FLUID MANAGEMENT & TRANSFUSION: INTRODUCTION All patients except those undergoing the most minor surgical procedures

require venous access and intravenous fluid therapy. Some patients may require transfusion of blood or blood components. Maintenance of a normal intravascular volume is highly desirable in the perioperative period. The anesthesiologist should be able to assess intravascular volume accurately and to replace any fluid or electrolyte deficits and ongoing losses. Errors in fluid replacement or transfusion may result in considerable morbidity or even death. EVALUATION OF INTRAVASCULAR VOLUME Clinical evaluation and assessment of intravascular volume must generally be relied upon, because measurements of fluid compartment volumes are not readily available. ntravascular volume can be assessed using physical or laboratory examinations or !ith the aid of sophisticated hemodynamic monitoring techniques. "egardless of the method employed, serial evaluations are necessary to confirm initial impressions and guide fluid therapy. Moreover, modalities should complement one another, because all parameters are indirect, nonspecific measures of volume# reliance on any one parameter may be erroneous and, therefore, ha$ardous. PHYSICAL EXAMINATION %hysical examination is most reliable preoperatively. nvaluable clues to hypovolemia &Table '()*+ include s,in turgor, the hydration of mucous membranes, fullness of a peripheral pulse, the resting heart rate and blood pressure and the &orthostatic+ changes from the supine to sitting or standing positions, and urinary flo! rate. -nfortunately, many drugs used during anesthesia, as !ell as the physiological effects of surgical stress, alter these signs and render them unreliable in the immediate postoperative period. ntraoperatively, the fullness of a peripheral pulse &radial or dorsalis pedis+, urinary flo! rate, and indirect signs, such as the response of blood pressure to positive.pressure ventilation and the vasodilating or negative inotropic effects of anesthetics, are most often used.

Table 291 S!"#$ %& Fl'!( L%$$ )H*+%,%le-!a. Fl'!( L%$$ )E/+0e$$e( a$ Pe01e#2a"e %& 3%(* 4e!"52. S!"# Mucous membranes Sensorium 3rthostatic changes n heart rate n blood pressure -rinary flo! rate Mildly /ecreased 5% /ry 1ormal 1one 10% 0ery dry 2ethargic %resent 15% %arched 3btunded Mar,ed 4 *5 bpm
*

4 *6 mm 7g Mar,edly decreased

Fl'!( L%$$ )E/+0e$$e( a$ Pe01e#2a"e %& 3%(* 4e!"52. S!"# 5% decreased %ulse rate 8lood pressure 1ormal or increased 1ormal ncreased 4 *66 bpm Mildly decreased !ith respiratory variation Mar,edly increased 4 *'6 bpm /ecreased 10% 15%

%itting edema9presacral in the bedridden patient or pretibial in the ambulatory patient 9and increased urinary flo! are signs of hypervolemia in patients !ith normal cardiac, hepatic, and renal function. 2ate signs of hypervolemia include tachycardia, pulmonary crac,les, !hee$ing, cyanosis, and pin,, frothy pulmonary secretions. LA3ORATORY EVALUATION Several laboratory measurements may be used as surrogates of intravascular volume and adequacy of tissue perfusion. These measurements include serial hematocrits, arterial blood p7, urinary specific gravity or osmolality, urinary sodium or chloride concentration, serum sodium, and the serum creatinine to blood urea nitrogen &8-1+ ratio. These measurements are only indirect indices of intravascular volume and often cannot be relied upon intraoperatively because they are affected by many other variables and results are often delayed. 2aboratory signs of dehydration include a rising hematocrit, a progressive metabolic acidosis, a urinary specific gravity greater than *.6*6, a urinary sodium less than *6 mEq:2, a urinary osmolality greater than ;56 m3sm:,g, hypernatremia, and a 8-1.to.creatinine ratio greater than *6<*. 3nly radiographic signs of increased pulmonary vascular and interstitial mar,ings &=erly >8> lines+ or diffuse alveolar infiltrates are reliable measures of volume overload. HEMODYNAMIC MEASUREMENTS 7emodynamic monitoring is discussed in Chapter ?. Central venous pressure monitoring is indicated in patients !ith normal cardiac and pulmonary function !hen volume status is difficult to assess by other means or !hen rapid or ma@or alterations are expected. Central venous pressure readings must be interpreted in vie! of the clinical setting. 2o! values &A 5 mm 7g+ may be normal unless associated !ith other signs of hypovolemia. Moreover, the response to a fluid bolus &'56 m2+ is equally as important< a small elevation &*)' mm 7g+ may indicate the need for more fluid, !hereas a large increase &4 5 mm 7g+ suggests the need for a slo!er rate of administration and a reevaluation of volume status. Central venous pressure readings greater than *' mm 7g are considered elevated and imply hypervolemia in the absence of right ventricular dysfunction, increased intrathoracic pressure, or restrictive pericardial disease. %ulmonary artery pressure monitoring is necessary if central venous pressures do not correlate !ith the clinical assessment or if the patient has primary or secondary right ventricular dysfunction# the latter is usually due to pulmonary or left ventricular disease, respectively. %ulmonary artery occlusion pressure &%A3%+ readings of less than B mm 7g indicate hypovolemia in the presence of confirmatory clinical signs# ho!ever, values less than *5 mm 7g may be associated !ith relative hypovolemia in patients

!ith poor ventricular compliance. %A3% measurements greater than *B mm 7g are elevated and generally imply left ventricular volume overload. The presence of mitral valve disease &particularly stenosis+, severe aortic stenosis, or a left atrial myxoma or thrombus alters the normal relationship bet!een %A3% and left ventricular end.diastolic volume &see Chapters ?, *(, '6, and '*+. ncreased thoracic and pulmonary air!ay pressures also introduce errors# consequently, all pressure measurements should al!ays be obtained at end expiration and interpreted in the context of the clinical setting. 1e!er techniques of measuring ventricular volumes !ith transesophageal echocardiography or by radioisotopes are more accurate but are not as !idely available. INTRAVENOUS FLUIDS ntravenous fluid therapy may consist of infusions of crystalloids, colloids, or a combination of both. Crystalloid solutions are aqueous solutions of lo!.molecular.!eight ions &salts+ !ith or !ithout glucose, !hereas colloid solutions also contain high. molecular.!eight substances such as proteins or large glucose polymers. Colloid solutions maintain plasma colloid oncotic pressure &see Chapter 'B+ and for the most part remain intravascular, !hereas crystalloid solutions rapidly equilibrate !ith and distribute throughout the entire extracellular fluid space. Controversy exists regarding the use of colloid versus crystalloid fluids for surgical patients. %roponents of colloids @ustifiably argue that by maintaining plasma oncotic pressure, colloids are more effective in restoring normal intravascular volume and cardiac output. Crystalloid proponents, on the other hand, maintain that the crystalloid solutions are equally as effective !hen given in sufficient amounts. Concerns that colloids may enhance the formation of pulmonary edema fluid in patients !ith increased pulmonary capillary permeability appear to be unfounded, because pulmonary interstitial oncotic pressure parallels that of plasma &see Chapter ''+. Several generali$ations can be made< *. Crystalloids, !hen given in sufficient amounts, are @ust as effective as colloids in restoring intravascular volume. '. "eplacing an intravascular volume deficit !ith crystalloids generally requires three to four times the volume needed !hen using colloids. C. Most surgical patients have an extracellular fluid deficit that exceeds the intravascular deficit. ;. Severe intravascular fluid deficits can be more rapidly corrected using colloid solutions. 5. The rapid administration of large amounts of crystalloids &4 ;)5 2+ is more frequently associated !ith significant tissue edema. Some evidence suggests9but does not prove9that mar,ed tissue edema can impair oxygen transport, tissue healing, and return of bo!el function follo!ing ma@or surgery. CRYSTALLOID SOLUTIONS Crystalloids should be considered as the initial resuscitation fluid in patients !ith hemorrhagic and septic shoc,, in burn patients, in patients !ith head in@ury to maintain cerebral perfusion pressure, and in patients undergoing plasmapheresis and hepatic resection. f C); 2 of crystalloid has been given, and the hemodynamic response is inadequate, colloids may be added.

A !ide variety of solutions is available &Table '()'+. Solutions are chosen according to the type of fluid loss being replaced. Dor losses primarily involving !ater, replacement is !ith hypotonic solutions, also called maintenance.type solutions. f losses involve both !ater and electrolytes, replacement is !ith isotonic electrolyte solutions, also called replacement.type solutions. Elucose is provided in some solutions to maintain tonicity or to prevent ,etosis and hypoglycemia due to fasting. Children are prone to developing hypoglycemia &A 56 mg:d2+ follo!ing ;. to B.h fasts. Fomen may be more li,ely to develop hypoglycemia follo!ing extended fasts &4 '; h+ than men.

Table 292 C%-+%$!2!%# %& C0*$2all%!( S%l'2!%#$

S%l'2!%#

T%/!1!2* Na7 Cl 97 Ca27)-E86L. M"27)-E86L. Gl'1%$ )-O$-6L. )-E86L. )-E86L. )-E86L. )"6L. 7ypo &'5C+ 56

5G dextrose in !ater &/5F+ 1ormal saline &1S+ /5*:;1S /5H1S /51S 2actated "ingerJs in@ection &2"+ /52" H1S CG S 5G S I.5G 1a7C3C

so &C6B+

*5;

*5;

so &C55+ 7yper &;C'+ 7yper &5B?+ so &'IC+

CB.5 II *5; *C6

CB.5 II *5; *6( ; C

56 56 56

7yper &5'5+

*C6

*6( II 5*C B55

56

7ypo &*5;+ II 7yper &*6'?+ 7yper &*I*6+ 7yper &*IB?+ 5*C B55 B(C

S%l'2!%#

T%/!1!2* Na7 Cl 97 Ca27)-E86L. M"27)-E86L. Gl'1%$ )-O$-6L. )-E86L. )-E86L. )-E86L. )"6L. *;6 (B 5 C

%lasmalyte so &'(;+

8ecause most intraoperative fluid losses are isotonic, replacement.type solutions are generally used. The most commonly used fluid is lactated "ingerJs solution. Although it is slightly hypotonic, providing approximately *66 m2 of free !ater per liter and tending to lo!er serum sodium to *C6 mEq:2, lactated "ingerJs generally has the least effect on extracellular fluid composition and appears to be the most physiological solution !hen large volumes are necessary. The lactate in this solution is converted by the liver into bicarbonate. 45e# "!,e# !# la0"e ,%l'-e$: #%0-al $al!#e +0%('1e$ a (!l'2!%#al 5*+e015l%0e-!1 a1!(%$!$ be1a'$e %& !2$ 5!"5 $%(!'- a#( 15l%0!(e 1%#2e#2 )1;< -E86L.: +la$-a b!1a0b%#a2e 1%#1e#20a2!%# (e10ea$e$ a$ 15l%0!(e 1%#1e#20a2!%# !#10ea$e$ 1ormal saline is the preferred solution for hypochloremic metabolic al,alosis and for diluting pac,ed red blood cells prior to transfusion. Dive percent dextrose in !ater &/5F+ is used for replacement of pure !ater deficits and as a maintenance fluid for patients on sodium restriction. 7ypertonic CG saline is employed in therapy of severe symptomatic hyponatremia &see Chapter 'B+. Three to I.5G saline solutions have been advocated for the resuscitation of patients in hypovolemic shoc,. These solutions must be administered slo!ly &preferably through a central venous catheter+ because they readily cause hemolysis. COLLOID SOLUTIONS The osmotic activity of the high.molecular.!eight substances in colloids tends to maintain these solutions intravascularly. Although the intravascular half.life of a crystalloid solution is '6)C6 min, most colloid solutions have intravascular half.lives bet!een C and ? h. The substantial cost and occasional complications associated !ith colloids tend to limit their use. Eenerally accepted indications for colloids include &*+ fluid resuscitation in patients !ith severe intravascular fluid deficits &eg, hemorrhagic shoc,+ prior to the arrival of blood for transfusion, and &'+ fluid resuscitation in the presence of severe hypoalbuminemia or conditions associated !ith large protein losses such as burns. n burn patients colloids should also be considered if the in@ury involves more than C6G of the body surface area or if more than C); 2 of crystalloid has been given over *B)'; h postin@ury. Many clinicians also use colloid solutions in con@unction !ith crystalloids !hen fluid replacement needs exceed C); 2 prior to transfusion. t should be noted that these solutions are prepared in normal saline &Cl)*;5)*5; mEq:2+ and can also cause hyperchloremic metabolic acidosis &above+. Several colloid solutions are generally available. All are derived from either plasma proteins or synthetic glucose polymers and are supplied in isotonic electrolyte solutions. 8lood.derived colloids include albumin &5G and '5G solutions+ and plasma protein fraction &5G+. 8oth are heated to ?6KC for at least *6 h to minimi$e the ris, of transmitting hepatitis and other virally transmitted diseases. %lasma protein fraction contains . and .globulins in addition to albumin and has occasionally resulted in hypotensive reactions. These reactions are allergic in nature and may involve activators of pre,alli,rein.

Synthetic colloids include dextrose starches and gelatins. Eelatins are associated !ith histamine.mediated allergic reactions and are not available in the -nited States. De/20a# is available as dextran I6 &Macrodex+ and dextran ;6 &"heomacrodex+, !hich have average molecular !eights of I6,666 and ;6,666, respectively. Although dextran I6 is a better volume expander than dextran ;6, the latter also improves blood flo! through the microcirculation, presumably by decreasing blood viscosity. Antiplatelet effects are also described for dextrans. nfusions exceeding '6 m2:,g per day can interfere !ith blood typing, may prolong bleeding time &dextran ;6+, and have been associated !ith renal failure. /extrans can also be antigenic, and both mild and severe anaphylactoid and anaphylactic reactions are described. /extran * &%romit+ may be administered prior to dextran ;6 or dextran I6 to prevent severe anaphylactic reactions# it acts as a hapten and binds any circulating dextran antibodies. 7etastarch &hydroxyethyl starch+ is available as a ?G solution !ith an average molecular !eight of ;56,666. Small molecules are eliminated by the ,idneys, !hereas large molecules must be first bro,en do!n by amylase. 7etastarch is highly effective as a plasma expander and is less expensive than albumin. Moreover, hetastarch is nonantigenic, and anaphylactoid reactions are rare. Coagulation studies and bleeding times are generally not significantly affected follo!ing infusions of up to 6.5)*.6 2. Fhether ,idney transplant patients do !orse follo!ing hetastarch infusions is controversial. Similarly, controversy exists as to an association bet!een hetastarch use in patients undergoing cardiopulmonary bypass. %entastarch, a lo!er molecular !eight starch solution, is less li,ely to cause adverse effects and may replace hetastarch. PERIOPERATIVE FLUID THERAPY %erioperative fluid therapy includes replacement of preexisting fluid deficits, of normal losses &maintenance requirements+, and of surgical !ound losses including blood loss. NORMAL MAINTENANCE RE=UIREMENTS n the absence of oral inta,e, fluid and electrolyte deficits can rapidly develop as a result of continued urine formation, gastrointestinal secretions, s!eating, and insensible losses from the s,in and lungs. 1ormal maintenance requirements can be estimated from Table '()C.

Table 29> E$2!-a2!#" Ma!#2e#a#1e Fl'!( Re8'!0e-e#2$ 4e!"52 Dor the first *6 ,g Dor the next *6)'6 ,g Dor each ,g above '6 ,g Ra2e

; m2:,g:h Add ' m2:,g:h Add * m2:,g:h

Example< Fhat are the maintenance fluid requirements for a '5.,g childL Ans!er< ;6 M '6 M 5 N ?5 m2:h. PREEXISTING DEFICITS

%atients presenting for surgery after an overnight fast !ithout any fluid inta,e !ill have a preexisting deficit proportionate to the duration of the fast. The deficit can be estimated by multiplying the normal maintenance rate by the length of the fast. Dor the average I6.,g person fasting for B h, this amounts to &;6 M '6 M 56+ m2:h x B h, or BB6 m2. & n reality, this deficit !ill be some!hat less as a result of renal conservation.+ Abnormal fluid losses frequently contribute to preoperative deficits. %reoperative bleeding, vomiting, diuresis, and diarrhea are often contributory. 3ccult losses &really redistribution# see belo!+ due to fluid sequestration by traumati$ed or infected tissues or ascites can also be substantial. ncreased insensible losses due to hyperventilation, fever, and s!eating are often overloo,ed. deally, all deficits should be replaced preoperatively in all patients. The fluids used should be similar in composition to the fluids lost &Table '();+.

Table 29< Ele120%l*2e C%#2e#2 %& 3%(* Fl'!($ Fl'!( S!eat Saliva Eastric @uice 7igh acidity 2o! acidity *6)C6 I6)*;6 5);6 5);6 5 5 5)C6 *6);6 B6)*56 55)(5 55)(5 (6)*'6 '6)(6 C6)*'6 5)'5 ?6)**6 C6);6 '6)C6 C6)56 Na7 )-E86L. 97 )-E86L. Cl )-E86L. HCO> )-E86L. C6)56 ');6 5 *6)C6 ;5)55 ?)C6 C6

%ancreatic secretions **5)*B6 8iliary secretions leal fluid /iarrheal stool *C6)*?6 ;6)*C5 '6)*?6

SURGICAL FLUID LOSSES 3l%%( L%$$ 3ne of the most important and difficult tas,s of the anesthesiologist is to continually monitor and estimate blood loss. Although estimates are complicated by occult bleeding into the !ound or under the surgical drapes, accuracy is important to guide fluid therapy and transfusions The most commonly used method for estimating blood loss is measurement of blood in the surgical suction container and visually estimating the blood on surgical sponges and laparotomy pads &>laps>+. A fully soa,ed sponge &; x ;+ is said to hold *6 m2 of blood, !hereas a soa,ed >lap> holds *66)*56 m2. More accurate estimates are obtained if sponges and >laps> are !eighed before and after use &particularly during pediatric procedures+. -se of irrigating solutions complicates estimates, but their use should be noted and some attempt made to compensate for them. Serial hematocrits or hemoglobin concentrations reflect the ratio of blood cells to plasma, not necessarily blood loss# moreover, rapid fluid shifts and

intravenous replacement affect measurements. 7ematocrits may be useful during long procedures or !hen estimates are difficult. O25e0 Fl'!( L%$$e$ Many surgical procedures are associated !ith obligatory losses of fluids other than blood. Such losses are due mainly to evaporation and internal redistribution of body fluids. Evaporative losses are most apparent !ith large !ounds and directly proportionate to the surface area exposed and the duration of the surgical procedure. nternal redistribution of fluids9often called >third spacing>9can cause massive fluid shifts and severe intravascular depletion. Traumati$ed, inflamed, or infected tissue &as occurs !ith burns, extensive in@uries, surgical dissections, or peritonitis+ can sequester large amounts of fluid in its interstitial space and can translocate fluid across serosal surfaces &ascites+ or into bo!el lumen. The result is an obligatory increase in a nonfunctional component of the extracellular compartment, as this fluid does not readily equilibrate !ith the rest of the compartments. This fluid shift cannot be prevented by fluid restriction and is at the expense of both the functional extracellular and intracellular fluid compartments. Cellular dysfunction as a result of hypoxia can produce an increase of the intracellular fluid volume, also at the expense of the functional extracellular compartment. 2astly, significant losses of lymphatic fluid may occur during extensive retroperitoneal dissections. INTRAOPERATIVE FLUID REPLACEMENT ntraoperative fluid therapy should include supplying basic fluid requirements and replacing residual preoperative deficits as !ell as intraoperative losses &blood, fluid redistribution, and evaporation+. Selection of the type of intravenous solution depends upon the surgical procedure and the expected blood loss. Dor procedures involving minimal blood loss and fluid shifts, maintenance solutions can be used. Dor all other procedures, lactated "ingerJs solution or fluid is generally used even for maintenance requirements. Re+la1!#" 3l%%( L%$$ deally, blood loss should be replaced !ith crystalloid or colloid solutions to maintain intravascular volume &normovolemia+ until the danger of anemia out!eighs the ris,s of transfusion. At that point, further blood loss is replaced !ith transfusions of red blood cells to maintain hemoglobin concentration &or hematocrit+ at that level. Dor most patients, that point corresponds to a hemoglobin bet!een I and B g:d2 &or a hematocrit of '*)';G+. 8elo! a hemoglobin concentration of I g:d2, the resting cardiac output increases to maintain a normal oxygen delivery. A level of *6 g:d2 is generally used for elderly patients and those !ith significant cardiac or pulmonary disease. 7igher limits may be used if continuing rapid blood loss is expected. n practice, most clinicians give lactated "ingerJs solution in approximately three to four times the volume of the blood lost, or colloid in a *<* ratio, until the transfusion point is reached. At that time, blood is replaced unit for unit as it is lost, !ith reconstituted pac,ed red blood cells.

The transfusion point can be determined preoperatively from the hematocrit and by estimating blood volume &Table '()5+. %atients !ith a normal hematocrit should generally be transfused only after losses greater than *6)'6G of their blood volume. The exact point is based on the patientJs medical condition and the surgical procedure. The amount of blood loss necessary for the hematocrit to fall to C6G can be calculated as follo!s< *. Estimate blood volume from Table '()5. '. Estimate the red blood cell volume &"8C0+ at the preoperative hematocrit &"8C0preop+. C. Estimate "8C0 at a hematocrit of C6G &"8C0C6G+, assuming normal blood volume is maintained. ;. Calculate the red cell volume lost !hen the hematocrit is C6G# "8C0 lost N "8C0preop ) "8C0C6G. 5. Allo!able blood loss N "8C0lost x C.

Table 29; A,e0a"e 3l%%( V%l'-e$ A"e 1eonates %remature Dull.term nfants Adults Men Fomen I5 m2:,g ?5 m2:,g (5 m2:,g B5 m2:,g B6 m2:,g 3l%%( V%l'-e

EXAMPLE An B5.,g !oman has a preoperative hematocrit of C5G. 7o! much blood loss !ill decrease her hematocrit to C6GL Estimated blood volume N ?5 m2:,g x B5 ,g N 55'5 m2. "8C0C5G N 55'5 x C5G N *(C; m2. "8C0C6G N 55'5 x C6G N *?5B m2. "ed cell loss at C6G N *(C; ) *?5B N 'I? m2. Allo!able blood loss N C x 'I? m2 N B'B m2. Therefore, transfusion should be considered only !hen this patientJs blood loss exceeds B66 m2. ncreasingly, transfusions are not recommended until the hematocrit

decreases to ';G &hemoglobin A B.6 g:d2+, but it is necessary to ta,e into account the rate of blood loss and comorbid conditions, ie, cardiac disease in !hich case transfusion might be indicated if only B66 m2 of blood is lost. 3ther useful guidelines commonly used are as follo!s< &*+ one unit of red blood cells !ill increase hemoglobin * g:d2 and the hematocrit ')CG &in adults+# and &'+ a *6.m2:,g transfusion of red blood cells !ill increase hemoglobin concentration by C g:d2 and the hematocrit by *6G. Re+la1!#" Re(!$20!b'2!,e & E,a+%0a2!,e L%$$e$ 8ecause these losses are primarily related to !ound si$e and the extent of surgical dissections and manipulations, procedures can be classified according to the degree of tissue trauma. These additional fluid losses can be replaced according to Table '()?, based on !hether tissue trauma is minimal, moderate, or severe. These values are only guidelines, and actual needs vary considerably from patient to patient.

Table 29? Re(!$20!b'2!%# a#( E,a+%0a2!,e S'0"!1al Fl'!( L%$$e$ De"0ee %& T!$$'e T0a'-a Minimal &eg, herniorrhaphy+ Moderate &eg, cholecystectomy+ Severe &eg, bo!el resection+ A((!2!%#al Fl'!( Re8'!0e-e#2 6)' m2:,g '); m2:,g ;)B m2:,g

TRANSFUSION 3LOOD GROUPS 7uman red cell membranes are estimated to contain at least C66 different antigenic determinants. At least '6 separate blood group antigen systems are ,no!n# the expression of each is under genetic control from separate chromosomal loci. Dortunately, only the A83 and the "h systems are important in the ma@ority of blood transfusions. ndividuals often produce antibodies &alloantibodies+ to the alleles they lac, !ithin each system. Such antibodies are responsible for the most serious reactions to transfusions. Antibodies may occur >naturally> or in response to sensiti$ation from a previous transfusion or pregnancy. T5e A3O S*$2eSimplistically, the chromosomal locus for this system produces t!o alleles< A and 8. Each represents an en$yme that modifies a cell surface glycoprotein, producing a different antigen. &Actually, there are multiple variants of A and 8.+ Almost all individuals not having A or 8 >naturally> produce antibodies &mainly immunoglobulin M & gM+ against those antigens &Table '()I+ !ithin the first year of life. The 7 antigen is the structural precursor of the A83 system but is produced by a different chromosomal locus. Absence of the 7 antigen &hh genotype, also called the 8ombay phenotype+

prevents expression of the A or 8 genes# individuals !ith this very rare condition !ill have anti.A, anti.8, and anti.7 antibodies.

Table 29@ A3O 3l%%( G0%'+!#" T*+e Na2'0all* O11'00!#" A#2!b%(!e$ !# Se0'- I#1!(e#1e1 A 8 A8 3 Anti.8 Anti.A 9 Anti.A, anti.8 ;5G BG ;G ;CG

"ates are based on persons of !estern European ancestry.

T5e R5 S*$2eThe "h system is encoded by t!o genes located on chromosome *. There are about ;? "h.related antigens, but in most clinical settings, the five principal antigens &/, C, c, E, and e+ and their corresponding antibodies account for most issues involving the "h system. Dor simplicity, only the presence or absence of the most common and most immunogenic allele, the / antigen, is considered. Approximately B6)B5G of the !hite population has the / antigen. ndividuals lac,ing this allele are called "h.negative and usually develop antibodies against the / antigen only after exposure to a previous &"h.positive+ transfusion or pregnancy &an "h.negative mother delivering an "h. positive baby+. O25e0 S*$2e-$ 3ther systems include the 2e!is, %, i, M1S, =idd, =ell, /uffy, 2utheran, Og, Sid, Cartright, P=, and Chido "odgers antigens. Dortunately, !ith some exceptions &=ell, =idd, /uffy, and S+, alloantibodies against these systems rarely cause serious hemolytic reactions. COMPATI3ILITY TESTING The purpose of compatibility testing is to predict and to prevent antigen)antibody reactions as a result of red blood cell transfusions. /onor and recipient blood are typed and chec,ed for the presence of adverse antibodies. A3OAR5 Te$2!#"

The most severe transfusion reactions are due to A83 incompatibility# naturally acquired antibodies can react against the transfused &foreign+ antigens, activate complement, and result in intravascular hemolysis. The patientJs red cells are tested !ith serum ,no!n to have antibodies against A and against 8 to determine blood type. 8ecause of the almost universal prevalence of natural A83 antibodies, confirmation of blood type is then made by testing the patientJs serum against red cells !ith a ,no!n antigen type. The patientJs red cells are also tested !ith anti./ antibodies to determine "h. f the sub@ect is "h.negative, the presence of anti./ antibody is chec,ed by mixing the patientJs serum against "h.positive red cells. The probability of developing anti./ antibodies after a single exposure to the "h antigen is 56)I6G. C0%$$-a215!#" A crossmatch mimics the transfusion< donor cells are mixed !ith recipient serum. Crossmatching serves three functions< &*+ it confirms A83 and "h typing &in less than 5 min+, &'+ it detects antibodies to the other blood group systems, and &C+ it detects antibodies in lo! titers or those that do not agglutinate easily. The latter t!o require at least ;5 min. A#2!b%(* S10ee# The purpose of this test is to detect in the serum the presence of the antibodies that are most commonly associated !ith non.A83 hemolytic reactions. The test &also ,no!n as the indirect Coombs test+ requires ;5 min and involves mixing the sub@ectJs serum !ith red cells of ,no!n antigenic composition# if specific antibodies are present, they !ill coat the red cell membrane, and addition of an antiglobulin antibody results in red cell agglutination. Screens are routinely done on all donor blood and may be done for a potential recipient instead of a crossmatch &belo!+. T*+e & C0%$$-a215 ,e0$'$ T*+e & S10ee# The incidence of a serious hemolytic reaction after transfusion of an A83. and "h. compatible transfusion !ith a negative screen but !ithout a crossmatch is less than *G. Crossmatching, ho!ever, assures optimal safety and detects the presence of less common antibodies not usually tested for in a screen. Crossmatches are no! performed only for elective surgical procedures in !hich the probability of transfusion is high. 8ecause of the time involved, &;5 min+ if t!o previous type and screen procedures have been documented, some centers have begun computer crossmatching9no actual crossmatch is performed. Ma/!-'- S'0"!1al 3l%%( O0(e0!#" S15e('le Most hospitals compile a list of their most commonly performed operations and the maximum number of units that can be crossmatched preoperatively. Such practices prevent needless, excessive crossmatching of blood. 2ists are usually based on each institutionJs o!n experience. A crossmatch.to.transfusion ratio less than '.5<* is considered acceptable. 3nly a type and screen is performed if the incidence of transfusion for a procedure is less than *6G. f transfusion is required, a crossmatch is performed. Allo!ances are typically made for anemic patients and those !ith coagulation disorders. EMERGENCY TRANSFUSIONS Fhen a patient is exsanguinating, the need to transfuse arises prior to completion of a crossmatch, screen, or even blood typing. f the patientJs blood type is ,no!n, an

abbreviated crossmatch, requiring less than 5 min, !ill confirm A83 compatibility. I& 25e 0e1!+!e#2B$ bl%%( 2*+e !$ #%2 C#%D# D!25 1e02a!#2* a#( 20a#$&'$!%# -'$2 be $2a02e( be&%0e (e2e0-!#a2!%#: 2*+e O R5A#e"a2!,e )'#!,e0$al (%#%0. bl%%( -a* be '$e( 3LOOD 3AN9 PRACTICES 8lood donors are screened to exclude medical conditions that might adversely affect the donor or the recipient. The hematocrit is determined, and if it is greater than CIG for allogeneic or C'G for autologous donors, the blood is collected, typed, screened for antibodies, and tested for hepatitis 8, hepatitis C, syphilis, human T cell leu,emia virus &7T20+.* and 7T20.', and human immunodeficiency virus &7 0+.* and 7 0.'. Most centers are doing nucleic acid testing for viral "1A to detect hepatitis 8 and C, and 7 0 viruses, and !or, is on.going to detect Fest 1ile virus. There are extremely sensitive tests, and they should narro! even further the !indo! of positive virus but negative test. 3nce blood is collected, a preservative)anticoagulant solution is added. The most commonly used solution is CPDAA1: !hich contains citrate as an anticoagulant &by binding calcium+, phosphate as a buffer, dextrose as a red cell energy source, and adenosine as a precursor for adenosine triphosphate &AT%+ synthesis. C%/A.*.preserved blood can be stored for C5 days, after !hich the viability of the red cells rapidly decreases. Alternatively, use of either AS.* &Adsol+ or AS.C &1utrice+ extends the shelf. life to ? !ee,s. All units collected are separated into their component parts, namely, red blood cells, platelets, and plasma. Fhen centrifuged, one unit of !hole blood yields about '56 m2 of pac,ed red blood cells &hematocrit I6G+# follo!ing the addition of more saline preservative, the volume of a unit of pac,ed red cells often reaches C56 m2. "ed cells are normally stored at *)?KC. "ed cells may be fro$en in a hypertonic glycerol solution for up to *6 years. The latter technique is usually reserved for storage of blood !ith rare phenotypes. The supernatant is centrifuged to yield platelets and plasma. The unit of platelets obtained generally contains 56)I6 m2 of plasma and can be stored at '6)';KC for 5 days. The remaining plasma supernatant is further processed and fro$en to yield fresh fro$en plasma# rapid free$ing helps prevent inactivation of labile coagulation factors &0 and 0 +. Slo! tha!ing of fresh fro$en plasma yields a gelatinous precipitate &cryoprecipitate+ that contains high concentrations of Dactor 0 and fibrinogen. 3nce separated, this cryoprecipitate can be refro$en for storage. 3ne unit of blood yields about '66 m2 of plasma, !hich is fro$en for storage# once tha!ed, it must be transfused !ithin '; h. %latelets may alternatively be obtained by automated plateletpheresis, !hich yields the equivalent of up to six regular units from a single patient. INTRAOPERATIVE TRANSFUSION PRACTICES Pa1Ce( Re( 3l%%( Cell$ 8lood transfusions should be given as pac,ed red blood cells, !hich allo!s optimal utili$ation of blood ban, resources. %ac,ed red blood cells are ideal for patients requiring red cells but not volume replacement &eg, anemic patients in compensated congestive heart failure+. Surgical patients require volume as !ell as red blood cells# crystalloid can be infused simultaneously through a second intravenous line for volume replacement.

%rior to transfusion, each unit should be carefully chec,ed against the blood ban, slip and the recipientJs identity bracelet. The transfusion tubing should contain a *I6. m filter to trap any clots or debris. A similar si$ed but charged filter is used to reduce leu,ocyte content to prevent febrile transfusion reactions in sensiti$ed patients &see belo!+. 8lood for intraoperative transfusion should be !armed to CIKC during infusion, particularly if more than ')C units is going to be transfused# failure to do so can result in profound hypothermia. The additive effects of hypothermia and the typically lo! levels of ',C.diphosphoglycerate &',C./%E+ in stored blood can cause a mar,ed left!ard shift of the hemoglobin)oxygen dissociation curve &see Chapter ''+ and, at least theoretically, promote tissue hypoxia. 8lood !armers should be able to maintain blood temperature 4 C6KC even at flo! rates up to *56 m2:min. F0e$5 F0%Ee# Pla$-a Dresh fro$en plasma &DD%+ contains all plasma proteins, including all clotting factors. Transfusions of DD% are indicated in the treatment of isolated factor deficiencies, the reversal of !arfarin therapy, and the correction of coagulopathy associated !ith liver disease. Each unit of DD% generally increases the level of each clotting factor by ') CG in adults. The initial therapeutic dose is usually *6)*5 m2:,g. The goal is to achieve C6G of the normal coagulation factor concentration. DD% may also be used in patients !ho have received massive blood transfusions &see belo!+ and continue to bleed follo!ing platelet transfusions. %atients !ith antithrombin deficiency or thrombotic thrombocytopenic purpura also benefit from DD% transfusions. Each unit of DD% carries the same infectious ris, as a unit of !hole blood. n addition, occasional patients may become sensiti$ed to plasma proteins. A83. compatible units should generally be given but are not mandatory. As !ith red cells, DD% should generally be !armed to CIKC prior to transfusion. Pla2ele2$ %latelet transfusions should be given to patients !ith thrombocytopenia or dysfunctional platelets in the presence of bleeding. %rophylactic platelet transfusions are also indicated in patients !ith platelet counts belo! *6,666)'6,666 x *6 (:2 because of an increased ris, of spontaneous hemorrhage. %latelet counts less than 56,666 x *6 (:2 are associated !ith increased blood loss during surgery. Thrombocytopenic patients about to undergo surgery or invasive procedures should receive prophylactic platelet transfusions preoperatively< the platelet count should be increased to approximately *66,666 x *6 (:2. 0aginal delivery and minor surgical procedures may be performed in patients !ith lo!er platelet counts but !ith normal platelet function and counts greater than 56,666 x *6(:2. Each single unit of platelets may be expected to increase the count by *6,666) '6,666 x *6(:2. %lateletpheresis units contain the equivalent of six regular, single donor units &above+. 2esser increases can be expected in patients !ith a history of prior platelet transfusions. %latelet dysfunction can also increase surgical bleeding even !hen the platelet count is normal and can be diagnosed preoperatively !ith a bleeding time. %latelet transfusions may also be indicated in patients !ith dysfunctional platelets and increased surgical bleeding. A83.compatible platelet transfusions are desirable but not necessary. Transfused platelets generally survive only *)I days follo!ing transfusion. A83 compatibility may increase platelet survival. "h sensiti$ation can occur in "h.negative recipients due to the presence of a fe! red cells in "h.positive platelet units. Moreover, anti.A or anti.8

antibodies in the I6 m2 of plasma in each platelet unit can cause a hemolytic reaction against the recipientJs red cells !hen a large number of A83.incompatible platelet units is given. Administration of "h immunoglobulin to "h.negative individuals can protect against "h sensiti$ation follo!ing "h.positive platelet transfusions. %atients !ho develop antibodies against 72A antigens &present on lymphocytes in platelet concentrates+ or specific platelet antigens require 72A.compatible or single.donor units. -se of plateletpheresis transfusions may decrease the li,elihood of sensiti$ation. G0a#'l%1*2e T0a#$&'$!%#$ Eranulocyte transfusions, prepared by leu,apheresis, may be indicated in neutropenic patients !ith bacterial infections not responding to antibiotics. Transfused granulocytes have a very short circulatory life span, so that daily transfusions of *6 *6 granulocytes are usually required. rradiation of these units decreases the incidence of graft.versus.host reactions, pulmonary endothelial damage, and other problems associated !ith transfusion of leu,ocytes &see belo!+, but may adversely affect granulocyte function. The availability of filgrastim &granulocyte colony.stimulating factor, or E.CSD+ and sargramostim &granulocyte.macrophage colony.stimulating factor, or EM.CSD+ has greatly reduced the use of granulocyte transfusions. COMPLICATIONS OF 3LOOD TRANSFUSION IMMUNE COMPLICATIONS mmune complications follo!ing blood transfusions are primarily due to sensiti$ation of the recipient to donor red cells, !hite cells, platelets, or plasma proteins. 2ess commonly, the transfused cells or serum may mount an immune response against the recipient. He-%l*2!1 Rea12!%#$ He-%l*2!1 0ea12!%#$ usually involve specific destruction of the transfused red blood cells by the recipientJs antibodies. 2ess commonly, hemolysis of a recipientJs red blood cells occurs as a result of the transfusion of red cell antibodies. ncompatible units of platelet concentrates, DD%, clotting factor concentrates, or cryoprecipitate may contain small amounts of plasma !ith anti.A or anti.8 &or both+ alloantibodies. Transfusions of large volumes of such units can lead to intravascular hemolysis. 7emolytic reactions are commonly classified as either acute &intravascular+ or delayed &extravascular+. Ma#a"e-e#2 %& 5e-%l*2!1 0ea12!%#$ 1a# be $'--a0!Ee( a$ &%ll%D$: *. 3nce a hemolytic reaction is suspected, the transfusion should be stopped immediately. '. The unit should be rechec,ed against the blood slip and the patientJs identity bracelet. C. 8lood should be dra!n to identify hemoglobin in plasma, to repeat compatibility testing, and to obtain coagulation studies and a platelet count. ;. A urinary catheter should be inserted, and the urine should be chec,ed for hemoglobin. 5. 3smotic diuresis should be initiated !ith mannitol and intravenous fluids. ?. n the presence of rapid blood loss, platelets and DD% are indicated.

Dela*e( He-%l*2!1 Rea12!%#$ A delayed hemolytic reaction9also called extravascular hemolysis9is generally mild and is caused by antibodies to non./ antigens of the "h system or to foreign alleles in other systems such as the =ell, /uffy, or =idd antigens. Dollo!ing an A83 and "h /.compatible transfusion, patients have a *)*.?G chance of forming antibodies directed against foreign antigens in these other systems. 8y the time significant amounts of these antibodies have formed &!ee,s to months+, the transfused red cells have been cleared from the circulation. Moreover, the titer of these antibodies subsequently decreases and may become undetectable. "eexposure to the same foreign antigen during a subsequent red cell transfusion, ho!ever, triggers an anamnestic antibody response against the foreign antigen. This phenomenon is seen more !ith the =idd antigen system. The hemolytic reaction is therefore typically delayed ')'* days after transfusion, and symptoms are generally mild, consisting of malaise, @aundice, and fever. The patientJs hematocrit typically fails to rise in spite of the transfusion and the absence of bleeding. The serum uncon@ugated bilirubin increases as a result of hemoglobin brea,do!n. /iagnosis of delayed antibody.mediated hemolytic reactions may be facilitated by the antiglobulin &Coombs+ test. The direct Coombs test detects the presence of antibodies on the membrane of red cells. n this setting, ho!ever, this test cannot distinguish bet!een recipient antibodies coated on donor red cells and donor antibodies coated on recipient red cells. The latter requires a more detailed reexamination of pretransfusion specimens from both the patient and the donor. The treatment of delayed hemolytic reactions is primarily supportive. The frequency of delayed hemolytic transfusion reactions is estimated to be approximately *<*',666 transfusions. %regnancy &exposure to fetal red cells+ can also be responsible for the formation of alloantibodies to red cells. N%#5e-%l*2!1 I--'#e Rea12!%#$ 1onhemolytic immune reactions are due to sensiti$ation of the recipient to the donorJs !hite cells, platelets, or plasma proteins. Feb0!le Rea12!%#$ Fhite cell or platelet sensiti$ation is typically manifested as a febrile reaction. Such reactions are relatively common &*)CG of transfusion episodes+ and are characteri$ed by an increase in temperature !ithout evidence of hemolysis. %atients !ith a history of repeated febrile reactions should receive !hite cell.poor red cell transfusions only. "ed cell transfusions can be made leu,ocyte.poor by centrifugation, filtration, or free$e)tha! techniques. U02!1a0!al Rea12!%#$ -rticarial reactions are usually characteri$ed by erythema, hives, and itching !ithout fever. They are relatively common &*G of transfusions+ and are thought to be due to sensiti$ation of the patient to transfused plasma proteins. -rticarial reactions can be treated !ith antihistaminic drugs &7* and perhaps 7' bloc,ers+ and steroids. A#a+5*la12!1 Rea12!%#$ Anaphylactic reactions are rare &approximately * in *56,666 transfusions+. These severe reactions may occur after only a fe! milliliters of blood has been given, typically in gA.deficient patients !ith anti. gA antibodies !ho receive gA.containing blood transfusions. The prevalence of gA deficiency is estimated to be *<?66)B66 in the

general population. Such reactions call for treatment !ith epinephrine, fluids, corticosteroids, and 7* and 7' bloc,ers. %atients !ith gA deficiency should receive thoroughly !ashed pac,ed red cells, deglyceroli$ed fro$en red cells, or gA.free blood units. N%#1a0(!%"e#!1 P'l-%#a0* E(e-a An acute lung in@ury syndrome & Transfusion.Related Acute Lung In@ury QT"A2 R+ is a rare complication of blood transfusion &A *<*6,666+. t is thought to be due to transfusion of antileu,ocytic or anti.72A antibodies that interact !ith and cause the patientJs !hite cells to aggregate in the pulmonary circulation. /amage to the alveolar:capillary membrane triggers the syndrome. Alternatively, transfused !hite cells can interact !ith leu,oagglutinins in the patient. nitial treatment of T"A2 is similar to that for acute respiratory distress syndrome &A"/S+ &see Chapter ;(+, but it typically resolves !ithin *');B h !ith supportive therapy. G0a&2AVe0$'$AH%$2 D!$ea$e This type of reaction may be seen in immune.compromised patients. Cellular blood products contain lymphocytes capable of mounting an immune response against the compromised &recipient+ host. -se of special leu,ocyte filters alone does not reliably prevent graft.versus.host disease# irradiation &*566)C666 cEy+ of red cell, granulocyte, and platelet transfusions effectively inactivates lymphocytes !ithout altering the efficacy of such transfusions. P%$220a#$&'$!%# P'0+'0a %rofound thrombocytopenia can rarely occur follo!ing blood transfusions and is due to the development of platelet alloantibodies. Dor un,no!n reasons, these antibodies also destroy the patientJs o!n platelets. The platelet count typically drops precipitously * !ee, after transfusion. %lasmapheresis is generally recommended. I--'#e S'++0e$$!%# Transfusion of leu,ocyte.containing blood products appears to be

immunosuppressive. This is most clearly evident in renal transplant recipients, in !hom preoperative blood transfusions appear to improve graft survival. Some studies suggest that recurrence of malignant gro!ths may be more li,ely in patients !ho receive a blood transfusion during surgery. Available evidence also suggests that transfusion of allogenic leu,ocytes can activate latent viruses in the recipient. 2astly, blood transfusion may increase the incidence of serious infections follo!ing surgery or trauma. INFECTIOUS COMPLICATIONS V!0al I#&e12!%#$ HEPATITIS -ntil routine testing for hepatitis viruses !as implemented, the incidence of hepatitis follo!ing blood transfusion !as I)*6G. At least (6G of these cases !ere due to the hepatitis C virus. The incidence of posttransfusion hepatitis is presently bet!een

*<?C,666 and *<*,?66,666# I5G of these cases are anicteric, and at least 56G develop chronic liver disease. Moreover, of this latter group, at least *6)'6G develop cirrhosis. AC=UIRED IMMUNODEFICIENCY SYNDROME )AIDS. The virus responsible for this disease, 7 0.*, is transmissible by blood transfusion. All blood is tested for the presence of anti.7 0.* and .' antibodies. The requirement of nucleic acid testing by the Dood and /rug Administration &D/A+ greatly narro!s the !indo! to less than a !ee, and decreases the ris, of transfusion.transmitted 7 0 to *<*,(66,666 transfusions. OTHER VIRAL INFECTIONS Cytomegalovirus &CM0+ and Epstein)8arr virus usually cause asymptomatic or mild systemic illness. -nfortunately, some individuals become asymptomatic infectious carriers# the !hite cells in blood units from such donors are capable of transmitting either virus. mmunocompromised and immunosuppressed patients &eg, premature infants and organ transplant recipients+ are particularly susceptible to severe CM0 infections through transfusions. deally, such patients should receive only CM0.negative units. 7o!ever, recent studies indicate that the ris, of CM0 transmission from transfusion of leu,ocyte.reduced blood products is equivalent to CM0 test.negative units. Therefore, issuing leu,ocyte.reduced

ALTERNATIVE STRATEGIES FOR MANAGEMENT OF 3LOOD LOSS DURING SURGERY AUTOLOGOUS TRANSFUSIONS %atients undergoing elective surgical procedures !ith a high probability for transfusion can donate their o!n blood for use during that surgery. Collection is usually started ;)5 !ee,s prior to the procedure. The patient is allo!ed to donate a unit as long as the hematocrit is at least C;G or hemoglobin at least ** g:d2. A minimum of I' h is required bet!een donations to ma,e certain that plasma volume returns to normal. Fith iron supplementation and recombinant erythropoietin therapy &;66 - !ee,ly+, at least three or four units can usually be collected prior to the operation. Some studies suggest that autologous blood transfusions do not adversely affect survival in patients undergoing operations for cancer. Although autologous transfusions li,ely reduce the ris, of infection and transfusion reactions, they are not completely free of ha$ard. "is,s include those of immunological reactions due to clerical errors in collection and labeling, contamination, and improper storage. Allergic reactions can occur due to allergens &eg, ethylene oxide+ that dissolve into the blood from collection and storage equipment. %reoperative autologous blood collection is being used !ith decreasing frequency. 3LOOD SALVAGE & REINFUSION This technique is used !idely during cardiac and ma@or reconstructive vascular and orthopedic surgery &see Chapter '*+. The shed blood is aspirated intraoperatively together !ith an anticoagulant &heparin+ into a reservoir. After a sufficient amount of blood is collected, the red blood cells are concentrated and !ashed to remove debris and anticoagulant and then reinfused into the patient. The concentrates obtained usually have hematocrits of 56)?6G. To be used effectively, this technique requires blood losses greater than *666)*566 m2. Contraindications include septic contamination of the !ound and perhaps a malignant tumor, though concerns about the possibility of reinfusing malignant cells via this technique may not be @ustified. 1e!er, simpler systems allo! reinfusion of shed blood !ithout centrifugation. NORMOVOLEMIC HEMODILUTION Acute normovolemic hemodilution relies on the premise that if the concentration of red blood cells is decreased, total red cell loss is reduced !hen large amounts of blood are shed# moreover, 1a0(!a1 %'2+'2 0e-a!#$ #%0-al be1a'$e !#20a,a$1'la0 ,%l'-e !$ -a!#2a!#e( 8lood is typically removed @ust prior to surgery from a large bore intravenous catheter and is replaced !ith crystalloid and colloids such that the patient remains normovolemic but has a hematocrit of '*)'5G. The blood that is removed is stored in a C%/ bag at room temperature &up to ? h+ to preserve platelet function# the blood is given bac, to the patient after the blood loss or sooner if necessary.

DONORADIRECTED TRANSFUSIONS %atients can request donated blood from family members or friends ,no!n to be A83 compatible. Most blood ban,s discourage this practice and generally require donation at least I days prior to surgery to process the donated blood and confirm compatibility. Studies comparing the safety of donor.directed units to that of random donor units have found either no difference, or that blood ban, units are safer.