Profiling the metabolic response to traumatic brain injury (TBI) has been reported for decades. In 1984, Clifton et al (1) reported a hypermetabolic response by indirect calorimetry (IC) in adults with TBI compared with healthy adults. Since that time, our understanding of the metabolic response has evolved. Brain injury can induce activation and dysregulation of metabolic, inflammatory, and neuroendocrine systems (2). The modern approach to therapy in children with TBI is aimed at decreasing metabolic demand and preventing cerebral hypoperfusion to limit secondary brain injury (3). This approach counteracts hypermetabolism, yet the net effect remains unknown. Reports have also showed hypometabolism after pediatric TBI (4). Given that the metabolic response varies between each individual child, generalizations are often inaccurate. An individualized assessment is likely necessary.

Energy is essential to maintain growth and support reparative functions during acute illness. It is encouraging that nutrition is being initiated earlier (within 48–72 hr) in patients with TBI to support caloric needs and recovery (5). However, how much should we be feeding these patients? We know that underfeeding and overfeeding critically ill patients can affect patient outcomes, but calculating proper energy prescription can be a moving target. To date, there are no reliable methods of energy expenditure estimations that provide both validity and precision.

In an ideal framework, measured resting energy expenditure (mREE) by IC would be desirable in all patients with TBI, through sampling of oxygen consumption and carbon dioxide elimination from modern ventilators (6,7). This remains the current recommended gold standard (8,9). However, despite decades of work in the field of metabolism and energy expenditure, the widespread clinical application of IC has not been realized. Limited resources and outdated technology have prevented rapid progress in this area. There has yet to be a randomized controlled trial showing improved outcomes with an IC-driven nutrition prescription strategy. Despite best efforts, predicting energy expenditure in the acutely ill child is fraught with error and often inaccurate. Predictive equations were derived in healthy children, often use static variables for estimation and are historically inaccurate in critically ill children. A recent updated validation of 16 predictive equations to estimate resting energy expenditure (REE) compared with mREE in 153 critically ill children reported wide inaccuracy in measurements (10). Yet, it remains the best alternative option when IC is not available.

There now appears to be a renewal of energy in the science of IC. New technology may make routine IC measurements more feasible. There are also an increasing number of published reports focusing on special populations in the PICU. In a recent single center, prospective pilot study, seven children receiving extracorporeal membrane oxygenation (ECMO) support had IC measurements on day 2 of ECMO and before discontinuation of support (11). Children receiving ECMO for septic shock were vastly more hypermetabolic than the rest of the ECMO cohort (measured/predicted REE ranging from 270% to 450%). All children had a reduction in mREE before decannulation from ECMO. This data is consistent with known hypermetabolism on ECMO. Yet, there was a wide variability in mREE among all patients and predictive equations would have resulted in profound underfeeding in the septic shock cohort. Even in this therapy-specific pilot, there was no generalizable metabolic response. Examining these special populations may give us the information necessary to move toward a more tailored approach.

In this issue of Pediatric Critical Care Medicine, a report by Beggs et al (12) provides an important addition to our understanding of the metabolic response to TBI. In this retrospective case-series study, the authors analyzed 34 studies from 26 patients who underwent IC testing. Although this was a small sample (10%) of the 245 patients admitted with moderate or severe TBI during the study period, it is understandable given the already known challenges of obtaining IC measurements in the PICU. Despite this limitation, the study provides a wealth of informative data on pediatric patients with TBI.

There was wide variability in metabolic state among children in the study by Beggs et al (12) with no trend in either direction. The median time of IC testing was on day 3 of admission, with most patients tested between days 3 and 17. When interpreting the results, it is helpful to know that patients were tested at different points of illness, had varying degrees of TBI severity, more than half of patients (56%) had total body cooling, and patients had varying degrees of sedation. Only one patient received neuromuscular blockade (NMB). Overfeeding or underfeeding occurred in 97% of patients receiving nutrition therapy based on predicted REE, with 58% of patients classified as underfed. In 10 patients who were overfed (intake > 110% mREE), eight patients were hypometabolic (mREE < 90% predicted). Actual energy intake matched mREE (within 10% variability) in only one patient. Many patients (62%) were receiving enteral nutrition at the time of IC testing, representing early initiation of nutrition therapy. Only two patients received parenteral nutrition (PN).

There were notable differences in the study by Beggs et al (12) compared with a previous similar study by Mtaweh et al (4) in 2014. The study by Mtaweh et al (4) found that mREE was 70% of estimated REE by the Harris-Benedict and Schofield equations. All patients in the study by Mtaweh et al (4) received NMB and almost all patients received PN. This is an important historical study, given the limited IC data in children with TBI. The addition of the study by Beggs et al (12) provides renewed data that reflects our current management approach based on updated guidelines (3,8,9).

As we look forward, there are several areas to consider as priorities in the metabolic assessment of critically ill children. First, we need a better understanding of how energy expenditure changes throughout the evolution of illness (13). We should work to prioritize identifying high-risk patients to collect serial measurements during an ICU stay. In an adult study published in 2020, serial IC measurements were recorded every 72 hours in adult patients mechanically ventilated due to acute COVID-19 infection (14). Patients were found to have a profound, delayed wave of hypermetabolism that eventually resolved. This would have been unrecognized without serial measurements during the rise and fall of the inflammatory response. In the next phase of understanding the metabolic response to critical illness, IC should be a central focus. Future studies in children should describe longitudinal measurements over the course of an ICU admission. This will require a multidisciplinary approach, beginning with an investment in our dietitians. This renewed focus will be a necessary component in providing tailored, individualized therapy based on the unique metabolic profile of each child.

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