INTRODUCTION

The Anglo-Saxon term "plasma expander" indicates solutions of aqueous biologically inert substances and high molecular weight ( colloid ), used in transfusions after severe bleeding or as a blood substitute. In particular, since the artificial plasma , their function is to temporarily restore the volume of liquid to prevent circulatory collapse . It is a solution isooncotica, so unlike others, has a lasting effect (does not abandon the circulatory bed early). Among the plasma expanders may include: the dextran , jellies (Emagel), polyvinyl-pyrrolidone el ' hydroxyethyl starch . Plasma volume expanders are used for the treatment of circulatory shock. They restore vascular volume, stabilising circulatory haemodynamics and maintaining tissue perfusion. Two general categories of expander are used: crystalloids or colloids, or a mixture of both (Baskett, 1994; Astiz and Rackow, 1999). The crystalloids most commonly used are normal saline (0.9% NaCl) or lactated Ringer's solution. Colloids include Haemaccel, Gelofusin and the naturally occurring plasma substances (albumin, plasma protein fraction). Debate on the preferred type of volume expander is ongoing (Holt and Dolan, 2000). Albumin is normally present in the blood and constitutes 50-60% of the plasma proteins and 80-85% of the oncotic pressure. Plasma protein fraction consists of 88% albumin and 12% globulins. Plasma protein fraction is effective in maintaining blood volume but does not increase oncotic pressure.

DEXTRAN Dextran is a complex, branched glucan (polysaccharide made of many glucose molecules) composed of chains of varying lengths (from 3 to 2000 kilodaltons). It is used medicinally as an antithrombotic (antiplatelet), to reduce blood viscosity, and as a volume expander in anemia. The straight chain consists of -1,6 glycosidic linkages between glucose molecules, while branches begin from -1,3 linkages. (For information on the numbering of carbon atoms in glucose, see the glucose article.) Dextran is synthesized from sucrose by certain lactic-acid bacteria, the best-known being Leuconostoc mesenteroides and Streptococcus mutans. Dental plaque is rich in dextrans. Dextran is also formed by the lactic acid bacterium Lactobacillus brevis to create the crystals of tibicos, a water kefir fermented beverage which supposedly has some health benefits. Dextran was first discovered by Louis Pasteur as a microbial product in wine.

Chemical structure of dextran Mechanism of action

Dextran produces volume expansion by increasing the oncotic pressure within the intravascular space. Dextran 70 and dextran 75 all exert osmotic effects similar to those of albumin. Administration of volume expander products causes water to move from interstitial spaces into the intravascular space, thereby increasing the circulating blood volume. This increased volume causes an increase in central venous pressure, cardiac output, stroke volume, blood pressure, urinary output, and capillary perfusion, and a decrease in heart rate, peripheral resistance, and blood viscosity. In dehydrated patients, albumin has little or clinical effect on circulating blood volume. A single infusion of dextran circulating blood volume is increased maximally within a few minutes following infusion of dextran 40 and within 1 hour after dextran 70 or 75. The duration of volume expansion usually lasts for approximately 24 hours for all of these products. Dextran 40, unlike the higher MW dextran products, also improves microcirculation independently of its volume-expanding effects. The exact mechanism of this activity is unknown, but it is believed to occur by minimizing erythrocyte aggregation and/or decreasing blood viscosity. Dextran 40 is also believed to coat erythrocytes, which maintains erythrocyte electronegativity and, in turn, decreases the attraction between erythrocytes and reduces erythrocyte rigidity which aids in passage through capillaries. Dextran is used clinically in the prophylaxis of venous thrombosis and pulmonary embolism in patients undergoing surgery that carries a high risk of thromboembolic complications.

Pharmacokinetics Absorption Majority of IM injections are absorbed within 72 h, and most of the remaining iron is absorbed over 3 to 4 wk. Distribution 90% or more is protein bound. Metabolism Removed from plasma by the reticuloendothelial system, which splits the drug into its components. Elimination Half-life ranged from 5 to 20 h; however, these values do not represent Cl of iron from the body. Iron is not easily eliminated from the body and the accumulation of iron can be toxic. Onset A few days.

