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Frostbite (Clinical)

Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. There are multiple cold-related injuries, with frostbite being the most common. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0℃ (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Clinical signs include skin pallor, anesthesia, blistering, and tissue necrosis. Initial treatment is rapid rewarming. Further interventions (including thrombolysis) will depend on the timing of presentation, severity of injury, and presence of other comorbidities.

Last updated: Mar 4, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite is injury to tissue resulting from cold exposure at temperatures below 0°C (32°F). Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite exists on the severe end of a spectrum, with frostnip Frostnip Frostbite and pernio Pernio Recurrent localized itching, swelling and painful erythema on the fingers, toes or ears, produced by exposure to cold. Frostbite at the milder end.

Epidemiology[1,2,4]

  • Poor population statistics (no formal reporting) 
  • Vulnerable populations:
    • Homeless
    • Military personnel
    • Children
    • Elderly
  • Risk factors:
    • Low ambient temperature
    • High-velocity wind
    • Exposure to water or snow
    • Clothing that is wet, constrictive, or inadequately insulating
    • Impaired judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment (ethyl alcohol, drugs, fear/panic)
    • History of peripheral vascular disease or Raynaud’s phenomenon 
  • Commonly affected areas: poorly vascularized periphery:
    • Fingers 
    • Toes 
    • Nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal) 
    • Ears 
    • Penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis: Anatomy

Pathophysiology[1,2,4]

Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite injury results from:

  • Immediate cold-induced cell death Cold-Induced Cell Death Frostbite 
    • Tissue cools below subfreezing → extra and intracellular ice crystals form
    • Fluid and electrolyte fluxes → lysis of cell membranes with subsequent cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death
    • Inflammatory process mediated by thromboxane A2 Thromboxane A2 An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS). Arterial Pressure Regulation, prostaglandin F2-alpha, bradykinins, and histamine
    • Leads to tissue ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage 
    • Worsened in setting of thawing followed by refreezing 
  • Tissue ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage
    • Decreased temperatures increase blood viscosity Blood viscosity The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. Vascular Resistance, Flow, and Mean Arterial Pressure → microthrombi
    • Vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs and stasis result in tissue hypoperfusion and ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage.
  • Reperfusion-related localized inflammatory processes 
    • Caused by return of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure to ischemic areas
    • Activated endothelial cells release activated oxygen species, initiating inflammatory response.
    • WBCs flood to perfused area, releasing inflammatory mediators.
    • Leads to cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death

4 phases:

  1. Pre-freeze:
  2. Freeze-thaw:
  3. Vascular stasis: microvascular thrombus formation
  4. Late progressive ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage:
    • Hypoperfusion
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Tissue necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
Frostbite

Stages of frostbite

Image by Lecturio.

Clinical Presentation and Diagnosis

The diagnosis of frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite is clinical and should be distinguished from less severe forms of cold injury Cold injury A physical injury caused by exposure of the body to extremely low ambient temperatures that may lead to loss of body parts, or in extreme cases, death. Examples of cold injury are frostbite and chilblains. Frostbite ( frostnip Frostnip Frostbite).

Forms of cold injury Cold injury A physical injury caused by exposure of the body to extremely low ambient temperatures that may lead to loss of body parts, or in extreme cases, death. Examples of cold injury are frostbite and chilblains. Frostbite and classification

