Doctrine about a blood. Tests at a transfusion of blood.

 

Transfusion of blood, preparations of blood and plasma substitutions.

 

Complications at a blood transfusion.

 

The treatment of blood disorders and the management of bleeding during surgery have traditionally relied upon therapies involving the transfusion of donor blood and blood products.

Blood is fluid substance of organism, which executes the most important functions. On this you are acquaint in the course of physiology. However with this tissues in the clinic you will be meet several on especial, because with old - and on today it presents a riddle, but attempts its use for the treatment stay tempting, because in number of events are magic efficient.

Considered that blood is a source of life, exactly a soul inheres in it and so under bleeding leaves a soul. Many researchers linked an action of blood with the nature of person, power, and its physical abilities. That is why in ancient Egypt recommended use blood baths, but in Rome - to drink a blood of died gladiators.

The idea of replacement of lost blood appeared in XIV-XV century. But, as Harvey described the anatomy-physiological bases of circulation only in 1728, therefore transfusion of blood could not be carried out before this time.

In 1666, Richard Lower published the results of experiments on transfusion of blood to animals. These results were so convincing that Deni and Emerez in 16th repeated Lower's experiments on dogs and poured blood from lamb to a seriously ill patient. Despite the imperfect technique, the patient recovered.

In 1697 Merklin and in 1682 Attenmuller reported the results of the observation, according to which at mixing blood of two individuals agglutination sometimes occured. That specifies incompatibility of blood. Despite of obscurity of this phenomenon, in 1820, Blandel (England) successfully carried out transfusion of blood from man to man.

A large obstacle to blood transfusion was its fast coagulation. Therefore, in 1835 Bishoff offered to pour difibrinated blood. However, after transfusion of such blood there were a lot of complications, therefore the method was not widely used.

However, agglutination and coagulation of blood prevented the application of blood transfusion. After opening blood groups by K.Landsteiner and Y.Yansky (1901-1907) these obstacles were eliminated. Hustin in Brussels carried out the first successful use of sodium citrate as an anticoagulant for stored blood in 1914 at St. Jean Hospital. Thus, the elements were in place for the development of blood bank, anticoagulation, cold storage, and the addition of sugar to prolong the life of the red cell.

Blood transfusion has become a common operation, but to prevent grave complications and produce good results it requires strict observance of certain rules. These include sterility in preparing the apparatus, precision in determining the blood groups, proper preservation of the sera and observance of other rules which at times seem trifling.

From a moment of blood transfusions and before our days hemotrunsfusiology passed complex, time tragic, way. This is stipulated by an absence of knowledge on that length of time-knowledge in anatomy, physiology, knowledges about the role of blood in the organism of person.

Before Garveys period physicians transfused blood in emergency situations, in spite of forbid and punishments. In 1820 in England Blandel, and in 1832 in Russia Volf and in 1848 Filomalfiyskiy successfully had transfused a blood from the person to the person, trying explaining a mechanism of its action. Beginning of current age was signified by the opening of blood types in 1901 by Landshteiner (three groups) and 1907 Yanskiy (fourth group). Studied mechanisms of action transfuse blood (Filomalfiyskiy), condition of its keeping (1914 Yurevich and Rozengard - had offered a citrate of Na), sources of getting blood (1919 Shamov- a putrid blood).

Created system of organizations of blood's service (in 1926 by the efforts of Bogdanov in Moscow for the first time in the world was opened an institute of blood transfusion).

And today lasts a work on studying specificity of blood, on use it or separate components.

Clinical practice under settle a problem on hemotransfusion comes from number of bloods particularities, which had been opened us today the immunologists we always must remember that this is liquid fabrics and transfusion of it is nothing else than transplantation tissues, in which is discovered more than 300 different antigens, forming number of systems. But clinic takes into account not all, but only system defining blood type and rh-factor.

Blood type - is genetic stipulate sign and showing by the combination of antigens, which basing in forming elements and plasma of blood. As far back as 1901 years Lanshteyn - a Viennese physician had opened such phenomena as agglutination, having separated people on 3 groups, he had installed that under the first blood type a serum agglutinating with erythrocytes of II and III groups. In II blood type a serum is agglutinating erythrocytes of III groups, but III group agglutinating erythrocytes of II group. Later Yanskiy had opened IVth group. Such a phenomena was explained by existence of system AB0, in other words a kit of agglutinogens and agglutinins within one individual.

On statistical Europe data 42-44% people have a second blood type; 38-39% first; 12-14% - third; 4-6% - fourth.

Each blood type define a combination an agglutinins and agglutinogens. So, in the first group there are agglutinins a and b and agglutinogen 0; in second accordingly - A and b; in third- B and a; and in fourth AB0.

Indication of blood type is accepted on presence of agglutinogen: 0(I); A(II); B(III); AB(IV).

Agglutinogens A and B - are termolabile organic substance. They base on erythrocytes and cause a formation an antibody. These antigens appear beside 3-h month intrauterine growth already and are not changed the whole life. Earlier considered that in the first group of antigen no, therefore have mark its 0; however is today proved, as in the first group is an antigen, but it does not give reactions of agglutination, so its indication have leave 0 and do not settle accounts with the blood transfusion. Agglutinins a and b are termolabile globulins. They base in the plasma, also in liquid tissue. Accumulation them in the plasma go gradually, reaching that level (titre) when they are able to cause a reaction of agglutination. Beside newborn their titre is low, but it gradually growing, reaching maximum to 10-12 years. Titre a of agglutinins is usually composed in adult from 1:32 to 1:128; b - 1:16, 1:64. Than is above titre, that is big possibility for reaction of agglutination under meeting of the same agglutinogens of erythrocytes.

Otenbergs rules were held under hemotransfusion. These rules stated that during blood transfusion agglutinating introduced erythrocytes (agglutinogens) because the incorporated plasma (agglutinins) are diluting in general volume of liquid and their titre becomes to be insufficient for agglutination of patient's erythrocytes. Truth, clinicists forewarned that in events an edge of anemia, attempt of quick indemnity of bleeding by the donors blood of first group was observe agglutination of patients erythrocytes because was saved high concentration introduced agglutinins -named else "inverse agglutination". So, it is recommended dont transfuse the greater amounts compatible blood, add in the system a liquid. Manifestations of agglutination steel observe in the clinic and at the transfusion a same group, particularly second blood type.

Studies of immunologists and hemotransfusiologists of last years allow consider reasons of these manifestations.

Render that there are several subgroups of agglutinogens. So A1, A2, A3, A4; AO, Ah, Az and others are discovered. The most strong antigen - Al, it is meet approximately beside 88% people with the second blood type. It causes a quick reaction of agglutination. Several more weak actions A2, it is meet approximatelly in 12% people with the second blood type. The rest subgroups of antigen A are weak and practically in the clinic are not taking into account.

Agglutinogen B also has several subgroups (Bl, B2, B3), but their titre and antigen action are small, so in the clinic there do not take into consideration.

Antigens Al and A2 are capable to work out against it antibodies, they have name extraagglutinins a1 and a2. Their combination and reactions at the blood transfusion can be unpredictable within one (second) blood types. So, if beside the patient has the blood type A1(II)ba2, but beside the donor A2(II)b can approach hemolisis of erythrocytes.

When in the process of life antigen A, B to fall into the organism (beside the pregnant women, if embrio its has, during autohemotherapy, during the transfusion of other group blood) are forming immune agglutinins a and b they enlarge titre of natural agglutinins by the time before 1:512 and then no possibility its weaken a dilution in liquids of organism, that can bring about agglutination.

That is why, rules of Ottenberge losed in the practice their power (value) and we transfused only the some group blood. Beside the children this already become a law.

At the blood transfusion is take into account not only system AB0, but and system a Rhesus of factor.

What is it?

At 1940 years Landshtein and Vinner, entering erythrocytes of manlike monkeys to the rabbit had found that beside it is worked out antibodies, capable to agglutinate erythrocytes. Render that in blood of human in erythrocytes, but at last years and in fluid its part, inheres a factor, capable to cause antibodies, and named rh factor. Before the end a structure of this antigen is not reveal, consider that this polimucoproteid compound. The blood of 85% of the people contains an antigenic Rhesus factor (a rh-positive). About 15% of the people are rh-negative.

Consequently, transfusing blood, always we had a danger a rh-conflict, or under the recurrent transfusion a rh-negative patient the rh-positive blood, or during the transfusion a rh-negative blood, containing antibodies, rh-positive sick. Such simple system in modern medicine not exact because its render that there are beside the person 6 system antigens Rh-Hz (D, C, E, d, c, e). The first three antigens are a variety an rh of factor D (Rho), C (rh'), E (rh"), the most antigenety is D, very weak - E. So it is taking into account (Rho) the presence of antigen D. In 2-3% rh-negative donors contain antigens C(rh'), E(rh"), but recipients must be considered a rh-negative only, when it does not be kept an antigen D. Thereby, in blood of person can be one type of the rh-factor or combination several types, moreover to each of they are worked out specific antibodies.

In erythrocytes exist system antigens H2 - H20; h2', h2", but their antigens characteristics weak. Together with that, at presence them in blood of rh-negative sick donor at the transfusion to rh-positive recipients this can cause postransfusional reaction. That is why in the clinic follows remember on these particularities of immune systems and at the transfusion necessary to define a rh attribute and to carry out a test on the rh-compatibility, but in general better transfuse the one type and one name on the rh factor a blood.

Determination of blood type:

Exists several ways of determination of blood type (see appendix 9):

1.       with the help of standard serums (known agglutinin);

2.       with the help of the standard erythrocytes (known agglutinogen);

3.       and modern method, which falls into the life, this use monoclonal antibodies anti-A and anti-B.

At the determination of blood types with the help of standard serums value their fitness serum must be transparent, not to contain additional including, correspond to the shelf time. Determination realized in conditions of temperature of surround ambience 17-20C, on Petrys cup or special plates.

 

 

 

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Shaeme of blood compatibility

 

As rule, serums of first, second and third groups are taken. Serum of fourth group is used seldom. Always use serums of two titres, so to the cup inflict on two dripped standard whey, each of three groups. The testing blood is adding there, moreover its taken in 5-10 once less; serums mix and take an answer account into reactions of agglutination. If testing blood of first group, agglutination absent. If second - there is agglutination in the whey of first and third group. If third there is agglutination present with first and second serums. And if agglutination is in all three wheys this is fourth group.

At the determination of blood types by this method, either as the others with the help of the standard erythrocytes is possible get an unauthentic result.

Using the standard erythrocytes are conducting, as a rule, on stations of blood transfusion, because theyre keeping and moving is labored. Follows to remember that we know agglutinogens, so to the drop of standard erythrocytes we must add testing serum, which is gets by defending, or centrifuging patients blood.