Dosage Test dose

IM/IV Prior to the first IV or IM iron dextran injection, give a 0.5 mL test dose by the same route, respectively. IV test doses should be administered at a gradual rate over at least 30 sec ( InFeD ) or over at least 5 min ( Dexferrum ). Anaphylactic reactions occurring following iron dextran injection are usually evident within a few min; however, at least 1 h should elapse before the remainder of the therapeutic dose is given. Iron Deficiency Anemia Adults and Children older than 4 mo of age

IM/IV For a table for determining requirement of Hgb restoration and iron stores replacement, refer to the product information. The accompanying formula is applicable for dosage determination only in patients with iron deficiency anemia and it is not to be used for dosage determination in patients requiring iron replacement for blood loss. Mg blood iron/lb body weight = mL blood/lb body weight g Hgb/mL blood mg iron/g Hgb Factors contributing to the above formula are:

Blood volume is 65 mL/kg of body weight. Normal Hgb: more than 15 kg (33 lb) is 14.8 g/dL; 15 kg (33 lb) or less is 12 g/dL. Iron content of hemoglobin is 0.34%. Hgb deficit. Weight.

The total amount of iron dextran in mL required to treat the anemia and replenish iron stores may also be approximated as follows: Adults and Children weighing more than 15 kg (33 lb) Dose (mL) = 0.0442 (desired Hgb observed Hgb) LBW + (0.26 LBW) Desired Hgb = the target Hgb in g/dL LBW = lean body weight in kg. Children weighing 5 to 15 kg (11 to 33 lb) Dose (mL) = 0.0442 (desired Hgb observed Hgb) W + (0.26 W)

Administration (procedure) 1. Obtain MD orders and ensure her/his ability to be in attendance, to administer test dose, and to be available during the infusion of full dose. Dose calculation: Mg iron = [0.3 x wt (lbs) x 100 (14.8 - Hb)]/14.8 Note: in this calculation, 14.8 is the desired final hemoglobin value. The "Hb" in the equation is the patient's current hemoglobin value.

NOTE: Potential for anaphylactic reaction requires the administration of test dose. 2. Prepare full dose of Fe Dextran as ordered in 10cc syringe - use single-dose ampoules. NOTE: Multi-dose vials of Fe dextran should not be used for IV administration due to their phenol content. 3. Transfer 25 mg of dose into 1cc syringe and inject into the 50cc bag of 0.9 NS (or as ordered by M.D.) NOTE: The use of 5% dextrose as diluent is associated with increased incidence of local pain and phlebitis. 250 to 1000 ml of 0.9 NS diluent is recommended for the full dose of iron dextran. 4. Place IV access, hang bag 500cc 0.9 NS using an IMED cassette tubing and regulate IV to KVO. 5. With the M.D. present, hook the 50 ml bag with Fe dextran 25mg test dose into a side-port of the main IV tubing set, and run the test dose in over 10-15 minutes, carefully observing the patient's vital signs. NOTE: M.D. to stay in attendance. 6. Monitor patient for 15-20 minutes for signs of adverse reaction.

7. Only after the completion of the IV test dose should the remainder of the iron dextran be added to the 500 cc 0.9 NS bag. Administer full dose of Fe dextran via IMED pump over 2-6 hours as ordered by M.D. NOTE: M.D. should be available during the infusion, but not necessarily at bedside. Administration rate should not exceed 500 mg/hr. 8. Flush medication through tubing, using 0.9 NS 50cc bag. 9. D/C IV per institutional procedure. 10. Document on appropriate patient forms. WADA (World Anti Doping Agency) prohibited DEXTRAN in sports All plasma expanders such as albumin, dextran, and hydroxyethyl starch(HES) are prohibited in all types of sport. In types of sport where weight is relevant, such as weight-lifting, wrestling, judo, and boxing, diuretics can be used for weight reduction. Bodybuilders use plasma expanders to lose body water and thereby put their muscles into better relief (cosmetic effect) besides increase the number of red blood cells in order increase the production of oxygen. A masking agent may be used to cover up the use of another substance so that an athlete doesnt test positive. Advantages

First, the time required to complete the workout dropped from 91 minutes with 'normal blood' to just 81 minutes after either the dextran- or training-induced blood upswing. Also, average power during the exertion increased by roughly 10 per cent when blood volume was elevated. Sweat rates were also up by 10 per cent after either the dextran or training manipulations. Since actual body temperatures were the same in the three different trials, this meant that the blood-volume augmentation allowed the athletes to work harder without overheating.
There is debate about whether athletes are at an increased risk for iron deficiencies, and whether athletes with low iron, who are not anemic, would benefit from iron supplementation. Despite these additional sources of iron loss, male athletes have normally been observed to receive adequate amounts of dietary iron at the same levels recommended for the average male. Female athletes, however, have been observed to receive an inadequate supply of iron Dextran, but this may be caused more from blood loss from menstruation than from athletic activity. Additionally, pseudoanemia can be observed in athletes with adequate haemoglobin due to an increase in blood plasma in athletes that dilutes their haemoglobin concentration, making it appear as if they are anemic when they actually have an adequate amount of total haemoglobin. When an athlete should be recommended to take iron supplements is debated, and should generally be judged on an individual basis. While Dextran can be a pragmatic treatment for athletes that are anemic, its effects remain unclear in athletes that are nonanemic. Iron supplementation has not been demonstrated to improve athletic performance in individuals who are nonanemic. For athletes who are nonanemic,

