Surgery, anesthesia and TBI outcomes: Lions and tigers and bears, Oh My!
Kumaran Senthil, MD, Myron Yaster MD, Justin L. Lockman, MD MSEd
“The world is full of obvious things, that no one ever sees.” – Sherlock Holmes
Original article
Roberts CJ, Barber J, Temkin NR, Dong A, Robertson CS, Valadka AB, Yue JK, Markowitz AJ, Manley GT, Nelson LD; Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) Investigators; Badjatia N, Diaz-Arrastia R, Duhaime AC, Feeser VR, Gopinath S, Grandhi R, Jha R, Keene CD, Madden C, McCrea M, Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study. JAMA Surg. 2023 Dec 13:e236374. doi: 10.1001/jamasurg.2023.6374. Epub ahead of print. PMID: 38091011; PMCID: PMC10719833.
Editorial
Collins CR, Campbell A. Surgery, Anesthesia, and TBI Outcomes-Unraveling the Complex Interplay. JAMA Surg. 2023 Dec 13. doi: 10.1001/jamasurg.2023.6371. Epub ahead of print. PMID: 38091018.
Today’s PAAD1 (and accompanying editorial2) is a retrospective secondary analysis of adults (42.2 +/- 17.8 years of age) who underwent extracranial surgery and anesthesia during the acute phase of mild to severe traumatic brain injuries (TBI). The investigators found an association between exposure to extracranial surgery (and anesthesia) and worse functional outcomes 6 months later among patients with either moderate/severe TBI or mild TBI with CT positive findings (based on NINDS consensus). These data are compelling and fit into a schema that many support: the brain is vulnerable after injury, and additional surgical stress, anesthetic exposure or associated hemodynamic perturbations can worsen neurocognitive and functional outcomes.
Albeit enticing, we must be careful about drawing causal conclusions from these data. There are always limitations of a retrospective analysis, and in this case the authors identification of their own inability to balance even the known covariates, not to mention any unknown confounders. As easily as we can say that extracranial surgery (and all things associated with it) can lead to neurocognitive and functional decline after TBI, we could also posit that this is another example of “confounding by indication” and that trauma patients who require extracranial surgeries are just… sicker/more complex. Nevertheless, these results were the first human data to demonstrate “worse functional and cognitive outcomes associated with exposure to extracranial surgery and anesthesia after TBI,” which is a powerful and important finding.
Traumatic brain injury follows a two-stage pathophysiologic framework. The primary injury is the direct physical injury to the brain leading to tissue deformation, axonal shearing, and blood brain barrier disruption. Secondary injury occurs over minutes to days after the initial insult and affects numerous pathways, invoking mitochondrial dysfunction, oxidative injury and neuroinflammation. Because primary injury can only be prevented rather than treated, neuroprotective strategies aim to minimize secondary injury, including strict adherence to physiologic parameters to maintain adequate cerebral blood flow, avoid intracranial hypertension, minimize hypoxemia and hypoglycemia, and modulate cerebral oxygen consumption. Control of these physiologic parameters are important targets to guide our anesthetic clinical care when we care patients with acute traumatic brain injuries.
Notably, Roberts et al. looked only at patients undergoing surgery. This paper was, after all, published in the journal JAMA Surgery! On the other hand, in pediatric anesthesia and critical care medicine, we routinely anesthetize patients with all sorts of acute TBIs, including sports-related concussions, for myriad medical and radiologic procedures as well as for patients undergoing extracranial surgery. Indeed, we often routinely anesthetize TBI patients for diagnostic imaging studies as part of their diagnostic workups! Should we? Is it safe? Are we making things worse? And what about in the ICU, where these patients often receive sedation/anesthesia for days or even weeks?
The results of this study make a strong case to investigate the effect of single or repetitive anesthetic exposures after traumatic brain injury in the pediatric population. Prospective clinical trial study design focusing on severe TBI will be difficult due to the urgent or emergent nature of most surgeries and anesthetic exposure, but this question may lend itself to study in a high fidelity pre-clinical large animal model.
A specific target for study in humans could be the post-concussion sports injury population and patients undergoing diagnostic imaging studies following TBI. Should we use general anesthesia? Should we control ventilation and prevent hypo-or hypercarbia? What blood pressures should we target assuming that for many there is a loss of autoregulation? We simply do not know - but we should and hopefully in the future we will. We are counting on SPA members to collaborate and help answer these questions.
This exciting study is not equipped to say that extracranial surgeries and anesthetics cause worsening functional neurologic outcomes, but it sure makes for an exciting opportunity for a career of pre-clinical and clinical study. Ultimately, a better understanding of both the window of neuronal vulnerability after a traumatic injury and of which factors actually worsen injury and lead to worsened functional outcome would have an immense impact on how we treat pediatric TBI patients in the operating rooms and the intensive care units, and we anticipate this time is coming (eventually).
What do you think? Is it time for form a multi-institutional collaborative to answer this question? Should we be refusing to anesthetize patients for “elective” repair of fractures after TBI? What is your threshold for postponing surgery after a sports concussion? Send your thoughts to Myron at MYasterster@gmail.com and he’ll post in a Friday Reader Response.
References
1. Roberts CJ, Barber J, Temkin NR, et al. Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery: A TRACK-TBI Study. JAMA surgery 2023.
2. Collins CR, Campbell A. Surgery, Anesthesia, and TBI Outcomes—Unraveling the Complex Interplay. JAMA surgery 2023.