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Magnesium therapy in a hypocalcemic African grey parrot

(Psittacus erithacus).
Abstract: Hypocalcemic-induced seizure activity is actually a clinical entity that's generally
diagnosed in neurologic African grey parrots (Psillacus erithacus). Plasma calcium ranges tend to be
typically under 6.0 mg/dL at the period of seizure activity, as well as although the underlying cause
of the hypocalcemia features not necessarily but been determined, many theories have been
proposed. An African grey parrot which had been fed a seed diet program with regard to 8 many
years had been given hypocalcemia as well as seizures and exhibited precipitously declining plasma
calcium levels, despite aggressive calcium and vitamin A, D, along with E supplementation
pertaining to 4 days. Baseline magnesium levels in this parrot were decided to become 1.9 mg/dL;
therefore, magnesium sulfate ended up being administered at a dose regarding 20 mg/kg IM once.
Twenty-four hours following supplementation, your plasma magnesium level ended up being 3.3
mg/dL, with no further seizure activity had been observed. We think in which a main dietary
magnesium deficiency may happen in order to be existing on this African grey parrot, just like a
syndrome inside leghorn chicks, that is frequently seen as an progressive hypocalcemia that's not
able to become corrected by calcium supplementation alone.
Key words: hypocalcemia, hypomagnesemia, seizures, calcitriol, calcium, magnesium, avian, African
grey parrot, Psittacus erithacus
Clinical Report
An approximately 10-year-old Congo African grey parrot (Psittacus erithacus erithacus) regarding
mysterious sex has been introduced to the referring veterinarian for that chief complaint of
abnormal neurologic behavior regarding 24-hour duration. The Particular abnormal behavior
exhibited through the African grey parrot included the inability to always be able to right itself,
frantic vocalization, as well as the inability to perch. The Particular bird have been fed a commercial
seed diet supplemented using occasional fruit as well as veggies since acquisition eight years
earlier. Right After receiving a history and conducting a physical examination on the bird, the
veterinarian referred your parrot to the Institution associated with Veterinary Medicine in the
Louisiana State University Or College with regard to further diagnostic testing and hospitalization.
On physical examination (day 1), the actual bird had been observed being mentally depressed, but
still responsive. Although simply no overt seizure activity was observed during the examination, the
actual bird has been sternal, not in a new position to right itself, and also hypertonic. Its ventrum
lacked feathers (chronic feather picking had been observed by the owner), and also the choanal
papilla were blunted. Original emergency stabilization remedy included the administration
associated with diazepam (0.5 mg/kg IM); calcium glubionate (100 mg/kg PO); calcium gluconate
(100 mg/kg IM); supplemental fluids (45 mL/kg SC; Normosol-R, Hospira, Inc, Lake Forest, IL, USA);
doxycycline (60 mg/kg IM; Vibravenos formulation, Pfizer Laboratories, London, Ontario, Canada);
vitamins A, D, as well as E (3300 IU/kg IM; Northwest Pharmacy and Compounding Center,
Houston, TX, USA); and also edetate calcium disodium (35 mg/kg IM; calcium disodium versenate,
3M Pharmaceuticals, Northridge, CA, USA).
The bird has been then placed in an incubator at 26.7[degrees]C (80[degrees]F) and 65% humidity.
Approximately 4 hrs later, 0.3 mL of blood had been drawn in the right jugular vein, along along
with a plasma biochemical analysis has been performed with a point-of-care chemistry analyzer
(VetScan Classic, Abaxis Inc, Union City, CA, USA). The Actual outcomes confirmed the actual
following abnormalities: aspartate aminotransferase (AST; 559 IU/L; reference range, 100-350 IU/
L), creatine kinase (6270 IU/L; reference range, 123-875 IU/L), uric acid (22 mg/dL; reference
range, 4-10 mg/dL), along with calcium (5.5 mg/dL; reference range, 8-13 mg/dL). (1)
On day 2, the particular bird had been noted to be brighter and more alert. The Particular bird was
able to get up on its really own on the flat surface yet had been struggling to walk or perhaps
properly perch. the bird was positioned under general anesthesia together with isoflurane and
oxygen, along with another phlebotomy has been performed from your proper jugular vein. Your
collected blood taste ended up being submitted for any total blood count (CBC) and hefty metal
panel (lead, zinc, copper). Ventrodorsal and lateral radiographs were additionally obtained even
even though the bird was under general anesthesia. the CBC outcomes along with radiographs had
been inside reference range. the heavy metal outcomes were as follows: lead (<0.02 ppm; reference
range, <0.02 ppm), zinc (0.6 ppm; reference range, 1.25-2.29 ppm), and also copper (0.5 ppm;
reference range, 0.074). 19 ppm). (2) These kind of heavy metal reference ranges refer particularly
to Amazon parrots, and the elevated copper degree may become because of to be able to species
variation as well as dietary influence. Diazepam (0.5 mg/kg IM q12h), calcium glubionate (100 mg/kg
PO q12h), as well as Normosol-R (45 mL/kg SC q12h) treatments were continued.
