Cryoanalgesia and Therapeutic Cold

Number: 0297

Policy

1. Aetna considers the use of cryoanalgesia medically necessary for the temporary relief of pain due to chronic refractory trigeminal neuralgia (see Appendix for selection criteria).

2. Aetna considers intra-operative and post-operative cryoanalgesia for the management of post-thoracotomy pain, post-operative analgesia in repair of pectus excavatum, and the reduction of post-tonsillectomy pain experimental and investigational because the effectiveness of these approaches has not been established.

3. Aetna considers passive cold compression therapy units (e.g., Aircast Cryo/Cuff products, the Polar Care Cub, and Polar Care Packs) medically necessary DME to control swelling, edema, hematoma, hemarthrosis and pain.  Aetna considers the passive cold compression therapy units experimental and investigational for all other indications because their effectiveness for indications other than the ones listed above has not been established.

4. Aetna considers active cold units with mechanical pumps and portable refrigerators with or without compression therapy (e.g., AutoChill, BioCryo Cold Compression System, Breg Polar Care Cube, Game Ready control units with attached cooling systems, Donjoy IceMan products, Ossur Cold Rush Cold Therapy System, Hilotherm devices, and VPULSE) experimental and investigational because they have not been proven to offer clinically significant benefits over passive cold compression therapy units. Note: Aetna considers active cold units with compression therapy are considered experimental and investigational, even if they are only prescribed for the compression component of the device. 

5. Aetna considers the use of devices that deliver both hot and cold therapy (e.g., Aqua Relief System, Waegener cTreatment, NanoTherm therapy system, ProThermo PT-9 therapy system, Thermacure Contrast Compression Therapy, Kinex ThermoComp device, VascuTherm 4, VascuTherm 5, Recovery+ Thermal Compression System, Thermo Plus-System) experimental and investigational for reducing pain and swelling after surgery or injury, or for other indications.  Studies in the published literature have been poorly designed and have failed to show that these devices offer any benefit over standard cryotherapy with ice bags/packs; and there are no studies evaluating their use as a heat source.

6. Aetna considers prophylactic hypothermia for the management of traumatic brain injury experimental and investigational because the effectiveness of this approach has not been established.

7. Aetna considers therapeutic hypothermia for the treatment of hemorrhagic stroke experimental and investigational because the effectiveness of this approach has not been established.

8. Aetna considers cryoneurolysis for the treatment of post-herpetic neuralgia experimental and investigational because the effectiveness of this approach has not been established.

9. Aetna considers ultrasound-guided percutaneous intercostal cryoanalgesia for analgesia following mastectomy experimental and investigational because the effectiveness of this approach has not been established.

Note: Aetna considers passive hot and cold therapy medically necessary.  Mechanical circulating units with pumps have not been proven to be more effective than passive hot and cold therapy.

See also CPB 0725 - Post-Herpetic Neuralgia

Background

Cryoanalgesia for Trigeminal Neuralgia

Trigeminal neuralgia (TN), also known as tic douloureux, is a disorder characterized by excruciating episodic pain in the areas innervated by one or more divisions (usually the mandibular and maxillary, rarely the ophthalmic divisions) of the trigeminal nerve.  The anti-epileptic drug carbamazepine (Tegretol) is the drug most frequently used for the management of TN.  For patients who can not tolerate carbamazepine because of its adverse side effects (poor liver function, confusion, ataxia, drowsiness, and allergic responses), the literature indicates baclofen and other anticonvulsant drugs such as clonazepam (Klonopin) may be useful.

Cryoanalgesia, cryotherapy, or cryoneurotomy has also been used in the treatment of TN.  It entails the use of high pressure (approximately 600 pounds per square inch) gas (nitrous oxide or carbon dioxide) administered by a 12- to 14-G needle-shaped cryoprobe.  Studies have shown that cryoanalgesia provides temporary pain relief or cure with minimal morbidity (e.g., no permanent sensory loss) in patients with refractory TN.

