ACTA VET. BRNO 2007, 76: S11-S15; doi:10.2754/avb200776S8S011
`
`Intramuscular versus Subcutaneous Administration of Iron Dextran in Suckling
`Piglets
`
`M. SVOBODA, J. DRÁBEK
`Clinic of Pig Diseases, Faculty of Veterinary Medicine,
`University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic
`Received August 15, 2006
`Accepted April 26, 2007
`
`Abstract
`Svoboda M., J. Drábek: Intramuscular versus Subcutaneous Administration of Iron Dextran in
`Suckling Piglets. Acta Vet. Brno 2007, 76: S11-S15.
`The aim of the study was to compare the development of red blood cell indices after
`subcutaneous versus intramuscular administration of iron dextran to suckling piglets during
`early postnatal period. The piglets in group I (n = 17) were injected subcutaneously (into
`groin) with 200 mg Fe3+ as iron dextran on day 3 of life. In group II (n = 16), the piglets
`received intramuscular injection (into gluteal muscles) of 200 mg Fe3+ as iron dextran on
`day 3 of life. In group III (n = 10), the piglets did not receive any iron till the age of 3 days.
`The blood was taken and analyzed (Hb, PCV, RBC, MCV, MCH, MCHC, Fe) on days 3,
`7, 14, 21, 28 and 35. Haematological indices of piglets in group III were characteristic for
`hypochromic anaemia. Anaemia in group III had a detrimental effect on the growth rate of
`piglets. The development of red blood cell indices and iron concentration in blood plasma
`in subcutaneously treated piglets did not differ significantly from that of intramuscularly-
`treated group. Both treatments prevented development of anaemia.
`Haemoglobin, packed cell volume, anaemia, neonatal
`
`Administration of iron to suckling piglets is a routine practice in swine production.
`The piglet is born with a limited reserve of iron (ca 50 mg) (Venn et al. 1947), and the
`sow’s milk is not a sufficient source of iron for piglets. From the sow’s milk, the piglets
`can receive 1-2 mg Fe daily (Czapó 1995). However the daily requirement of piglets for
`adequate haemoglobin formation and growth is 7-10 mg of iron per day (Kleinbeck and
`McGlone 1999). Therefore, without any additional iron administration the piglets develop
`anaemia within 10-14 days after birth (Egeli et al. 1998; Zimmernann 1995).
`The most common method is intramuscular injection of 200 mg Fe3+ in the form of iron
`dextran, although this method has been associated with some side effects. Firstly, Süveges
`and Glávits (1976) and Kolb and Hoffman (1989) described cases of acute toxicosis
`following iron dextran injection in antioxidant deficient piglets. Secondly, intramuscular
`injection of iron dextran can lead to myopathy in piglets deficient in vitamin E (Patterson
`et al. 1969; Chu et al. 1984; Kolb and Hoffman 1989). It has been suggested that free
`iron released from iron dextran activates the formation of free radicals, initiating lipid
`peroxidation leading to polymyositis and rhabdomyolysis (Foulkes et al. 1991). Thirdly,
`intramuscular injection into gluteal muscles can cause damage to nervus fibularis and
`nervus tibialis resulting in transient lameness of piglets (Heinritzi and Plonait 1997).
`The subcutaneous administration of iron dextran into the groin would prevent the two
`latter complications. Surprisingly, the producers of iron dextran preparations recommend
`only i.m. administration. The choice of injection technique seems to be governed more by
`tradition than facts, since an extensive search of the literature revealed little published data
`concerning the merits of either technique. We therefore decided to compare the efficiency
`of the two routes of administration.
`
`Address for correspondence:
`MVDr. Martin Svoboda, Ph.D.
`University of Veterinary and Pharmaceutical Sciences
`Palackého 1-3, 612 42 Brno
`Czech Republic
`
`Phone: +420 541 562 433
`E-mail: svobodama@vfu.cz
`http://www.vfu.cz/acta-vet/actavet.htm
`
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`Fig 1. Haemoglobin concentration
`
`Fig. 2. Packed cell volume
`
`Fig. 3. Red blood cell count
`
`Materials and Methods
`Experimental design
`A total of 43 piglets were used in the study. They
`were divided into 3 groups using split litters, i.e. each
`litter was divided into three different groups. The
`creep feed (Seltek, Tekro s.r.o. Praha, iron content 238
`mg/kg Fe) was offered to piglets from day 7 to day
`35. They were weaned at the age of 28 days. Animals
`in group I (n = 17) received subcutaneous injection
`of 200 mg Fe 3+ as iron dextran into groin on day 3 of
`life. In group II (n = 16) the piglets were i.m. injected
`into gluteal muscles with 200 mg Fe3+ in the form of
`iron dextran at the age of 3 days. The piglets in group
`III (n = 10) did not receive any iron till the age of 21
`days. On day 21, they were treated with iron dextran
`(200 mg Fe 3+, i.m.).
