Perioperative fluid therapy and complications of blood and blood byproducts

Amir B. Channa FFARCS King Khalid Univ. Hosp. Riyadh

IV Fluid Therapy & Complication of Blood Transfusion

Importance of Water
Major homeostatic mechanisms operating through kidneys & lungs, manitain:
Volume Tonocity Specific ionic composition & H+ ion concentration

Distribution of Water

Intracellular fluid 66% ICF

28L

Total body water

33% ECF

Interstitial fluid 11L Plasma 3L

70 kg male TBW 42 L

Channa AB

Comparison of Whole Blood & Packed Red Blood cells

Value
Volume(mL) Erythrocyte mass(mL) Hematocrit(%) Albumin (g) Globulin (g) Total protein (g) Plasma sodium (mEq)

Whole Blood
517 200 40 12.5 6.25 48.8 45

Packed RBCs
300 200 70 4 2 36 15

Plasma potassium (mEq)

Plasma acid (citric-lactic) (mEq) Donor/recipient ratio

15
80 1 unit/patient

4
25 1 unit every 4-6 patients

Questions
1. Physiological changes during surgery & anaesthesia lead to shifts in fluid balance i.e.. Stress response with secretion of epi or norepi, cortisol, ADH 2. CNB spinal & epidural do chemical or pharmacological sympathectomy which fluids will you use, patients may be elderly and on DIG, Diuretics, or anti-hypertensive 3. Volatile agents BLUNT the normal physiological response to hypovolemia & stress in addition to it they affect myocardium, venous return blood pressure & release of ADH

Questions
4. You may have to use vasopressors viz ephidrine, phenylephrine or other inotropic agents. How will

you titrate IV fluids & vasopressors

5. Mechanical ventilators affects preload decreases ANH & increase ADH therefore increase water &

salt and if blood loss then what?

6. PCO2 & its vasopressor response 7. PEEP, CPAP & CVP interactions

Clinical scenarios
Periop. fluid balance
Bowel resection Liver failure Heart failure Cerebral edema Cerebral edema + hypernatremia ARF ARDS Acutely burned patient Pregnant patient with pre-eclampsia

Goals of Intraop. fluid Administration

Maintain good tissue perfusion & Adequate oxygen delivery Normal electrolyte concentration Normoglycemia & pH

Total fluid requirement address the

following issues
Deficit replacement
Compensatory intra-vascular vol. Expansion

Maintenance fluids
Restoration of losses

Substitution for fluid redistribution (third space fluids)

Overview
Clear understanding of water & electrolyte physiology Major disturbance of fluid & electrolyte balance that may alter
CVS Neurologic & Neuromuscular Sick alv. cap. membrane Cell membrane & Intracellular functions
Volume & composition, H2O, ionic pumps, enzymatic & messenger signalling functions

Drug dynamics & kinetics

Distribution
Extra cellular fluid (int. + IV)
Interstitial fluid
Very little in the form of free fluid Associated with proteoglycan forming gel -ve pressure (-5 mmHg) If interstitial fluid volume increases +ve pressure rises Free fluid in gel increases Edema Very little plasma proteins cross capillary clefts (protein=2gm/dl) Returned to vascular compartment as lymph

Distribution
Intravascular fluid
Plasma Small electrolyte cross freely to form interstitial compartments Identical electrolyte composition Tight intracellular junctions do not allow albumin to go to interstitial comp.