Accounts of results are made after 5 minutes of mixes of whey and standard erythrocytes. If there is agglutination with erythrocytes of second and third groups - this is first group. If erythrocytes agglutinate only third group, so this patient second group; if agglutination is in the second group, this is testing third group. When agglutination is absent in all erythrocytes this is the fourth group.

At the account of reactions possible to find agglutination where it practically is absent and reason to this phenomena (pseudoagglutination) are to be:

1.       low temperature indoors, this below 15 C;

1.       account to reactions later 5 minutes;

2.       eating of erythrocytes (momental columns), their easy find of staggering of plate;

3.       concentrate (is sub narrow) standard whey;

4.       at presence infesting blood the immune antibody, if patient suffers a sepsis, system disease of blood.

Sometimes agglutination is impossible to notice, this can be at number of conditions:

1.       Determination of blood types is lead at temperature over 25-30C;

2.       If it is take reaction less than 5 minutes into account;

3.       If low titre of agglutinins (below 1:32), in other words, you define blood type by one series of serum;

4.       Unless it is keep correlation a whey-blood and last much.

The most reliable method of determination of blood types is a using Coliclons anti-A and anti-B. They are a product of gibridome cellar lines, getting in a result of mergings of mousy antibodyprodacting B-lymphocits with ceils of mousy myelome. Coliclons are not the products of human's cells, this is ascetical divorced liquid of mousses - carriers corresponding gibridome, in which are kept in specific immunoglobulins class M, which are directed against antigens A or B of the person. Coliclons anti-A and anti-B are releasing like liquids in vials or ampules on 20, 50, 100 and 200 doses. Liquid keep a preservative 0,1% acid sodium, is tinted in the blue color anti-B and rose anti-A. Vials are keeping near two years in the refrigerator at the temperature +2 - +8C.

Determination of blood type is conducting in native form, blood with the preservative and without it, best result cans be with high concentration erythrocytes.

On the tablet or plate, in conditions of temperature indoors +15 - +25C, inflict on one drop (0,1 ml) coliclons anti-A and B, then inflict testing blood (drop its must be in 10 once less), mix 3 minutes, observe a reaction.

If there is no agglutination in both coliclons - a first group; if agglutination with colicions anti-A second; if with anti-B - third and, if agglutination in both coliclons - a fourth group.

Determination of rh- factor

Several methods are exists to install the presence rh-factor in blood of human. In emergency situations can be used an express-method. The investigated blood are adding to the standard anti-rh serum (containing antibodies) on cups Petry, and take a reaction account into 3-5 minutes. Presence of agglutination means presence of rh-factor. This method is possible in specifically emergency situations, but is hereinafter require determination by laboratory methods. There are two methods: on Petrys cups and in test tubes.

On Petrys cups is inflicting two times (different titre) three dripped wheys a anti-rh, then add 50% suspension of testing erythrocytes, but in two other times add a standard rh- positive and negative 50% suspension of testing erythrocytes for checking the conditions of experience. During 10 minutes cup is placed on the water bath at the temperature 42-46C. On reactions of agglutination mean the presence of rh-factor.

Other laboratory method allows more clearly see agglutination because it can be not clear. Its take into account in weight or gelatines, or polyglucin. In two times on 3 test tubes infuse standard whey of anti-rh (0,1 ml), there add testing and standard erythrocytes and dissolve gelatines. Test tubes are put in the thermostats for one hour at the temperature 37C. After that stir up a test tube stir up for definition of agglutination. At keeping conditions take into account presence or absence of agglutination in a test tube. If we observe agglutination, the blood consist rh-factor.

The Sources of getting blood:

Main source of blood is sound people - donors. Rarefied to take a blood beside persons, reached adult, which didnt suffer from tuberculosis, syphilis, malaria, arent base in a period of recovery after carrying infectious diseases, virus hepatitis.

To take a blood beside the people with exhausting, breaking an exchange of materials, oncological patient, also suffering suppurating diseases is inadmissible. The single dose taken blood must not exceed 450 ml. Break between delivery of blood must be 2 months.

Attitude to donors in different countries are different. So in Italics donors are interpreted as a deal "Christian mercy, love and brotherhoods", but donor, gave blood, gets in the manner of setting free sin compensations. In Holland a person, gave 10 once its blood, gets a medal of Landshteyner. In our country the donorship can be payed, when donor gets a material compensation, as well as free, when people will once a year deliver a blood.

Blood, which were taken from the donor, must be preserved at particular conditions. History of preservations of blood begins from 1865, when physician V.Sutugin had offered to defibrinate blood and keeps at the temperature 0 degrees. At 1867 Rautenberg had offered a blood to mix with solution of sodium carbonate. This prevented it from the rolling up. At 1914 Yurevich and Rozengard had offered to use a citrate of sodium in the correlation 1:10 for warning of coagulation. At present, blood is preserving by the solution of gludicir (sodium of hydroquotings, glucose and distillate water) from the calculation 25 ml on 100 ml of blood. Earlier were used preservatives of different composition COLIPK 7b-12 and the others, which included except the preservative glucose and levomecitin. Blood, prepared by such method, is keeping in sterile vials at the temperature +4 - +6 degrees in the refrigerator. Shelf times before 10-11 days, but optimum term is 7 days.

By accompaniments 50-60 mg of geparins on 1 litre blood is possible to preserve. This blood is used in devices of artificial circulation of the blood; shelf time 24 hours.

Is claims attention the preservation of blood under low (-196C) temperatures. Such frozen blood ready for the transfusion from 2 before 10 years. However complex standard specifications of its keeping did not allow spreading this method broadly.

Exist and other sources of getting blood:

1.       Utilate Blood - a blood, which is received at the phlebotomy on the cause of number of diseases, not render influences upon the composition of blood. This hypertonic cris, uremias.

2.       Autoblood - a fence of blood is realized beside patient or on the eve of operations, or during operations; when blood is pour out in cavities as a result of container breakup. This blood must not contain some admixtures (bile, intestine and gastric contents; urine).

3.       Professor Malinovskiy had offered to use an umbilical cord-placentar blood. It is kept an increased amount of fermentive elements, squirrel, and hormones- folliculine. Amount this blood varies from 100 to 400 ml. Today it use broadly for preparing the components of blood.

4.       The Shamov's work had shown that after 10-12 hours after the death a blood saves their own qualities. So it had offered to store up a blood beside dead bodies, understandable, this are to be people, died as a result of sudden, more often traumatic damages. Blood must be stored up in sterile conditions not later 6-8 hours after the death.

Thereby, all foregoing shows that using blood has do a way from purely clinical before scientifically-motivated methods of stocking up, keeping and use it as a powerful treatment factor. Pack stocking up system, keeping and using it. In large hospitals there are points of blood's fence, but the main are: departments and institutes of blood transfusion. What source of blood fence was not use, follows to remember that blood of donor is necessary subject to studies, to not vaccinated sick number of diseases.

As acts a transfuse blood, after all this in the end total and defines the showing to hemotransfusion.

Mechanism of transfused blood action

The effect of transfused blood depends on amounts, method, velocities of transfusion. Incorporated blood renders replacing and haemostatic action, intensifies an exchange of materials, possesses by immunobyological, desintoxical and nourishing action.

In the surgical practice the most significant is a replacement action, when is necessary fill a lost blood under bleeding because this threatens patients life. Substituting must be conduct rationally, it is impossible tend on 100% change of bleeding. Usually transfuse before 1/3 loss blood, then enter saline dissolve and newly transfuse a blood. Transfuse blood, irritating promote to tonus of vascular system enlarges a volume of circulating blood, respiratory surface of erythrocytes, influences upon organs own circulation of blood.

Haemostatic effect is due to entering the factors of blood coagulation, platelets (thrombocytes). Particularly this is showing at the transfusion fresh blood (direct or after 1-3 day after preservations). Together with donor blood are entering antibodies, globulins, which take place in immune correcting of patients organism. Incorporated blood substitutes squirrels, carbohydrates and fat, rendering hereunder feeding sick. Entered blood replace proteins, carbohydrates, and fats, rendering the nourishment of sick. Except this, proteins of blood absorb the bad materials (poisons, bacterial toxins). Intensify the exchanging oxidation processes, producting of urine, hereunder turns out to be desintoxicating action.

The indications and contraindications to the blood transfusion

Coming from the mechanism of action transfuse blood, are determined absolute and relative contraindications to haemotransfusion. At first, no contraindications to the account do not undertake when we talking about the blood transfusion (bleeding) under the evident threat life of sick.

The showing (indications) to haemotransfusion:

1.       The commonest indication for blood transfusion is profuse haemorrhage, either external or internal;

2.       It is indicated during certain major operations, where a large amount of blood loss is inevitable, e.g. radical mastectomy, abdominoperineal resection, etc.;

3.       In case of deep burns blood transfusion is indicated besides initial fluid plasma administration, as there is considerable haemolysis;

4.       Preoperatively blood transfusion is required when the patient is already anemic and there is no adequate time for Iron Replacement Therapy before operation. This is particularly needed before operations for malignant diseases;

5.       In postoperative cases blood transfusion is required when the patient has become considerably anemic and debilitated, either due to excessive bleeding during operation, or as a result of infection or septicemia;

6.       In anemic patients, particularly when the hemoglobin level is below 100g/l, blood transfusion is often indicated to treat of anemia. It must be remembered that in chronic anemia, it is better to tranfuse packed cells rather than whole blood to reduce more burden to the already burdened heart due to hypervolemia

7.       In severe malnutrition and hypoproteinaemia, blood transfusion is indicated before any type of surgery.

8.       In certain coagulation disorders like hemophilia, thrombocytopenic purpura, leukemia, aplastic anemia whole blood transfusion is required.

9.       In treating cases of erythroblastosis foetalis due to Rh incompatability, exchange transfusion is often performed through umbilical vein of the newborn.

10.  During chemotherapy for malignant diseases, blood transfusion is often indicated if the routine blood examination considerable diminution of RBC level.

Contraindications to hemotransfusion are:

1.       Acute violaton a function livers, kidneys, heart;

2.       Inflammatory diseases of vessels (tromboflebits, phlebitis, embolisms);

3.       Allergic conditions;

4.       Active tuberculoses process, also inflammation disease pulmonary tissues.

As was it already says above, all these contraindications become relative, when the question is edge poor blood. Certainly, risk increases, so possible use separate components of blood, fractional transfusion, follow to adjust a velocity and amount introduced blood.

Methods and technology of blood transfusion

Distinguish direct, indirect, inverse, exchanged and extrocorporal methods of blood transfusion.

Direct transfusion - a direct using donors blood, which is take now and immiditely transfused to recipient, avoiding stage of preservations, and such blood is the most valuable. However it hides in itself danger of infecting sick beside disease, which can suffer a donor, time not being aware of this.

