When Is Air Travel Safe after Mild Traumatic Brain Injury/Sports-Related Concussion?

Abstract

While the literature regarding return to play and recovery protocols from mild traumatic brain injury (mTBI) and sports-related concussions (SRC) is growing, there continues to be a paucity of data regarding when air travel is safe for athletes after sustaining certain brain injuries, such as mTBI and SRC. Although it is known hypoxia can negatively affect severe TBI patients, it is unclear whether mild hypoxia, which may be experienced during commercial air travel, is clinically significant for athletes who have recently sustained mTBI injuries. Further research is required to provide more standardized recommendations on when air travel is safe. With the current available literature, clinicians still need to weigh the evidence, consider how it applies to each individual patient, and engage in shared decision making to ultimately decide what is best for the patient.

Introduction

It is well known that severely brain injured patients are susceptible to a variety of pathologic states, such as brain edema, hypoxia, hypotension, and systemic inflammatory states that may worsen immediate and long-term outcomes. However, there is still an overall lack of understanding of the nuances pertaining to milder derangements in the setting of mild traumatic brain injury (mTBI) (^1,2). Because of known detrimental effects of hypoxia on severe TBI patients and plausible concern of the negative impacts of hypoxia in mTBI, hypobaric hypoxia must be considered. Hypobaric hypoxia is the phenomenon of low atmospheric/barometric pressure and consequential reduction in the partial pressure of oxygen (PO₂), similar to what is experienced at high elevation (³). This can occur during flight in commercial airlines even in pressurized cabins. There is some evidence to suggest that hypoxic conditions can unmask deficits associated with prior mTBIs during cognitive testing when compared with individuals who have never had a brain injury. However, there is very little evidence to suggest what air travel and/or mild hypoxic conditions can do to a recently injured brain when it comes to symptom duration, severity, and long-term effects on recovery and brain function and how this may relate to an athlete's ability to return to play (^4,5). Currently, the CDC's Head's Up Concussion initiative outlines a set of guidelines for return to play progression after concussion in athletes but currently there is no similar stepwise algorithm to guide the decision on timing for air travel after mTBI based on symptomatology nor serology. There are some biomarkers being studied, which may 1 d be predictive of severity of TBI and may help guide both return to air travel and return to play algorithms, which will be discussed. This article reviews the relevant research literature regarding air travel, mild hypoxia, mild traumatic brain injury, serum biomarkers in TBI, and considers existing return to play guidelines and duration of recovery period.

Evidence

An online medical subheadings (MeSH) literature review was conducted searching the terms “brain concussion, air travel, and hypoxia” in PubMed. There is very little research directly addressing the question of timing of air travel after TBI and the risks, if any, are associated with flight at any time after mild brain injury.

Discussion

Because of the known detrimental effects of hypoxia and hypoperfusion on the critically brain injured patient especially within the first 6 h after injury, one of the major points to be considered regarding air travel is hypobaric hypoxia. This is a small risk passengers assume when flying on pressurized commercial airlines (⁵). In healthy adults, this potential mildly decreased blood oxygen saturation appears to be nearly always clinically insignificant (³). According to the Federal Aviation Regulations, the equivalent effective cabin altitude of most airlines, also known as the cabin altitude, has a regulatory maximum of 8000 ft. In one study, peak cabin altitude during commercial air travel was 6341 ± 1813 ft, and is usually lower with flights of shorter distance, with up to 70% of flights achieving cabin altitude of less than 5000 ft on flights less than 500 miles (³). Flying altitudes can be as high as 39,000 ft but on average, the in-cabin altitude is about 5000 to 6000 ft and corresponds to a fraction of inspired O₂ between 15% and 17%, compared with 21% at sea level (⁶). In a study of 84 passengers, the mean SpO₂ at ground level was 97% and at cruising altitude (mean in-cabin altitude of 6214 ft) the mean SpO₂ was 93% without any significant change in pulse rate. While this difference in passenger SpO₂ may seem significant, in young healthy populations, it does not seem to lead to noticeable physiologic changes. This is in large part due to the characteristics of the oxygen dissociation curve (^3,7).

There are many components to the question “when is air travel safe after a mild TBI?” that make it difficult to answer. There are no completely objective measures of brain injury such as imaging nor blood biomarker assays that reliably predict severity, expected symptomatology, and/or prognosis in mTBI patients. In addition, added variables such as air travel and possible hypoxia, which will likely never be studied in a randomized controlled manner, make it all the more difficult to answer the question of interest. There are a variety of widely used clinical assessment tools aiming to measure somatic and psychiatric symptoms, such as the Sport Concussion Assessment Tool 5th edition, the Standardized Assessment of Concussion, and the Brief Symptom Survey. Unfortunately, there is no way to objectively measure inherently subjective scores. In addition, reliability of athletes self-reporting symptoms is often not consistent. The scoring tools are dependent on many possibly confounding variables such as concussion knowledge, pressure to continue playing, and roster spot. Athletes often lack the insight to understand the potential long-term ramifications of repeat brain injury and/or failing to have attained complete recovery before returning to sport (⁸). In addition, high-level athletes often have various perceived pressure to continue performing at a high level. This is likely confounded by gaps in concussion education for athletes, coaches, and the entire interdisciplinary athletic team. This pressure to continue training and competing despite persistent concussion symptoms may be external. Families, coaches, fans, and/or teammates often play a large role as well. This desire to continue despite persistent symptoms also may be internally driven by potential loss of competitive opportunities and isolation from the team. If an athlete has previously experienced these negative psychosocial effects from previous SRC, this also makes them less likely to report symptoms in the event of another future concussion (⁸). It has been shown in many retrospective studies athletes underreport postconcussive symptoms across somatic, cognitive, and psychiatric symptom domains after sustaining a concussion, and their subjective reporting is not consistent with their objectively diminished performance on cognitive testing (^9–12). There are slightly more concrete measures used to assess concussion, such as balance testing and memory recall, but even the Balance Error Scoring System may have limited clinical utility in trying to diagnose severity of mTBI, especially in adolescents (¹³). To date, we do not seem to have reliable and accurate ways to measure nuances related to severity of various mTBIs, expected symptoms, and prognosis after concussion but the clinical tools listed above at least do aid physicians in making the diagnosis. We have even less data to prove when the timing of air travel after mTBI is safe, and therefore we are left with clinical gestalt, a small literature base, and joint decision making between the clinician and the patient in determining if air travel is safe immediately following mTBI.

There are some observational data indicating early air travel after SRC leads to longer recovery time. In an abstract presented at the IOC World Conference on Prevention of Injury and Illness in Sport in 2014, Milzman et al. (¹⁴) report National Hockey League (NHL) players who flew after suffering mTBI within 6 h of injury missed 32.9% more games than those who did not fly during that time period. It has been hypothesized this discrepancy is possibly due to lack of brain rest following injury and likely increased concussion penumbra in the setting of decreased oxygen tension that may be experienced during the pressurized cabin flight (¹⁴). This study is limited by the fact that it is a single-center study of 239 hockey players over three seasons. Oxygen saturations of the athletes were not measured while in flight, and there is no mention of the distance traveled. Therefore, it is only theoretical that there was decreased oxygen tension while in flight, especially considering shorter flights (<500 miles) reach a cabin altitude of less than 5000 ft 70% of the time. This elevation rarely leads to clinically significant decreases in peripheral oxygen saturation of any clinical significance (³). In addition, the NHL schedule has a higher frequency of games played, and therefore, a potential to miss a higher number of games within a given period. This is in contrast to American football for instance, which tends to have one game per week. However, the time frame of flight within 6 h of injury is of particular interest. Almost all published literature addresses flight within <72 h of travel but does not discuss the differences between immediate air travel (such as travel within 6 h after injury) versus delayed air travel (such as flight after 6 h). This may be particularly relevant to Division 1 collegiate football players who often fly home on the same day the game was played, often within less than 6 h of finishing the game in which they suffered a SRC. This may have specific implications on challenges with return to learning, as athletes would fly back within hours of sustaining a SRC and potentially be expected to report to educational requirements within 2 d, at the start of the week. High school and collegiate education uses increasing amounts of screen time for schooling, which can be a major contributor to duration of recovery (¹⁵). In addition, although there is evidence to support sleep disturbances are common in athletes after sports-related concussion, there are no studies specifically addressing if symptoms of concussion are worsened by altering the sleep cycle within 6 h of the injury (¹⁶). It is plausible if the athlete flies home late in the evening immediately after a SRC was sustained and causes a disturbance in their normal sleep cycle, symptoms may be exacerbated. However, there is no literature to support this hypothesis, and the downfalls of preventing the athlete from flying home with the team may outweigh the theoretical benefit. Expecting the athlete to have quality sleep in a hotel room, delaying travel, and incurring added expenses that go along with this delayed travel simply to reduce sleep disturbances is not yet grounded in evidence. The hypothesis of decreased oxygen tension and its effect on the recently injured brain mentioned in the Milzman study does have some merit and should be considered; theories exist regarding the postconcussive brain's vulnerability to hypoxic stress, based in part from studies performed by Ewing et al. (¹⁷) in 1980 and a similar study by Temme et al. (⁴) in 2013. In these studies, various cognitive tests were performed on previously brain injured individuals and control subjects who had never sustained TBI. Their results suggest at higher elevations, and therefore lower FiO₂, subjects with previously injured brains performed worse than their matched controls, unmasking cognitive deficits that could possibly be attributed to prior brain injury (^4,17). Unfortunately, these studies were not performed in the “recently” injured brain, with the median interval between the mTBI and participation in this study of 1.9 years (mean, 3.1 years) (⁴). The smallest time interval was 0.6 years and therefore, when trying to extrapolate this information on return to flight and the acute phase after mTBI, it becomes more challenging.

Furthermore, various types of brain imaging modalities may be considered. Noncontrasted head computed tomographies (CTs) and standard magnetic resonance imagings (MRIs) do not reveal abnormalities in SRC. Despite an absence of definitive brain imaging diagnostic criteria in mTBI, Hofman et al. (¹⁸) used single positron emission CT to evaluate brain perfusion. This revealed 40% of patients had perfusion abnormalities occurring more frequently in patients with multiple mTBIs. This included a significant relationship between basal ganglion hypoperfusion and the incidence of post concussive headache (^5,18). In a study by Vacchiano and Silva (⁵), researchers aimed to describe cerebral oxygen saturation values in patients with mTBI compared with those without history of TBI while breathing both room air and reduced oxygen concentration during cognitive activity. This study suggests there may be a vascular component to mTBI and exposure to hypoxic environments may unmask latent cognitive deficits in individuals with previous mTBI, but does not indicate how exposure to hypoxic environments in the immediate hours following a mTBI may affect long term outcomes (⁵). Likewise, in a study by Mutch et al. (¹⁹), the authors address the real need for quantifiable neuroimaging biomarkers in concussion and outline a blood oxygenation level-dependent (BOLD) MRI CO₂ stress test to assess the condition. In this study, researchers demonstrated a provocative CO₂ challenge during BOLD MRI showed abnormal cerebrovascular responsiveness to CO₂ in concussion patients. Some patients with symptomatic postconcussive syndrome expressed hyporesponsiveness to CO₂, while a subset expressed hyperresponsiveness. Ultimately, whole brain BOLD cerebrovascular resistance did not significantly differ between concussion patients and control subjects and is not something readily available for most athletes. Regardless, alveolar pCO₂ differences at sea level versus at cruising altitude are negligible, with pCO₂ at sea level measuring about 40 mm Hg compared with 38 mm Hg at cruising altitude (²⁰). Although this certainly requires more research before it can be used as a prognostic indicator, we also must consider the difficulty of extrapolating these data to recently brain injured athletes. This study does not address the subjects' duration of time since the mTBI; it is only stated the concussion occurred within the last 12 months. When considering the decision of when to fly after concussion, we are often in the acute period of less than 2 wk and even more likely to be discussed within the first 24 h after injury. There are even less data on brain imaging within the acute phase after mTBI. Unfortunately, we are still not able to reliably use imaging tools as a way to screen who can safely fly on a plane because there are still no validated and readily available imaging techniques used in the diagnosis of SRC or mTBI.

Following severe TBI, the damage sustained at the time of the initial injury is known as the initial TBI. In the context of critical brain injury, the phenomenon of secondary TBI must be considered, which is characterized by the injury pattern over the next several days and can be influenced by a variety of factors, one of which is hypoxia (²). However, the pathophysiology of mild TBI compared with critical brain injury is vastly different and relatively healthy young athletes experiencing hypoxemia on a commercial flight flying at an average cabin altitude of 5000 to 6000 ft is quite unlikely. In one study by Muhm et al. (²¹), hypobaric conditions like those experienced in commercial airlines only decreased oxygen saturation by 4%, which is often not clinically significant and was not even enough to cause symptoms of acute mountain sickness (AMS) or other discomfort. Similarly, another study showed an average difference of SpO₂ of 5% when comparing sea level oxygenation to cabin altitude of 5000 to 6000 ft (⁷). Although the rate of ascent is one important factor in the development of AMS, symptoms usually do not develop until after a few hours and are rapidly relieved by descent (²²). With domestic flights, it is plausible that concussion symptoms of headache, dizziness, or nausea could be exacerbated, but the duration of the majority of these flights seems unlikely to allow much time for these symptoms of AMS to compound concussion symptoms. Young healthy athletes also are likely to be able to tolerate the rapid acclimatization and physiologic changes induced by air travel and have been shown to have no significant change in pulse rate while in flight. In addition, the sedentary nature of air travel is unlikely to pose increased risk of any significant hypoxia or excessive physiologic demand, which would lead to negative neurologic outcomes (^3,7). Exposure to hypoxic insult shortly after a TBI may not lead to noticeable adverse outcomes in the moment, but could early air travel ultimately be causing longer-term negative outcomes yet to be measured or identified? With the available literature, it seems that although hypoxemia can unmask some cognitive deficits in mTBI patients but when the hypobaric exposure is removed, they return back to their normal baseline and remain this way. This suggests that these conditions may only exacerbate symptoms temporarily without long-term sequelae (⁷). In addition, in another study published by Sharma et al. (²³) in the 2019 Sports Concussion Abstracts, the question of the time period between the initial mTBI and air travel was investigated more directly. This prospective cohort of 3480 National Collegiate Athletic Association athletes and United States Armed Forces Academy cadets with concussions, demonstrated 165 athletes who flew within 31.8 ± 52.3 h after injury did not have a significant difference in recovery or severity of concussion symptoms compared with the 2235 athletes who did not fly at all. However, similar to the previous studies discussed, there are minimal data looking at an even more acute period after injury, such as fewer than 6 h after the SRC was sustained.

In humans, it seems many studies show no differences in concussion recovery or symptoms related to air travel. Interestingly, animal studies have shown increases in neurologic biomarkers in mice exposed to hypobaric conditions 3 h after mTBI but not in delayed (>24 h) exposure. This suggests that it is possible that there are neuroinflammatory marker changes occurring in human subjects but have yet to be identified. To date, serum and CSF biomarkers have not been validated when evaluating mTBI or SRC. There are many markers currently being investigated such as glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, total tau protein, and neurofilament light chain. However, there are many inconsistencies in the data and at this point we are left with observational studies, clinical gestalt, and shared decision making for individual athletes to consider when it is safe to fly on an airplane after a mTBI (^24,25).

Conclusions

The decision of when it is safe to fly on a commercial airline flight after mTBI is a nuanced and challenging one to make considering the limited reliable research to guide clinical decision making. There are some theories suggesting there may be some risk associated with hypobaric hypoxia and other pathologic states especially in the acutely and critically injured brain. In addition, there also are a few studies to suggest flight within the first 6 h after injury may lead to longer recovery periods. However, there is a paucity of data to truly guide decision making and recommend a clear time duration from injury when it is completely safe to fly. Clinicians should engage in shared decision making with athletes on a case-by-case basis and consider all variables including severity of initial injury, current symptoms, acclimatization to elevation, underlying medical issues that predispose to hypoxia (i.e., acute asthma exacerbations), as well as how important it is for the athlete to fly immediately versus a short delay. For instance, if the athlete is not feeling well and has headaches, dizziness, nausea, or other symptoms and the athlete is able to delay flight travel until they are improved, then it may be reasonable to delay. On the other hand, an athlete who has minimal or no symptoms, and has other reasons where flight travel very soon after the injury is required, the data are not compelling enough to state this athlete must be withheld from air travel. There are promising objective measures of concussion severity being studied such as brain imaging modalities and blood biomarkers, but they are not ready for clinical use at this time. Overall, with the available literature on the subject, it appears most athletes who travel by air in pressurized cabins shortly after sustaining a sports-related concussion are unlikely to experience acute or long-term negative effects.