On day 3, yet another plasma biochemical analysis ended up being performed and the following
abnormalities were identified: AST, 1831 IU/L; bile acids, 184 [micro]mol/L (reference range, 13-90
[micro]mol/L); (3) creatine kinase, >14000 IU/L; along with calcium, 4.5 mg/dL. the calcium
glubionate dose had been consequently doubled (200 mg]kg PO q12h). In day 5, the bird exhibited
seizure-like exercise and has been administered diazepam (0.5 mg/kg IM) in order to treat the actual
clinical condition, after that it absolutely was placed within an oxygen cage. A New blood taste
ended up being once again submitted to acquire a plasma biochemical analysis on day 5
postpresentation, and furthermore the following abnormalities had been noted: AST, 1979 IU/L; bile
acids, 53 [micro]mol/L; calcium, <4 mg/dL; along with phosphorus, 1.8 mg/dL (reference range, 3.2-
5.4 mg/dL). (1) An ionized calcium level ended up being established being 0.54 mmol/L (reference
range, 0.96-1.22 mmol/L). (4)
Despite your administration regarding calcium glubionate in 100 mg/kg PO q12h for that first two
days of treatment, a heightened dose of calcium glubionate (200 mg/kg PO q12h) administered for
enter now yet another two days, and a single dose involving vitamins A, D, and also E, the bird's
plasma calcium amounts continued for you to drop precipitously. In the afternoon associated with
presentation, your bird's plasma calcium level had been 5.5 mg/dL, but, by treatment day 5, the
particular plasma calcium level had fallen in order to lower than 4.0 mg/dL. because with the
declining plasma calcium degree inside the face associated with aggressive calcium
supplementation, a blood test had been submitted for magnesium, amylase, along with lipase ranges
in day 5 following presentation. Even though the particular amylase and also lipase ranges were
established being within revealed reference ranges, the magnesium degree is discovered being
reduced at 1.9 mg/dL (reference range, 2.1-3.4 mg/dL). (5) Magnesium sulfate (20 mg/kg IM once;
Magnesium Sulfate Injection, USP 50%, Abraxis Pharmaceutical Products, Schaumberg, IL, USA)
had been administered. (6) Calcium glubionate administration has been discontinued, as well as
treatment along with calcium gluconate (50 mg/kg IM once, then 10 mg/kg IM q12h) had been
initiated. A New second injection regarding vitamins A, D, and E (3300 IU/kg IM once) has been
furthermore administered.
A blood trial had been submitted for a repeat biochemical analysis in day 9 (24 hours following your
administration of the magnesium) as well as the next abnormalities had been identified: AST, 851
IU/L; creatine kinase, >14 000 IU/L; along with calcium, 7.7 mg/dL. The Actual bird has been
steadily weaned off Normosol-R, diazepam, along with calcium gluconate, and a final plasma
biochemical analysis had been run on day 12 following presentation (4 times following the
administration in the magnesium). The next abnormalities had been identified: creatine kinase, >14
000 IU/L; as well as calcium, 8.3 mg/dL. Your plasma magnesium level ended up being established
being 3.3 mg/dL as well time. The Particular bird was launched from the hospital with just about all
the recommendations to provide calcium supplementation within the water, progressively adjust to
balanced commercial pelleted diet, and also carry on using cuttlebone and/ or mineral block access
inside the cage. The Actual referring veterinarian performed follow-up examinations, and the bird's
owner studies in which no more seizure activity had occurred since discharge in the hospital.
Hypocalcemic-induced seizure activity can be a well-recognized syndrome associated with African
grey parrots. (1,7-9) Clinical indicators are reported to always be able to occur in birds among 2 and also many years old. (8,10) the clinical manifestation with the
syndrome varies greatly, depending around the individual bird along with its absolute calcium
status. Incoordination, for example stumbling or even falling off a perch, might become the initial
observed signs. Patients exhibiting mild neurologic abnormalities usually demonstrate calcium
amounts within your published laboratory reference range (8-13 mg/dL). (1,9) The Particular
episodes steadily increase in frequency and also in many cases are exacerbated using excitement or
even stress. Eventually, overt seizure activity can be observed, and plasma calcium ranges measured
with this occasion around tend to be generally less than 6.0 mg/dL. (8) Occasionally, clinically
affected birds exhibit low plasma ionized calcium amounts as well as concurrent total plasma
calcium concentrations inside the particular reference range. (4)
Many theories which have been proposed to explain the actual hypocalcemic syndrome associated
with African grey parrots, but the underlying pathophysiologic etiology in the condition remains
elusive. 1 hypothesis postulates that African grey parrots, secondary to end up being able to viral
damage towards the parathyroid gland, absence the chance to mobilize skeletal calcium in reaction
in order to hypocalcemia. (8) Yet Another theory proposes in which a loss of calcium through the
actual kidney can be responsible for that hypocalcemia, although any mechanism regarding this
provides yet to be described. (7) Any third supposition indicates that simple dietary insufficiency
regarding calcium and also vitamin D, along with excess fat intake, leads to eventual hypocalcemia
inside African grey parrots. Substantial dietary fatty acids, commonly related with seed-based diets,
may form insoluble salts using calcium along with thereby prevent intestinal absorption of calcium.
