Hyperbaric Management of Frostbite

Anatomy and Physiology

The primary mechanism of injury in frostbite involves prolonged, progressive damage to peripheral tissues. As the body cools, the first adaptive response is to preserve thermal homeostasis by redirecting blood flow to the body’s core—the critical internal organs—while restricting circulation to the cooler peripheral tissues. Maximum peripheral vasoconstriction occurs at skin temperatures as low as 15 °C (59 °F), reducing cutaneous blood flow from approximately 200 ml/min to between 20 ml/min and 50 ml/min. At lower temperatures, vasoconstriction must be interrupted to maintain metabolic function in soft tissues. Vasoconstriction is disrupted through the hunting response, or Lewis reaction, a reflex vasodilation that occurs in rhythmic bursts of 3 to 5 cycles per hour, each lasting 5 to 10 minutes.

Below 10 °C (50 °F), sensory nerves experience neuropraxia, leading to numbness. As temperatures drop further, blood viscosity increases, causing erythrocyte sludging and thrombus formation. These changes result in endothelial inflammation and the release of chemotactic factors, such as prostaglandins (PGF), thromboxane (TXA), cellular adhesion molecules (CAMs), matrix metalloproteinases (MMPs), and reactive oxygen species (ROS). Leukocyte adhesion indicates the onset of endothelial inflammatory responses, which ultimately lead to progressive dermal ischemia. Continued congestion and stasis result in circulatory collapse, endothelial plasma leakage, and tissue ischemia.[4]

Up to this point, the tissue changes are considered reversible. However, as cooling progresses below 0 °C (32 °F), cutaneous blood flow becomes negligible. Without circulation, skin temperature drops rapidly (> 0.5 °C per minute), and dermal tissues freeze. Smaller blood vessels freeze before larger ones, and venous circulation freezes before arterial.

As cooling continues, ice crystals form first in the extracellular fluid, then in the intracellular fluid, causing an osmotic fluid shift into the extracellular space. Cell death occurs due to a combination of metabolic disinhibition from tissue hypoxia, cellular dehydration from the fluid shift, and likely further damage from physical destruction caused by abrasive mechanical forces exerted on the crystal-laden tissues.

Indications

HBOT may be a therapeutic option for frostbite, either as a standalone treatment or in combination with vasodilating, anticoagulation, or hemorheologic agents like pentoxifylline. Initially limited to case studies, evidence now includes a few prospective clinical studies. The 15th Edition of the Hyperbaric Medicine Indications Manual lists HBOT for frostbite as a potential treatment in the Emerging Indications chapter.[5][6][7][8][9][10][11][12][13][14]

Contraindications

HBOT is generally safe when administered by trained personnel in an accredited facility. The most common side effect is barotrauma to the ears or sinuses. The only absolute contraindication is an untreated pneumothorax. Caution is advised for patients with respiratory infections, seasonal allergies, sinusitis, recent surgeries, emphysema, or chronic obstructive pulmonary disease with open gas pockets or blebs. HBOT should not be administered with doxorubicin, Sulfamylon, or disulfiram, nor should it follow the discontinuation of bleomycin or cisplatinum for extended periods.

Patients with asthma should be assessed for air trapping, though the condition can be managed with education and training. Sedation may be required for patients with confinement anxiety. Patients with implantable devices should have the device cleared by the manufacturer for effective delivery under pressure.

Equipment

Only approved multiple or monoplace chambers, certified by the American Society of Mechanical Engineers (ASME) or an equivalent non-American body for safe construction as a pressure vessel for human occupancy (PVHO), should be used. Accreditation for facilities and staff is provided by the Undersea and Hyperbaric Medical Society (UHMS) to ensure adherence to safety standards and proper usage.

Personnel

All HBOT sessions must be supervised directly by a physician trained in hyperbaric medicine. Physicians with the minimum required 40-hour introductory course training should be precepted by a physician Board Certified in Undersea and Hyperbaric Medicine (UHM) or possess a certificate of additional training (Certificate of Added Qualifications or CAQ) in Undersea and Hyperbaric Medicine. Support personnel should include nursing staff, preferably a certified hyperbaric nurse (CHRN), and certified hyperbaric technicians (CHTs). For multiple chamber treatments, an inside attendant should accompany the patient, with a chamber "driver" and an outside observer. For monoplane chambers, a CHT may monitor 2 monoplane chambers.

Preparation

Patients must wear clothing with low potential for static discharge. Cotton-polyester blends with a ratio of up to 60:40 are acceptable. To minimize fire risk, patients are screened for the absence of oil or petroleum-based products in hair, skin, makeup, nail polish, or deodorants. All electronic devices, including phones, watches, and hearing aids, must be left outside the chamber. Chemical or gas heating devices are prohibited inside the chamber. Transdermal patches should either be avoided or checked and covered. Patients with diabetes should have glucose levels checked before and after treatment, following approved treatment guidelines based on their levels.