  • Chilblain ( pernio Pernio Recurrent localized itching, swelling and painful erythema on the fingers, toes or ears, produced by exposure to cold. Frostbite):[6] 
    • Local inflammatory injury associated with extended or repeated exposure (1–5 hours) to cold (above freezing temperatures), wet conditions
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions blood vessels constrict → hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome, vessel wall inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, and possibly edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema in the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions
    • Purplish or reddish lesions, which can be pruritic or painful
    • Commonly affects the hands and feet
  • Trench (immersion) foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy:[6] 
    • Non-freezing cold injury Cold injury A physical injury caused by exposure of the body to extremely low ambient temperatures that may lead to loss of body parts, or in extreme cases, death. Examples of cold injury are frostbite and chilblains. Frostbite
    • Prolonged (> 12 hours) exposure of the feet to cold, wet conditions
    • Tight shoes/boots make the condition worse.
    • Extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema affects the soft tissues (including the blood vessels and nerves) → pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, numbness, bullae Bullae Erythema Multiforme
    • Can result in tissue loss
  • Frostnip Frostnip Frostbite:[5,6]
    • Most common freezing cold injury Cold injury A physical injury caused by exposure of the body to extremely low ambient temperatures that may lead to loss of body parts, or in extreme cases, death. Examples of cold injury are frostbite and chilblains. Frostbite
    • No ice formation, no tissue loss
    • Cannot clinically distinguish between frostnip Frostnip Frostbite and frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite initially
    • Numbness and pallor resolve with passive rewarming.
  • Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite:
    • Classic 4-tier staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis (derived from burn classification):[6]
      • Based on acute physical examination findings
      • Assessed after rewarming, but before imaging
      • Graded from 1st-degree to 4th-degree
    • Alternative: 2-tier classification
      • Easier to use in the field setting
      • Assessment of severity (after rewarming) can be done without imaging.
      • Superficial: no or minimal expected tissue loss (1st- or 2nd-degree)
      • Deep: expected tissue loss (3rd- or 4th-degree)
    • Once in a field hospital or clinic, use Cauchy classification (grade based on anatomical extent of frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite after rewarming, with higher grades indicating higher risk of amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation):[9,11]
      • Grade 1: no lesion → no amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
      • Grade 2: lesion on distal phalanx → tissue amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation
      • Grade 3: lesion on the intermediary and proximal phalanx (beyond the distal phalanx) → amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation of the digit
      • Grade 4: lesion on the carpal/tarsal → amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation of the limb
    • Classifying frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite is helpful to healthcare workers, as risk of tissue loss and amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation is an important factor in evaluation decisions.
Table: 2-tier and 4-tier classification systems of frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite[5,12]
2-tier classification 4-tier classification Depth of damage Signs
Superficial 1st-degree Partial-thickness skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions freezing
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
  • White/yellow, firm plaque Plaque Primary Skin Lesions may develop
  • Mild edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Slight epidermal sloughing
  • 2nd-degree Full-thickness skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions freezing
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Superficial skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions blisters (with clear or milky fluid)
  • Deep 3rd-degree Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess freezing
  • Deep, hemorrhagic blisters
  • Substantial edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • May have blue/black appearance
  • 4th-degree Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, subcutaneous tissue Subcutaneous tissue Loose connective tissue lying under the dermis, which binds skin loosely to subjacent tissues. It may contain a pad of adipocytes, which vary in number according to the area of the body and vary in size according to the nutritional state. Soft Tissue Abscess freezing which extends to deeper structures (e.g., muscle, tendon, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types)
  • Red, mottled appearance
  • Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
  • Necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Table: Cauchy classification for the severity of frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite injury[9.11]
    Grade Initial lesion (day 0) Blisters Amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation
    1 No lesion None No amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation
    2 Lesion/ cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination in distal phalanx Clear blisters Tissue amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation
    3 Lesion/ cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination beyond distal phalanx (to the proximal phalanx) Hemorrhagic blisters on the digit Amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation of the digit
    4 Lesion on the carpal/tarsal Hemorrhagic blisters on the carpal/tarsal region Amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation of the limb

    Related videos

    Additional evaluation of severity

    In both the field and the hospital, assess perfusion after rewarming.[9]

    • Examine the following:
      • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions color and temperature
      • Sensation
      • Pulses
      • Capillary refill
    • Equipment (found in expedition camps or field clinics) to help in assessment includes:
      • Fast-response infrared thermometers
      • Pulse oximeters
      • Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) devices

    In the hospital setting, imaging helps with evaluating the extent of injury and other comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus:[12]

    • Radiography:
      • Initial survey of the limb
      • Can show trauma-related fractures and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types destruction
    • Standard or digital subtraction angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery:
      • Imaging method of choice for those presenting within 24 hours after deep (3rd- or 4th-degree) frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite injury 
      • Used to assess perfusion deficits in frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite injuries; identifies candidates for thrombolytic therapy
    • Technetium (Tc)-99m scintigraphy Scintigraphy Sjögren’s Syndrome ( bone scan Bone Scan Osteosarcoma):[11]
      • Indicated in those presenting with 2nd-, 3rd-, or 4th-degree frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite injuries
      • In candidates for thrombolysis, the test is performed within 24 hours after thawing.
      • For those not undergoing thrombolysis, the test is generally performed 2 days after the original injury.
      • Also used after angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery and treatment with intra-arterial thrombolysis
      • Assesses perfusion and tissue viability
      • Accurately predicts level of amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation in majority of cases (when performed on day 2)
    • Single-photon emission computed tomography Single-photon emission computed tomography An imaging technique using a device which combines tomography, emission-computed, single-photon and tomography, x-ray computed in the same session. Nuclear Imaging ( SPECT SPECT An imaging technique using a device which combines tomography, emission-computed, single-photon and tomography, x-ray computed in the same session. Nuclear Imaging)/computed tomography (CT) combined with bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types scanning can identify areas of tissue necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage even before physical manifestations are observed.
    • Magnetic resonance angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery:
      • Visualizes both blood vessels and tissues
      • An alternative to digital subtraction angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery to assess vascular patency but has no therapeutic potential
      • Limited availability and less studied than above methods

    Management

    Individual protocols may vary based on location. The following recommendations are based on US and UK guidelines. 

    Prevention[5,6,11]

    • Educate individuals who participate in activities involving cold exposure about injuries from the cold.
    • Measures:
      • Use of proper clothing:
        • Internal layer: allows evaporation of sweat with minimal absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
        • Middle layer: for insulation (e.g., fleece)
        • Removable outer layer: wind and water-resistant; allows for evaporation of moisture
        • Protect toes, fingers, ears, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions (when wind-chill temperatures can cause frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite within ≤ 30 minutes). 
        • Remove wet clothing as soon as possible.
      • Pack blankets, external warmers, and additional clothing.
      • Proper hydration and well-balanced diet
      • Communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence access (phone) in case of emergency

    Prehospital[2,5,6,8]

    • Remove any wet clothing.
    • Bring patient to a warm environment and try to warm the area/limb with body heat Heat Inflammation (e.g., place in axilla Axilla The axilla is a pyramid-shaped space located between the upper thorax and the arm. The axilla has a base, an apex, and 4 walls (anterior, medial, lateral, posterior). The base of the pyramid is made up of the axillary skin. The apex is the axillary inlet, located between the 1st rib, superior border of the scapula, and clavicle. Axilla and Brachial Plexus: Anatomy).
    • Do not put pressure on frostbitten extremities (e.g., rubbing frostbitten extremities or walking on feet affected by frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite).
      • Remove any constricting material or jewelry from the body part.
      • Avoid rubbing or applying friction (to warm the part), as this worsens the injury.
    • Do not rewarm if there is a chance that freezing will recur:
      • More extensive injury occurs with thawed tissue that refreezes.[11]
      • ↑ Prostaglandin and thromboxane release in the freeze–thaw cycle leads to vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure, platelet aggregation Platelet aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Hemostasis, thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus → more injury
      • AVOID refreezing if thawing occurs in the field.
    • Oral, and possibly IV, hydration
    • Supplemental O2, if SPO2 < 88% or at altitudes > 4000 m[11]

    Rewarming[2,5,6,8]

    In the hospital, first treat hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia (decrease in core temperature to < 95℉ (35℃)), if present, and/or other life-threatening conditions. Manage the associated cold injury Cold injury A physical injury caused by exposure of the body to extremely low ambient temperatures that may lead to loss of body parts, or in extreme cases, death. Examples of cold injury are frostbite and chilblains. Frostbite as follows:

    • Rewarm in warm water (37°C–39°C (98.6°F–102.2°F)) bath.
    • Provide analgesia Analgesia Methods of pain relief that may be used with or in place of analgesics. Anesthesiology: History and Basic Concepts during rewarming:
      • NSAIDs NSAIDS Primary vs Secondary Headaches: ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 12 mg/kg daily, divided into 2 doses, until the wound has healed (4–6 weeks)[9]
      • IV opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics as needed
    • Thawing completed when tissue is red or purple and soft to the touch:
      • Generally takes 20–40 minutes
      • Air dry → do not towel dry (to avoid friction)
      • Avoid ambulation on lower extremity that is thawed.
    • IV hydration Iv Hydration Crush Syndrome

    Wound care[5,7,8,10,11]

    • Application of bulky dressing (using non-adherent gauze as the 1st layer).
    • Topical aloe vera applied every 6 hours with dressing changes.
    • Elevation of the limb to reduce edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) and nonsteroidal antiinflammatory drugs Nonsteroidal Antiinflammatory Drugs Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs) ( NSAIDs NSAIDS Primary vs Secondary Headaches) to help reduce inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Blisters:
      • Do not debride in the field.
      • No clear consensus on managing clear tense (non-hemorrhagic) blisters, but may be drained at the provider’s discretion (especially if movement is impaired).
      • Hemorrhagic blisters are a sign of deeper tissue damage and should be left intact (not debrided).

    Infection prophylaxis Prophylaxis Cephalosporins[5,7,8,10,11]

    • Tetanus prophylaxis Tetanus Prophylaxis Overview of Bone Fractures recommended (follow usual guidelines)
    • Antibiotics:
      • Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite is not inherently prone to infection.
      • Administer only if there is significant trauma, or signs or symptoms of cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis or sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
      • Coverage should include:
        • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus spp.
        • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus spp.
        • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas spp.

    Thrombolysis[10]

    Vascular thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus is associated with frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite injury; in those at risk for amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation, thrombolytic therapy is considered.

    • Used in severe injury presenting within 24 hours:
      • Treatment option for grades 3 or 4
      • Patient should be hemodynamically stable, with absent blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure in affected limb after rewarming.
    • Perform subtraction angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery within the 1st 24 hours (or technetium-99m scanning):[5,11]
      • Best outcomes if thrombolysis performed within 12 hours
      • If in a remote area, transfer patient to a capable facility if therapy can be given within 24 hours.
    • Options include intravenous or intra-arterial tissue plasminogen activator Tissue plasminogen activator A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to fibrinolysin. It has fibrin-binding activity and is immunologically different from urokinase-type plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. Hemostasis ( tPA tPA Ischemic Stroke), or intravenous or intra-arterial heparin or enoxaparin Enoxaparin Low-molecular-weight fragment of heparin, having a 4-enopyranosuronate sodium structure at the non-reducing end of the chain. It is prepared by depolymerization of the benzylic ester of porcine mucosal heparin. Therapeutically, it is used as an antithrombotic agent. Anticoagulants:
      • tPA tPA Ischemic Stroke 0.15 mg/kg IV bolus over 15 minutes, followed by infusion of 0.15 mg/kg/hr for 6 hours; total maximum dose, 100 mg, plus
        • Heparin 500–1000 units/hr IV (with goal of 2x the control PTT) for 6 hours, or
        • Enoxaparin Enoxaparin Low-molecular-weight fragment of heparin, having a 4-enopyranosuronate sodium structure at the non-reducing end of the chain. It is prepared by depolymerization of the benzylic ester of porcine mucosal heparin. Therapeutically, it is used as an antithrombotic agent. Anticoagulants 1 mg/kg SC for 1 dose
      • tPA tPA Ischemic Stroke 3 mg intra-arterial bolus, followed an intra-arterial infusion of 0.5–1 mg/hr (via femoral or brachial artery Brachial Artery The continuation of the axillary artery; it branches into the radial and ulnar arteries. Cubital Fossa: Anatomy) plus heparin 500 units/hr intra-arterial 
    • Important tPA tPA Ischemic Stroke considerations:
      • tPA tPA Ischemic Stroke should not be given to individuals with risk factors for bleeding, including (but not limited to):
      • Treatment should be discontinued:
        • When perfusion is restored ( angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery or technetium-99m scanning every 12–24 hours), or 
        • When 72 hours is reached
      • Potential risks and complications:
        • Systemic and catheter-site bleeding
        • Compartment syndrome Compartment Syndrome Compartment syndrome is a surgical emergency usually occurring secondary to trauma. The condition is marked by increased pressure within a compartment that compromises the circulation and function of the tissues within that space. Compartment Syndrome
        • Failure to restore blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure and salvage the tissue
    • IV prostacyclins (e.g., iloprost Iloprost An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. Pulmonary Hypertension Drugs):[5,11]
      • Effects:
        • Potent vasodilator
        • Platelet aggregation Platelet aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Hemostasis, lymphocyte adhesion Adhesion The process whereby platelets adhere to something other than platelets, e.g., collagen; basement membrane; microfibrils; or other ‘foreign’ surfaces. Coagulation Studies to endothelial cells 
      • Considered in grade 3 or 4 injuries (< 72 hours after the injury)
      • May be given with or without tPA tPA Ischemic Stroke in the 1st 48 hours
        • 0.5 ng/kg/min, increasing by 0.5 ng/kg/min every 30 minutes, up to 2 ng/kg/min
        • If headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess or hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension occurs, reduce to highest rate without side effects
        • Infusion is a 5- to 8-day treatment for 6 hours per day.
    • Monotherapy with low-molecular-weight heparin or unfractionated heparin Unfractionated heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Anticoagulants is not recommended (insufficient data).[5]

    Surgical management[1,5,7,8,10,11]

    • Initial assessment might overestimate real extent of tissue injury
    • No surgical treatment until demarcation occurs (unless overwhelming infection or sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock is present).
    • For many years, the axiom “ Frostbite Frostbite Injuries due to cold weather are common among children and athletes who are involved in sports played in cold conditions. Frostbite is a direct freezing injury to the peripheral tissues and occurs when the skin temperature drops below 0°C (32°F). Common sites of frostbite include the nose, ears, fingers, and toes. Frostbite in January, amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation in July” applied to practice:
      • Indicates that a waiting period is needed to determine viability, and early amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation increases morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status.
      • In general, it takes up to 3 months to fully determine whether tissue is viable.
      • Most amputations can be done 6–12 weeks after injury.
    • Indications for early surgical procedures:
      • Necrotic tissue and/or blisters → debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome
      • Compartment syndrome Compartment Syndrome Compartment syndrome is a surgical emergency usually occurring secondary to trauma. The condition is marked by increased pressure within a compartment that compromises the circulation and function of the tissues within that space. Compartment Syndrome fasciotomy Fasciotomy Surgical incision on the fascia. It is used to decompress compartment pressure (e.g. in compartment syndromes; circumferential burns and extremity injuries) or to release contractures (e.g. in dupuytren’s contracture). Compartment Syndrome

    Additional recommendations and therapies[1,5,11]

    • Recommendations:
    • Post-thaw hydrotherapy, once to twice daily at 37℃–39℃ (98.6℉–102.2℉):
      • Increases circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment
      • Removes superficial bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
      • Debrides devitalized tissue
    • Hyperbaric oxygen Hyperbaric oxygen The therapeutic intermittent administration of oxygen in a chamber at greater than sea-level atmospheric pressures (three atmospheres). It is considered effective treatment for air and gas embolisms, smoke inhalation, acute carbon monoxide poisoning, caisson disease, clostridial gangrene, etc. The list of treatment modalities includes stroke. Decompression Sickness therapy (HBOT):
      • Mixed results
      • Theoretically, HBOT increases tissue oxygenation, but this requires effective blood supply.
    • Chemical or surgical sympathectomy:
      • Sympathetic tone affects the blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure.
      • Effects:
        • If performed immediately, sympathectomy actually increases edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and tissue loss.
        • If performed 24–48 hours after thawing, sympathectomy has been observed to reduce edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and tissue loss.
        • May have benefits in decreasing long-term pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, hyperhidrosis Hyperhidrosis Excessive sweating. In the localized type, the most frequent sites are the palms, soles, axillae, inguinal folds, and the perineal area. Its chief cause is thought to be emotional. Generalized hyperhidrosis may be induced by a hot, humid environment, by fever, or by vigorous exercise. Malassezia Fungi, and paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome.
      • Results are still conflicting, and no solid recommendation has been given.

    Treatment of other cold injuries[6,8]

    • Chilblains Chilblains Recurrent localized itching, swelling and painful erythema on the fingers, toes or ears, produced by exposure to cold. Frostbite:
      • Remove wet clothing.
      • Dry the area and massage.
      • Permanent damage is not common; symptoms clear up in 2 weeks.
    • Trench foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy: 
      • Rewarm gradually.
      • Elevate the legs or hands.
      • Air dry at room temperature.
      • Tetanus prophylaxis Tetanus Prophylaxis Overview of Bone Fractures
      • Proper foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy hygiene (replace wet socks; use moisture-wicking socks)

    Clinical Relevance

    • Raynaud’s phenomenon: exaggerated vascular response to cold temperatures or emotional stress causing sharply demarcated color changes of digits. Blood vessels constrict, which leads to digits turning blue. Digits return to normal color 10–20 minutes after cold is removed.
    • Hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia: drop in core body temperature Body Temperature The measure of the level of heat of a human or animal. Heatstroke < 35°C (95°F). Classified into mild, moderate, and severe forms. Management involves rewarming of patient by external or internal methods, depending on severity.

    References

    1. Petrone, P., Kuncir, E. J., Asensio, J. A. (2003). Surgical management and strategies in the treatment of hypothermia and cold injury. Emergency Medicine Clinics of North America, 21(4), 1165–1178. https://doi.org/10.1016/S0733-8627(03)00074-9
    2. Murphy, J. V., Banwell, P. E., Roberts, A. H., McGrouther, D. A. (2000). Frostbite: pathogenesis and treatment. Journal of Trauma and Acute Care Surgery, 48(1), 171. https://doi.org/10.1097/00005373-200001000-00036
    3. Long, W. B., 3rd, Edlich, R. F., Winters, K. L., Britt, L. D. (2005). Cold injuries. Journal of Long-Term Effects of Medical Implants, 15(1), 67–78. https://doi.org/10.1615/JLongTermEffMedImplants.v15.i1.80
    4. Imray, C. H., Oakley, E. H. (2005). Cold still kills: cold-related illnesses in military practice freezing and non-freezing cold injury. Journal of the Royal Army Medical Corps, 151(4), 218–222. https://doi.org/10.1136/jramc-151-04-02
    5. McIntosh, S. E., Freer, L., Grissom, C. K., Auerbach, P. S., Rodway, G. W., Cochran, A., Giesbrecht, G. G., McDevitt, M., Imray, C. H., Johnson, E. L., Pandey, P., Dow, J., Hackett, P. H. (2019). Wilderness Medical Society clinical practice guidelines for the prevention and treatment of frostbite: 2019 update. Wilderness & Environmental Medicine, 30(4), S19–S32. https://doi.org/10.1016/j.wem.2019.05.002
    6. Cappaert, T. A., Stone, J. A., Castellani, J. W., Krause, B. A., Smith, D., Stephens, B. A. (2008). National athletic trainers’ association position statement: environmental cold injuries. Journal of Athletic Training, 43(6), 640–658. https://doi.org/10.4085/1062-6050-43.6.640
    7. Kaufman, E., Imray, C. (2021). Frostbite. BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/997
    8. McLeron, K. (20140.  State of Alaska Cold Injury Guidelines (7th ed.). Juneau, AK: Department of Health and Social Services Division of Public Health Section of Community Health and EMS. Retrieved November 16, 2022, from https://health.alaska.gov/dph/Emergency/Documents/ems/documents/Alaska%20DHSS%20EMS%20Cold%20Injuries%20Guidelines%20June%202014.pdf
    9. Cauchy, E., Davis, C. B., Pasquier, M., Meyer, E. F., Hackett, P. H. (2016). A new proposal for management of severe frostbite in the austere environment. Wilderness & Environmental Medicine, 27(1), 92–99. https://doi.org/10.1016/j.wem.2015.11.014
    10. Hickey, S., Whitson, A., Jones, L., Wibbenmeyer, L., Ryan, C., Fey, R., Litt, J., Fabia, R., Cancio, L., Mohr, W., Twomey, J., Wagner, A., Cochran, A., Bailey, J. K. (2020). Guidelines for thrombolytic therapy for frostbite. Journal of Burn Care & Research, 41(1), 176–183. https://doi.org/10.1093/jbcr/irz148
    11. Handford, C., Buxton, P., Russell, K., Imray, C. E., McIntosh, S. E., Freer, L., Cochran, A., Imray, C. H. (2014). Frostbite: a practical approach to hospital management. Extreme Physiology & Medicine, 3(1), 7. https://doi.org/10.1186/2046-7648-3-7
    12. Millet, J. D., Brown, R. K., Levi, B., Kraft, C. T., Jacobson, J. A., Gross, M. D., Wong, K. K. (2016). Frostbite: spectrum of imaging findings and guidelines for management. RadioGraphics, 36(7), 2154–2169. https://doi.org/10.1148/rg.2016160045

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