Wednesday, December 11, 2013

Needing some cheering on

Frost free is frozen in the barn again. I just don't have the energy to haul water from the house today...I'm hoping the heater I put in there will thaw it in a few hours. 
 
I'm trying to psyche myself up to do the guinea treatments-they are a LOT of work to deal with.
The agility and strength of a cat, the skittishness of a starling, and beaks as sharp as gulls. And ear piercing vocals like cockatoos...Oh--and what comes out the other end is as bad as sea lion _ _ _ _. Still waiting for potentially life-saving meds to arrive UPS.
 
 
 
 
 
From Vetlearn.com:
 
 
 
 
Frostbite in Birds:
Pathophysiology
and Treatment
 
 
University of Florida
 
James F. X. Wellehan, DVM, MS
ABSTRACT: Frostbite is a common problem in birds in colder climates and may also be seen
 
with cold weather in southern climates. The pathophysiology involves both the initial freezing
injury and secondary vascular impairment. Inflammatory mediators released by damaged tissue
cause thrombosis. Pharmaceutical therapy should be directed toward maintaining optimal
blood supply to damaged tissue, avoiding secondary infection, and providing analgesia. The
line of demarcation of necrosis may take several weeks to become evident.
 
Frostbite is a localized tissue injury sustained as a result of cooling and
 
 
thawing of tissues. Although much of the work done on frostbite has been
with mammals, birds are susceptible, and it is not an uncommon injury in
 
birds in colder climates. Risk factors in birds include unseasonable weather,1 use
of anesthetics,2 use of wire caging,3 metal leg bands,4 missed migrations, and
 
 
(author’s observations) previous injury or overaggressive bandaging resulting in
impaired blood supply. Nonnative species placed in colder habitats are especially
 
at risk, and peafowl (Pavo cristatus; Figure 1) and European starlings (Sturnus
vulgaris) are two of the more common species seen with frostbite in upper midwestern
 
 
North America. Although the majority of frostbite cases involve the feet,
 
a syndrome of distal wing necrosis in falcons may be due to cold injury.5
 
 
 
 
PATHOPHYSIOLOGY
 
 
 
Numerous methods of adapting to colder environments, including arteriovenous
countercurrent heat exchange and shunting via arteriovenous anastomoses,
 
have evolved in birds.6 As the environment cools beyond a bird’s ability to maintain
 
 
homeothermy, heat is conserved in vital organs. Initially, vasoconstriction of
vessels of the extremities is seen, with regular, intermittent vasodilation to preserve
 
tissue viability. This vasodilation is known as the hunting reflex and has been
demonstrated in the feet of pigeons,7 ducks, chickens, and fulmars.6 As cooling
 
 
continues, vasodilation ceases. Tissue damage occurs as a result of both direct
freezing injury and ischemia resulting from impaired vascular supply (Figure 2).
Initially, freezing of tissue leads to extracellular ice crystal formation. As extracellular
water freezes, the osmotic gradient is altered, resulting in intracellular dehydration.
As crystals become larger, direct mechanical damage to cells also occurs.
Initial freezing is typically less significant than resultant ischemic injury. Skin
 
www.VetLearn.com
 
 
 
n The most clinically significant
 
 
component of frostbite is
vascular injury.
 
n Therapy should be directed
 
 
toward maintaining blood
supply.
 
n Early surgical intervention is
 
 
contraindicated.
 
n For efficacy in saving frostbitten
 
 
tissue, therapy must be initiated
before gross lesions are visible.
 