Intra-Operative and Post-Operative Cryoanalgesia for the Management of Post-Thoracotomy Pain

Thoracotomy, the establishment of an opening into the chest cavity for the management of various cardiopulmonary disorders/diseases, is one of the most painful surgical incisions.  Post-thoracotomy pain impairs patients' ability to breathe deeply and cough frequently to prevent atelectasis.  Pain relief medication may decrease the coughing reflex as well as depress respiratory functions when the dosage is high enough to achieve analgesia.  On the other hand, if the dosage of analgesics is too low to relieve pain, it may render patients with shallow breathing and inadequate coughing reflex.  Epidural anesthesia or analgesia may produce some pain relief, but the side effects of severe hypotension, nausea, and urinary retention, as well as the variability of effect limit the usefulness of this approach.  Intercostal or paravertebral nerve blocks by means of local anesthetics and severing of the intercostal nerves have also been used to reduce incisional pain following thoracotomy.  However, the duration of relief for neural blockade is only a few hours and the procedure is painful, while severing of the intercostal nerves during thoracotomy may result in neuromas, which cause late post-operative pain.

Cryoanalgesia has been used on the intercostal nerves to reduce post-thoracotomy pain.  Although the procedure is generally performed prior to closure of the chest at the completion of thoracotomy and may add 10 to 15 mins to the total operating time, it can also be carried out percutaneously in a clinical setting.  Cryoanalgesia of the intercostal nerves circumvents the need for repetitive injections of nerve blocks and avoids the toxicity of long acting agents, which may lead to chemically induced intercostal neuritis. 

Khanbhai et al (2014) examined if cryoanalgesia improves post-thoracotomy pain and recovery.  A total of 12 articles were identified that provided the best evidence to answer the question.  The authors, date, journal, study type, population, main outcome measures and results were tabulated.  Reported measures were pain scores, additional opiate requirements, incidence of hypoesthesia and change in lung function.  Half of the articles reviewed failed to demonstrate superiority of cryoanalgesia over other pain relief methods; however, additional opiate requirements were reduced in patients receiving cryoanalgesia.  Change in lung function post-operatively was equivocal.  Cryoanalgesia potentiated the incidence of post-operative neuropathic pain.  Further analysis of the source of cryoanalgesia, duration, temperature obtained and extent of blockade revealed numerous discrepancies; 3 studies utilized CO2 as the source of cryoanalgesia, and 4 used nitrous oxide but at differing temperatures and duration; 5 studies did not reveal the source of cryoanalgesia.  The number of intercostal nerves anesthetized in each study varied; 7 articles anesthetized 3 intercostal nerves, 3 articles used 5 intercostal nerves, 1 article used 4 intercostal nerves and 1 used 1 intercostal nerve at the thoracotomy site.  Thoracotomy closure and site of area of chest drain insertion may have a role in post-operative pain; but only 1 article explained method of closure, and 2 articles mentioned placement of chest drain through blocked dermatomes.  No causal inferences can be made by the above results as they are not directly comparable due to confounding variables between studies.  The authors concluded that currently, the evidence does not support the use of cryoanalgesia alone as an effective method for relieving post-thoracotomy pain.

Humble et al (2015) noted that peri-operative neuropathic pain is under-recognized and often undertreated.  Chronic pain may develop after any routine surgery, but it can have a far greater incidence after amputation, thoracotomy or mastectomy.  The peak noxious barrage due to the neural trauma associated with these operations may be reduced in the peri-operative period with the potential to reduce the risk of chronic pain.  These investigators performed a systematic review of the evidence for peri-operative interventions reducing acute and chronic pain associated with amputation, mastectomy or thoracotomy.  A total of 32 randomized controlled trials (RCTs) met the inclusion criteria.  Gabapentinoids reduced pain after mastectomy, but a single dose was ineffective for thoracotomy patients who had an epidural.  Gabapentinoids were ineffective for vascular amputees with pre-existing chronic pain.  Venlafaxine was associated with less chronic pain after mastectomy.  Intravenous and topical lidocaine and peri-operative EMLA (eutectic mixture of local anesthetic) cream reduced the incidence of chronic pain after mastectomy, whereas local anesthetic infiltration appeared ineffective.  The majority of the trials investigating regional analgesia found it to be beneficial for chronic symptoms.  Ketamine and intercostal cryoanalgesia offered no reduction in chronic pain.  Total intravenous anesthesia (TIVA) reduced the incidence of post-thoracotomy pain in 1 study, whereas high-dose remifentanil exacerbated chronic pain in another.  The authors concluded that

1. appropriate dose regimes of gabapentinoids, anti-depressants, local anesthetics and regional anesthesia may potentially reduce the severity of both acute and chronic pain for patients;
2. ketamine was not effective at reducing chronic pain;
3. intercostal cryoanalgesia was not effective and has the potential to increase the risk of chronic pain; and
4. TIVA may be beneficial but the effects of opioids are unclear.

