to 10] in the liberal group, P=0.04) which seems predominantly mediated by decreased time to extubation in the conservative group. No differences in mortality or PICU/hospital length of stay were detected. There was a significant reduction in health-care costs for the conservative oxygenation group.
We’ll admit that after an initial read of this abstract, we were excited to promote conservative oxygenation as the preferred strategy, but perioperative specific considerations may be warranted. The population studied was a large and heterogenous group of critically ill kids, making this study more generalizable than many earlier studies evaluating more focused populations (i.e., ARDS). While it is possible, perhaps even likely, that a greater difference could be found in more vulnerable children, even this diverse study group is very different than our perioperative children who present for elective surgery. The ICU study intervention was simple and executed in a pragmatic fashion, but most children with normal lung function will have high oxygen saturation on 0.21 FiO2. The question for these children is how much extra oxygen to give; it would be very tough to ever advocate for weaning oxygen below 21% to aim for <94% oxyhemoglobin saturation (even though at least one of us is old enough to remember doing that for single ventricle patients).
Finally, the positive results are most likely mediated by decreased time to extubating. This makes sense, targeting (or allowing) lower oxygen saturations should encourage more aggressive weaning of ventilator parameters for critically ill children, especially in the modern era of ventilator weaning pathways. While an important finding for PICU management, it’s unclear how applicable this outcome is to the perioperative space. The absence of data regarding other organ injury and no change in mortality may indicate minimal to no physiologic harm from hyperoxia even in the PICU population, let alone among healthy kids presenting for short procedural intubation.
So how are we, as perioperative experts, to integrate these results into our practice? Here are some considerations:
1) Lower oxygen saturation goals in critically ill children have not been found to cause harm, but do reduce hospital costs, and may lead to earlier extubation.
2) In children with ARDS, conservative oxygenation may improve clinical outcomes, though this data is primarily observational.
3) Increased FiO2 continues to be recommended as a strategy to minimize surgical site infections (SSI)3. However, SSIs occur infrequently in children and minimal data exist to support hyperoxia in prevention of pediatric SSI.
Interpreting these data, conservative oxygenation goals appear non-harmful for critically ill children who will require ongoing invasive ventilation post-operatively, especially for procedures with low SSI risk. Increasing minute ventilation parameters to increase oxygen saturation beyond a conservative goal is likely to only introduce more lung injury and cause harm. The effect of increasing FiO2 is unclear for a relatively short anesthetic in most patients.
For non-critically ill children, there is no evidence of harm from either hyperoxia or low FiO2, but there is reason to believe reactive oxygen species cause cellular harm. Oxygen saturation in the 94-99% range rather than maintaining 100% may help avoid high PaO2 which is likely unnecessary and unhelpful. Additionally, minimizing FiO2 may facilitate earlier detection of changes in lung function or endotracheal tube malposition/obstruction. High FiO2 tends to hide diminished compliance or changes in ventilation/perfusion matching. We tend to keep FiO2 low (<0.3) during the maintenance phase of anesthesia; in addition to the above, we find that any patient who cannot maintain normal saturations without higher oxygen supplementation warrant more thorough evaluation.
As always, it seems, there is no free lunch. We admit some comfort with a theoretical safety net of high FiO2/PaO2. Unfortunately, this may not serve our patients, especially those who are sick and at highest risk for organ injury. Regardless of how you interpret this data, you should know it and carefully select oxygen treatment rather than applying a “set it and forget it” strategy. Does your division or hospital system have a systematic approach to oxygen treatment? How do you interpret hyperoxia data? Send your thoughts and comments to Myron who will post in a Friday Reader Response.
References
1. Peters MJ, Gould DW, Ray S, et al. Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial. Lancet 2024;403(10424):355-364. DOI: 10.1016/S0140-6736(23)01968-2.
2. 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(1):e2142105. DOI: 10.1001/jamanetworkopen.2021.42105.
3. Meoli A, Ciavola L, Rahman S, et al. Prevention of Surgical Site Infections in Neonates and Children: Non-Pharmacological Measures of Prevention. Antibiotics (Basel) 2022;11(7). DOI: 10.3390/antibiotics11070863.