Up to this point, we have learned of the incredible evolution of anesthesia since its advent, allowing millions of life-saving, painless, sterile, successful surgeries to take place every day. We have also learned of careful considerations in vulnerable populations. This last blog post will top off the topic of surgery in the brain injured patient.
Surgery can be lifesaving and can also vastly improve quality of life. Over the past decade, however, growing evidence has linked surgery, such as cardiac and orthopedic procedures, to brain pathology similar to that of other neurologic diseases in which the brain is the primary target of injury.
Nature Immunology1
Are the effects of general anesthesia on the brain entirely reversible?
The question of whether the brain reverts entirely to the state it was in preoperatively once the anesthetic agent is removed, remains. Mounting evidence suggests that the effects may be longer lasting than once thought or anticipated due to long-term changes within the brain. Due to the mechanism of these agents acting on receptor targets throughout the brain, the compensating capacity in vulnerable populations is reduced. These populations include developing children and older adults, though focus is emerging towards another group in this population of vulnerability being those with brain injury of any severity as well as other brain diagnoses.
This remains unanswered though some studies suggest the negative effects in attention and memory can languish for days, months or even years.
The stress of surgery: Can we separate the potential long-term effects of general anesthesia from the stress of surgery itself?
Aside from the anesthesia, consider all the different factors that play into surgery. Consider the bright lights in a light-sensitive patient, the various noises of beeping and monitors in a noise-sensitive patient, the blood sugar fluctuations from overnight fasting which may already be erratic, the anxiety and stress associated with the procedure, and the inflammation produced.
There is no doubt that this type of environment could be very triggering to a concussed or post-concussed patient already struggling to be present in such environments. It’s important to note that while this environment can be very triggering to a brain injured patient, if it were solely the culprit those symptoms would likely not languish for months after the exposure. Once removed from the stimuli, the brain should calm depending on the individual within days to a few weeks.
Does the surgical site play a role?
This question emerged from my personal experience following my concussion. It got me thinking that maybe a huge component of my negative outcome after shoulder labrum repair during the early days of my TBI recovery was at least partially a result of the proximity to the neck leading to a favoring of the shoulder and thus further imbalance in the musculature of the neck and surrounding structures.
The surgical site may certainly play a role although there is no clarifying answer on this. In theory, a surgery to the knee or foot may have a more favorable outcome in a concussed patient versus a surgery of the upper body. It’s important to remember that every concussion has neck involvement but every injury to the neck is not accompanied by a concussion. Unfortunately, the neck is often overlooked and left untreated in a good majority of concussed patients. This in combination with a surgical procedure in close proximity may exacerbate the already prevalent issue, though this remains theoretical at this point.
Inflammation and the immune response after surgery
Any trauma to the body produces inflammation, and surgery is a controlled trauma to the body. The link between cognitive impairment from systemic inflammation is not well understood. There is now mounting evidence that the inflammatory cascade can also trigger the brain’s innate immune system leading to long-term cognitive impairment and the development or worsening of other symptoms.
A review article1 addresses neuroinflammation after surgery. The cellular damage that is a result of surgery activates immune cells that are important in restoring homeostasis, but this activation leads to systemic inflammation. If this immune function is impaired or dysregulated, it can drive perioperative neurocognitive disorders (PNDs).
…seemingly harmless interventions like a common surgery to repair a broken limb can overwhelm the immune system and become the driver of further complications such as delirium and other perioperative neurocognitive disorders.
Nature Immunology1
Also triggered by surgical trauma is the coagulation system. This is also necessary for body homeostasis but on the other hand can be a driving force for cognitive deficits. This process could go haywire if fibrinogen, a protein necessary for clotting, enters the brain through the blood brain barrier (BBB). Fibrinogen deposition was found in the brain’s hippocampus just 24 hours after orthopedic surgery. This very deposition has been implicated in traumatic brain injury, Alzheimer’s and MS.
The BBB protects and regulates what goes in and out of the brain. A consideration is that the BBB is often damaged after brain trauma leaving it exceptionally vulnerable. This may be an important mechanism for systemic inflammation to cause inflammation within the brain. Preclinical models demonstrated surgery and anesthesia can lead to increased permeability of the BBB, allowing inflammatory cells into the hippocampus which plays a huge role in learning and memory. A good majority of TBI patients already have a leaky BBB so this combination may be bad news.
Researchers discovered the two proteins associated with Alzheimer’s went from normal levels pre-surgery to increased levels associated with mild cognitive impairment six months post-surgery in human patients. This has also been seen in other studies to increase just 48 hours post-surgery.2 A separate study3 looking at the immune response before and after surgery showed interesting results. The researchers used brain PET scans to image this response and found a significant decrease in brain glial activity early post-operatively and also months after. This study demonstrates an association between the immune response and cognitive impairment. The more dysregulated the immune response, the worse the cognitive impairment.
Certain anesthetics may strengthen areas in the brain
Researchers have looked into whether anesthetics can help protect or benefit the brain as well. Ketamine has been used for its anti-depressant effects and may strengthen neural connections and reset the brain’s award and disappointment centers. It may reduce post-operative cognitive impairment and is theorized it does this by modifying the immune response. Other anesthetics such as propofol and isoflurane in certain doses have also been used as antidepressant therapy.
Bottom line: The negative effects from surgery are likely multifactorial
Is general anesthesia the culprit for decline in cognition and other symptoms after surgery? Is it the inflammation produced? Is this due to a leaky blood brain barrier or dysregulated immune response? Is it a combination of all of the above?
While many questions remain unanswered, it seems most plausible to be a combination of all of the above – systemic inflammation, the hospital setting, an already vulnerable brain with pre-existing cognitive deficiencies, leaky blood brain barrier, dysfunctional immune response. Elective surgery should be carefully considered in the concussed and post-concussed patient and the risks and benefits should be discussed thoroughly before proceeding. Careful consideration should also be placed on anesthesia and a conversation with the anesthesiologist can be helpful.
How can we better protect the brain when going under the knife?
- Support the immune system
- Optimize nutrition
- Protect the blood brain barrier
- Curcumin, resveratrol, vitamin D, B vitamins, magnesium, omega 3
- Discuss the possibility of using EEG to fine-tune anesthesia dosing with your anesthesiologist
- Discuss the risks and benefits of the surgery with your physician and surgeon before proceeding
- Discuss the established intra-operative goals for TBI patients with your surgeon
If time slowly steals our memories, let us at least ensure that interventions like surgery do not accelerate the natural course of time, especially on an already vulnerable brain
Nature Immunology1
1. https://www.nature.com/articles/s41590-020-00812-1
2. https://www.pbs.org/wgbh/nova/article/pocd/
3. https://escholarship.org/content/qt1dt4532r/qt1dt4532r.pdf?t=p0hi0b