Definitions
Colloids
Substances unable to pass through semi permeable membrane It is a suspension of particle rather than a solution Remains confined to intra-vascular compartment (at least initially) Do not correct water and electrolyte deficiencies Imbibe (suck) fluid from int. comp. Plasma volume expansion Haemodilution Lower hematocrit

Definitions
Colloids (cont)
Increase flow in the microcirculation & Prevent DVT O2 delivery / unit time E.g. albumin, PPF, hetastarch, dextran, gelfusine, haemacel, hypotonic saline, perfluoro carbons, flusol DA

Definitions
Crystalloids
True solution No particulate matter Accelerate coagulation DVT (4 X the fluid restricted group - Janvarin)

 Colloid/Crystalloid Controversy
(in shock & hemorrhage) Arguments in favor of COLLOID
Most logical choice for intravascular expansion Since greater portion remains in IVC & for longer time ( t/2 3-6 hours) BP Less volume required to restore CVP PA WP Colloids enter int. space & increase int. osmotic pressure exacerbating edema Thus initial resuscitation is rapid Less peripheral/pul. edema if used within minutes Costly Risk of anaphylaxis Coagulopathy Poor clot quality

 Colloid/Crystalloid Controversy
(in shock & hemorrhage) Arguments in favor of CRYSTALLOID
Expands IVC adequately but 2-4 times of colloid Replaces the extravascular losses It leaves IVC faster ( t/2 20-30 minutes) Replenishes interstitial compartment Thus small increase in plasma volume They do not produce interstitial compartment edema Cheap Increase GFR

Increases coagulation
Periphral edema is not problem No risk of allergic reaction

Dynamics of IV Fluids
Water solution Intracellularly

All hypotonic solns e.g. 5% dextrose called as

maintenance type of fluids Electrolyte solution
Interstitial compartment Isotonic

Called replacement of fluids

Dynamics of IV Fluids
Colloids
IV compartment
For losses of palsma blood etc. Since most of intraop. Losses Isotonic therefore replacement type of fluids RL solution (hartmanns soln) Normal (or abnormal) saline Dilutional hyperchloremic acidosis

Difficulties in assessing fluid resuscitation

Infusion of Colloid/Crystalloid is guided by: CVS end points viz BP, CVP, which have
No relation with interstitial fluid or ECF etc. Lung water increase markedly before gas exchange is impaired Certain clinical conditions e.g sepsis, CHF, ARDS, contused lung have different

Pathophysiology Dynamics of crystalloid & colloid e.g. -CV disease -impaired gas exchange USA- prefer crystalloids -increased vascular permeability -edema interfering with oxygenation and healing and UK- prefer colloids return of blood functions

Signs of fluid loss (hypovolemia)

Fluid loss (Expressed as Percentage of Body Weight) Sign
Mucous membrane Sensorium Dry Normal

5%

10%
Very dry Lethargic Present

15%
Parched Obtunded Marked >15mmHg increase

Orthostatic changes None in heart rate

in blood pressure
Urinary flow rate Pulse rate Mildly decreased Normal or increased Decreased Increased >100bpm

>10mmHg decreased
Markedly decreased Markedly Increased >120bpm

Blood pressure

Normal

Mildly increased with Decreased respiratory variation

Mentation, capillary refill time > 5sec

 Physical examination Laboratory evaluation

as surrogate of IV volume & adequacy of tissue perfusion

Hemodynamic measurements
CVP PAP PAWP etc

Albumin
Single polypeptide 585 amino acids Synthesized in endoplasmic reticulum of hepatocytes 9-12 gm/day Can increase 2-3 times if needed or stimulated
COP ECF pressure in liver Insulin Thyroxine & Cortisol

5% removed / hour

Albumin
Clinical properties
Binding & transport Strong ve charge binds
Ca++ 40 % Ca Thyroxin Bilirubin Amino acids Warfarin NSAIDs Digoxin

Maintains COP 80%

Albumin
Clinical properties
Free radical scavenging Platelet inhibition & Anti thrombotic effects Affects vascular permeability by bindingsubendothellium of capillary

Serum Albumin Decreases

Dilutional effect crystalloid or colloid Redistribution due to altered capillary permeability e.g. sepsis (5X increase) Decreased synthesis (sepsis) Increased loss from kidneys & IL-6 mediated inhibiton- in SIRs, sepsis Correlation between albumin & COP POOR Therefore edema associated with hypo albuminemia may be due to lymphatic obstruction