`Blood sampling
`Blood was collected from vena cava cranialis
`of the piglets on days 3, 7, 14, 21, 28 and 35. The
`EDTA (ethylenediaminetetraacetic acid) was used as
`anticoagulant for the haematological examination.
`Heparin was used as anticoagulant for determination
`of iron concentration in blood plasma. The piglets
`were weighed at the age of 3, 7, 14, 21, 28 and 35
`days.
`Haematological analysis
`Haematological examination included: haemoglobin
`concentration (Hb), packed cell volume (PCV), red
`blood cell count (RBC), mean corpuscular volume
`(MCV), mean corpuscular haemoglobin (MCH)
`and mean corpuscular haemoglobin concentration
`(MCHC). These
`indices were determined by
`haematological analyzer Celtac Alfa (Nihon Kohden).
`Iron concentration
`Iron concentration in blood plasma (Fe) was
`determined photometrically measuring iron complex
`with ferrozin (Iron liquid 917, Roche Diagnostic,
`Manheim, Germany).
`Statistical analyses
`The results were evaluated statistically by Kruskal
`Wallis ANOVA test. The results are presented as
`mean values and standard deviations of each index in
`Figs 1-5. Values with *p < 0.05, **p < 0.01 express
`significant differences among groups.
`Results
`of
`
`haematological
`
`Development
`indices
`haemoglobin
`in
`differences
`No
`concentration (Hb) and iron concentration
`in blood plasma (Fe) between group I (s.c.)
`and group II (i.m.) were found in any period of the trial. At the age of 7 days, 23.5 % of
`piglets in group I had Hb below 80 g/l (anaemic limit). In group II, Hb values below 80 g/l
`were found in 18.7 % of 7 days old piglets. From day 7 to day 14 Hb values in groups I and
`II increased significantly and no piglets become anaemic (Hb < 80 g/l) in any remaining
`period of the trial. From day 3 to day 7, Fe in groups I and II increased significantly and it
`was decreasing from day 7 till the weaning (day 28). No differences in Fe between groups
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`Fig. 4. Iron concentration in blood plasma
`
`I and II were found during the trial. No
`differences in MCV, MCH and MCHC were
`found between the groups I and II during the
`trial.
`In group III, starting from day 7, Hb,
`PCV, MCV, MCH and iron concentration
`in blood plasma (Fe) were found to be
`significantly lower than in groups I and II.
`After application of iron on day 21, Hb and
`Fe in group III increased significantly.
`Development of body weight
`No differences in body weight were found
`between the groups I and II during the trial.
`The iron deficiency in group III resulted in
`significantly lower body weights compared
`to iron dextran treated groups.
`Discussion
`In order to discuss the merits of either
`technique, it is important to understand the
`mechanism of action of iron dextran. Iron
`dextran belongs to iron complexes of the
`robust and stable type with a molecular
`mass of 100 000 daltons and more. These
`complexes are composed of a polynuclear
`iron
`(III) hydroxid
`complexed with
`dextran (polyisomaltose) or with dextrin
`(polymaltose) (Geisser 1999).
`Because of its high molecular size, the iron
`dextran is not directly absorbed from the site
`of injection into the blood stream, but enters the lymphatics (Thorén-Tolling 1977, Kolb
`et al. 1992). Consequently 3-4 hours after deep intramuscular injection into gluteal muscles
`the iron content of inguinal and iliac lymph nodes is already increased (Kolb et al. 1992).
`The iron complex is transported via the lymphatics to body lymph nodes and further to the
`general circulatory system (Thorén-Tolling 1977). The iron dextran is taken from plasma
`by macrophages of RES (reticuloendothelial system), the iron is split off and partially re-
`enters plasma, from where it reaches the marrow as transferrin for haemoglobin synthesis
`(Kolb et al. 1992).
`A study concerning the rate of iron dextran absorption from injection site after i.m.
`injection showed that 7 days were necessary for almost complete absorption of administered
`dose (150 mg Fe as iron dextran). Information concerning the rate of absorption after s. c.
`administration is missing. The works of Miller et al. (1967) and Kolb et al. (1992) show
`that the iron dextran is absorbed considerably more slowly from adipose tissue.
`The importance of the site of injection was demonstrated in vaccination experiments.