For the direct transfusion use a number of devices "Beca", "Jubalio", as well as syringe method. Blood is distilled from the donor to recipient. All this procedures is conduct in sterile conditions.

Indirect method. Blood withdrew from the donor, mix with the preservative, and is kept under certain conditions and, after 5-10 days, possible use for the transfusion.

Disposable systems for the indirect transfusion are used. Co cost from the kit a tubes and filters.

When blood is entering intraarterialy, we used bladder and manometer in the system, which allows creating a pressure in the system. Pressure in the system must be within I80-200 mm Hg.

The following researches are necessary for carrying out before a hemotransfusion:

        definition of blood group of the donor;

        definition of blood group of the recipient;

        determination of group compatibility of donor and recipient;

        determination of rhesus compatibility of donor and recipient;

        biological test.

Exchange transfusion or reinfusion

This using of blood, pour out in the cavity, on essences of deal this autotransfusion. This blood in the event of the absence of clots, different admixtures, is then and there bringing back into the patients circulatory system. In the process of reinfusion blood is filtered through filters and sterile bandage lying; small quantity of geparine is adding in it. Technically this is realized as an indirect transfusion. Exchanging transfusion is using during acute poisoning (arsenic, mushrooms, carbon monoxide, lead, quicksilver and other poisons). In cases of phlebotomy sometimes take equivalent amount of donors blood.

Thereby we have pack with you approach system to hemotransfusion and previously than its produce, physician must execute a number of actions:

1.       Install the showing to hemotransfusion - with what aim you will enter a blood.

2.       Take account of possible contraindications and with provision for this define the ways of introduction the blood, amount, velocity of introduction.

3.       Define a blood type and rh-factor of recipient and donor.

4.       Put (deliver) a direct test on compatibility, beforehand having value fitness of blood to the transfusion.

5.       Making a test on the rh compatibility.

6.       Check biological compatibility by a way of fractional introduction 15-20 ml of blood with intervals 3 minutes.

Arrange special documentation or special protocol of blood. For checking the possible complications first two hours are take measurements temperatures of sick, as well as urinalysis during the first day.

Coming from different a showing possible to use the following ways of introduction the blood:

1.       Intravenous;

2.       Intraarterious;

3.       Intrabones;

4.       Intramuscular;

5.       Subdermal;

6.       Through mouth;

7.       Through rectum;

8.       Through corpus cavernosus.

Incompatibility by rhesus-factor
father Rh +, mother Rh -, child Rh +

Rh +

Rh

Rh antibodies

 
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BLOOD TRANSFUSSION COMLICATIONS.

TREATMENT AND PREVENTION

THE NATURE OF BLOOD TRANSFUSION REACTIONS

Until 1935, only three types of transfusion reactions were recognized. They were classified as hemolytic, pyrogenic and allergic. As further experience has accumulated, additional untoward manifestations have been recognized as resulting from certain reactions from the transfusions of blood. Many of these relate directly or indirectly to the larger volumes of blood replacement employed in extensive operative surgery in the fields of cancer, heart surgery and trauma; all are related to the prolonged storage of blood. They include post-transfusion hepatitis, circulatory overload, potential citrate intoxication, leukopyrogens, and the growth of bacteria under prolonged periods of refrigeration, as well as the increases in serum potassium as blood ages or hemolyzes; also, acute hemolytic reactions from autohemolysis or from the presence of unusual family groups to which either the donor or the patient is sensitized.

Excess acidity of stored bank blood may lead to cardiac arrest. The extent and the seriousness of such acidity has not been recognized sufficiently in the past.

Hemolytic Reactions

Hemolytic transfusion reactions may or may not be of importance. Stated otherwise: some hemolytic reactions are serious; some are not. Hemolytic reactions are always a source of concern to the clinician, and their origin always must be determined as soon as possible. Only when the cause is known can proper treatment be implemented and the importance of the reaction be assessed.

Common to all hemolytic reactions usually is the early but transient occurrence of hemoglobinemia and hemoglobinuria and, a few hours later, an increase in serum bilirubin and usually clinical icterus. Ordinarily, hemoglobinuria can be detected only within the first urine sample after the reaction has occurred, as free circulatory hemoglobin is soon converted to bilirubin. Hemoglobinemia will be detected only if the serum is examined early and for the same reason. Whether or not acute and pronounced anemia occurs depends upon the extent of hemolysis; in extensive hemolytic reactions, severe anemia may develop. The effect of the hemolytic reaction upon renal function, particularly urine secretion, depends upon its cause and kind. In general, hemolytic reactions are one of two varieties: rapid hemolysis of aged (14 to 28 days) donor blood, or the hemolysis of mismatched blood. The latter is a serious threat to the life of the patient and his renal function.

Causes of Less Serious Types of Hemolytic Reactions.

Aged blood, 14 to 21 days or older: The "life" span of the normal erythrocyte, freshly drawn and transfused without delay to the normal recipient of the same blood groups, is approximately 120 days. However, the length of life span rapidly falls off as blood ages in vitro under blood-banking conditions. The residual life span of erythrocytes of a 2-week unit of blood may be less than 1 week, even when transfused into a recipient of the same blood groupings, including subtypes. If several units of aged blood are transfused within a day or two, physiologic hemolysis of the donors' erythrocytes may proceed at a rate sufficiently rapid to produce hemoglobinuria, to elevate materially the serum bilirubin levels and cause extensive clinical icterus, especially in patients with liver disease. Transfusion icterus of this origin is generally unimportant except that the beneficial effects of such transfusions upon the patient's anemia are short-lived and renal failure may occur if the patient is hypotensive. Urine flow generally is not affected appreciably. However, the diagnosis as to the origin of the hemolytic reaction is one made by exclusion. All typing and cross-matching must be rechecked and found satisfactory before the conclusion can be justified that hemolysis is due to outdated erythrocytes.

Impaired hepatic bilirubin excretion. As the liver is the prime organ of bilirubin clearance, impaired hepatic excretion of bilirubin of any origin may result in an increased retention of serum bilirubin. If icterus is already present, it is obvious that the patient cannot clear his plasma of his own erythrocytic breakdown products. Thus, after the transfusion of relatively aged blood, an increase in clinical icterus and of the serum bililrubin level is observed so frequently as to be the rule rather than the exception. The larger the number of transfusions of properly matched bloods the icteric patient receives, the greater the post-transfusion icterus is likely to be. The extent of the increase in icterus is likely to be greater when aged bloods are given to patients with normal liver function and when Group 0 bloods are administered when the recipient is of another blood group.

The high agglutinin titer universal donor. The results of hemolysis, this time the destruction of the patient's cells, can be more serious. The use of group 0 rh-positive blood whose titer is low, as Crosby and Akeroyd found, rarely causes icterus when the recipient is of another blood group, even when administered in large quantities, unless the recipient suffers from a high degree of impairment in his bilirubin clearance or the blood was old.

Cold agglutinins. When the patient's serum has a high titer of cold agglutinins, the administration of chilled blood usually incites hemolysis of donor cells containing this antigen. This is an agglutinative and/or hemolytic reaction, which may be prevented by warming the donor's blood slowly (several hours) to 37 C. before transfusion and by selection of donors free of cold agglutinins and leukocyte-poor blood. Hemolytic reactions from cold agglutinins are not generally as severe as those following the transfusion of the incompatibility of the major AB, A, B and 0 groups or of an Rh-positive blood given to a sensitized Rh-negative patient. On the other hand, the patient with cold agglutinins appears to acquire this antigen-antibody phenomenon in many instances in association with serious disease, if he does not possess it by inheritance. In the critically ill patient, any reaction is likely to be tolerated poorly and can contribute to, if not occasionally cause, his death.

Fresh versus aged blood

The date of expiration of ACD blood refrigerated at 2 to 6 C. is usually considered to be about 21 days after it is drawn. While blood aged for this period is satisfactory for many transfusion purposes, changes that can be harmful do occur, which should encourage the use of shorter time limits for refrigeration storage. The younger blood, the longer the survival of the transfused red cells in the recipient. The older the blood the higher the concentration of free hemoglobin and the higher the concentration of plasma potassium.

Glycolysis in the erythrocytes diminishes, and formation of ATP is said to be impaired as blood ages. The result is that metabolic acidosis occurs in vitro in the blood to be administered to the patient who, if suffering from acute hypovolemic shock, is already in a mild to severe degree of metabolic acidosis for reasons of impaired tissue perfusion or glycolytic metabolism. The degree of acidosis in aged blood may be lessened with the use of citrate-phosphate-dextrose as a substitute for acid-citrate-dextrose (ACD).

ATP appears to increase the survival time of erythrocytes, but when added to blood and used repeatedly, it may cause renal damage.

Hyperkalemia. One of the features of aging blood is the diffusion of potassium into plasma from the erythrocytes. Diffusion of this ion continues at a fairly steady rate from the cells of citrated blood, from the moment they are withdrawn until they are given. As potassium in blood is largely an intracellular erythrocyte action, plasma potassium levels are higher in hemolyzed blood. It is a safe assumption that the greater the degree of hemolysis of refrigerated blood, the greater the concentration of potassium in its plasma. Also, plasma potassium may increase to as much as 10 times the normal level by diffusion alone, with little or no evidence of concurrent hemolysis. Concentration of potassium in citrated blood, stored under refrigeration with little or no evidence of hemolysis, may reach levels as high as 35 to 40 mEq. per liter.

The diffusion of potassium into the plasma of aging blood occurs at a slower rate when glucose is added to the citrate solution into which blood is drawn. There is some evidence that the addition of glucose to the hyperkalemic plasma of aged blood can drive potassium back into the cells, but thus far the addition of glucose to outdated blood has not proved to be a practical technic in blood banking practices.

The possibility that potassium intoxication will result from the transfusion of large volumes of aged blood is difficult to determine. Melrose and Wilson were unable to detect any significant changes in electrocardiographic tracings attributable to potassium intoxication when aged blood with elevated potassium concentration in the plasma was administered. It should be remembered that the increase in serum potassium levels of the patient under abnormal conditions is largely at the expense of his intracellular potassium and often is associated with a depletion of intracellular protein. It may be that hyperkalemia from blood transfusion in the nonclepleted patient is tolerated better in man than is generally believed.

Although many deaths, including those from cardiac arrest, occur in the cases of the use of massive transfusions, the relationship between these deaths and hyperkalemia from blood is not established. Again, the excellent results obtained by Crosby and Akeroyd are to be cited, for in their use of massive transfusions of blood (10 to 30 pints per patient) in the Korean war, the chief source of their Rh positive Group 0 blood was blood drawn in this country, flown to Korea, in which the agitation of the blood in flight should be expected to favor an accelerated hemolysis and hyperkalemia. No suggestion of potassium intoxication was reported among the recipients.