776 Vol. 25, No. 10 October 2003
 
 
Article #5 (1.5 contact hours)
 
Refereed Peer Review
 
CE
 
KEY FACTS
 
 
Compendium October 2003 Frostbite in Birds 777
 
 
 
www.VetLearn.com
 
 
 
transplants from frostbitten areas to undamaged areas
survive, whereas healthy skin transplanted to frostbitten
 
areas does not.8 Tissue ischemia occurs because of several
 
 
reasons. Initially, vasoconstriction and sludging of
blood results in inadequate blood supply. In a mouse
model, a return of blood flow to apparent normal prefreeze
rates, followed by the onset of a gradual sludging
 
of blood 15 to 20 minutes postthaw, was seen.9 Freezing,
 
 
osmotic, and hypoxic damage to cells results in
release of inflammatory mediators, especially by the
vascular endothelium. Frostbite blisters in humans and
experimentally frostbitten rabbit tissue have been
shown to have markedly elevated levels of
 
prostaglandin F2a and thromboxane B2 (a metabolite of
thromboxane A2).10,11 Increased numbers of mast cells
 
 
and polymorphonuclear leukocytes (PMN) are seen in
frostbitten rabbit ears, and degranulation of these cells
 
may also be a source of inflammatory mediators.11,12
 
 
Frostbitten rabbits treated at the time of rewarming,
with antibodies blocking PMN adhesion, had significantly
 
less tissue loss.13
 
 
Inflammatory mediators trigger further vasoconstriction,
platelet aggregation, and thrombosis, leading to a
cycle of further microvascular damage, hypoxia, tissue
damage, and inflammatory mediator release. Vascular
inflammation and thrombosis may not be limited to
the damaged extremity. Cardiac lesions have been associated
 
with frostbite in birds.1,2,14,15 In a study of 26
 
 
birds that died because of cold injury, six (23%) had
 
aseptic vegetative valvular endocarditis.1 In another
 
 
study, seven of 10 birds (70%) with frostbite had
 
myocardial, valvular, or vascular lesions.14 Sterile vegetative
 
 
valvular lesions have also been documented in
 
mammals subjected to cold stress.16
 
 
There are significant differences between avian and
mammalian coagulation. Activated partial thromboplastin
times in birds are much longer than those in mammals,
indicating that the intrinsic coagulation pathway
 
in birds is much less significant than in mammals.17 The
 
 
extrinsic coagulation pathway, which depends on tissue
 
factor, is of primary importance in birds.18 Tissue factor
 
 
expressed by damaged vascular endothelium may result
in more significant coagulation abnormalities in birds.
Alternatively, it is possible that bacterial infection secondary
to frostbite leads to endocarditis. However, in
one of the studies, only one of seven birds with vegetative
 
valvular endocarditis had septic lesions.1
 
 
 
 
CLINICAL MANIFESTATION
 
 
 
The most important part of frostbite diagnosis is the
history. It is essential that treatment be initiated as soon
as possible, before necrosis is evident. An early sign may
be proprioceptive deficit of the affected extremity
resulting from nerve injury (Figure 3). Pain may also be
present, resulting in self-mutilation. Although coldstressed
birds have been shown to have increased levels
 
of serum lactate dehydrogenase, uric acid, and triglycerides19
 
 
and frostbitten birds typically have elevated levels
of aspartate transferase and creatine kinase, biochemistries
are less useful for diagnosing frostbite.
In mammals, blister formation occurs during the first
24 hours. This is not typically evident in bird legs, possibly
because of the anatomy of the scaled skin on the
avian leg. As the injury progresses, edema may be seen
within the first 24 hours. Demarcation of viable and
nonviable tissue typically occurs slowly. Early detection
 
Cold
Freezing Vasoconstriction
Cell
death
Increased
blood viscosity
Ischemia
Endothelial
cell injury
Inflammatory
Thrombosis mediators
 
Figure 2—Pathophysiology of frostbite injury based on mammalian
 
 
models. Potential sites for intervention are shown in red.
 
Figure 1—Late-stage frostbite injury in a peacock (Pavo cristatus).
 
 
The tissue is mummified from the level of the distal
tarsometatarsus.
 