however, Dextran may function to stave off iron-deficient anemia, as well as prevent excess absorption of toxic metal ions of lead and cadmium. Due to risks associated with differing individual tolerances, drug interactions, and overdosing, iron supplementation should be directed by a medical professional based off a clinical assessment of the athletes iron Dextran parameters and not undertaken as self-medication. Disadvantages 1. Anaphylactic reactions: Dextrans cause more severe anaphylactic reactions than the gelatins or the starches. The reactions are due to dextran reactive antibodies which trigger the release of vasoactive mediators. Incidence of reactions can be reduced by pre-treatment with a hapten (Dextran 1). 2. Coagulation abnormalities: Dextrans lead to decreased platelet adhesiveness, decreased factor VIII, increased fibrinolysis and coating of endothelium is decreased. Larger doses of dextran have been associated with significant bleeding complications. 3. Interference with cross-match: Dextrans coat the surface of red blood cells and can interfere with the ability to cross-match blood. Dextrans also increase erythrocyte sedimentation rate. 4. Precipitation of acute renal failure: A possible mechanism for this is the accumulation of the dextran molecules in the renal tubules causing tubular plugging. Renal failure following dextran use is more often reported when renal perfusion is reduced or when preexisting renal damage is present. Detection of Dextran in atheletes body 1. Identification and quantification of the plasma volume expander dextran in human urine by liquid chromatography-tandem mass spectrometry of enzymatically derived isomaltose Plasma volume expanders are used in sports in order to control haematological parameters and/or to mask erythropoietin (EPO) misuse. A reliable method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for doping control purposes, enabling the identification and quantification of the plasma volume expander dextran in human urine. The dextran polymer was enzymatically hydrolysed by alpha-1,6-glucosidase (dextranase) followed by acetylation of the generated isomaltose subunits, allowing the chromatographic separation of different disaccharides, such as lactose, saccharose and isomaltose, as well as the identification and quantification of the analyte in human urine. The method was used to determine the basal concentration of isomaltose resulting from the enzymatic hydrolysis of polymeric 1,6-linked glucose in 238 routine doping control samples. In addition the concentration of dextran measured as isomaltose was estimated in seven urine specimens obtained from patients treated with dextran. Calibration curves for dextran were linear and reproducible. The inter- and intra-assay coefficients of variation for dextran ranged from 4.9 to 7.3% at three concentration levels between 53 and 1186 microg/mL. Recovery ranged from 97 to 112% (mean 106.9%). The assay limit of detection was 3.8 microg/mL and the lower limit of quantification was 12.5 microg/mL. In 96% of the investigated doping control samples, the concentrations of isomaltose were below the LLOQ of 12.5 microg/mL. Even the highest concentrations were approximately 100-300-fold lower than concentrations found in urine samples of patients after intravenous application of dextran. The presented results demonstrate the capability and reliability of the developed LC-MS/MS method for the identification and quantification of dextran in human urine and can be regarded as a method revealing the misuse of dextran in sports.

Examples of sports that needed the use of Dextran Cycling Skiing Basketball Football Swimming Rugby Volleyball

CONCLUSION Dextran may cause many serious side effects to the users, in order to winning a game a player should not put himself under the risks of Dextran and harm his life. Besides that being disqualified due to the presence of this plasma expanders in the body of athletes is even shameful than losing after the competition. In conclusion, athletes should go for other supplements which are recognized by the WADA( World Anti- Doping Agency) and as well as by the IOC( International Olympic Committee). Healthy lifestyle should be maintained and gained in order to win any competition.

REFERENCES: BOOKS: 1. Iron and health, TSO information and publishing solutions, Norwich. 2. WHO DRUG INFORMATION, 3rd edition, Vol 1,1989.

INTERNET: 1. 2. 3. 4. 5. 6.
http://www.aerzteblatt.de/pdf/DI/103/49/a3340e.pdf http://www.drugs.com/drug-class/plasma-expanders.html http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2439527/ http://apps.who.int/medicinedocs/documents/h5774e/h5774e.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962812/#!po=55.0000 http://www.wada-ama.org/