Frostbite and Cold Injury
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Transcript Frostbite and Cold Injury
FROSTBITE AND DERMAL COLD
INJURY
Katie Dolbec, MD
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.
Frostbite Definition
Freezing injury of tissue
Ice crystal formation in superficial or deep
structures
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
Excessive sweating
(Elderly, Young children)
Age 30-49
Male Sex (10:1)
Psych/Behavioral
(and car troubles)
Vascular
Genetic/Inherent
Epidemiology
Incidence unknown
Common anatomic locations
Feet
Hands
Ears
Nose
Cheeks
Penis
Hershkowitz M. Penile Frostbite, an Unforseen Hazard of Jogging. New England Journal of Medicine. Jan 20, 1977.
Travis S, Roberts D. Arctic Willy. BMJ, Vol. 299, 23-30 December 1989.
Epidemiology
Population at risk for co-existing conditions
Consider & manage:
Hypothermia
Trauma
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
Pathophysiology –
Prefreeze Phase
Tissue cooling <10oC
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
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
Pathophysiology –
Vascular Stasis Phase
Vessels alternate between constriction and
dilation
Blood leaks from vessels or coagulates within
them
Pathophysiology –
Late Ischemic Phase
Ongoing reperfusion injury
Inflammatory cascade
Intermittent vasoconstriction
Microvascular emboli/macrovascular thrombi
Progressive tissue ischemia and infarction
Pathophysiology
Mechanisms of Tissue Damage:
Cellular injury
Tissue ischemia
Inflammatory mediator release
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***
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
Immediately after thawing blood flows freely
Five-ten minutes post-thaw blood begins to
sludge
Clot
Ischemia
Necrosis
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.
Pathophysiology - Inflammatory
Mediator Release
Secondary effect of pro-inflammatory cytokine
release
Thromboxane A2
Prostaglandin F2-alpha
Bradykinin
Histamine
Found in frostbite blister fluid
Exacerbates cellular damage
Causes further ischemia
Vasoconstriction
Platelet aggregation
Blood vessel thrombosis
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
Reamy BV.Frostbite: Review and Current Concepts. Journal of American Board of
Family Practice, Jan. – Feb. 1998, Vol. 11, No. 1
Classifying Frostbite
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***
First-degree Frostbite
White or yellow firm, slightly raised plaque
Numbness
No gross tissue infarction
Slight epidermal sloughing
Mild edema
Second-degree Frostbite
Superficial skin vesiculation
Clear or milky fluid in blisters
Surrounding erythema and edema
Third-degree Frostbite
Deeper, hemorrhagic blisters
Injury has extended into reticular dermis and
dermal vascular plexus
Fourth-degree Frostbite
Extends through the dermis
Involves subcutaneous tissues
Necrosis extending into muscle and to bone
Two-Tiered Classification System
Better in the field
More of a clinical diagnosis
Superficial frostbite
Deep frostbite
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
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)
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
Maintaining Peripheral Perfusion
Maintain core temperature
Hydration
Adequate nutrition
Minimize effects of known diseases or perfusionlimiting 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
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
Weather Conditions & Frostbite
Ambient air temperature
Frost nip doesn’t 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 > 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.
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.
Management
In the field:
If re-freezing is likely
If thaw is maintainable
Hospital setting:
Early treatment
Long-term treatment options
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
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
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
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 (>4000m)
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.
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
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
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
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
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
Hospital Management of Frostbite
Imaging options
Technetium 99 (Tc-99) triple phase scanning
Magnetic resonance angiography
Angiography
These help determine extent of tissue ischemia
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)
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.
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; 142:546-553.
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.
Hospital Management of Frostbite
Vasodilator therapy
Prostaglandin E1
Iloprost
Nitroglycerin
Pentoxifylline
Phenoxybenzamine
Nifedipine
Reserpine
Buflomedil
Vasodilate and prevent platelet aggregation and
microvascular occlusion
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
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
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
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.