Aged blood administered intra-arterially has the benefit of greater dilution by its passage through the peripheral circulation before reaching the heart and the coronary circulation than when administered by the intravenous route. This suggestion in principle is doubtless correct, but until it can be shown that the elevated serum potassium concentration of this origin in the no depleted recipient is definitely harmful, this consideration is not sufficient to advocate use of the intra-arterial route of transfusion. Arterial transfusions carry certain special hazards, which seemingly are not compensated for by any demonstrated superiority over blood administered at the same rate by vein. Among the reported hazards of intra-arterial blood is arterial damage, with gangrene of the extremity peripheral to the arterial puncture, as well as the need for greater technical skill in the introduction of the intra-arterial needle; the latter introduces the hazard of delay as well as that of arterial injury. Although certain other theoretical considerations have been advocated for the intra-arterial route of administration of blood in the patient in peripheral collapse, such as reducing the hazard from air embolus, should this occur, and the reported greater ease with which the artery may be entered in shock, the author docs not recommend or employ this route for ordinary blood administration.

Acidosis and Cardiac Arrest. The acidosis from the ACD blood transfused, plus that which the patient already suffers because of impaired perfusion, along with the additional hazard of diminished free calcium ion due to the binding of free calcium by the citrate contained in the transfusions, set the stage for cardiac arrest. This threat can be reduced in part by the administration of 1 Gm. of calcium chloride or calcium gluconate after every 2nd or 3rd transfusion when blood is being given rapidly.

An ingenious technic to remove excessive potassium and ammonium from bank blood prior to transfusion. This method may help in solving the problem of such excess in instances of blood subjected to prolonged storage, but to date it has not gained wide usage.

Bacterial Contamination. Another hazard of aged blood is that certain of the gram-negative bacterial contaminants, when present, may reach fairly luxuriant growth by the 21st day of refrigerated storage. Whereas, by the 10th day their growth and endotoxic products are minimal and may be tolerated, the same blood may cause a fatality if allowed to incubate at 2 to 6 C. for 18 to 21 days.

Thus, the arguments that 21-day-old blood is as useful as 5- to 10-day-old blood similarly stored is theoretically sound but can be spurious. From the standpoint of patient care, the number of man-made errors and the chemical changes that occur are enough greater in the use of 21-day-old blood compared with 5- to 10-day-old blood, that, when possible, we should try to administer most transfusions before the 10th day.

Those blood banks preparing plasma from out-dated blood will find it advantageous to declare blood available for plasma production by the 10th day and to separate the plasma from the cellular elements as soon thereafter as possible.

Deficiencies in the factors of blood coagulation in aged blood are seldom a contraindication for blood transfusion, except for hemophilia and Christmas disease in which the administration of whole freshly drawn blood, rapidly frozen plasma from freshly drawn blood, or antihemophilic globulin and Factor IX are often of value. Deficiency or absence of fibrinogen, whether from fibrinolysis or extensive intra vascular coagulation (usually both) can best be treated by the administration of purified fibrinogen in 6- to 12-gram quantities or more. To supply the same amount from whole bloody about 6 to 10 units would be required and would overload the circulation. When platelets arc needed, transfusions of platelet concentrates may be useful temporarily. Whole blood transfusion is of little value for this purpose.

Of the clotting factors that are relatively stable in blood up to the 21st day of storage, fibrinogen (Factor I), prothrombin (Factor II), proconvertin (Factor VII) and plasma thromboplastin component (Factor IX) are known to retain satisfactory activity under the usual conditions of blood storage. Platelets and antihemophilic globulin (Factor VIII) are not. Ac-globulin (Factor V) is moderately unstable in refrigerated blood.

What then has fresh blood to offer that cannot be supplied by 10- to 20-day-old blood? Primarily antihemophilic globulin and Ac-globulin. Platelets are present to a limited extent in fresh blood but not enough can be supplied in whole blood without the risk of circulatory overload. There may be other clotting factors, yet to be discovered, that may give more evidence that fresh blood has merits sufficiently superior to that of older blood to make its use more desirable.

Pyrogenic Reactions

Febrile reactions occur in association with the administration of any intravenous fluids, including blood and plasma. They have been recognized as long as transfusions have been employed. Halsted, in 1883, describing a transfusion given in the treatment of monoxide poisoning, remarked: "the usual post-transfusion recurrence lasted for half an hour."

Server demonstrated that certain nonpathogenic bacteria often multiply in distilled water and cause fever when injected into animals.

Second common sources of pyrogens are the chemical contaminants in intravenous tubing, glassware or unclean needles. Now that most blood banks employ disposable administration sets, pyrogenic reactions have largely disappeared.

Allergic reactions

Urticarial or allergic reactions are characterized by the appearance of hives and occasionally by attacks of angioneurotic edema and asthma. The exact mechanism of this phenomenon is not clearly understood. Occasionally, a patient, sensitive to a particular food or drug, will display urticarial or allergic reactions when the donor has eaten a food recently or is under a drug therapy to which the patient is sensitive. For example, the donor may have eaten tomatoes or shrimp recently, or he may be under sulfonamide therapy to which the patient is sensitive. Then the recipient may develop urticaria, angio-neurotic edema or an acute asthmatic attack.

Reactions of this type usually occur in less than 1 per cent of the patients transfused with either blood or plasma. The administration of calcium gluconate is often beneficial if given promptly. In more severe reactions, especially asthmatic attacks, corticoids, anti-histaminics and/or ephedrine sulfate may be administered. In general, reactions of this type are more troublesome than serious.

Circulatory overload

Circulatory overload from excessive transfusion is seldom seen in surgical patients undergoing an operation. This does not imply that the circulation cannot be overloaded. The volume of blood lost at operation or in trauma is underestimated much more often than it is overestimated; therefore, overload is seldom encountered under these conditions. Circulatory overload is observed more commonly in the case of preoperative transfusions where an attempt is made to correct anemia or hypo-proteinemia with blood and/or plasma being administered either too rapidly or in too large volume at one time. However, it is remarkable that even under these circumstances this complication seldom occurs. Its failure to do so is excellent testimony to the ability of the vascular system to compensate for the increase in blood volume if fluids are not administered too rapidly and if cardiopulmonary reserve is reasonable. Usually, little if any increase in plasma volume can be detected 6 hours after the administration of a liter of plasma, serum albumin or dextran. The water in transfused blood or plasma is lost from the circulation fairly rapidly, either by diffusion into the extravascular spaces or via the kidney as urine. Overload from plasma transfusions is less likely to be encountered than from blood, because the transfused red cells remain within the circulation. The transfusion of blood is tolerated best in patients with anemia, provided that they are without marginal cardiovascular reserve; the increase in total blood volume probably is compensated in part by the rapid disappearance of plasma and water from the circulation.

The symptoms of circulatory overload are primarily those of left-sided heart failure with pulmonary congestion and/or edema. This complication can be rapidly fatal if not recognized promptly and treated appropriately. Its treatment may consist of the intravenous administration of digitalis preparations in patients with marginal cardiovascular function. It may be necessary also to perform phlebotomy promptly. But first one should apply the usual blood pressure tourniquets to 3 of the 4 extremities, elevating the constricting pressure to about halfway between the systolic and diastolic pressures. By rotating one tourniquet to the unconstricted extremity once every 20 minutes, no extremity remains occluded for more than 1 hour at a time.

Central venous pressure monitoring is a great help in avoiding circulatory overload.

Abnormal Bleeding

Abnormal bleeding is occasionally a disastrous complication of blood transfusions. Its pathogenesis is by no means clearly understood, although certain disorders in coagulation can be detected in some patients. The importance of such a defect probably varies from patient to patient. This is principally a complication of transfusions administered during operation and is seen more frequently under hypothermic than under normothermic conditions.

The clinical pattern is frightening indeed. The exposed surfaces suddenly begin to ooze blood from even the minutest of vessels. Death may occur in a few hours in spite of any treatment.

Although abnormal bleeding of this type usually is encountered more frequently in patients receiving massive transfusions in the course of an operative procedure, occasionally it is observed when only 1 or 2 transfusions have been administered. Characteristically, the blood is unusually dark in spite of the administration of oxygen in seemingly adequate quantities or of the type of anesthesia employed. The blood appears less viscid than usual and clotting appears to be delayed. As puddles of blood accumulate in the tissues or on drapes, coagulation usually takes place. Coagulation will not take place at all if the fibrinogen has been destroyed. Once this condition occurs, the continued administration of blood seems to be more harmful than beneficial; the author prefers to change to plasma but for no well-documented reason. Continued effort at hemostasis appears to be essentially hopeless, for the bleeding points are so numerous as to preclude satisfactory results by the ligature technic.

Blood samples examined under these conditions usually disclose more than one type of clotting disorder. The platelet count is usually at near thrombocytopenic levels (10,000 to 50,000 per cu. mm.). Prothrombin activity also may be depressed sharply, and in some patients the circulating heparin like anticoagulant may be found.

Another of the more important disorders is an increased tendency of the fibrin clots to undergo lysis. The enzyme responsible for lysis appears to be similar to, if not identical with, that normally present in the activated fibrinolytic (plasmin) system. Fibrinolysin normally exists as a relatively inactive substance; its precursor is abundantly present in plasma and is known as profibrinolysin. Although it is normally activated at all times, its rate of activation in the course of thrombin generation or fibrin formation is accelerated. In the highly active fibrinolytic state, fibrinogen and, to some extent, prothrombin is attacked as well as fibrin. Therefore, fibrinogen and prothrombin deficiencies also may exist along with thrombocytopenia.

There is also normally present an inhibitor of fibrinolysin known as antiflbrinolysin (anti-plasmin). An increasing fibrinolytic activity may result then from two mechanisms. There may be an actual increase in the rate at which fibrinolysin is activated, or fibrinolysin may accumulate because it is not destroyed by its inhibitor antiflbrinolysin, or both.

The liver apparently produces the inhibitor. In far-advanced liver disease, the loss of the inhibitor appears to account for some of the fibrinolytic states described. The prostatic secretions contain the fibrinolytic enzyme or a similar enzyme whose properties affect fibrin, fibrinogen and prothrombin in a manner indistinguishable from that of fibrinulysin. Abnormal bleeding from the prostatic bed is often from the fibrinolysin of prostatic origin but is mistaken for poor mechanical hemostasis. General hemorrhagic states characterized by lysis of both fibrinogens. A number of others have reported similar cases. In general, such patients are encountered infrequently.

The hemorrhagic complication of abruptio placenta is one illustration of a highly activated fibrinolytic system. Also, fibrinogen may disappear completely from the circulation. Fibrinogen is exhausted by the formation of multiple small thrombi throughout the circulation, caused by the introduction of thromboplastic juices of placental origin entering the circulation spontaneously under these conditions. It is possible to coagulate experimentally all of the fibrinogen within the circulation over a period of 15 minutes or less without fatal embolism. Minute quantities of fibrin can be demonstrated in the capillary bed of the liver, the lungs and the kidneys. Platelets arc trapped in these thrombi and probably account for the acute thrombopenia. The plasma remaining is essentially circulating serum and has considerable increase in fibrinolytic activity.