The physiologic roles regarding calcium, magnesium, and 1,25-dihydroxycholecalciferol (the active
metabolite associated with vitamin [D.sub.3]), are usually intimately associated. The Particular
primary functions associated with calcium in the entire body consist of its role like a regulatory ion
and the promotion regarding structural bone integrity, together with approximately 99% of calcium
getting stored inside the inorganic matrix involving bones. (12) Magnesium is definitely an crucial
dietary element which features as an activator or even cofactor regarding greater than 300 enzymes
inside the body, such as 1-[alpha]-hydroxylase; (12) 1-[alpha]-hydroxylase is definitely an enzyme
involved with vitamin [D.sub.3] metabolism. (13) Magnesium also complexes using parathyroid
hormone (PTH) receptors, along with decreased levels regarding magnesium result in an impaired
response to PTH. (14) The Actual PTH is secreted from the parathyroid gland in response to end up
being able to reduced plasma calcium concentrations. Your major capabilities involving PTH tend to
be stimulation associated with renal calcium reabsorption within the distal convoluted tubules,
elevated osteoclastic bone resorption, and also elevated intestinal absorption involving calcium. (15)
The principle active type of vitamin [D.sub.3] can be 1,25-dihydroxycholecalciferol (calcitriol). The
idea is actually produced through the conversion involving cholecalciferol to the circulating form of
vitamin [D.sub.3], 25-hydroxycholecalciferol. Your precursor 25-hydroxycholecalciferol then travels
for the kidney, exactly where it really is hydroxylated by simply 1-[alpha]-hydroxylase to form
calcitriol. Calcitriol acts in order to facilitate intestinal absorption associated with calcium by
helping the manufacture of calcium-binding proteins and by decreasing the renal excretion
associated with calcium through the augmentation regarding tubular resorption. This kind of occurs
synergistically together with PTH. (11,16) Calcitriol additionally increases osteoclast activity, which
in turn induces bone resorption along with increases the total calcium level. (11,16) a wide range of
study regarding the connection in between calcium, PTH, calcitriol, and also magnesium has been
performed throughout growing leghorn chicks. Many significantly, main magnesium depletion in
leghorn chicks continues to always be able to be discovered to be seen as a progressive
hypocalcemia as well as insufficient manufacture of calcitriol. (15,17)
Research in leghorn chicks provides said that a normocalcemic, magnesium-deficient diet plan
induces low plasma magnesium and calcium levels. (15,17) Notably, the particular secondary
hypocalcemia can not really be corrected through calcium supplementation alone; the particular
hypomagnesemia must be rectified before the calcium levels normalize. Additionally, the particular
calcium- as well as magnesium-deficient chicks fail to demonstrate the expected compensatory boost
in plasma calcitriol levels, yet chicks fed the calcium-deficient, normomagnesemic diet exhibit a new
threefold boost in calcitriol as well as attain higher calcium levels. (17) The Particular not enough
calcitriol production inside chicks fed the actual magnesium-deficient diet program just isn't
connected along with inadequate circulating 25-hydroxycholecalciferol (ie, the particular precursor
for you to calcitriol). Additionally, 1-[alpha]-hydroxylase activity within the renal tubules is not
elevated, as could be expected within calcium-deficient individuals. (17) This kind of suggests that,
even within the confront of exogenous cholecalciferol supplementation, elevated output of calcitriol
does not ensue inside magnesium-deficient chicks. That will be probable that phenomenon occurs
simply because magnesium is truly a cofactor with regard to 1-[alpha]-hydroxylase. (13) This specific
exact same trend associated with reduced calcitriol production, within the deal with regarding
adequate cholecalciferol concentrations, may exist in affected African grey parrots in which still
exhibit decreasing plasma calcium ranges despite cholecalciferol administration inside the kind of
vitamin A, D, and E injections.
