Frostbite and Dermal Cold Injury

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Frostbite and Dermal Cold Injury

• Katie Dolbec, MD

2
The Case

• A 48-year-old gentleman is brought to the ED by
  EMS.
• His roommate found him staggering back into his
  house after being outside. The patient got into
  a fight with his roommate and overdosed on Ambien
  - possibly up to sixty 5-mg tablets.
• The patient went outside for an unclear period of
  time. He fell while he was outside, striking his
  face on a woodpile. He apparently lost
  consciousness and then was outside in the bitter
  cold with temperatures at 0 degrees.
• His core temperature on arrival is 32oC by Foley
  catheter. He has evidence of significant
  frostbite of both hands with limited range of
  motion of his fingers and toes his hands are
  frozen, discolored red and white and without
  capillary refill. He also has evidence of
  superficial frostbite of his knees and his left
  elbow.
• His tetanus is up-to-date.
• He does not smoke cigarettes.

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Frostbite Definition

• Freezing injury of tissue
• Ice crystal formation in superficial or deep
  structures

5
Epidemiology Risk Factors

• Alcohol consumption (46)
• Motor vehicle problems (19)
• Psychiatric illness (17)
• Vehicular failure (15)
• Drug misuse (4)
• Homelessness
• Military
• Recreational and athletic participants
• Improper clothing
• History of previous cold injury
• Fatigue
• Dehydration
• Wound infection
• Atherosclerosis
• Diabetes
• Smoking
• High Altitude, Hypoxia
• African American race
• Being raised in the south

Psych/Behavioral (and car troubles)
Vascular
Genetic/Inherent
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Epidemiology

• Incidence unknown
• Common anatomic locations
• Feet
• Hands
• Ears
• Nose
• Cheeks
• Penis

7
Hershkowitz M. Penile Frostbite, an Unforseen
Hazard of Jogging. New England Journal of
Medicine. Jan 20, 1977.
8
Travis S, Roberts D. Arctic Willy. BMJ, Vol. 299,
23-30 December 1989.
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Epidemiology

• Population at risk for co-existing conditions
• Consider manage
• Hypothermia
• Trauma

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Pathophysiology

• Frostbite occurs when tissue heat loss exceeds
  the ability of local tissue perfusion to prevent
  freezing of tissues
• 4 Overlapping phases of tissue cooling
• Prefreeze phase
• Freeze-thaw phase
• Vascular stasis phase
• Late ischemic phase

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Pathophysiology Prefreeze Phase

• Tissue cooling lt10oC
• Sensation is lost at 10oC
• Vasoconstriction
• Hunting reflex (cold-induced vasodilation)
• Episodes of transient vasodilation every 7-10 min
• Disappears with prolonged exposure to cold
• Ischemia
• No ice crystal formation

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Pathophysiology Freeze-Thaw Phase

• Temperatures between -6oC and -15oC
• Ice crystals form intracellularly (rapid freeze)
  and/or extracellularly (slow freeze)
• Cellular damage
• Thawing initiates reperfusion injury and
  inflammatory response

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Pathophysiology Vascular Stasis Phase

• Vessels alternate between constriction and
  dilation
• Blood leaks from vessels or coagulates within them

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Pathophysiology Late Ischemic Phase

• Ongoing reperfusion injury
• Inflammatory cascade
• Intermittent vasoconstriction
• Microvascular emboli/macrovascular thrombi
• Progressive tissue ischemia and infarction

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Pathophysiology

• Mechanisms of Tissue Damage
• Cellular injury
• Tissue ischemia
• Inflammatory mediator release

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Pathophysiology Cellular Injury

• Extracellular and intracellular ice crystal
  formation
• 1) Extracellular ice increases extracellular
  oncotic pressure
• Water moves out of cells
• Cellular electrolyte, pH shifts
• Cellular dehydration
• Protein and lipid derangement
• Cell membrane lysis
• 2) Intracellular ice causes disruption of cell
  membranes
• With thawing, tissue edema ensues
• Cellular necrosis