Cold Therapy Units and Hot/Ice Machine

Cold therapy devices combine cold temperatures and compression to decrease discomfort and swelling following injury or surgery to an extremity. The theory behind cold therapy is that by decreasing the temperature of the tissue, which produces vasoconstriction, pain is lessened, muscle spasm is decreased and inflammation is reduced.

Active cold therapy devices and combined heat and cold therapy devices utilize pneumatic or mechanical pumps that may be battery or electrically operated. The intended function of the pump is to provide cyclical compression and cooling or heating to the affected area. The devices generally consist of two basic parts: a wrap or wrap system and a control unit or pump, which is filled with ice and/or water. The control unit or pump circulates the cooled or heated water through the wrap system to the affected area.

Active cooling or heating devices

Examples of active cooling or heating devices include, but may not be limited to:

• Auto Chill Device –

  Cold therapy device in which a pump is used in conjunction with the Cryo/Cuff System. The pump automatically exchanges water from the pump to the cooler and eliminates the need for manual water recycling.

• cTreatment -

  Computer controlled heat and cold.

• Hilotherm -

  Heat and cold water pump with pads.

• Game Ready Accelerated Recovery System -

  System that combines cold and intermittent pneumatic compression therapies. It includes a computer that controls treatment time, level of compression and temperature. The unit continuously cycles liquid through circumferential wraps for consistent, long lasting cold treatment, even over large surface areas.

• Hot/Ice Thermal Blanket –

  Provides heat/cold therapy by the application of rubber pads (blankets) that are connected by a hose to a main cooling unit. The pads receive fluid that has circulated from the main unit and can be either hot or cold.

• IceMan Cryotherapy Unit –

  Utilizes a semi-closed loop system with a mechanical pump that allows warm water to circulate, at a constant flow rate, with cooler water providing consistent cold distribution throughout the pad.

• Kinex ThermoComp Device –

  Another example of a device that combines cold therapy with intermittent pneumatic compression.

• NanoTherm –

  System that combines cold or heat with intermittent pneumatic compression therapies. 

• Ossur Cold Rush Cold Therapy System –

   Combines cold pump with compression. 

• Thermocure Contrast Compression Therapy –

   Combines heat or cold pump with compression. 

• VitalWrap System –

  Consists of three components: a control unit, a tubing set and a thermal fabric wrap. The control unit, which includes a fluid reservoir, manages the temperature of water used by the system to supply heat or cold to the fabric wrap attached to the body. Compression is delivered through the wrap itself. 

• VPULSE -

  Intermittent pneumatic compression with cold water pump.

Passive cold therapy devices operate by gravity or a hand pump without the use of a battery or electricity. Generally, they consist of a cuff or wrap and a cooler. Ice water is placed in the reservoir or cooler. The cooler is placed above the affected body area or joint and then utilizes gravity to fill the cuff and compress the joint. 

Passive Cold Therapy Devices

Examples of passive cold therapy devices include, but may not be limited to:

• AirCast Cryo/Cuff System–

  Therapy system consisting of a cuff, a cooler and a hose. The hose exchanges cooled ice water between the cooler and the cuff which covers the injured area. Elevating the cooler fills and pressurizes the cuff. Compression is controlled by gravity and is proportional to the elevation of the cooler.

• Polar Care (PC) Cub Unit–

  Cold therapy system which includes a PC Cub cooler, manual pump and wrap on pads. The pads are held in place with elastic straps or an ace wrap. The built-in hand pump circulates the cold water through the polar pad, while at the same time increases the compression around the joint.

Cold therapy units are devices in which fluid flows through a blanket or cuff, providing immediate cooling to an affected area.  The AirCast Cryo/Cuff uses a insulated jug filled with cold water attached to a cuff.  Elevating the jug fills and pressurizes the cuff.  Compression is controlled by gravity, and is proportional to the elevation of the cooler.  When body heat warms the water, it is re-chilled simply by lowering the cooler.  Another passive cold compression therapy unit is the Polar Care Cub unit.

More complicated cold therapy units may employ mechanical pumps and refrigerators that are powered by battery or electricity (e.g., IceMan).  The Game Ready system is an example of an active cooling device that combines cold and intermittent pneumatic compression therapies.  The system consists of a wrap, a connector hose, and a control unit.  The wrap contains two internal chambers, one for air and the other for cooling water.  The microprocessor control unit features various adjustable compression cycles and temperature controls.  However, there is no evidence that these more complicated cold therapy units provide any additional benefit over the CryoCuff or conventional ice bags or packs.  Aetna's current policy on mechanical cold therapy pumps is consistent with Medicare DME MAC policy.