? Should Albumin be used in Critical Patients

60% albumin leaves IVC in 4 hours Potentially worsening Edema
Stokwell Greenhalgh Cocharne study

Hypoalbuminemia not indication for albnumin therapy

Expansion of IV Compartment
1000ml of 5% dextrose expands plasma by

1000 x 4/6 = 67ml

1000 ml of crystalloid expands plasma by 1000 x 4/20 = 167 200 ml 1000 ml of colloids expands plasma by 1000 x 4/4 = 1000ml

Periop. Fluid Therapy

Pre-existing deficits

Normal maintenance requirements

Abnormal losses Pre-existing losses
Fasting (100-110 ml x no. of HR) Perop. Bleeding, fistulae Vomitting Diarrhea Diuresis ketosis Occult losses -

Pre-existing losses
Fasting (100-110 ml x no. of HR) Perop. Bleeding, fistulae Vomitting Diarrhea Diuresis ketosis Occult losses
inflammatory traumatic edema Sequestration in third comp.

Increased insensible losses (0.5 ml/kg/hr)

Fever (add 12% for 1oC) Hypoventilation Sweating

Redistribution of Evaporative Losses

Degree of Tissue Trauma
Minimal (e.g. hemiorraphy) Moderate (e.g. cholecystectomy) Severe (e.g. bowel resection)

Additional Fluid Requirement

0-2 mL/kg/hr 2-4 mL/kg/hr 4-8 mL/kg/hr

Surgical Losses
Blood
Always underestimated by surgeon Occult losses:
occult bleeding into wound Under surgical drapes

Swabs: 4x4 Laps:

= 10ml = 100-150ml

Obligatory losses of fluids

Evaporation Redistribution third space

Surgical Losses
Traumatized Inflammed Infected tissues
Burns Extensive injuries Peritonitis

Surgical dissections Serosal surfaces

Ascites Pleural effusions Pericardial effusion etc

Bowel lumen

Replacing Blood Losses

Crystalloid or Colloid
Maintain normovolemia till the danger of anemia out weighs the risk of transfusion ie. 7-8 Gm/dl (or HCTof 21-24%)
1:1 2:4

Colloid the ratio of Crystalloid the ratio of Or mixture if both

Average Blood Volumes

Age
Neonates Premature 95mL/kg 85mL/kg 80mL/kg

Blood volume

Full term
Infants

Adults
Men Women 75mL/kg

65mL/kg

Average Blood Volumes

Patients with normal HCT should only be transfused after 10-20% loss of blood volume One unit of blood pack cells
Increases Hb by 1Gm/dl Or HCT by 2-3%

10 ml pack cells/kg
Increases Hb by 3gm/dl Or HCT by 10%

Changes in Blood During Storage

RBC become
Spherical Cell wall thickened Easy rupture Hemolysis
0.5-1%/day 10-20% may be destroyed with in 24 hrs

WBC become
Looses their phagocytic & bactericidal properties with in 4-6 hrs But maintain antigenic properties

Changes in Blood During Storage

Plateletes
Non functional with in 48 hours at 4oC Otherwise 5-7 days

Factors V & VII

V decreased 50% by 21 days VII decreased 75% in 24 days

ATP & 2,3 DPG K Ca++ NH3 O2 O2 dissociation curve shifted to left Lactic/Pyruvic acids

Blood & Blood By products

Whole blood Packed red blood cells (PCV) Leuko depleted blood Fresh frozen plasma Platelets Factors
Freeze dried factor VII can transmit infection Cryoprecipitate (VIII) antihemophilic Christmas (IX) concentrate

Blood & Blood By products

Granulocyte transfusions Frozen RBC Albumin
5% 20% 25%

Plasma protein fraction Immunoglobulins

Blood Components
Component
Whole blood Concentrated red cells

Volume
450+45ml 280+60ml

Comments
HCT 0.35-0.45 HCT 0.55-0.75

Red cells with additive(SAGM)