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Pathophysiology Tissue Ischemia

• Local vasoconstriction
• Increased blood viscosity
• Microvascular damage
• Endothelial disruption
• Transcapillary plasma loss
• Edema
• Further limitation of blood flow
• Endothelial damage ? microthrombi formation
• Freeze-thaw-refreeze increases severity of
  thrombosis and ischemia

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• Immediately after thawing ? blood flows freely
• Five-ten minutes post-thaw ? blood begins to
  sludge
• Clot
• Ischemia
• Necrosis

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• Frostbitten skin from rabbit ear transplanted
  autogenously to normal ear
• Normal skin transplanted to frozen area
• Frostbitten skin survived on normal tissue bed
• Normal skin necrosed on frostbitten bed

Weatherly-White RCA, Sjostrom B, Paton BC.
Experimental Studies in Cold Injury. Journal of
Surgical Research 1964 (Jan) Vol. IV, No. 1.
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Pathophysiology - Inflammatory Mediator Release

• Secondary effect of pro-inflammatory cytokine
  release
• Thromboxane A2
• Prostaglandin F2-alpha
• Bradykinin
• Histamine
• Exacerbates cellular damage
• Causes further ischemia
• Vasoconstriction
• Platelet aggregation
• Blood vessel thrombosis

Found in frostbite blister fluid
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• Tissue frozen and thawed twice sustained greater
  injury
• Double 3-min freezes caused more damage than a
  continuous 6-minute freeze

Hardenbergh E, Ramsbottom R. Experimental
Frostbite The Effect of Double Freeze on
Tissue Survival in the Mouse Foot. Cryobiology,
Vol. 5, No. 5, 1969
22
Reamy BV.Frostbite Review and Current Concepts.
Journal of American Board of Family Practice,
Jan. Feb. 1998, Vol. 11, No. 1
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Classifying Frostbite
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Frostnip

• Superficial non-freezing cold injury
• Tends to occur on exposed skin
• Ears, cheeks, nose
• Intense vasoconstriction
• Ice crystals (frost) form on skin surface
• Indicates favorable conditions for frost bite
• DOES NOT EQUAL FROSTBITE
• RESULTS IN NO TISSUE LOSS
• NO LONG-TERM SEQUELAE

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First-degree Frostbite

• White or yellow firm, slightly raised plaque
• Numbness
• No gross tissue infarction
• Slight epidermal sloughing
• Mild edema

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Second-degree Frostbite

• Superficial skin vesiculation
• Clear or milky fluid in blisters
• Surrounding erythema and edema

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Third-degree Frostbite

• Deeper, hemorrhagic blisters
• Injury has extended into reticular dermis and
  dermal vascular plexus

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Fourth-degree Frostbite

• Extends through the dermis
• Involves subcutaneous tissues
• Necrosis extending into muscle and to bone

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Two-Tiered Classification System

• Better in the field
• More of a clinical diagnosis
• Superficial frostbite
• Deep frostbite

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Superficial Frostbite

• No or minimal anticipated tissue loss
• Corresponds with 1st- and 2nd-degree injury
• Treat conservatively
• Favorable prognostic factors
• Retained sensation
• Normal skin color
• Clear blisters
• Blisters only in distal phalanges

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Deep Frostbite

• Deeper injury and anticipated tissue loss
• Corresponds with 3rd- and 4th-degree injury
• Requires aggressive management
• Poor prognostic features
• Nonblanching cyanosis
• Absent Doppler pulses
• Firm skin
• Dark, fluid-filled (hemorrhagic) blisters
• OR
• Little or no blister formation (even worse)

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Prevention

• Pathophysiology told us that tissue perfusion has
  to exceed heat loss
• Maintain peripheral perfusion
• Blood flow heat
• Allow heat to get to tissues
• Protection from the cold
• Prevent heat loss