Although the mechanism that excites fibrinolytic activity in transfusions at operation is not precisely known it may be due to the entrance of thromboplastic substances into the circulation, either from the operative wound or from an unrecognized transfusion reaction with release of thromboplastic materials.

Fibrinolysis should be suspected if a sample of blood drawn from the patient cither should not clot at all or clot quickly and lysc within 5 to 10 minutes. If 1 ml. of the patient's blood is mixed with 1 ml. of normal blood (proved with another ml. of the same normal blood that it, is capable of clotting) the mixture of the patient's and the control blood should lyse in part or completely in 30 minutes at 37 C.

This type of acute fibrinogen deficiency is generally caused by an increased clotting tendency in the patient. It is best to administer heparin 50 ml. initially and then as a slow drip to prevent the patient's blood from clotting fibrinogen as it is administered. This is another example of treating a clotting syndrome with a hemorrhagic agent. Fatal pulmonary emboli have been occasionally observed when fibrinogen is administered without protection against further intravascular clotting by the use of heparin.

The above considerations would seem to contraindicate the use of EACA (epsilon-amino-caproic acid), though its use is still continued by some.

The all-important feature of this type of abnormal bleeding in the surgical patient receiving blood is its self-limiting nature. Consequently, prompt and heroic measures with reference to the administration of these agents are imperative. If they prove to be effective, the patient will recover, and hemorrhage is unlikely to recur. The surgeon should check with the anesthesiologist to make certain that adequate calcium gluconate has been administered in the course of transfusions to obviate the possibility of citrate intoxication, though hemorrhage from this cause rarely occurs before cardiac arrest.

Citrate Intoxication

On repeated occasions during the past 50 years, warnings have been issued that toxic concentrations of citrate occasionally occur following the use of citrated blood or plasma transfusion. Abnormal bleeding, hypotension and other difficulties relative to the depletion of the calcium ion have been suggested.

Practically, these observations led to routine administration of 1 Gm. of calcium gluconate after the 2nd or the 3rd transfusion during surgery involving rapid blood loss and entailing rapid infusion of citrated blood as replacement therapy (see below). One precaution is necessary; the calcium gluconate must be administered through a separate venous infusion set; if added to the blood transfusion, coagulation of the blood in the transfusion container occurs. No evidence of calcium intoxication has been observed with this regimen.

Although it is doubtful that calcium gluconate so administered prevents the occasional hemorrhage associated with blood transfusion, it may be useful in reducing toxic effects of excessive citrate, and the author has continued its use.

Special Transfusions

Under certain circumstances it may be desirable to administer "washed" red cell concentrates, platelet transfusions, freshly prepared citrate transfusions, in some instance "direct" transfusions wherein no anticoagulant is employed, autotransfusions, exchange transfusions, and blood fur extracorporeal circulation.

Exchange Transfusions

Such transfusions are limited principally to 3 general types of situations: (1) when the patient's hemoglobin has been rendered incapable of carrying oxygen; (2) to eliminate or reduce as far as possible the abnormally sensitized blood cells of the infant suffering from erythroblastosis foetalis; and (3) excessive volume of operative blood loss in the surgical patient, so that the replacement volume assumes exchange proportions in an attempt to sustain life by supporting the blood volume until hemorrhage is under control and the vital signs become stabilized. Exchange transfusions may have some value in patients in hepatic coma, as reported by others, but the author has experienced no success in this procedure.

Erythroblastosis foetalis was first explained on a rational basis by Landsteiner and developed by Levine, his pupil, in a series of papers. They attributed this disease to Rh-positive cells, which enter the mother's circulation from the fetus, she having Rh-negative blood and being vulnerable. It has been presumed with good evidence that the blood antigen is the Rh-positive red cell of the infant in most instances and that, in the course of pregnancy, small quantities of the infant's blood enter the maternal circulation by one means or another. The production of Rh antibodies is thereby stimulated in the Rh-negative mother. These maternal antibodies then pass freely across the placental barrier, inducing hemolysis of the infant's red cells and other serious disorders.

Erythroblastosis foetalis is treated by means of exchange transfusions as soon after birth as the diagnosis is made. The purpose of blood exchange in this disease is to remove the infant's own red cells which are sensitized to the maternal anti-Rh antibodies that have been transmitted across the placental barrier. The use of exchange transfusions in this disease has reduced effectively the incidence of kern icterus, although jaundice alone probably is not responsible for the damaged basal nuclei often associated with this disease. Exchange transfusions where severe hydroptic changes have occurred prenatally have little to offer. The diagnosis of impending erythroblastosis is anticipated by a detection of a rise in anti-Rh titer in the maternal blood. Other antigens are also believed to be responsible occasionally for this disease in some patients.

If treatment is to succeed, exchange transfusions should be started within the first hours of infant life. Into the umbilical vein is threaded a polyethylene catheter, and the exchange is carried out by repeatedly withdrawing 20 ml. of the infant's blood and replacing this with 20 ml. of donor blood until from 300 to 500 ml. have been transferred. The donor considered best suited is an Rh-negative individual of the same blood group who has no Rh antibodies. Intermittently, calcium gluconate is administered to prevent possible citrate intoxication. In some instances, repetition of the exchange may be necessary on several occasions during the first day or two. Usually, the umbilical vein can be re-entered, but should it be thrombosed by that time, a femoral vein may be used.

Monoxide poisoning is the other usual reason for the use of exchange transfusions. In this instance, as in other types of hemoglobin poisoning affecting the oxygen-carrying capacity of red cells, the immediate problem is to provide compatible donor cells in sufficient quantity to meet oxygen transport needs. No problem of isosensitization exists in these patients. In many instances, the prompt administration of 2 or 3 units of blood in monoxide poisoning is all that is necessary. In the course of their administration, bloodletting can be instituted to avoid circulatory overload. Because of the extreme urgency, the use of Group 0 Rh-negative blood without resorting group typing may necessary in many instances. Usually, if the transfer of 40 to 50 per cent of the patient's estimated blood volume in monoxide or similar types of poisoning does not prove to be beneficial, further exchange is likely to be fruitless.

Hyperbaric oxygen therapy at 3 atmospheres, if available, may be very useful. At 3 atmospheres pressure, O2 displaces CO from monoxyhemoglobin.

Direct Transfusions

A "direct" transfusion, as opposed to an "indirect" one, refers to the rapid intravascular transfer of blood from the donor to the recipient without the use of an anticoagulant. This, of course, is the type of transfusion used early and was one of the reasons why blood transfusion was such a formidable procedure prior to the citrate era. Any specific merit that this procedure has over the more deliberate and carefully planned citrated transfusion is sharply limited, if indeed a benefit actually does exist other than in the hemophilic patient.

Many clinicians believe that direct transfusion has certain beneficial properties in the treatment of patients with abnormal bleeding that are not possible with freshly prepared citrated blood or plasma. The available facts do not support this contention, except for the treatment of hemophilia, assuming that the citrated blood is less than a day or two in age. Of greater importance is the fact that the in-vivo turnover times are so rapid that their beneficial effect is evanescent in many of the clotting disorders.

Autotransfusions

Many obstetricians have advised their patients to contribute blood to the hospital blood bank a few days before delivery in order that they may receive their own particular blood as a transfusion should it be needed at the time of delivery. This practice obviated the need for concern about special Rh and other blood group problems as the patient often needed no more than the one unit of blood she donated.

Packed And/Or Washed Red Cells

Under certain circumstances it may be advisable to administer "packed" red cells. The unit of blood is centrifuged; its plasma withdrawn and only the red cell mass is transferred. Several units of transfused packed red cells will permit the rapid correction of anemia with only about half of the volume entailed when whole blood is given. However, the use of packed cells in this connection overlooks the fact that transfused plasma diffuses rapidly from the circulation of the recipient when whole blood is given. Plasma is of considerable nutritive value, whereas red cells are metabolized very slowly. In essence, the patient retains the transfused red cells for days to weeks, whereas plasma in transfusions leaves the circulation in a matter of hours. Thus the patient performs his own plasma-phoresis and thereby packs the transfused red cells himself. One should remember that packed red cell transfusions are nearly twice as effective in blood volume expansion as compared with whole blood. Therefore, if the circulation is it not to be overloaded, only half the volume of packed cells should be transfused when compared with whole blood. The use of red cell concentrates in the patients with cardiac disease suffering from severe anemia does have definite advantages over that of whole blood. Undoubtedly, anemia under these conditions is corrected more safely by the administration of red cell transfusions. Not only are smaller volumes required, but also red cell concentrates carry a minimum of sodium chloride. Some maintain that fewer pyrogenic reactions occur following transfusions of red cells than when whole blood is given; at best, these data show only a minor difference in rates of reactions and are not observed consistently or generally in most patients.

Most advocates of transfusion of red cell suspensions believe it to be the treatment of choice for anemia when the blood volume is normal. However, unless the anemia cannot treated otherwise by appropriate medication, or its rapid correction is essential before surgery can be undertaken safely, the use of transfusions under these conditions carries in addition to the risk of errors incurred in typing and cross matching the unpreventable hazard of transmission of serum hepatitis. Hence, in the decision to employ blood transfusions for the correction of anemia alone, whether as packed red cells or whole blood, the risk of transfusion hazards must be weighed carefully against the benefits expected, the needs of the patient, and the possibility that these needs can or cannot be met satisfactorily by alternative procedures (iron, liver, vitamin B12 and a sound diet).

If the anemia can be treated only by transfusion or with greater safetyfor many patients this is the case - blood transfusion as packed red cells or whole blood should be used without hesitation. On the other hand, the use of the "cosmetic" transfusion carries too great a risk to warrant its use. This risk does not exist when conservative therapy and a little patience will do equally well or better.

The cosmetic transfusion constitutes one of the major abuses of blood transfusion.

Transfusion for Extracorporeal Circulation and Other Forms of Perfusion

In order to prevent coagulation by the use of citrate as the anticoagulant in extracorporal circulation procedures, the amounts required would result in fatal citrate intoxication. Therefore, heparinized blood must be used for these procedures. Because of heparinase in blood, the long-term storage of heparinized blood is not safe, if indeed it is feasible. Blood is usually drawn into a solution of 1,250 to 2,500 units of heparin per 500 ml. of blood not longer than 1 or 2 days prior to the planned procedure. Twice these values are used for similar volumes of plasma.

Heparin may be neutralized readily by the intravenous administration of protamine sulfate at the end of the procedure. Two variables arc often overlooked that, if taken into account, would afford more effective neutralization of heparin by protamine and less hemorrhage from heparin. First, platelets are excellent antiheparins and, as such, the anti-coagulant effectiveness of the same dose of heparin is increased in linear fashion as the concentration of platelets decreases. A similar effect is also noticed in severe pro-thrombin deficiency.

When circulating heparin is neutralized by the formation of heparin protaminatc, the protamine moiety is metabolized more rapidly than heparin so that there may be a return of enough free heparin to give rise once again to troublesome bleeding. As mild-to-moderate thrombocytopenia may develop in the course of extracorporal circulation, these patients may become more sensitive to heparin; consequently, the small amounts of residual heparin freed as the more rapid metabolism of protamine occurs may, in the presence of postperfusion thrombocytopenia, cause abnormal bleeding.

Some prefer the use of up to 50 per cent volume low molecular weight dextran added to the heparinized blood for purposes of pump-priming. This kind of dextran reduces the rate of red cell sedimentation and thereby may facilitate the perfusion of tissues.

Platelet Transfusions

Platelet transfusions can be prepared which permit the transfusion of platelet concentrates. Many units of fresh blood are needed to accumulate sufficient platelets for transfusion purposes if the resulting platelet concentrates are to elevate the platelet count in thrombocytopenic patients. Unfortunately, the increased thrombocyte level achieved is transient, lasting for only a day or two. Platelet transfusions present interesting opportunities for physiologic studies, and they offer essential therapeutic assistance in the preparation of the thrombocytopenic patient for splenectomy necessitated by hypersplenism. Once the diagnosis of idiopathic thrombocytopenia is made, there may be greater safety to the patient in prompt splenectomy than in delaying until platelet concentrates can be prepared. In some patients platelet concentrates may be better delayed until after splenectomy and transfused if the platelet count does not rise promptly and if bleeding continues.

Platelet transfusions in the bleeding patient who suffers from thrombocytopenic purpura of other origin, i.e., leukemia, aplasia of marrow, etc., are also of therapeutic value.

Fibrinogen Transfusion

In afibrinogenemia, whether congenital or acquired, or from acute fibrinolysis, the transfusion of the fibrinogen (Cohn Fraction I) offers an immediate means for the restoration of the plasma fibrinogen concentration and effectively controls hemorrhage of this origin for short periods of time. Because of the high incidence of serum hepatitis, fibrinogen transfusions should be used only when in the clinical judgment of the surgeon the potential advantages outweigh the risk.

Plasma Transfusion

Its Development, Use and Problems in the Treatment of Hypovolemic Shock. Although serum transfusions in the treatment of hypovolemic shock had been employed prior to the turn of the century, the need for serum or plasma as a substitute for blood transfusion did not receive serious attention prior to World War I. Abel, Rowntree and Turner demonstrated that healthy dogs withstood great losses of blood when they were infused quickly with plasma. Rous and Wilson reported that rabbits could be bled to a hemoglobin concentration of 20 per cent of the initial level when plasma infusions were given as replacement. They pointed out that at slightly lower hemoglobin concentrations, death occurred with regularity. They did not believe that death was due to lack of oxygen-carrying power hut rather to the inability to maintain "blood bulk," which we now call blood volume. Today these conclusions may appear as an oversimplification. Most agree that a blood loss of more than 15 per cent of the calculated total from acute hemorrhage in man requires that a major portion of the replacement therapy be in the form of whole blood transfusion rather than as plasma therapy. Nonetheless, most agree that in the absence of available blood for transfusion, pooled plasma, 10 per cent low molecular weight dextran, and 6 per cent albumin are the safest and most effective blood substitutes currently available.

Icteric Serum Hepatitis This complication, previously mentioned for blood transfusion, formerly was of much more serious consequence for pooled plasma. The presence of this virus in the carrier donor may possibly be detected by testing for the presence of the Australian antigen. Because the blood of one carrier goes to only one recipient when the donor's blood is transfused as such, only one recipient is exposed. The hazard for pooled plasma proved to be of much more serious consequence because the plasma from one donor carrying the virus contaminates the entire plasma pool and exposes all of its recipients to the disease. The virus carrier rate among healthy donors appears to be about 1 donor among every 15 to 40 if skid-row and prison donors comprise 30 to 40 per cent of the donor population used. The attack rate among recipients of blood or plasma containing virus appears to be approximately of the order of 25 per cent. It is obvious that many of the recipients of an infected pool of plasma will contract serum hepatitis; the larger the number of recipients, the greater will be the number of cases. Actual attack rates among the recipients of a single pool of virus-infected plasma were 10 to 70 per cent, whereas that for blood alone ranges between 0.5 to 1.0 per cent. There are specific attack rates for specific lots or pools of plasma.

After the war, it became increasingly evident that hepatitis of this origin often carries a morbidity of weeks to months and in a few instances of years' duration and is accompanied by a mortality rate ranging between 5 and 50 per cent, increasing sharply in the older patient. There was nothing else to do but abandon the use of plasma except as an emergency fluid to be used where no other fluid was available, until some method to eradicate this hazard could be developed.

The serum hepatitis problem is made even more difficult because of the prolonged incubation period. Usually, 2 to 4 and even 6 months elapse from the time of exposure to the time of onset of symptoms. Moreover, about 10 to 20 times more patients develop an icteric hepatitis than develop icteric hepatitis. Usually, the shorter the period of incubation, the more severe the attack, but exceptions to this generalization are numerous.

Serum hepatitis was first described by Lurmann in 1883. A vaccine for smallpox was prepared by pooling human lymph obtained from vesicles; this was pooled and stored in glycerine; 191 of 1,293 persons vaccinated developed the disease. Several other outbreaks of icteric hepatitis of this origin were reported prior to World War II, particularly during the 1930's when pooled immune serum was employed in the treatment of various infectious and contagious diseases. In the early stages of World War II, yellow fever vaccine was prepared, using pooled plasma or serum as a stabilizing agent. Over 32,000 of those vaccinated were reported to have developed serum hepatitis believed due to the yellow fever vaccine prepared by this method. This complication immediately disappeared as soon as plasma was removed from the vaccine.

The emergency conditions of World War II undeniably made necessary the continued use of pooled plasma. The numbers of cases of hepatitis arising from the virus in pooled plasma in World War II never will be known, for one of the common diseases of wartime conditions is infectious hepatitis. No means of distinguishing between these two diseases exists, although usually in infectious hepatitis, the incubation period is about 3 weeks. Whether they represent two separate diseases or the same disease acquired by different portals of entry is still debated, especially as the Au antigen can now be tested for.

In lyophilizing, freezing, or refrigerating of pooled plasma, the preservation of the hepatitis virus, should it be present, is clearly augmented. Conversely, storing plasma in the liquid state at room temperature inevitably leads to its deterioration. The rate at which virus activity deteriorates upon standing in liquid cell-free medium increases exponentially as the ambient temperature is elevated. To general, for each 10 C increase in temperature, the time required to achieve the same extent of virus inactivation is reduced by 50 per cent or more. Contrariwise, for each 10 the temperature is reduced, the storage time required to achieve comparable virus inactivation by the storage technic should be doubled (Arrhenius and Van't Hoff). These are very conservative estimates. Data are now available from several sources relating to time and temperature storage of liquid pooled plasma and its safety. These can be applied in general to this important problem, thereby materially assisting in the achievement of safety.

All evidence currently available, with the exception of Redeker's work (1968), suggests that 6-month storage at a mean temperature of 31.6C produces a pooled plasma essentially free from the risk of transmitting icteric serum hepatitis. No cases of clinical hepatitis have been known to occur at these temperatures when properly controlled.

As the stability of plasma prepared from citrated blood is remarkably good, plasma can be stored under these conditions for several years without concern of deterioration. However, plasma collected in A.C.D. (glucose) solution is much less stable but still serviceable if administered between 6 and 24 months of age. In both instances however, the proteins concerned with blood coagulation lose their activity sufficiently rapidly so that plasma is not suited for the correction of coagulation defects.

immunity and serum hepatitis. In 1964, Alien reported that it was possible to immunize against serum hepatitis in man, using the principle of active-passive immunization. Krugman, in 1967 reported similar findings. In neither case, however, was it possible to determine the duration of the immunity obtained. Both studies must be considered experimental and not as indicating that extensive clinical trials should yet be undertaken unless further small clinical trials yield similar results.

Intravenous Plasma for the Correction of Hypoprotcinemia and Protein Depletion. Surgical patients whose pathology prevents or seriously interferes with the oral intake or absorption of food often-present important systemic disorders in nutrition which increase the surgical risk over and above that presented by the local pathology. These nutritive disorders are likely to involve depletion of body fat, carbohydrate and protein reserves as well as those of minerals, vitamins and body water. Mineral, water and vitamin deficiencies are easy to correct by the parenteral administration of each according to estimated needs. However, if the patient cannot eat or assimilate enough food to meet the total caloric and protein requirements, operative mortality as well as morbidity is likely to be increased.

If the benefits of plasma transfusion were limited only to those of improving the oncotic relationships of the circulation in depleted patients, its administration on this basis alone could be justified. Fortunately, plasma serves as an excellent source of protein nutrition as well as a substitute for blood. A state of strongly positive nitrogen balance exists under plasma therapy and the patient's general condition likewise usually improves. Admittedly, plasma and glucose alone do not supply the desired daily caloric intake, but in many cases the correction of hypoproteinemia by plasma transfusion and the restoration of the normal hemoglobin values with blood assist materially in the preparation and in the tolerance of the patient for operation. This regimen is not the final answer to the correction of malnutrition, but it does serve as well if not better than any other parenteral feeding currently available. Plasma is used more rapidly than originally believed possible.

It has been demonstrated that littermate pups grow at least as well with intravenous plasma as their only source of protein over a 3-month period as do their sisters and brothers fed the same amount of protein by mouth (horse meat and liver).

The concentration of the calcium and potassium ions in plasma is governed partly by their being bound to some extent to plasma proteins. In the protein-depleted patient occasionally the serum levels of these ions may be reduced simply because the extent of hypoproteinemia is so severe as to reduce the quantity of these ions that can be bound. In a few such patients, the administration of calcium or potassium salts will not correct existing deficiencies, presumably because there is insufficient plasma protein to hold these ions within the circulation. If the protein deficits can be corrected by any means, calcium and potassium arc retained more easily. The reverse also appears to be true: namely, that protein repletion is difficult if not impossible to accomplish without the presence of potassium, calcium, magnesium, and possibly other trace elements. Proteins fed orally or given by vein as plasma contain both calcium and potassium. Usually, the correction of hypoproteinemia automatically corrects any existing potassium or calcium deficiency unless there are other continuing losses of these minerals.

MODERN PREPARATIONS OF BLOOD

PLASMA SUBSTITUTES

Clinical practice is the best indicative from this, as far as from always is need to transfuse an unadulterated blood. They are sometimes used separate its components, blood's elements or fluid part, but sometimes we used separate component their part, which are prepared on special technologies. Much modern preparations of blood are known sufficiently today.

9.       Packed red blood cells canned blood, from which is removed plasma. Its reasonable use at anemia.

10.  Washed erythrocytes same erithromass, in which plasma is absent.

11.  Erithroweigh the blood, which is pour plasmas, which change physiological solution, with the accompaniment of levometicine, rivanole and glucoses.

12.  Leucocitar-trombocitar mass or dredge is got after centrifuging of blood and branches of leucocytes and erythrocytes.

Follows to remember that all preparations, which contain in it erythrocytes, are carry in the human organism, since concentrate blood - with transfusion rule observance and technology (technicians). These preparations are also keep either as a canned blood. The leuco - trombo-masses (packed white cells, platelet concentrate) is entering without observance group accessories and is using during 24-72 hours from a moment of their preparing. They enter intramuscular.

13.  Native plasma fluid part of blood without form elements. It is getting after centrifuging of canned blood. Keep also, either as a blood, not more than 72 hours. Enter with observance group accessories. The ways of introduction such either as for preserves.

At present designed methods to preservations a plasma are or with frosting, or drying.

Dry plasma is keep 3-5 years. Dry plasma is divorcing with physiological solution or distillate water before using. It is entering in the organism of person by same fetters, as the blood. Last years are broadly used special types of plasmas, antigangrenous, antistaffilococcus, antitetanus, specific, which are got after immunizations of donors by weaken toxins corresponding to agent of disease.

14.  Fibrinogenum. Stands out from native plasma, is kept in vials on 1 gram. It hasnt group specificity. Before using is divorce by water or physiological solution and is enter intravenous.

15.  Whey is plasma, pour fibrinogenum, is keep and enter as native plasma. Sometimes it transfused with calcium, vitamins, alcohol.

16.  Fibrinolisin is ferment, chosen from the plasma, is kept in vials in the manner of dry powder. Possesses a possibility to dissolve clots.

Chosen apart convolve system patches as an independent preparation trombin, fibrinous membrane, hypo steady-state sponge, which are broadly using for the stop of bleeding by the method an application.

17.  Albumin and protein. Stand out from the plasma 20 or 25% dissolve, specificity have not, is entered intravenously.

18.  Specific immunoglobulins (antistafrilococcus, antitetanus, countercoroar, antiinfluence), stands out from the plasma of persons, which illed by corresponding diseases or immunized weaken by the toxin. Group accessories has not, are entered intramuscularly.

19.  Blood substistutions (plasma substitutes). Separate functions of blood are change by different preparations, biological or chemical derived.

 

Complications at blood transfusion and their preventive maintenance.

Being powerful facilitator of activity of all life organism systems, blood and its preparations arent pour number of negative moments and cause a number of serious complications. As a rule, they cause where the rules of blood transfusions, on which we already spoke are by force of circumstances break. Time an underestimation of condition of sick, breach of conditions of keeping blood and technology of transfusion - possible inflict a harm sick. So, underestimation of condition of patient, breach of conditions of keeping blood and technology of transfusion - can inflict a harm sick. So, underestimation of carrying diseases of donor, ignoring number of clinic-biochemical studies of blood of donor can bring about infection sick hepatitis, malaria, syphilis, sepsis, aids disease and variety of infectious diseases. Wrong keeping blood, absence of sterility, breach of correlation of preservative and shelters can bring about the sepsis, to tromboembolia. Breach of technology of transfusion can cause inflammation of vascular system, air or fatty embolism. Underestimation of accompanying diseases beside sick can bring turn for the worse (nephritis, hepatitis) or cause a warmhearted activity decompensation. Under long keeping blood, when breaking a temperature of keeping blood can approach hemolysis of erythrocytes, changing a protein composition, that is show in the manner of pyrogenes reactions, which can be light, average and heavy degrees depending on the increased temperature of tell from 38 before 40C. As a rule, these complications are become apparent through 10-15 minutes after the beginning of transfusion chill, pains in the loin and region of heart, sickness. Treatment is concluded in that, to stop a transfusion, enter desinsibilising preparations: calcium chloride, dymedrol, pinolphen, warm sick, enters fever-killer piramidon, analgin. In events of increased sensitivity of organism to the squirrel and ignoring a biological test are to be show allergic reactions, itching, rash, edemas, increasing of temperature, dispnoe, but sometimes and anafilacting shock, retching, frustration of breath, fall of arterial pressure, bronchospasm, edema of light, transfusion stop, patient enter the enumerate preparations, but in the event of anafilaxy an introduction an glucocorticoids, warmhearted preparations, translation of the patient on artificial respiration.

The heaviest complication is hemolytic transfusion shock, which can appear as a result of incompatible on the group or rh-factor blood, also when entering a big amount blood, unfit for transfusion. At the transfusion incompatible on the blood type beside sick appears chill, sickness, pain for the breastbone, falls an arterial pressure, increases a temperature, appear signs of irritating the buds, albuminuria, hematuria, oliguria, but sometimes and anuria, appear a jaundice, develops kidney-liver block, which brings about the fatal upshot. Follows to remember that in pathogenesis these complications are lies hemolises incorporated erythrocytes. Sometimes this complication develops bore, but sometimes even can be abble to show to 2-3 day after hemotransfusion. If sick inhered under anaesthesia or took desinsibilising preparations a development of hemotransfusial shock can be long. In the event of the manifestation of this complication hemotransfusion follows to stop, to give the patient a greater amount of liquid, desinsibilising preparations, and peryrheral blocade. Produce hemodialysis; sometimes produce a phlebotomy and transfusion of one-group blood.

Wrong using rh-priventing or no stating a test on rh-compatibility can cause rh-conflict, but beside newborn this complication was identified a haemolytic jaundice. Sometimes this complication causes haemolytic shock. Base of its development is a meeting a rh factor with the rh-antibody, herewith occurs all-out hemolis erythrocytes sick, so and donor.

Clinical picture develops sufficiently quickly and practically corresponds to a picture transfusions of other group blood, but in the complex of treatment never is reached success, unless produce exchanging blood transfusion, i.e. produce a phlebotomy with following infusion a rh-negative blood, not containing antibody.

Substituting passive bleeding can bring about the development of syndrome anhemolytic transfusion reaction. Observe thrombocyteoenia, leukopenia, and kidney-liver insufficiency, breach brain circulation of blood. Appear tachicardy (rapid pulse), low blood pressure, and crisis. For eliminating this syndrome citrate intoxication, on each 500 ml canned blood dissolved 10 ml 10% chloride calcium. Thereby, that blood, executing most important function in the organism of person, can be used for the treatment of number of diseases. Efficiency of transfusions well known, and from purely observant clinical profit hemotransfusion pass a way of studying the characteristics blood of its mechanism of action in the organism of person and must be use in the surgical practice around the world, but follows clearly to observe a rules of fence, keeping and blood transfusion.

Plasma substitutes are medical solutions for substitution of lost blood functions or normalization of disordered blood functions.

Nowadays there are several thousands of preparations, which belong to group of plasma substitutes. They are widely used in the whole world for keeping and correction of the main hemostasis constants during different pathological states. Plasma substitutes have high effectivity, directions of action; their transfusion is provided without taking into account patients blood group. They have long term of storage, can be well-transported and can be used for many sick and injured people in extreme situations.

By their functional properties and direction of action plasma substitutes are divided into the several groups (see appendix 11):

20.  plasma substitutes of hemodynamic action

21.  desintoxicative solutions

22.  plasma substitutes for parenteral nutrition

23.  regulators of water-salt exchange and acid-base balance

24.  oxygen transmitters.

1. Plasma substitutes of hemodynamic action

Plasma substitutes of hemodynamic action (anti-shock plasma substitutes) are mainly used for normalization of indexes of central and peripheral hemodynamics, which disorder in blood loss, mechanic trauma, burn chock, different diseases of inner organs (perforative gastric ulcer and duodenal ulcer, intestinal obstruction, acute cholecystitis, acute pancreatitis, exogenous and endogenous intoxication).

Solutions of this group have high molecular mass and noticeable colloid and osmotic properties, due to which they circulate in the blood for a long time and attract the interstitial fluid into the blood flow, increasing the volume of circulating blood (volemic effect). Besides their main action hemodynamic plasma substitutes have also desintoxicative action, improve microcirculation and rheologic properties of the blood.

Anti-shock plasma substitutes are devided into three groups:

-            preparations originating from dextrane;

-            preparations of gelatine;

-            preparations on the base of oxyethylstarch.

(1) Preparations originating from dextrane

Depending on their molecular mass solutions of this group are:

-            medium-molecular (polyglucin, polyfer, rondex, macrodex, intradex, dextrane, plasmodex, chemodex, oncovertine);

-            low-molecular (rheopoluglucin, rheogluman, rheomacrodex, lomodex, dextrane-40, hemodex).

The main medium-molecular preparation of dextrane is polyglucin, low-molecular is rheopoluglucin.

Polyglucin is 6% solution of medium-molecular dextrane fraction (molecular weight is 60 000 80 000) in isotonic solution of sodium. During intravenous injection it rapidly increases the volume of circulating blood, increases and keeps arterial pressure. Polyglucin increases the volume of circulating blood on the order more than volume of injected preparation; it is due to its high colloid-osmotic pressure. It circulates in the organism from 3 to 7 days; during first day 45-55% of solution is excreted, the main way of excretion is through kidneys. Injection of polyglucin increases oxidative-reductive processes in the organism and utilization of oxygen from flowing blood by tissues. Flow injection of the preparation increases vessel tone.

Polyglucin is indicated in treatment of traumatic, operation and burn shock, acute blood loss and acute circulatory insufficiency in different diseases. Side effects during injection of poliglucin are extremely rare. But in some people (less than 0,001%) there is observed individual increased sensitivity to the preparation, which is reflected by symptoms of anaphylaxia even to anaphylactic shock. For prevention of this reaction, it is needed to provide the biologic test, when using polyglucin.

Rheopolyglucin is 10% solution of low-molecular dextrane (molecular weight is 20 000 40 000) in isotonic solution of sodium chloride or 5% solution of glucose. Like polyglucin, it is hyperonkotic colloid solution and during intravenous injection it considerably increases the volume of circulating fluid.

Every gram of preparation connects 20-25 ml of water in blood. This explains its hemodynamic action. Rheopolyglucin circulates in the organism during 2-3 days, 70% of the preparation is excreted for the first day with the urine.

The main effect of rheopoliglucin is improvement of rheologic properties of the blood and microcirculation. It is due to preparations ability cause desaggregation of erythrocytes, to stop the blood stasis and prevent thromb formation. Occurred high concentration of preparation leads to coming out of fluid from tissues to blood flow, which causes hemodilution and decrease of blood viscosity. Molecules of dextrane cover the surface of cell blood elements and change the electrochemical properties of erythrocytes and thrombocytes. Antithrombotic action of rheopolyglucin is probably due to increase of negative thrombocytes charge and decrease of their ability to adhere and aggregate. Indications for rheopolyglucin usage are disorders of microcirculation in shock of different origin, thromboembolic complications, operations on the opened heart, vessel diseases, surgical invasions on the vessels, prophylaxis of acute kidney insufficiency.

Reactions and complications in rheopolyglucin usage are the same as in poluglucin usage. Before injection biologic test is also needed.

(2) Preparations of gelatin.

They are gelatinole, modegel, hemodel, gelofusin, plasmogel. Originator of this group and the most vide-spread preparation is gelatinol.

Gelatinol is 8% solution of partly decomposed food gelatin in isotonic solution of sodium chloride (molecular weight is 15 000-25 000). Gelatinol is protein, which contains some aminoacids: glycin, proline etc. Treating action is mainly connected with its high colloid-osmotic pressure, which provides fast coming of interstitial fluid into blood flow. As hemodynamic preparations gelatinol and its analogs are less effective than dextranes. They leave the blood flow faster and localize in interstitium. Gelatinol is nontoxic, apyrogenic, does not cause antigenic reactions. Kidneys excrete main part of the preparation. Indications for usage are acute hypovolemia, different kinds of shock, and intoxication. Preparation is contraindicated in acute kidney diseases and lipid embolia.

(3) Preparations on the base of oxyethylstarch.

Last years in USA, Germany, Japan the solutions of oxyethylated starch found their usage. These are plasmosteryl, plasmotonin, rolex, and NAES-steryl.

Structurally these preparations are close to glycogen of animal tissues and are able to decompose in blood by amylolytic enzymes. Solutions on the base of oxyethylstarch have good hemodynamic action, which are not followed side effects.

2. Desintoxicative solutions.

Plasma substitutions of desintoxicative action provide desintoxication of the organism by connecting, neutralization and excretion of toxic substances. They are preparations of polyvinylpyrolidone (hemodes, neohemodes, periston-N, neocompensan, plasmodan, colidone) and solution of low-molecular polyvinyl alcohol polydes. Desintoxicative action of suchsolution is based on high ability of polymer to complex equation with toxin.

Hemodes is 6% solution of low-molecular polyvinylpyrolidon with molecular weight of 12 000 27 000. Most of it is excreted by kidneys in 6-8 hours after intravenous injection. It is active to many toxins, excluding diphteria, and tetanus, and toxins formed during radiation disease. It also stops stasis of erythrocytes in capillaries during acute bleeding, shock, burn disease, and other pathological processes. Depending on the level of intoxication adults are injected with 200 400 ml a day and children get 15 ml for every kg of body weight. Contraindications are bronchial asthma, acute nephritis, hemorrhage into brain. At present time this preparation dont used, because during treatment takes many complications.

Neohemodes is 6% solution of low-molecular polyrinylpyrolidon with molecular weight 6000 10000 with addition of sodium, potassium, calcium ions. Neohemodes has higher detoxicative effect than hemodes.

Indications are the same as hemodes has. Besides, neohemodes has noticeable treating action in thyrotoxicosis, ray disease (radiation disease), different diseases of liver and other pathologies. Preparation is injected intravenously with speed of 20 40 drops per minute, maximum single dose for an adult is 400 ml, for children this is 5 10 ml / kg.

Polydes is 3% solution of polyvinyl alcohol in isotonic of sodium chloride. Molecular weight is 10000 20000. It is fully excreted by kidneys during 24 hours. Polydes is used intravenously drop by drop for treating of intoxication caused by peritonitis, acute pancreatitis, acute cholecystitis, acute purulent infection, burn disease, liver injury etc. Adults are injected with 200 500 ml / day, children 5 10 ml / kg of body weight. In fast injection of preparation there may occur dizziness and nausea.

3. Plasma substitutes for parenteral feeding

They are indicated in cases of full or portional exclusion of natural nutrition of the patient, as a result of some diseases and after operation on the organs of alimentary tract, during purulent septic injuries, traumatic, ray and thermic injuries, severe complications of postoperative period (peritonitis, abscesses and intestinal anastomoses), and also in hypoproteinemia of any origin. Parenteral nutrition is provided with protein preparations, lipid emulsions and carbohydrates. First help the aminoacids go into the organism, and lipid emulsions and carbohydrates provide it with energy for protein digestion.

(1) Protein Preparations

Among protein preparations are hydrolysates of proteins and mixtures of aminoacids.

The sources of protein hydrolysates are casein, proteins of cattles blood, muscle proteins, and also erythrocytes and thrombs of donor blood. When getting protein hydrolysates, enzymes or acid hydrolyses the products. The most widely used are hydrolysate of casein, hydrolysin, aminocrovin, amicin, aminopeptide, fibrinosol, aminozol, aminone, amigen, etc.

Protein hydrolysates are injected drop by drop slowly 10-30 drops / minute, by different ways: intravenously, through the tube into the stomach, or duodenum. The volume of injected hydrolysates may reach 1.5-2 l per day. Contraindications for their usage are acute disorders of hemodynamics (shock, massive blood loss), decompensation of heart activity, hemorrhage into the brain, kidney and liver insufficiency, and thromboembolic complications.

Separate group contains solutions of aminoacids, which are easily digested by the organism, because theres no need to decompose peptides. The advantage of mixtures of crystallic aminoacids is easier technology of preparation, high concentration of aminoacids, possibility to create the preparation with any correlation of aminoacids and adding into the mixture electrolytes, vitamins and energy substances. The main preparations are: polyamine, infusamine, vamine, moramine, freamine etc. Aminoacid mixtures are injected intravenously drop-by-drop, 20 30 drops / minute in full parenteral feeding in dose 800 1200 ml every day. They can be injected through the tube into the stomach or duodenum.

When transfusing any protein preparation, its needed to provide the biological test.

(2) Lipid emulsions.

Inclusion of lipid emulsions into the complex of parenteral nutrition improves the energetics of patients organism has considerable nitrogen-keeping action, corrects the lipid content of plasma and structures of cell membranes. Lipids provide the organism with essential fatty acids (linolic, linolenic and arachidonic), fat-soluble vitamins (A, K, D) and phospholipids. In clinical practice its used lipid emulsions (emulgated lipids do not cause lipid embolia). The most popular are intralipid, lipiphysian, infusolipid, lipofundin, lipomool, infonutrol, fatgen etc.

Preparates of lipid emulsions are injected intravenously with the speed of 10 20 drops/minute or through the tube into the intestine.

Usage is contraindicated in chock, craniocerebral trauma, disorder of liver function, and acute arteriosclerosis. Biological test is needed before using.

(3) Carbohydrates.

Carbohydrates are used in parenteral nutrition for providing with energy needs, and also energetic addition to protein hydrolysates. Injected carbohydrates stimulate the decomposition of protein hydrolysates and formation of own proteins from aminoacids.

The most widely used are solutions of glucose (5%, 10%, 20%, 40%). Contraindication is diabetes mellitus.

From the other carbohydrates fructose and carbohydrate alcohols (xylite, sorbite, mannite) are used. The digestion of those preparations is not connected with insulin and may be possible in patients with diabetes mellitus.

4. Regulators of water salt exchange and acid base balance.

These are crystalloid (polyion) solutions and osmotic diuretics.

(1) Crystalloid solutions.

The most widely used are:

-            Physiologic (isotonic) solution

sodium chloride 0,9% solution

-            Ringers solution

sodium chloride 8,0 gm

potassium chloride 0,075 gm

calcium chloride 0,1 gm

sodium bicarbonate 0,1 gm

distilled water to 1 liter

-            Ringer Locks solution

sodium chloride 9,0 gm

sodium bicarbonate 0,2 gm

calcium chloride 0,2 gm

glucose 1,0 gm

bidistilled water to 1 liter

-            Lactasole

sodium chloride 6,2 gm

potassium chloride 0,3 gm

calcium chloride 0,16 gm

magnesium chloride 0,1 gm

sodium bicarbonate 0,3 gm

sodium lactate 3,36 gm

distilled water to 1 liter

In clinical practice these solutions are used for correction of water-salt balance, they contain the most adequate set of ions to blood content. Ringer Locks solution and lactasole contain also anti-acidotic components like bicarbonate or lactate of sodium. For acidosis correction it is provided intravenous injection of 4 5% solution of sodium bicarbonate.

Polyionic solutions have low molecular mass and fastly go through the capillary wall into the interstitium, renewing the fluid content. They comparatively fastly leave blood flow. Thats why it makes sense to use both crystalloid and osmotic solutions.

Crystalloids and hemodynamic colloid plasma substitutes are included into complex therapy of traumatic and hemorrhage shock, septic diseases, and also they are used for prophylaxis and correction of disorders of water-salt balance and acid-base equilibrium in blood during big operations and in postoperative period. It is not only that interstitial fluid becomes more, and compensation of metabolic acidosis and detoxication take place, but also some hemodynamic effect appears, which is in partial correction of hypovolemia and stabilization of arterial pressure.

(2) Osmodiuretics

These are multiatomic alcohols: sorbite and mannite.

Mannitole is 15% solution of mannite in isotonic solution.

Sorbitole is 20% solution of sorbite in isotonic solution.

The mechanism of diuretic action of these preparations is connected with increased plasma osmotic level and going of interstitial fluid into blood flow, which increases the volume of circulating blood and venal blood flow.

As a result of increased renal filtration the excretion of sodium, chlorum, and water increases; their reabsorbtion in renal canaliculi is decreased. Preparations are injected intravenously drop by drop or by single flow (1 2 gm/kg of body weight per day).

Indications for osmodiuretics usage are early stage of acute renal insufficiency, hemolytic shock, heart insufficiency, brain edema, paresis of intestine (stimulate the peristalsis), liver diseases and diseases of bile-excreting tracts etc. Contraindications to their usage are disorder of filtration in kidneys, heart insufficiency with evident anasarka and other states of extra cellular hyperhydratation, intracranial hematomas.

5. Oxygen Transmotters.

Creation of plasma substitutes, which provide such function as oxygen transmission to the tissues of the organism, so called artificial blood, is difficult, but very important task.

Nowadays there are created oxygen-transmitting preparations (perftoran, perfucole, flusol-Da) and soluble hemoglobin (erygem, conjugated hemoglobin), but they have a little oxygen capacity and have some toxicity. The questions of their decomposition and excretion from the organism are studied not enough.

Till this time the problem of sterilization and cheeping of their making is not solved. Thats why in clinical practice oxygen transmitters are almost not used.

Usage of plasma substitutes solutions in some cases causes allergic, pyrogenic and toxic reactions, but their frequency and severity are considerably less than those in transfusion of blood and its components.