Leutz and Harris (1995) described a retrospective study that assessed 52 consecutive patients who underwent total knee arthroplasty (TKA).  A total of 33 patients underwent TKA and received cold therapy pads placed over a thin dressing in the operating room; 19 patients underwent TKA using an identical operative and post-operative procedure, but did not receive continuous cold therapy.  Continuous cold therapy consisted of 2 sterile plastic pads connnected by rubber hoses containing cool water from an electric main unit that maintained a constant temperature of 42 degrees F for the immediate post-operative period.  Cold therapy pads were used an average of 3 days and removed with the first dressing change.  Patients who had continuous cold therapy averaged a 200 ml decrease in post-operative blood loss.  There was no significant difference in the amount of narcotic use, transfusion requirements, or hospital stay between the two groups.  Post-operative swelling and range of motion were not consistently recorded.  Twenty-eight other variables were also examined, but no significant differences were found between groups.  Based on these results, the authors stated that they can not recommend continuous cold therapy or justify the extra expense for all patients who undergo TKA.

A Hot/Ice Machine consists of 2 rubber pads connected by a rubber hose to a unit that circulates hot or cold fluid through the pads.  Studies in the published literature have been poorly designed and have failed to show that the Hot/Ice Machine offers any benefit over standard cryotherapy with ice packs, and there are no studies evaluating the use of this device as a heat source.

The VitalWrap (VitalWear Inc. South San Francisco, CA) is an active heating/cooling device that allows the user to circulate either hot or cold fluid through the system.  The VitalWrap system consists of a bladder filled body wrap/pad, tubing, and a reservoir/pump device.  Cooled or heated water may be added to the pump reservoir and then circulated through the tubing to the body wrap/pad and then back to the reservoir.  The benefits of this type of device above other cooling or heating methods have not been established at this time.

Vascutherm (ThermoTek, Carrollton, TX) is an active cold compression therapy unit with a pneumatic pump.  It provides heating, cooling and compression therapies.  The device also includes a deep vein thrombosis (DVT) mode -- this is a compression (or air) only mode, that is intended to prevent DVT.  However, it provides no additional clinical utility or impact on health outcomes than the use of ice or compression wraps.

The TEC Thermoelectric Cooling System (Maldonado Medical, Phoenix, AZ) is marketed to reduce post-operative pain and edema.  It is an iceless cold therapy compression/DVT prophylaxis machine that can also provide heat.  It is limited to a cold temperature of 49 degrees F to minimize the potential for frostbite.  However, it provides no additional clinical utility or impact on health outcomes than the use of ice or compression wraps.

According to the manufacturer, the Kinex ThermoComp^™ Device provides 3 separate pre-programmed therapies that are activated by a push of a button:

1. cold-compression,
2. contrast-compression, and
3. intermittent pneumatic compression for DVT prophylaxis.

Continuous cold is delivered by a solid-state system without ice.  Cold temperature is microprocessor-controlled within 1^° making this one of the safest devices for unsupervised use in a patient's home.  Contrast therapy cycles every 30 mins with cold at 49° for 20 mins followed by heat at 105^° for 10 mins.  Intermittent compression is delivered distal-to-proximal through a segmented pad.  Deep vein thrombosis prophylaxis is delivered from a rapid inflation pump at 50 mm Hg through a calf pad or 100 mm Hg through a foot pad.  All 3 therapies are delivered separately, however cold-compression and DVT compression can run at the same time with the device cycling DVT compression separate from limb compression.  The Kinex ThermoComp^™ Device is intended to treat post-operative injuries in the home, to reduce edema and pain, to improve blood flow to the surgical site, and to provide DVT prophylaxis therapy for high-risk patients. However, there is a lack of evidence regarding the safety and effectiveness of this device.

According to the manufacturer, the VascuTherm2 solid state device provides heat, cold (without ice), compression, and/or DVT prophylaxis therapy.  The system is pre-programmed per written physician's instructions for fully automatic, safe, trouble-free use in the patient's home.  It is indicated for pain, edema, and DVT prophylaxis for the post-operative orthopedic patient.  The precisely controlled temperature range of 43 degrees F to 105 degrees F insures against frost-bite or burns.  Therapy times are also pre-programmed to insure maximum patient compliance.  It is extremely easy for patients to set up and use. However, there is a lack of evidence regarding the safety and effectiveness of this device.