FFP(random donor) Cryoprecipitate Platelets(adult theraputic dose)

350+70ml
150-300ml 15-25ml 200-300ml

HCT 0.50-0.70

>140 mg fibrinogen/unit >240x109 platelets

Blood Preservative (Additives)

Heparin medium 24-48 hrs EDTA medium ACD medium 3 weeks CPD medium 4 weeks CPDA medium 5-6 weeks SAGM (UK) 4 weeks

At 4 C (6 )

Products
Whole blood
500 ml per bag with a HCT of 0.40 No functioning platelets after 2-3 days: 2,3 DPG by 2 weeks Normal concentrations of albumin & clotting factors, except factors V & VIII, which are reduced to 10-20% of normal Not sterilized, so there is a risk of transmitted pathogens

Products
Red cell concentrate (packed cells)
250 ml per bag with HCT of 0.60 No functioning platelets; 2,3-DPG levels maintained for 14 days Storage is 35 days with SAGM; 42 days with A-CPD

Products
Platelet concentrates
Single donor Usually as a pool of 5-6 single unit donations; 4 units of platelets contain 1 unit FFP Small numbers of red cells & leukocytes Infection risk as for whole blood, but increased by multiple donors Use ABO-compatible platelets. Maximum storage is 5 days at 4oC 1 unit will increase 10x109/l/m2 BSA

Products
Fresh frozen plasma (FFP)
Prepared from plasma from single donation;150ml per bag at 3oC Shelf life 1 year Contains all clotting factors, albumin & gammaglobulin Use immediately after thawing. Usually give at least 4 units Must be ABO-compatible & Rh(D)-negative if recipient is a Rh(D) fertile female Risk of anaphylactic reactions

Products
Cryoprecipitate
Prepared from freshly prepared plasma frozen at 70oC Precipitates from FFP when slowly thawed; supplied as 6-8 units High in factor VIII, fibrinogen, von Willerband factor & fibrinonectin Indicated for DIC and von Willerbands disease Shelf life 1 year

Products
Human albumin solution
Prepared by fractioning of multiple units of plasma giving 96% albumin & 4% globulin. Available as 4.5 or 20% (hypotonic) solution. Each 20g of albumin requires 20000 blood donations. Pasteurized at 60% for 10 h to kill all microorganisms including viruses

Products
Plasma protein factor (PPF)
Prepared in a similar manner to albumin but contains more globulin (83% albumin, 17% globulin)
Freeze-dried protein as 250 units Sterilized to inactivate viruses Freeze-dried protein as 250 units Sterilized to inactivate viruses Also contains factors II & X

Factor VIII concentrate

Factor IX concentrate

Products
Immunoglobulin products
Fractionation of plasma to produce pool with >90% IgG No risk of viral transmission Used for immune thrombocytopenia and immunodeficiency states

Transfusion Reactions
Acute
Heamolysis due to antibodies directed against red cells Fever donor leukocytes attack host red cells Anaphylaxis due to antibodies directed against recipient IgA Transfusion-related acute lung injury due to donor antibodies directed against leukocytes. Clinically identical to ARDS resolves in 48 hrs

Transfusion Reactions
Acute
Hyperkalemia 5-10 mmol K+ in a unit of blood stored for 4-5 weeks. Effects of additional K+ are exacerbated by acidosis and hypothermia. Hyperkalemia is usually transient Citrate toxicity citrate is added as a preservative to bind excess calcium and prevent clotting. Metabolized to bicarbonate. Excess causes metabolic alkalosis

Transfusion Reactions
Acute
Acid-base disturbance citrate from preservative and lactate from red cells Hypocalcemia citrate anticoagulant binds ionized calcium; BP, pulse pressure. Give CaCl2 only if there are symptoms / signs (not Ca2+ gluconate, which must be metabolized to release free Ca2+)

Transfusion Reactions
Acute
Febrile reaction due to bacterial contamination Microemboli aggregates of all cellular components, increase with age of blood. Cause complement activation, hemolysis and thrombocytopenia. Removed by 170um filter; +/- 40um screen and depth filters Hypothermia left shift of dissociation curve, platelet & clotting dysfunction Air embolus Fluid overload

Transfusion Reactions
Delayed
Hemolytic transfusion reaction from red cell antibodies Graft-versus-host disease Alloimmunization (reaction to minor foreign antigens) 10% of all transfusion reactions:
Red cell antibodies including anti-Rh(D) Leukocyte antibodies Platelet antibodies

Transfusion Reactions
Delayed
Viral infection
hepatitis B(1:20000 units) hepatitisC(1:1000 units) HIV (1:400000 units) cytomegalovirus parovirus (causes aplastic anemia in sickle cell patients)

Other infections
Syphillus Malaria trypanosomiasis

Transfusion Reactions
Delayed
Tumor recurrence increased risk Sensitization resulting in antibody formation and subsequent difficulties with cross-matching Iron overload occurs with repeated transfusions - haemochromatosis

Massive Blood Transfusion

Defined as the acute administration of more than 1.5 times the patients blood volume, or replacement of the patients total blood volume within 24h Transfusion of 10 units of blood within 6 hrs Transfusion of 5 units of blood within 1 hrs

Massive Blood Transfusion

Blood groups for urgent transfusion are:
O Rh(D) negitive if patient not cross matched Uncross-matched blood (type-specific) if patients blood group is known

Blood transfusion may be avoided by:

Reducing blood loss hypotensive anesthesia, antifibrinolytic agents Tolerating a lower HCT Transfusing autologus blood prior donation, use of cell saver Artificaial blood erythropoietin

Massive Blood Transfusion

Cell saver
Returned blood is warm, with normal levels of 2,3DPG: contraindicated with sepsis, contamination with intestinal contents or tumor cells

Artificial blood
Perfluorocarbons oxygen sol. 20 x plasma Recombinant Hb (rHb1.1) Purified Hb

Massive Blood Transfusion

Complications:
Impaired O2 delivery to tissues Impaired coagulation (FFP+platelets only if lab suggests) Hypothermia Hypocalcemia (if rapid transfusion) Hyperkalemia Metabolic acidosis followed by alkalosis Fluid over load TRALI

Massive Blood Transfusion

Filters
Particularly due to micro emboli Post transfusion pul. insufficiency Ordinary blood set filters 200m
Paul Utlipore Bently 70m 40m 70-80m

O2 dissociation curve for O2 carrying molecules

Blood
20

15 O2 content (ml/dl) 10

Hb solution

Perflurocarbons

10

20

30

40

50

60

PO2 (kPA)

Mechanism of Transfusion-induced Immunomodulation

Overload of reticuloendothelial system with iron salts causing most of the changes
Prostaglandin E2 production by monocytes is increased, which down regulates macrophages calls II antigen expression, inhibits interleukin-2 production Inhibition of interleukin-2 by TH lymphocytes will decrease B-cell stimulation and antibody production

Mechanism of Transfusion-induced Immunomodulation

Clonal depletion theory remove or
incapacitiate cells that would reject graft Decrease suppressor T-lymphocyte production

Anti-idiotypic production T-cell receptors or

antibodies generated against blood transfusion form new antigens that compete for binding locations on initial antibodies

Down regulated Immune Functions Following Allogenic Blood Transfusions

Reduced response in mixed lymphocyte culture
Decreased cytokine production Decreased response to mitogens (substance that

stimulates mitosis and lymphocyte

transformation) or soluble antigens in vivo or in

vitro
Increased suppresser-cell number or function Decreased natural killer-cell activity

Down regulated Immune Functions Following Allogenic Blood Transfusions

Decreased monocyte function
Decreased cell-mediated cytotoxicity against certain target cells

Enhanced production of soluble mediators and

anti-idiotypic antibodies suppressive or mixed lymphocyte response