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
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%)
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
L Hand
R Hand
tPA 1mg/hr
Heparin 500u/hr
24 Hrs
48 Hrs
Treatment Protocol
Initial Therapy
Immediate rewarming
Fluid resuscitation
Tdap
Ibuprofen 600mg
Pain Control
(Debridement of blisters)
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
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 (>48 hours)
Post-warming time >24 hours
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
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
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
Treatment Protocol
Healing wounds
Debridement
Burn dressing (aloe vera)
Skin-grafting
Non-healing wounds
(Obvious necrosis)
(Mummification)
Amputation
MMC Treatment Algorithm
•Treat
hypothermia
or trauma
•Rapid Rewarming
•IV hydration
•TDap
•Ibuprofen 600mg
•Pain Control
•(Debride blisters)
•(Aloe vera)
•Assessment of damaged tissue
•Assessment for contraindications
•IR Consult
•Angiography
•Trauma surgery consult
•ICU Admission
Mimickers of Frostbite
Chilblains/Pernio
Trench Foot
Raynaud’s Phenomenon/Syndrome
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
Chilblains/Pernio
Presentation
Violaceous color to skin with plaques or nodules
Pain and pruritis with cold exposure
Treatment
Avoidance of cold
Proper clothing
Nifedipine
Trench Foot
Epidemiology
Associated with immobility and dependency
Military
Pathophysiology
Wet cold injury
Temperatures above freezing
Long duration of exposure (1 day – several days)
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
Raynaud’s Phenomenon
Epidemiology
2% of the population
Pathophysiology
Episodic reduction in peripheral blood flow
Cold exposure
Stress
Raynaud’s 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
References
Arias-Santiago SA, Giron-Prieto MS, Callejas-Rubio JL, Fernandez-Pungnaire MA, Ortega-Centeno
N. Lupus Pernio or Chilblain Lupus?: Two Different Entities. Chest 2009; 136: 946-947.
Beitner R, Chen-Zion M, Sofer-Bassukevitz, Morgenstern H, Ben-Porat H. Treatment of Frostbite
with the Calmodulin Antagonists Thioridazine and Trifluoperazine. Gen. Pharmac. Vol. 20, No. 5,
pp. 641-646, 1989.
Biem J, Keohncke N, Classen D, Dosman J. Out of the cold: management of hypothermia and
frostbite. Canadian Medical Association Journal, February 4, 2003; 168 (3).
Bilgic S, Ozkan H, Ozenc S, Safaz I, Yildiz C. Treating frostbite. Canadian Family Physician 2008;
54: 361-3.
Bird D. Identification and Management of Frostbite Injuries. Emergency Nurse; Dec 1999-Jan
2000; 7, 8; pg. 17.
Bourne MH, Piepkorn MW, Clayton F, Leonard LG. Analysis of Microvascular Changes in
Frostbite Injury. Journal of Surgical Research, 40, 26-35 (1986).
Bouwman DL, Morrison S, Lucas CE, Ledgerwood AM. Early Sympathetic Blockade for Frostbite
– Is it of Value? The Journal of Trauma, Vol 20, No 9, September 1980.
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; 142:546-553.
Bruen KJ, Gowski WF. Treatment of Digital Frostbite: Current Concepts. Journal of Hand Surgery
2009 (March); Vol 34A, pp. 553-554.
Cauchy E, Cheguillaume B, Chetaille E. A Controlled Trial of a Prostacyclin and rt-PA in the
Treatment of Severe Frostbite. New England Journal of Medicine 2011; 364:2, 189-190.
References
Cauchy E, Chetaille E, Marchand V, Marsigny B. Retrospective study of 70 cases of severe frostbite
lesions: a proposed new classification scheme. Wilderness and Environmental medicine, 12, 248255 (2001).
Chandran GJ, Chung B, Lalonde J, Lalonde DH. The Hyperthermic Effect of a Distal Volar Forearm
Nerve Block: A Possible Treatment of Acute Digital Frostbite Injuries? Plastic and Reconstructive
Surgery 2010 (September); Volume 126, Number 3, 946-950.
Douglas JD. The Evaluation of the Use of Ultrasound in Frostbite Therapy. Tech Note Arct
Aeromed Lab (US), 1960 Aug;AAL-TN-60-11:1-9.
Dowd PM, Rustin MHA, Lanigan S. Nifedipine in the treatment of chilblains. British Medical
Journal 1986 (October 11); Vol. 293: 923-924.