Intra-Operative and Post-Operative Cryoanalgesia for Reduction of Post-Tonsillectomy Pain

In a systematic review, Raggio and colleagues (2018) examined the effectiveness of intra-operative cryoanalgesia in the management of post-operative pain among patients undergoing palatine tonsillectomy.  These investigators performed a systematic review of PubMed, Medline, Embase, Google Scholar, and Cochrane trial registries through January 2017 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards.  They included English-language RCTs evaluating patients of all age groups with benign pathology who underwent tonsillectomy with cryoanalgesia versus without.  A total of 3limited quality RCTs involving 153 participants (age range of 1 to 60 years) were included.  Cryoanalgesia was performed with a cryotherapy probe (-56°C) in 1 trial and ice-water cooling (4°C to 10°C) in 2.  In the 3 trials reviewed, patients who received cryoanalgesia reported 21.38 %, 28.33 %, and 31.53 % less average relative post-operative pain than controls on the visual analog scale (VAS).  Review of secondary outcomes suggested no significant difference in time to resume normal diet (2 studies) or post-operative bleeding (2 studies) between the 2 groups.  Cryoanalgesia allowed patients to return-to-work 4 days earlier than controls in 1 study; 2 studies reported a trend toward less post-operative analgesia use among the treatment group; however, no statistical conclusions could be drawn.  The authors concluded that available evidence suggested that patients undergoing tonsillectomy with cryoanalgesia experienced less average post-operative pain without additional complications.  These preliminary findings need to be validated by well-designed studies.

Furthermore, UpToDate reviews on “Tonsillectomy (with or without adenoidectomy) in children: Postoperative care and complications” (Messner, 2019), “Tonsillectomy in adults” (Gibber, 2019), and “Anesthesia for tonsillectomy with or without adenoidectomy in children” (Sadhasivam, 2019) do not mention intra-operative and post-operative cryoanalgesia as a management option.

Prophylactic Hypothermia for the Management of Traumatic Brain Injury

Cooper and colleagues (2018) stated that after severe traumatic brain injury (TBI), induction of prophylactic hypothermia has been suggested to be neuro-protective and improve long-term neurologic outcomes.  These researchers examined the effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe TBI.  The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury-Randomized Clinical Trial (POLAR-RCT) was a multi-center, randomized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments (EDs) after severe TBI.  The first patient was enrolled on December 5, 2010, and the last on November 10, 2017.  The final date of follow-up was May 15, 2018.  There were 266 patients randomized to the prophylactic hypothermia group and 245 to normothermic management.  Prophylactic hypothermia targeted the early induction of hypothermia (33° C to 35° C) for at least 72 hours and up to 7 days if intra-cranial pressures were elevated, followed by gradual re-warming.  Normothermia targeted 37° C, using surface-cooling wraps when required.  Temperature was managed in both groups for 7 days.  All other care was at the discretion of the treating physician.  The primary outcome was favorable neurologic outcomes or independent living (Glasgow Outcome Scale-Extended score, 5 to 8 [scale range of 1 to 8]) obtained by blinded assessors 6 months after injury.  Among 511 patients who were randomized, 500 provided ongoing consent (mean age of 34.5 years [SD, 13.4]; 402 men [80.2 %]) and 466 completed the primary outcome evaluation.  Hypothermia was initiated rapidly after injury (median of 1.8 hours [inter-quartile range [IQR], 1.0 to 2.7 hours]) and re-warming occurred slowly (median of 22.5 hours [IQR, 16 to 27 hours]).  Favorable outcomes (Glasgow Outcome Scale-Extended score, 5 to 8) at 6 months occurred in 117 patients (48.8 %) in the hypothermia group and 111 (49.1 %) in the normothermia group (risk difference, 0.4 % [95 % confidence interval [CI]: -9.4 % to 8.7 %]; relative risk (RR) with hypothermia, 0.99 [95 % CI: 0.82 to 1.19]; p = 0.94).  In the hypothermia and normothermia groups, the rates of pneumonia were 55.0 % versus 51.3 %, respectively, and rates of increased intra-cranial bleeding were 18.1 % versus 15.4 %, respectively.  The authors concluded that among patients with severe TBI, early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months.  These findings did not support the use of early prophylactic hypothermia for patients with severe TBI.

Guidelines on management of severe traumatic brain injury from the Brain Injury Foundation (Carney, et al., 2017) concluded that early (within 2.5 hours), short-term (48 hours post-injury) prophylactic hypothermia is not recommended to improve outcomes in patients with diffuse injury.