Further studies have demonstrated in which chicks fed a magnesium-deficient diet plan exhibit
significant parathyroid gland hyperactivity within the deficiency of bone resorption. (18) This
specific finding will be constant with affected African grey parrots, that typically demonstrate
enlarged parathyroid glands using severe, destructive, parathyroid degeneration. In spite of
apparent active secretion regarding PTH, cortical bones through affected African grey parrots
usually exhibit normal thickness, indicating an lack of bone resorption along with calcium
mobilization. (8) Your decrease in calcium mobilization through cortical bones inside the
magnesium-deficient chicks will be correlated using significant bone magnesium depletion as well as
an ensuing elevation in bone calcium content. (18) This specific suggests that, within the face
involving primary hypomagnesemia, supplemental calcium administered ahead associated with the
correction regarding the low magnesium may become sequestered within the bone rather than
leading to an elevated plasma calcium level. Evidence suggests this phenomenon happens in
magnesium-deficient leghorn chicks simply because of bone resistance towards the action associated
with PTH secondary towards the hypomagnesemia, (18) and this exact same mechanism regarding
action may be occurring throughout affected African grey parrots.
The African grey parrot introduced in this case statement exhibited the continued precipitous drop
within its plasma calcium amounts in spite of aggressive oral calcium and injectable vitamin A, D,
along with E supplementation. Although we propose that will the primary magnesium deficiency was
the primary reason for your lack of reaction in order to calcium as well as cholecalciferol
supplementation, other treatment options that get been administered, for example edetate calcium
disodium (Ca[Na.sub.2] EDTA) as well as injectable doxycycline, could get interfered with most the
bird's calcium balance. in domestic cows, it may be proposed that intravenous infusion associated
with edetate disodium ([Na.sub.2] EDTA) disrupts calcium homeostatic mechanisms. (19)
Additionally, nevertheless, there aren't any reported human cases of Ca[Na.sub.2]-EDTA--induced
hypocalcemia, you will find no much less than 2 studies regarding pediatric deaths attributed to
[Na.sub.2]-EDTA administration and associated hypocalcemia. (20) Zero research pertaining for the
affects involving both [Na.sub.2]-EDTA or perhaps Ca[Na.sub.2]-EDTA about calcium homeostatic
mechanisms in birds continues to become able to be published, to always be able to our knowledge.
The Particular bird within this case study received merely 4 doses regarding intramuscular
Ca[Na.sub.2]-EDTA over 48 hours, and also its serum calcium levels continued in order to drop
pertaining to 72 hours after discontinuing the particular drug. The Particular parrot additionally
received any dose involving injectable doxycycline on presentation. Though the particular
detrimental outcomes of calcium on the activity associated with orally administered tetracycline-
class drugs has been frequently reported, (21) doxycycline can be reported to always be able to
exhibit a minimal affinity for calcium binding. (22) Your administration associated with this drug
should, therefore, not have affected your bird's total plasma calcium levels.
Hypocalcemic-induced seizure exercise can end up being a clinical entity that's commonly diagnosed
within neurologic African grey parrots. Although several theories are already proposed in order to
explain this clinical entity, none possess fully accounted for your hematologic, histologic, along with
clinical findings. We propose the continual precipitous decline in plasma calcium levels, despite
aggressive calcium along with vitamin A, D, and also E supplementation, exhibited by the African
grey parrot in this case record had been the effect of the main hypomagnesemia caused with a
prolonged nutritionally poor diet. Following administration of magnesium sulfate (20 mg/kg IM once)
along with subsequent attainment of your normocalcemic state, this bird was progressively
transitioned to some nutritionally complete diet. the patient's neurologic abnormalities get certainly
not returned.
Because regarding their popularity as pets in supplement for you to their possible for long life,
further specifics of optimal dietary magnesium and also calcium levels within the African grey parrot
is actually needed. Until such details are available, it is strongly recommended that these birds be
fed an appropriately formulated avian diet plan that is well-balanced inside each magnesium and
also calcium.
Acknowledgments. We thank Dr James Rumore with regard to referring this case towards the
Louisiana State School Veterinary Teaching Hospital's small Animal Clinic and Drs Sara Schultz and
also Brook Fahrig Grasperge pertaining to their particular exemplary work with this particular
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Megan S. Kirchgessner, DVM, Thomas N. Tully Jr, DVM, MS, Dipl ABVP (Avian), Dipl ECAMS, Javier
Nevarez, DVM, PhD, David Sanchez-Migallon Guzman, Lic en Vet, MS, Dipl ECZM (Avian), Dipl
ACZM, as well as Mark J. Acierno, MBA, DVM, Dipl ACVIM
From your Virginia Department associated with Game and Inland Fisheries, 4010 W Broad St,
Richmond, VA 23230, USA (Kirchgessner); the actual Department involving Clinical Sciences,
Institution regarding Veterinary Medicine, Louisiana State University, Skip Bertman Dr, Baton
Rouge, LA 70803, USA (Tully, Nevarez, Acierno); as well as the Companion Exotic Animal Medicine
& Surgery Service, College involving California Davis school associated with Veterinary Medicine,
one Shields Ave, Davis, CA 95616, USA (Guzman).
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