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Maintaining Peripheral Perfusion

• Maintain core temperature
• Hydration
• Adequate nutrition
• Minimize effects of known diseases or
  perfusion-limiting drugs (including smoking)
• Cover skin prevent vasoconstriction
• Prevents restriction to blood flow
• Prevent hypoxemia with supplemental O2 if needed
• Exercise
• Raises core temperature and causes vasodilation
• Leads to exhaustion

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Protection from the Cold

• Protect skin
• Emollients DO NOT protect skin actually
  increase risk
• Avoid perspiration or wet extremities
• Increase insulation skin protection layers
• Avoid alcohol/drugs/hypoxemia
• Allows you to respond behaviorally to changing
  conditions
• Use chemical hand and foot warmers, electric foot
  warmers
• Perform cold checks
• Recognize frostnip superficial frostbite early
• Minimize duration of cold exposure
• Avoid environmental conditions favorable for
  frostbite

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Weather Conditions Frostbite

• Ambient air temperature
• Frost nip doesnt generally happen until skin
  temperature is below -6 degrees C
• Skin rarely freezes above -15 to -10 degrees C
  (5 to 14 F)
• Skin will readily supercool
• Cold-induced vasodilation occurs skin
  temperature levels off
• Rate of air movement (wind speed)
• Duration gt temperature of exposure
• Skin surface moisture
• Contact with cold objects

Wilson O, Goldman RF. Role of air temperature and
wind in the time necessary for a finger to
freeze. Journal of Applied Physiology. Nov 1970.
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Emollients

• Traditionally used by Finnish reindeer herders to
  prevent frostbite
• Large prospective epidemiological study
• 913 frostbite cases, 2,478 uninjured controls
• Use of protective ointments associated with
  increased risk of frostbite on face (OR 3.3),
  nose (OR 5.6) and ears (OR 4.5)
• Prospective experimental study
• 24 young, healthy male subjects (med students)
• Placed in a climatic chamber
• 4 emolients tested on ½ the face
• Thermistor and infra-red scanner temperatures
• Emolients do not delay cooling of facial skin
• Skin cooler on treated half in the majority of
  tests

Lehmuskallio E. Rintamaki H. Anttonen H. Thermal
Effects of Emollients on Facial Skin in the Cold.
Acta Derm Venereol. 2000. Lehmuskallio E.
Emollients in the Prevention of Frostbite.
International Journal of Circumpolar Health,
2000 59 122-130.
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Management

• In the field
• If re-freezing is likely
• If thaw is maintainable
• Hospital setting
• Early treatment
• Long-term treatment options

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Field Management of Frostbite

• General Guidelines
• Treat concomitant hypothermia
• Before treating frostbite if moderate-severe
• Maintain hydration
• Administer ibuprofen (600mg BID-QID)
• Blocks arachidonic pathway decreased PGF2 and
  TxA2
• Protect the frozen part
• Do not rub
• Do not actively thaw if re-freezing is possible
• Caveat consider thawing if hospital is in
  distant future
• Avoid re-freezing a thawed part
• Do not prevent thawing if it is going to happen
  spontaneously

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Field Management of Frostbite

• If re-freezing is possible or inevitable
• Apply clean, bulky dressings to the frozen part
  and between toes and fingers
• Avoid ambulation and pressure on frozen extremity
  minimize additional trauma
• If use is unavoidable
• Pad well
• Splint
• Immobilize as much as possible

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Field Management of Frostbite

• If thaw can be maintained
• Rapidly rewarm
• Warm water immersion bath (37-39 degrees C)
• Dry by blotting (avoid rubbing)
• Antiseptic solution
• Theoretical benefits, but no evidence
• Pain control
• NSAIDs
• Opiates

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Field Management of Frostbite