Therapeutic Hypothermia for the Treatment of Hemorrhagic Stroke

Choi and associates (2017) noted that therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic brain injury.  In a pilot study, these researchers studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after successful treatment.  Patients were allocated randomly to either the TH group (34.5° C) or control group after successful clipping or coil embolization.  A total of 11 patients received TH for 48 hours followed by 48 hours of slow re-warming.  Vasospasm, delayed cerebral ischemia (DCI), functional outcome, mortality, and safety profiles were compared between groups.  These investigators enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4, 5 and modified Fisher Scale 3, 4).  In the TH group, 10 of 11 (90.9 %) patients had a core body temperature of less than 36° C for greater than 95 % of the 48-hour treatment period.  Fewer patients in the TH than control group (n = 11, each) had symptomatic vasospasms (18.1 % versus 36.4 %, respectively) and DCI (36.3 % versus 45.6 %, respectively), but these differences were not statistically significant.  At 3 months, 54.5 % of the TH group had a good-to-moderate functional outcome (0 to 3 on the modified Rankin Scale [mRS]) compared with 9.0 % in the control group (p = 0.089).  Mortality at 1 month was 36.3 % in the control group compared with 0.0 % in the TH group (p = 0.090).  the authors concluded that mild TH was feasible and could be safely used in patients with poor-grade SAH.  Furthermore, it may reduce the risk of vasospasm and DCI, improving the functional outcomes and reducing mortality.  Moreover, these researchers stated that larger randomized controlled studies should be conducted to determine the safety and clinical impact of TH in poor-grade SAH patients following successful intervention.

The authors stated that this study had several drawbacks.  First, this was a pilot study and should be interpreted with caution.  Second, the observed clinical benefits of hypothermia were limited because of the small sample size (n = 11).  A larger sample size may be needed to identify a meaningful difference between TH and control groups.  Third, despite well-designed neuro-critical care treatment guidelines, a hidden bias may exist between TH and control groups in critical care because the treating physicians were not double-blinded.  Fourth, the induction time of TH was confined after successful intervention.  Fifth, the different use of cooling devices was not reflected in TH group.

Yao and colleagues (2018) stated that TH has shown good results in experimental models of hemorrhagic stroke.  The clinical application of TH, however, remains controversial, since reports regarding its therapeutic effect were inconsistent.  These researchers conducted a systematic review based on PRISMA comparing TH with a control group in terms of mortality, poor outcome, DCI, and specific complications.  The subgroup analyses were stratified by study type, country, mean age, hemorrhage type, cooling method, treatment duration, rewarming velocity, and follow-up time.  A total of 9 studies were included, most of which were of moderate quality.  The overall effect demonstrated insignificant differences in mortality (risk ratio [RR] 0.78; 95 % CI: 0.58 to 1.06; p = 0.11) and poor outcome rate (RR 0.89; 95 % CI: 0.70 to 1.12; p = 0.32) between TH and the control group.  However, sensitivity analyses, after omitting 1 study, achieved a statistically significant difference in poor outcome favoring TH.  Moreover, in the subgroup analyses, the results derived from randomized studies revealed that TH significantly reduced poor outcomes (RR 0.40; 95 % CI: 0.22 to 0.74; p = 0.003).  In addition, TH significantly reduced DCI compared with control (RR 0.61; 95 % CI: 0.40 to 0.93; p = 0.02).  The incidence of specific complications (re-bleeding, pneumonia, sepsis, arrhythmia, and hydrocephalus) between the 2 groups were comparable and did not reach significant difference.  The authors concluded that the overall effect showed TH did not significantly reduce mortality and poor outcomes but led to a decreased incidence of DCI.  Compared with control, TH resulted in comparable incidences of specific complications.