Folio LR, Arkin K, Butler WP. Frostbite in a Mountain Climber Treated with Hyperbaric Oxygen:
Case Report. Military Medicine 2007 (May); Vol. 172, 5:560-562.
Gage AA, Ishikawa H, Winter PM. Experimental Frostbite and Hyperbaric Oxygenation. Surgery.
Vol. 66, No. 6, pp. 1044-1050.
Glenn, WWL, Maraist FB, Braatens OM. Treatment of Frostbite with Particular Reference to the
use of Adrenocorticotrophic Hormone (ACTH). The New England Journal of Medicine; Vol. 247,
No. 6.
Golding MR, Mendoza MF, Hennigar GR, Fries CC, Wesolowski SA. On settling the controversy
on the benefit of sympathectomy for frostbite. Surgery 1964 (July);Vol. 56, No. 1.
Goodfield M. Cold-induced skin disorders. The Practitioner 1989 Dec 15;233(1480):1616, 1618-20.
Goodhead B. The comparative Value of Low Molecular Weight Dextran and Sympathectomy in the
Treatment of Experimental Frost-Bite. Brit J Surg, 1966, Vol. 53, No. 12, December.
References
Grace TG. Cold Exposure Injuries and the Winter Athlete. Clinical Orthopedics and Related
Research, No. 216, March 1987.
Grieve AW, Davis P, Dhillon S, Richards P, Hillebrandt D, Imray CHE. A Clinical Review of the
Management of Frostbite. J R Army Med Corps 2011 Mar;157(1):73-8.
Gulati SM, Kapur BML, Talwar JR. Sympathectomy in the Management of Frostbite: An
Experimental Study. Indian Journal of Medical Resuscitation, 58, 3, March 1970.
Hallam MJ, Cubison T, Dheansa B, Imray C. Managing Frostbite. BMJ. 341: 1151-1156, 2010
November.
Hamlet MP. Prevention and Treatment of Cold Injury. International Journal of Circumpolar Health
2000; 59: 108-113.
Hardenbergh E, Ramsbottom R. Experimental Frostbite: The Effect of “Double Freeze” on Tissue
Survival in the Mouse Foot. Cryobiology, Vol. 5, No. 5, 1969.
Hayes DW, Mandracchia VJ, Considine C, Webb GE. Pentoxifylline Adjunctive Therapy in the
Treatment of Pedal Frostbite. Clinics in Podiatric Medicine and Surgery, Volume 17, Number 4,
October 2000.
Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boertman JA, Smith DJ,
Sachs RJ. Experimental and Clinical Observations on Frostbite. Annals of Emergency Medicine,
16:9, September 1987.
Hershkowitz M. Penile Frostbite, an Unforseen Hazard of Jogging. New England Journal of
Medicine. Jan 20, 1977.
Imray C, Grieve A, Dhillon S, the Caudwell Xtreme Everest Research Group. Cold damage to the
extremities: frostbite and non-freezing cold injuries. Postgrad Med J 2009;85;481-488.
References
Kahn JE, Lidove O, Laredo JD, Bletry O. Frostbite arthritis. Ann rheum Dis 2005; 64: 966-967.
Kaplan R, Thomas P, Tepper H, Strauch B. Treatment of Frostbite with Guanethidine. The Lancet,
October 24, 1981.
Kapur BML, Gulati SM, Talwar JR. Low Molecular Dextran in the Management of Frostbite in
Monkeys. Ind. Jour. Med. Res. 56, 11, November, 1968.
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.
Leung AKC, Lai PCW. Digital Deformities from Frostbite. Canadian Medical Association Journal,
Vol. 132, January 1, 1985.
Lutz V, Cribier B, Lipsker D. Chilblains and antiphospholipid antibodies: report of four cases and
review of the literature. British Journal of Dermatology 2010; 163: 641-666.
MacNamarra, BS. Ultrasonic Therapy – Severe Frostbite Case. The Physical Therapy Review. Vol.
39, No. 3; pp. 160-161.
Malhotra MS, Mathew L. Effect of Rewarming at Various Water Bath Temperatures in Experimental
Frostbite. Aviation, Space, and Environmental Medicine, July 1978.