778 Small Animal/Exotics Compendium October 2003
 
 
 
www.VetLearn.com
 
 
Figure 3A—Proprioceptive deficit on presentation Figure 3B—Day 20
Figure 3C—Day 25 Figure 3D—Day 29
Figure 3E—Day 49
 
 
Figure 3—Frostbite in a hatch-year great blue heron (Ardea
herodias) that has just been found recumbent in a stream
 
 
during winter in Ontario, Canada. This heron had missed
migration.
 
of the line of demarcation in human frostbite may be
 
seen with bone scanning at 7 to 10 days,20 whereas
 
 
thermographic imaging in a rabbit ear model did not
 
clearly delineate viable tissue until 3 weeks.21 According
 
 
to the author’s observations, visual assessment of the
line of demarcation in birds may take 3 to 6 weeks. As
the line of demarcation forms, mummified tissue is evident
(Figure 4).
Long-term effects in surviving tissue in mammals
may include increased susceptibility to cold reinjury,
 
sensory loss, and osteoarthritis22 (all of which the author
 
 
has seen in birds).
 
Compendium October 2003 Frostbite in Birds 779
 
 
 
www.VetLearn.com
 
 
TREATMENT
 
 
 
If tissue is still frozen at presentation, rapid rewarming
in a warm (body temperature) water bath is indicated.
 
23 Although past recommendations for birds have
suggested more gradual rewarming,4,24 rapid rewarming
has been shown to be more efficacious in mammals,22,25
 
 
and no experimental data are available for birds.
Because massage is likely to cause mechanical trauma, it
 
is contraindicated,22,25 although it has been recommended
for birds in the past.24 Pharmaceutical therapy
 
 
should be directed toward maintaining optimal blood
supply to damaged tissue, avoiding secondary infection,
and providing analgesia. This therapy must be initiated
before microthrombi form and irreversible tissue
ischemia occurs.
Administration of NSAIDs serves to block inflammatory
products of cyclooxygenases, such as prostaglandin
 
F2a and thromboxane A2, preventing platelet aggregation
 
 
and thrombosis. Intramuscular flunixin or ketoprofen at
5 mg/kg has been shown to significantly decrease
 
thromboxane B2 in ducks, although flunixin resulted in
significant muscle necrosis.26 Pharmacokinetic data suggested
 
 
that administration every 12 hours might be
appropriate. Negative fecal occult blood tests suggested
that administration of this single dose did not produce
significant gastrointestinal bleeding. Ketoprofen has also
been shown to have analgesic effects in ducks at a dose
 
of 5 mg/kg IM.27 In humans, treatment with ibuprofen
 
 
in combination with aloe vera and penicillin resulted in
less tissue loss, a lower amputation rate, and shorter hospital
 
stays than other treatment regimens.28 Use of
 
 
cyclooxygenase-2–specific NSAIDs is not likely to be
 
useful; platelet thromboxane A2 is produced primarily
 
 
through the action of cyclooxygenase-1, and antithrombotic
prostacyclin is primarily a product of cyclooxygenase-
 
2.29 Therefore, the net effect of cyclooxygenase-
 
 
2–specific drugs may be prothrombotic and is not likely
to have an antithrombotic effect. Further study is
needed to establish the safety of multiple-dose administration
of ketoprofen and the safety, efficacy, and pharmacokinetics
of other NSAIDs in birds.
Pentoxifylline is a methylxanthine derivative that is
commonly indicated in treating peripheral vascular disease.
 
30 There are multiple mechanisms of action. Pentoxifylline
 
 
increases red cell flexibility, enabling passage
 
through damaged capillaries.31 Pentoxifylline also
 
 
decreases reperfusion-associated membrane injury and
 
leukocyte adhesion to ischemic tissue.32 Additionally,
 
 
pentoxifylline may inhibit PMN-oxidative bursts in
 
ischemic tissue,33 although the oxidative response of the
 
 
avian heterophil is significantly less than that of the
 
mammalian neutrophil.34
 
 
In experimental frostbite using a rabbit ear model,
pentoxifylline has been shown to significantly improve
tissue survival, both alone and in combination with
 
aloe vera cream.35 In another study using a rat foot
 
 
model of frostbite, pentoxifylline in combination with
 
aspirin significantly improved tissue survival.36 Extrapolating
from pharmacokinetic data in dogs,37 pentoxifylline
 
 
has been used for frostbite in birds at a dosage of
15 mg/kg PO q8–12h for 2 to 6 weeks without detection
of adverse effects (author’s observations). Further
study is needed to establish safety, efficacy, and pharmacokinetics
of pentoxifylline therapy in birds.
 