Technique or Treatment

No specific treatment protocol has been identified, but a commonly used regimen based on case studies is 2.0 to 2.5 ATA for 90 to 110 minutes, with or without an air break, twice a day for the first 8 to 12 treatments. This regimen continues daily until maximum medical benefit is achieved, which typically occurs after 10 to 20 treatments. The 2021 SOS-Frostbite study showed that combining HBOT with the potent vasodilator iloprost provided greater benefit in patients with severe frostbite compared to iloprost alone.[15]

Complications

The most common complications of HBOT involve barotrauma of the ears and, less frequently, the sinuses. Oxygen toxicity, though extremely rare, has been reported without recurrence or sequelae. Another rare complication is barotrauma to parenchymal lung tissue from blebs or emphysematous bullae, leading to pneumothorax, but this condition is also rarely reported after HBOT. A review of 782 patients undergoing 11,376 HBOT found that 17% experienced ear pain or discomfort, with barotrauma confirmed in only 3.8%.

No cases of barotrauma to teeth or sinuses were identified. Four patients experienced oxygen seizures, but none had recurrences or sequelae. Other complications include possible worsening of existing cataracts and a temporary increase in myopia, which resolves within weeks after treatment. Patients with confinement anxiety (claustrophobia) may require anxiolytic therapy.

Clinical Significance

Pathophysiologic evidence indicates that tissue damage in slow-onset frostbite primarily results from a multifactorial vascular response. Intracellular ice crystal formation in the final stage typically determines irreversible necrosis, eliminating the potential for tissue regeneration. A recoverable phase remains possible if rewarming precedes complete tissue destruction. However, endothelial reperfusion injury may occur within 4 to 8 hours after rewarming. All treatment strategies aim to restore and maintain microvascular flow while minimizing inflammation, with particular focus on endovascular inflammatory responses and prevention of reperfusion injury. Management is categorized into 3 phases: prethaw field care, the immediate rewarming phase (preferably in a hospital), and the postthaw phase, which can extend over several weeks to months.[16]

In most cases, postthaw phase treatment begins only after physical signs of tissue damage become evident. Wounds are staged and assessed, usually more than 24 to 48 hours after rewarming. This delay often results from the absence of early recognition protocols and the difficulty in identifying frostbite during its initial stages.[17][18] This diagnostic challenge may lead to the further loss of tissue that lies in a transitional zone between reversible and irreversible damage. Contributing factors include reperfusion injury and persistent or progressive vascular compromise driven by ongoing inflammation.[19][20]

In direct high thermal injuries such as burns, a penumbral region known as the zone of stasis surrounds the central zone of coagulation. Although viable, this zone remains vulnerable to secondary injury from vasoconstriction, vascular thrombosis, and endothelial fibrin deposition. Frostbite exhibits a similar pattern of injury, despite being caused by low thermal insult. Treatment in phase 3 focuses on preventing additional loss within this penumbral area. Since the opportunity for salvage is time-sensitive, early intervention is critical. Cauchy supports early diagnosis and management using a new classification system applied within the first 24 hours, based on the topographic distribution of lesions and supplemented by isotopic bone scanning with technetium-99m hydroxymethylene diphosphonate (99mTc-HMDP).[21]

Current treatment options remain limited by the absence of high-level evidence from well-designed randomized controlled trials. Nonetheless, all therapeutic strategies target the inhibition of endovascular inflammation and the early restoration of perfusion.

Vasodilators such as nitroglycerine and papaverine have shown utility. However, the effectiveness of these agents is not strongly supported when used in isolation. When incorporated into a stepwise approach alongside thrombolytic agents such as tissue plasminogen activator (rTPA) or streptokinase, the combined regimen receives a 1B-C recommendation under the classification criteria of the American College of Chest Physicians (ACCP). Iloprost, a prostacyclin analogue with potent vasodilatory effects, carries a 1B recommendation as well. However, this drug is currently unavailable in the U.S.

HBOT supports the metabolic demands of injured tissue by promptly reversing hypoxia and mitigating endothelial inflammation. This treatment also reduces reperfusion injury by limiting leukocyte adhesion. Although no randomized controlled trials have evaluated this approach, and the American College of Chest Physicians has not issued a recommendation, multiple case series have reported outcomes with HBOT initiated at various time points after rewarming. All suggest some degree of tissue salvage and reduced amputation rates, though these findings lack comparison with matched controls. Earlier initiation of treatment appears to yield more favorable outcomes, likely due to preservation of penumbral tissue. Several studies have combined HBOT with vasodilating, anticoagulant, or hemorheologic agents such as pentoxifylline, with reported success.[22]

Enhancing Healthcare Team Outcomes

Adjuvant therapy with HBOT for frostbite appears reasonable, well-tolerated, and safe. However, supporting evidence remains limited to level 4 studies, primarily case series with only historical outcomes for comparison. Nurses and clinicians involved in wound care should be reminded about HBOT as a potential intervention. Optimal outcomes typically require an interprofessional team involving hyperbaric medicine, nursing, wound care, plastic surgery, and trauma surgery.