Mazur P. Causes of Injury in Frozen and Thawed Cells. Federation Proceedings. 1965 MarApr;24:S175-82.
References
McGillion R. Frostbite: Case Report, Practical Summary of ED Treatment. Journal of Emergency
Nursing 2005 (Oct); 31: 5, pp. 500-502.
McIntosh SE. Hamonko M. Freer L. Grisson CK. Auerbach PS. Rodway GW. Cochran A. Giesbrecht
G. McDevitt M. Imray CH. Johnson E. Dow J. Hackett PH. Wilderness Medical Society practice
guideline for the prevention and treatment of frostbite. Wilderness Medical Society. Wilderness and
Environmental Medicine. 22(2):156-66, 2011 June.
McKendry RJR. Frostbite Arthritis. CMA Journal, Vol. 125, November 15, 1981.
Meryman HT. Tissue Freezing and Local Cold Injury. Physiol Rev, April 1957 vol. 37 no. 2 233-251.
Miller MB, Koltai PJ. Treatment of Experimental Frostbite with Pentoxifylline and Aloe Vera Cream.
Arch Otolaryngol Head Neck Surg, Vol 121, june 1995.
Mills WJ. Frostbite: A Method of management including rapid thawing. Northwest Medicine, 1966.
Mills WJ. Frostbite: Experience with Rapid Rewarming and Ultrasonic Therapy. Wilderness and
Environmental Medicine, 9, 226-247 (1998).
Minor TM, Shumacker HB. An evaluation of tissue loss following single and repeated frostbite
injuries. Surgery: 1967 (April), Vol. 61, no. 4, pp. 562-563.
Mohr WJ, Jenabzedeh K, Ahrenholz DH. Cold Injury. Hand Clinics 2009 Nov;25(4):481-96.
Mundth ED, Long DM, Brown RB. Treatment of Experimental Frostbite with Low Molecular Weight
Dextran. The Journal of Trauma 1964 Mar;4:246-57.
References
Murphy JV, Banwell PE, Roberts AHN, McGrouther DA. Frostbite: Pathogenesis and Treatment.
The Journal of Trauma, Vol. 48, No. 1, Jan 2000.
Okuboye JA, Ferguson CC. The Use of Hyperbaric Oxygen in the Treatment of Experimental
Frostbite. The Canadian Journal of Surgery. Vol. 11, January 1968.
Patel NN, Patel DN. Frostbite. The American Journal of Medicine 2008 (September); Vol 121, No 9,
pp. 765-765.
Penn I, Schwartz SI. Evaluation of Low Molecular Weight Dextran in the Treatment of Frostbite.
The Journal of Trauma; 1964 Nov;4:784-90.
Porter JM, Wesche DH, Rosch J, Baur GM. Intra-Arterial Sympathetic blockade in the Treatment of
Clinical Frostbite. The American Journal of Surgery. Volume 132, November 1976.
Poulakidas S, Cologne K, Kowal-Vern. Treatment of Frostbite with Subatmospheric Pressure
Therapy. Journal of Burn Care & Research 2008; Volume 29, Number 6, pp. 1012-1014.
Prakash S, Weisman MH. Idiopathic Chilblains. American Journal of Medicine 2009; 122: 11521155.
Probst F, Cox N, Anderson M. Oxpentifylline: An Advance in the Treatment of Frostbite.
Emergency Nursing 2003 Dec-2004 Jan;11(8):22-3.
Purkayastha SS, Roy A, Chauhan SKS, Verma SS, Selvamurthy W. Efficacy of pentoxifylline and
aspirin in the treatment of frostbite in rats. Indian Journal of Medical Resuscitation, 107, May 1998,
pp. 239-245.
Quintanilla R, Krusen F, Essex HE. Studies on Frost-Bite with Special Reference to Treatment and
the Effect on Minute Blood Vessels. American Journal of Physiology, 1947 Apr;149(1):149-61.
References
Raman SR, Jamil Z, Cosgrove J. Magnetic resonance angiography unmasks frostbite injury. Emerg Med j 2011;
28:450.
Reamy BV. Frostbite: Review and Current Concepts. JABFP, Vol. 11, No. 1, Jan-Feb 1998.