Aloe vera has a long history of use in thermal burns.38
 
 
Topical aloe vera has been shown to significantly
improve tissue survival in a rabbit frostbite model, both
 
alone and in combination with oral pentoxifylline.35
 
 
Specific mechanisms of action must still be elucidated,
and studies on safety, efficacy, and pharmacokinetics of
specific constituents remain to be done in birds.
Because frostbite is an extremely painful condition,
analgesia is essential in patients. In addition to NSAID
therapy, opioids may be used. Butorphanol at 1 mg/kg
IM has been shown to be efficacious for analgesia in
 
African grey parrots.39
 
 
Antibiotic therapy should be directed against common
skin flora and clostridial infection; pharmacokinetic
data have shown that oral clavulanic acid–amoxicillin
at a dosage of 125 mg/kg q8h is appropriate in
 
Amazon parrots.40 In passerine birds, clavulanic acid–
 
 
amoxicillin at a dosage of 200 mg/kg q8h has been
used without the detection of adverse effects (author’s
observations).
Early surgical debridement is contraindicated unless
uncontrolled infection is present. The line of demarcation
of viable tissue may take weeks to develop. An old
adage from human medicine is, “frostbite in January,
 
Figure 4—Mummified toes on a red-tailed hawk (Buteo
jamaicensis). The arrowheads indicate the line of demarcation.
 
780 Small Animal/Exotics Compendium October 2003
 
 
 
www.VetLearn.com
 
 
 
amputate in July,”22 and current recommendations in
 
 
humans are to debride mummified tissue at 4 to 6
 
weeks or longer.41
 
 
 
 
REFERENCES
 
 
 
1. Wallach JD, Flieg GM: Frostbite and its sequelae in captive
 
exotic birds. JAVMA 155:1035–1038, 1969.
2. Cooper JE: Birds of Prey: Health and Disease, ed 3. Malden, MA,
 
 
Blackwell Science, 2002, pp 80–81.
 
3. Coles BH: Avian Medicine and Surgery, ed 2. Malden, MA,
 
 
Blackwell Science, 1997, p 43.
4. Quesenberry KE, Hilyer EV: Supportive care and emergency
 
therapy, in Ritchie BW, Harrison GJ, Harrison LR (eds): Avian
Medicine: Principles and Applications. Lake Worth, FL, Wingers
 
 
Publications, 1994, pp 382–416.
5. Forbes NA, Harcourt-Brown NH: Wing tip oedema and dry
 
gangrene of raptors. Vet Rec 128:575–576, 1991.
 
 
6. Midtgard U: Circulatory adaptations to cold in birds, in Bech
 
C, Reinertsen RE (eds): Physiology of Cold Adaptation in Birds.
 
 
New York, Plenum Press, 1989, pp 211–222.
7. Ostnes JE, Bech C: Thermal control of metabolic cold defence
 
in pigeons Columbia livia. J Exp Biol 201:793–803, 1998.
 
 
8. Weatherly-White RCA, Sjostrom B, Paton B: Experimental
 
studies in cold injury: The pathogenesis of frostbite. J Surg Res
 
 
4:17–22, 1964.
9. Bourne MH, Piepkorn MW, Clayton F, Leonard LG: Analysis
 
of microvascular changes in frostbite injury. J Surg Res 40(1):
 
 
26–35, 1986.
10. Robson MC, Heggers JP: Evaluation of hand frostbite fluid as a
 
clue to pathogenesis. J Hand Surg 6:43–47, 1981.
 
 
11. Ozyazgan I, Tercan M, Melli M, et al: Eicosanoids and inflammatory
cells in frostbitten tissue: Prostacyclin, thromboxane,
 
polymorphonuclear leukocytes, and mast cells. Plast Reconst
Surg 101:1881–1886, 1998.
 
 
12. Waris T, Kyosola K: Cold injury of the rat skin. A fluorescence histochemical
study of adrenergic nerves, mast cells and patency of
 
cutaneous blood vessels. Scand J Plast Reconst Surg 16:1–9, 1982.
 