Cryoanalgesia for Post-Operative Analgesia in Repair of Pectus Excavatum

Parrado and colleagues (2019) noted that cryoanalgesia has been applied to minimally invasive repair of pectus excavatum (MIRPE).  After implementation of cryoanalgesia at the authors’ institution, these researchers had several cases of delayed post-operative pneumothorax.  These investigators examined the complications and efficacy of cryoanalgesia in MIRPE.  They carried out a single-center retrospective review of pediatric patients undergoing MIRPE from June 2017 to July 2018.  Multi-modal (MM) analgesia was used in all patients.  In addition, most patients received either cryoanalgesia or elastomeric pain pumps (EPPs) as adjuncts to post-operative analgesia.  Primary outcome was clinically significant late pneumothorax; and secondary outcomes included length of stay, pain scores, opiate use, and bar displacement requiring re-operation.  A total of 101 patients undergoing MIRPE were included: 45 had cryoanalgesia + MM, 45 EPP + MM, and 11 MM alone.  Post-operative tube thoracostomy was placed in 5 patients with cryoanalgesia (4 pneumothorax; 1 effusion), 1 patient with EPP (1 pneumothorax), and none in MM alone (p = 0.25).  Pain scores at discharge were similar in all groups.  Cryoanalgesia patients received less overall in-patient opioids than other groups (p < 0.05).  No patient required re-operation for bar displacement.  The authors concluded that cryoanalgesia was an effective therapy for pain control in MIRPE.  Because thermal injury could occur on the lung and chest wall with cryoanalgesia, these researchers implemented techniques to limit and prevent this injury.  They stated that cryoanalgesia offered a safe alternative for post-operative analgesia with significant reduction in inpatient opioid requirement.  Moreover, they stated that larger prospective studies are needed to examine the long-term impact and complications of cryoanalgesia.

Cryoneurolysis for the Treatment of Post-Herpetic Neuralgia

An evidence-based report on treatment of ost-herpetic neuralgia (PHN) was developed by the Quality Standards Subcommittee of the American Academy of Neurology (Dubinsky et al, 2004) and it stated that the effectiveness of carbamazepine, nicardipine, biperiden, chlorprothixene, ketamine, Helium:Neon (He:Ne) laser irradiation, intralesional triamcinolone, cryocautery, topical piroxicam, extract of Ganoderma lucidum, dorsal root entry zone lesions and stellate ganglion block are unproven in the treatment of PHN.

Weber and colleagues (2019) noted that PHN is a common and potentially debilitating neuropathic pain condition.  Current pharmacologic therapy can be inadequate and intolerable for patients.  These researchers presented a case of a man with refractory PHN in the intercostobrachial nerve (ICBN) distribution that was successfully treated with cryoneurolysis / cryoanalgesia therapy.  Given the severity of PHN and disabling pain to patients with limited options, these investigators believed that cryoablation offers an alternative that is minimally invasive, with less risk compared to other forms of neurolysis.  This case-report showed an ICBN neuralgia related to PHN, which to the authors’ knowledge has not been reported in the literature and treated with cryoablation.  While the authors acknowledged that additional studies are needed and the conflicting data on efficacy of cryoablation with intercostal blocks and with post-thoracotomy pain, there have been positive results for cryoanalgesia for PHN in the dermatologic literature with cutaneous use.  Furthermore, the minimal risk to ICBN cryoablation given the superficial nature, as compared to intercostal blocks, whose risks include pneumothorax and vascular uptake / bleeding, allowed for the ICBN cryoanalgesia to be a viable option that should be further examined in patients who presented with features of ICBN neuralgia related to PHN.

Furthermore, an UpToDate review on “Postherpetic neuralgia” (Ortega, 2020) states that “Cryotherapy involves freezing peripheral nerves. A small, unblinded study of cryotherapy for facial pain was unable to show a significant benefit in patients with PHN [89]. The authors did not provide inclusion criteria, concomitant therapies, or information on how the response was assessed. By contrast, a second trial reported "considerable" relief in 11 of 14 patients with cryotherapy to the intercostal nerves for PHN [90]. In most cases, however, the duration of relief was less than two weeks as assessed by questionnaire”.

Ultrasound-Guided Percutaneous Intercostal Cryoanalgesia for Analgesia Following Mastectomy

Gabriel and colleagues (219) stated that acute post-mastectomy pain is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration measured in multiple weeks.  These investigators reported 3 cases in which pre-operative ultrasound (US)-guided percutaneous intercostal nerve cryoneurolysis was performed to treat pain following mastectomy.  Across all post-operative days and all 3 patients, the mean pain score on the numeric rating scale (NRS) was 0 for each day.  Similarly, no patient required any supplemental opioid analgesics during the entire post-operative period; and, no patient reported insomnia or awakenings due to pain at any time-point.  This was a significant improvement over historic controls.  The authors concluded that US-guided percutaneous cryoanalgesia is a potential novel analgesic modality for acute pain management that had a duration that better-matched mastectomy than other currently-described techniques.  These researchers stated that appropriately powered RCTs are needed to determine and quantify both potential benefits and risks.