Rintamaki H. Predisposing Factors and Prevention of Frostbite. International Journal of Circumpolar Health, 2000;
59:114-121.
Roche-Nagle G, Murphy D, Collins A, Sheehan S. Frostbite: management options. European Journal of Emergency
Medicine 2008; 15:173-175.
Rustin MHA, Newton JA, Smith NP, Dowd PM. The treatment of chilblains with nifedipine: the results of a pilot
study, a double-blind placebo-controlled randomized study and a long-term open trial. British Journal of
Dermatology (1989) 120, 267-275,
Saemi AM, Johnson JM, Morris CS. Treatment of Bilateral Hand Frostbite Using Transcatheter Arterial
Thrombolysis After Papavarine Infusion. Cardiovasc Intervent Radiol (2009) 32: 1280-1283.
Salimi Z, Wolverson MK, Herbold DR, Vas W, Salimi A. Treatment of Frostbite with IV Streptokinase: An
Experimental Study in Rabbits. American Journal of Radiology, 149, October 1987.
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.
Shumacker HB, Kilman JW. Sympathectomy in the Treatment of Frostbite. Archives of Surgery; Vol. 89, Sept 1964.
Skolnick AA, Early Data Suggest Clot-Dissolving Drug May Help Save Frostbitten Limbs from Amputation. JAMA,
April 15, 1992, Vol. 267, No. 15.
References
Sumner DS, Simmonds RC, LaMunyon TK, Boller MA. Doolittle WH. Peripheral Blood Flow in
Experimental Frostbite. Annals of Surgery. 171(1); 1970 January.
Szego L, Lakos T. Treatment of Frostbite with Tetran-Hydrocortisone Ointment. Therapia
Hungarica, 1966;14(1):33-7.
Talwar JR, Gulati SM, Kapur BML. Use of Isoxsuprine Hydrochloride in Frostbite in Monkeys. Ind.
Jour. Med. Res. 56, 2, February 1968.
Talwar JR, Gulati SM, Kapur BML. Comparative Effects of Rapid Thawing, Low Molecular
Dextran and Sympathectomy in Cold Injury in the Monkeys. Indian Journal of Medical
Resuscitation, 59, 2, February 1971.
Travis S, Roberts D. Arctic Willy. BMJ, Vol. 299, 23-30 December 1989.
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.
Vayssairat M, Priollet P, Hagege A, Housset E. Does Ketanserin Relieve Frostbite? The Practitioner,
Vol. 230, may 1986.
Wagner C, Pannucci CJ. Thrombolytic Therapy in the Acute Management of Frostbite Injuries. Air
Medical journal 2011 (Jan-Feb); 30:1, 39-44.
Washburn B. Frostbite: What it is – How to prevent it – Emergency Treatment. The New England
Journal of Medicine, may 10, 1962; 974-989.
Weatherly-White RCA, Sjostrom B, Paton BC. Experimental Studies in Cold Injury. Journal of
Surgical Research; 1964 (Jan): Vol. IV, No. 1.
References
Webster DR, Bonn G. Low-Molecular-Weight Dextran in the Treatment of
Experimental Frostbite. Canadian Journal of Surgery; 1965 (Oct): vol. 8,
423-427.
Wilson O, Goldman RF. Role of air temperature and wind in the time
necessary for a finger to freeze. Journal of Applied Physiology. 29(5):
658-664, 1970 November.
Yang X, Perez OA, English JC. Adult perniosis and cryoglobulinemia: A
retrospective study and review of the literature. Journal of the American
Academy of Dermatology 2010 (June).
Yeager RA, Campion TW, Kerr JC, Hobson RW, Lynch TG. Treatment of
Frostbite with Intra-arterial Prostaglandin E1. The American Surgeon,
Vol. 49, No. 12, December 1983.
Zafren K. Prognostic Indicators in Frostbite. Wilderness and
Environmental Medicine, 10, 115-116 (1999).
Zook N, Hussmann J, Brown R, Russell R, Kucan J, Roth A, Suchy H.
Microcirculatory Studies of Frostbite Injury. Annals of Plastic Surgery,
Volume 40, Number 3, March 1998.