 
13. Mileski WJ, Raymond JF, Winn RK, et al: Inhibition of leukocyte
adherence and aggregation for treatment of severe cold
 
injury in rabbits. J Appl Physiol 74(3):1432–1436, 1993.
 
 
14. Calle PP, Montali RJ, Janssen DL: Distal extremity necrosis in
 
captive birds. J Wildl Dis 18(4):473–479, 1982.
 
 
15. Lumeij JT, Ritchie BW: Cardiology, in Ritchie BW, Harrison GJ,
 
Harrison LR (eds): Avian Medicine: Principles and Applications.
 
 
Lake Worth, FL, Wingers Publications, 1994, pp 695–722.
16. Angrist AA, Oka M, Nakao K, Marquiss J: Studies in experimental
 
endocarditis. Am J Pathol 36:181–190, 1956.
17. Lewis JH: Comparative Hemostasis in Vertebrates. New York,
 
 
Plenum Press, 1996, pp 97–114.
18. Thomson AE, Squires EJ, Gentry PE: Assessment of factor V,
VII, and X activities, the key coagulant proteins of the tissue factor
 
pathway in poultry plasma. Br Poult Sci 34:313–321, 2002.
 
 
19. Dabbert CB, Lochmiller RL, Teeter G: Thermal stress influences
 
clinical chemistry values of northern bobwhite (Colinus virginianus).
Comp Haematol Int 6(2):12–122, 1996.
 
 
20. Greenwald D, Cooper B, Gottlieb L: An algorithm for early
aggressive treatment of frostbite with limb salvage directed by
 
triple phase scanning. Plast Reconstr Surg 102:1069–1074, 1998.
 
 
21. Junila J, Kaarela O, Makarainen H, Waris T: Assessment of tissue
viability by thermography after experimentally produced
 
frostbite of the rabbit ear. Acta Radiologica 34:622–624, 1993.
 
 
22. Britt LD, Dascombe WH, Rodriguez A: New horizons in management
 
of hypothermia and frostbite injury. Surg Clin North
Am 71(2):345–370, 1991.
 
 
23. Entin MA, Baxter H: The influence of rapid rewarming on frostbite
 
in experimental animals. Plast Reconstr Surg 9:511–515, 1952.
24. Heidenreich M: Birds of Prey: Medicine and Management.
 
 
Malden, MA, Blackwell Science, 1995, p 211.
25. Murphy JV, Banwell PE, Roberts AHN, McGrouther DA:
 
Frostbite: Pathogenesis and treatment. J Trauma: Injury Infect
Crit Care 48(1):171–178, 2000.
 
 
26. Machin KL, Tellier LA, Lair S, Livingston A: Pharmacodynamics
 
of flunixin and ketoprofen in mallard ducks (Anas platyrhynchos).
J Zoo Wildl Med 32(2):222–229, 2001.
 
 
27. Machin KL, Livingston A: Assessment of the analgesic effects of
 
ketoprofen in ducks anesthetized with isoflurane. Am J Vet Res
 
 
63(6):821–826, 2002.
28. Heggers JP, Robson MC, Manavalen K, et al: Experimental and
 
clinical observations on frostbite. Ann Emerg Med 16(9):1056–
 
 
1062, 1987.
29. Fitzgerald GA: Cardiovascular pharmacology of nonselective
nonsteroidal antiinflammatory drugs and coxibs: Clinical considerations.
 
Am J Cardiol 89(6A):26D–32D, 2002.
 
 
30. Hayes DW, Mandracchia VJ, Considine C, Webb GE: Pentoxifylline:
Adjunctive therapy in the treatment of pedal frostbite.
 
Clinics Podiatric Med Surg 17(4):715–722, 2000.
31. Samlaska CP, Winfield EA: Pentoxifylline. J Am Acad Dermatol
 
 
30:603–621, 1994.
32. Kishi M, Tanaka H, Seiyama A: Pentoxifylline attenuates reperfusion
 
injury in skeletal muscle after partial ischemia. Am J Physiol
 
 
274:H1435–H1442, 1998.
33. Sener G, Akgun U, Satiroglu H, et al: The effect of pentoxifylline
 
on intestinal ischemia/reperfusion injury. Fundam Clin
Pharmacol 15(1):19–22, 2001.
 