Appendix

Selection Criteria of Cryoanalgesia for Trigeminal Neuralgia

1. Members have experienced pain for at least 6 months, and 

2. Members have tried and failed pharmacotherapies (e.g., baclofen, carbamazepine, phenytoin), or are unable to tolerate the side effects of the medication. 

Repeat cryoanalgesia may be medically necessary every 6 months.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered for indications listed in the CPB:
64600	Destruction by neurolytic agent, trigeminal nerve; supraorbital, infraorbital, mental, or inferior alveolar branch
CPT codes not covered for indications listed in the CPB:
Prophylactic hypothermia, therapeutic hypothermia – no specific code:
0442T	Ablation, percutaneous, cryoablation, includes imaging guidance; nerve plexus or other truncal nerve (eg, brachial plexus, pudendal nerve)
64605	Destruction by neurolytic agent, trigeminal nerve; second and third division branches at foramen ovale
64620	Destruction by neurolytic agent, intercostal nerve
64640	Destruction by neurolytic agent; other peripheral nerve or branch
Other CPT codes related to the CPB:
19301 - 19307	Mastectomy
21740 - 21743	Reconstructive repair of pectus excavatum or carinatum
64400	Injection, anesthetic agent; trigeminal nerve, any division or branch
64420	intercostal nerve, single
64421	intercostal nerves, multiple, regional block
HCPCS codes not covered for indications listed in the CPB:
cTreatment and Hilotherm, BioCryo Cold Compression System, Breg Polar Care Cube, ProThermo PT-9 Therapy System, Aqua Relief, Recovery+ Thermal Compression System, and Thermo Plus-System - no specific code:
A9273	Hot water bottle, ice cap or collar, heat and/or cold wrap, any type
E0217	Water circulating heat pad with pump
E0218	Water circulating cold pad with pump
E0236	Pump for water circulating pad
E0249	Pad for water circulating heat unit
E0650	Pneumatic compressor; non-segmental home
E0651	Pneumatic compressor, segmental home model without calibrated gradient pressure
E0652	Pneumatic compressor, segmental home model with calibrated gradient pressure
E0660	Non-segmental pneumatic appliance for use with pneumatic compressor; full leg
E0666	Non-segmental pneumatic appliance for use with pneumatic compressor, half leg
E0667	Segmental pneumatic appliance for use with pneumatic compressor, full leg
E0669	Segmental pneumatic appliance for use with pneumatic compressor, half leg
E0671	Segmental gradient pressure pneumatic appliance; full leg
E0673	Segmental gradient pressure pneumatic appliance, half leg
Other HCPCS codes related to the CPB:
E0676	Intermittent limb compression device (includes all accessories), not otherwise specified [not covered for active cold compression therapy units]
ICD-10 codes covered if selection criteria are met (not all-inclusive):
Numerous options	Contusion with intact skin surface [Codes not listed due to expanded specificity]
G50.0	Trigeminal neuralgia
G89.0 - G89.18	Pain, not elsewhere classified [not covered for post-tonsillectomy pain]
M25.00 - M25.08	Hemarthrosis
M25.40 - M25.48	Effusion of joint
M25.50 - M25.579	Pain in joint
M54.10 - M54.18	Radiculopathy
M54.5	Low back pain
M54.89 - M54.9	Other and unspecified dorsalgia
M60.9	Myositis, unspecified
M79.0	Rheumatism, unspecified
M79.10 - M79.18	Myalgia
M79.2	Neuralgia and neuritis, unspecified
M79.601 - M79.609	Pain in limb
M79.89	Other specified soft tissue disorders [swelling]
M79.9	Fibromyalgia
N64.4	Mastodynia
R07.1 - R07.9	Pain in chest
R10.10 - R10.13, R10.30 - R10.9	Abdominal pain
R52	Pain, unspecified
R60.0 - R60.9	Edema, not elsewhere classified
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
B02.21 - B02.29	Zoster with other nervous system involvement
C50.011 - C50.929	Malignant neoplasm of breast
C79.81	Secondary malignant neoplasm of breast
G89.21 - G89.29	Chronic pain, not elsewhere classified
I60.00 - I60.9	Nontraumatic subarachnoid hemorrhage
I61.1 - I61.9	Nontraumatic intracerebral hemorrhage
I62.00 - I62.9	Other and unspecified nontraumatic intracranial hemorrhage
Q67.6	Pectus excavatum
S06.0x0A - S06.9x9S	Intracranial injury
Z90.10 - Z90.13	Acquired absence of breast and nipple

The above policy is based on the following references: