Introduction and History

Humans have used cold for analgesia for thousands of years. The first written records of the use of ice for pain relief came from Hippocrates (460–377 BCE), who described how snow was applied to wounds for pain relief [1]. In 1812, Napoleon’s Surgeon General, Baron Dominique Jean Larre, noted that half-frozen soldiers were able to tolerate limb amputation with little or no pain [2]. In 1777, Hunter noted that the tissue of a roster comb healed without scarring after the tissues were killed by cold [3]. In 1851, Arnott [4] used mixtures of ice and salt to create solutions of temperatures down to –20°C to relieve certain types of cancer and nerve pain. Ether spray was introduced in 1866 by Richardson for topical anesthesia [5]; thus “to freeze” became synonymous with “to numb”. Trendelenburg [6] demonstrated that freezing tissues caused severe nerve damage and loss of function, but noted that the nerves regenerated without neuroma formation.

In 1961, Cooper et al. [7] developed a device that used liquid nitrogen in a hollow tube insulated at the tip and achieved a temperature of –190°C, introducing modern cryoneurolysis. The term “cryoanalgesia” was coined by Lloyd and his co-workers [8] for its use in pain management, and proposed that this technique, because it is not followed by neuritis or neuralgia, was superior to other methods of peripheral nerve destruction, e.g., alcohol, phenol, or surgical lesions.

The technique has gone by many names, including cryoablation, cryoneuroablation, cryosurgery, cryoanalgesia, and cryoneurolysis.

Physics of Cryoneuroablation

The cryoprobe consists of a hollow tube with a smaller inner tube. Pressurized gas (usually N₂O or CO₂) at 600 to 800 psi travels down the inner tube and is released into the larger outer tube at a low pressure (10 to 15 psi) through a very fine aperture (0.002 mm), which allows the gas to rapidly expand into the distal tip (Figure 10.1). This drop in the temperature of the tip of the probe to as cold as –89°C at the tip itself (Joule-Thomson effect) [9] forms an ice ball (Figure 10.2). The gas is then vented back to the machine through the outer tube and is scavenged through a ventilated outlet. The “closed system” construction of the probe and machine assures that no gas escapes into the patient’s tissues. The 2.0-mm probe forms a 5.5-mm ice ball while the 1.4-mm probe forms a 3.5-mm ice ball (Figures 10.1 and 10.2).

Precise gas flows are necessary for safe and effective cryoneuroablation; inadequate gas flows will not produce an ice ball while excessive flows can cause freezing proximally up the probe, which may increase the risk of skin burns. The probe also includes a sensory and motor nerve, which allows precise localization of the target nerve.

The application of cold to tissues creates a conduction block, similar to the effect of local anesthetics. At 10°C, larger myelinated fibers stop conducting, but all nerve fibers stop conducting at –20°C. The extent and duration of the analgesic effect, therefore, is a function of the degree of cold obtained and the length of exposure [3]. Long-term pain relief from nerve freezing occurs because ice crystals create vascular damage to the vasa nervorum, which produces severe endoneural edema, disrupting the nerve structure and creating Wallerian degeneration but leaving the myelin sheath and endoneurium intact [10]. The Schwann cell basal lamina is spared and ultimately provides the structure for regeneration. Although demyelination and degeneration of the axon occurs, Sunderland [11] demonstrated that when the endoneurium remains intact, neuroma formation does not occur, and the nerve is typically able to regenerate.

Indications for Cryoneuroablation

• Peripheral nerves
  
• Cancer pain
  
• Intercostal nerves: open dissection of the thorax has been used primarily for post-operative pain [12]
  
• Tumor mass or bone lesions [13]
  
• The nerves that provide sensation to that region [14].
  
• Figures 10.3– 10.7.

Contraindications for Cryoneuroablation

• lack of consent from patient
  
• infection at the insertion site
  
• any allergy or sensitivity to the anesthetic agent
  
• distortion of anatomical landmarks.

Technique for Peripheral Nerves

The skin is anesthetized using very small amounts of local anesthetic with special care not to anesthetize the nerve. Next, the subcutaneous tissues around the nerve are infiltrated with 1 to 2 ml of 0.9% preservative-free normal saline with 1:200 000 epinephrine (5 μg epinephrine per ml normal saline). This provides constriction of the surrounding blood vessels and will decrease bruising from the cryo probe. The introducer (usually an IV catheter) is gently advanced into the tissues to the target area, and tiny doses of local anesthetic added if needed to provide analgesia (taking care to avoid anesthetizing the target nerve). The probe is then advanced through the introducer until it lies over the nerve (Figure 10.8). The sensory function of the probe is used to place the probe as close as possible to the nerve, using a technique of “successive approximations”; the sensory stimulator is turned up to 1 mV and slowly moved until the patient feels the paresthesia (a tingle or burning sensation) and is then immediately turned off. After a few seconds, the stimulator is turned back up to 1 mV; if the patient does not feel stimulation, then it is a false paresthesia (Figure 10.8).

If the patient feels the paresthesia before 1 mV is reached, the stimulator is only turned up to 0.5 mV and the probe moved until the patient feels the paresthesia and is then turned off, and the process repeated until the stimulation is felt at 0.3 mV, each time getting closer and closer to the nerve. The motor function is then used to confirm the lack of motor stimulation at 2 mV. Two or three 2-minute freeze cycles are usually sufficient for clinical relief. Special care must be taken to make certain that a superficial “frostbite” burn of the dermis and epidermis is not occurring.

Complications of Cryoneuroablation

Complications from cryoneuroablation are quite rare. Because the myelin sheath remains intact, even motor nerves will regenerate entirely (Figure 10.9). Animal studies [16] have shown a restoration of function of rat sciatic nerves following multiple freezes. The risks involved with cryo are primarily the risks seen with any needle technique, but caution and gentle technique greatly reduce that risk. Even using large probes (up to 12 G) can be used safely. However, there are some complications that need to be evaluated for and protected against.

Bleeding

Because of the size of the probe, bleeding can be a potentially serious complication. Since most nerves have a blood vessel running beside it, these vessels are at risk for damage when rough techniques are used (Figure 10.10). Anticoagulants may not be a contraindication in areas where there is easy control of bleeding (such as on the wrist). However, caution needs to be used when performing cryoneuroablation at sites where bleeding might be difficult to control (such as intercostal or femoral). The use of a parallel, rather than perpendicular approach to the intercostal nerve, (Figure 10.11) and the use of ultrasound to check for vessels (Figure 10.12) should decrease the risk of bleeding.