• If thaw can be maintained, continued
• Do not debride blisters
• Apply topical aloe vera
• Reduces prostaglandin and thromboxane formation
• Only beneficial for superficial injuries
• Bulky, clean dressings wrapped loosely (swelling)
• Avoid ambulation if possible
• Elevate the injured extremity
• Provide supplemental oxygen if hypoxia is present
  or at high altitude (gt4000m)

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Field Management of Frostbite
McIntosh SE. Hamonko M, et al. Wilderness Medical
Society Guidelines for the Prevention and
Treatment of Frostbite. Wilderness and
Environmental Medicine, 2011(22)156-166.
43
Hospital Management of Frostbite

• Impossible to ascertain prognosis immediately
  after thawing
• Immediate therapeutic options
• Treatment of hypothermia, trauma
• Rapid rewarming of frozen tissues
• Water bath (37-39oC)
• Hydration
• Topical aloe vera

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Hospital Management of Frostbite

• Immediate therapeutic options, continued
• Debridement of blisters
• Selectively needle aspirate clear blisters
• Leave hemorrhagic blisters intact
• Systemic antibiotics
• Cover Staph aureus and Pseudomonas aeruginosa
• No need for universal antibiotic coverage
• Tetanus prophylaxis
• Low molecular weight dextran

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Low Molecular Weight Dextran

• Polysaccharide plasma expander
• Proposed mechanism of action in frostbite
• Decreases blood viscosity
• Inhibits intravascular cellular aggregation and
  improves small vessel perfusion

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Low Molecular Weight Dextran

• Pro
• Mundth ED, et al. 1964.
• Improves tissue survival if given PRIOR TO
  freezing
• May improve tissue survival if given one hour
  after rewarming and BID x5 days
• Webster DB, et al. 1965.
• Animals treated with LMWD before and after
  freezing injury had less necrosis than controls
• Con
• Penn I, et al. 1964.
• LMWD therapy associated with increased edema
• Increased compression of blood vessels
  interference of blood flow through injured area
• No significant reduction in the amount of tissue
  loss

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Low Molecular Weight Dextran

• Take-home
• LMWD is worth considering if you can get it into
  the patient before the injury or within a couple
  of hours of presentation
• but it should not be given immediately
• Most recent research is in the 1960s
• We probably have better options

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Hospital Management of Frostbite

• Imaging options
• Technetium 99 (Tc-99) triple phase scanning
• Magnetic resonance angiography
• Angiography
• These help determine extent of tissue ischemia

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Hospital Management of Frostbite

• Thrombolytic therapy
• Angiography, Technetium-99, or MR-A
• IV or IA tPA within 24 hours of thawing may
  salvage some or all tissue at risk
• Should only be considered in deep frostbite with
  potential for significant morbidity (proximal to
  interphalangeal joints)
• Consider risks and contraindications
• Heparin therapy as adjuvent to tPA (/- warfarin)

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• Prospective study
• 19 patients over 14 years
• 6 intra-arterial tPA
• 0.075 mg/kg/hr x6 hrs
• 13 intra-venous tPA
• 0.15 mg/kg bolus, then 0.15 mg/kg/hr x 6 hrs
• No complications with IV tPA 2 IA patients with
  bleeding
• 16/19 patients responded to tPA
• Equal efficacy with IV and IA
• IV tPA is safe reduced predicted digit
  amputations

Twomey JA, Peltier GL, Zera RT. An Open-Label
Study to Evaluate the Safety and Efficacy of
Tissue Plasminogen Activator in Treatment of
Severe Frostbite. The Journal of Trauma 2005
(Dec) Volume 59, Number 6, pp. 1350-1355.
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• Retrospective study
• 7 patients in experimental group
• 25 controls traditional treatment group
• IA tPA
• 0.5-1.0 mg/hr
• t-PA reduced digital amputation rate from 41 to
  10!

Bruen KJ, Ballard JR, Morris SE, Cochran A,
Edelman LS, Saffle JR. Reduction of the Incidence
of Amputation in Frostbite Injury with
Thrombolytic Therapy. Arch Surg 2007
142546-553.
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Sheridan RL, Goldstein MA, Stoddard FJ, Walker G.
Case 41-2009 A 16-year-old Boy with Hypothermia
and Frostbite. The new England Journal of
Medicine 2009 (December 31) 361 2654-2662.
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Hospital Management of Frostbite

• Vasodilator therapy
• Prostaglandin E1
• Iloprost
• Nitroglycerin
• Pentoxifylline
• Phenoxybenzamine
• Nifedipine
• Reserpine
• Buflomedil
• Vasodilate and prevent platelet aggregation and
  microvascular occlusion

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Hospital Management of Frostbite

• Other post-thaw options (medical)
• Hydrotherapy
• 37-39 degrees Celcius
• 1-2 times per day
• Theoretically increases circulation, removes
  superficial bacteria, debrides devitalized tissue
• No trials to support its use
• Hyperbaric oxygen therapy
• Unlikely to work in setting of lost blood supply
• Limited data

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Hospital Management of Frostbite

• Other post-thaw options (surgical)
• Sympathectomy (removal of sympathetic chain and
  ganglion)
• Theoretically alleviates vasospasm
• May also help prevent long-term pain,
  paresthesias, and hyperhidrosis
• Should be performed early (first 24 hrs) for
  tissue salvage or late for relief of chronic
  symptoms
• Fasciotomy/Escarotomy
• Should be performed if compartment syndrome

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Hospital Management of Frostbite

• Other post-thaw options (surgical)
• Amputation
• Should occur 1-3 months after injury
• Need complete demarcation of necrotic tissue
• Need protective orthoses and footwear while
  waiting
• Involve multi-disciplinary rehabilitation team
• Will need to occur sooner if sepsis develops

57
Hospital Management of Frostbite
McIntosh SE. Hamonko M, et al. Wilderness Medical
Society Guidelines for the Prevention and
Treatment of Frostbite. Wilderness and
Environmental Medicine, 2011(22)156-166.
58
Other Modalities That Have Been Tried

• Ultrasound therapy
• Adrenocorticotrophic Hormone (ACTH)
• Topical steroid (Tetran-hydrocortisone ointment)
• Subatmospheric Pressure (VAC Dressing)
• Distal Volar Forearm Nerve Block
• Causes hyperemia, warmth, and anesthesia in
  fingers anesthetized for carpal tunnel release
• Aspirin
• Blocks all prostaglandin synthesis, including
  beneficial

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Long term sequellae

• Single episode of frostbite
• Can result in cold intolerance (75)
• Can increase risk of recurrent frostbite injury
• Chronic pain (67)
• Amitriptyline
• Sympathectomy
• Bony involvement
• Localized osteoporosis or subchondral bone loss
• Frostbite arthritis 50
• Premature epiphyseal fusion in children
• Skin Involvement
• Hyperhidrosis (75)
• Dry, cracking skin
• Sensory loss (68)

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The Case - Revisited

• Admitted to trauma IR consultation
• Also psych, ortho, plastics consults
• Wound care nursing debrided blisters
• Angiography 1/16, 1/17, 1/18
• IA tPA (0.5mg/hr) was given 1/16 through 1/17
• Angio 1/18 showed good flow in the palmar arches
  no filling of bilateral digital arteries
• Transferred to P6 for his Ambien overdose, where
  he continues to reside

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L Hand
tPA 1mg/hr Heparin 500u/hr
24 Hrs
48 Hrs
R Hand
63
Treatment Protocol

• Initial Therapy
• Immediate rewarming
• Fluid resuscitation
• Tdap
• Ibuprofen 600mg
• Pain Control
• (Debridement of blisters)

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Treatment Protocol

• Consider tPA if
• Clinically significant frostbite
• Severe frostbite or 4th degree frostbite
• Physical exam
• Full-thickness tissue involvement
• Hemorrhagic blisters
• Vascular exam circulatory compromise
• Absence of pulses/doppler
• Black/deep purple discoloration

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Treatment Protocol

• Exclusion Criteria
• Recent trauma
• Neurologic impairment
• Recent surgery or hemorrhage
• Bleeding disorder
• Recent stroke
• Intoxication
• Uncontrolled hypertension
• Pregnancy
• Multiple freeze/thaw cycles
• Prolonged cold exposure (gt48 hours)
• Post-warming time gt24 hours

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Treatment Protocol

• Interventional Radiology Consult
• Perfusion evaluation on angiography
• Absent filling of digital arteries
• tPA 0.5 1 mg/h
• Femoral or brachial arterial catheter sheath
• Heparin 500 u/h
• Femoral or brachial arterial catheter sheath
• Surgery consult
• SCU admission

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Treatment Protocol

• Evaluation while on treatment
• Dedicated burn unit / Intensive Care Unit
• Local wound care
• Debridement with burn dressing (aloe vera)
• Repeat Angiography
• Q 8-12 hrs
• tPA discontinued when perfusion is restored to
  distal vessels OR at absolute limit of 48 hrs

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Angiograhic Findings that Predict Good Clinical
Outcome

• Restoration of arterial flow to terminal digital
  arteries
• Visualization of PAIRED digital arteries
• Persistent arterial flow on serial angiogram

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Treatment Protocol

• Healing wounds
• Debridement
• Burn dressing (aloe vera)
• Skin-grafting

• Non-healing wounds
• (Obvious necrosis)
• (Mummification)
• Amputation

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MMC Treatment Algorithm

• Rapid Rewarming
• IV hydration
• TDap
• Ibuprofen 600mg
• Pain Control
• (Debride blisters)
• (Aloe vera)

• Treat hypothermia or trauma

• Assessment of damaged tissue
• Assessment for contraindications

• IR Consult
• Angiography

• Trauma surgery consult
• ICU Admission

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Mimickers of Frostbite

• Chilblains/Pernio
• Trench Foot
• Raynauds Phenomenon/Syndrome

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Chilblains/Pernio

• Epidemiology
• 10 of population in England
• Hands, feet, face, lower leg
• Thighs, buttocks overweight young female
  horseback riders
• Pathophysiology
• Unknown
• Chronic vasculitis/vascular instability
• Vasodilation of superficial minute vessels and
  vasoconstriction of subcutaneous arteries and
  arterioles
• Repeated exposure to near freezing, humidity
• No ice crystal formation

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Chilblains/Pernio

• Presentation
• Violaceous color to skin with plaques or nodules
• Pain and pruritis with cold exposure
• Treatment
• Avoidance of cold
• Proper clothing
• Nifedipine

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Trench Foot

• Epidemiology
• Associated with immobility and dependency
• Military
• Pathophysiology
• Wet cold injury
• Temperatures above freezing
• Long duration of exposure (1 day several days)

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Trench Foot

• Treatment
• Rewarming
• Causes severe pain
• Immediate Sequellae
• Anesthesia
• Edema
• Parasthesias
• Anhydrosis
• Muscluar atrophy
• Ulceration
• Gangrene
• Long-term Sequellae
• Hypersensitivity to cold and weight bearing

76
Raynauds Phenomenon

• Epidemiology
• 2 of the population
• Pathophysiology
• Episodic reduction in peripheral blood flow
• Cold exposure
• Stress

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Raynauds Phenomenon

• Presentation
• Skin color changes
• White ischemia from vasoconstriction
• Blue venous stasis
• Red hyperemia
• Sensory changes
• Pain
• Parasthesias
• Treatment
• Nifedipine
• IV Prostacyclin or prostaglandin E1 for severe
  cases
• Evening primrose oil

78
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