Although public awareness of concussion has recently increased, our understanding of the pathophysiology of both acute and chronic repeated concussion is still limited. Aberrations in systemic physiology, such as those commonly encountered in the perianesthetic period, may serve as a source of secondary injury to the potentially vulnerable concussed brain. We provide a brief synopsis of epidemiology, pathophysiology, and anesthetic utilization in patients with concussion along with broad-based suggestions for the perianesthetic care of patients with concussion.
DEFINITION AND EPIDEMIOLOGY
The American Academy of Neurology defines concussion as a trauma-induced alteration in mental status that may or may not involve a loss of consciousness . However, the term ‘concussion’ is frequently used to describe the clinical manifestations that occur following a mild traumatic brain injury (i.e., those with a Glasgow Coma Score of 13–15 following restoration of consciousness). The diagnosis of concussion is independent of radiographic findings on computerized tomography of the head as patients with concussion may or may not have intracerebral contusion, hemorrhage, or diffuse axonal injury.
The true incidence of concussion is difficult to ascertain as many patients do not seek medical care following injury. The Centers for Disease Control and Prevention estimates that 2.2–2.7 million mild traumatic brain injuries occur in the United States annually . This estimate does not include individuals who either did not seek medical care or those who sought care at a clinic. When considering only sports-related concussions, Daneshvar et al. estimate 1.8–3.6 million occur annually in the United States; this estimate does not include concussions that result from other mechanisms such as falls, motor vehicle accidents, assaults, or injuries encountered by the military.
MANIFESTATIONS AND DIAGNOSIS OF CONCUSSION
Immediately following concussive injury, patients may suffer from confusion, amnesia, or even loss of consciousness. In the days to weeks following concussion, the prevalence of signs and symptoms of concussion are summarized in Table 1[4,5]. Typically, most manifestations resolve within 1 week but may persist longer in those with more severe injury or in those with a prior history of head injury .
Many screening tests for concussion are available that rely on a combination Glasgow Coma Score, presence of classic signs and symptoms, and ability to perform executive functions . Electroencephalographic slowing, with increases in theta and delta power, can occur following concussion although further study is required to determine if electroencephalography has an role in diagnosis or stratifying prognosis in those with concussion . There is a paucity of data describing a role for standard frontal near-infrared (IR) spectroscopy in those with concussion. However, functional near-IR spectroscopy was associated with an attenuation of oxyhemoglobin response while performing cognitive tasks and reduced interhemispheric motor coherence [9,10]. In 2018, the United States Food and Drug Administration approved a blood test for concussion based on an increase in two serum biomarkers: ubiquitin carboxy-terminal hydrolase-L1 and glial fibrillary acidic protein . This test, the Brain Trauma Indicator, had a sensitivity and specificity of predicting abnormal findings on computerized tomographic imaging of the head of 97.5 and 99.6%, respectively. However, the utility of the Brain Trauma Indicator test as well as other serum biomarkers in the diagnosis of concussion in those without abnormal imaging findings is unclear and a topic of ongoing research .
PATHOPHYSIOLOGY OF ACUTE CONCUSSION
During acute concussion, injury to the brain can occur as a result of the brain forcefully contacting the inner calvarium as well as due to stretching of inelastic axons. Immediately following injury, there is a significant increase in cerebral metabolic rate that may account for alterations in mental status and level of consciousness . In the minutes to hours after concussion, the brain enters a hypometabolic state that occurs in the setting of increased cerebral blood flow that may last for days to weeks [14–16]. This excess in cerebral perfusion may account for typical clinical manifestations. Stephens et al. showed that patients with persistent clinical manifestations at 6 weeks following injury had a tendency to have increased cerebral blood flow compared with those without manifestations as illustrated in Fig. 1. However, there are no reliable data to indicate that the resolution of clinical manifestations following concussion is associated with normalization of cerebral blood flow or metabolism. Churchill et al.[17▪▪] also found an increase in cerebral blood flow in the periconcussion period but reduced cerebral blood flow 1 year after athletes returned to sport.
The ability of the brain to autoregulate blood flow may be impaired following acute concussion. Vavilala et al. showed that, despite a normal Glasgow Coma Score, five of six individuals less than 18 years of age had impaired autoregulation or frank autoregulatory failure. Moir et al. also found attenuation of autoregulation soon after concussion that may be persistent for more than 12 weeks despite resolution of clinical manifestations. Responsiveness of the cerebral vasculature to hypercapnia may also be impaired following concussion with both hyporesponsiveness and hyperresponsiveness being described [20,21]. This discrepancy may be due to multiple factors including differences in timing of testing following injury and differences in injury severity. Using functional MRI, Jantzen et al. measured changes in regional cerebral blood flow that accompany performance of cognitive tasks. Despite no difference in the ability to perform complex tasks, those with recent concussion had exaggerated increases in regional cerebral blood flow compared with those without concussion.
Microstructural changes can also occur following concussion. The directionality of water movement within the brain, specifically within axonal tracts, can be measured with diffusion tensor MRI. Following concussion, the direction of axonal water flow becomes less unidirectional, manifested by decreased fractional anisotropy and increased radial diffusivity – indicating loss of integrity of axonal membranes. This may be due in part to stretching of axons during the concussion event when the brain moves quickly within the calvarium . These changes can be detected soon after injury and can last for at least weeks to months, especially in those with persistent clinical manifestations [24–26].
Collectively, the physiological and microstructural changes in the brain that accompany concussion may persist despite resolution of clinical signs and symptoms. Thus, the absence of clinical manifestations may not be a reliable indicator that physiological and microstructural changes of the brain have also resolved. The changes in the brain that follow concussion may potentially increase vulnerability of the brain to insults such as changes in systemic blood pressure (BP).
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that occurs in individuals who have sustained multiple concussions. CTE is associated with significant micropathologic changes first described in the brains of two American football players [27,28]. Significant findings included widespread deposition of both β-amyloid protein and neurofibrillary tangles comprised of hyperphosphorylated tau protein. These pathologic findings are also described in those with Alzheimer's dementia. Grossly, there is significant brain atrophy. The diagnosis of CTE can currently be only made at autopsy. However, it can be suspected in those with a history of multiple concussions who exhibit various signs and symptoms including problems with memory, performance of executive functions, and psychiatric changes such as changes in behavior and depression.
The Concussion Legacy Foundation has founded a Global Brain Bank for the study of CTE . Mez et al. reported data from next of kin and neuropathological findings from 202 brains donated to the Global Brain Bank by American football players. CTE was identified based on the presence of deposits of hyperphosphorylated tau protein and was identified in 21%, 91%, and 99% of brains donated from individuals who played American football only though high school, only through college, and as a profession, respectively. The authors stratified the severity of CTE based on the amount of deposition of hyperphosphorylated tau. Those with mild CTE had isolated epicenters of deposition, whereas those with severe CTE had more widespread deposition. Increased severity of CTE was associated with increased deposition of β–amyloid protein and insoluble deposits of α-synuclein, the protein that comprises Lewy bodies. The cerebellum is often less affected than supratentorial regions of the brain. A comparison of patient characteristics among those with mild versus severe CTE is provided in Table 2. Although cognitive changes, behavior, and mood problems, and substance abuse were common in both groups, dementia and motor manifestations such as ataxia, discoordination, and tremor, were more common in those with severe CTE. There are currently significant efforts being made to identify findings on brain imaging that can be used to diagnose CTE in the living patient [31▪]. On the contrary, there is a paucity of data describing cerebral hemodynamic changes associated with CTE.
CONCUSSION IN THE PERIPROCEDURAL PERIOD
As described earlier, the normal homeostasis and physiology of the brain are disrupted following concussion. Head trauma rarely occurs in isolation and patients may have concurrent bone fractures, spinal cord injury, intrathoracic, and intra-abdominal injuries that can lead to blood loss, hypovolemia, hypotension, and shock impairing perfusion and oxygen delivery to the brain and other vital organs. Hypoxia resulting from pulmonary contusion or aspiration as well as hyperglycemia secondary to trauma-related sympathetic nervous system activation can be a source of secondary injury to a vulnerable brain [32,33].
Cardiophysiologic disturbances, such as autonomic dysfunction and cardiovascular instability, have been well described after severe traumatic brain injury [34▪,35,36]. Cardiovascular and autonomic dysfunction can has been recently described in patients following concussion often manifest as altered heart rate variability [37,38]. These cardiovascular changes, occurring simultaneously with changes in cerebrovascular physiology, may hasten cognitive recovery following concussion [39▪▪].
Surgery and anesthesia are also associated with disruptions of systemic homeostasis that could potentially adversely impact a vulnerable brain. These include but are not limited to changes in systemic BP, arterial tensions of oxygen and carbon dioxide, activation of the inflammatory cascade, and effects of various drugs used in the perioperative period on cerebral physiology. Thus, given the changes in brain physiology that occur following concussion, the concussed brain may be vulnerable to secondary injury from changes in systemic physiology that occur in the perioperative period.
Abcejo et al. retrospectively quantified utilization of anesthesia in patients with concussion at a single institution. During a 10-year period, of 7699 patients identified with concussion, 1038 (13.8%) received at least one general or regional anesthetic or monitored anesthesia care to facilitate a surgical or diagnostic procedure within 1 year of injury. Demographics and tabulation of anesthetic cases are stratified by injury type and summarized in Table 3. Most concussions were due to motor vehicle accidents and falls. Patients with sport-related injuries were younger, and those who sustained a concussion due to a fall were older than those who sustained a motor vehicle accident or assault. Most sports-related concussions were evaluated in the outpatient setting, those due to assaults and falls were most often evaluated and dismissed from the emergency room, and those due to motor vehicle accidents are often admitted from the emergency room. Collectively, 93% of patients had a formal diagnosis of concussion documented within 1 week of injury. However, the time of greatest need for anesthesia services is soon after injury with 30% and 45% of all anesthetics occurring within 1 week and 1 month of injury respectively, a time when cerebral homeostasis is most disrupted. Motor vehicle accidents account for the greatest utilization of anesthesia per patient (2.4 anesthetics per year per patient). The fraction of patients receiving anesthesia for unrelated procedures within 1 year of injury ranged from 20 to 80% in those with concussions due to motor vehicle accidents and sports injuries, respectively. Twenty-nine of 554 (5.2%) anesthetics administered within 1 week of injury were to facilitate procedures that were deemed elective and unrelated to the injury that resulted in concussion. Taken collectively, patients who sustained a concussion frequently require anesthesia to facilitate procedures that may or may not be related to their injury, they may not have a formal diagnosis of concussion at the time of their procedure, and the greatest utilization of anesthesia occurs soon following concussion injury.
Currently, it is unclear how long elective procedures requiring anesthesia should be delayed following concussion injury. As noted earlier, resolution of clinical manifestations may not reliably indicate normalization of cerebral physiology. There are also currently no data (ND) to support whether or not abnormalities in the brain following concussion lead to increased risk for adverse outcomes in those requiring anesthesia soon following concussion. D'Souza et al.[41▪] retrospectively matched 60 patients requiring anesthesia within 90 days of injury with 178 similar patients who also required anesthesia for similar procedures but did not sustain concussion. There were no differences in physiologic variables either during surgery or in the postanesthesia recovery room between groups. On univariate analysis those with concussion having anesthesia within 30 day of injury had significantly higher rates of visual analog pain scores at least 7 out of 10 in the postanesthesia recovery room (21%) and higher rates of complaints of headaches within 90 days of anesthesia (24%) versus those without concussion [15% (P = 0.02) and 7% (P = 0.01) for pain score at least 7 and headache within 90 days, respectfully]. Also on univariate analysis, those with concussion having anesthesia between 31 and 60 days following injury had lower mean Richmond Agitation-Sedation Scale score in the recovery room (−1.61 ± 1.29) compared with those without concussion (−0.2 ± 0.45; P = 0.002) indicated greater sedation in those with concussion. However, when corrected for potential confounders and for multiple comparisons, no significant differences between groups were identified. These findings do not necessarily support the notion that there is no need to delay elective anesthetics following concussion as this small retrospective study may have had limited power and precision to identify differences. We may require investigation of other outcome variables, such as cognitive skills, that are assessed prospectively.
Currently, there are no standard guidelines specific to the management of patients with concussion in the periprocedural period. With the current available data, the following points are worth considering:
- (1) Anesthesia personnel should suspect concussion in any patient who recently sustained a traumatic injury.
- (2) Resolution of clinical manifestations of concussion do not reliably indicate a normalization of cerebral pathophysiology.
- (3) As of now, there are ND to guide delay of elective procedures but delay of completely elective procedures until resolution of clinical manifestations seems reasonable.
- (4) Those who have likely sustained multiple concussions (i.e., American football players, boxers), may represent a group of patients with a vulnerable brain in the perianesthetic period.
- (5) Although the Brain Trauma Foundation Guidelines  are not specific to the care of patients with concussion, anesthesia personnel should be familiar with these guidelines and may be helpful to guide periprocedural management of patients with concussion:
- (a) Avoidance of unnecessary hyperventilation.
- (b) Maintaining SBP more than 100 mmHg in patients 50–69 years old and more than 110 mmHg in those less than 50 and more than 69 years old.
- (c) Minimizing hypoxia (PaO2 < 90 mmHg and SaO2 < 90%).
- (d) Avoiding the unnecessary use of corticosteroids.
Concussion results in disruption of normal cerebral physiology and axonal microstructure. Repeated concussion can result in CTE that is associated with cerebral atrophy and pathologic changes similar to those encountered in other forms of organic dementia. Changes in the brain following both acute and chronic repeated concussion may make the brain vulnerable to secondary injuries as may be encountered in the periprocedural period. Further research is needed to better understand the risks of anesthesia in the concussed brain and to determine how risk can be minimized in the patient with concussion who require anesthesia to facilitate surgical and diagnostic procedures.
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Conflicts of interest
There are no conflicts of interest.
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