Pathophysiology of Perioperative Peripheral Nerve Injury: Stretch, Compression, and Ischemia

Peripheral nerve injury (PNI) occurring in the operative period can be attributed to a range of pathophysiological mechanisms. These mechanisms include nerve stretch, compression, hypoperfusion, direct trauma (surgical or needle transection and intraneural injection), and exposure to neurotoxic agents such as local anesthetics. In many cases, PNI arises from a combination of these factors, making the underlying etiology complex and sometimes unclear. While the direct cause of nerve damage may not always be immediately apparent, most forms of operative PNI share a common precipitant: nerve hypoperfusion and the resulting ischemia.

Hypoperfusion and Ischemia

The vasa nervorum, the delicate blood vessels supplying the peripheral nerves, plays a crucial role in maintaining nerve function by delivering oxygen and nutrients to the nerve tissue. When these vessels are compromised due to physical forces such as compression, stretch, or trauma, blood flow to the nerve is reduced, leading to ischemia. Ischemia deprives the nerve of essential oxygen, which in turn impairs its metabolic processes and leads to a cascade of pathophysiological changes within the nerve.

One key consequence of ischemia is the development of endoneurial edema and intraneural hemorrhage, both of which can exacerbate the disruption of the nerve's microcirculation. This leads to further ischemic injury, ultimately impairing axoplasmic transport, the process by which nutrients, enzymes, and other critical substances are moved along the axon. This impairment can disrupt the transmission of nerve impulses and interfere with nerve function.

Cellular and Histological Changes

The histological changes that occur in response to nerve ischemia can vary widely, depending on the severity and duration of the ischemic insult. In mild cases, these changes may include Schwann cell damage and myelin destruction, which lead to segmental demyelination. In such cases, the nerve sheath is damaged, but the axon remains largely intact, resulting in temporary impairment of nerve conduction.

In more severe cases, the ischemia may cause axonal degeneration and eventually lead to Wallerian degeneration, a process in which the axon and its surrounding myelin sheath degenerate distal to the site of injury. This type of damage significantly affects nerve function and often results in longer recovery times, or even permanent nerve dysfunction, depending on the extent of the injury.

Compression and Stretch Injuries

Nerve compression is a well-known mechanism of PNI in the operative setting, especially during prolonged surgeries where patient positioning may place undue pressure on certain nerves. Compression impairs both blood flow and axoplasmic transport, leading to ischemia and, eventually, structural nerve damage. The degree of histological damage in cases of compression has been shown to correlate with both the intensity and duration of the compression. Animal models have demonstrated that more prolonged or severe compression results in greater nerve damage, reinforcing the importance of preventing sustained mechanical pressure on nerves during surgery.

Similarly, nerve stretch can compromise the structural integrity of peripheral nerves. A nerve tolerates roughly 5 to 10 percent elongation; beyond about 8 percent the vasa nervorum begin to collapse and intraneural blood flow falls, and at around 15 percent flow stops. Excessive stretching therefore disrupts the vasa nervorum and causes localized ischemia, and mechanical stretch may also directly damage the axonal structures, further contributing to nerve dysfunction. Arm abduction beyond 90 degrees, a steep head-down position with shoulder braces, and lithotomy with the hips flexed and the knees extended are the typical operative stretch injuries.

Needle, Injection and Local Anesthetic Injury

Regional anesthesia adds three mechanisms of its own. The first is mechanical: a needle that enters a fascicle, or a catheter threaded into one, tears axons directly. The second is injection pressure: injecting into a fascicle raises pressure inside the inelastic perineurium, and in animal models the combination of intraneural needle placement with high opening pressure (above about 15 to 20 psi) produced fascicular injury and persistent deficits, whereas injection outside the perineurium at low pressure did not. The third is chemical: local anesthetics are toxic to nerve cells and Schwann cells in a concentration- and time-dependent way, an effect that matters little for a normal nerve bathed in anesthetic outside the perineurium but adds to the damage when the drug is injected inside a fascicle or onto a nerve already compromised by ischemia or disease. Because fascicles occupy only a fraction of the nerve cross-section and the needle tip is often not in the plane of the ultrasound image, neither ultrasound nor a nerve stimulator excludes intraneural placement: a motor response may be absent at currents above 0.5 mA despite needle-nerve contact, and a response below 0.2 mA suggests intraneural placement. Injection that meets resistance or causes pain or paresthesia should be stopped and the needle repositioned.

Double-Crush Phenomenon

A notable concept in the pathophysiology of PNI is the double-crush phenomenon. According to this theory, an existing subclinical nerve abnormality along the course of a peripheral nerve reduces the threshold for injury at a secondary site. This means that when a nerve is already compromised, either by pre-existing pathology or prior injury, it becomes more susceptible to a secondary insult, such as compression or stretch during surgery. The combination of the two insults results in clinically significant nerve damage, even if each insult alone would not have caused the injury. The concept was described by Upton and McComas in 1973 for patients with carpal tunnel syndrome who also had a cervical root lesion. In the operative setting the first "crush" is often a pre-existing diabetic, alcoholic, or chemotherapy-related neuropathy, a hereditary neuropathy, or a subclinical entrapment such as cubital tunnel syndrome, and the second is the positioning pressure, stretch, tourniquet, or nerve block that would have been harmless to a healthy nerve. Diabetic nerves are the most important example: they are more susceptible to ischemia, more sensitive to local anesthetic, and more likely to be blocked with no motor response at normal stimulating currents, so blocks in these patients are performed with ultrasound guidance, lower concentrations and volumes, and particular attention to padding and positioning.