 
34. Harmon BG: Avian heterophils in inflammation and disease
 
resistance. Poult Sci 77:972–977, 1998.
 
 
35. Miller MB, Koltai PJ: Treatment of experimental frostbite with
 
pentoxifylline and aloe vera cream. Arch Otolaryngol Head Neck
Surg 121:678–680, 1995.
 
 
36. Purkayastha SS, Roy A, Chauhan SKS, et al: Efficacy of pentoxifylline
 
with aspirin in the treatment of frostbite in rats. Indian J
Med Res 107:239–245, 1998.
 
 
37. Marsella R, Nicklin CF, Munson JW, Roberts SM: Pharmacokinetics
of pentoxifylline in dogs after oral and intravenous administration.
 
Am J Vet Res 61(6):631–637, 2000.
 
 
38. Cera L, Heggers J, Robson M, et al: The therapeutic efficacy of
aloe vera cream (Dermaide Aloe) in thermal injuries: Two case
 
reports. JAAHA 16:768–772, 1980.
 
 
39. Paul-Murphy JR, Brunson DB, Miletic V: Analgesic effects of
butorphanol and buprenorphine in conscious African grey parrots
 
(Psittacus erithacus erithacus and Psittacus erithacus timneh).
Am J Vet Res 600(10):1218–1221, 1999.
 
 
40. Orosz SE, Jones MP, Cox SK, et al: Pharmacokinetics of amoxicillin
 
plus clavulanic acid in blue-fronted Amazon parrots (Amazona
aestiva aestiva). J Avian Med Surg 14(2):107–112, 2000.
41. Hamlet MP: Prevention and treatment of cold injury. Int J Circumpolar
Health 59:108–113, 2000.
 
Compendium October 2003 Frostbite in Birds 781
 
 
 
www.VetLearn.com
 
 
 
5. _________ is an early sign of frostbite that may be
seen in birds.
a. Blistering c. Purulent discharge
b. Mummification d. Proprioceptive deficit
6. Proposed mechanisms of action of pentoxifylline do
not include
a. increasing red cell flexibility.
b. decreasing ice crystal formation.
c. decreasing leukocyte adhesion.
d. decreasing PMN oxidative bursts.
7. Antibiotic therapy should primarily be directed against
a. skin flora and clostridial infection.
b. coliform bacteria.
c. Mycobacterial infection.
d. Mycoplasma infection.
8. Surgical amputation should
a. occur as soon as it has been determined that frostbite
injury has occurred.
b. never occur.
c. occur after mummification.
d. occur after 1 to 2 weeks.
9. Frostbite diagnosis is typically based on
a. physical examination. c. radiographic changes.
b. biochemical changes. d. patient history.
10. A lesion that has been associated with frostbite in birds is
a. proliferative ileitis.
b. aseptic vegetative valvular endocarditis.
c. encephalomalacia.
d. chemodectoma.
1. The majority of avian frostbite cases involve the
a. beak. c. tail.
b. feet. d. tongue.
2. The hunting reflex
a. reduces body temperature in response to predators.
b. shunts blood away from penetrating wounds.
c. conserves core temperature while maintaining tissue
viability.
d. conceals predatory birds from their prey.
3. Proinflammatory mediators associated with frostbite
injury in mammalian models include
 
a. prostaglandin F2a.
 
 
b. prostacyclin.
c. ibuprofen.
d. antithrombin III.
4. A recommended antiinflammatory for treating frostbite
is
a. celecoxib.
b. prednisolone.
c. ketoprofen.
d. dexamethasone.
 
CE ARTICLE #5 CE TEST
The article you have read qualifies for 1.5 contact
hours of Continuing Education Credit from
the Auburn University College of Veterinary Medicine.
 
Choose the best answer to each of the following
 
 
questions; then mark your answers on the
 
postage-paid envelope inserted in Compendium.

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