`Since the way of absorption of injected vaccines from injection site is similar to that of
`iron dextran (i.e., transport of high molecular complex via lymphatics), we present here
`following examples.
`Injecting a vaccine into a layer of subcutaneous fat may result in slow mobilization
`and processing of antigen and in vaccination failure – for example in rabies and influenza
`vaccines (Groswasser et al. 1997). Compared with intramuscular injection, subcutaneous
`injection of hepatitis B vaccine leads to significantly lower seroconversion rates and more
`
`Fig. 5. Body weight
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`rapid decay of antibody response (Poland et al. 1997). This is in agreement with Michaels
`and Poole (1970) who demonstrated that adipose tissue, having much poorer drainage
`channels, retains injected material for much longer. Therefore the antigen takes longer
`to reach the circulation after being deposited in fat, leading to a delay in processing by
`macrophages (Seale and Zuckerman 2001).
`The rapidity of iron dextran processing is an important factor for development of
`erythrocyte profile in early postnatal period of life of piglets. It has been demonstrated
`that after i.m. administration of iron dextran, certain percentage of piglets develop
`anaemia at the age of 7 days with values of Hb being below 80 g/l (Lemacher and
`Bostedt 1995; Iben 1998). This can be explained by delayed availability of iron for
`haemoglobin synthesis. We suggest that further delay in iron dextran processing would
`cause more pronounced and longer anaemia in this life period of piglets. In our study,
`23.5 % of piglets in subcutaneously treated group had Hb below 80 g/l at the age of 7
`days. In intramuscularly treated group Hb below 80 g/l was found in 18.7% of piglets.
`No differences in mean values of haematological indices between i.m. and s.c. treated
`piglets were found at the age of 7 days.
`The subcutaneous administration of iron dextran has been employed in studies of Behrens
`and Lauprecht (1963) and Egeli et al. (1998). Behrens and Lauprecht (1963) found
`comparable growth intensity between i.m. and s.c. treated piglets, although haematological
`analysis was not included in the study. More recently Egeli et al. (1998) evaluated
`efficiency of oral administration of iron chelates in comparison with s.c. injection of iron
`dextran. They found good efficiency of s.c. injected iron dextran, however, comparison
`with i.m. technique was not included in the study.
`The development of haematological parameters in group III was as expected. The
`piglets developed hypochromic anaemia. The piglets were not injected with iron till
`the age of 21 days to be certain of development of anaemia. At the age of 21 days, the
`piglets were injected with iron to avoid further impaired welfare. The iron deficiency in
`group III resulted in significantly lower body weights compared to iron dextran treated
`groups.The body weights remained lower till the end of the trial. The detrimental effect
`of iron deficiency has been documented in several studies (Egeli et al. 1998; Svoboda
`and Drábek 2002).
`In our study, we found comparable efficiency of s.c. injection of iron dextran to that of
`i.m. administration in all periods of the trial. We suggest that this could be explained by
`relatively small amount of subcutaneous fat in 3-day-old piglets and by the proximity of
`the injection site (groin) to inguinal and iliac lymph nodes.
`We conclude that subcutaneous injection of iron dextran into the groin represents
`a suitable method for iron administration in piglets.
`Intramuskulární versus subkutánní aplikace dextranu železa u sajících selat
`Cílem práce bylo porovnat vývoj ukazatelů červeného krevního obrazu po subkutánní
`versus intramuskulární aplikaci dextranu železa u sajících selat v časném postnatálním
`období. Selatům ve skupině I (n = 17) bylo ve věku 3 dnů aplikováno subkutánně
`(do předkolenní řasy) 200 mg Fe3+ ve formě dextranu železa. Ve skupině II (n = 16) bylo
`3denním selatům aplikováno intramuskulárně (do gluteální svaloviny) 200 mg Fe3+ ve
`formě dextranu železa. Selatům ve skupině III (n = 10) nebylo aplikováno žádné železo
`do věku 21 dní.Vzorky krve byly odebrány a analyzovány (Hb, PCV, RBC, MCV, MCH,
`MCHC, Fe) ve věku 3, 7, 14, 21, 28 a 35 dnů. Hematologické parametry ve skupině III byly
`charakteristické pro hypochromní anémii. Anémie ve skupině III měla negativní vliv na
`intenzitu růstu. Vývoj ukazatelů červeného krevního obrazu a koncentrace železa v krevní
`plazmě ve skupině selat se subkutánní aplikací se významně nelišil od intramuskulárně
`ošetřené skupiny. Obě metody zabránily vzniku anémie u selat.
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`Acknowledgements
`The study was supported by the project MSM 6215712403.
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